Archive for the ‘ vitamins ’ Category

Source: Facts About Vitamin D and Rheumatoid Arthritis – Rheumatoid Arthritis

Dr. Mercola discusses the role of B vitamins and other valuable nutrients to support brain health.

Reprinted with the kind permission of Dr. Mercola.

By Dr. Mercola

A number of studies have investigated the impact of vitamin supplementation to prevent and/or treat cognitive dysfunction and decline.

It’s well-established that healthy fats such as animal-based omega-3 fats are really important for brain health, but other nutrients such as vitamins are also necessary for optimal brain function.

Most recently, a Korean studyconcluded that giving a multivitamin supplement to seniors suffering from mild cognitive impairment and depression helped improve both conditions.

B vitamins in particular, especially folate (B9, aka folic acid in its synthetic form) and vitamins B6 and B12, have made headlines for their powerful role in preventing cognitive decline and more serious dementia such as Alzheimer’s disease.

Mental fogginess and problems with memory are actually two of the top warning signs that you have vitamin B12 deficiency, indicating its importance for brain health.

B Vitamins and Omega-3 — An Important Combo for Brain Health

Although Dr. Michael Greger’s video is a good review on the research about B vitamins, being a vegetarian he does not include information about animal-based omega-3 fats, which are also beneficial in reducing dementia.
Low plasma concentrations of omega-3 and high levels of the amino acid homocysteine are associated with brain atrophy, dementia, and Alzheimer’s. Vitamins B6, B9, and B12 help convert homocysteine into methionine — a building block for proteins.
If you don’t get enough of these B vitamins, this conversion process is impaired and as a result your homocysteine levels increase. Conversely, when you increase intake of folic acid (folate), vitamin B6, and vitamin B12, your homocysteine levels decrease.
In one placebo-controlled trial2 published in 2015, 168 seniors diagnosed with mild cognitive impairment were randomly assigned to receive either placebo, or daily supplementation with 0.8 mg of folic acid, 20 mg of vitamin B6, and 0.5 mg of B12.
It’s worth noting that these are quite high doses — far above the U.S. RDA. All participants underwent cranial magnetic resonance imaging (MRI) scans at the outset of the study, and at the end, two years later.
The effect of the vitamin B supplementation was analyzed and compared to their omega-3 fatty acid concentrations at baseline. Interestingly, only those who had high omega-3 levels reaped beneficial effects from the B vitamins.
As noted by the authors:

“There was a significant interaction between B vitamin treatment and plasma combined omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates.

In subjects with high baseline omega-3 fatty acids (>590 ?mol/L), B vitamin treatment slowed the mean atrophy rate by 40 percent compared with placebo.
B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline omega-3 fatty acids (<390 ?mol/L). High baseline omega-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group…
It is also suggested that the beneficial effect of omega-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status.”

B Vitamins Significantly Slow Brain Shrinkage

As mentioned above, elevated homocysteine is linked to brain degeneration, and B vitamins are known to suppress homocysteine.
A 2010 study,3 in which participants again received higher than normal doses of B vitamins, also found that people receiving B vitamins experienced far less brain shrinkage than the placebo group.
Here the participants received either a placebo or 800 micrograms (mcg) folic acid, 500 mcg B12, and 20 mg B6. The study was based on the presumption that by controlling homocysteine levels you might be able to reduce brain shrinkage, thereby slowing the onset of Alzheimer’s.
Indeed, after two years those who received the vitamin B regimen suffered significantly less brain shrinkage compared to those who had received a placebo. Those who had the highest levels of homocysteine at the start of the trial experienced brain shrinkage at half the rate of those taking a placebo.
Research Shows B Vitamins Specifically Slow Alzheimer’s Disease
A 2013 study4 takes this research a step further, showing that not only do B vitamins slow brain shrinkage, but they specifically slow shrinkage in brain regions known to be most severely impacted by Alzheimer’s disease. Moreover, in those specific areas the shrinkage is decreased by as much as seven-fold!
The brain scans clearly show the difference between placebo and vitamin supplementation on brain atrophy. As in the studies above, participants taking high doses of folic acid and vitamins B6 and B12 lowered their blood levels of homocysteine, and brain shrinkage was decreased by as much as 90 percent.
As noted by the authors:

” … B vitamins lower homocysteine, which directly leads to a decrease in GM [gray matter] atrophy, thereby slowing cognitive decline.

Our results show that B vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD [Alzheimer’s disease] process and that are associated with cognitive decline.”

B12-Rich Foods Reduce Risk of Alzheimer’s in Later Years
Other supporting research includes a small Finnish study5 published in 2010. It found that people who consume vitamin B12-rich foods may reduce their risk of Alzheimer’s in their later years.
For each unit increase in the marker of vitamin B12 (holotranscobalamin), the risk of developing Alzheimer’s was reduced by 2 percent. This makes a strong case for ensuring your diet includes plenty of B vitamin foods, such as meat, poultry, eggs, dairy products and wild-caught fish.
Leafy green vegetables, beans, and peas also provide some of the B vitamins, but if you eat an all vegetarian or vegan diet, you’re at a significantly increased risk of vitamin B12 deficiency, as B12 is naturally present in foods that come from animals, including meat, fish, eggs, milk and milk products.
In such a case, supplementation is really important. Another concern is whether your body can adequately absorb the B12. It’s the largest vitamin molecule we know of, and because of its hefty size, it’s not easily absorbed.
This is why many, if not most, oral B12 supplements fail to deliver any benefits. Vitamin B12 requires a gastric protein called intrinsic factor to bind to it, which allows it to be absorbed in the end of your small intestine (terminal ileum). The intrinsic factor is absorbed first, pulling the attached B12 molecule along with it.
As you grow older, your ability to produce intrinsic factor decreases, thereby increasing your risk for vitamin B12 deficiency. Use of metformin (Glucophage, Glucophage XR, Fortamet, Riomet, and Glumetza) may also inhibit your B12 absorption, especially at higher doses. Drinking four or more cups of coffee a day can reduce your B vitamin stores by as much as 15 percent, and use of antacids will also hinder your body’s ability to absorb B12.
Other Valuable Vitamins for Brain Health
Besides B vitamins, vitamins C and D are also important for optimal brain health.6 Vitamin C plays a role in the production of neurotransmitters, including serotonin, which has antidepressant activity. Vitamin C has also been shown to improve IQ, memory, and offer protection against age-related brain degeneration and strokes.
In one study,7 the combination of vitamin C and E (which work synergistically) helped reduce the risk of dementia by 60 percent. Vitamin C also has detoxifying effects, and due to its ability to cross your blood-brain barrier, it can help remove heavy metals from your brain.
Vitamin D, a steroid hormone produced in your skin in response to sun exposure, also has profound effects on your brain. Pregnant women need to be particularly cognizant of this, as vitamin D deficiency during pregnancy can prevent proper brain development in the fetus, plus a host of other problems. After birth, children need vitamin D for continued brain development, and in adulthood, optimal levels have been shown to help prevent cognitive decline.8,9
Where to Find These Valuable Brain Nutrients
There’s nothing “normal” about cognitive decline. More often than not, it’s due to poor lifestyle choices, starting with a nutrient-deficient diet that is too high in sugars, non-vegetable carbs, unhealthy fats like trans fats, and too many toxins (pesticides and artificial additives, etc).
As a general rule, I recommend getting most if not all of your nutrition from REAL FOOD, ideally organic to avoid toxic pesticides, and locally grown. Depending on your situation and condition however, you may need one or more supplements.
To start, review the following listing of foods that contain the brain nutrients discussed in this article: animal-based omega-3s, vitamins B6, B9, and B12, C, and D. If you find that you rarely or never eat foods rich in one or more of these nutrients, you may want to consider taking a high-quality, ideally food-based supplement. I’ve made some suggestions to keep in mind when selecting a good supplement.


Nutrient Dietary Sources Supplement Recommendations
Animal-based omega-3 Fatty fish that is low in mercury, such as wild-caught Alaskan salmon, sardines, and anchovies, as well as organic grass-fed beef.10

Sardines, in particular, are one of the most concentrated sources of omega-3 fats, with one serving containing more than 50 percent of your recommended daily value.

Antarctic krill oil is a sustainable choice. It also has the added benefit of containing natural astaxanthin, which helps prevent oxidation.

Another good option is wild-caught Alaskan salmon oil.

Vitamin B6 Turkey, beef, chicken, wild-caught salmon, sweet potatoes, potatoes, sunflower seeds, pistachios, avocado, spinach and banana.11,12 Nutritional yeast is an excellent source of B vitamins, especially B6.13One serving (2 tablespoons) contains nearly 10 mg of vitamin B6.

Not to be confused with Brewer’s yeast or other active yeasts, nutritional yeast is made from an organism grown on molasses, which is then harvested and dried to deactivate the yeast.

It has a pleasant cheesy flavor and can be added to a number of different dishes. For tips, see this vegan blog post.14

Folate (B9) Fresh, raw, and organic leafy green vegetables, especially broccoli, asparagus, spinach, and turnip greens, and a wide variety of beans, especially lentils, but also pinto beans, garbanzo beans, navy and black beans, and kidney beans.15 Folic acid is a synthetic type of B vitamin used in supplements; folate is the natural form found in foods.

Think: folate comes from foliage(edible leafy plants).

For folic acid to be of use, it must first be activated into its biologically active form — L-5-MTHF.

This is the form able to cross the blood-brain barrier to give you the brain benefits noted.

Nearly half of the population has difficulty converting folic acid into the bioactive form due to a genetic reduction in enzyme activity.

For this reason, if you take a B vitamin supplement, make sure it contains natural folate rather than synthetic folic acid.

Nutritional yeast is an excellent source.16

Vitamin B12 Vitamin B12 is found almost exclusively in animal tissues, including foods like beef and beef liver, lamb, snapper, venison, salmon, shrimp, scallops, poultry, eggs, and dairy products.

The few plant foods that are sources of B12 are actually B12 analogs that block the uptake of true B12.

Also consider limiting sugar and eating fermented foods.

The entire B group vitamin series is produced within your gut, assuming you have healthy gut flora.

Eating real food, ideally organic, along with fermented foods will provide your microbiome with important fiber and beneficial bacteria to help optimize your internal vitamin B production.

Nutritional yeast is also high in B12, and is highly recommended for vegetarians and vegans.

One serving (2 tbsp) provides nearly 8 micrograms (mcg) of natural vitamin B12.17

Sublingual (under-the-tongue) fine mist spray or vitamin B12 injections are also effective, as they allow the large B12 molecule to be absorbed directly into your bloodstream.

Vitamin C Sweet peppers, chili peppers, Brussel sprouts, broccoli, artichoke, sweet potato, tomato, cauliflower, kale, papaya, strawberries, oranges, kiwi, grapefruit, cantaloupe, and lemon.

To boost your intake of fruits and vegetables, consider juicing. As an alternative, you can also make fermented vegetables at home.

The vitamin C in sauerkraut (fermented cabbage) is about six times higher than in the same helping of unfermented cabbage, so it’s an excellent way to boost your vitamin C intake.

The most effective form of oral vitamin C is liposomal vitamin C.

It’s not associated with many of the complications of traditional vitamin C or ascorbic acid (such as gastrointestinal distress), which will allow you to achieve higher intracellular concentrations.

You can expect a significant rise in plasma vitamin C concentration at doses between 30 and 100 mg/day.

Taking vitamin C frequently throughout the day is more effective than taking one large dose once a day.

Vitamin D Vitamin D is created naturally when your skin is exposed to sunshine.

While you can get some vitamin D from grass-fed meats and other whole foods and fortified foods, sun exposure is an ideal primary source.

When taking supplemental vitamin D, also be sure to increase your intake of vitamin K2 and magnesium, either from food or a supplement.

Sources and References

1 Journal of Nursing Scholarship February 15, 2016 DOI: 10.1111/jnu.12201

2 American Journal of Clinical Nutrition July 2015: 102(1); 215-221

3 PLoS ONE 5(9): e12244.

4 PNAS 2013 Jun 4;110(23):9523-8

5 Neurology. 2010 Oct 19;75(16):1408-14.

6 Be Brain Fit, Brain Vitamins

7 Psychology Today November 20, 2015

8 Journal of Neurology, Neurosurgery, and Psychiatry 2009 Jul;80(7):722-9

9 Vitamin D Council, Cognitive Impairment

10, Omega-3 Oils

11 Worlds Healthiest Foods, Vitamin B6

12, Top 10 Foods High in Vitamin B6

13, 17 Self Nutrition Data, Nutritional Yeast

14 Fat Free Vegan Kitchen, Nutritional Yeast

15 Worlds Healthiest Foods, Folate

16 Chalkboard, Nutritional Yeast

Source: The Importance of B Vitamins for Brain Health and Combating Dementia

She was proud to be a vegan and wanted her son to live like she did. But her family members said she took her food choices too far — her diet became a danger, in their eyes, something closer to an obsession than a healthy lifestyle.

“She was going to live on water and sunlight,” her sister-in-law told CBS Pittsburgh.

When the 33-year-old woman from western Pennsylvania, Elizabeth Hawk, began feeding her 11-month-old child sparse meals of only fruit and nuts, however, that was beyond the pale.

The boy developed what the sister-in-law, Brandy Hawk, described as a severe rash. He seemed to have lost control of his motor skills, she said, rendering his hands useless. Elizabeth Hawk said allergies were the reason for his apparent malaise, not the diet.

That argument did not convince Jerry Hawk, Elizabeth’s separated husband and the father of the child. He removed his son from his estranged wife’s care, taking the boy to a Children & Youth Services agency in nearby Fayette County. From there, reported, the agency took the child to a hospital in West Virginia.

An attending physician said the lack of nutritious food, according to Pennsylvania’s WKBN, caused a “failure to thrive.” Malnourishment had hindered the boy’s ability to develop, and ignoring the skin condition could have led to septic shock.

It is not inevitable that a vegan-only menu would doom young children to sickness or starvation, as The Washington Post wrote in July. But a commitment to veganism can make raising a healthy child more challenging, as parents must ensure that a child ingests sufficient calories and the correct balance of nutrients. In 2001, for instance, a pair of vegetarian nutritionists published recommendations for vegan infants in the Journal of the American Dietetic Association:

“For the first 4 to 6 months, breast milk should be the sole food with soy-based infant formula as an alternative. Commercial soymilk should not be the primary beverage until after age 1 year. Breastfed vegan infants may need supplements of vitamin B-12 if maternal diet is inadequate; older infants may need zinc supplements and reliable sources of iron and vitamins D and B-12. Timing of solid food introduction is similar to that recommended for non-vegetarians. Tofu, dried beans, and meat analogs are introduced as protein sources around 7-8 months. Vegan diets can be planned to be nutritionally adequate and support growth for infants.”

The young boy now lives with his father. Brandy Hawk, the sister-in-law, told CBS Pittsburgh the child is “doing great” and has “turned completely around.”

Elizabeth Hawk faces charges of child endangerment and was released on her own recognizance. A preliminary hearing has been set for Nov. 14, reported.

Source: Vegan mom fed her 11-month-old only fruit and nuts. Now she faces child endangerment charges. – The Washington Post

INFLAMMATION: The Cardiac Killer


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Source: The Cardiac Killer

Autophagy – the housekeeper in every cell that fights aging

By James P Watson and Vince Giuliano

Background and introduction

There is a wide variety of genetic manipulations, pharmacologic manipulations, and nutrient manipulations that have been shown to alter lifespan in model organisms.  These include caloric restriction, “loss of function” mutations, “gene knock out” models, phytochemicals, and drugs that down regulate aging pathways (mTOR, insulin/IGF-1, etc.).  It also includes “gain of function mutations”, transgenic models, phytochemicals, and drugs that up regulate longevity promoting pathways (AMPK, FOXO, Klotho, etc.).  At first glance, all these interventions may seem to be unrelated, suggesting that aging is a multifactorial problem with no common denominator to longevity.  On further examination, however, there is a common denominator to all of these interventions – autophagy.  Autophagy (“self eating”) is an old, evolutionarily conserved stress response that is present in all living cells. Like apoptosis, autophagy is a programmed response and has several sub-pathways.  Unlike apoptosis, autophagy promotes life rather than death.  Recent discoveries have shown that almost every genetic, dietary, and pharmacologic manipulation proven to extend lifespan activates autophagy as part of its mechanism of action.

Autophagy is the way your cells “clean house” and “recycle the trash”.  Along with the ubiquitin proteasome system, autophagy is one of the main methods that cells use to clear dysfunctional or misfolded proteins.  Autophagy can clear any kind of trash: intracellular viruses, bacteria, damaged proteins, protein aggregates and subcellular organelles. Although autophagy has long been known to exist, only recently has there been a clear understanding of the genes and pathways related to it.  This recent evidence suggests that the declining efficacy of autophagy may be a driver of many of the phenotypic phenomena of aging.  This blog entry explores the “evidence for the autophagy theory of aging” and builds a strong case that defective autophagy is a central driver for age-related diseases and aging itself.

Autophagy now appears to be a downstream event following insulin/IGF-1 pathway down-regulation, mTOR inhibition, Klotho activation, AMPK activation, Sirtuin dependent protein deacetylation, and histone acetyl transferase inhibition.  Autophagy explains in part, the beneficial effects of caloric restriction, caffeine, green tea, rapamycin, resveratrol, metformin, spermidine, lithium, exercise, hypoxia, Torin-1, trehalose, and a host of other natural and synthetic compounds.

There is much stronger evidence of a link between autophagy activation and longevity than there is with any other longevity interventions such as exogenous anti-oxidant supplementation, endogenous anti-oxidant up regulation, micronutrient replacement, hormone replacement, anti-inflammatory therapy, telomerase activation, or stem cell therapy.   For this reason, we have listed below the top reasons why “eating yourself for dinner” mauy well be the best way to promote health and longevity.

What is autophagy?

Biological entities employ various mechanisms to keep themselves functioning healthily, including mechanisms to get rid of defective or no longer wanted components.  Inter and intra-cell signaling can drive a cell to destroy itself, for example (cell apoptosis).  Short of apoptosis, on the cell level there are several mechanisms for getting rid of defective or no longer needed components including organelles and proteins.  From the 2008 publication Autophagy and aging:  “All cells rely on surveillance mechanisms, chaperones and proteolytic systems to control the quality of their proteins and organelles and to guarantee that any malfunctioning or damaged intracellular components are repaired or eliminated [1,2]. Molecular chaperones interact with unfolded or misfolded proteins and assist in their folding [3]. However, if the extent of protein damage is too great, or the cellular conditions are not adequate for re-folding, the same molecular chaperones often deliver proteins for degradation. Two proteolytic systems contribute to cellular clearance: the ubiquitin-proteasome and the lysosomal systems [4].”  Autophagy is concerned with the lysosomal system and involves the “degradation of any type of intracellular components including protein, organelles or any type of particulate structures (e.g. protein aggregates, cellular inclusions, etc.) in lysosomes(ref)”


Image source

Autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell’s own components through the lysosomal machinery. It is a tightly regulated process that plays a normal part in cell growth, development, and homeostasis, helping to maintain a balance between the synthesis, degradation, and subsequent recycling of cellular products. It is a major mechanism by which a starving cell reallocates nutrients from unnecessary processes to more-essential processes. Autophagy is an evolutionarily conserved mechanism of cellular self-digestion in which proteins and organelles are degraded through delivery to lysosomes. Defects in this process are implicated in numerous human diseases including cancer(ref).”

Top 16 Key Facts about Autophagy

There are three main pathways of Autophagy – Macroautophagy, Microautophagy, and Chaperone-mediated Autophagy (CMA).

All 3 autophagy pathways are constitutively active (i.e. they can occur at basal levels) but can also be up regulated by cellular stress). Macroautophagy is the primary “broom” that sweeps the house. Macroautophagy is initiated when the material to be removed is tagged with ubiquitin.  This signals a complex series of molecular events that leads to the formation of a membrane  around the material to be removed and recycled.  This membrane formation around the debris is called a autophagosome.  Once formed, the autophagocome fuses with a lysosome to form an autolysosome.  Once fusion occurs, the acid hydrolases found inside the lysosomes start digesting the damaged proteins and organelles.  When damaged mitochondria are digested by macroautophagy, it is called mitophagy, which is a specific type of macroautophagy. Macro-autophagy can also remove and recycle mutated or free-radical damaged proteins or protein aggregates.  Macroautophagy  and other sub cellular organelles (peroxisomes, endoplasmic reticulum, etc.)  Even part of the cell nucleus can undergo autophagy (called “piecemeal microautophagy of the nucleus” – PMN).

Macroautophagy   Image source


Chaperone-mediated autophagy (CMA) is a specific mechanism of autophagy that requires protein unfolding by chaperones.   The other two mechanisms do not require protein unfolding (macroautophagy and microautophagy).  Since protein aggregates cannot be unfolded by chaperone proteins, both the ubiquitin-proteasome system and chaperone-mediated autophagy are unable to clear these protein aggregates.  For this reason, macroautophagy may be the most important pathway for preventing Alzheimer’s disease, Parkinson’s disease, Fronto-temporal dementia, and all of the other neurodegenerative diseases associated with protein aggregate accumulation.

Microautophagy is essentially just an invagination (folding in) of the lysosomal membrane and does not require the formation of an double-membrane autophagosome.  Both CMA and microautophagy appear to play a minor role in “house keeping”.  Here are diagrams of these types of autophagy.


Image source


Image sourcekindsofautophagy

 2. Autophagy is the only way to Get Rid of Old Engines  i.e. damaged mitochondria

Autophagy is the best way to get rid of bad mitochondria without killing the cell.  The process is called “mitophagy.” Since bad mitochondria produce most of the “supra-hormetic doses of ROS”, this is really, really, important. This is explained in our recent blog entries related to mitochondria, Part 1, and Part 2.  For brain cells, heart cells, and other post mitotic cells that we all want to “hang on to”, mitophagy is probably the most important anti-aging value of mitophagy.  Bad mitochondria are phosphorylated by the kinase PINK1.  Then these bad mitochondria are ubiquinated by the E3 ligase Parkin.  The ubiquinated bad mitochondria are then selectively destroyed by mitophagy, which is a form of macroautophagy.

mitophagy1Mitophagy   Image source

The 2007 publication Selective degradation of mitochondria by mitophagy reviews the topic.  “Mitochondria are the essential site of aerobic energy production in eukaryotic cells. Reactive oxygen species (ROS) are an inevitable by-product of mitochondrial metabolism and can cause mitochondrial DNA mutations and dysfunction. Mitochondrial damage can also be the consequence of disease processes. Therefore, maintaining a healthy population of mitochondria is essential to the well-being of cells. Autophagic delivery to lysosomes is the major degradative pathway in mitochondrial turnover, and we use the term mitophagy to refer to mitochondrial degradation by autophagy. Although long assumed to be a random process, increasing evidence indicates that mitophagy is a selective process.”

3. Autophagy is the best Way to Get Rid of Junk.    – protein aggregates, etc.

Autophagy is the best way to get rid of protein aggregates like those associated with all of the neurodegenerative diseases, like amyloid beta, tau tangles, alpha synuclein aggregates, TDP-43 aggregates, SOD aggregates, and Huntington protein aggregates.  These aggregates are NOT digested via the ubiquitin-proteasome system, since they cannot be “unfolded”.   For this reason, autophagy is probably the most important cellular mechanism for clearing protein aggregates found in neurodegenerative diseases.  Autophagy can also clear out bad cytoplasm (Cvt), endoplasmic reticulum, peroxisomes (micro and macropexophagy), Golgi apparatus,  and even damaged parts of the nucleus (PMN).  See for example (2012) Degradation of tau protein by autophagy and proteasomal pathways and (2009) Autophagy protects neuron from Abeta-induced cytotoxicity

Autophagy is protective by quietly getting rid of multiple other unwanted substances.  For example, it protects against alcohol-induced liver damage.  Consider what is going on in this diagram from the 2011 publication The emerging role of autophagy in alcoholic liver disease:

alcoholmitophagyImage source     “Alcohol consumption causes hepatic metabolic changes, oxidative stress, accumulation of lipid droplets and damaged mitochondria; all of these can be regulated by autophagy. This review summarizes the recent findings about the role and mechanisms of autophagy in alcoholic liver disease (ALD), and the possible intervention for treating ALD by modulating autophagy(ref).”

4. Aging = Autophagy decline. 

According to the 2008 publication Autophagy in aging and in neurodegenerative disorders: “Growing evidence has indicated that diminished autophagic activity may play a pivotal role in the aging process. Cellular aging is characterized by a progressive accumulation of non-functional cellular components owing to oxidative damage and a decline in turnover rate and housekeeping mechanisms. Lysosomes are key organelles in the aging process due to their involvement in both macroautophagy and other housekeeping mechanisms. Autophagosomes themselves have limited degrading capacity and rely on fusion with lysosomes. Accumulation of defective mitochondria also appears to be critical in the progression of aging. Inefficient removal of nonfunctional mitochondria by lysosomes constitutes a major issue in the aging process. Autophagy has been associated with a growing number of pathological conditions, including cancer, myopathies, and neurodegenerative disorders.”

The relationship of autophagy decline to hallmarks of aging has been known for a long time and have been best studied in liver cells.  The auto florescent protein lipofuscin is the oldest and simplest biomarker of declining autophagy and represents undigested material inside of cells.  The Lewy bodies seen in several neurodegenerative diseases (including “Parkinson’s disease with dementia”) are also biomarkers of declining autophagy and may specifically be due to “declining mitophagy”.  Declining autophagy is particularly important in post-mitotic cells such as those in the brain, heart, and skeletal muscle where very little cell regeneration via stem cells occurs.  For mitotic tissues such as the GI tract, bone marrow, and skin, autophagy decline may not be as detrimental, since apoptosis is another normal method for getting rid of bad cells.

The failure of autophagy with aging has several possible causes:

a. Fusion problems – Autophagic vacuoles accumulate with age in the liver.  This may be due to a problem of fusion between the autophagosomes and the lysosomes.

b. Glucagon deficiency – Glucagon is a hormone that enhances macroautophagy. “—the stimulatory effect of glucagon [on autophagy] is no longer observed in old animals.  See item (b) in the next list below.(ref)“

c. Negative signaling via the Insulin receptor – Insulin activates the Insulin/IGF-1 pathway which activates mTOR.  mTOR activation inhibits autophagy (see below).  Even in the absence of insulin, there is up-regulation with aging of the insulin/IGF-1 signaling via the insulin receptor tyrosine kinase.  This would activate mTOR.

d. Inadequate turnover of damaged mitochondria – Mitophagy decline may be one of the mechanisms that is responsible for the decline in autophagy with aging.  Specifically, if mitophagy does not keep up with the demand for damaged mitochondrial clearance, a higher baseline ROS would occur, which would damage proteins, cell membrane lipids, and cell nucleus DNA.

e. Energy compromise – With aging, there is a decline in energy production by the cells.  This may be one of the reasons for the decline in autophagy seen in aging.

Here is a depiction of some of the main problems associated with decline of autophagy in aging:


Some consequences of failure of autophagy with aging  “Possible causes and consequences of the failure of macroautophagy in old organisms are depicted in this schematic model (brown boxes”   Image source

(a) The accumulation of autophagic vacuoles with age could result from the inability of

lipofuscin- loaded lysosomes to fuse with autophagic vacuoles and degrade the sequestered content.

(b) In addition, the formation of autophagosomes in old cells might be reduced because of the inability of macroautophagy enhancers (such as glucagon) to induce full activation of this pathway. The stimulatory effect of glucagon is compromised in old cells because of maintained negative signaling through the insulin receptor (IR) even under basal conditions (i.e. in the absence of insulin). Maintained insulin signaling would activate mTOR, a known repressor of macroautophagy.

(c) Inadequate turnover of organelles, such as mitochondria, in aging cells could increase levels of free radicals that generate protein damage and

(d) Aging could also potentiate the inhibitory signaling through the insulin receptor.

(e) An age-dependent decline in macroautophagy can also result in energetic compromise of the aging cells.

5.  Genetic manipulations that increase lifespan in all model organisms stimulate autophagy.

Knocking out macroautophagy takes away at least 50% of the long-lived mutant’s added lifespan.  This same “loss of longevity” is seen with Caloric restriction in “macroautophagy knockouts”.    The following diagram shows how important autophagy is in long-lived mutant nematodes and how this is important for increasing lifespan, reducing cellular damage, and increasing function.


Image source

The most well studied “mutants” are model organisms where one of the following pathways are altered by a gene mutation or a gene knock out.  When an additional “knocking out” of an autophagy gene is done, approximately 1/2 of the added lifespan of the long lived mutants (vs wild type) appears to be “wiped out” by loosing autophagy.   Similar findings occur in “macroautophagy  knock-outs” subjected to caloric restriction, etc.  This suggests to me that 1/2 of the benefits of caloric restriction are due to stimulating autophagy.  Caloric restriction down regulates all of the”nutrient sensing pathways that are negative regulators of autophagy” and up regulates other “ nutrient sensing pathways that are positive regulators of autophagy”.  The following interconnected “nutrient -sensing pathways” affect macroautophagy:

a. IGF-1: two mechanisms:

i. decreasing Insulin-IGF-1 pathway => tyrosine kinase => inhibits Akt phosphorylation of TSC =>  inhibition of raptor in mTOR complex

ii. decreasing insulin/IGF-1 pathway => Foxo transcription factor translocation to nucleus  => FOXO stimulates autophagy via activating two  autophagy genes – LC3 and BNIP3.

b. mTOR:  three mechanisms account for the activation of autophagy by mTOR inhibition

i.  mTOR inhibition => decreases phosphorylation of Atg1 (aka ULK1/2). Also decreases phosphorylation of  Atg13 and Atg17.  Phosphorylation of ULK1/2, Atg13, and Atg17 inhibits autophagy initiation.

ii. decreasing mTOR pathway => decreases phosphorylation of 4EBP1 => blocks effect of eIF4F => autophagy activation.

iii. decreasing mTOR pathway => decreases phosphorylation of S6K => S6K no longer active => inhibition of autophagy.

Microsoft PowerPoint - Final IBDMN Fig 2

Signaling pathways that affect autophagy Image source

“The (mammalian) target of rapamycin (mTOR) is a primordial negative regulator of autophagy inorganisms from yeast to man. mTOR is inhibited under starvation conditions, and this contributes to starvation-induced autophagy via activation of mTOR targets Atg13, ULK1, and ULK2. This inhibition can be mimicked by mTOR inhibitory drugs like rapamycin (Ravikumar et al., 2010).  One of the important pathways regulating mTOR is initiated when growth factors like insulin-like growth factor bind to insulin-like growth factor receptors (IGF1R) (Figure 2). These receptors signal, via their tyrosine kinase activities, to effectors like the insulin receptor substrates (IRS1 and IRS2), which in turn activate Akt. Akt inhibits the activity of the TSC1/TSC2 (proteins mutated in tuberous sclerosis) complex, a negative regulator of mTOR. In this way, IGF1R signaling activates mTOR and inhibits autophagy, and the converse occurs when nutrients are depleted(ref).”

c. Ras/PKA:  decreasing Protein Kinase A pathway (aka Ras/cAMP) => decreases phosphorylation of 3 autophagy proteins (Atg1, Atg13, Atg18).

d. PKB/Akt: decreasing Protein Kinase B pathway (aka PkB/Akt or Sch9) => reduces inhibition of TSC-1 => decreased mTOR activity.

e. Sirtuin 1:  CR activates Sirtuin 1 => deacetylation of several autophagy gene products: Atg5, Atg7, Atg8/LC3.   Sirt1 also activates AMPK, activates FOXO3a, and inhibits mTOR via TSC-1/2

f. AMPK: AMPK pathway (aka LKB1-AMPK) activates autophagy via two methods:

i. AMPK activation => phosphorylates TSC2 and raptor => inhibits TORC1  (this requires glucose starvation).

ii. AMPK activation => direct phosphorylation of Atg1 (aka ULK1) => autophagy activation (this does NOT require glucose starvation).

g. Less-important pathways:

i.  Rim15:  increasing Rim15 Kinase pathway => Msn2 and Msn4 transcription factor translocation to nucleus => inhibits mTOR, PKA, and PKB pathways.

ii  ERK1/2:  ERK pathway – the extracellular signal-regulated kinase (ERK) also mediates starvation-induced autophagy.  (see #6 below for more details)

iii. JNK: JNK pathway – This is a MAPK that mediates starvation-induced autophagy. (see #6 below for more details).

The main pathways are depicted in the following diagram of how Calorie Restriction works (Ras/PKA and less important pathways not depicted).


Autophagy regulation      Image source

6. There are many other pathways that regulate autophagy that are not dependent on “nutrient sensing pathways.” 

(i.e. not those described above).

Although caloric restriction or fasting are clearly the most “potent” autophagy stimulators, since they can activate macroautophagy via the above “nutrient sensing pathwaysthere are many other pathways that can activate autophagy.  Here an explanation of the roles of the key kianses involved:

a. PI3Ks and Akt – PI3Ks are kinases that are mainly activated by growth factors, not starvation.  There are 3 classes of PI3Ks and the Class III PI3Ks directly positively activate autophagy (Vps34) whereas the Class I PI3Ks indirectly inhibit autophagy via mTOR and Akt.

b. MAPKs – Mitogen-Activated Protein Kinase – these are kinases that are mainly activated by growth factors, not starvation.  There are 3 classes:

i. ERK – Extracellular signal-Regulated Kinases (ERK) positively regulate autophagy by maturing autophagic vacuoles.  EKR also seems to specifically be involved with mitochondrial-specific autophagy (i.e. mitophagy).  Mitochondrial ERK may help protect from neurodegenerative diseases.  Cancer cells also activate mitochondrial ERK to cause chemoresistance.  ERK is activated downstream from Ras.  Ras activates Raf, which activates MEK.  MEK phosphorylates and activates ERK1 and ERK2.

This is the mechanism by which you can kill cancer with soy extracts, capsaicin, and Cadmium.  Here is how this works:

  • Soyasaponins (found in soybeans) => activates ERK => autophagy-induced death in colon cancer cells
  • Capsaicin (found in chili peppers) => activates ERK => autophagy-induced death in breast cancer cells
  • Cadmium (toxic metal) => activates ERK => autophagy-induced death in mesangial cells

ii. p38 – p38 is a MAPK that is a tumor suppressor.  p38 regulates autophagy but there is still controversy if it activates or inhibits autophagy.

iii. JNK – JNK is a MAPK that is activated by heat shock, osmotic shock, UV light, cytokines, starvation, T-cell receptor activation, neuronal excitotoxic stimulation, and ER stress.  With starvation, JNK does not phosphorylate Bcl-2, which prevents it from binding to beclin 1.  Beclin 1 can then induce autophagy.  Bcl-2 is an anti-apoptotic protein and can prevent apoptosis.  There are multiple phosphorylation sites on Bcl-2.  The degree by which JNK phosphorylates/dephosphorylates Bcl-2 may determine cell fate – i.e. apoptosis (death) vs autophagy (survival). See (2011) The Beclin 1 network regulates autophagy and apoptosis.

c. PKC – Protein Kinase C (PKC) is a family of kinases that were once thought to be associated mostly with apoptosis/anti-apototis.  Recent research has shown that PKCs also play a role in autophagy.  The effects of PKC depend on if the cellular stress is acute or chronic.  For instance, PKCg is an example of one of the PKCs where it stimulates autophagy with acute, short periods of hypoxia (via JNK activation) but suppresses autophagy with chronic hypoxia (via Caspace-3).   Another PKC, PKC0  is involved with ER-stress induced autophagy.  Acadesine (AICAR) induces autophagy via a PKC/Raf1/JNK pathway.  Acadesine (AICAR) in combination with GW1516 has shown to improve endurance-type exercise by converting fast-twitch muscle fibers into the more energy-efficient, fat-burning, slow-twitch muscle fibers.  These two compounds turned on 40% of the genes that were turned on when exercise + GW1516 were used together.  For this reason, acadesine (AICAR) has been termed an “exercise mimetic” and has been banned for use by athletes, since it is a performance enhancing drug, even though it is very safe.  The mechanism of action of AICAR may be in part its induction of autophagy.

d. Endoplasmic Reticulum Stress Kinases (i.e. the ER unfolded protein response) – Several kinases involved with the endoplasmic reticulum unfolded protein response (ER-UPR) have been found to activate autophagy.  They include the following:

i. IRE-1 – Inositol-requiring enzyme (IRE1) is one of the first proteins activated by the ER-UPR.  It up regulates autophagy genes (Atg5, 7, 8, 19).

ii. PERK – PERK must phosphorylate the eukaryotic initiation factor 2alpha (eIF2alpha) for LC3 conversion with ER-UPR induced autophagy.     PERK also up regulates Atg5.

iii. CaMKKbeta – ER stress results in calcium release from the ER.  This Ca++ release induces autophagy via the Ca dependent kinases.  The main one is called Ca/Calmodulin-dependent kinase beta (CaMKKbeta).  This is an “upstream activator” of AMPK, which in turn inhibits mTOR.  This is how calcium can induce autophagy.

iv. DAPK1 – Death-associated protein kinase 1 (DAPK1) is another Ca++/Calmodulin-regulated kinase that is important in ER-UPR induced autophagy. It induces autophagy by phosphorylating beclin 1, which is necessary for autophagosome formation.


Mechanisms connecting  ER stress and autophagyImage Source  “Mechanisms connecting ER stress and autophagy. Different ER stresses lead to autophagy activation. Ca2+ release from the ER can stimulate different kinases that regulate autophagy. CaCMKK phosphorylates and activates AMPK which leads to mTORC1 inhibition; DAPK phosphorylates Beclin-1 promoting its dissociation from Bcl-2; PKCθ activation may also promote autophagy independently of mTORC1. Inositol 1,4,5-trisphosphate receptor (IP3R) interacts with Beclin-1. Pharmacological inhibition of IP3R may lead to autophagy in a -independent manner by stimulating its dissociation from Beclin-1. The IRE1 arm of ER stress leads to JNK activation and increased phosphorylation of Bcl-2 which promotes its dissociation from Beclin-1. Increased phosphorylation of eIF2 in response to different ER stress stimuli can lead to autophagy through ATF4-dependent increased expression of Atg12. Alternatively, ATF4 and the stress-regulated protein p8 promote the up-regulation of the pseudokinase TRB3 which leads to inhibition of the Akt/mTORC1 axis to stimulate autophagy(ref).”

7. Excess baseline ROS from bad mitochondria induces Mitophagy.

 – ROS induces autophagy via a non-canonical pathway

This may be the mitochondrial signal for “selective destruction” of damaged mitochondria.  Exogenous ROS can also induce autophagy, however.  For instance, there is evidence that abnormal levels of H202 in the cytoplasm will induce macroautophagy. Hydrogen peroxide induces a “non-canonical autophagy” that is “beclin-1 independent” but requires the JNK-mediated activation of Atg7.  on of Atg7.


ROS induces autophagy: Roles of Akt, ERK, JNK and BeclinsImage source

8. Most all of the Pharmacologic manipulations that extend lifespan increase autophagy.

Here are some of the main ones:

a. Rapamycin – Autophagy explains most of the longevity and health benefits (mechanism of action) of Rapamycin

Since the protein kinase mTOR phosphorylates the 3 key autophagy initiating proteins (Atg1, Atg13, and Atg17),  it is considered the  “Master of Autophagy”.  Rapamycin inhibits both TORC1 and TORC2.  TORC1 inhibition is the the “direct” and primary mechanism by which rapamycin activates autophagy, but TORC2 inhibition has an “indirect” and independent method of activating autophagy via inhibiting Akt or Protein Kinase C.  (This is why Blagonosky in NY likes rapamycin over TORC1-specific mTOR inhibitors).


Image source  mTOR and autophagy, showing impacts of lithium and rapamycin

b. Metformin – .Autophagy may explain as much as 50% of the benefits (mechanism of action) of Metformin.

Metformin activates AMPK and therefore stimulates autophagy via TORC1-dependent and TORC-1 independent methods (see above).  For this reason, metformin is a good “autophagy drug”.  Metformin probably has many other mechanisms of action, however, which cannot be explained by the induction of autophagy.


Image source

c. Resveratrol – Resveratrol directly or indirectly activates the NAD+-dependent deacetylase, SIRT1.

SIRT1 activates autophagy by several different mechanisms, the 4 major ones being deacetylation of multiple cytoplasmic proteins including several involved with autophagy, such as ATG5, ATG7, and ATG8/LC3.  SIRT1 also deacetylates the FOXO transcription factors (FOXO3a, FOXO, and FOXO4), but the FOXO proteins are not required for autophagy induction.  It is likely that the effects of SIRT1 on FOXO deacetylation mediate other beneficial effects of resveratrol (not autophagy).

d. Spermidine – The benefits of spermidine can be partially explained by its effects on autophagy.  Spermidine is a histone acetylase inhibitor.  By inhibiting histone acetylase, spermidine allows for the up regulation of autophagy (Atg) genes.  It appears that like resveratrol, spermidine also stimulates overlapping deacetylation reactions of cytoplasmic proteins. See the 2009 publication Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol.


Image source

Microsoft Word - Figure 1

Spermidine and autophagy in normal and diabetic states  Image source


e. Lithium – The beneficial effects of Lithium for aging and for bipolar illness may be mediated in part by autophagy(ref).

9.  Exercise can both activate and inhibit autophagy.  

For this reason, the benefits of exercise are mostly due to non-autophagy factors.

Decreased autophagy mechanisms with exercise:  Exercise up regulates mTOR, especially resistance exercises like weight lifting.  Exercise also activates the IGF-1 pathway by increasing growth hormone secretion by the pituitary gland, which then in turn stimulates  IGF-1 production by the liver.  IGF-1 inhibits autophagy via the Insulin/IGF-1/PI3K/Akt pathway.

Increased autophagy mechanisms with exercise:   ROS increases with exercise.  Since ROS activates autophagy, this is one mechanism by  which exercise could activate autophagy, but it is unclear if this activates “selective mitochondrial destruction” this way (i.e. mitophagy).

Hypoxia also activates autophagy via a HIF-1a pathway.  This would occur with exercise if you reached your anaerobic threshold during exercise or did IHT exercise (intermittent hypoxia with exercise).

Conclusion:  Exercise can both inhibit and activate autophagy.  This may be why it is difficult to show exactly how exercise prolongs lifespan.

10.  Autophagy exercises anti-aging effects on postmitotic cells.

– There are primarily 5 cytoprotective effects:

  1. Reduced accumulation of toxic protein aggregates, described above
  2. Destroying bad mitochondria via mitophagy, described above
  3. Reduced apoptosis
  4. Reduced necrosis
  5. Improved hormesis

Cells that do not divide are particularly vulnerable to the build-up of protein aggregates seen in neurodegenerative diseases.  Autophagy inducers such as rapamycin, rapalogs, valproate, and lithium have been shown to help in experimental models of Huntington’s disease, tauopathies, Alzheimer’s disease, and Parkinson’s disease.

When mitochondria are defective due to ROS-induced damage, asymmetric fission occurs, allowing for a good mitochondria and a bad mitochondria to “split up”.  The bad mitochondria has a low membrane potential and is tagged by PINK1 and then ubiquinated by Parkin.  At this point, it is recognized by the autophagy system and is destroyed by macroautophagy.

Autophagy also has an anti-apoptotic function in post mitotic cells.   Autophagy helps damaged cells recover and thereby avoid apoptosis.  Autophagy also has an “anti-necrosis” function in post mitotic cells.

Autophagy is also a stress response involving hormesis.  Hormesis is how low (sublethal) doses of cellular stressors result in an up regulation of cellular stress adaptation mechanisms. See the blog entries Multifactorial hormesis II – Powerpoint presentation and Multifactorial Hormesis – the theory and practice of maintaining health and longevityAutophagy has a hormetic dose response curve.  Depending on the strength or duration of the stressor, autophagy or a negative consequence could ensue, as exemplified in this diagram:

hormesis- 2

Image source

11. Anti-aging effects of Autophagy on Proliferating Cells 

– Autophagy has cytoprotective effects and other unique effects in dividing cells:

  1.  Cytoprotective effects – see #10 above
  2. Reduced stem cell attrition
  3. Reduced ROS-induced cellular senescence
  4. Reduced oncogenic transformation
  5. Improved genetic stability
  6. Increased p62 degradation
  7. Anti-cancer effects via increased oncogene-induced senescence and oncogene-induced apoptosis

With aging, there is a decline in bone marrow stem cell function (hematopoeitic stem cells and mesenchymal stem cells) and stem cell number (MSCs only).  Rapamycin restores the self-renewal capability of hematopoietic stem cells (HSCs).  This improves the function of the immune system, of course assuming a lower dose of rapamycin than the immunosuppressive rapamycin dose given for preventing organ transplant rejection.  Rapamycin can also reverse the stem cell loss that occurs in hair follicles and thereby prevent alopecia.  mTOR accelerates cellular senescence by increasing the expression of p16/INK4a, p19/Arf, and p21/Cip1.  These are all markers of cellular senescence and up regulating these tumor suppressors induces cellular senescence.

The tumor suppressor PTEN is just the opposite, however.  Loss of the tumor suppressor PTEN induces a unique type of cellular senescence called “PTEN loss-induced cellular senescence” (PICS).  PICS occurs with mTOR activation and can be reduced by inhibiting MDM2, which leads to an increase in p53 expression.  This would inhibit autophagy. Rapamycin can preclude  permanent (irreversible) cell-cycle arrrest due to inducible p21 expression.  In this aspect, mTOR decreases proliferative potential and mediates stem cell attrition via senescence.  Rapamycin can suppress this.  This effect may be mediated by autophagy or by an autophagy-independent effect of mTOR inhibition.

More importantly, several oncogenes suppress autophagy.  This includes Akt1, PI3K, Bcl-2 family anti-apoptotic proteins.  Most of the proteins that stimulate autophagy also inhibit oncogenesis.  This includes DAPK1, PTEN, TSC1, TSC2, LKB1/STK11, and Beclin-1.  Autophagy can suppress oncogenesis through cell-autonomous effects described below:

  1. Improved quality control of mitochondria (less baseline ROS production)
  2. Enhanced genetic stability
  3. Removal of potentially oncogenic protein p62 via autophagy.
  4. Autophagy up regulation results in oncogene-induced senescence (via Ras)

The diagram below shows the beneficial effects of autophagy on all cell types, specific benefits in proliferating cells, and specific benefits in post-mitotic cells.



Systemic Anti-Aging Effects of Autophagy   Image source

 12. Autophagy can reduce age-related dysfunction through systemic effects – 

Autophagy also confers several beneficial anti-aging effects that are not due to cytoprotection, or other localized effects within the cell itself.  This includes the following systemic benefits of autophagy:

  1. Defense against infections
  2. Innate immunity
  3. Inhibition of pro-inflammatory signaling
  4. Neuroendocrine effects of autophagy

Autophagy in dying antigen-presenting cells improves the presentation of the antigens to dendritic cells.  In dendritic cells, autophagy improves antigen presentation to T cells.  Autophagy in dying cells is also required for macrophage clearance of these dead/dying cells.   This is how autophagy reduces inflammation.  Autophagy helps keep ATP production going in these dying cells, providing energy for the key step in the lysophosphatidylcholine “find me” signaling as well as the phosphatidylserine “flip flop” that is the “eat me” recognition signal for macrophage ingestion of the dying/dead cells.  By helping macrophages find these cells and recognize that they are ready for macrophage ingestion, these cells do not rupture and spill their intracytoplasmic contents (this is what causes the inflammation with necrosis, where cell membrane rupture occurs).

When autophagy is working hand-in-hand with apoptosis, no inflammation occurs when a cell dies. This is a key beneficial role of autophagy in reducing inflammation.   The decline in autophagy seen in aging may be in part the cause of age-induced type-2 diabetes.  Here the peripheral tissues become insulin resistant.  This may be due to the hepatic suppression of the Atg7 gene, which results in ER stress and insulin resistance.  Induction of autophagy in specific neural populations may be sufficiency to reduce pathological aging.



More effects of autophagy     Image source

Beyond its cell-autonomous action, autophagy can reduce age-related dysfunctions through systemic effects. Autophagy may contribute to the clearance of intracellular pathogens and the function of antigen-presenting cells (left), reduce inflammation by several mechanisms (middle), or improve the function of neuroendocrine circuits (right).

13.  Autophagy is necessary for maintaining the health of pools of adult stem cells

Frequent readers of this blog know that the writers believe that age-related decline of the health and differentiation capability of adult stem cells and increasing sensescence of those cells may be responsible for many of the effects we associate with aging.  Thus, the positive roles of autophagy in keeping stem cells viable is of great interest to us.

See the comments under 11 above.  Also, the June 2013 review publication Autophagy in stem cells provides “a comprehensive review of the current understanding of the mechanisms and regulation of autophagy in embryonic stem cells, several tissue stem cells (particularly hematopoietic stem cells), as well as a number of cancer stem cells.”  Another such review is the June 2012 e-publication Tightrope act: autophagy in stem cell renewal, differentiation, proliferation, and aging.


Image Source  “Tightrope act inhibition of mTOR via caloric restriction (CR) or rapamycin induces autophagy. Autophagy clears away damaged proteins and organelles like defective mitochondria, thereby decreasing ROS levels and reducing genomic damage and cellular senescence, thus playing a crucial role in enhancing stem cell longevity. CR may also have a role in maintaining low levels of p16ink4a, a tumor suppressor protein, thus reducing the risk of cancer and promoting proliferation of stem cells. Oncogenesis is countered by loss of PTEN which elicits a p53-dependent prosenescence response to decrease tumorigenesis(ref)”

Only now are studies beginning to emerge that characterize the detailed roles of autophagy in maintaining stem cell health and differentiation viability.  Autophagy in stem cells recapitulates the current state of understanding:  “As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis as well as remodeling during normal development, and dysfunctions in autophagy have been associated with a variety of pathologies including cancer, inflammatory bowel disease and neurodegenerative disease. Stem cells are unique in their ability to self-renew and differentiate into various cells in the body, which are important in development, tissue renewal and a range of disease processes. Therefore, it is predicted that autophagy would be crucial for the quality control mechanisms and maintenance of cellular homeostasis in various stem cells given their relatively long life in the organisms. In contrast to the extensive body of knowledge available for somatic cells, the role of autophagy in the maintenance and function of stem cells is only beginning to be revealed as a result of recent studies. Here we provide a comprehensive review of the current understanding of the mechanisms and regulation of autophagy in embryonic stem cells, several tissue stem cells (particularly hematopoietic stem cells), as well as a number of cancer stem cells. We discuss how recent studies of different knockout mice models have defined the roles of various autophagy genes and related pathways in the regulation of the maintenance, expansion and differentiation of various stem cells. We also highlight the many unanswered questions that will help to drive further research at the intersection of autophagy and stem cell biology in the near future.”

Another very-recent finding related to autophagy and stem cells is reported in the March 31, 2013 paper FIP200 is required for maintenance and differentiation of postnatal neural stem cells.These data reveal that FIP200-mediated autophagy contributes to the maintenance and functions of NSCs through regulation of oxidative state.” FIP200 is “a gene essential for autophagy induction in mammalian cells.”

Exercising control over autophagy may prove useful for efficiently generating induced pluripotent stem cells.  According to the 2012 publication Autophagy in stem cell maintenance and differentiation: “We also discuss a possible role for autophagy during cellular reprogramming and induced pluripotent stem (iPS) cell generation by taking advantage of ATP generation for chromatin remodeling enzyme activity and mitophagy. Finally, the significance of autophagy modulation is discussed in terms of augmenting efficiency of iPS cell generation and differentiation processes.”

A steady stream of research continues to reveal new insights on the roles that autophagy plays in stem cells.  For example, the April 2013 publication FOXO3A directs a protective autophagy program in haematopoietic stem cells reports: “Here we identify autophagy as an essential mechanism protecting HSCs from metabolic stress. We show that mouse HSCs, in contrast to their short-lived myeloid progeny, robustly induce autophagy after ex vivo cytokine withdrawal and in vivo calorie restriction. We demonstrate that FOXO3A is critical to maintain a gene expression program that poises HSCs for rapid induction of autophagy upon starvation. Notably, we find that old HSCs retain an intact FOXO3A-driven pro-autophagy gene program, and that ongoing autophagy is needed to mitigate an energy crisis and allow their survival. Our results demonstrate that autophagy is essential for the life-long maintenance of the HSC compartment and for supporting an old, failing blood system.”

14.  Autophagy is a key step in activating the Nrf2 pathway.  And Nrf2 expression can in turn regulate autophagy.

The importance of the Nrf2 stress-response pathway and its role in generating health has been one of the frequent topics of discussion in this blog.  See specifically the blog entries The pivotal role of Nrf2. Part 1, Part 2, Part 3, and Nrf2 and cancer chemoprevention by phytochemicals.  We know now that autophagy plays a key role in Nrf2 activation, via p62-dependent autophagic degradation of Keap1.  See, for example, the 2012 publication Sestrins Activate Nrf2 by Promoting p62-Dependent Autophagic Degradation of Keap1 and Prevent Oxidative Liver DamageWe also know that, in turn, Nrf2 expression can regulate autophagy.  See for example the March 2013 publication Regulation of Cigarette Smoke (CS)-Induced Autophagy by Nrf2.

15.  Autophagy and aging

We are starting to understand why autophagy stops working well when a person grows old – why autophagy does not work as well as you age.  Among the reasons are:

a. Failure to form autophagosomes – with aging, there appears to be a failure for autophagosomes to form, possibly due to macroautophagy enhancers (glucagon).

b. Failure of fusion – with aging, there appears to be a failure of lysosomes to fuse with autophagosomes.

c. Negative signaling from insulin or insulin receptors – with aging, insulin signaling or insulin receptor signaling activates mTOR in cells.

d. Mitophagy does not work as well in aging.

e. Autophagy decline probably also results in energy (ATP production) decline.

16.  Practical interventions to promote autophagy

There are a number of practical ways to promote autophagy.  Specifically, in partial recap of the above:

  • Fasting activates Autophagy –   caloric restriction affects 5 molecular pathways that activate autophagy
  • Sunlight, Vitamin D and Klotho activate Autophagy – there are three ways through which UV light, Vitamin D, and the Klotho pathway activate autophagy via inhibiting the insulin/IGF-1 pathway
  • Rapamycin activates Autophagy – there are two ways through which mTOR inhibitors activate autophagy –  TORC1 and TORC2 mechanisms
  • Caffeine activates Autophagy – Caffeine can activate autophagy via an mTOR-dependent mechanism
  • Green tea activates Autophagy – ECGC can activate autophagy via an mTOR-dependent mechanism
  • Metformin activates Autophagy – metformin can activate autophagy via AMPK activation – mTOR-dependent and mTOR-independent mechanisms
  • Lithium activates Autophagy –  lithium and other compounds can activate autophagy by inhibiting inositol monophosphate and lower IP3 levels – an mTOR-independent mechanism
  • Resveratrol activates Autophagy – there are four 4 ways through which resveratrol can activate autophagy – via mTOR-dependent and mTOR-independent mechanisms
  • Spermidine activates Autophagy – how spermidine activates autophagy via histone protein deacetylation – mTOR-indepdendent mechanism
  • Hypoxia activates Autophagy –  intermittent hypoxia can increase autophagy via HIF-1a
  • Phytosubstances which activate the Nrf2 pathway can activate Autophagy.  These are many and include soy products and hot chili peppers.

In addition, these lesser-known substances can also activate autophagy:

Amiodarone low dose Cytoplasm – midstream yes Calcium channel blocker =>  TORC1 inhibition.  Also, a mTOR-independent autophagy inducer

  • Fluspirilene low dose Cytoplasm – midstream yes Dopamine antagnoists  => mTOR-dependent autophagy induction
  • Penitrem A low dose Cytoplasm – midstream yes high conductance Ca++activated K+ channel inhibitor => mTOR-dependent autophagy inducer
  • Perihexilenelowdose Cytoplasm- midstream yes 1. TORC1 inhibition
  • Niclosamidelowdose Cytoplasm- midstream yes 1. TORC1 inhibition
  • Trehalose 100 mM Cytoplasm – midstream supplement 1. activates autophagy via an mTOR-independent mechanism
  • Torin-1 low dose Cytoplasm – midstream no 1. mTOR inhibition (much more potent than rapamycin)
  • Trifluoperazine low dose Cytoplasm – midstream  yes Dopamine antagonists => mTOR-dependent autophagy induction

Wrapping it up

Here are some of the main points above covered:

  • Autophagy is like having a Pac man inside each of your cells, chasing down, eating up and recycling dysfunctional organelles, proteins and protein aggregates.  It has three forms: i. chaperone-mediated autophagy, ii. microautophagy and iii. macroautophagy.  The last is the most important one.
  • Autophagy is a stress response and behaves according to the principles of hormesis.
  • Autophagy can retire and eat up old mitochondria which have become electron-leaking engines.
  • Autophagy solves the problem of high baseline levels of reactive oxygen and nitrogen species.
  • Autophagy  does not require proteins to be unfolded for it to work and therefore can perform housekeeping tasks undoable by the other cell-level house cleaning system, the ubiquitin-proteasome system.
  • Autophagy gets rid of the protein aggregates that can make you loose your memory or walk slow as you grow old – those associated with Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, ALS, CTE, and other neurodegenerative conditions.
  • Autophagy keeps adult stem cells healthy and facilitates their capability to differentiate to make normal somatic body cells.
  • Autophagy prevents inflammation – it works hand-in-hand with apoptosis to help the body get rid of dying cells without inducing cell rupture and inflammation.
  • Autophagy prevents cancer – it helps maintain genetic stability, prevents epigenetic gene silencing.  And it helps promote oncogene-induced cellular senescence for cancer prevention.
  • Autophagy saves the lives of cells by preventing unnecessary cellular apoptosis and cell necrosis.
  • Autophagy is involved in Nrf2 activation and to some extent Nrf2 expression negatively regulates autophagy.
  • Autophagy keeps your bone marrow stem cell population alive and functional.
  • Autophagy helps with infections – it helps clear intracellular pathogens such as bacteria and viruses.
  • Autophagy improves the innate immune response.
  • We are starting to understand why autophagy declines with aging.
  • While autophagy declines with aging, it can exercise multiple effects to slow aging down.  It inhibits the major mechanisms of aging such as cellular senescence, protein aggregate build-up, stem cell loss, epigenetic gene silencing, telomere shortening, and oxidative damage to proteins, lipids, and DNA.
  • There are many practical ways to activate Autophagy like consuming green tea and caffeine, and some less-practical ones.



About James Watson

I am a physician with a keen interest in the molecular biology of aging. I have specific interests in the theories of antagonistic pleiotropy and hormesis as frameworks to understand cellular senescence and mechanisms for coping with cellular stress. The hormetic “stressors” that I am interested in exploiting at low doses include exercise, hypoxia, intermittent caloric restriction, radiation, etc. I also have a very strong interest in the epigenetic theory of aging and pharmacologic/dietary maintenance of histone acetylation and DNA methylation with age. I also am working on pharmacologic methods to destroy senescent cells and to reactivate quiescent endogenous stem cells. In cases where there is a “stem cell exhaustion” in the specific niche, I am very interested in stem cell therapy (Ex: OA)

Source: Autophagy – the housekeeper in every cell that fights aging | AGINGSCIENCES™ – Anti-Aging Firewalls™

Alzheimer’s disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer’s disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published [1]. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had had to discontinue work were able to return to work, and those struggling at work were able to improve their performance. The patients, their spouses, and their co-workers all reported clear improvements. Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4-, who were treated with the MEND protocol for 5-24 months. The magnitude of the improvement is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective. These results have far-reaching implications for the treatment of Alzheimer’s disease, MCI, and SCI; for personalized programs that may enhance pharmaceutical efficacy; and for personal identification of ApoE genotype.

Source: Reversal of cognitive decline in Alzheimer?s disease – AGING Journal

Light-harvesting chlorophyll pigments enable mammalian mitochondria to capture photonic energy and produce ATP
Chen Xu, Junhua Zhang, Doina M. Mihai, Ilyas Washington


Sunlight is the most abundant energy source on this planet. However, the ability to convert sunlight into biological energy in the form of adenosine-5′-triphosphate (ATP) is thought to be limited to chlorophyll-containing chloroplasts in photosynthetic organisms. Here we show that mammalian mitochondria can also capture light and synthesize ATP when mixed with a light-capturing metabolite of chlorophyll. The same metabolite fed to the worm Caenorhabditis elegans leads to increase in ATP synthesis upon light exposure, along with an increase in life span. We further demonstrate the same potential to convert light into energy exists in mammals, as chlorophyll metabolites accumulate in mice, rats and swine when fed a chlorophyll-rich diet. Results suggest chlorophyll type molecules modulate mitochondrial ATP by catalyzing the reduction of coenzyme Q, a slow step in mitochondrial ATP synthesis. We propose that through consumption of plant chlorophyll pigments, animals, too, are able to derive energy directly from sunlight.


Determining how organisms obtain energy from the environment is fundamental to our understanding of life. In nearly all organisms, energy is stored and transported as adenosine-5′-triphosphate (ATP). In animals, the vast majority of ATP is synthesized in the mitochondria through respiration, a catabolic process. However, plants have co-evolved endosymbiotically to produce chloroplasts, which synthesize light-absorbing chlorophyll molecules that can capture light to use as energy for ATP synthesis. Many animals consume this light-absorbing chlorophyll through their diet. Inside the body, chlorophyll is converted into a variety of metabolites (Ferruzzi and Blakeslee, 2007; Ma and Dolphin, 1999) that retain the ability to absorb light in the visible spectrum at wavelengths that can penetrate into animal tissues. We sought to elucidate the consequences of light absorption by these potential dietary metabolites. We show that dietary metabolites of chlorophyll can enter the circulation, are present in tissues, and can be enriched in the mitochondria. When incubated with a light-capturing metabolite of chlorophyll, isolated mammalian mitochondria and animal-derived tissues, have higher concentrations of ATP when exposed to light, compared with animal tissues not mixed with the metabolite. We demonstrate that the same metabolite increases ATP concentrations, and extends the median life span of Caenorhabditis elegans, upon light exposure; supporting the hypothesis that photonic energy capture through dietary-derived metabolites may be an important means of energy regulation in animals. The presented data are consistent with the hypothesis that metabolites of dietary chlorophyll modulate mitochondrial ATP stores by catalyzing the reduction of coenzyme Q. These findings have implications for our understanding of aging, normal cell function and life on earth.


Light-driven ATP synthesis in isolated mammalian mitochondria

To demonstrate that dietary chlorophyll metabolites can modulate ATP levels, we examined the effects of the chlorophyll metabolite pyropheophorbide-a (P-a) on ATP synthesis in isolated mouse liver mitochondria in the presence of red light (λmax = 670 nm), which chlorin-type molecules such as P-a strongly absorb (Aronoff, 1950), and to which biological tissues are relatively transparent. We used P-a because it is an early metabolite of chlorophyll, however, most known metabolites of chlorophyll can be synthesized from P-a by reactions that normally take place in animal cells. Control samples of mitochondria without P-a, and/or kept in the dark were also assayed. In the presence of P-a, mitochondria exposed to red light produce more ATP than mitochondria without P-a (Fig. 1A) or mitochondria kept in the dark (supplementary material Fig. S1A–D). Mitochondrial membrane potential (Fig. 1B) and oxygen consumption (Fig. 1C) increased upon increased light exposure in P-a-treated mitochondria. Light or P-a alone had no effect on any of the above measures of mitochondrial activity (supplementary material Fig. S1E–G). With too much added P-a, ATP concentrations and the rate of oxygen consumption started to return to the levels in mitochondria not incubated with P-a (supplementary material Fig. S1G). Addition of the electron transport inhibitor, sodium azide, reduced the light- and P-a-fueled oxygen consumption by 57% (supplementary material Fig. S1H–I), consistent with oxygen consumption occurring through the electron transport system. Observations were consistent with enhanced ATP production driven by oxidative phosphorylation.

Fig. 1.

Chlorophyll metabolite P-a allows isolated mouse liver mitochondria to capture light to make ATP. (A) ATP synthesis in mouse liver mitochondria incubated with P-a (treated) and exposed to light compared to controls (no P-a). Light exposure started at time zero and ADP was added at 30 seconds. Aliquots were obtained at times shown and relative ATP levels measured using the firefly luciferase assay. Means and standard deviations are shown for each time point. The experiment was run in triplicate with the same batch of mitochondria. *P<0.05 for treated versus control samples. (B) Mitochondrial membrane potential (Δψm) under different treatments as measured by safranin fluorescence. Lower fluorescence equals higher membrane potential. Mitochondria, with or without P-a, were exposed to light for 2 minutes or kept in the dark. Safranin was added at time zero and safranin fluorescence was continuously measured while samples remained under the light. The experiment was run in triplicate with the same batch of mitochondria. Curves shown are the average traces for triplicate runs. (C) Representative oxygraph trace (black line) for mitochondria treated with 4 µM P-a. The light was turned on or off at the times indicated by the arrows. Steeper slope denotes faster oxygen consumption. Dotted lines show slopes when the light was off. When the light was turned on the slope of the black line increased by twofold. That is, oxygen consumption increased when the light was turned on. When the light was turned off, oxygen consumption returned to baseline levels (i.e. the two gray lines have the same slope).

To determine whether P-a associates with mitochondria, we measured P-a fluorescence at 675 nm in the presence of increasing amounts of heart mitochondrial fragments obtained from sheep (Fig. 2A,B). After increasing the concentration of mitochondria, P-a fluorescence increased abruptly, by fivefold, and quickly reached a plateau (Fig. 2B). The abrupt change in fluorescence reflects a change in the environment of P-a, consistent with its change from an aqueous environment to one in which it is presumably associated with a protein. This threshold-sensitive behavior is consistent with zero-order ultrasensitivity, or positively cooperative binding, as described by Goldbeter and Koshland, and suggests a coordinated interaction between the metabolite and mitochondrial fragments (Goldbeter and Koshland, 1981). In contrast, this threshold sensitivity was not observed when increasing amounts of bovine serum albumin (BSA) were added to a solution of P-a; instead, fluorescence steadily increased (supplementary material Fig. S1J).

Fig. 2.

Cooperative binding of P-a to mitochondrial fragments. (A) Fluorescence spectra of P-a before and after addition of sheep heart mitochondrial fragments. Upon addition of mitochondrial fragments, the fluorescence intensity of P-a increased and shifted to a longer wavelength, and the shape of the curve (ratio of the shoulder to main peak) changed. (B) Ultrasensitive steady state response of the P-a–mitochondrial interaction. We measured fluorescence intensity for a 1 µM P-a solution while increasing the concentration of mitochondrial fragments. A Hill coefficient of 36, with a 95% confidence interval from 7 to 65, was obtained by fitting the data to the Hill equation [y = axb/(cb+xb)+offset]. Fit (R2): 0.96.

Catabolic reduction of coenzyme Q10 (CoQ10) is a rate limiting step in respiration (Crane, 2001). The majority of CoQ10 molecules exist in two alternate states of oxidation: ubiquinone, the oxidized form, and ubiquinol, the reduced form. To show that the P-a metabolite could catalyze the photoreduction of mitochondrial CoQ10, we measured the oxidation state of CoQ10 in the above sheep heart mitochondrial fragments in response to exposure to red light. We exposed the mitochondria to light for 10 minutes and measured the percentage of reduced and oxidized CoQ10 by high performance liquid chromatography (HPLC) (Qu et al., 2013). In the freshly isolated mitochondria fragments, nearly all the CoQ10 was oxidized in the form of ubiquinone. However, when we incubated the mitochondria with P-a and exposed the suspension to light, 46% of CoQ10 was reduced (Table 1, entry 1). In comparison, as a positive control, we energized the mitochondria with glutamate/malate and kept the suspension in the dark, yielding a 75% reduction of CoQ10 within 10 minutes (entry 2). In the absence of light, no reduction occurred (entry 3). Upon denaturing the mitochondrial proteins with heat, no reduction occurred (entry 4). Likewise, there was a lack of CoQ10 reduction with CoQ10, P-a and light in the absence of mitochondria (entry 5). These observations are consistent with the fluorescence data in Fig. 2A,B, showing that mitochondrial proteins sequester and organize P-a. In the absence of added P-a, a 2–14% reduction was observed, depending on the mitochondrial preparation used (entry 6). We attribute this ‘background reduction’ to the actions of endogenous chlorophyll metabolites, which we were able to detect by fluorescence spectroscopy (see Distribution of light-absorbing dietary chlorophyll, below).

Table 1. Photoreduction of CoQ10 is an early event in light-stimulated ATP synthesis

Light-driven ATP synthesis in rodent tissue homogenates

To determine whether chlorophyll metabolites and light could influence ATP production in whole tissues, we treated mouse brain homogenates with P-a and exposed them to 670-nm light. The treated brain homogenates synthesized ATP at a 35% faster rate than a control homogenate that was not incubated with P-a [relative ATP synthesis rates (means with standard error and 95% confidence intervals (CI) were: treated, 171.7±8.1 (CI: 154.6–188.7); control, 111.3±9.1 (CI: 92.5–130.0); Fig. 3A]. No linear correlation between the increase in ATP concentrations and the amount of added P-a was observed. Increasing concentrations of P-a elicited the same increase in ATP (supplementary material Fig. S2A,B).

Fig. 3.

Chlorophyll metabolite P-a allows mouse brain tissue homogenates to capture light to make ATP. (A) ATP synthesis in mouse brain homogenate with light exposure. Homogenates were incubated with ADP ± P-a and exposed to light starting at time zero. Aliquots were withdrawn at the times shown. Relative ATP in the aliquots was measured using the firefly luciferase assay. The experiment was run in triplicate with the same batch of homogenized brains. Means and standard errors are shown for each time point. For the control, the standard errors are smaller than the line markings and thus cannot be seen. *P<0.05 for treated versus untreated samples. (B) Overlay of the absorption spectrum of P-a (dotted line) and the wavelengths tested for ATP production in samples treated with P-a and exposed to light for 20 minutes. Peak ATP production correlated with peak P-a absorption. Experiments were done in triplicate. Means and standard errors were calculated, however, standard errors are smaller than the markings and thus cannot be seen.

To demonstrate that photon absorption by P-a was necessary to enhance ATP production, we exposed the P-a-treated brain homogenates to greenish (500 nm) and red (630, 670 and 690 nm) light, all with the same total energy. Wavelengths of light that were more strongly absorbed by P-a produced the largest increase in ATP. For example, the ATP concentration increased by ∼16-fold during exposure to 670 nm light; relative to the same sample kept in the dark, it increased by two-to-fivefold during exposure to 500, 630 and 690-nm light of equal energy (Fig. 3B).

In addition to brain homogenates, P-a also enhanced ATP production in adipose, lens and heart homogenates (supplementary material Fig. S2C–E). Quantification of ATP by both the luciferase assay and high-performance liquid chromatography (HPLC) gave similar results (supplementary material Fig. S2E–F).

Distribution of light-absorbing dietary chlorophyll

Chlorophylls and its metabolites, both chlorins, have signature absorption and admission spectra (Aronoff, 1950). Namely they absorb strongly (ε≈50,000 M−1 cm−1) at ∼665–670 nm and demonstrate intense fluorescence emissions at ∼675 nm, which differentiate chlorins from endogenous molecules in mammals (Aronoff, 1950). To examine whether dietary chlorophyll and/or its metabolites were present in animal tissue after oral consumption, we fed mice a chlorophyll-rich diet. Brain (Fig. 4A) and fat (Fig. 4C) extracts from these mice exhibited red fluorescence at 675 nm when excited with a 410-nm light [brain: treated, 15.4±6.7 (n = 6); control: 4.2±2.6 (n = 6; means ± s.d.); P<0.01]. The excitation spectrum of this 675-nm peak (Fig. 4B) was similar to that of known chlorophyll metabolites with an intact chlorin ring: with maxima at 408, 504, 535, 562 and 607 nm. This red fluorescence diminished, as measured by the area under the 675 nm peak, when animals were given a chlorophyll-free diet for 2 weeks. Red fluorescence could also be seen using fluorescence imaging; fluorescence was stronger in the bodies and brains of animals fed chlorophyll than in animals given a chlorophyll-poor diet [Fig. 4D; mean gray value in the boxed areas with standard deviation and minimum and maximum gray value shown in brackets were: treated brain, 118 (97–138); control brain, 82 (60–100); treated back fat pad, 116 (97–132) and control back fat pad, 35 (25–46)]. The red fluorescence was enriched in the gut and intestines, consistent with dietary chlorophyll being the source of the fluorescence.

Fig. 4.

Dietary chlorophyll results in chlorophyll-metabolite-like fluorescence in tissues. (A) Representative fluorescence spectra of brain extracts following excitation at 410 nm. Relative peak areas for a total of six control animals fed a chlorophyll-poor diet and six treated animals fed a chlorophyll-rich diet. (B) Representative excitation spectrum (emission at 675 nm) of a brain extract from mice fed a chlorophyll-rich diet. (C) Representative fluorescence spectra of abdominal fat extracts from mice fed chlorophyll-poor and rich diets. (D) A 675±10-nm fluorescence image of skinned mice raised on chlorophyll-rich and -poor diets.

To determine whether the red fluorescence was localized to mitochondria, we measured the relative 675-nm fluorescence in whole liver homogenates and mitochondria isolated from these homogenates. As measured by fluorescence intensity, isolated mitochondria contained 2.3-fold as much of the 675-nm fluorescent metabolite(s) per milligram of protein as did the whole liver homogenate. This observation suggests that P-a was concentrated in the mitochondria, consistent with data summarized in Fig. 2A,B, and literature reports (MacDonald et al., 1999; Tang et al., 2006).

Fat and plasma extracts from rats fed chlorophyll-rich diets were further analyzed by HPLC to elucidate the source of the red 675-nm fluorescence. Fig. 5A shows a representative chromatogram with compounds in the eluting solvent that displayed 675-nm fluorescence when excited with 410-nm light. Rat fat extracts and plasma extracts both contained similar chlorophyll-derived metabolites (similar chromatograms not illustrated). Two groups of compounds eluting at 23–30 minutes and 40–46 minutes were detected. Compounds eluting between 23 and 30 minutes had similar retention times to those of the chlorophyll metabolites without the phytyl tail, with at least one carboxylate group, such as P-a. The absorption spectra (the locations of the absorbance maxima and the Soret-to-Qy-band ratios) of this group of compounds were consistent with demetalated chlorophylls (Rabinowitch, 1944), as shown in Fig. 5B. In addition, the spectra of this group of peaks were indicative of coordination to a metal ion. A representative spectrum of such a presumably metalated metabolite is shown in Fig. 5C, showing a red shifted Soret band, a blue shifted Qy-band and a Soret-to-Qy-band ratio of ∼1. The compounds eluting between 40 and 46 minutes had similar retention times to that of the demetalated chlorophyll-a standard (pheophytin-a). In addition, these compounds partitioned with hexanes (polarity index = 0.1) when mixed with hexanes and acetonitrile (polarity index = 5.8). This latter characteristic is consistent with a lack of a carboxylic acid group, or an esterified P-a, such as pheophytin-a. Similar HPLC chromatograms from fat extracts of swine fed chlorophyll rich diets (Mihai et al., 2013) were recorded (supplementary material Fig. S2G), suggesting that uptake and distribution of chlorophyll metabolites were not unique to mice and rats.

Fig. 5.

Light-absorbing metabolites of chlorophyll are present in adipose tissue. (A) HPLC chromatogram of an adipose extract. 2.5 grams of abdominal adipose tissue from a rat fed a chlorophyll-rich diet was extracted with acetone and the acetone concentrate subjected to HPLC. In the chromatogram, only compounds that displayed 675-nm fluorescence, characteristic of chlorophyll and its metabolites possessing a chlorin ring, are shown. Five major peaks are observed along with several minor peaks. For peaks with letters, the corresponding absorption spectra are shown below. (B–D) Absorption spectra of labeled peaks in A (b–d, respectively). Numbers above peaks are peak maxima in nm. Numbers in the center are the ratios of the Soret band, around 400 nm, to the Qy band at around 655 nm. All spectra are consistent with those of metabolites of chlorophyll. Spectrum C has been assigned to a metalated porphyrin.

We quantified total blood pigments from rats that absorbed at 665 nm. Using an extinction coefficient of 52,000 at 665 nm (Lichtenthaler, 1987), which is typical of chlorophyll-a-derived pheophytins, we estimated a plasma concentration of 0.05 µM in two rats fed a chlorophyll-rich diet. The 665-nm peak was absent in animals fed a chlorophyll-poor diet. The amount of measured total metabolite was five- and two-times higher than that reported for the fat soluble vitamins K (Tovar et al., 2006) and D (Halloran and DeLuca, 1979), respectively, in the rat.

Light-driven ATP synthesis in C. elegans

Next, we used C. elegans to evaluate the effects of light-stimulated ATP production in a complex organism. As C. elegans age, there is a drop in cellular ATP (Braeckman et al., 1999; Braeckman et al., 2002). We hypothesized that the worm would live longer if it could offset this decline in ATP by harvesting light energy for ATP synthesis. As our model system, we used firefly luciferase-expressing C. elegans, which upon incubation with luciferin emit a luminescence that is proportional to their ATP pools (Lagido et al., 2009; Lagido et al., 2008; Lagido et al., 2001). Upon incubation with P-a, worms incorporated the metabolite, as measured by fluorescence spectroscopy (supplementary material Fig. S3A). To determine whether there were changes in ATP stores in response to light, we plated two groups of worms into 96-well plates containing luciferin substrate. We measured worm luminescence at time zero. We then exposed one group to 660-nm light and kept the other in the dark and periodically measured luminescence in both groups of worms (summarized in Fig. 6A,B). To determine whether ATP increased in light-exposed animals, we subtracted the luminescence signal of the worms kept in the dark from that of the worms exposed to light (Fig. 6C). Worms that were given P-a had a statistically significant increase in ATP when exposed to light, whereas control worms showed no increase. The metabolite alone had no effect on ATP levels when the worms were kept in the dark (i.e. luminescence intensity remained constant throughout the experiment). The elevated luminescence signal persisted for 1 hour after the light was turned off, at which time measurement ceased. However, the luminescence intensity did not further increase during the time the light was off. It was unclear whether this persistent signal reflected the kinetics of the luciferase–luciferin reaction, luciferase expression, or actual ATP pools. Thus ATP was quantified by additional methods.

Fig. 6.

P-a treatment enables worms to capture light to generate ATP. Black lines show results from worms incubated with P-a at the indicated concentrations; gray lines show results from worms not incubated with P-a. (A) In vivo, real-time ATP levels in 1-day-old worms were tracked during exposure to light. Luciferase-expressing worms were incubated with luciferin and exposed to light at time zero. Luminescence was measured at the times shown. Data represent triplicate experiments of 12 separate sets of worms plated in 12 wells of a 96-well pate. Means and standard deviations are shown for each of the three separate runs. (B) In vivo, real-time ATP levels in worms kept in the dark. The same experiment as in A in the same 96-well plate, but the worms were kept in the dark. (C) Percentage ATP increase for worms in A relative to worms in B. (D) In vivo, real-time ATP monitoring. Groups of worms were incubated with or without P-a; light exposure began at time zero and in vivo ATP levels were determined at the times shown in each group of worms by measuring worm luminescence after the addition of luciferin. Each time point represents a different group of worms exposed to light for the times shown. Each experiment was performed in triplicate sets of 12; averages and standard deviations are shown. P-values of Student’s t-tests are also shown, representing the significance compared with the controls at the same light exposure. (E) The same experiment as described in D, but using 10-day-old worms.

As an alternative means of determining whether light stimulated ATP synthesis, we plated luciferase-expressing worms into a 96-well plate without the luciferin substrate, and exposed them to light. ATP status was determined at time zero, immediately before light exposure, and at 15-minute intervals for a total of 45 minutes by adding the luciferin substrate to a group of worms and measuring luminescence (Fig. 6D,E). We found an increase in ATP when 5-day-old and 10-day-old adult worms were fed the metabolite and exposed to light.

We further confirmed the in vivo increase in ATP using two additional ex vivo methods. After light treatment, we lysed the worms, extracted their ATP and quantified ATP in the homogenate using either the firefly luciferase assay or HPLC (supplementary material Fig. S3B,C). Both methods were consistent with the in vivo ATP measurements.

In addition to an increase in ATP, worms treated with P-a exhibited a 13% increase in respiration when exposed to light, as measured by oxygen consumption. However, light had no effect on the respiration rates in untreated worms (supplementary material Fig. S3D). This observation is consistent with an increase in ATP through oxidative phosphorylation, in accordance with the mitochondrial data. Despite the increase in ATP, the levels of reactive oxygen species (ROS) were equivalent in treated and untreated worms during 5 hous of light exposure, as measured using 2′,7′-dichlorofluorescin diacetate (supplementary material Fig. S3E). In fact, although the difference was not statistically significant, treated worms exhibited, on average, lower levels of ROS.

Light harvesting to extend life span

We next tested whether photonic energy absorption by P-a could prolong life. Life span measurements were taken in liquid cultures according to the method of Gandhi et al. and Mitchell et al. (Gandhi et al., 1980; Mitchell et al., 1979). Adult worms were incubated with P-a for 24 hours. Beginning at day 5 of adulthood, we exposed the worms to red light in a daily 5 hours:19 hours light∶dark cycle. Control worms were not given P-a or exposed to light, but otherwise were kept under identical conditions. Counts were made at 2- to 3-day intervals and deaths were assumed to have occurred at the midpoint of the interval. To obtain the half-life, we plotted the fraction alive at each count verses time and fitted the data to a two-parameter logistic function, known to accurately fit survival of 95% of the population (Vanfleteren et al., 1998). The group treated with P-a and light had a 17% longer median life span than the group that was not treated with P-a, but exposed to light (Fig. 7A,B). P-a treatment alone, in the absence of light, had no effect on life span (supplementary material Fig. S4B). Light treatment alone decreased life span by 10% (supplementary material Fig. S4B), in accordance with reports that nematodes survive better in complete darkness (Thomas, 1965). This decrease in median life span brought on by light was reversed when the worms were treated with P-a. The increased median life span with light and P-a was reproducible with different batches of worms (supplementary material Fig. S4B–E). Increasing the amount of P-a past a certain threshold, however, lead to a gradual decrease in lifespan approaching that of animals not treated with P-a (supplementary material Fig. S4B,C).

Fig. 7.

P-a and light increase C. elegans median life span. (A) Median life spans of worms treated with P-a and exposed to light versus those exposed to light but not treated with P-a. Numbers in parentheses are 95% confidence intervals (CI). (B) Life span plots of the values used for A. P-value is from an f-test. Experiments were run in triplicate. The L4 molt was used as time zero for life span analysis. Worms were grown in liquid culture at 500 worms/ml. For counting, aliquots were withdrawn and placed in a 96-well plate to give ∼10 worms per well; the worms were scored dead or alive on the basis of their movement, determined with the aid of a light microscope. A total of 60–100 worms, representing 1–2% of the total population, were withdrawn and counted at each time point for each flask.

We also examined life span longitudinally. We placed 6-day-old adult P-a- and non-P-a-treated worms into a 96-well plate, exposed them to red light for 5 hours per day and compared the percentage dead and alive after 15 days. Result: 47% of the P-a-treated worms were alive (175 alive; 200 dead) after 15 days, versus 41% of the control worms (111 alive; 163 dead), consistent with the cross-sectional experiments above.


Photoreduction of coenzyme Q

Upon incubation of: (1) isolated mouse mitochondria; (2) mouse brain, heart and lens homogenates; (3) homogenized duck fat; and (4) live C. elegans, with a representative metabolite of chlorophyll, light exposure was able to increased ATP concentrations. These observations in a variety of animal tissues perhaps demonstrate the generality of this phenomenon. To synthesize ATP, mitochondrial NADH reductase (complex I) and succinate reductase (complex II) extract electrons from NADH and succinate, respectively. These electrons are used to reduce mitochondrial CoQ10, resulting in ubiquinol (the reduced form of CoQ10). Ubiquinol shuttles the electrons to cytochrome c reductase (complex III), which uses the electrons to reduce cytochrome c, which shuttles the electrons to cytochrome c oxidase (complex IV), which ultimately donates the electrons to molecular oxygen. As a result of this electron flow, protons are pumped from the mitochondrial matrix into the inner membrane space, generating a trans-membrane potential used to drive the enzyme ATP-synthase.

The ‘pool equation’ of Kröger and Klingenberg describes the total rate of electron transfer: Vobs = VoxVred/(Vox+Vred), where Vred is ubiquinone reduction and Vox is ubiquinol oxidation (Kröger and Klingenberg, 1973). Based on this equation, the major roles of complexes I and II can be considered to maintain the mitochondrial ubiquinol pool, and to reduce ubiquinone, which should result in increased ATP synthesis. We reasoned the reduction of CoQ10 could be a potential step in the respiratory pathway in which chlorophyll metabolites could influence ATP levels, as it is known that chlorophyll-type molecules can photoreduce quinones (Chesnokov et al., 2002; Okayama et al., 1967). Indeed, a primary step during photosynthesis is the reduction of the quinone, plastoquinone, by a photochemically excited chlorophyll a (Witt et al., 1963). We hypothesized that if the reduction of mitochondrial ubiquinone could be catalyzed by a photoactivated chlorophyll metabolite, such as P-a, then ATP synthesis would be driven by light in mitochondria with these dietary metabolites. In the proposed mechanism, electrons would be transferred by a metabolite of chlorophyll to CoQ10, from a chemical oxidant present in the mitochondrial milieu. Many molecules, such as dienols, sulfhydryl compounds, ferrous compounds, NADH, NADPH and ascorbic acid, could all potentially act as electron donors. Throughout mammalian evolution, photons of red light from sunlight have been present deep inside almost every tissue in the body. Photosensitized electron transfer from excited chlorophyll-type molecules is widely hypothesized to be a primitive form of light-to-energy conversion that evolved into photosynthesis (Krasnovsky, 1976). Thus it is tempting to speculate that mammals possess conserved mechanisms to harness photonic energy.

Photoexcitation of chlorophyll and derivatives produces the excited singlet state (*1). Oxidative quenching of this singlet state by ubiquinone is possible. Electron transfer could take place through proteins or in solution. Escape from the charge transfer complex and protonation would yield ubisemiquinone, which accounts for 2–3% of the total ubiquinone content of mitochondria (De Jong and Albracht, 1994). Ubisemiquinone can be reduced to ubiquinol by repeating the above sequence or by disproportionation to give one molecule of ubiquinol and one molecule of ubiquinone. Back-electron transfer, from the photoreduced metabolite to the oxidized quinone, could be inhibited by disproportionation or by organizing the chlorophyll derivative and ubiquinol through protein binding. In line with the CoQ10 photoreduction hypothesis, we observed mitochondrial CoQ10 was reduced when isolated mitochondria were exposed to light and P-a (Table 1). Also consistent with light and/or P-a acting upstream of complexes I and II, in isolated mitochondria we observed an increase in ATP in the absence of added electron transport substrates, such as glutamate and malate (Fig. 1A; supplementary material Fig. S1A–C). However, further evidence is needed to confirm this mechanistic hypothesis.

The effect of light in vivo

Intense red light between 600 and 700 nm has been reported to modulate biological processes (Hashmi et al., 2010; Passarella et al., 1984; Wong-Riley et al., 2005), and has been investigated as a clinical intervention to treat a variety of conditions (Hashmi et al., 2010). Exposure to red light is thought to stimulate cellular energy metabolism and/or energy production by, as yet, poorly defined mechanisms (Hashmi et al., 2010). In the presence of P-a, we observed changes in energetics in animal-derived tissues initiated with light of intensity and wavelengths (≈670 nm at ≈0.8±0.2 W/m2) that can be found in vivo when outdoors on a clear day. On a clear day the amount of light illuminating your brain would allow you to comfortably read a printed book (Benaron et al., 1997). In humans, the temporal bone of the skull and the scalp attenuate only 50% of light at a wavelength of ∼670 nm (Eichler et al., 1977; Wan et al., 1981). In small animals, light can readily reach the entire brain under normal illumination (Berry and Harman, 1956; Massopust and Daigle, 1961; Menaker et al., 1970; Vanbrunt et al., 1964). Sun or room light over the range of 600–700 nm can penetrate an approximately 4-cm-thick abdominal wall with only three-to-five orders of magnitude attenuation (Bearden et al., 2001; Wan et al., 1981). Photons between 630 and 800 nm can penetrate 25 cm through tissue and muscle of the calf (Chance et al., 1988). Adipose tissue is bathed in wavelengths of light that would excite chlorophyll metabolites (Bachem and Reed, 1931; Barun et al., 2007; Zourabian et al., 2000). Thus, identification of pathways, which might have developed to take advantage of this photonic energy, may have far-reaching implications.

Dietary chlorophyll in animals

A potential pathway for photonic energy capture is absorption by dietary-derived plant pigments. Little is known about the pharmacokinetics and pharmacodynamics of dietary chlorophyll or its chlorin-type metabolites in human tissues. Here, we observed the accumulation of chlorin-type molecules in mice, rats and swine administered a diet rich in plant chlorophylls (Figs 4, 5; supplementary material Fig. S2G). Data suggests that sequestration from the diets of chlorophyll-derived molecules, which are capable of absorbing ambient photonic energy, might be a general phenomenon.

To date, the reported chlorophyll metabolites isolated from animals have been demetalated (Egner et al., 2000; Fernandes et al., 2007; Scheie and Flaoyen, 2003). The acidic environment of the stomach is thought to bring about loss of magnesium from the chlorophyll (Ferruzzi and Blakeslee, 2007; Ma and Dolphin, 1999). Our absorbance data from extracted pigments from rat fat is consistent with the presence of chlorophyll metabolites bonded to a metal (Fig. 5). If true, the presence of a metal derivative in fat tissue suggests that the pigment was actively re-metalated to take part in coordination chemistry. The identification of several metabolites in the fat and plasma of rats and swine fed a chlorophyll-rich diet that are similar to ones found in plants is significant. However, the structures of the metabolites remain to be elucidated. Chlorin-type molecules are similar in structure and photophysical properties and thus can carry out similar photochemistry (Gradyushko et al., 1970). Our data demonstrate that dietary metabolites of chlorophyll can be distributed throughout the body where photon absorption may lead to an increase in ATP as demonstrated for the chlorin P-a. Indeed, P-a could have been transformed into other metabolites, as most known metabolites of chlorophyll can be formed from P-a by reactions that normally take place in animal cells.

There relationship between the increase in ATP and the amount of added P-a was not linear (supplementary material Fig. S2A,B). ATP stimulation by light in the presence of P-a better fitted a binary on/off, rather than a graded response to P-a. Increasing concentrations of P-a elicited the same increase in ATP, after light exposure. However, with too much added P-a, ATP levels began to fall. This on/off response was also consistent with the observed cooperative binding mode of P-a with mitochondria fragments, suggesting that the threshold response may be regulated by mitochondrial binding of P-a. If chlorophyll metabolites are found to be involved in energy homeostasis, a better understanding of their pharmacodynamics and pharmacokinetics will be needed.

ATP stores and life span

Light of 670 nm wavelength that penetrates the human body, yields ∼43 kcal/mol (1.18×10−22 kcal/photon). Given estimated concentrations of chlorophyll derivatives in the body (Egner et al., 2000; Fernandes et al., 2007; Scheie and Flaoyen, 2003) and the photon flux at 670 nm (Bachem and Reed, 1931; Barun et al., 2007; Bearden et al., 2001; Benaron et al., 1997; Chance et al., 1988; Eichler et al., 1977; Menaker et al., 1970; Vanbrunt et al., 1964; Wan et al., 1981; Zourabian et al., 2000), each chlorophyll metabolite would be expected to absorb only a few photons per second. As such, one might anticipate negligible amounts of additional energy. Organization of chlorophyll metabolites into supramolecular structures, similar to chlorophyll antenna systems in photosynthetic organisms, would increase the effective cross-sectional area of photon absorption and, thus, photon catch. Indeed, our observed positively cooperative binding with mitochondrial fragments is evidence for such organization. Even so, to approach the rate of ATP synthesis powered by NADH or FADH2, sufficient P-a pigment would have to be added to turn animals green. Nevertheless, in model systems, we measure an increase in ATP upon light absorption and changes in fundamental biology (extention in life span). Regardless of the mechanism by which ATP is increased or the measured amount of the increase, perhaps the larger question is: how much of an increase in ATP is enough to make a biological difference?

In animals, treatment with P-a and light both increased ATP and median life span, suggesting that light in the presence of these light absorbing dietary metabolites can significantly affect fundamental biological processes. We previously observed that chlorophyll metabolites enabled photonic energy capture to enhance vision using a mouse model (Isayama et al., 2006; Washington et al., 2004; Washington et al., 2007). Because ATP can regulate a broad range of biological processes, we suspect that ATP modulation also played a role in vision enhancement. The increase in life span may seem contradictory, given that there are studies suggesting that limiting metabolism and ATP synthesis increases the life span of C. elegans. It has been proposed that the life span of this worm might be determined by the metabolic status during development (Dillin et al., 2002) and that there might be a coupling of a slow early metabolism and longevity (Lee et al., 2003). Other observations have led to the hypothesis that increased life span may be achieved by decreasing total energy expenditure across the worm’s entire life span (Van Raamsdonk et al., 2010). However, most studies decrease ATP synthesis from hatching through genetic engineering. By contrast, here, we were able to increase ATP during adulthood at a time when ATP stores reportedly begin to decline. For example, by day 4 of adulthood, the level of ATP and oxygen consumption can drop by as much as 50% compared to day zero (Braeckman et al., 1999; Braeckman et al., 2002). This difference in timing might account for why we observed an increase in life span in response to an increase in ATP. We note that besides caloric restriction, there are only a few interventions that are known (Petrascheck et al., 2007) to increase life span when given to an adult animal.

Alternative mechanisms of life-span extension cannot be ruled out. For example, an increase in reactive oxygen species (ROS) is thought to increase life span in C. elegans (Heidler et al., 2010; Schulz et al., 2007). Upon photon absorption, metabolites of chlorophyll can transfer energy to oxygen, resulting in the generation of singlet oxygen, a ROS. Thus life-span extension seen here might be a result of an increase in ROS due to the generation of singlet oxygen. However, our published data with blood plasma (Qu et al., 2013) and data here from C. elegans do not show an increase in ROS. As ubiquinol is a potent lipid antioxidant (Frei et al., 1990) any ROS increase might be offset by an increase in ubiquinol, generated from the photoreduction of coenzyme Q. Indeed, by producing ubiquinol, P-a might have increased life span by an alternative method by protecting against long-term oxidative damage, which is also a mechanism that has been shown to increase C. elegans life span (Ishii et al., 2004). Further research will be needed to distinguish between the above possible mechanisms.


Both increased sun exposure (Dhar and Lambert, 2013; John et al., 2004; Kent et al., 2013a; Kent et al., 2013b; Levandovski et al., 2013) and the consumption of green vegetables (Block et al., 1992; Ferruzzi and Blakeslee, 2007; van’t Veer et al., 2000) are correlated with better overall health outcomes in a variety of diseases of aging. These benefits are commonly attributed to an increase in vitamin D from sunlight exposure and consumption of antioxidants from green vegetables. Our work suggests these explanations might be incomplete. Sunlight is the most abundant energy source on this planet. Throughout mammalian evolution, the internal organs of most animals, including humans, have been bathed in photonic energy from the sun. Do animals have metabolic pathways that enable them to take greater advantage of this abundant energy source? The demonstration that: (1) light-sensitive chlorophyll-type molecules are sequestered into animal tissues; (2) in the presence of the chlorophyll metabolite P-a, there is an increase in ATP in isolated animal mitochondria, tissue homogenates and in C. elegans, upon exposure to light of wavelengths absorbed by P-a; and (3) in the presence of P-a, light alters fundamental biology resulting in up to a 17% extension of life span in C. elegans suggests that, similarly to plants and photosynthetic organisms, animals also possess metabolic pathways to derive energy directly from sunlight. Additional studies should confirm these conclusions.


General procedures

Two light sources were used for all experiments, either a 300 W halogen lamp equipped with a variable transformer and band pass interference filters [500, 632, 670, 690 nm with full-width half maximum (FWHM) of 10 nm] or a 1.70 W, 660 nm, LED light bulb. Luminous power density was set to 0.8±0.2 W/m2 as measured by a LI-250A light meter (LI-COR Biosciences, Lincoln, NE). The intensity of red light used was 30–60 times less than the level of red light that we measured on a clear March afternoon in New York City and is less than the level that several organs are exposed to in vivo. Pyropheophorbide-a (P-a, 95% purity) was obtained from Frontier Scientific, Logan, UT. For all experiments, prior to exposing samples to light, we minimized light exposure by preparing samples/experiments with laboratory lights turned off, using a minimum amount of indirect sunlight that shone through laboratory windows (>0.001 W/m2).

Animal protocols were approved by the Institutional Animal Care and Use Committee of Columbia University. Mice (ICR, Charles River, Wilmington, MA) weighing 22–28 g and rats (Fisher 344, Harlan Teklad, Indianapolis, IN), weighing 300 g were used. Swine, fed a chlorophyll-rich diet have been described previously (Mihai et al., 2013).

Continuous ATP monitoring in isolated mouse liver mitochondria

Mice were fed a chlorophyll-poor, purified rodent diet supplied by Harlan (Indianapolis, IN) for a minimum of 2 weeks. We isolated mouse liver mitochondria by differential centrifugation according to existing procedures (Frezza et al., 2007) and used only preparations with a minimum respiratory control ratio above 4.0 [state III/II, using glutamate (5 mM final) and malate (2.5 mM final) as measured with an oxygen electrode from Qubit Systems Inc., Kingston, ON, Canada]. Mitochondria at a final concentration of ≈1 mg protein/ml as determined by the Coomassie Plus (Bradford) protein assay (Thermo Fisher Scientific, Rockford, IL) in buffer A (0.250 M mannitol, 0.02 M HEPES, 0.01 M KCl, 0.003 M KH2PO4, 0.0015 M MgAc2·H2O, 0.001 M EGTA, 1 mg/ml fatty acid–poor BSA, pH 7.4) were incubated with P-a for 30 minutes at 0°C. ADP was added (0.5 mM final concentration) and then 250 µl aliquots of this suspension were placed in nine wells of a 96-well plate for exposure to light at room temperature. At various times, 20 µl aliquots were withdrawn, added to 150 µl lysis buffer (10 mM Tris, pH 7.5; 100 mM NaCl; 1 mM EDTA and 1% Triton X-100), and ATP levels were determined with a commercial kit (Invitrogen, Carlsbad, CA) according to the manufacturer’s instructions. Controls were treated in the same way, except they were: (1) incubated at 0°C without P-a (shown), (2) not exposed to light and (3) were incubated without P-a and not exposed to light.

Membrane potential measurement

Mitochondrial membrane potential was monitored in buffer A as described by Feldkamp et al. (Feldkamp et al., 2005). Measurements were made in a 3 ml cuvette placed inside a fluorescence spectrometer (Fluorormax-4, HORIBA Jobin Yvon, Horiba Scientific, Kyoto, Japan) with a final reaction volume of 1 ml. For light exposure, we used a fiber optic light guide to capture and direct light from a 660 nm LED light bulb into the spectrometer. The end of the fiber optic cable was positioned 1 cm above the reaction mixture. Prior to these experiments, light power was measured 1 cm from the end of the fiber optic cable.

Oxygen consumption measurement

Mitochondrial oxygen consumption was measured using an oxygen electrode cuvette (OX1LP-1 ml; Qubit Systems Inc., Kingston, ON, Canada) according to the manufacturer’s instructions. Reactions were run with mitochondria at a concentration of ≈1 mg protein/m’ in buffer A. For light exposure, a 660-nm LED was directed at the plastic [poly-(methyl methacrylate)] chamber.

For inhibition of respiration, sodium azide was added at a final concentration of 0.005 M from a stock solution in water. Sodium azide inhibits cytochrome oxidase (complex IV): oxygen consumption during state 3 respiration is progressively inhibited by increasing concentrations of azide (Bogucka and Wojtczak, 1966).

Analysis of zero-order ultrasensitivity

Mitochondria from sheep hearts were prepared as previously described (Smith, 1967) on two separate occasions from 2 and 1 sheep heart(s) using ‘Procedure 1’. We used mitochondrial fragments to allow P-a direct access to the respiratory chain, to minimize potential complications due to variable rates of P-a import. Mitochondrial isolation started within 1 hour of the death of the animal and the hearts were transported to the laboratory in a bath of 0.25 M sucrose, 0.1 M tris(hydroxymethyl)aminomethane (Tris) at pH 7.5, which was surrounded by ice. Mitochondria were isolated and stored in 250 µl aliquots at a concentration of ∼60 mg of protein/ml in 300 mM trehalose, 10 mM HEPES–KOH pH 7.7, 10 mM KCl, 1 mM EGTA, 1 mM EDTA and 0.1% BSA at −80°C (Yamaguchi et al., 2007) until use. The thawed mitochondria exhibited a respiratory control ratio of ∼1, indicating mitochondrial fragmentation.

Analysis of coenzyme Q redox status

We used sheep heart mitochondria because they contain relatively large amounts of CoQ10, which expedited analysis. For evaluation of CoQ10 redox ratios, frozen mitochondria were thawed at 37°C and diluted with 500 µl buffer A to create a mitochondrial stock solution, which was kept on ice until use. For reactions, 50 µl of this stock suspension was added to 500 µl of buffer A, containing 0.5 µg/ml antimycin A from a 25 µg/ml stock solution in ethanol. Antimycin A binds to the Qi site of cytochrome c reductase (complex III), thereby inhibiting the upstream oxidation of any produced ubiquinol. Pa was added (25 µM final concentration) from a 1.3 mg/ml stock solution in DMSO. The suspension was added to a test tube, mixtures purged with argon and the reactions initiated by placing the tube between two LED light bulbs (previously described). We irradiated the samples for 10 minutes at room temperature. For negative controls, we repeated the above sequence changing the following: (1) in the absence of light; (2) in the absence of added P-a; (3) with heat denatured mitochondria; and (4) in the absence of added mitochondria but with added coenzyme Q. For a positive control we added 10 µl of a stock solution of 0.25 M glutamate/0.125 M malate in Tris buffer at pH 7. For mitochondrial denaturing, 200 µl of stock mitochondrial suspension was purged with argon and placed in a bath at 70°C for 5 minutes. For control reactions without added mitochondria, a coenzyme Q stock solution in buffer A was prepared by adding ALL-QTM (DSM Nutritinal products, Switzerland), a water-soluble coenzyme Q solution containing 10% coenzyme Q, modified food starch, sucrose and medium chain triglycerides, to buffer A. For these reactions 50 µl of the water-soluble Coenzyme Q stock or the denatured suspension was used as above in place of the mitochondrial stock solution. All reactions were adjusted to give the same amount of coenzyme Q in the reaction mixture as measured by HPLC.

To quantify relative ubiquinone and ubiquinol concentrations, a 50 µl aliquot was taken from the reaction mixture and was added to 200 µl of 0.4 M perchloric acid and 100 µl isopropyl ether containing 1 mg of butylated hydroxytoluene/ml as an antioxidant. The solution was vortexed for 1 minute, centrifuged for 2 minutes at 15,000 r.p.m. and the organic phase analyzed by HPLC. HPLC conditions have been reported previously (Qu et al., 2009; Qu et al., 2011). Briefly, we used an isocratic elutent consisting of 1% sodium acetate 3% glacial acetic acid, 5% butanol in methanol at 0.6 ml/minute. The HPLC column was 50×2.1 mm, C-18, 2.6 u, 100 Å (Phenomenex, Torrance, CA). A PDA detector set at 290 nm for ubiquinol and 275 nm for ubiquinone was used. We determined relative ubiquinol and ubiquinone concentrations by their online absorption spectra using extinction coefficients of 14,200 M−1 cm−1 at 275 nm in ethanol for ubiquinone and 4640 M−1 cm–1 at 290 nm in ethanol for ubiquinol (Lester et al., 1959).

Analysis of ATP synthesis in mouse brain homogenates

To produce homogenates of mouse brain, the frontal lobe was homogenized using two strokes of a Potter S homogenizer (Sartorius AG, Goettingen, Germany) at 4°C (20 mg of brain to 1 ml buffer A). The homogenate (80 µl) was added to buffer A (920 µl) and treated as described above for liver samples. Reactions were run in triplicate and data obtained between 5 and 50 minutes after lysis. ATP production showed a linear increase during this time, which was fitted to a line, the slope of which is reported as the relative ATP synthesis rate.

Analysis of ATP synthesis in mouse lens and heart homogenates

Lenses from mice were homogenized (KONTES® DUALL® tissue grinder with glass pestle) in ATP assay buffer (0.15 mM sucrose, 0.5 mM EDTA, 5 mM magnesium chloride, 7.5 mM sodium phosphate, 2 mM HEPES) at 50 µl buffer per lens. We added 1 µl of P-a stock (1 mM) and 1 µl of ADP stock (10 mM) to 100 µl lens homogenate. The mixture was exposed to red light (671 nm at 0.8 W/m2) or kept in dark for 20 minutes. ATP concentrations were determined using a luciferase-based ATP quantification kit according to the manufacture’s instructions (Life Technologies, Grand Island, NY).

Heart tissue (20 mg) was homogenized as above in 1 ml ATP assay buffer. 10 µl of P-a (1 mM) and 10 µl of ADP (10 mM) and 940 µl of ATP assay buffer were added into 40 µl tissue homogenate. The mixture was exposed to red light and ATP was determined as described above using a luciferase based ATP kit.

Analysis of ATP concentrations in duck adipose

We removed visceral fat from a duck (Anas platyrhynchos domestica) less then 30 minutes after death by decapitation and homogenized the fat at 4°C (without buffer) in a loose-fitting Potter-Elvehjem homogenizer. We then added P-a (70 µl of a 3.3 mg/ml stock solution) and ADP (800 µl of a 10 mg/ml stock solution). The homogenate was divided into two groups: one group was kept in the dark, while the other was exposed to red light (671 nm at 0.8 W/m2); both dishes were kept at 37°C. 200-µl aliquots were taken from each dish and ATP was measured using the luciferase assay or by HPLC, as described in the literature (Ally and Park, 1992).

Analysis of the effect of light wavelength

The entire brain of a mouse was homogenized with a Dounce homogenizer (20 mg of brain to 1 ml buffer C: 0.15 mM sucrose, 0.5 mM EDTA, 5 mM MgCl2, 7.5 mM Na2HPO4, 2 mM HEPES) at 4°C. We took a 40-µl aliquot of the homogenate and added it to 940 µl buffer C. We added 10 µl P-a (from a 1 mM stock in DMSO) and placed the sample on ice for 1 hour. We then added 10 µl ADP (from a 10 mM stock). Five 100-µl portions of the suspension were added to each well of a 96-well plate and exposed to light for 40 minutes. Then, 20-µl aliquots of the mixture were lysed with 200-µl lysis buffer for 1 hour on ice, and ATP levels were determined as above using a luciferase-based ATP kit.

Analysis of red fluorescence in tissue extracts

The chlorophyll-rich diet (Harlan Teklad, Indianapolis, IN) contained 15% by weight spirulina [a food supplement produced from cyanobacteria (Ciferri, 1983)], which is equivalent to ∼0.15% by weight chlorophyll-a. The control diet was a purified diet devoid of dietary chlorophylls (Harlan Teklad). The swine chlorophyll-rich diet has been described previously (Mihai et al., 2013).

For fluorescence spectroscopy, five pigs each were given these respective diets ad libitum for 2 weeks. Whole brain or 2–7 grams of abdominal fat was homogenized with a hand-held homogenizer (Omni Micro Homogenizer (μH), Omni International, Kennesaw, GA), HPLC grade acetone (40 ml) was added and the sample was vortexed for 1 minute. Insoluble material was precipitated by centrifugation and the acetone evaporated with a rotary evaporator. The samples were resuspended in 3 ml chloroform and measured directly.

For HPLC and UV spectroscopy, we extracted 2.5 grams of fat, as described above, from rats or swine that had been given a chlorophyll-rich diet, to give a clear oil. We then added 10 ml of absolute ethanol, cooled the sample to −20°C for 30 minutes, pelleted the insoluble material by centrifugation, separated and evaporated the ethanol with a rotary evaporator and re-suspended the sample in 500 µl of absolute ethanol. For plasma, we added 4 ml of plasma to 1 ml of saturated NaCl and 10 ml ethyl acetate, vortexed the sample for 1 minute and separated the layers by centrifugation. We removed the ethyl acetate layer, evaporated the ethyl acetate and re-suspended the resulting film in 300 µl of absolute ethanol. The samples were then used for HPLC and UV spectroscopy. A Waters (Milford, MA) HPLC system with a 600 pump, a 2475 fluorescent detector, a 2998 photodiode array (PDA) detector and a C18, 2.6 u, 100 Å, 150×2.10 mm column (Phenomenex, Torrance, CA) was used for HPLC. Excitation was set to 410 nm and emission set to 675 nm. Absorbance between 275 and 700 was recorded. We used a mobile phase of acetonitrile containing 10% isopropyl alcohol and 0.1% formic acid (solvent A) and water containing 0.1% formic acid (solvent B). Compounds were eluted at a flow rate of 0.3 ml/minute with a 50∶50 mixture of A∶B for 5 minutes, which was changed linearly to 100∶0, A∶B over 15 minutes. At 35 minutes, the flow was increased to 0.5 ml/minute.

In vivo imaging

Animals were imaged with a Maestro™ In-Vivo Imaging System (CRi, Hopkinton, MA), as described by Bouchard et al.; the animals were skinned to reduce interference from skin autofluoresence (Bouchard et al., 2007).

General C. elegans maintenance

Worms were a gift from Dr Cristina Lagido (Department of Molecular and Cell Biology, University of Aberdeen Institute of Medical Sciences, Foresterhill, Aberdeen, UK) (Lagido et al., 2009; Lagido et al., 2001). Nematode husbandry has been described previously (Wood, 1988). Briefly, animals were maintained on nematode growth medium (NGM) agar (Nunc) using E. coli strain OP50 as a food source. To obtain synchronous populations, we expanded a mixed population on egg yolk plates (Krause, 1995). Worm eggs were isolated from the population by treatment with 1% NaOCl/0.5 M NaOH solution (Emmons et al., 1979) and transferred to a liquid culture with E. coli strain OP50, carbenicillin (50 µg/ml) and amphotericin B (0.1 µg/ml; complete medium).

Real-time ATP monitoring in C. elegans

We administered the P-a chlorophyll metabolite by adding it to the culture medium for a minimum of 24 hours. To confirm P-a uptake, we washed away the culture medium containing P-a, suspended the worms in fresh medium and determined the fluorescence spectra in the worms. Treated worms had signature chlorophyll-derived fluorescence, whereas control worms that were not given P-a exhibited no such fluorescence, confirming metabolite uptake.

Method A

Worms were grown in liquid culture at a density of 10,000 worms/ml. Twenty-four hours before the experiment, the culture was split into control and treatment groups and varying amounts of a P-a stock solution in DMSO were added to the treated groups. Control worms were given DMSO vehicle. Worms were washed with M9 buffer (IPM Scientific, Eldersburg, MD) to remove food and unabsorbed P-a and resuspended at 3000 worms/ml. 50 µl of worm suspension from each of these groups were plated into a well of a 96-well plate. Each experimental group was plated into a minimum of 12 wells. To assay ATP stores by luminescence, 100 µl of luminescence buffer containing D-luciferin was added to each well, according to the literature (Lagido et al., 2009; Lagido et al., 2001) and luminescence was recorded in a plate reader. The luminescence buffer was a citric phosphate buffer at pH 6.5, 1% DMSO, 0.05% Triton X-100 and D-luciferin (100 µM). After initial ATP measurements, half of the worms from each experimental group were exposed to LED light centered at 660 nm at 1±2 W/m2; the other half was kept in the dark by covering the plate with aluminium foil. ATP (luminescence signal) was recorded periodically. The amount of ATP synthesized was reported as the difference within an experimental group between the luminescence signal of worms kept in the dark and the worms exposed to light. All experimental procedures outside of red light exposure were performed under dim light. The experiment was repeated three times with different populations of worms.

Method B

Worms were plated as above, with each experimental group divided into 12 wells of a 96-well plate. Four identical 96-well plates were made, each containing worms treated with varying concentrations of P-a and control worms. At time zero, 100 µl of luminescence buffer was added to a plate and in vivo ATP was assayed as luminescence. The remaining three plates were exposed to light and ATP assays were performed every 15 minutes for 45 minutes by the addition of 100 µl of luminescence buffer and the recording of luminescence.

In vitro ATP monitoring in C. elegans

One-day-old adult worms in liquid culture were incubated with P-a for 24 hours, washed with M9 buffer and re-suspended in M9 buffer at 50,000 worms/ml. The control group was incubated in DMSO vehicle without P-a. 100 µl of each worm suspension was placed into 18 centrifuge tubes. At time zero, six tubes from each group were placed in liquid nitrogen and the remaining tubes exposed to red light. Then, at 15 and 30 minutes, six tubes from each group were placed into liquid nitrogen. To measure ATP, we removed the centrifuge tubes from the liquid nitrogen and placed them in boiling water for 15 minutes to lyse the worms (Artal-Sanz and Tavernarakis, 2009). The resulting solution was cleared by centrifugation for 5 minutes at 15,000 rpm and ATP in the lysate was measured using the luciferase assay according to the manufacturer’s instructions or by HPCL according to established protocols (Ally and Park, 1992).

Analysis of C. elegans oxygen consumption

Oxygen consumption was measured using a Clark-type oxygen electrode (Qubit Systems Inc.), as described (Anderson and Dusenbery, 1977; Zarse et al., 2007). One-day-old adult worms in liquid culture at a density of ∼10,000 worms/ml were incubated with P-a (25 µM) for 24 hours in complete medium. Animals were washed three times with M9 buffer to remove bacteria and excess P-a and resuspended in M9 buffer at 10,000 worms/ml. One-ml aliquots of this suspension were transferred into the respiration chamber and respiration was measured at 25°C for 10 minutes while being exposed to an LED light centered at 660 nm at 1±2 W/m2. The control group was treated in the same way but not incubated with P-a.

Analysis of ROS formation in C. elegans

ROS formation was quantified as described by Schulz et al. (Schulz et al., 2007). Three-day-old worms were synchronized in liquid culture at a density of 500 worms/ml in complete medium, then divided into control and treatments groups. The treatment group was incubated for 24 hours with 12 µM P-a and the control group in DMSO vehicle. Bacterial food and P-a were removed by three repeated washes with M9 and the worms resuspended to 500 worms/ml M9 buffer. 50 µl of the suspension from each group was added to the wells of a 96-well plate with opaque walls and a transparent bottom. A 100 µM 2′,7′-dichlorofluorescin diacetate (Sigma-Aldrich, St. Louis, MO) solution in M9 buffer was prepared from a 100 mM 2′,7′-dichlorofluorescin diacetate stock solution in DMSO. 50 µl of this solution were pipetted into the suspensions, resulting in a final concentration of 50 µM. Additional controls included worms without 2′,7′-dichlorofluorescin diacetate and wells containing 2′,7′-dichlorofluorescin diacetate without animals; these were prepared in parallel. Five replicates were measured for each experimental and control group. Immediately after addition of 2′,7′-dichlorofluorescin diacetate, the fluorescence was measured in a SpectraMax M5 microplate reader (Molecular Devices, LLC, Sunnyvale, CA) at excitation and emission wavelengths of 502 and 523 nm. The plates were then exposed to red LED light and fluorescence was re-measured at 2.5 and 5 hours under conditions equivalent to those used previously.

Life span analysis

Population studies

Life span measurements were performed according to the method of Gandhi et al. and Mitchell et al. (Gandhi et al., 1980; Mitchell et al., 1979) with some modifications. Eggs were harvested and grown in darkness in a liquid culture at room temperature. To prevent any progeny developing, 5-fluoro-2′-deoxyuridine (FUDR) (Sigma-Aldrich, 120 µM final) was added at 35 hours after egg isolation, during the fourth larval molt. At day 4 of adulthood, the culture was split into control and experimental groups. The experimental group was treated with 12 µM P-a from a stock solution in DMSO. The control group was given the DMSO vehicle alone. The treated and control cultures were then split into two or three. The final density of worms in all reaction flasks was 500 worms/ml; each flask contained 10 ml, therefore a total of 5000 worms. The following day (day 5 of adulthood), worms were exposed to LED light centered at 660 nm at 1±2 W/m2 for 5 hours. Light exposure was repeated every day until the end of the experiment. For counting, aliquots were withdrawn and placed in a 96-well plate to give ∼10 worms per well; the worms were scored dead or alive on the basis of their movement, determined with the aid of a light microscope. A total of 60–100 worms (representing 1–2% of the total population) were withdrawn and counted at each time point for each flask. Counts were made at 2–3-day intervals and deaths were assumed to have occurred at the midpoint of the interval. Any larvae that hatched from eggs produced before the FUDR was added remained small in the presence of FUDR and were not counted. We used the L4 molt as time zero for life span analysis. To obtain the half-life, we plotted the fraction alive at each count verses time and fitted the data to a two-parameter logistic function using the software GraphPad Prism (GraphPad Software, Inc., La Jolla, CA). The two-parameter model is known to fit survival of 95% of the population fairly accurately (Vanfleteren et al., 1998). Because changes in environment, such as temperature, worm density and the amount of food, can influence life span, control measurements were conducted at the same time under identical conditions. The concentration of P-a dropped (∼75%) throughout the life span studies and it was not adjusted (supplementary material Fig. S4F).

Life span measurements in 96-well microtiter plates

Life span was measured as described in the literature (Solis and Petrascheck, 2011), except that P-a was added at day 4 and light treatment commenced at day 5. Scoring (fraction alive) was done once on day 15.


  • Competing interests

    The authors declare no competing interests.

  • Author contributions

    C.X. conducted studies with worms, and ATP measurements in mitochondria and tissue homogenates. J.Z. conducted ATP measurements in mitochondria and tissue homogenates. D.M. conducted metabolite-binding distribution studies. I.W. designed and supervised the study and wrote the manuscript.

  • Funding

    This work was supported by the Department of the Navy, Office of Naval Research [grant number N00014-08-1-0150 to I.W.]; the Nanoscale Science and Engineering Initiative of the National Science Foundation [grant numbers CHE-0117752, CHE-0641532 to I.W.]; and the New York State Office of Science, Technology and Academic Research (NYSTAR).

  • Supplementary material available online at

  • Received April 30, 2013.
  • Accepted October 15, 2013.


Sunlight is the most abundant energy source on this planet. However, the ability to convert sunlight into biological energy in the form of adenosine-5′-triphosphate (ATP) is thought to be limited to chlorophyll-containing chloroplasts in photosynthetic organisms. Here we show that mammalian mitochondria can also capture light and synthesize ATP when mixed with a light-capturing metabolite of chlorophyll. The same metabolite fed to the worm Caenorhabditis elegans leads to increase in ATP synthesis upon light exposure, along with an increase in life span. We further demonstrate the same potential to convert light into energy exists in mammals, as chlorophyll metabolites accumulate in mice, rats and swine when fed a chlorophyll-rich diet. Results suggest chlorophyll type molecules modulate mitochondrial ATP by catalyzing the reduction of coenzyme Q, a slow step in mitochondrial ATP synthesis. We propose that through consumption of plant chlorophyll pigments, animals, too, are able to derive energy directly from sunlight.

Source: Light-harvesting chlorophyll pigments enable mammalian mitochondria to capture photonic energy and produce ATP | Journal of Cell Science

Though research on migraines has come a long way, the reason why some people are much more prone to them is largely still a mystery. Physicians will often try to find the cause of recurrent migraine attacks by evaluating patients for other underlying medical conditions, food intolerances and sleep problems.

New research suggests doctors may want to consider screening for something even more simple: vitamin deficiencies. Recent work presented June 10 at the 58th Annual Scientific Meeting of the American Headache Society in San Diego finds that certain vitamin supplements could potentially help stop the occurrence of frequent migraines.

In a study on children, teens and young adults, the researchers found migraineurs (people who suffer from frequent migraine headaches) were much more likely to have mildly lower levels of vitamin D, riboflavin (B-2) and coenzyme Q10 (a naturally occurring, vitamin-like enzyme made by the body). All of these vitamins are needed for the mitochondria, the energy production centers of our cells, to function properly. “Deficient function, possibly through vitamin deficiency or over-utilization of vitamins, may put the migraineur at increased risk of energy deficiency,” says Dr. Andrew Hershey, director of the Migraine Center at the Cincinnati Children’s Hospital Medical Center and one of the researchers working on the project.

For the study, researchers at Cincinnati Children’s looked at existing data on 7,691 young patients who were migraine sufferers and their records of blood tests for baseline levels of vitamin D, riboflavin, coenzyme Q10 and folate. Of the study participants, 15 percent were found to have riboflavin levels below the standard reference range. A significant number of patients—30 percent—had coenzyme Q10 levels at the low end of the standard reference range. Significantly lower vitamin D was seen in nearly 70 percent of the patients.

The researchers also found that patients with chronic migraines were more likely to have coenzyme Q10 deficiencies than patients who had episodic migraines. Girls and young women were more likely than boys and young men to have coenzyme Q10 deficiencies at baseline. Boys and young men were more likely to have vitamin D deficiency, but the reasons behind these trends need further investigation. It is important to note that both Q10 and D3 can be created in the body by exposure to the sun.

Sunlight is the most abundant energy source on this planet. However, the ability to convert sunlight into biological energy in the form of adenosine-5′-triphosphate (ATP) is thought to be limited to chlorophyll-containing chloroplasts in photosynthetic organisms. Here we show that mammalian mitochondria can also capture light and synthesize ATP when mixed with a light-capturing metabolite of chlorophyll. The same metabolite fed to the worm Caenorhabditis elegans leads to increase in ATP synthesis upon light exposure, along with an increase in life span. We further demonstrate the same potential to convert light into energy exists in mammals, as chlorophyll metabolites accumulate in mice, rats and swine when fed a chlorophyll-rich diet. Results suggest chlorophyll type molecules modulate mitochondrial ATP by catalyzing the reduction of coenzyme Q, a slow step in mitochondrial ATP synthesis. We propose that through consumption of plant chlorophyll pigments, animals, too, are able to derive energy directly from sunlight

From here PUBMED

What if conventional wisdom regarding our most fundamental energy requirements has been wrong all along and we can directly harness the energy of the Sun when we consume ‘plant blood’?

Plants are amazing, aren’t they? They have no need to roam about hunting other creatures for food, because they figured out a way to capture the energy of the Sun directly through these little light-harvesting molecules known as chlorophyll; a molecule, incidentally, which bears uncanny resemblance to human blood because it is structurally identical to hemoglobin, other than it has a magnesium atom at its core and not iron as in red blooded animals.

The energy autonomy of plants makes them, of course, relatively peaceful and low maintenance when compared to animal life, the latter of which is always busying itself with acquiring its next meal, sometimes through violent and sometimes through more passive means. In fact, so different are these two classes of creatures that the first, plants, are known as autotrophs, i.e. they produce their own food, and the animals are heterotrophs, i.e. they depend on other creatures for food.

autotroph and heterotroph

While generally these two zoological classifications are considered non-overlapping, important exceptions have been acknowledged. For instance, photoheterotrophs — a sort of hybrid between the autotroph and heterotroph — can use light for energy, but cannot use carbon dioxide like plants do as their sole carbon source, i.e. they have to ‘eat’ other things. Some classical examples of photoheterotrophs include green and purple non-sulfur bacteria, heliobacteria, and here’s where it gets interesting, a special kind of aphid that borrowed genes from fungi[1] to produce it’s own plant-like carotenoids which it uses to harness light energy to supplement its energy needs!

To learn more about this amazing creature read the study published in 2012 in Scientific Reports titled, “Light- induced electron transfer and ATP synthesis in a carotene synthesizing insect.”


A green carotenoid tinted aphid that is capable of capturing sunlight to produce energy. Interesting right?  But we need not look for exotic bacteria or insects for examples of photoheterotrophy. It turns out that animals, including worms, rodents and pigs (one of the closest animals to humans physiologically), have recently been found to be capable of taking up chlorophyll metabolites into their mitochondria, enabling them to use sunlight energy to ‘super-charge’ the rate (up to 35% faster) and quantity (up to 16-fold increases) of ATP produced within their mitochondria. In other words, a good portion of the animal kingdom is capable of ‘feeding off of light,’ and should be reclassified as photoheterotrophic!

The truly groundbreaking discovery referred to above was published last year in the Journal of Cell Science in a study titled, “Light-harvesting chlorophyll pigments enable mammalian mitochondria to capture photonic energy and produce ATP“, [contact me for the full version:] which I reported on recently, and which completely overturns the classical definition of animals and humans as solely heterotrophic.

Light-harvesting chlorophyll pigments enable mammalian mitochondria to capture photonic energy and produce ATP

Animals are Not Just Glucose-Burning Biomachines, But Are Light-Harvesting Hybrids

For at least half a century it has been widely believed among the scientific community that humans are simply glucose-dependent biomachines that can not utilize the virtually limitless source of energy available through sunlight to supplement our energy needs. And yet, wouldn’t it make sense that within the extremely intelligent and infinitely complex design of life, a way to utilize such an obviously abundant energy source as sunlight would have been evolved, even if only for the clear survival advantage it confers and not some ethical imperative (which is a possibility worth considering … vegans/Jainists, are you listening?).

As the philosopher of science Karl Popper stated, a theory can only be called scientific if it is falsifiable. And indeed, the scientific theory that humans are solely heterotrophic has just been overturned in light of empirical evidence demonstrating that mammals can extract energy directly from sunlight.

Deeper Implications of the New Study

First, let’s start by reading the study abstract, as it succinctly summarizes what may be of the most amazing discoveries of our time:

Sunlight is the most abundant energy source on this planet. However, the ability to convert sunlight into biological energy in the form of adenosine-59-triphosphate (ATP) is thought to be limited to chlorophyll-containing chloroplasts in photosynthetic organisms. Here we show that mammalian mitochondria can also capture light and synthesize ATP when mixed with a light-capturing metabolite of chlorophyll. The same metabolite fed to the worm Caenorhabditis elegans [roundworm] leads to increase in ATP synthesis upon light exposure, along with an increase in life span. We further demonstrate the same potential to convert light into energy exists in mammals, as chlorophyll metabolites accumulate in mice, rats and swine when fed a chlorophyll-rich diet. Results suggest chlorophyll type molecules modulate mitochondrial ATP by catalyzing the reduction of coenzyme Q, a slow step in mitochondrial ATP synthesis. We propose that through consumption of plant chlorophyll pigments, animals, too, are able to derive energy directly from sunlight.”

And so, to review, the new study found that animal life (including us, mammals) are capable of borrowing the light-harvesting capabilities of ‘plant blood,’ i.e. chlorophyll and its metabolites, and utilize it to photo-energize mitochondrial ATP production. This not only helps to improve energy output, but the research found several other important things:

  • Despite the increased output, the expected increase in Reactive Oxygen Species (ROS) that normally attends increased mitochondrial function was not observed; in fact, a slight decrease was observed. This is a highly significant finding, because simply increasing mitochondrial activity and ATP output, while good from the perspective of energy, may accelerate aging and other oxidative stress (ROS) related adverse cellular and physiological effects. Chlorophyll, therefore, appeared to make animal mitochondria function in a healthier way.
  • In support of the above finding, worms administered an optimal range of chlorophyll were found to have significant extended life span. This is in accordance with well-known mechanisms linked to improved mitochondria function (in the absence of increased ROS) that increases cell longevity.

The last point in the abstract above is especially interesting to me. As a fan of coenzyme q10 supplementation for sometime, I have noticed profound differences qualitatively between ubiquinone (the oxidized form) and ubiquinol (the reduced, electron rich form), the latter of which has lead me to experience far greater states of energy and well-being than the former, even at far lower quantities (the molecular weight of a USP isolate does not reveal its bioavailability nor biological activity). The study, however, indicates that one may not need to take supplemental coenzyme Q10, even in its reduced form as ubiquinol, because chlorophyll-mediated sunlight capture and subsequent photo-energization of the electron transport chain will naturally ‘reduce’ (i.e. donate electrons) ubiquinone converting it into ubiquinol, which will result in increased ATP production and efficiency. This may also explain how they observed no increase in ROS (reactive oxygen species) while increasing ATP production: coenzyme q10 in reduced form as ubiquinol is a potent antioxidant, capable of donating an electron to quench/neutralize free radicals. This would be a biological win-win: increased oxidative phosphyloration-mediated energy output without increased oxidative damage.

From here: GreenMedInfo

And of course see more at Nutrition Facts

Hershey says the study adds to an ongoing observation that a significant number of people with migraines have lower levels of these vitamins. However, this trend is not seen in all patients across the board.

It’s been suggested for some time that vitamins play a role in this painful and debilitating chronic condition, but research on the topic is inconsistent. For example, a 2014 analysis in BioMed Research International of seven previously published papers on migraines and vitamin D deficiency suggested there isn’t enough evidence to back the claim that lower levels of the vitamin could make a person more prone to migraines. The researchers of that study found vitamin D deficiency  in 13.2 to 14.8 percent of migraine patients. These rates didn’t differ widely from the general population.

Even though evidence is limited, the nutraceutical industry has picked up on the potential for vitamins to alleviate and control migraines. A number of over-the-counter supplement cocktails are currently marketed to migraine sufferers. These typically combine the vitamins identified in this study, as well as magnesium, an organic mineral that when deficient has also been found to increase risk for chronic migraines. One study published in May in International Clinical Psychopharmacology found the odds of acute migraine headaches increased 35.3 times in patients who were identified as magnesium deficient. However, Hershey questions the use of magnesium supplements for treating migraines because he says only about 1 percent is absorbed by the body, and it is also difficult to measure in the blood.

In general, taking these vitamin supplements at recommended doses probably can’t hurt, but much more research is needed to determine whether vitamins alone could help stop migraines. One challenge researchers face is that vitamin supplements are often an intervention used in addition to medications and other experimental therapies. It’s therefore difficult to determine whether improvements in the condition can be explained for reasons other than supplement use

Source: Vitamin Deficiencies May Prompt Chronic Migraines

A 60-year-old Beachwood woman whose parents lost their memories at about age 70 wrote for advice, worried she might lose her memory, too. There are ways to minimize that possibility, even though one in five will experience some form of brain drain, ranging from fuzzy thinking to Alzheimer’s disease.

While some causes of memory loss are genetic, you can build a bigger brain and postpone memory loss. One study found that there are nine risk factors for Alzheimer’s, ranging from obesity to inflammation to plaque in the arteries, and most of them are modifiable.

Because your brain is plastic (a good word in brain talk), it is flexible enough to grow and strengthen if you empower it to do so. Some specific tactics for creating a brain built for a centenarian follow:

• Avoid foods with sugar. Sugar for the slightly and very diseased brain is like cocaine; short-term increases in sugar improve function, but chronic, slightly raised sugar levels, even if you don’t have diabetes or pre-diabetes, will affect your memory. That excess blood glucose in that sugar doughnut (made worse by its saturated fat) and from the sugar in your coffee cause inflammation, which damages brain cells. Higher blood sugar is linked to a smaller hippocampus, which means poorer ability to form and store new memories. The same thing (or at least its rat equivalent) occurs when mouse were fed the equivalent of a liter of sugared soda a day.

• Manage stress or eradicate your stressor. Stress is the greatest cause of memory loss linked to a shrinking hippocampus. It seems that the inflammation caused by stress prunes old and makes new connections for establishing memories more difficult. You can use meditation and behavioral modification to control your reaction to stressful events, or learn to deal with the stress and eradicate its cause or causes.

• Do physical activity. Any physical activity for 45 minutes three times a week, even walking, expands your hippocampal region. New data would indicate that maybe intense exercise for 20 seconds three times in a 10-minute period three times a week may be even better, but check with your doctor before increasing the intensity of your exercise program.

• Learn something new. Try a new skill, hobby or game, or even try to find new directions – without GPS – to a place you visit regularly. These will create more connections that also help enlarge your hippocampus, lowering your risk of memory loss.

• Take in enough magnesium, foliate, B12, B6, and Vitamin D3. Magnesium ensures strong links between your brain cells, so you have a big network ready to solve problems. You need 420 milligrams daily, but most of us fall short. Turn to brown rice, almonds, hazelnuts, spinach, shredded wheat, lima beans, and bananas to top off your tank, or just get ½ a multimineral and vitamin supplement twice a day. The B vitamins are key for brain functioning, too. Vitamin D3, like DHA Omega-3, protects your DNA and seems to prevent damage from free radicals (rogue oxygen molecules that attack DNA). Aim for 1,000IU daily from a D3 supplement. Get it measured; you want to aim for a level over 35.

• Don’t short-change sleep. When you’re busy, it’s easy to say the thing you want to sacrifice is sleep. But you need sleep for lots of reasons, and one of the biggies is that it acts as a brain scrub and gets your brain in condition for optimal learning, problem-solving and memory.

Source: Avoid sugar, boost intelligence | Health |

Testosterone is the main male sex hormone, but females also have small amounts of it.

It is a steroid hormone, produced in men’s testicles and women’s ovaries (1).

The adrenal glands also produce small amounts.

During puberty in boys, testosterone is one of the main drivers of physical changes like increased muscle, deeper voice and hair growth.

However, having optimal levels is also important throughout adulthood and even during old age.

In adults, healthy levels are important for general health, disease risk, body composition, sexual function and just about everything else (1, 2, 3, 4, 5, 6, 7).

Additionally, increasing your testosterone levels can cause rapid gains in muscle mass and vitality in only a matter of weeks (8, 9, 10).

Interestingly, it also plays an important role in female health and sexual well-being (11, 12, 13).

The research is pretty conclusive: both genders should ensure they have healthy levels of testosterone, especially as they age (13, 14).

Here are 8 evidence-based ways to increase testosterone levels naturally.

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1. Exercise and Lift Weights

Exercise is one of the most effective ways to prevent many lifestyle-related diseases. Interestingly, it can also boost your testosterone.

A large review study found that people who exercised regularly had higher testosterone levels. In the elderly, exercise increases testosterone levels, fitness and reaction time (15, 16).

Fit Young Man Lifting Weights

New research in obese men suggests that increased physical activity was even more beneficial than a weight loss diet for increasing testosterone levels (17).

Resistance training, such as weight lifting, is the best type of exercise to boost testosterone in both the short- and long-term (18, 19).

High-intensity interval training (HIIT) can also be very effective, although all types of exercise should work to some extent (18, 19, 20, 21, 22).

Taking caffeine and creatine monohydrate as supplements may further boost your levels when combined with a training program (23, 24).

Bottom Line: All forms of exercise may increase your testosterone levels. Weight lifting and high-intensity interval training are the most effective.

2. Eat Protein, Fat and Carbs

Plate of Fish, Potatoes and Broccoli

What you eat has a major impact on testosterone as well as other hormone levels (25).

Therefore, you must pay attention to your long-term calorie intake and diet strategy.

Constant dieting or overeating may disrupt your testosterone levels (26, 27, 28, 29, 30).

Eating enough protein can help maintain healthy levels and aid in fat loss, which is also associated with your testosterone (28, 31, 32).

Carb intake also plays a role, with research showing carbs can help optimize testosterone levels during resistance training (22, 33).

However, research demonstrates that sufficient healthy fats are also beneficial for testosterone and health (25, 34, 35, 36, 37).

A diet based mainly on whole foods is best, with a healthy balance of fat, protein and carbs. This can optimize both hormone levels and long-term health.

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Bottom Line: Don’t overeat and don’t restrict calories too much for too long. Try to eat balanced amounts of carbs, fat and protein.

3. Minimize Stress and Cortisol Levels

Research is always highlighting the dangers of long-term stress, which can elevate levels of the hormone cortisol (38, 39, 40).

Unnatural elevations in cortisol can quickly reduce testosterone. These hormones work in a seesaw-like manner: as one goes up, the other comes down (40, 41, 42).

Stress and high cortisol can also increase food intake, weight gain and the storage of harmful body fat around your organs. In turn, these changes may negatively impact your testosterone levels (43, 44, 45).

For both optimal health and hormone levels, you should try to reduce repetitive stressful situations in your life.

Focus on a diet based on whole foods, regular exercise, good sleep, laughter and a balanced lifestyle, all of which can reduce stress and improve your health and testosterone levels (46, 47, 48, 49, 50).

Bottom Line: High levels of stress are bad for your long-term health and can reduce your testosterone levels.

4. Get Some Sun or Take a Vitamin D Supplement

Bottle of Vitamin D Capsules

Vitamin D is quickly becoming one of the world’s most popular vitamins.

Research has shown that it has various health benefits, and may also work as a natural testosterone booster (51, 52, 53, 54, 55).

Despite its importance, nearly half of the US population is deficient in vitamin D, and an even higher percentage has sub-optimal levels (56, 57).

A 12-month study found that supplementing with around 3,000 IU of vitamin D3 per day increased testosterone levels by around 25% (54).

In the elderly, vitamin D and calcium also optimized testosterone levels, which led to a reduced risk of falling (58).

To boost testosterone and reap the other benefits of vitamin D, try to get regular exposure to sunlight or take around 3,000 IU of a vitamin D3 supplement daily.

More information on vitamin D here: Vitamin D 101 — A Detailed Beginner’s Guide.

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Bottom Line: Vitamin D3 supplements may boost testosterone levels, especially in the elderly and people who have low blood levels of vitamin D.

5. Take Vitamin and Mineral Supplements

Young Man with a Pill and a Glass of Water in Hand

Although the benefits of multivitamins are hotly debated, specific vitamins and minerals may be beneficial (59).

In one study, zinc and vitamin B supplements increased sperm quality by 74%. Zinc also boosts testosterone in athletes and those who are deficient in zinc (60, 61, 62).

Other studies also suggest vitamins A, C and E can play a role in your sex hormone and testosterone levels, although more research is needed (25, 63, 64, 65).

Out of all the vitamins and minerals available, the research on testosterone shows vitamin D and zinc supplements may be best (54, 66, 67).

Bottom Line: Vitamin D and zinc have the strongest evidence as testosterone boosters. Other micronutrients may also have benefits, but require further research.

6. Get Plenty of Restful, High-Quality Sleep

Silver Alarm Clock

Getting good sleep is just as important for your health as diet and exercise (68, 69, 70, 71, 72, 73).

It may also have major effects on your testosterone levels.

The ideal amount of sleep varies from person to person, but one study found that sleeping only 5 hours per night was linked to a 15% reduction in testosterone levels (73).

One long-term study observed that those who slept only four hours per night had borderline deficient levels (46).

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Other long-term studies support this. One study calculated that for every additional hour of sleep you get, testosterone levels rise 15% higher, on average (74, 75).

Although some people seem to do fine with less sleep, research suggests around 7–10 hours of sleep per night is best for long-term health and your testosterone.

Bottom Line: Make sure you get plenty of high-quality sleep to maintain healthy testosterone levels and optimize your long-term health.

7. Take Some of These Natural Testosterone Boosters

Bottle of Herb Capsules

Only a few natural testosterone boosters are supported by scientific studies.

The herb with the most research behind it is called ashwagandha.

One study tested the effects of this herb on infertile men and found a 17% increase in testosterone levels and a 167% increase in sperm count (76).

In healthy men, ashwagandha increased levels by 15%. Another study found it lowered cortisol by around 25%, which may also aid testosterone (77, 78).

Ginger extract may also boost your levels. It is a delicious herb that also provides various other health benefits (79, 80, 81, 82, 83).

Most of the research on ginger has been done in animals. However, one study in infertile humans found that ginger can boost testosterone levels by 17% and increase levels of other key sex hormones (80, 84).

Other popular herbs that are supported by some studies in both animals and humans include horny goat weed, Mucuna pruriens, shilajit and tongkat ali.

Yet it’s important to note that most of the positive research has been conducted in mice or infertile humans with low testosterone levels.

If you have healthy testosterone function and normal levels, it is unclear whether you will benefit much from these supplements.

Bottom Line: Several herbal supplements are a natural way to boost testosterone for those with infertility or low levels.

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8. Follow a Healthy Lifestyle and Avoid Estrogen-like Compounds

BPA Free Logo

There are several other factors that may affect your hormone levels.

A healthy sex life plays an important role in regulating your sex hormone and testosterone levels (85, 86).

High exposure to estrogen-like chemicals may also affect your levels, so try to minimize daily exposure to BPA, parabens and other chemicals found in some types of plastic (86, 87, 88, 89).

It’s probably no surprise that excess alcohol or drug use, whether it’s medical or recreational, can also decrease testosterone levels (90, 91, 92, 93, 94, 95).

In contrast, laughter, happiness and success may help boost your health and testosterone levels — so make sure they’re a part of your daily life (96, 97, 98, 99).

Bottom Line: Reducing exposure to estrogen-like chemicals, alcohol and drugs can positively affect your testosterone levels and health.

Why Do Testosterone Levels Matter?

From the age of 25–30, a man’s testosterone levels naturally start to decline.

This is a problem because strong research shows a link between low testosterone and obesity, increased disease risk and premature death.

Healthy testosterone levels are also important for women, along with other key hormones such as estrogen and progesterone.

Therefore, everyone should take the necessary lifestyle steps to optimize testosterone levels. You will improve your health and body at the same time.

The article “8 Proven Ways to Increase Testosterone Levels Naturally” appeared first on

Testosterone is the main male sex hormone, but females also have small amounts of it. It is a steroid hormone, produced in men’s testicles and women’s ovaries (1). The adrenal glands also produce small amounts.

Source: 8 Proven Ways to Increase Testosterone Levels Naturally

The weird history of vitamin D | IOL

Washington – As you soak in rays of sunshine, your thoughts may turn to vitamin D – because you probably know it has something to do with the sun. But do you actually know what it is?

Humans are kinda capable of photosynthesis, and they use it to produce what scientists believe to be the oldest hormone that has ever existed on earth. It’s vitamin D, and it’s been around 750 million years, ever since tiny phytoplankton began cranking out the stuff in what is now the Atlantic Ocean.

Scientists aren’t sure exactly why vitamin D developed, but one theory is that it functioned as a kind of early sunscreen. It also helped with another stumbling block on the evolutionary road out of the water and on to land: calcium. Going from the calcium-rich environment of the sea on to dry land presented certain difficulties, namely getting enough of it, and it just so happens that the production of vitamin D in the body changes the ability of calcium to get into each cell. This likely made more of the calcium already present in the body usable.

Much like the noble phytoplankton, when rays from the sun strike your body you (along with amphibians, reptiles, all bird species, and most mammals) “photosynthesise” vitamin D to allow the body to metabolise calcium. It isn’t actually the same process by which plants create food from sunlight, but it is literally a form of photosynthesis – the use of light to synthesise a chemical.

So necessary is this process to life on this planet that some have theorised the dinosaurs died out in part because – when the debris from an infamous asteroid blocked out the sun – the creatures couldn’t produce enough vitamin D to carry on.

After all, it was tiny, nocturnal rodents that survived the dinosaurs – and then the apocalypse – to give rise to the age of mammals, and such organisms would have already sorted out how to acquire enough vitamin D without abundant sunlight.


So what is vitamin D, anyway?

First, a word on vitamins: The story of vitamins begins with a bunch of scientists trying to understand what we now know as deficiency syndromes, like scurvy and beriberi. Their work differentiating these types of diseases from those of an infectious nature led to our modern understanding of vitamins as organic compounds (that’s organic as in carbon-containing, not as in “the more expensive bananas.”) Vitamins are compounds that an organism requires for survival and cannot make enough of itself.

Today, there are 13 vitamins (that we know of) that keep the ol’ human meat sack in running order – vitamins that must be consumed, because the body cannot make enough to meet meat sack demands. But vitamin D is a weird one: Your body can make just plenty, provided some sunshine and perhaps a bit of nudity.

We can make all the vitamin D we need by flashing bare skin at a carcinogenic ball of plasma nearly 93 million miles away, but we can also get some of it from our food. And if you’re ever wondered how a blast of midday UVB rays to the epidermis can get your body to synthesise the same compounds food chemists are out there fortifying milk with, then today is your lucky day.

The modern understanding of vitamin D begins with a bunch of researchers torturing puppies in the name of science. Yes, really. Aren’t you glad you started down this sunny rabbit hole?

Rickets, a disease that causes bones to soften, became especially prevalent as the industrial revolution sent child workers indoors and factory pollution began to blot out the sun. When a rash of urban children developed skeletal deformities, researchers stepped up to find the cause and figure out a solution.


Enter the puppies

In 1919, a scientist named Edward Mellanby successfully induced rickets in puppies by feeding them only bread and low-fat milk, noting that the resulting bone imaging and physical appearance of the dogs mimicked that of children suffering from rickets. Supplementing the diets of the wee puppers with yeast and orange juice (for B vitamins and scurvy-prevention, respectively) did nothing to stave off the bone disease; however, supplementation with both butterfat and cod liver oil did the trick. And with that, rickets was officially outed as a disease of deficiency. And where there’s a deficiency, so too there must be a vitamin to be deficient in.

Today we know that rickets can be caused by a lack of or malfunction in the metabolism of phosphorus or calcium, and that the syndrome primarily results from vitamin D deficiency. During the early 20th century, it was discovered that certain foods – like cod liver oil and whole milk – could heal rickets, but then research threw science a little curveball: it seemed as if going outside could also cure the disease.

In a most plant-like fashion, the bodies of these factory-working tykes could use sunlight to make an essential vitamin.

The term vitamin D refers to a group of fat-soluble steroids with a special “broken ring” formation. The shape of the compound is notable because it helps the body absorb critical nutrients like calcium, iron, magnesium, phosphorus and zinc through the gut wall. This is all well and good, and explains in part why we add vitamin D to calcium-rich milk, but what does any of this have to do with sunlight?

As mentioned, there are two avenues to acquiring vitamin D: food and sun. And while yes, fatty fish flesh is a decent source of vitamin D compared to other foods – few of which naturally contain the compound – the bulk of vitamin D is produced in the skin thanks to a process known as photosynthesis, photodissociation, photolysis, and – my personal favourite – photodecomposition.


Here’s how it works:

Human skin contains a compound that functions as a precursor to vitamin D, called 7-dehydrocholesterol; the compound is also a precursor to cholesterol. (Cholesterol gets a bad rap for giving bankers heart attacks, but is, in fact, completely necessary for the production of steroid hormones like androgens and estrogens, among other things.)

When light from our neighbourhood star lands on the skin, a specific portion of the light is able to transform 7-dehydrocholesterol into vitamin D3 by breaking a bond in the precursor molecule. The light that can do this is ultraviolet, meaning the length of the waves in which it travels are too short for the human eye to see. Specifically, it’s the UVB portion of the spectrum, which moves at a faster wavelength than its slower cousin, UVA rays. Simply put, sunlight breaks a bond in a molecule in your skin and then your body uses the new, sun-altered compound to manage its calcium needs.

And that’s how your body uses the photons streaming out of a 6 billion year old star to make its own vitamin D.

It doesn’t take much time to make enough vitamin D, if you time your light exposure correctly and you live in the right place. For a pale person – they make vitamin D the fastest – around 10 minutes in the midday summer sun with their arms and legs exposed is enough to make 50 times the vitamin D you need in a day. (But don’t worry, it’s impossible to OD on vitamin D in the sun.)

However, even though it’s astronomically easy for most people meet their vitamin D needs on a nice day, vitamin D deficiency is rampant in modern life. This is a significant problem, as those with the lowest levels of the vitamin may have more than twice the risk of death from heart disease, compared to those with the highest levels.

And while it doesn’t take much summer light to make lots of the vitamin, those north of Atlanta are virtually doomed to not synthesise enough of the vitamin during the wintertime. This is because the angle of the light hitting the earth makes it so UVB rays cannot penetrate the atmosphere; this can be mitigated with supplementation, but has always struck me as curious, given that people have been living in darker, colder areas for millennia without the synthetic bolstering of vitamin D levels.

Then I remember that cultures in the darkest, coldest parts of the world often eat a lot of fatty fish – a great source of vitamin D.

Researchers estimate that many Americans are vitamin D-deficient, which can lead to heart trouble, cognitive impairments in older adults, severe asthma in children, increased risk of cancer, and, of course, rickets. One 2010 study found 41 percent of Americans to be vitamin D deficient, a staggering number with wide-reaching implications for an already-burdened healthcare system.

All the more reason to get outsideto make like a plant and photosynthesise

How exactly do human beings get Vitamin D from the sun?

Source: The weird history of vitamin D | IOL

About one man in seven will be diagnosed with prostate cancer during his lifetime and the average age at the time of diagnosis is about 66.

Source: Vitamin D3 appears to fight prostate cancer – Hammond Star: Columnists

Let’s take a look at the top stories trending on the health channel.

Source: Healthbeat: Vitamin D3 is good for the heart

BOCA RATON, FL–(Marketwired – May 12, 2016) – Cubic Pharmaceuticals, a company based in the UK that focuses on developing and distributing high-quality, unique medicines and supplements, announced its Cubicole D3 is more available in the US Market than ever, on and the supplement can help people manage depression.

“It is incredible that research has found Vitamin D to be effective with anti-depressants and to help manage the disorder. It is unbelievably important in this day and age to have more effective treatments for depression when millions of people worldwide are diagnosed with it,” said Saumil Bhatt, CEO of Cubic Pharmaceuticals.

An international study has discovered taking Vitamin D can have a potential impact on mental health and clinical depression according to a recent article on Vitamin D had been found to increase the effectiveness of antidepressants and Dr. Jerome Sarris, who led a study by ARCADIA Mental Health Research Group at the University of Melbourne, described the results as significant.

Sarris discovered Vitamin D, also known as the sunshine vitamin, has been found to boost mood in combination with anti-depressants. These results were determined after researchers examined 40 clinical trials worldwide, where participants were prescribed with Vitamin D, some other nutraceuticals and placebo pills. Participants who took the Vitamin D supplement experienced less symptoms of depression than those taking the placebo.

Results of the trial is linked to certain receptors in the brain for vitamin D and these receptors are found in the areas of the brain that are linked to the development of depression. For this reason, vitamin D has been linked with depression, according to the Vitamin D Council, and the supplement may increase the amount of monoamines, which can help treat depression.

“People with depression now have a Vitamin D supplement to try in combination with medication to bring results and better treat their condition. I hope with Cubicole D3 more people can treat depression than ever,” Bhatt said.

Cubic Pharmaceuticals Ltd was founded in 2008 and by two pharmacists, Mr. Arun Jangra and Mr. Anwar Ali, who brought in their substantial experience of pharmacy and formulations whilst working with NHS. Since its inception, Cubic Pharmaceuticals Ltd has distributed and traded Ethical, Generics, OTC and Unlicensed Medicinal Products (SPECIALS) sharing knowledge and experiences. For more about the brand, visit:

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Source: Cubicole D3 Vitamin D Supplement May Help Treat Depression

Dr Gitte Bloch Rasmussen, Aarhus University Hospital, Denmark

The news was announced in Rome today by the Danish medical doctor and PhD Gitte Bloch Rasmussen, speaking at ECTS 2016, the 43rd annual congress of the European Calcified Tissue Society (ECTS).

Dr Rasmussen was reporting on trials that had been conducted among 193 women with low levels of vitamin D, who were all planning pregnancy and all attended a single centre in Aarhus, Denmark. The trials had been conducted by Dr Rasmussen with colleagues from Aarhus University Hospital, in Denmark.

Dr Rasmussen said:

Fertile women are often found to have low vitamin D levels, which are associated with low birth weight, reduced fertility and adverse pregnancy outcomes. Our aim was to look at the effects of vitamin D supplements on these areas in women with low levels of vitamin D.

The 193 women were aged 20 – 40, were planning pregnancy and had levels of 25-hydroxyvitamin D (known as 25OHD, the most accurate way to measure vitamin D levels) below 50 nmol/L, which is bordering on insufficiency. Before conceiving, they were allocated to groups, one being given a 70mcg daily supplement of vitamin D3 and one a 35mcg daily dose, with matching groups given placebos. The women continued the trial until 16 weeks after birth and were evaluated for their 25OHD level, birth weight, fertility and any complications.

56% of the women conceived within 12 months, 38% in the placebo group, 29% taking the 70mcg supplement and 33% taking the 35mcg supplement. 44% did not conceive.

Dr Rasmussen continued:

We found a noticeable difference in two of the four areas we evaluated. Whilst the lower daily dose of vitamin D3 did not significantly affect the chances of pregnancy, the higher 70mcg daily supplement significantly reduced the chances of conceiving. On the other hand, supplementation showed to be beneficial on risk of complications during labour, as these were significantly less frequent in the combined vitamin D3 groups (a 23% risk) than in the placebo group (a 52% risk).

However, birth weight did not differ significantly between those treated with vitamin D3 and those receiving placebos; there were also no differences between groups on any safety measures.

Dr Rasmussen concluded:

High doses of vitamin D3 may reduce the likelihood of conceiving, but may also be associated with fewer complications during childbirth, though without improving birth weight.

New research has established that high doses of vitamin D supplements can lead to fewer complications during childbirth but reduce a woman’s chances of getting pregnant in the first place.

Source: High doses of vitamin D supplements could lead to fewer birth complications but reduce fertility

Say someone came up to you selling a dietary supplement—a pill that you take once a day—that could boost your energy, improve your body’s ability to repair its DNA, and keep you healthier as you get older.

It might sound like a scam, or more likely just another in a sea of confusing, undifferentiated claims that make up the $20 billion dollar supplement industry.

But let’s say that someone is MIT’s Lenny Guarente, one of the world’s leading scientists in the field of aging research. And he’s being advised by five Nobel Prize winners and two dozen other top researchers in their fields. You might pay a little more attention.

Elena Ray via Shutterstock

The Scientist And The Startup

Cofounding a supplement company seems an unlikely career move for someone like Guarente, a man who is one of the most well-respected scientists in his field. (“It is a departure,” Guarente admits). Mostly, for him, getting involved in Elysium Health is a decision born out of opportunity and frustration. The opportunity is the chance to make a difference by translating findings in the booming field of aging research directly to consumers today. The frustration is that doing this has taken so long in the first place.

“My biggest hope is that we can make available to people something that is currently unavailable, and that it will have a positive impact on their health,” Guarente says.

Elysium Health actually had its beginnings in conversations between its other two, younger cofounders, Eric Marcotulli and Dan Alminana, who were then tech investors and gym buddies. Even though they’re both quite health-conscious, they knew they couldn’t halt the march of aging and all the ailments that come with it. Far more than diet or anything else people can control, the biggest risk factor for many of the diseases that kill us—including diabetes, cancer, and cardiovascular disease—is simply getting older.

Straight 8 Photography via Shutterstock

Marcotulli knew something about the market opportunity too, which has also lately attracted the likes of Google (with its Calico Labs project) and other SIlicon Valley investors. He had studied the story of a company called Sirtris Pharmaceuticals, which in the mid-2000s was working to take resveratrol, the natural anti-aging compound found in red wine, and alter it into a more potent form that could be patented and developed into a medical drug. In 2008, Sirtris—founded by Guarente’s former postdoc David Sinclair—was acquired by the drugmaker GlaxoSmithKline for a jaw-dropping $720 million.


Learn More

“The fundamental question was: Are there other natural products out there that could be meaningful? I think resveratrol was the first, and I was thinking there’s maybe the potential for many others,” Marcotulli remembers thinking as he studied the story while in business school.

The two started cold-calling scientists involved in aging research and were surprised how many were enthusiastic about the idea, including Guarente. The FDA doesn’t recognize aging itself as a condition, so, instead, companies like Sirtris and GSK are are taking scientific findings about how we age and translating them into drugs that treat specific age-related diseases. The issue is that the clinical trials involved in doing this can take more than a decade, and even then that is no guarantee a drug will be approved. The result has been that, though scientists have made major strides in understanding how and why we age and demonstrating that this aging can be delayed, they’ve so far seen few results in translating their work to help people.

The two entrepreneurs wanted to take a very different approach than the drug makers: sell only unaltered natural products, which generally aren’t patented and don’t need FDA approval, and create new kinds of supplements that make no claim to treat a specific disease but promote general wellness instead.

“If there’s a benefit that can be had now, then I think it doesn’t make sense to wait a decade or more until some derivative [from a drug company] becomes available—though I’m not saying that’s not a good thing to do too” says Guarente.

The three cofounders have been taking the company’s first product, a pill they are calling BASIS, for the last three to five months. Through its website, Elysium Health will sell a one-month supply to consumers for $60, or $50 with a monthly subscription.

Boosting NAD

The theory behind the pill is built on work first pioneered in Guarente’s lab on sirtuins, a group of enzymes involved in cell metabolism and energy production that are common to a wide range of living organisms. Researchers have found that boosting the activity of sirtuins, which is sometimes done by calorie restriction diets, can extend lifespan of yeasts, worms, mice, and other animals. Efforts to develop a drug that can have the same effect, without the lack of calories, have been going on for the last two decades, including at Sirtris and GlaxoSmithKline. There are also natural compounds that elevate sirtuins—one is resveratrol, which is already sold as a dietary supplement today. Another is called NAD.

NAD—Nicotinamide adenine dinucleotide—is one of the most compelling bits of chemistry related to aging. Its presence in the body is directly correlated with the passage of time: An elderly man will have about half the levels of NAD is his body as a young person. There’s no amount of healthy eating or exercise that can stop the decline. But in a scientific paper published in 2013 that generated headlines about “reversing aging,” Harvard’s Sinclair showed that after a week of giving two-year-old mice a boost of NAD, their tissues looked more like six-month-old mice.

Elysium’s pill is an attempt to replicate that process naturally in humans. It contains the building blocks of NAD, so the body can easily absorb the smaller molecules and synthesize its own. The pill also contains pterostilbene, a compound, that is a close relative of resveratrol, but which Guarente says is potentially more potent and effective.

Elysium explicitly wants to avoid the charlatan feel of the countless “anti-aging” products on the market today. It isn’t selling the pill as a key to a longer life or to preventing any particular disease, since there isn’t any evidence the pill will do that. A press release the company put out with its launch hardly mentions aging at all. (Another reason is they want to appeal to young people too, who don’t necessarily care about aging, but may want to feel healthier and more energetic). Instead, the founders talks about enhancing basic biological functions: improving DNA repair, cellular detoxification, energy production, and protein function.

“We have no interest in being an anti-aging company and extending lifespan,” says Marcotulli. “For us this is about increasing healthspan, not lifespan.”

The Future Of Dietary Supplements

There is a downside to the model: They can’t patent their work. Some companies already sell supplements for each of the two ingredients in BASIS, and others could copy Elysium as soon as it releases its next products. That’s where Elysium’s business model— and its scientific superstars—come in.

The company aims to be very different type of dietary supplement company—the founders cite the hip, design savvy consumer brands Warby Parker, Oscar Health, Harry’s, and Nest as their role models. (Warby Parker co-CEO Dave Gilboa and one of its early investors, Kal Vepuri, are angel investors in Elysium. Martin Lotti, creative director for Nike’s soccer division, is a strategic advisor.)

“Our vision and mission is to bring scientifically validated natural health products to market through these traditional retail channels,” says Marcotulli. “But it also takes the best aspects of the pharmaceutical model—the R&D focus, clinical rigor, and following these consumers over time.”

Its products will only be sold on its website, where Elysium can control more nuanced messaging than on store shelves. Branding, trust, and scientific expertise are what the team hopes differentiates them from the faceless companies that line Whole Foods’ shelves. At the most basic level, that means trust that the pill contains what it says it contains, but also beyond that, trust that it is doing a person any good.

Elysium assures the ingredients in its products will all be pure, and it will do its own safety testing, as well as test for a basic level of efficacy. Already, says Guarente, it has tested BASIS at a range of doses for safety and to assure that NAD levels in the body actually increase from taking its pill. Over time, the team hopes to also collect data back from customers to start demonstrating some of the longer-term benefits over months and eventually years.

Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine, says Elysium has a good business idea based on sound science and an impressive team. As someone who is not involved in the company, his one fear is that if something went wrong with a top scientist like Guarente’s name attached, it might set back the whole field of research. Though not required by the FDA, he urges the company to go above and beyond in all of its testing. “People are going to overuse it, and I’m sure if you have too much of it, it could have some effect we can’t predict,” he says.

For Elysium’s next products, which might touch on other areas such as brain health or musculoskeletal health, it will start to tap into the expertise of the formidable list of more than 30 scientific advisors signed on—everyone from Eric Kandel, a brain scientist who received the 2000 Nobel Prize in medicine to Tom Sudhof, a cellular physiologist at Stanford who received the prize in 2013. Eventually, it hopes to expand this network of scientific expertise further to as many scientists that want to get involved.

If anything, Elysium might make more people aware that aging is becoming something that we may one day treat.

“There has been an explosion of science in the field of aging. And I think the public doesn’t really realize how far aging research has come. We have a lot of ideas about the mechanisms of aging, and tons and tons of pathways that can be optimized, tweaked, or activated to possibly extend lifespan,” says Stanford University aging researcher Stuart Kim, who is on Elysium’s scientific advisory team. “I think the public is probably about 30 years behind our thinking about aging. It’s as if we thought about cancer in the way we did in 1960.”

Source: One Of The World’s Top Aging Researchers Has A Pill To Keep You Feeling Young | Co.Exist | ideas + impact

Fish oil, Vitamin D and other nutrients appear to raise the potency of medication

The multibillion-dollar supplement industry spews many dubious claims, but a new study suggests that some nutritional supplements, including omega-3 fatty acids and vitamin D, may boost the effectiveness of antidepressants. If so, the supplements might help relieve symptoms for the millions of people who don’t immediately respond to these drugs.

The meta-analysis—published Tuesday in the American Journal of Psychiatry—reviewed the results of 40 clinical trials that evaluated the effects of taking nutritional supplements in conjunction with several major classes of antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants. It revealed that four supplements in particular upped the potency of the medications, compared with a placebo.

The researchers, based at Harvard University and the University of Melbourne, found the strongest evidence for an omega-3 fish oil called eicosapentaenoic acid, or EPA. In general, people with depression who took an antidepressant drug and an omega-3 sourced from fish oil experienced a significant reduction in their symptoms as assessed by a the Hamilton Depression Rating Scale, a common measure used by most of the studies in the review. The same was true, although to a lesser extent, for S-adenosylmethionine, methylfolate (a form of the B vitamin folic acid) and Vitamin D. A few isolated studies found some benefit from augmenting treatment with creatine, while adding zinc, vitamin C, the amino acid tryptophan and folic acid produced mixed results. The authors deemed all of these supplements relatively safe.

Lead study author Jerome Sarris of the University of Melbourne’s ARCADIA Mental Health Research Group notes that a large percentage of people with depression do not fully respond during one or two trials of an antidepressant. By some estimates, two-thirds don’t respond to the first antidepressant they try and a third fail to get better after several treatment attempts. “The implications are that clinicians and the public can consider [adding] therapeutic doses of nutrients such as omega-3s as a potential low-cost approach to reducing depression in people who are non-responsive to antidepressants,” he says.

Sarris and his colleagues speculate that the supplements may enhance the efficacy of antidepressants in various ways, perhaps directly by altering neurostransmitter activity or indirectly by reducing inflammation, known to contribute to depression. Leading nutritional psychiatry researcher Felice N. Jacka of Deakin University and the University of Melbourne explains that conditions like depression can trigger a cascade of physical concerns that certain supplements, when combined with accepted antidepressant therapies, could help mitigate.

“Serious illnesses such as major depression can result in increased inflammation and oxidative stress, which can in turn result in nutritional deficiencies and a depletion of essential fatty acids,” she notes. “Nutrients form the substrate of the essential biological processes of the body and brain, so ensuring that nutrient levels are adequate in patients suffering from any serious illnesses is important.”

Doctors and scientists often come down hard on nutritional supplementation. There is little to no scientific evidence backing many of the products crowding the shelves at health food stores and pushed by celebrity doctors. In fact, many come in mega-doses associated with serious side effects. And countless manufacturers produce these supplements, many with no standardized processes and varying degrees of quality control.

Indeed, the supplement industry exists largely outside of any oversight by the Food and Drug Administration (FDA). In December last year, the FDA announced the formation of a new Office of Dietary Supplement Programs to help tighten regulation, but for now when it comes to supplements, consumers often don’t know what they are getting.

Sarris acknowledges that supplements can differ greatly in quality and that his results should be approached with caution. “We’re not telling people to rush out and buy buckets of supplements,” he wrote in a press release accompanying the new paper. “Always speak to your medical professional before changing or initiating a treatment.”

But researchers like Sarris are gradually disentangling potential fact from fiction. A number of vitamins and supplements are coming under scientific scrutiny. Vitamin D in particular has been the focus of a host of recent studies and may be beneficial in treating a variety of conditions, from multiple sclerosis to schizophrenia.

For brain health, all—or at least most—roads lead to the sea.  Many small trials have reported associations between omega-3 fatty acids—obtained either through diet or supplements—and improved depression symptoms. In practice, omega-3s derived from fish appear to reach significantly higher blood levels than those sourced from plants. And there is a fast accumulating body of data linking a reduced risk for depression to traditional diets—including the Mediterranean, Scandinavian and Japanese diets—that are high in vegetables, whole grains and fish.

How does the evidence sit in light of the new study’s findings? “It is important to advise that a balanced whole-food diet is important for physical as well as mental health, and that supplements should not replace this,” Sarris notes. “However, I believe a good diet in addition to select nutraceutical prescriptions can still be recommended in some cases, such as when people have inadequate responses to antidepressant medication.”

As a next step, Sarris believes that researchers should move beyond specific supplements and study augmenting antidepressant treatment with, say, the Mediterranean diet. Both he and Jacka also feel that more work needs to be done to determine which supplements may benefit patients as individuals, based on their specific nutrient deficiencies, brain conditions and genetic profiles.

“A key imperative for nutritional psychiatry is to develop a clear understanding of what supplements are useful for whom, and under what conditions, and also to understand the baseline factors that might influence nutrient metabolism, such as gut health,” Jacka says. “This sort of knowledge should help us to begin to design targeted and personalized nutritional interventions for psychiatric illnesses.”

Source: Do Vitamins and Supplements Make Antidepressants More Effective?

Study compared Finnish adults with and without multiple sclerosis, but more research is needed

Source: Low Prenatal Vitamin D Linked to Later MS in Offspring – US News


January 2006

By Terri Mitchell

Back when Europe was stone huts and the Mayans were playing soccer, the Chinese were drinking tea. Tea goes back at least 5,000 years as medicine and more than 1,000 years as a simple beverage. Made from the leaves of a bush related to flowering camellia, tea has had a starring role in major features such as the American Revolution and Zen Buddhism. The Japanese regard tea so highly that they’ve created a ceremony for it, and a separate little tea house in which to serve it.

The tea ceremony is remarkable in that it dramatizes tea’s physical effects on the human body. Tea causes changes in body chemistry that rejuvenate, relax, enhance the ability to think, and change mood.1-6 The biochemical changes provoked by tea are scientifically supported, and they’re not due to caffeine.6

Among the latest discoveries about tea is that it can prevent depression and lower blood pressure.7,8 Both green and black teas have beneficial health effects, the main difference being that black tea is oxidized. That would seem to destroy tea’s bioactivity, but it does not. Black tea continues to prove itself in scientific studies. Researchers with the US Department of Agriculture, for example, recently reported that five cups of black tea a day can lower potentially harmful low-density lipoprotein (LDL) and total cholesterol in people with mildly elevated cholesterol.9

Black tea has benefits, but green tea has undergone more investigation, especially in Japan, where it’s the most popular beverage. Many new reports have come out about green tea’s amino acid, theanine, since Life Extension introduced it. The only other known source of this unique amino acid is a mushroom.10 Discovered in 1949, yet just now undergoing substantial research, theanine occupies a place on the shelf quite different from that of other dietary supplements. It has to do with the tea ceremony.

Balancing Sleep/Wake

Millions of Americans will have trouble sleeping tonight. They won’t be able to fall asleep, won’t be able to stay asleep, or won’t feel like they slept. The primary reason is stress, followed by illness, inactivity, medications, and bad sleep environment. The net effect is a lot of grouchy, depressed, and accident-prone people.11 Most won’t see a doctor, even though insomnia can lead to depression, traffic accidents, and a pink slip. Instead, most people will reach for America’s favorite drug: caffeine.

Every day, millions of people take caffeine in one form or another. It’s not only in coffee, it’s in fruity sodas, over-the-counter drugs, and diet elixirs. “Energy drinks” and espresso are popular caffeine fixes with megadoses of caffeine. Caffeine keeps Americans alert during the day, but it has a price. It can stay in the body for about 10 hours. That’s if you have a fully functioning liver. If you drink alcohol or take cimetidine (Tagamet®) and other drugs, it will stick around even longer.12,13 That means the cappuccino you had at three in the afternoon is still around at midnight.

To relax at night, Americans don’t have many choices except prescription sleeping pills. But these drugs don’t work for everyone, and have undesirable side effects. Better solutions are needed.

Tea Ceremony in a Capsule

Relaxation, rejuvenation, focus. The tea ceremony energizes without draining, calms without putting to sleep, and motivates without causing a jagged edge. Although tea can have as much or more caffeine than some coffees, it doesn’t have the same “speedy” effect.14,15 The reason is its secret ingredient, L-theanine. Research shows that L-theanine neutralizes the speedy, jagged, bad effects of caffeine without reducing its mind-energizing, fat-burning features.16,17

L-theanine’s effect on the brain can be visualized on an EEG. Brain waves are actually smoothed out—but not flattened out—by supplemental L-theanine.16 The body is relaxed, the mind is calmed, but no drowsiness occurs.5 This is exactly the type of relaxation prescribed by sleep therapists. The person seeking help will be asked to listen to music or engage in a similarly relaxing activity immediately before retiring. Studies show that pre-sleep relaxation is very effective against insomnia, even in tough cases.18-20

Falling asleep is one thing; staying asleep and getting quality sleep is another. Researchers in Japan gave volunteers 200 mg of L-theanine daily and recorded their sleep patterns on devices worn around their wrists. The L-theanine didn’t cause the subjects to sleep longer, but it did cause them to sleep better. It was documented that sleep quality, recovery from exhaustion, and refreshed feelings were all enhanced by L-theanine. Those taking L-theanine felt like they slept longer than they actually did.21 This is good news for people who don’t get enough sleep, or those who want to sleep less and do more.

One of the other effects of the tea ceremony is that it leaves people in a better mood. Knowing that L-theanine can cross the blood-brain barrier and positively affect brain chemistry, scientists investigated its mood-modulating effects. The results of those studies have led to L-theanine being patented as a mood enhancer.22 How it works is not completely understood, but one thing researchers have discovered is that L-theanine changes levels of amino acids affecting serotonin and other neurotransmitters in the brain.5

Balancing Brain Chemistry

Memory impairment is frequently associated with old age or Alzheimer’s disease, but there are other causes. Stress and depression, for example, cause memory loss. Although usually thought of as mere psychological states, stress and depression cause physical changes in body chemistry. The brain is notably affected.

Stress hormones known as glucocorticoids are activated by both stress and depression. In turn, they cause imbalances in brain chemistry that interfere with mood and memory.23-26 The effect is biochemical. Glucocorticoids disrupt serotonin, dopamine, norepinephrine, and other brain chemicals.27,28 These “neurotransmitters” are the target of prescription antidepressants such as Prozac® and Wellbutrin®. And it has been shown that glucocorticoids can interfere with the ability of Prozac® and other drugs to work.29 Worse still, glucocorticoids can cause the brain to shrink.30,31 Counteracting glucocorticoids is extremely important.

Drugs that block glucocorticoids have been proposed as a treatment for depression, and strangely enough, people have been treated successfully with ketoconazole (Nizoral®), an antifungal drug with the side effect of suppressing glucocorticoids.32,33 Theanine also suppresses glucocorticoids, and it is one of the few dietary supplements that crosses the blood-brain barrier.

Theanine’s connection to the suppression of glucocorticoids is through glutamate. Researchers have discovered that this natural component of brain chemistry, which is not traditionally associated with depression, in fact plays a major role.34 In people who are depressed, glutamate levels are out of balance.35 Preliminary studies show that blocking certain signals in the brain activated by glutamate may be as effective as prescription antidepressants.36,37 L-theanine may act as a glutamate antagonist.38 Researchers believe that glutamate receptor antagonists may offset the harmful effects of high glucocorticoid levels and offer neuroprotective effects against both acute and chronic neurodegenerative diseases.39

Glutamate-activated signals not only affect mood, they affect memory and learning.40 Memory and learning are similar biochemical processes in the brain. If an animal can’t remember, it can’t learn. Stroke, Alzheimer’s disease, and alcohol all cause memory loss involving disruptions in glutamate-related signals that inhibit the storage and retrieval of memories.41-44

If theanine is present in the body at the time stroke occurs, the damaged area will be significantly reduced.45 This is supported by a Chinese study of 14,000 people, which found that drinking tea slashes the risk of stroke by 40%.46 Maintaining healthy levels of L-theanine and other tea-related compounds in the body may thus help prevent memory loss and stroke-induced damage to brain tissue.

Balancing the Liver: Alcohol

Another part of the body that responds positively to theanine is the liver. Research from Japan shows that theanine is a powerful antidote to the effects of alcohol. If theanine is given to mice before or after they drink alcohol, it significantly lowers blood levels of alcohol.47 It works by modulating alcohol chemistry.

Alcohol is converted to a toxic chemical known as acetaldehyde, which is similar to formaldehyde and more toxic than alcohol itself. Theanine accelerates the break- down of acetaldehyde and blocks toxic radicals.47 The remarkable powers of theanine to intercept free radicals was demonstrated in the same study. It not only blocked radicals caused by alcohol, it suppressed levels to below normal for five hours.

One reason theanine is able to reverse damage caused by alcohol is that it restores the liver’s all-purpose antioxidant and detoxifier known as glutathione. Drinking alcohol causes significant suppression of this critical factor. If the suppression is infrequent, the liver bounces back; if suppression is chronic, however, the liver can’t overcome the stress. It breaks down and the effects are felt throughout the body. Theanine helps counteract the alcohol-induced loss of glutathione.47

Glutathione is not only something people who drink alcohol have to worry about, it’s something that oncologists have to worry about. Depletion of glutathione in vital organs like the heart is a major cause of chemotherapy toxicity. Because of it, some drugs that could otherwise be useful in treating certain types of cancers can’t be used. Researchers looking into the possibility of adding theanine to chemotherapy have found that it counteracts drug-induced losses of glutathione in vital organs like the heart, but not in tumors.48 In fact, it blocks tumors from getting glutathione, thus enabling some types of chemotherapeutic drugs to work better.49 By enhancing glutathione where it’s beneficial and reducing it where it’s not, theanine again shows its propensity to restore balance.

Balancing Fat and Muscle

If there’s one place people want to restore balance, it’s in the area of body fat. As everyone knows,when fat loss is the goal, calorie expenditure is the game plan. One of the differences in people who are overweight and those who are not is that overweight people sit about two hours longer every day.50 Clearly, inactivity causes imbalance in the system, yet the mere thought of exercising makes some people tired. Motivation is lacking, and they might as well try to climb Mt. Everest as do a round on the stair climber.

But what if they really did have to climb Mt. Everest? Researchers in the United Kingdom made a surprising discovery in a study of mountain climbers. Hot tea, they found out, does wonders for fatigue and vigor (as in let’s get up and go!).51 Finnish researchers made a similar discovery when questioning people about depression. None of the subjects who drank five or more cups of tea a day was depressed, whereas those drinking no tea had the highest rate of depression.7 Neither research team attributed the motivational effects of tea to caffeine. Caffeine is effective for a different aspect of weight loss: speeding up metabolism. But 100 milligrams of caffeine only increases the resting metabolic rate 3-4%.52 Upping the dose can leave a person tired and shaky. So, caffeine by itself isn’t the answer to weight loss. Enter green tea.

Researchers know that green tea extract promotes thermogenesis above and beyond its caffeine content.53 They have been aware for several years that compounds in green tea increase caffeine’s calorie-burning effects. What those compounds are was a mystery until Japanese researchers decided to look into it in 2004. They divided green tea into its various components and investigated how catechins, theanine, caffeine, and green tea powder itself affect weight gain in female mice.54 They found that all the components suppressed weight gain. Green tea powder, catechins, and theanine also reduced triglyceride levels. The researchers concluded that not only can caffeine help prevent weight gain and fat accumulation, but theanine can, too. It’s not known whether the same results occur in humans.

In Japan, you will more likely find theanine in your beverage than caffeine. The Japanese value the rejuvenating, mind-clearing qualities of theanine. It’s not surprising that something that restores balance is very popular in a culture where restoring balance is the foundation of medicine. Westerners would do well to take note of this gift from the East.

Theanine is unique in a sea of supplements that promise much but deliver little. It’s one of the few supplements that crosses the blood-brain barrier. Research to date indicates that theanine is very useful for restoring balance to systems neglected by people who are on the go. It helps counteract the stimulating effects of caffeine, but complements caffeine’s positive aspects such as fat burning. It relaxes and rejuvenates. It reduces alcohol levels in the bloodstream and supports liver health. It restores mood and motivation, increases thermogenesis, and protects the brain. Supplemental theanine thus helps recreate the calming and centering effects of a tea ceremony in a convenient and accessible form.

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7. Hintikka J, Tolmunen T, Honkalampi K, et al. Daily tea drinking is associated with a low level of depressive symptoms in the Finnish general population. Eur J Epidemiol. 2005;20(4):359-63.

8. Negishi H, Xu JW, Ikeda K, et al. Black and green tea polyphenols attenuate blood pressure increases in stroke-prone spontaneously hypertensive rats. J Nutr. 2004 Jan;134(1):38-42.

9. Davies MJ, Judd JT, Baer DJ, et al. Black tea consumption reduces total and LDL cholesterol in mildly hypercholesterolemic adults. J Nutr. 2003 Oct;133(10):3298S-3302S.

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13. Broughton LJ, Rogers HJ. Decreased systemic clearance of caffeine due to cimetidine. Br J Clin Pharmacol. 1981 Aug;12(2):155-9.

14. Gilbert RM, Marshman JA, Schwieder M, Berg R. Caffeine content of beverages as consumed. Can Med Assoc J. 1976 Feb 7;114(3):205-8.

15. McCusker RR, Goldberger BA, Cone EJ. Caffeine content of specialty coffees. J Anal Toxicol. 2003 Oct;27(7):520-2.

16. Kakuda T, Nozawa A, Unno T, Okamura N, Okai O. Inhibiting effects of theanine on caffeine stimulation evaluated by EEG in the rat. Biosci Biotechnol Biochem. 2000 Feb;64(2):287-93.

17. Kimura R, Kurita M, Murata T. Influence of alkylamides of glutamic acid and related compounds on the central nervous system. III. Effect of theanine on spontaneous activity of mice (author’s transl). Yakugaku Zasshi. 1975 Jul;95(7):892-5.

18. Nicassio PM, Boylan MB, McCabe TG. Progressive relaxation, EMG biofeedback and biofeedback placebo in the treatment of sleep-onset insomnia. Br J Med Psychol. 1982 Jun;55(Pt 2):159-66.

19. Friedman L, Bliwise DL, Yesavage JA, Salom SR. A preliminary study comparing sleep restriction and relaxation treatments for insomnia in older adults. J Gerontol. 1991 Jan;46(1):1-8.

20. Coursey RD, Frankel BL, Gaarder KR, Mott DE. A comparison of relaxation techniques with electrosleep therapy for chronic, sleep-onset insomnia a sleep-EEG study. Biofeedback Self Regul. 1980 Mar;5(1):57-73.

21. Available at: news/news-ng.asp?id=50679-green-tea-lulls. Accessed October 12, 2005.

22. US Patent Application 20040171624; Japanese Patent Application 2001-253740.

23. Calabrese JR, Kling MA, Gold PW. Alterations in immunocompetence during stress, bereavement, and depression: focus on neuroendocrine regulation. Am J Psychiatry. 1987 Sep;144(9):1123-34.

24. Ou XM, Storring JM, Kushwaha N, Albert PR. Heterodimerization of mineralocorticoid and glucocorticoid receptors at a novel negative response element of the 5-HT1A receptor gene. J Biol Chem. 2001 Apr 27;276(17):14299-307.

25. Bhatia V, Tandon RK. Stress and the gastrointestinal tract. J Gastroenterol Hepatol. 2005 Mar;20(3):332-9.

26. Schleimer RP, Jacques A, Shin HS, Lichtenstein LM, Plaut M. Inhibition of T cell-mediated cytotoxicity by anti-inflammatory steroids. J Immunol. 1984 Jan;132(1):266-71.

27. Price LH, Cappiello A, Malison RT, et al. Effects of antiglucocorticoid treatment on 5-HT1A function in depressed patients and healthy subjects. Neuropsychopharmacology. 1997 Oct;17(4):246-57.

28. Janowsky DS, Risch SC, Huey LY, Judd LL, Rausch JL. Hypothalamic=pituitary-adrenal regulation, neurotransmitters and affective disorder. Peptides. 1983 Sep-Oct;4(5):775-84.

29. Gartside SE, Leitch MM, Young AH. Altered glucocorticoid rhythm attenuates the ability of a chronic SSRI to elevate forebrain 5-HT: implications for the treatment of depression. Neuropsychopharmacology. 2003 Sep;28(9):1572-8.

30. McEwen BS. Glucocorticoids, depression, and mood disorders: structural remodeling in the brain. Metabolism. 2005 May;54(5 Suppl 1):20-3.

31. Sapolsky RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry. 2000 Oct;57(10):925-35.

32. Reus VI, Wolkowitz OM. Antiglucocorticoid drugs in the treatment of depression. Expert Opin Investig Drugs. 2001 Oct;10(10):1789-96.

33. Murphy BE. Antiglucocorticoid therapies in major depression: a review. Psychoneuroendocrinology. 1997;22 Suppl 1S125-32.

34. Paul IA, Skolnick P. Glutamate and depression: clinical and preclinical studies. Ann NY Acad Sci. 2003 Nov;1003:250-72.

35. Sanacora G, Gueorguieva R, Epperson CN, et al. Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry. 2004 Jul;61(7):705-13.

36. Trullas R, Skolnick P. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol. 1990 Aug 21;185(1):1-10.

37. Huber TJ, Dietrich DE, Emrich HM. Possible use of amantadine in depression. Pharmacopsychiatry. 1999 Mar;32(2):47-55.

38. Shinozaki H, Ishida M. Theanine as a glutamate antagonist in crayfish neuromuscular junction. Brain Res. 1978 Jul 28;151(1):215-9.

39. Danilczuk Z, Ossowska G, Lupina T, Cieslik K, Zebrowska-Lupina I. Effect of NMDA receptor antagonists on behavioral impairment induced by chronic treatment with dexamethsome. Pharmacol Rep. 2005 Jan-Feb;57(1):47-54.

40. Hinoi E, Takarada T, Tsuchihashi Y, Yoneda Y. Glutamate transporters as drug targets. Curr Drug Targets CNS Neurol Disord. 2005 Apr;4(2):211-20.

41. Kolb JE, Trettel J, Levine ES. BDNF enhancement of postsynaptic NMDA receptors is blocked by ethanol. Synapse. 2005 Jan;55(1):52-7.

42. Yamada KA, Covey DF, Hsu CY, et al. The diazoxide derivative IDRA 21 enhances ischemic hippocampal neuron injury. Ann Neurol. 1998 May;43(5):664-9.

43. Bao HY, Zhang J, Yeo SJ, et al. Memory enhancing and neuroprotective effects of selected ginsenosides. Arch Pharm Res. 2005 Mar;28(3):335-42.

44. Tyszkiewicz JP, Yan Z. Beta-Amyloid peptides impair PKC-dependent functions of metabotropic glutamate receptors in prefrontal cortical neurons. J Neurophysiol. 2005 Jun;93(6):3102-11.

45. Egashira N, Hayakawa K, Mishima K, et al. Neuroprotective effect of gamma-glutamylethylamide (theanine) on cerebral infarction in mice. Neurosci Lett. 2004 Jun 3;363(1):58-61.

46. Chen Z, Li Y, Zhao LC, et al. A study on the association between tea consumption and stroke. Zhonghua Liu Xing Bing Xue Za Zhi. 2004 Aug;25(8):666-70.

47. Sadzuka Y, Inoue C, Hirooka S, et al. Effects of theanine on alcohol metabolism and hepatic toxicity. Biol Pharm Bull. 2005 Sep;28(9):1702-6.

48. Sugiyama T, Sadzuka Y. Theanine, a specific glutamate derivative in green tea, reduces the adverse reactions of doxorubicin by changing the glutathione level. Cancer Lett. 2004 Aug 30;212(2):177-84.

49. Sadzuka Y, Sugiyama T, Suzuki T, Sonobe T. Enhancement of the activity of doxorubicin by inhibition of glutamate transporter. Toxicol Lett. 2001 Sep 15;123(2-3):159-67.

50. Levine JA, Lanningham-Foster LM, McCrady SK, et al. Interindividual variation in posture allocation: possible role in human obesity. Science. 2005 Jan 28;307(5709):584-6.

51. Scott D, Rycroft JA, Aspen J, Chapman C, Brown B. The effect of drinking tea at high altitude on hydration status and mood. Eur J Appl Physiol. 2004 Apr;91(4):493-8.

52. Dulloo AG, Geissler CA, Horton T, Collins A, Miller DS. Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers. Am J Clin Nutr. 1989 Jan;49(1):44-50.

53. Dulloo AG, Seydoux J, Girardier L, Chantre P, Vandermander J. Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity. Int J Obes Relat Metab Disord. 2000 Feb;24(2):252-8.

54. Zheng G, Sayama K, Okubo T, Juneja LR, Oguni I. Anti-obesity effects of three major components of green tea, catechins and theanine, in mice. In Vivo. 2004 Jan-Feb;18(1):55-62.

Source: Theanine: Natural Support for Sleep, Mood, and Weight – 2 – Life Extension

The advice changes all the time

The advice changes all the time

Are the official dietary guidelines useful to average Americans? I’m not so sure.

Every five years, numerous dietary experts are tasked with putting together a summary of the most up-to-date nutritional science. Their end product is intended to be a series of dietary recommendations that will help public-health agencies, health-care providers, and educational institutions create federal nutrition policy, health programs and disease-prevention initiatives.

This past February, the Dietary Guidelines for Americans advisory panel issued a 571-page report that upended a lot of conventional thinking. After reviewing all the data, they eased restrictions on cholesterol and urged us to eat less sugar and meat. But they also introduced concepts of sustainability and “dietary patterns”—which include how much and how frequently we should eat different foods—into the conversation. The official recommendations were released Jan. 7.

The new recommendations feel odd and a bit touchy-feely compared to the previous, more stern editions that had us go low-fat, avoid eggs, and micromanage the molecules of our meals. Yet regardless of whether the suggestions are ultimately right or wrong, there are two main issues that make them just north of useless.

1. The advice changes all the time.

It seems like there’s a giant Price Is Right wheel, but for nutrition advice. Every five years, we give it a spin, and up comes the dietary guidelines.

For example, all that cholesterol that we were supposed to watch is “no longer a nutrient of concern.” So have an egg with your shrimp scampi and don’t worry as much about counting up the grams of fat in your dinner. Remember the added sugars in the low-fat products we ate before? Eat less of those. But wait, there’s more: you can have coffee again!

It’s no wonder that a 2012 survey by the International Food Information Council found that more than half of Americans said it’s easier to do their taxes than to figure out a healthful diet. And 76% stated that all the constant changes to nutritional guidance make it harder to know what to believe.

We used to visualize dietary guidelines as food groups in a square. That changed into a pyramid that focused on low-fat eating and drinking eight 8-ounce glasses of water every day. Now it’s a plate.

As the rubric changed, so did the specific foods that we could or couldn’t eat: eggs, no eggs; nuts, no nuts; cholesterol, no cholesterol; don’t drink wine, now you can.

With this level of change and outright reversal of opinion, there’s never any guarantee that this year’s advice will be next year’s advice. This undermines the impact of the guidelines.

2. There’s too much nutritional noise.

The ink on the Dietary Guidelines for Americans wasn’t dry before the vegan Physicians Committee for Responsible Medicine was suing the government. The committee, which has sued over the guidelines in the past, disagreed with the conclusion that dietary cholesterol is not as bad as we thought, worried that the egg and meat industries unduly influenced the recommendations, and didn’t like that the guidelines neglected to tell people to eat less meat.

Some of the criticism has merit: The cattle industry did not like the government telling people about data indicating that red meat (particularly processed meats) can contribute to heart disease and cancer, so its lobbying group convinced a government agency to keep out language stating that you should eat less meat. Congress used the appropriations process to set limits on what the guidelines could even say.

For ordinary Americans, the reversals of recommendations, the lawsuits and the Congressional conflicts of interest all cast doubt on the validity of the guidelines. The combination of these influences makes the dietary guidelines mostly useless for most Americans.

In the midst of all the cacophony, we need dietary principles that we can rely upon. To do this, we might start by looking at the habits of healthy eating practiced in the Mediterranean. This would involve returning to meals at the family table; eating real food (mostly vegetables); and doing that without over-consuming. That’s a three-step healthy prescription that will remain as true today as it will be when the next dietary guidelines come out five years from now.

Source: Our Official Dietary Guidelines Are Useless | TIME

A 2010 article published in Oncology Reports states pancreatic cancer is among the most aggressive forms of human cancer, characterized by a very high mortality rate. It represents the fourth leading cause of cancer death in United States, killing 32,000 people annually. With a 5-year survival rate of only 3 percent and a median survival rate of less than six months, pancreatic cancer carries one of the poorest prognoses. The diagnosis of pancreatic cancer is one of the worst things a doctor ever has to tell a patient. The only FDA-approved therapies for it, Gemcitabine and Erlotinib, produce objective responses in less than 10 percent of patients, while causing severe side-effects in the majority. There is a desperate need for new options.

Clinical research to test new treatments is split into phases. Phase I trials are just to make sure the treatment is safe, to see how much you can give before it becomes toxic. Curcumin, the natural yellow pigment in the spice turmeric has passed a number of those. In fact, there was so little toxicity, the dosing was limited only by the number of pills patients were willing to swallow.

Phase II trials are conducted to see if the drug actually has an effect. Curcumin did, in 2 of the 21 patients that were evaluated. One patient had a 73 percent tumor reduction, but the effect was short-lived. One lesion remained small, but a curcumin-resistant tumor clone emerged. The other patient, who had a stable disease for over 18 months, showed slow improvement over a year. In fact, the only time that patient’s cancer markers bumped up was during a brief three-week stint where the curcumin was stopped.

Love This? Never Miss Another Story.

So curcumin does seem to help some patients with pancreatic cancer, and most importantly, there appears to be little downside. No curcumin-related toxic effects were observed in up to doses of eight grams per day. What happens after eight grams? We don’t know because no one was willing to take that many pills. The patients were willing to go on one of the nastiest chemotherapy regimens on the planet, but didn’t want to be inconvenienced with swallowing a lot of capsules.

The only surefire way to beat pancreatic cancer is to prevent it in the first place. In 2010 I profiled a study conducted by the National Institutes of Health, the largest such study in history, which found that dietary fat of animal origin was associated with increased pancreatic cancer risk.

Which animal fat is the worst? The second largest study has since chimed in to help answer that question. Researchers found that poultry was the worst, with 72 percent increased risk of pancreatic cancer for every 50 grams of daily poultry consumption. Fifty grams is just about a quarter of a chicken breast. The reason white meat came out worse than red may be because of the cooked meat carcinogens in chicken, the heterocyclic amines that build up in grilled and baked chicken. These mutagenic chemicals have been associated with doubling pancreatic cancer risk.

Meat has been associated with significantly increased risk, whereas fake meat is associated with significantly less risk. Those who eat plant-based meats like veggie burgers or veggie dogs three or more times a week had less than half the risk of fatal pancreatic cancer. Legumes and dried fruit appear to be similarly protective.

My grandfather died of pancreatic cancer. By the time the first symptom arose, a dull ache in his gut, it was too late. That’s why we need to work on preventing it.

Carcinogens in grilled and baked chicken may increase the risk of pancreatic cancer, while curcumin may help even in advanced stages of the disease.

Source: Turmeric Curcumin and Pancreatic Cancer | Care2 Healthy Living

For decades, scientists believed that excess body fat was mere storage for unused calories. However, research conducted over the past 20 years suggests added fat is more than a little extra cushion—fat cells are actually “toxic factories,” each one producing inflammatory cytokines (chemical messengers of inflammation) throughout the body and causing potentially serious damage to your health. It is this understanding that has led experts to more closely examine the effects of being overweight, even when an individual is considered physically fit.

In 1998, the National Institutes of Health (NIH) published Clinical Guidelines on the Identification, Evaluation and Treatment of Overweight and Obesity in Adults. These guidelines noted being overweight but in good physical health would reduce the risk of premature death— in other words, being physically fit mattered more than body fat percentage.

But in 2015, the International Journal of Epidemiology released the results of a study that suggested the “fat but fit” theory wasn’t true, based on the health data of more than 1.3 million Swedish men whom researchers followed for 30 years. Those study authors found that the beneficial effects of exercise declined as obesity rates increased. Compared to physically fit obese men, normal-weight men who were not physically fit had a lower risk of dying.

These results are backed by a prior study published in January 2015 that identified a link between increased levels of fat in the body— regardless of physical fitness— and high levels of inflammation. Inflammation is the root cause of all disease, especially chronic conditions, such as heart disease, diabetes, cancer and Alzheimer’s disease. Another study published in the journal Clinical Cancer Research in 2015 observed a correlation between increased levels of white fat tissue and poorer prognosis in early-stage breast cancer. White fat, known as white adipose tissue, is fat stored for energy, but it also plays a role in raising inflammation levels when found in excess throughout the body.

Abdominal obesity, which is fat centralized in the belly, is a sign of high levels of visceral fat in the body. Visceral fat is the type of fat that accumulates in arteries and around organs, and has been credited with increased inflammation and disease risk. Emerging research has found that while this still holds true, fat may be further differentiated. A December 2014 study found that fat deposits may exist on the surface of the myocardium (muscular wall of the heart) and be contained completely beneath the membrane that encloses the heart— in contact with major coronary arteries and their branches. This fat, known as epicardial adipose tissue (EAT), is highly correlated with obesity, and thought to play a role in the development and vulnerability of plaque in the coronary arteries.

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If being fit doesn’t protect against the dangers of excess weight gain, what can?

While fitness is still an important component of optimal health, it is not a standalone marker.

If you are struggling with losing weight, you will reap significant benefits by increasing lean body mass with exercise.

Here are 3 other tactics that can help you lose weight and lower your disease risk:

1. Assess body fat rather than BMI
One of the primary challenges facing the nation today is the standard of measurement for obesity. At present, obesity is defined by body mass index (BMI), which is essentially a height-to-weight ratio. For example, a man who is 5 feet 10 inches tall weighs 220 pounds and has 12 percent body fat would be considered obese, according to the BMI scale. However, anyone with 12 percent body fat is not overweight or obese. This person is likely a bodybuilder with very high levels of lean muscle. His body fat percentage is a better indicator of his health risk. BMI drastically underscores fat levels in the aging population, particularly postmenopausal women who have lost substantial muscle mass that has been replaced with fat and yet their weight remains steady.

A bioelectrial impedance assessment (BIA) is a more comprehensive look at body composition, assessing lean body mass, body fat, and body water percentages, as well as showing where primary fat stores exist. These assessments are generally available through a physician’s office. Monitoring your body fat rather than BMI will help you better assess your overall health and weight management goals.

2. Add a probiotic to your supplement regimen
Research continues to identify the gut flora as a contributing factor to multiple aspects of health, including weight management and inflammation levels. Unfortunately, the typical American diet often leads to imbalances in the microbiota of the gut favoring the development of intestinal inflammation and increased risk of disease. A daily probiotic (not a dairy-based, sugar-laden probiotic) can help promote healthy bacteria in the gut. According to one study, the Lactobacillus plantarum strain offers the greatest potential for suppressing chronic inflammation in the gut. In November 2015, one study uncovered evidence that the landscape of the bacteria in your gut may be the greatest factor in determining which foods will optimally improve an individual’s weight and general health.

3. Consume a clean, nutrient-rich, whole-foods diet
While certain research may say that the Mediterranean diet is good for some people and that the Paleo diet is good for others, one fact remains: Whole foods are best. Strive to consume a wide variety of fresh vegetables and low-sugar fruits organically or locally sourced. Enjoy a mix of lean proteins from animal sources along with plant-based proteins that are high in fiber, like quinoa. Keep sugar, artificial sweeteners and ingredients, and processed foods out of your diet. These foods contribute to toxins in the body and negatively impact healthy gut microbiota.

Achieving optimal health is always a work in progress. Set small goals every month, week, and day that will drive progress. You don’t have to be perfect, but you should try to make everyday choices, a choice that will maximize your wellbeing— mind, body, and spirit.

Dr. Jennifer Landa is Chief Medical Officer of BodyLogicMD, the nation’s largest franchise of physicians specializing in bioidentical hormone therapy. Dr. Jen spent 10 years as a traditional OB-GYN, and then became board-certified in regenerative medicine, with an emphasis on bio-identical hormones, preventative medicine and nutrition. She is the author of “The Sex Drive Solution for Women.”  Learn more about her programs at

For decades, scientists believed that excess body fat was mere storage for unused calories.

Source: ‘Fat but fit’: How carrying excess weight can have long-term health consequences | Fox News

Potassium Is Like Sex and Money

Hughes explains that potassium rich foods generate alkali and that bone is the great reservoir for the storage of alkali. Alkali is needed to counteract acid produced by protein rich foods such as meat, poultry, fish or dairy products. She adds that if the body gets more acid than it can excrete, it breaks down bone to add alkali to the system. If this situation continues over a long period of time, bone loss can lead to osteoporosis and fractures. The article in Nutrition Action reminded me of a column I’d written years ago about Dr. David Young, Professor of Physiology at the University of Mississippi. He hit a home run when he said, “Potassium is like sex and money. You can never get too much!” This is good news for me. Thank God, there are more ways to consume potassium than eating a cup of spinach. I’d die for roast beef and potatoes, both loaded with potassium, especially when you eat the skin of the potato. You can also get 1,200 milligrams of potassium by drinking three glasses of milk. A banana contains 450 mg and there’s potassium in citrus fruits, nuts and green leafy vegetables.

Source: Potassium Is Like Sex and Money

There are multiple ways to determine if that carton of milk in your fridge should be thrown out (smell test, taste test or just checking the “sell-by” date). But what’s the best way to figure out if your food should be tossed or saved?

“Sell-by” dates may seem like an easy way to tell when to throw out food, but it turns out that in most cases, a “sell-by” or “best used by” date isn’t an automatic warning sign that the food is spoiled.

According to the U.S. Department of Agriculture, the “sell-by” date tells the store how long to display the product for sale. It doesn’t mean the product has gone bad once it reaches the “sell-by” or “best used by” date.

A “best used by” date actually has nothing to do with spoilage. In this case, the date is recommended for flavor or quality standards. A canned item like soup with a “best if used by” date might be safe to eat long after the date passes, but expect a little less flavor with each passing day.


There are no federal requirements for putting expiration dates on food, except for infant formula. A “best used by” date indicates the last date of the product’s peak quality. In the case of infant formula, using a product after the “best used by” date can mean there are less nutrients and the quality may have degraded so that the formula separates or clogs.

Dr. Michael Hansen, senior staff scientist with Consumers Union, a consumer trade group, told ABC News that the dates listed on food don’t give much indication if a product has spoiled or not.

“What most people think is that the food is bad after that date,” Hansen said, “and that it could be a hazardous.”

The USDA has guidelines on how long to keep perishable items in the fridge here. The guidelines should be followed regardless of the “sell-by” date. Food with a “use-by” date shouldn’t be consumed after that date passes.


Source: Food Sell-By Dates: What They Really Tell You – ABC News

The debate over vitamin D3 and what it can or can’t do in the body has taken a positive spin. Using biopsies of actual tissues samples, scientists in the UK have documented actual regeneration or repairs in muscle fibers.

Source: Study says vitamin D3 may speed up recovery process |

Antioxidant Use May Promote Melanoma Metastasis Click Image To Enlarge + Results from a new study suggest that cancer patients should not supplement their diet with large doses of antioxidants. [grThirteen/iStock] Decades ago Nobel laureate and American chemist Linus Pauling espoused the benefits of taking megadoses of vitamin C to prevent and treat various diseases. This controversial practice has led many to promote the taking of antioxidant supplements to prevent everything from the common cold to cancer and has become an almost engrained practice for individual healthcare—unfortunately, with little scientific evidence to support the ritual. Now, researchers at the Children’s Research Institute at UT Southwestern (CRI) has uncovered evidence that suggests cancer cells benefit more from antioxidants than normal cells, raising concerns about the use of dietary antioxidant supplements by patients with cancer. The investigators utilized a specialized mice model that had been transplanted with melanoma cells from patients, which previous work showed recapitulated metastasis of human melanoma cells and was predictive of their metastasis in patients. The CRI team found that when antioxidants were administered to the mice, the cancer spread more quickly than in mice that did not get antioxidants. “We discovered that metastasizing melanoma cells experience very high levels of oxidative stress, which leads to the death of most metastasizing cells,” explained senior author Sean Morrison, Ph.D., CRI director and chair in pediatric genetics at UT Southwestern Medical Center. “Administration of antioxidants to the mice allowed more of the metastasizing melanoma cells to survive, increasing metastatic disease burden.” The findings from this study were published online today in Nature through an article entitled “Oxidative stress inhibits distant metastasis by human melanoma cells.” It has long been known that the spread of cancer cells from one part of the body to another is an inefficient process in which the vast majority of cancer cells that enter the blood fail to survive, due to the highly oxidative environment and exposure to immune cells. “The idea that antioxidants are good for you has been so strong that there have been clinical trials done in which cancer patients were administered antioxidants,” noted Dr. Morrison. “Some of those trials had to be stopped because the patients getting the antioxidants were dying faster. Our data suggest the reason for this: cancer cells benefit more from antioxidants than normal cells do.” The CRI researchers were intrigued by their findings and acknowledged that although the study’s results have not yet been tested in people, they surmise that cancer should be treated with pro-oxidants and that cancer patients should not supplement their diet with large doses of antioxidants. “This finding also opens up the possibility that when treating cancer, we should test whether increasing oxidative stress through the use of pro-oxidants would prevent metastasis,” Dr. Morrison stated. “One potential approach is to target the folate pathway that melanoma cells use to survive oxidative stress, which would increase the level of oxidative stress in the cancer cells.”

Source: Antioxidant Use May Promote Melanoma Metastasis | GEN News Highlights | GEN

Source: The Mega Sleep Thread … Melatonin, Ambien, GABA – Page 3 – Brain Health

Researchers at Beth Israel Deaconess Medical Center (BIDMC) have identified a new vitamin B3 pathway that regulates liver metabolism. The discovery provides an opportunity to pursue the development of novel drug therapies to address obesity, type 2 diabetes and related metabolic diseases.

Published in the August 2015 issue of Nature Medicine, the new findings show that a small molecule called N1-methylnicotinamide prevents metabolic complications caused by a high-fat diet.

“Our laboratory investigates the metabolic effects of nicotinamide adenine dinucleotide [NAD+], a metabolite derived from a form of vitamin B3 called nicotinamide,” explained senior author Pavlos Pissios, PhD, an investigator in the Division of Endocrinology, Diabetes and Metabolism at BIDMC and Assistant Professor of Medicine at Harvard Medical School. NAD+ is central to intermediary metabolism, the intracellular process by which food is converted into cellular components in the body.

“Like reservatrol, which is found in red wine, NAD+ boosts the effects of the protein sirtuin 1 [Sirt1], which is known to provide many health benefits,” said Pissios. “Interest in the metabolic effects of NAD+ has spurred the production of several new dietary supplements to improve metabolic health and delay aging. While these results have yet to be demonstrated in humans, recent research has shown that boosting tissue levels of NAD+ can improve health and reduce metabolic complications in mice that have been fed a high-fat diet.”

The liver plays a central role in all metabolic processes, including breaking down fats to produce energy. Because a number of different proteins are involved in the metabolic effects of NAD+, Pissios and his colleagues hypothesized that there might be an as-yet-unidentified vitamin B3 pathway that was directly regulating liver metabolism. “We thought that, in addition to boosting NAD+, vitamin B3 might be positively impacting liver metabolism by acting directly on another pathway,” he explained.

To test this hypothesis, the researchers conducted a variety of experiments that assessed these proteins. Their results showed that nicotinamide N-methyltransfersase (NNMT), a “clearance” enzyme that helps the body excrete excess vitamin B3, also plays a more prominent metabolic role.

“Our lab had been gathering evidence that NNMT not only functions to clear nicotinamide from the liver, but is also involved in the regulation of liver metabolism,” said Pissios. “We confirmed this in our new study, which found that N1-methylnicotinamide, the product of nicotinamide methylation by NNMT, increases Sirt1 protein levels and improves metabolism.”

In subsequent experiments, Pissios and colleagues found that NNMT correlated positively with Sirt1 and a healthy metabolic profile in mice, and also showed that humans with low cholesterol and low triglycerides exhibited high levels of NNMT and Sirt1 in their livers.

“Since N1-methylnicotinamide is a small molecule, we were able to feed it directly to mice to find out if it would prevent the metabolic complications caused by a high-fat diet,” said Pissios. As predicted, N1-methylnicotinamide increased liver Sirt1 protein and suppressed triglyceride and cholesterol synthesis resulting in a healthier liver — with fewer inflammatory markers, less liver fat and lower cholesterol compared to control groups.

“We have now identified a new vitamin B3 pathway that regulates liver metabolism and provides us with an opportunity to pursue development of novel treatments for metabolic diseases,” said Pissios.


Beth Israel Deaconess Medical Center


BIDMC scientists discover new vitamin B3 pathway that regulates liver metabolism.

The Journal of the American College of Nutrition is pleased to offer Open Access to a scientific consensus paper, Sunlight and Vitamin D: Necessary for Public Health, authored by scientists from the University of California, San Diego, Creighton University, Boston University Medical Center, and the Medical University of South Carolina, along with other research contributors. The paper presents information to illustrate that UV exposure not only provides the benefits of vitamin D production, but also many additional health benefits not related to vitamin D. The current culture of sun avoidance in the United States carries with it both health risks and quantifiable harm.

The consensus was developed by GrassrootsHealth, a nonprofit public health research organization, and was led by Dr. Cedric Garland, professor of family and preventive medicine at the University of California, San Diego and Dr. Robert P. Heaney, Professor of Medicine and John A. Creighton University Professor Emeritus of Creighton University.

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“Humans have adapted to sun exposure over many thousands of years and derive numerous physiological benefits from UV exposure in addition to vitamin D,” said Carole Baggerly, executive director of GrassrootsHealth and co-author of the paper. “These benefits far outweigh those derived from vitamin D intake by supplements, and therefore sun avoidance being recommended by the US Surgeon General and others is unnecessarily putting Americans at risk.” The paper concludes that moderate UV exposure is a natural way to improve human health. In fact, patients suffering from cutaneous tuberculosis and other conditions stand to benefit immediately from the use of heliotherapy in their treatments. This is consistent with the results of a survey released this week by GrassrootsHealth, which can be accessed at, in which 99% of dermatologists surveyed believe that UV exposure is a viable form of treatment for non-lethal skin conditions like psoriasis.

“We urge the US Surgeon General’s office and other public health entities to do the work needed to recommend UV exposure levels that are both beneficial and safe, and which favor scientifically-researched information over current cultural norms,” Baggerly added.The paper notes that further study is needed to better understand the additional health benefits of UV light beyond vitamin D, including those related to the release of nitric oxide, production of beta-endorphin, and regulation of circadian rhythms – all important components of life-long health and well-being.

via Scientific consensus paper highlights health benefits of UV exposure and vitamin D.

In what is regarded as the first large, population-based study of its kind, a team of researchers has found a link between vitamin D consumption and the risk of developing dementia. Older people who do not get enough vitamin D could double their risk of developing the condition.

Oily fish

Vitamin D is important for the body’s immune function, growth and repair of bones, and normal calcium and phosphorus absorption. It can be obtained from fish, milk, eggs and cheese.

Dementia is a collective term used to describe the problems that people with various underlying brain disorders can have with their memory, language and thinking. Alzheimer’s disease is the best known and most common disorder under the umbrella of dementia.

Alzheimer’s disease is the sixth leading cause of death in the US and is believed to currently affect 5.3 million Americans, according to the Centers for Disease Control and Prevention (CDC). It is most common in people aged over 65, in which a tenth of the population has the condition.

The authors of the study, published in Neurology, state that low concentrations of vitamin D are associated with the development of Alzheimer’s disease. Worryingly, there are high rates of vitamin D deficiency in older adults – the group most at risk from developing dementia.

The CDC report that one third of the US population do not get sufficient amounts of vitamin D, with 8% of the population at risk of vitamin D deficiency. Vitamin D is obtained from sun exposure and foods such as milk, eggs, cheese and fatty fish.

Vitamin D and dementia: a strong association

For the study, the researchers tested 1,658 dementia-free people aged over 65 who had participated in the US population-based Cardiovascular Health Study. The vitamin D levels in their blood were tested, and they were followed up for an average of 5.6 years.

During this follow-up period, 171 of the participants developed dementia and 102 participants developed Alzheimer’s disease. The researchers found the participants with low levels of vitamin D were 53% more likely to develop dementia, and those who were severely deficient were 125% more likely, when compared with participants with regular levels of vitamin D.

Similarly, participants with low levels of vitamin D saw a 70% increased risk of developing Alzheimer’s disease, and those with severe deficiency had an increased risk of 120%, again when compared with participants with normal levels of the vitamin.

Study author David J. Llewellyn, of the University of Exeter Medical School in the UK, was surprised by the extent of their results, saying, “we actually found that the association was twice as strong as we anticipated.”

The results of the study remained the same even after adjusting for other variables – such as alcohol consumption, smoking and education – that could affect the risk of developing dementia.

‘Encouraging findings’

Llewellyn urges caution following the findings of the study, stating that the results do not demonstrate that low vitamin D levels cause dementia. He suggests the direction that future research needs to take:

“Clinical trials are now needed to establish whether eating foods such as oily fish or taking vitamin D supplements can delay or even prevent the onset of Alzheimer’s disease and dementia.”

The study was unable to account for all forms of dementia, as by excluding participants with cardiovascular disease and stroke at the beginning of the study, the researchers encountered few cases of vascular dementia. The authors acknowledge that further research will be required to incorporate this area of the population.

Despite this, the study could provide a good starting point for this area of research. “Our findings are very encouraging,” says Llewellyn, “and even if a small number of people could benefit, this would have enormous public health implications given the devastating and costly nature of dementia.”

Medical News Today also reported on the benefits of oily fish earlier in the week, with a study suggesting that eating baked or broiled fish every week is good for the brain.

via Link found between dementia and vitamin D deficiency – Medical News Today.

n this study, Dr. Patrick and Dr. Ames show that vitamin D hormone activates the gene that makes the enzyme tryptophan hydroxylase 2 (TPH2), that converts the essential amino acid tryptophan, to serotonin in the brain. This suggests that adequate levels of vitamin D may be required to produce serotonin in the brain where it shapes the structure and wiring of the brain, acts as a neurotransmitter, and affects social behavior. They also found evidence that the gene that makes the enzyme tryptophan hydroxylase 1 (TPH1) is inhibited by vitamin D hormone, which subsequently halts the production of serotonin in the gut and other tissues, where when found in excess it promotes inflammation.

This mechanism explains many of the known, but previously not understood, facts about autism including: 1) the “serotonin anomaly” low levels of serotonin in the brain and high levels in the blood of autistic children; 2) the preponderance of male over female autistic children: estrogen, a similar steroid hormone, can also boost the brain levels of serotonin in girls; 3) the presence of autoimmune antibodies to the fetal brain in the mothers of autistic children: vitamin D regulates the production of regulatory T-cells via repression of TPH1. The Patrick/Ames mechanism is relevant to the prevention of autism, and likely its treatment.

The current guidelines for adequate vitamin D levels are concentrations above 30 ng/ml. Most Americans’ vitamin D is made in the skin from exposure to UVB radiation; however, melanin pigment and sunscreen inhibit this action. This is an important cause of the well-known widespread vitamin D deficiency among dark-pigmented Americans, particularly those living in Northern latitudes. The most recent National Health and Examination survey reports that greater than 70% of U.S. population does not meet this requirement and that adequate vitamin D levels have plummeted over the last couple of decades. This precipitous drop in adequate levels of vitamin D in the US is concurrent with the rise in autism rates.

The study suggests dietary intervention with vitamin D, tryptophan and omega 3 fatty acids would boost brain serotonin concentrations and help prevent and possibly ameliorate some of the symptoms associated with ASD without side effects. There is little vitamin D present in food and fortification is still inadequate as is the amount in most multivitamin and prenatal supplements. Vitamin D supplements are inexpensive and offer a simple solution to raise vitamin D levels to an adequate status. In addition, vitamin D levels should be routinely measured in everyone and should become a standard procedure in prenatal care.

For the full text of Dr. Patrick and Dr. Ames’s research article, please see click here

Journal Reference: R. P. Patrick, B. N. Ames. Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. The FASEB Journal, 2014; DOI: 10.1096/fj.13-246546

via Causal Link between Vitamin D, Serotonin Synthesis and Autism.

Scientists and organizations have different opinions of what is considered a deficiency of vitamin D. Vitamin D levels between 0-30 ng/mL are considered deficient according to the Vitamin D Council and the National Institutes of Health. The Endocrine Society believes that a level lower than 20 ng/mL is a deficiency. The Food and Nutrition Board considers 0-11 ng/mL as deficient.

Patients in this study, though, who experienced the much lower brain functioning after cardiac arrest had a vitamin D level of 7.9ng/mL, while good brain functioning was found in people with a level over 12.5 ng/mL, according to Medical News Today.

via Vitamin D Deficiency Linked To Seven-Fold Increased Risk Of Lower Brain Functioning After This Serious Event.

In recent years, a deficiency of vitamin D has been linked to type 2 diabetes and heart disease, two illnesses that commonly occur together and are the most common cause of illness and death in Western countries. Both disorders are rooted in chronic inflammation, which leads to insulin resistance and the buildup of artery-clogging plaque.

Now, new research in mice at Washington University School of Medicine in St. Louis suggests vitamin D plays a major role in preventing the inflammation that leads to type 2 diabetes and atherosclerosis. Further, the way key immune cells behave without adequate vitamin D may provide scientists with new therapeutic targets for patients with those disorders.

The study appears March 19 in the journal Cell Reports.

Studying mice that lacked the ability to process vitamin D in immune cells involved in inflammation, the researchers found that the animals made excess glucose, became resistant to insulin action and accumulated plaques in their blood vessels.

“The finding that vitamin D helps regulate glucose metabolism may explain previous epidemiological studies identifying an increased risk of diabetes in patients with vitamin D deficiency,” said senior investigator Carlos Bernal-Mizrachi, MD, associate professor of medicine and of cell biology and physiology. “In our study, inactivation of the vitamin D receptor induced diabetes and atherosclerosis, so normalizing vitamin D levels may have the opposite effect.”

In addition, he said inadequate vitamin D turned immune cells into transporters of fat. That may help researchers better understand how diabetes and atherosclerosis are linked and provide new possibilities for therapy.

For years, researchers have been studying vitamin D’s possible roles in inflammation and inflammatory diseases, such as type 2 diabetes and atherosclerosis. By engineering mice without the vitamin D receptor on important immune cells called monocytes and macrophages, the researchers were able to learn how those conditions are linked, according to Bernal-Mizrachi.

Monocytes are white blood cells made in the bone marrow that circulate in the bloodstream. After a few days, they typically move into the body’s tissues where they mature into cells called macrophages.

“Inactivating the vitamin D receptor on monocytes and macrophages promotes inflammation of the liver and in artery walls,” he said. “It also increases the ability of monocytes in the blood to adhere and migrate into blood vessel walls, where they deposit cholesterol and secrete inflammatory substances that lead to diabetes and heart disease.”

He said the findings suggest that getting enough vitamin D may reduce those properties in immune cells, decreasing inflammation and reducing the onset of a combination of heart disease and diabetes, which is often referred to as cardiometabolic disease. In addition, the researchers found that without vitamin D, monocytes carried fat to the walls of blood vessels, which is something that hadn’t been observed previously.

“We knew that when monocytes matured and became macrophages, they would eat cholesterol deposited inside the blood vessel wall,” said co-first author Amy E. Riek, MD, assistant professor of medicine. “But in these experiments, we found that when they don’t have vitamin D, the monocytes, while they’re still in circulation, also eat up cholesterol and carry it in the bloodstream.”

That’s an important discovery, Riek explained, because it’s much easier to find treatments that target something in the blood than it is to target the same cells after they move into the wall of a blood vessel.

“So that provides us, potentially, with a new target for therapy,” she said.

It also changes the way that scientists think about how lipids are carried into the blood vessel wall to cause plaques. Scientists already knew that LDL, the so-called bad cholesterol, carried fat deposits to the vessel wall. Now this study suggests that when monocytes don’t have enough vitamin D, they can do it, too.

“The monocytes were laden with fat in the absence of vitamin D receptor,” Bernal-Mizrachi said. “And they carried that fat into the artery, so that’s a new understanding of another way fat may get into blood-vessel walls in patients who are vitamin D deficient.”

Interestingly, the problem was reversible in the mice. When the animals that had developed type 2 diabetes and atherosclerosis received bone marrow transplants from mice with healthy vitamin D receptors on their monocytes and macrophages, their inflammation levels decreased, and the animals had lower blood glucose and became more sensitive to insulin.

Currently, Bernal-Mizrachi and Riek are conducting clinical studies in people who have type 2 diabetes, treating them with vitamin D to see whether it can prevent some of the complications of diabetes and inflammation in humans, too.

“As part of that study, we’re actually isolating monocytes from the blood of patients before and after vitamin D therapy,” Riek said. “So we can look at the inflammatory properties of those cells to see whether vitamin D is causing any changes.”

More information: Cell Reports, Oh et al.:”Deletion of Macrophage Vitamin D Receptor Promotes Insulin Resistance and Monocyte Cholesterol Transport to Accelerate Atherosclerosis in Mice”

via Vitamin D helps immune cells prevent atherosclerosis and diabetes.

Now in her mid-50’s, Charlotte Seefeldt finally feels like she’s back in a good place after a bumpy few years.

The Sandy Springs mom had her two children late in life, at 43 and 45, after several attempts at I-V-F.

Then, as Charlotte went through menopause a few years later, things kind of came apart.

She gained 20 pounds, and started feeling tired all the time. So she went to the doctor,

“I would sit there and tell them that something is not right. I don’t feel like I used to,” said Seefeldt.

She says the doctors told her blood tests were normal.

“Overwhelmingly, women often struggle with this,” Dr. Tasmeen Bhatia.

“Dr. Taz,”,as she goes by professionally, sees it all the time here at The Atlanta Center for Holistic and Integrative Medicine: women going through hormonal shifts, who feel depressed, but don’t know why.

“Women and their hormones are hugely connected. And their mood is very connected to that,” said Dr. Bhatia “So, women will experience everything from feeling a little blue at certain times of the month to feeling full out like they’re foggy, they can’t focus, they can’t remember words. They’re down.”

When Charlotte came in to see her last winter, Dr. Taz could tell something was wrong.

“She had trouble looking me in the eye. So, oftentimes, patients that are depressed, they’re looking down at their paper, they can’t meet you, that’s the level of their depression,” said Dr. Dr. Bhatia.

“She just spent the time listening and took in the information and started processing it in her brain and was like, ‘Okay, these are the tests we need to do. If you want to find the answers, then let’s start this,” said Seefeldt.

Charlotte’s blood work showed she was extremely low on Vitamin D, which some studies show may be connected to mood disorders like depression – seasonal affective disorder – and PMS. Dr. Taz recommended a Vitamin D supplement, to see if it could help boost Charlotte’s mood.

“I don’t, by any means, want to suggest, ‘Oh, no matter what’s happened, you take Vitamin D, you’re going to be fine.’ That’s not true. It’s just a piece of the puzzle, but it’s an important part of the puzzle.”

Dr. Taz also helped Charlotte rethink her eating, encouraged her to start exercising again – and recommended supplements to balance out her hormones.

Ten months later, Charlotte says she feels like she finally has the answers – she’d been looking for – for so long.

“You are your best judge, and if you feel something is not right, there’s probably something is not right.”

via Depression and Vitamin D – Atlanta News, Weather, Traffic, and Sports | FOX 5.

A new study conducted by researchers at Purdue University has found a metabolite resulting from the breakdown of vitamin A acts as a sort of GPS, directing certain disease- fighting cells to the body’s intestine.

“It is known that vitamin A deficiencies lead to increased susceptibility to disease and low concentrations of immune cells in the mucosal barrier that lines the intestines,” study author Chang Kim, a microbiologist and immunologist in Purdue’s College of Veterinary Medicine, said in a press release. “We wanted to find the specific role the vitamin plays in the immune system and how it influences the cells and biological processes.”

“The more we understand the details of how the immune system works, the better we will be able to design treatments for infection, and autoimmune and inflammatory diseases,” he added.

Published in the journal Immunology, the new study focused on immune system cells called innate immune cells that move quickly to eliminate an infection. These cells collect in lymph nodes before going their final destination.

In the lymph nodes, a vitamin A metabolite called retinoic acid acts upon two of three subsets of innate immune cells meant for the intestines. Kim and his team discovered that retinoic acid activates particular receptors in the cells that behave as tracking devices for the intestines. When the innate immune cells later traverse the circulatory system, the receptors seize and bind to molecules in the intestines whilst holding the cells in place.

The final location for these immune system cells is crucial because they both fight pathogens there and call for back up in the form of adaptive immune cells that are custom-made by the body to kill or neutralize the invaders.

“It is important that these cells be concentrated in mucosal barrier tissues (in the intestines), as opposed to scattered throughout the body, because these tissues are the point of entry for many infections from bacteria, viruses, and parasites,” Kim said. “Now that we have established the system of migration for these cells, we can play with it a little and see what changes the behavior and function of the cells.”

Kim added that vitamin D has also been found to guide immune cells, sending sets of them to the skin.

“We all know that what we eat significantly affects our overall health and immunity,” he said. “While there are other important regulators of immune system function, the role vitamins play is significant. How this works on a molecular level is a growing field of study.”

via Vitamin A directs immune cells to intestines – Redorbit.

Very high doses of vitamin D may help critically ill patients with respiratory failure leave the hospital sooner, a small study suggests.

Vitamin D is thought to increase the ability of immune cells to fight infection—but hospitalized patients often have insufficient levels of it because of their lack of exercise and exposure to the sun.

For the study, 31 patients were divided into three groups. Two of the groups received high doses of vitamin D3 (a total of 250,000 or 500,000 international units over five days), and one received a placebo.

Significantly shorter stay

“These dosages were significantly higher than normal daily doses and were intended to quickly restore vitamin D levels in patients who have low levels,” says Jenny Han, assistant professor of medicine at Emory University.

Study participants who received a placebo had an average blood level of 21 ng/ml vitamin D. The Endocrine Society defines deficiency as less than 20 ng/ml and insufficiency as between 20 and 30 ng/ml.

The average length of hospital stay was statistically significant for those who received the higher dose of vitamin D: 36 days for placebo, 25 days for lower dose, and 18 days for higher dose.

The length of stay in intensive care also tended to decrease (average 23 days for placebo, 18 days for lower dose vitamin D, 15 days for higher dose vitamin D), but the change was not statistically significant. A similar result was observed for duration of ventilator support.

The majority of the patients in the study had severe sepsis or septic shock; 43 percent had some type of infection upon admission. Some had cardiovascular or neurologic diseases.

More research is needed to determine the effect of vitamin D on patient recovery, the authors say.

“These data can inform the design of a larger, adequately powered randomized controlled trial on the efficacy of high-dose vitamin D3 on host immunity and other indices associated with recovery,” they write.

The findings were presented at a recent meeting of the American Thoracic Society.

Can a super-dose of vitamin D cut hospital stays? – Futurity.

I keep getting the same email over and over again, and my heart aches each time I read it: “I have tried everything to overcome my depression, but nothing has helped. Is there anything else I can do or will I have to live the rest of my life plagued with sadness?”

First, hear these three words: There is hope. If there wasn’t any, I would not be alive writing my blog. I am one of the worst cases out there like you are. I have spent more years of my life fantasizing about death than wanting to be alive. I get it. But now I do enjoy some really good days — where I feel better than I ever have. And those good days keep me motivated to get through the harder ones.

From my own 43 years of experience fighting the demon of hopelessness and from all my conversations with folks in my online depression community, Project Beyond Blue, here are some suggestions that you might try.

1. Get a Physical

The reason that you may not be getting better despite trying 20 different combinations of medication is that your symptoms of irritability, fatigue, and apathy may not be caused by a lack of serotonin or norepinephrine in your brain, but rather by a tear in your diaphragm or a problem with your aortic valve. A few conditions that are often misdiagnosed as depression are: hypothyroidism, vitamin D deficiency, vitamin B-12 deficiency, insulin resistance or blood sugar imbalances, and anemia. (See my piece, 6 Conditions That Feel Like Depression But Aren’t).

You should really get a physical and have some bloodwork done by an integrative or functional doctor; however, that can be costly, especially if you get a functional doctor who wants to run every test on you.

I asked my integrative doctor, Alan Weiss of Annapolis Integrative Medicine, to give me a list of the three or four most important blood tests a person with chronic depression should ask their primary care physician to do for them, if they can’t afford to go outside their insurance network for a consultation. He suggested:

  • Complete blood count (CBC)
  • Comprehensive metabolic profile (CMP)
  • Thyroid testing, including TSH, free T4, free T3, and thyroid antibodies
  • 25-OH vitamin D, B-12 levels

2. Check Your Thyroid

I want to return to the thyroid for a moment since this is so tricky and so critical. Every person I know who suffers from chronic depression has a thyroid issue. That is no lie or exaggeration. Every person. I was seeing an endocrinologist, someone who specializes in thyroid disease, for six years and she never tested me for an underactive thyroid. She was merely testing my TSH levels, not the full panel, which is what most primary care physicians, endocrinologists, and psychiatrists do.

If you are sluggish, gaining weight, have brain fog, need to lie down all the time, and are depressed, please have a FULL panel of your thyroid done. Your T3 and T4 levels are needed to detect slight problems that can wreak havoc with your mood and energy level. Now that I am taking natural medicine for that, I have much more energy.

Dana Trentini has a great post on her blog Hypothyroid Mom called “The Top Five Reasons Doctors Fail to Diagnose Hypothyroidism.

3. Load Up on Vitamin D and Vitamin B-12

I was relieved that Dr. Weiss included blood tests to check vitamin D and vitamin B-12 levels, as well, because deficiencies in both of those vitamins can cause severe depression. They are included in my list of 10 Nutritional Deficiencies That Can Cause Depression.

According to a 2009 study published in the Archives of Internal Medicine, as many as three-quarters of U.S. teens and adults are deficient in vitamin D. Last year Canadian researchers performed a systematic review and analysis of 14 studies that revealed a close association between vitamin D levels and depression. Researchers found that low levels of vitamin D corresponded to depression and increased odds for depression. In another 2009 study, more than a quarter of severely depressed older women were deficient in B-12. I take each of those vitamins in liquid form so that they absorb quickly and efficiently.

4. Adjust Your Diet

If you are annoyed at this suggestion, let me say I understand. I was annoyed for the first 40 years of my life when someone would insinuate that there was a tight connection between my diet and my distorted thinking. I thought I ate well. By most American standards, I was a health freak. However, I didn’t realize how much insulin I was throwing into my bloodstream until I stopped eating all sugar cold turkey one day, as well as processed flour, dairy, and caffeine. (Alcohol is bad news too, but I gave that up 25 years ago.)

All those nut and fruit KIND bars that are supposed to be good for you, the honey in my tea, the cereal and pumpkin bread in the morning … all of them were creating a blood sugar nightmare that got me high only to make me crash … and hard. No street drugs were involved. Just a lame granola bar that I thought was sanctioned by Dr. Oz. Consider eliminating sugar and white flour from your diet for a few months. As much as I’d like to tell you that the effect was immediate, it took up to nine months before I really started to feel better, before I was free of death thoughts.

5. Get a Consultation With a Teaching Hospital

Before my husband begged me to have a consultation at Johns Hopkins Mood Disorders Center, I had been to six psychiatrists. One of my blogs, in fact, is called The Psychiatric Guide to Annapolis. Let me just say that there are a lot of people who shouldn’t be practicing medicine, like one I dubbed “Pharma King,” who received generous kickbacks from a pharmaceutical company.

The reason I trust teaching hospitals like Johns Hopkins, is that they never stop researching, and they are not afraid to use the older drugs like lithium that have proven track records but aren’t lucrative. Kay Redfield Jamison, a professor of psychiatry at Johns Hopkins, wrote an excellent op-ed piece in the New York Times just after the death of Robin Williams entitled Depression Can Be Treated, But It Takes Competence.

She writes: “Many different professionals treat depression, including family practitioners, internists and gynecologists, as well as psychiatrists, psychologists, nurses and social workers. This results in wildly different levels of competence. Many who treat depression are not well trained in the distinction among types of depression. There is no common standard for education about diagnosis.” Go to a teaching hospital. You won’t regret it.

6. Consider Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a non-invasive procedure that stimulates nerve cells in the brain with short magnetic pulses. A large electromagnetic coil is placed against the scalp which generates focused pulses that pass through the skull and stimulate the cerebral cortex of the brain, a region that regulates mood. The procedure was approved by the FDA in 2008.

In September, I featured a story about Stephanie, a woman in Project Beyond Blue, who underwent 30 sessions of TMS and was transformed into a new person. She now moderates a group on Project Beyond Blue called Exploring TMS. Several other people I know have had success as well.

7. Try EMDR

My friend Priscilla Warner first turned me on to eye-movement desensitization and reprocessing (EMDR) therapy. She devotes a chapter in her bestselling memoir, Learning to Breathe, about it, and how it was instrumental in breaking down her anxiety. It is mostly used for people with some form of post-traumatic stress disorder, but it has also been used to address generalized anxiety from a dysfunctional childhood, a bad marriage, or a boss from hell.

According to the EMDR Institute, “EMDR psychotherapy is an information processing therapy and uses an eight phase approach to address the experiential contributors of a wide range of pathologies. It attends to the past experiences that have set the groundwork for pathology, the current situations that trigger dysfunctional emotions, beliefs and sensations, and the positive experience needed to enhance future adaptive behaviors and mental health.”

8. Find a Way to Lower Your Stress

I don’t mean putting a few less to-do items on your list. I’m talking about radical lifestyle changes — like changing jobs in order to work in a less toxic and stressful environment, moving into a smaller home so that you don’t have to moonlight, deciding against adopting a rescue dog or having a third child. It can be practically impossible to keep your mood resilient if you are under chronic stress because it increases the connection between the hippocampus part of your brain and the amygdala (worry central), impairs your memory retention, affects your cortisol production (making it difficult for you to handle more stress), and weakens your immune system.

There are other ways to try to lower your stress besides quitting your job, like practicing mindfulness meditation. I took the eight-week Mindfulness-Based Stress Reduction (MBSR) program at my local hospital because I read numerous studies on how mindfulness meditation can reset neural passageways and change rumination patterns. As a result of the class, I am now more aware of my thinking, and I try my best to keep coming back to the present. However, nothing beats the anesthesia from depression and the calm I experience after an intense aerobic workout. I swim and run for my sanity.

In summary, the road to my recovery has been rocky as hell. I had to throw out the old system — my belief that medication, therapy, and exercise was all I needed — that the brain lived in another solar system as my body. I now believe that you must approach the illness of depression systematically: there is nothing that you eat, say, or do in your day that doesn’t affect your mood. While that thought can be overwhelming, it also points the way to hope.

You are not a lost cause.

Join conversations like “Hypothyroidism & Depression” and “Nutrition” on Project Beyond Blue,” a new community for persons with treatment-resistant depression.

Originally posted on Sanity Break at Everyday Health.

8 Things to Consider When Your Depression Is Not Getting Better | World of Psychology.

Buck research: Vitamin D extends worm lives | North Bay Business Journal.

(HealthDay News) — For patients with systemic lupus erythematosus, vitamin D3 supplementation does not affect interferon signature, according to a study published in the Arthritis & Rheumatology.

Cynthia Aranow, MD, from the Feinstein Institute for Medical Research in Manhasset, New York, and colleagues examined the effects of vitamin D supplementation on the interferon signature (expression level of three interferon genes) in 57 patients with stable, inactive systemic lupus erythematosus.

Patients were randomly assigned into a 12-week trial of vitamin D3 at doses of 2,000 IU or 4,000 IU, or placebo.

Repletion of 25-hydroxyvitamin D (≥30 ng/mL) was observed in 16 of the 33 patients receiving vitamin D3, but in none of the patients receiving placebo, according to the data. There was no difference between the treatment groups in the percentage of patients with an interferon signature response.

Furthermore, the percentage of patients with an interferon signature response did not differ between those who remained vitamin D deficient and those who demonstrated repletion of vitamin D.

No changes from baseline were seen in any of the treatment groups in modular microarray analysis of a subset of 40 patients; there were also no differences in expression among patients with vitamin D repletion vs. those with persistent vitamin D deficiency.

“Vitamin D3 supplementation up to 4,000 IU daily was safe and well tolerated but failed to diminish the [interferon] signature in vitamin D-deficient [systemic lupus erythematosus] patients,” the researchers wrote.

One author is an employee of Rho Federal Systems, a division of Rho, a contract research organization.


  1. Aranow C et al. Arthritis Rheumatol. 2015;67(7):1848-1857.

Interferon Response Not Affected by Vitamin D in Systemic Lupus Erythematosus.

Calcium and vitamin D supplements have been shown repeatedly to have no beneficial effect on preventing or treating osteoporosis, as I’ve pointed out here many times before.

In fact, the evidence has not only demonstrated that calcium and vitamin D supplements do not reduce the risk of bone fractures, it has also found that they may cause harm in some cases. This harm includes a greater risk of developing kidney stones, gastrointestinal symptoms that require hospitalization, heart attacks, stroke and even (paradoxically) hip fractures.

Yet doctors continue to recommend the supplements to their patients. And people keep taking them. Indeed, studies have revealed that more than half of older Americans (70 percent of older women) take either prescription or over-the-counter calcium and/or vitamin D supplements — mostly because they’ve been told the products will strengthen their bones.

Why has the evidence about the ineffectiveness of these supplements in preventing broken bones and about their potential for harm — evidence that has been around since 2002 — failed to dampen people’s belief in them?

After all, other therapies once recommended for the prevention and treatment of osteoporosis — estrogen, calcitonin and fluoride — were essentially abandoned once they were shown to be ineffectual or harmful.

‘A complex web’

The answer can be found in the “complex web” of interactions between the supplement industry and advocacy groups, academics and medical specialty societies, according to a commentary published this week in the British-based journal BMJ.

All those stakeholders benefit financially by promoting the use of the supplements, write Dr. Andrew Grey and Dr. Mark Bolland, associate professors of medicine at the University of Auckland in New Zealand.

“Industry gains scientific credibility, which protects or enhances the sales of its products, and indirect marketing through advocacy groups,” they explain. “Advocacy organisations and specialist societies gain funds to support their existence. Academics gain by maintenance of their status and by obtaining access to research funds and career enhancing publications and presentations.”

And who loses? The public.

“Failure to reverse inappropriate practice leads to overtreatment, systematic waste of healthcare resources, unnecessary costs for patients, and missed opportunities for application of interventions with provide efficacy,” say Grey and Bolland. “Ultimately, the cost is erosion of trust in the medical system.”

Following the money

Here are just a few of the reasons Grey and Bolland cite for why medical specialty societies, advocacy groups and academia continue to discount the science and promote supplements for preventing and treating osteoporosis:

  • Calcium and vitamin D supplements are enormously profitable — and not just for the companies that make and sell them.

Global annual sales of calcium supplements in 2013 were about $6 [billion], and those of vitamin D in the US in 2012 were $748 [million]. Companies that market foods rich in calcium or vitamin D also profit from the notion that these nutrients prevent osteoporosis. … Other industries benefit from enthusiasm for use of supplements for osteroporosis. Measurement of [blood levels of vitamin D] has become widely used, benefiting both the manufacturers of assay kits and the laboratories that perform the tests.

  • Health-advocacy groups, such as the National Osteoporosis Foundation (NOF) in the United States and the International Osteoporosis Foundation (IOF) in Europe, rely heavily on money from commercial sponsors.

Both [the NOF and the IOF] state their aim as improving patient outcomes, but their objectivity may be compromised by the influence of a range of commercial sponsors, including companies that market supplements, dairy products, and nutrition related laboratory tests.  … Twelve of the 22 NOF corporate sponsors and 14 of the 25 IOF corporate sponsors are active in nutrition related commercial enterprises. … Members [of the NOF’s Board of Trustees] include supplements manufacturers, companies that produce vitamin D tests kits, and the Council for Responsible Nutrition, which describes itself as the “leading trade association representing dietary supplements manufacturers and ingredient suppliers.” … After evidence accrued that calcium and vitamin D do not safely reduce fracture risk, the nutrition industry continued to partner osteoporosis advocacy organisations to promote their widespread use.

  • Some academic researchers also rely heavily on the support of the nutrition and supplement industry, although they have often failed to disclose that financial connection.

Financial involvement of the nutrition industry in calcium and vitamin D publications has been inconsistently acknowledged. For example, in publications about vitamin D coauthored with bone nutrition academics, employees of [the Council for Responsible Nutrition and the supplement manufacturing giant DSM] acknowledged their affiliations but declared no financial conflicts of interest. In addition, prominent academics wrote manuscripts about vitamin D and calcium without disclosing relevant conflicts of interest, including receiving money for research support, participation in speakers bureaus and payments for consultancies and writing manuscripts. Other groups of academics that are sponsored by companies that market nutritional supplements, dairy foods, or vitamin D assay kits, such as the Belgian Bone Club and the International Institute for Nutrition and Bone Health, formulate “consensus” documents and publish manuscripts that endorse nutritional interventions without always acknowledging, or incompletely acknowledging, their commercial conflicts of interest. …

Setting aside finances, academic leaders may also have academic conflicts of interest. For example, their career development may be enhanced by the persistence of beliefs that nutritional supplements benefit the skeleton. Such conflicts of interest may have influenced the Endocrine Society’s endorsement of widespread moderate dose vitamin D supplementation in contrast with the Institute of Medicine (IOM), which recommended low level supplementation for older adults, and the Preventive Services Task Force, which advised against vitamin D supplementation.

It is, indeed, a tangled web of vested interests. You can read Grey and Bolland’s commentary on the BMJ website.

A ‘complex web’ of vested interests promote calcium and vitamin D for osteoporosis, despite lack of evidence | MinnPost.

Vitamin D has been known for promoting strong bones, regulating blood pressure and even improving one’s mood. Could it be the key to fighting one of the most deadly cancers? U.S. researchers are testing the impact of adding vitamin D to the treatment regimen for some pancreatic cancer patients.

Daryl Fair, 76, retired from teaching American politics to travel and spend time with family. Earlier this year, doctors treating him for pneumonia discovered something unexpected.

Fair told ABC30, “It was a small tumor on the head of the pancreas.”

Doctors caught Fair’s cancer very early, unusual for pancreatic cancer. Patients often have no early symptoms. Because he caught it early, Fair qualified for a clinical trial, testing the impact of vitamin D on treatment.

Jeffrey Drebin, MD, PhD, Chairman of the Department of Surgery at Perelman School of Medicine of the University of Pennsylvania explained, “This is not vitamin D that you can get at the drug store.”

Researchers found that this potent vitamin D inactivates the body’s cells, called stromal cells that protect and feed pancreatic tumors.

“Vitamin D acts on these cells to make them quiescent,” Dr. Drebin told ABC30.

If the stromal cells aren’t working, researchers say chemotherapy drugs will reach the tumors and hopefully, wipe out the cancer. For now, patients are receiving vitamin D three times a week.

Peter O’Dwyer, MD, Professor of Medicine at Perelman School of Medicine of the University of Pennsylvania told ABC30, “To get the high levels that we think we need within the tumor, we’re giving it as an IV in the initial trial of this.”

Fair explained, “I think studies like this are the things that are eventually going to make cancer readily curable.”

And bring hope to patients facing a tough battle.

Researchers say they would like to develop an oral form of the synthetic vitamin D, so patients in future trials could have the treatment at home. They say the results of this trial may also impact treatment for other stubborn tumors. Doctors Drebin and O’Dwyer are part of a team of collaborators being funded by “Stand Up To Cancer.”

For more information on this report, please contact:

Steve Graff

Vitamin D for pancreatic cancer |

Vitamin D is a key player in bone health, but do we need to take supplements to get enough of it?

The United Kingdom’s independent Scientific Advisory Committee on Nutrition, a community of experts that advises government agencies, thinks so. It announced draft recommendations last week for a 10 microgram dietary supplement of vitamin D for U.K. citizens aged 1 year or older.

Last year, the vitamin supplement industry was worth about $36.7 billion, a record high, according to the Nutrition Business Journal, and industry experts expect it will continue to grow. While sales of most letter vitamin supplements decreased in that time, sales of vitamin D — which helps the body absorb calcium from foods and supplements — increased 8.1%.

The Institute of Medicine, a nonprofit public policy consulting organization, recommends a daily dose of 600 international units, or 15 micrograms, for the average American or Canadian.

Dr. John Cannell, founder of the vitamin D Council, said natural levels, or those of people exposed to the sun for the majority of their day, are around 5,000 to 10,000 IUs. He added that changing attitudes toward sun damage have limited people’s opportunities to produce vitamin D in the skin.

“There are two choices, to get it from sunlight or take it as a supplement. There is no third choice,” Cannell said. “People have to make a choice.”

Cannell said there is no definitive answer to how much sun exposure will allow your skin to produce an adequate amount of vitamin D.

He added that vitamin D is incredibly important for growth and development, especially in pregnant women and young children.

Cannell said he recommends people take 5,000 IU a day if they are not out in the sun, though in an ideal world the most effective method of administration would be to eat foods fortified with vitamin D. Most foods don’t currently contain a lot of vitamin D, but he said manufacturers could add it to more foods.

Deficiency in the nutrient has been linked to poor health conditions, including heart disease, cancer and osteoporosis. However, as two studies — published in the January 2014 issue of The Lancet — from researchers in France and New Zealand suggest, low vitamin D levels may be a result of poor health rather than a cause.

“What [the researchers] concluded was that there are associations with many different health problems that lead to low vitamin D levels,” said Steven Salzberg, a biomedical engineering, computer science and biostatistics professor at Johns Hopkins University.

Unless your doctor finds that you have a vitamin D deficiency, “routine supplementation of vitamin D does not provide any benefits,” Salzberg said.

Exposing your skin to sunlight for half the time it takes for it to turn pink can give you the adequate amount of vitamin D, according to the vitamin D Council, a nonprofit organization.

Dr. A. Marc Gillinov, a heart surgeon at the Cleveland Clinic, wrote in a blog for the Huffington Post that just 10 minutes of direct sun exposure to your arms and legs while not wearing sunscreen can give you about 3,000 IUs of vitamin D — five times the recommended daily dosage.

“Most healthy adults do not need to take vitamin D supplements,” Gillinov wrote. “Extra vitamin D does not improve health in those without bone disease. Get your vitamin D the old fashioned way.”

Too much vitamin D, which the National Institute of Health states as more than 10,000 IUs for children 9 years and older and adults, can cause nausea, vomiting, disorientation, problems with heart rhythm and kidney damage.

“You think that since a little bit is good for you, more is probably better,” Salzberg said. “But it’s not.”

Do we all really need to take vitamin D supplements? – MarketWatch.

Low vitamin D levels are linked to a greater risk of bone fractures in women after menopause — but taking high doses of supplements is not the answer, according to new research.

A study published online Monday in JAMA Internal Medicine suggests the common practice of prescribing vitamin D supplements to fill the gap does not have any benefit for older women’s bones or muscle strength.

“While high-dose vitamin D did indeed increase calcium absorption, the increase was only 1 percent and [it] did not translate into gains in spine, hip or total body bone mineral density,” study author Dr. Karen Hansen, an associate professor of medicine at the University of Wisconsin School of Medicine and Public Health in Madison, told HealthDay. Her team “did not find any benefit of vitamin D, in either high or low dose, on muscle mass, two tests of muscle fitness or fall.”

The study included 230 women younger than 75, but past menopause, who had low vitamin D levels. The women did not have risk factors for other kinds of bone complications. They were divided into three groups and given various doses of vitamin D3, or cholecalciferol, over a year: none (placebo), 800 IUs daily (low-dose) and 50,000 IUs twice monthly (high-dose).

Although the high-dose supplement group achieved the goal of raising their vitamin D levels to 30 nanograms per milliliter, they did not show any benefit in bone density testing, muscle strength measures or a sit-and-stand test, which assesses risk for falls.

Long-standing debates about what level of vitamin D should be the baseline — 20, 25 or 30 nanograms per milliliter — in addition to how much supplementation is necessary have limited attempts to set recommendations for vitamin D. Researchers say the results of this study are more evidence that the higher level is unwarranted for post-menopausal women.

In an editor’s note published in the same journal, Dr. Deborah Grady, a professor of medicine at the University of California, San Francisco, and deputy editor of JAMA Internal Medicine, writes, “It is possible that treatment beyond 1 year would result in better outcomes, but these data provide no support for use of higher-dose cholecalciferol replacement therapy or indeed any dose of cholecalciferol compared with placebo.”

“I think this is the final, and negative, word on vitamin D supplementation,” Dr. Rita Redberg, a professor of medicine with the University of California, San Francisco’s Philip R. Lee Institute for Health Policy Studies and editor of JAMA Internal Medicine, told HealthDay. “There are a lot of women getting vitamin D blood tests and taking vitamin D supplements of various doses. This study suggests that those practices should stop. In other words, if you are going to start vitamin D to improve bone health, and if you are currently taking it for that reason, you can stop. I know of no other benefits for vitamin D supplementation.”

Vitamin D is the companion to calcium, working to help the body utilize more of the mineral necessary to strengthen bones and help muscles function. The amount of vitamin D is less important than how much is “bio-available,” or readily absorbed. The NIH says there is some risk that too much vitamin D in the bloodstream can cause digestive problems and kidney damage, though complications are rare.

In addition to added risk for bone fractures and falls in older adults, low levels of vitamin D have been associated with higher risk of cardiac disease, dementia and Alzheimer’s disease.

The U.S. Preventative Services Task Force does not recommend vitamin D supplements to prevent fractures and falls in post-menopausal women until age 65 or older.

And ongoing research suggests that people of various races, ages or sexes may need different amounts of vitamin D because their bodies absorb and produce the vitamin differently.

Although vitamin D is called the “sunshine vitamin” because it is most easily produced through skin exposure to the sun, doctors caution against extra UV exposure through sun or tanning beds because it raises the risk of skin cancer.

Vitamin D is also found in foods like fatty fishes, some whole grains, eggs and dairy products that are fortified with added vitamin D. Recommended dietary allowances for the vitamin are between 400-800 IU per day and this study does not affect those baseline recommendations.


Vitamin D supplements don’t protect bones of older women, study finds – CBS News.

Autism symptoms dramatically improved after treatment with Vitamin D.

Anti Angiogenesis Foods


This is your last chance, after this there is no turning back.
You take the blue pill, the story ends; you wake up in your bed, and believe whatever you want. You take the red pill, you stay in wonderland and I show you how deep the rabbit hole goes.I know you’re out there, I can feel you now.
I know that you’re afraid of us…You’re afraid of change. I don’t know the future, I didn’t come here to tell you how this will all end…I came here to tell you how it’s going to begin

Clip3.jpg JPEG Image, 464 × 329 pixels.



April 2 at 2:40 AM

It happens in an instant just before you fall asleep. You’re startled by a loud noise — the thud of a book slamming to the floor, or worse, the bang of a shotgun nearby. You a jump up and look around, but everything seems normal. Well it is, but you did hear a noise that wasn’t real. It was in your brain.

It’s a phenomenon called “exploding head syndrome.”

“It can sound like explosions, gunshots in your head, giant guitar strings breaking beside you or something heavy being dropped,” Brian Sharpless, assistant professor and director of the psychology clinic at Washington State University, told The Washington Post. He’s also the lead author of a study on the disorder. “A small number of people will see lightning, flashes of light or visual static like you see on a TV screen. It’s scary, and people wake up confused.”

Exploding head syndrome has received little clinical attention over the years. Scientists have hypothesized the condition is rare and seen mostly in people older than 50. But when Sharpless and his researchers assessed 211 undergraduate students for sleep paralysis as well as exploding head syndrome — which appear to be connected — they found the phenomenon is more common than clinic lore led them to believe. The researchers recently published the findings in the Journal of Sleep Research.

Its symptoms were first described some 150 years ago. Doctors have noted it in literature as “sensory discharges” and, later, “snapping in the brain.” In 1988, neurologist J.M.S. Pearce dubbed it “exploding head syndrome.”

Sharpless and his colleagues found that 18 percent of the people they interviewed had experienced the disorder at least once. More than 16 percent had recurring cases. However, when the researchers removed those who had also experienced sleep paralysis, the number fell to 13.5 percent — which is still “shockingly high,” he said.

The sensation occurs during “sleep state misperception,” the moment right before people doze off, though it can also happen as they are waking up.

“Your brain essentially has a hiccup in the reticular formation, which is the part of the brain that helps shut down your body for sleep,” Sharpless said. “It shuts down your motor, visual and auditory neurons. But with exploding head syndrome, instead of the auditory neurons shutting down, they fire all at once.”

That hiccup can make people hear a noise that isn’t there — sometimes in their ears, other times in their heads. In some instances, people have seen lightning or other flashes of light, or felt an intense heat all over, according to Sharpless’s research. But despite how scary the name is, “it’s physically harmless,” he said.

“Some people with exploding head syndrome thought they were having a seizure or a subarachnoid hemorrhage or something really bad,” he said. “There is some evidence that just learning about it can reduce the frequency of the episodes.”

Less than 3 percent of those who had experienced it had it to an extent that it interfered with their lives, according to the research. “If it happens that much, it’s not doing good things for your sleep,” Sharpless said, but that’s about it.

The next phase it to try to understand what might make people more likely to have it.

That loud bang that startles you awake: It may be ‘exploding head syndrome’ – The Washington Post.

A 1,000-year-old Anglo-Saxon salve of onion, garlic, and part of a cow’s stomach could potentially eradicate the MRSA superbug problem.

An Anglo-Saxon Expert, Christina Lee, of the University of Nottingham, spotted the eye infection remedy in a medical volume called Bald’s Leechbook that was held in the British Library in London. According to CBS News, it is one of the earliest known textbooks in medicine dating back to the 10th Century.

When they tested the mixture to the superbug Methicillin-resistant Staphylococcus aureu (MRSA) in lab-cultured Petri dishes and on the infected wounds of mice, they found that it killed 999 out of 1,000 bacterial cells.


“We thought that Bald’s eye salve might show a small amount of antibiotic activity, because each of the ingredients has been shown by other researchers to have some effect on bacteria in the lab,” says Freya Harrison, one of the lead Nottingham researchers, in a statement. “But we were absolutely blown away by just how effective the combination of ingredients was.”


Lee and her team were “astonished” as they studied the results of their experiments. She believes that modern research can learn more from past knowledge and findings that are found in old world tomes and medical books.


“When we built this recipe in the lab I didn’t really expect it to actually do anything,” microbiologist Steve Diggle said, noted CBS. “When we found that it could actually disrupt and kill cells in S. aureus biofilms, I was genuinely amazed. Biofilms are naturally antibiotic resistant and difficult to treat so this was a great result.”


The group of researchers recreated the 10th century concoction according to its original instructions. The text was translated from Old English, and in the recipe they made use of two species of Allium (garlic and onion or leek), wine, and bile from a cow’s stomach. They let the potion brew in a brass pot, then strained through a cloth, and left to sit for nine days, according to ABC News.


The AncientBiotics team at the University of Nottingham is currently looking for more funding to further their research. The preliminary study was presented at the conference of the Social for General Microbiology in Birmingham in England last Wednesday.

According to the U.S. CDC, the MRSA has become a major problem in the healthcare industry. It affects around 90,000 Americans yearly and has already costed billions of dollars. The MRSA kills off around 20,000 people each year.

The end of doctors:


Hospital admissions plummeted at Vidant Health-operated facilities after it started remotely monitoring patients suffering from heart failure, diabetes and high blood pressure. Patients at the University of Pittsburgh Medical Center send doctors pictures of their wounds from offsite in order to find out if they need antibiotics. And a patient at the hospital had his blood-pressure medication adjusted after he wirelessly sent the doctors biometrics from his home.

Such stories, which were just chronicled in The Wall Street Journal, are becoming increasingly common. Remote monitoring can empower patients and lead to more fine-tuning of care while saving hospitals money and helping hospitals meet their Affordable Care Act (ACA) goals, like reducing hospitals readmissions (or else facing a reduction in Medicare reimbursement).


Sales of remote-monitoring devices are expected to top $32 billion this year, according to Market Research Group, and will grow at a compounded annual growth rate of 9.2% between 2014 and 2019.



MRSA Superbug Killed by 1000-Year-Old Medieval Eye Infection Treatment : Latinos Health News : Latinos Health.

A book worth reading and a blog worth looking into:

Magnesium is important in over 325 enzyme reactions in the body.1 It is used to regulate blood sugar in the body, and to help prevent you from developing diabetes.2 Magnesium relaxes arteries that carry blood throughout the body, which lowers blood pressure. Magnesium also chelates extra calcium in the body; this keeps the arteries from hardening due to excess calcium. Finally, magnesium supplementation can help lower stress and anxiety levels.


Let’ us take a look at the many magnesium types and their functions, but the best form I can recommend is magnesium glycinate. The body absorbs the most elemental magnesium from glycinate.3 The extra glycine, an amino acid, relaxes nerves, and relieves anxiety.


Possible Symptoms of A Magnesium Deficiency




This is a list of possible symptoms a patient might have if they have a magnesium deficiency. If a magnesium deficiency is present, you can still have a magnesium deficiency and not have any of these symptoms as well. This often occurs in patients that are younger (age helps reduce the symptoms of a magnesium deficiency,) and it can also depend on the gender (men tend to have less symptoms than women.) Most people should supplement with 400 mg of elemental magnesium (as long as their kidney function is normal) even if they do not know if they are deficient.4


·        Tingling in legs – Magnesium deficiency is the main cause of restless legs syndrome


·        Leg cramps (charlie horse)


·        Weakness


·        Asthma


·        Elevated blood pressure and/or pulse


·        Heart disease


·        Diabetes


·        Dizziness


·        Shaking


·        Irregular heartbeat (palpitations)


·        Constipation5


 Diagnostic Tests for Magnesium Deficiency




Here is a simple guide of the different tests that are used to determine if you have a magnesium deficiency or not.


Magnesium Serum Test – A magnesium serum test is the most common magnesium test performed and also the most inaccurate. Less than 1% of the body’s total magnesium is in the blood plasma and the body does whatever it takes to keep that number regular. If you score low on a plasma test then you are in dire need of magnesium and you are definitely deficient in your bones, organs, and muscles.6 This test is used to measure extracellular magnesium levels. Normal plasma magnesium levels are, 1.6 – 2.4 mEq/L.7 This test does not accurately measure the body’s total magnesium level, but is the test most often used for diagnostic testing.


Magnesium RBC Test – A magnesium RBC test is a more accurate test that quantifies the amount of magnesium stored in the red blood cells. This test measures intracellular magnesium levels. This test gives you the amount of magnesium that has been stored in your cells for the past four months.  Results of six mg / dl or higher indicate strong magnesium reserves in the body.8


Magnesium WBC Test – A magnesium WBC test is more accurate than the RBC test. Like the magnesium RBC test, the WBC test also measures intracellular magnesium levels. This test gives you the amount of magnesium that is currently in your cells, it does not show an average of magnesium in the cells over a period of time like the RBC test. This test is not available to many doctors or diagnostic labs.9


Magnesium EXA Test – A magnesium EXA test is the best test to determine magnesium deficiency. This test is performed by scraping your cheek buccal cells for a sample so that levels of magnesium stored in your cells, bones, and muscles can be determined. Like the WBC test, the EXA test is considered an intracellular magnesium test. The EXA test will account for 99% of the body’s total magnesium, and is the most accurate diagnostic test for magnesium currently.10


Part 1
Part 2
Part 3
Part 4
Part 5
Part 6



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  1. Magnesium: Most Overlooked Mineral For Improving Health – Part 5 – Fix Your GutDecember 30, 2014[…] Part 1 Part 2 Part 3 Part 4 Part 5 Part 6 […]
  2. Magnesium: Most Overlooked Mineral for Improving Health – Part 4 – Fix Your GutDecember 30, 2014[…] Part 1 Part 2 Part 3 Part 4 Part 5 Part 6 […]
  3. Magnesium: Most Overlooked Mineral for Improving Health – Part 2 – Fix Your GutSeptember 30, 2014[…] Part 1 Part 2 Part 3 Part 4 Part 5 Part 6 […]
  4. Magnesium: Most Overlooked Mineral For Improving Health – Part 6 – Fix Your GutSeptember 30, 2014


Magnesium and Your Digestive Health


Magnesium is used in the body to help active digestive enzyme reactions in your body as well as regulate the proper transit time of your bowels.1 2 The enzyme reactions in your body help further break down fats, proteins, and carbohydrates. Magnesium chloride can help increase stomach acid to help assimilate food better if you have digestion problems it might be the type you want to use.3 Most all other magnesium (unless chelated with an acid like citrate or malate) lower stomach acid so they should be taken before bed so problems with digestion will not occur.




Magnesium is used by your intestines as an osmotic laxative.4 This means that your large intestine uses magnesium to bring in water into the bowl so that your stool becomes softer and easier to pass. This is why magnesium supplementation is a great treatment for someone who has constipation issues.5 Magnesium is very important for the functioning of your digestive system as well as your complete health as well.


Different Forms of Magnesium


Recommended Forms of Magnesium:




Magnesium glycinate – The most bio-available form of magnesium. The extra glycine as an amino acid can help with sleep and provide a calm feeling. This form of magnesium is the least likely to cause loose stools. Taken at bedtime.6


Magnesium malate – Magnesium malate is important for people who have a lot of fatigue or suffer from Chronic Fatigue Syndrome. Magnesium supplementation increases ATP, which is a molecule that provides energy to our cells. Malic Acid has also been shown to increase ATP levels. Magnesium malate should be taken during the day with meals. The extra malic acid will increase stomach acid and assimilation.7


Magnesium chloride – Magnesium chloride is one of the best forms of magnesium for people with Gerd or stomach problems. It must be taken with food because the extra chloride will definitely make more HCL in the stomach. Can also be used topically as a spray for transdermal supplementation.8


Magnesium taurate – Magnesium taurate is a lifesaver for people with heart disease. The extra taurine is an amino acid helps increase heart function. Taken at bedtime.9


Magnesium citrate – Magnesium citrate should mostly only be used for bowel irrigation, it is also one of the most well-known forms of magnesium supplementation. It causes some loose stools and its absorption is average. Magnesium citrate should be taken with meals because the extra citric acid will increase stomach acid and assimilation.10


Magnesium sulfate – Honestly only used to stop pre-eclampsia and used in bath salts as epsom salt. Has okay absorption but does leave some extra organic sulfur in the body can be absorbed by the skin. Sulfate can help heal muscle sprains better than most other forms of magnesium because of skin permeability. Taken soaking in a bath or before bed.11


Magnesium arginate – Arginine is a vasodilator amino acid that is good for increasing blood flow.12 This form of magnesium is very good for bodybuilders. Taken with meals throughout the day due to the possibility of increased energy.


Magnesium lysinate – A good source of magnesium and the amino acid lysine. Lysine is an excellent anti-viral. Taken before bed.13


Magnesium ascorbate – A good source of magnesium and vitamin C. Can cause some loose stools. Taken before bed.14


Magnesium ZMK- A great form of magnesium that uses magnesium from all of the Krebs cycle: citrate, fumarate, malate, succinate & alpha-keto-glutarate. This supplement form of magnesium ZMK is great for athletes, and is very good for recovery. A ZMK supplement should be taken before bed.


Magnesium fumerate, succinate, alpha-keto glutarate – See Magnesium ZMK, All Krebs cycle forms of magnesium.15


Magnesium gluconate – A form of magnesium that is chelated with gluconic acid, which occurs from the fermentation of glucose. Magnesium gluconate has above average absorption in the body (better than even magnesium citrate)16, rarely causes loose stools. Taken before bed.


Magnesium carbonate – This is probably the lowest form of magnesium I can recommend. Has one of lowest levels of assimilation and is a good osmotic laxative. It can also lower stomach acid levels and is used in most antacids. Taken at bedtime.17


Magnesium With Special Uses:




Magnesium orotate – This is one least known forms of magnesium, but let me tell you if you just had a surgery or exercise constantly then it will be your godsend. The extra orotate will help muscle regeneration.18 It also has been shown to support heart health greater than even magnesium taurate. Taken at bedtime.19


Magnesium L-threonate – Magnesium L-threonate may greatly increase magnesium in the brain and spinal column for increased cognitive function.20 To be honest there isn’t a lot of in vivo research to prove if this is true yet though. L-threonate is an isomer of ascorbic acid.21 (New research has shown that it increases magnesium levels about the same as magnesium sulfate, granted magnesium sulfate is injected which might make it be able to cross the blood brain barrier then oral magnesium.22) Taken at bedtime.


Magnesium 2-AEP – This is a form of magnesium that is chelated with phosphorylethanolamine which is a vital component of the structure and integrity of cell membranes. Magnesium 2-AEP has been theorized to help patients with MS, because it can help with cellular function and integrity and can help protect myelin in the brain. Taken with meals during the day.23


Magnesium peroxide – ONLY AS COLON CLEANSER. Taken before bed.


Magnesium Phos 6X – Normally I do not recommend homeopathic supplements (if they work for some people I’m glad they do, I rather recommend nutriceuticals), but for homeopathic minerals I feel they still can be beneficial because some of the trace mineral should be left in the product. I would suggest on using this in a person who is extremely sensitive to all forms of magnesium supplementation. If magnesium glycinate still causes loose stools and magnesium chloride causes allergic reactions on the skin then this is the magnesium for you to try. 24 This magnesium contains some phosphorus so I would suggest if you have kidney problems to stay away from this form. Taken before bed.25


Garbage forms of Magnesium:




Most of these forms of magnesium I consider are garbage because they either do damage in the body or are very poorly absorbed.


Magnesium yeast chelate – A “natural” form of magnesium that is very easily assimilated by the body, what sounds so wrong about that? This form of magnesium is found in most of your “natural” vitamins like New Chapter, Garden of Life, and Megafood. The main problem I have with this form of magnesium is that you have to ingest a lot of brewers yeast (which some people are sensitive to) in the whole supplement to get a tiny amount of magnesium.26 Most vitamins that use this form of magnesium have very little magnesium actually in the vitamin (less than 100 mg elemental). There are just a lot better options out there. Taken with food.


Magnesium aspartate – Absorption is notworth extra aspartic acid. Too much aspartic acid can be neurotoxic. Can you say ASPARTAME? Taken at bedtime. This includes magnesium ZMA supplements.27


Magnesium pidolate (Magnesium 5-Oxo Proline) – Absorption is DEFINITELY not worth the extra free glutamic acid. Too much free glutamic acid can be excitotoxic and neurotoxic. Can you say MSG? Taken with meals.


Magnesium hydroxide – Not greatly absorbed and most magnesium is released into the bowels. Most commercial preparations (Milk of Magnesium) have sodium hypochlorite added (bleach.) Taken at Bedtime.28


Magnesium oxide – VERY POORLY ABSORBED – Out of 400 mg only AT MOST 80 mg of elemental magnesium is absorbed by the body. Magnesium oxide is one of the worst absorbed forms of magnesium, and sadly the most common supplement form of magnesium taken. Taken at Bedtime.29


Magnesium glycerophosphate – This magnesium is chelated with phosphorus. The problem with this magnesium is that most people get too much phosphate in their diet. People with kidney problems should also definitely stay away from this supplement because it is harder for them to eliminate excess phosphates. Taken at bedtime.30


Magnesium lactate – Extra lactic acid is FUN! Should not definitely not be used for people who have kidney disease because the extra lactic acid can cause complications for the kidneys. I do not generally recommend this form at all. Taken during meals.


Magnesium: Most Overlooked Mineral for Improving Health – Part 2 – Fix Your Gut.

Ashely Judd

Billy Joel

Hugh Laurie

Jim Carrey

How can somebody so funny be secretly struggling with depression? Such is the case with celebrated comedic actor Jim Carrey, who has been very open about his long-term depression battle. In a 2008 interview with the British newspaper The Sun, Carrey described how his mental health issues began just as he was breaking through to stardom, adding that his perspective on depression has changed over the years.

Sheryl Crow

This Grammy-winning singer has released hit single after hit single through the years, but even a woman famous for singing “all I wanna do is have some fun” can be depressed. According to a 2002 write-up in Blender, Crow states that depression has been part of her everyday life as long as she can remember. She credits antidepressants and therapy with helping her recovery.


10 Celebrities Coping With Depression – Depression Center – Everyday Health.

TaurineTaurine plays a major role in good liver function via detoxification and the formation of bile. Inadequate levels of taurine are common in many patients with chemical sensitivities and allergies. Taurine is the major amino acid required by the liver for the removal of toxic chemicals and metabolites from the body. Impaired body synthesis of taurine will reduce the ability of the liver to detoxify environmental chemicals such as chlorine, chlorite bleach, aldehydes produced from alcohol excess, alcohols, petroleum-based solvents and ammonia. Recent findings are demonstrating, that taurine is one of the major nutrients involved in the body’s detoxification of harmful substances and drugs, and should be considered in the treatment of all chemically sensitive patients. Taurine is helpful for high blood cholesterol and gall bladder problems, alcohol withdrawal, hepatitis and jaundice.

via Positive Health Online | Article – A Healthy Liver and Weight Loss.