4 Reasons to Take Whey Protein for Muscle and Health

I made this short video to discuss the 4 reasons to take whey protein for muscle and health. (Article continues below.)


Fast Protein

Whey protein is “fast”, which in this case doesn’t mean that you can prepare it and down it quickly, although you certainly can – prep time from start to stomach is about a minute. But here it refers to speed of digestion. The proteins in whey have a structure that makes them easily broken down into their constituent amino acids, and they therefore hit the blood stream and the muscles quickly. In contrast, a protein like casein, or meat proteins, take much longer to digest. In certain cases, slow digestion is beneficial, otherwise nature wouldn’t have made them that way.

But when we’ve been lifting weights, muscles are primed to grow. Researchers have suggested several reasons for why this happens, but very simple reason may be that the blood vessels going to the muscles have all opened up greatly to increase the movement of blood to them, facilitating the provision of oxygen and nutrients and the removal of the cellular waste products of metabolism. Whey digests quickly, and then its amino acids hit the muscles right when they’re most susceptible to growth stimulation. Therefore, timing of protein ingestion can be important.

Other studies have found a lesser or even no effect, and much of this seems due to nutrient status of the trainee, e.g. whether he’s fasted or fed, other types of foods he eats, calorie intake, etc. But since I want to ensure that I get the biggest bang for my workout buck, I take whey protein immediately after every workout. Research shows that taking it immediately before a workout may be just as effective.

Branched-Chain Amino Acids

The branched-chain amino acids (BCAAs) are leucine, isoleucine, and valine, and they’re important for muscle growth. While past researched focused on all three, more recent research has fingered leucine as the most important, as it acts as a signal for muscular growth. (Absence of leucine promotes autophagy, the cellular self-cleansing process, and when enough tissue has been broken down via this process, leucine rises in the blood stream and shuts off autophagy via a feedback mechanism.)

Whey contains about 25% BCAAs, which is the highest of any protein, therefore it’s the best muscle growth stimulant.

Essential Amino Acids

Amino acids, the building blocks of protein, are of two types, essential and inessential. Inessential amino acids are those that the human body can make from other molecules, and therefore they don’t need to be supplied by food. The body can’t make the essential amino acids, of which there are nine, and therefore the diet must supply them.

Only essential amino acids build muscle. Provision of extra inessential amino acids does not stimulate extra muscle growth, and if sufficient essential amino acids are not present, muscle won’t grow.

Whey protein is about 50% essential amino acids, again among the highest of any protein.


Cysteine is a sulfur-containing amino acid, and whey contains an abundant amount of it. Cysteine is important in the synthesis of glutathione, the body’s most important internal antioxidant.

When the body metabolizes to create energy, it also creates free radicals as a byproduct, and these are reactive molecules that can cause molecular and cellular damage. The cells endeavor to keep free radicals under control, neither too many nor too few of them, since besides their potential for damage, they are also important signaling molecules. (Free radicals drive much of hormesis, for example.) It does this through a tripeptide (a string of three amino acids) called glutathione.

Glutathione is made from cysteine, glutamine, and glycine, and of these three, cysteine is the rate-limiting constituent, the bottleneck. Provision of cysteine therefore promotes glutathione synthesis. Lack of cysteine promotes excess free radicals, leading to oxidative stress, a condition to be avoided.

This has benefits not just for athletes, but in aging as well, which has been characterized as a cysteine-deficiency syndrome.


Whey is of great benefit to athletes, and can help the elderly too.

Between 20 and up to 40 grams of whey can be taken before or after a heavy exercise session (yes, endurance athletes benefit too), although amounts higher than 20 grams appear to give diminishing returns.

By the way, if you watch the video above, I display a container of NutraBio Grass-Fed Whey Isolate. In view of the fact that I’ve said that grass-fed isn’t necessarily a big improvement over regular whey, I should explain that the NutraBio company comped me the whey. Nevertheless, it’s chocolate, has no sugar (it’s sweetened with stevia), and is quite tasty, and you can buy it here.

PS: I discuss whey and other proteins in my new book, Best Supplements for Men.

PPS: Check out my Supplements Buying Guide for Men.

Longer Life Through Lower Blood Sugar

Many experiments and studies on life extension have found the interesting and important result that lowering blood glucose (blood sugar) and/or restricting dietary carbohydrates means longer life. This has been found using several different lab animals and in humans as well. It’s possible to have longer life through lower blood sugar.


Acarbose is an anti-diabetic drug that works by inhibiting enzymes in the gut that break down carbohydrates to glucose, and therefore less glucose is absorbed.

Male mice that were fed acarbose lived 22% longer than controls, although the female mice lived only about 7% longer.


A lifespan increase of 22% is large, among the longer lifespan extensions seen with other interventions, comparable to rapamycin and a larger increase than fat-tissue insulin receptor knockout. Acarbose reduced fasting insulin in male mice but not in females, which may account for the difference in lifespan extension.

IGF-1 was decreased in both sexes, and fibroblast growth factor 21 (FGF21) was increased, and both of these hormonal changes could be involved in life extension.

In humans with type 2 diabetes, long-term acarbose treatment was associated with a huge 50% decrease in the risk of cardiovascular events such as heart attack and stroke. Importantly, the risk reduction was associated with a decrease in postprandial hyperglycemia, or a rise in blood sugar after eating.

A meta-analysis of acarbose found similar large reductions in CVD events.

Since dietary carbohydrates, especially grains, sugar, and starches, are the primary determinant of blood sugar, why not just cut carbohydrates instead?


Metformin is the most prescribed anti-diabetic drug, and it lowers blood sugar and insulin. Similar large reductions in death rates have been found with metformin use, so much so that diabetics using metformin may outlive non-diabetics who don’t use it.

Would cutting carbohydrates cause the same life extension and anti-aging as metformin?

An argument against that is that diabetics taking metformin may live longer than non-diabetics who don’t take it. Therefore, metformin may be causing a real anti-aging effect.

An argument for it is that most non-diabetics eat large amounts of carbohydrates, with the average American eating about 50% of his or her calories as carbohydrate. And among average people, Dr. Joseph Kraft showed that large numbers, perhaps up to 80%, have some degree of impaired glucose tolerance, i.e. they’re insulin resistant.

If metformin increased lifespan in animals or people who ate little or no carbohydrates, that would be convincing, but to my knowledge, it has not.


Glucosamine is an over-the-counter supplement commonly taken for arthritis and joint pain. Glucosamine extends lifespan in mice through

an induction of mitochondrial biogenesis, lowered blood glucose levels, enhanced expression of several murine amino-acid transporters, as well as increased amino-acid catabolism. Taken together, we provide evidence that GlcN [glucosamine] extends life span in evolutionary distinct species by mimicking a low-carbohydrate diet. [My emphasis.]

Glucosamine impairs glycolysis (glucose metabolism) and therefore lowers blood glucose levels.

Glucosamine also activates autophagy, the cellular self-cleansing process that retards aging, and inhibits mTOR, the cellular growth engine that accelerates aging.

In humans, use of glucosamine is associated with an 18% lower death rate.

Again, if glucosamine mimics a low-carbohydrate diet, why not just eliminate the middleman and refrain from eating carbohydrates?


Fasting, eating a very low amount of carbohydrates (usually less than 50 grams daily), or taking ketone supplements or MCT oil raises the amount of molecules known as ketones in the bloodstream. Increased ketones mimic the effects of food restriction by lowering blood glucose and insulin.

While ketone supplements are generally beneficial in my opinion, if you cut the carbohydrates, albeit radically, you’re in ketosis (producing ketones) and presumably extending your lifespan and fighting aging by doing so.


Feeding glucose to the worm C. elegans shortens its lifespan.

Restricting glucose extends its lifespan.

When carbohydrates are digested, they become glucose inside the body, since most carbohydrates are just long chains of glucose. (Sugars may incorporate other molecules, such as fructose and galactose.)

So why not just restrict carbohydrates?

Multiple lines of evidence lead to carbohydrate restriction

As we’ve seen from the studies above, multiple lines of evidence lead to the conclusion that restricting carbohydrates and thus preventing high blood glucose, whether spikes in it or a higher average glucose, leads to longer life.

These same lines of evidence lead to the conclusion that carbohydrates can promote aging and shorten life.

Note that some carbohydrates, namely complex carbohydrates found in non-starchy vegetables, don’t raise blood sugar much if at all.

The foods that contain abundant carbohydrates and increase blood glucose are the ones to restrict or eliminate, and they include grains (wheat, rice, corn, etc.), sugar, and starchy tubers such as potatoes.

Someone who is very insulin sensitive may not be harmed much by carbohydrates. These people include athletes and other lean people who exercise or labor at physically demanding jobs.

Anyone else, and that includes most people, would likely see a big improvement in health by restricting carbohydrates.

PS: See my new book, Best Supplements for Men, for more tips on how to live longer.

PPS: Check out my Supplements Buying Guide for Men.

The Normal Values for Testosterone and Why They Matter

If you get a lab test for testosterone, the hormone that gives men their distinctively male characteristics, your result will be accompanied by a “normal range” (or “normal values”, or “reference range”, all the same thing), which allow you and your doctor to see where your test result fits in relation to other healthy men. Normal laboratory values are very important for medical decision making, so anyone changing them should have good reasons for doing so. The biggest clinical laboratory in the U.S., LabCorp, recently changed its normal values for testosterone, which has implications for anyone getting tested. Hence this article on the normal values of testosterone and why they matter.

Labs are lowering the reference range for testosterone

LabCorp changed its reference range for testosterone from 348-1197 ng/dL to 264-916 ng/dL. Note that the entire range has been shifted lower. The company explains their reasoning and says the downward shift reflects two changes: 1) a new CDC standardization for the method used to assay testosterone (since different labs may use different methods, giving somewhat varying results), and 2) the new range “reflects a difference in average subjects with higher BMIs”.  Reason number 2 is the most important for our purposes.

The new range comes directly from a recently published paper, “Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe“.

Normal values are constructed such that 95% of apparently healthy people have values within that range, and the present paper is no different.

But it depends on what you mean by healthy. The paper uses values for men age 19 to 40 with a body mass index (BMI) of < 30, i.e. “healthy non-obese” men. Since it’s been found that obesity in men is associated with lower testosterone levels, they looked at only non-obese men.

However, it’s obvious that “non-obese” doesn’t mean “healthy”. Anyone with a BMI of ≥ 25 is considered overweight, and many men with a BMI less than that have high body fat, a more accurate measure of health risks. (A few, very muscular men may be normal at a BMI of 25 or more, but they’re a small fraction of the population.)

Basically, around 80% of the population has excessive body fat, which is a prime contributor to excessive aromatase activity, which lowers testosterone.

Normal lab values are constructed from the results of fat, sick people.

Do you want to compare yourself to them? I know I don’t.

Secular decline in testosterone and the obesity epidemic

Testosterone levels in men are declining. That means that men of a given age have lower testosterone levels than men of the same age a few decades ago. See chart below.

testosterone secular decline

We can only speculate on the causes of the decline. Obesity has been suspected, but much of the decline remains even when it’s been accounted for. Other causes might be environmental chemicals, less smoking (nicotine inhibits aromatase), processed garbage food (think soy and sugar), and others.

Whatever the cause, it’s clearly happening, and so much so that laboratories are lowering their normal ranges to account for it. Then, when you get tested, they compare you to a group that includes many overweight, unhealthy men who don’t exercise and eat bad food.

Men are getting fatter, which may or may not account for declining testosterone. But just because they’re getting fatter, that doesn’t mean it’s normal or that you should get fatter.

Since LabCorp is the largest clinical laboratory in the country, their decision reverberates to other labs, as well as to doctors and even insurance companies.

If you go to a doctor for evaluation of your testosterone levels, you may not get any treatment unless your test has a value less than 264 ng/dL, because that’s “normal”.

Insurance companies may refuse to pay, even when a doctor is willing, because you don’t technically have low testosterone.

Most unsuspecting men (for instance, those who don’t read this) will just accept their results at face value. If their testosterone comes in at, say, 300, they’ll consider the case closed and that whatever the symptoms they have must come from elsewhere.

Solution: get educated, and don’t compare yourself to fat, sick people.

Ultimately, for any test or for any treatment your doctor proposes, you simply must educate yourself enough to be able to evaluate them yourself.

To be uneducated in health matter is to leave yourself at the mercy of an increasingly impersonal, profit-oriented medical system that doesn’t care about you. The days of your kindly family doctor are over.

Don’t be fooled that being healthy just means being less sick than normal.

Because normal people are fat and sick, they don’t exercise, and are at high risk of diabetes, heart disease, cancer, and a host of other diseases.

Normality today means obesity, depression, SSRIs, statins, sugar, and soy. Not to mention no sense of purpose and 7 hours a day watching television.

The same study cited above found that 5% of men in from age 80 to 89 had testosterone levels above 897 ng/dL. These men are likely healthy and fit, and I call attention to this fact to show that decline isn’t necessary if you actively fight it.

Compare your health, your test results, and your progress only to truly healthy people and to your former condition.

PS: I devote a major section of new book, Best Supplements for Men, to testosterone and how to increase it.

PPS: Check out my Supplements Buying Guide for Men.

The Low-Salt Fiasco

For several decades, mainstream health authorities have recommended that we avoid saturated fat in our food and keep our cholesterol low. For about the same length of time, they’ve also warned us about the dangers of salt: that it causes hypertension – high blood pressure, a major risk factor for cardiovascular disease – and that we should all keep our salt intakes low, as low as possible. The first dogma, on cholesterol and fat, has come under increasing scrutiny and skepticism in recent years, exemplified by books like Good Calories, Bad Calories and The Big Fat Surprise. Now, James DiNicolantonio’s new book, The Salt Fix, aims to do for salt what others have done for fat and cholesterol.

Why low salt?

Humans have prized salt and gone out of their way to get it since before recorded history, and animals also seek it out. And of course they do, since salt is a required nutrient.

Chemically, ordinary table salt is sodium chloride, and it makes up about 90% of all minerals in the blood and other body fluids, and is present at a concentration of about 0.8%. Given its importance in maintaining electrolyte balance, the body closely regulates the concentration of sodium and chloride, mainly through the action of the kidneys and various hormones secreted by them and acting on them. Both abnormally low and abnormally high blood sodium lead to, or are associated with, serious illness and even death.

Prehistoric humans and modern hunter-gatherers seek out salt, and DiNicolantonio cites evidence that salt consumption in Europe a few hundred years ago – 16th to 18th centuries – was many times higher than today. Due to the use of salt as a food preservative, early modern Europeans consumed 40 to 70 grams of salt daily, and in some places as much as 100 grams, compared to the average American’s current consumption of about 8 grams, or about 3.4 grams of sodium. (Keep in mind that sodium makes up about 40% of the weight of salt, and authorities often speak in terms of sodium, not total salt, consumption, so the numbers can be confusing.)

Salt consumption in the U.S. has been quite stable since the first half of the 20th century, yet the rate of hypertension is about 3 times higher. So why have health authorities argued that decreasing salt intake is critical for controlling hypertension?

DiNicolantonio traces the history of how the low-salt ball got rolling, and that story bears many similarities to the story of Ancel Keys and saturated fat. Several researchers became convinced, through dubious experiments and case reports, that salt caused hypertension, and went on a crusade to convince doctors and the public that salt was a villain.

Among those researchers was Dr. Walter Kempner, who devised the well-known (or infamous, perhaps) Kempner Rice Diet, which he put into use at a clinic for the treatment of severe hypertension, at a time when no drugs were available to treat it. The Kempner Rice Diet was low in sodium, protein, and calories, and consisted mainly of rice, sugar, fruit, and fruit juice. Kempner made extraordinary claims for his diet, but even by his own less-than-scientific standards, it didn’t help everyone, and in those it did help, results were modest. It also led to serious illness in some patients. Other researchers were unable to replicate his results. Furthermore, the diet was low in calories and caused weight loss, which may have been responsible for whatever success it had in lowering blood pressure.

A later study done at the Cleveland Clinic found that a low salt diet helped only about 25% of severe hypertensives, and even then results were modest.

Nevertheless, due to relentless campaigning, the McGovern committee recommended in 1977 that Americans limit their salt intake to 3 grams daily (about 1200 mg sodium). This was the same committee that recommended we stay away from saturated fat.

Low salt has less than impressive results and may be harmful

Severe sodium restriction has little effect on the blood pressure of normotensives, that is, people with normal blood pressure; it lowers their systolic blood pressure by around 1 mm Hg, or less than about 1%. Around 80% of normotensives see no rise in blood pressure from increased salt intake; among hypertensives, around 55% are unaffected by salt, and a reduction of sodium intake in them leads to an average reduction in systolic blood pressure of only about 3.6 mm Hg, an unimpressive result.

It’s even possible that blood pressure can rise with low salt intake, since low salt activates the renin-angiotensin system, the purpose of which is to raise blood pressure. As we saw in a recent article, inhibition of the renin-angiotensin system can increase lifespan even beyond its effects on blood pressure, so higher salt could be life-extending by decreasing renin-angiotensin activation. (Although that’s my idea, and not from the book.)

Low salt consumption leads to a higher heart rate, which is independently associated with higher mortality. Therefore any benefit from lower blood pressure could be negated by a higher heart rate.

Low salt consumption could even lead to obesity, since if we’re starving for salt we may eat more food to get it.

Increasing our salt intake may even be a healthy thing to do.

DiNicolantonio cites fascinating evidence regarding the effects of salt on sex and reproduction. In livestock, cutting sodium reduces birth weights and litter size, and may act as a “natural contraceptive”. In humans, low salt causes a reduced sex drive, reduced odds of pregnancy, increased erectile dysfunction, fatigue, and poor sleep.

How much salt do we really need? DiNicolantonio believes that we have a “salt set point” that “seems to hover around 3 to 4 grams of sodium per day”. (Around 7 to 10 grams of salt.) While sodium balance can be maintained on a low salt intake, that doesn’t mean that that intake is optimal.  We may be driven to maintain a sodium surplus, since someone with enough or excess sodium is more likely to survive a sodium-depleting event such as blood loss, diarrhea, or infection. More salt may also be required for heavy exercise, low-carbohydrate diets, and in pregnancy and lactation.

If salt didn’t cause the rising epidemic of hypertension, what did? The author makes a good case for our huge consumption of sugar, and the obesity that goes with it.

The low-salt fiasco

Ultimately, there seems no good reason for a population-wide restriction of sodium consumption, and in fact the urging of health authorities for everyone to restrict sodium may be doing considerable harm. In hypertensives, sodium restriction may benefit some, but even there, results may be modest and harm may result.

For most of us, limiting salt probably does more harm than good. Far from being a health panacea, eating less salt may be another fiasco brought about by bad science and overzealous health authorities.

Full disclosure: I’ve had a good deal of online contact with James DiNicolantonio, consider him a friend, and he sent me the book for review.

PS: My new book is Best Supplements for Men.

PPS: Check out my Supplements Buying Guide for Men.

Much of Aging Is Just Poor Health Habits

Aging means a deterioration in the body and an increasing propensity to breakdown and disease. Scientists who study aging are keen to discover the driving force(s) that cause it, but they often seem to be unable to distinguish between aging in itself and poor health, especially when studying human beings. I believe that much of aging is just poor health habits.

Is gaining fat, losing muscle, or developing insulin resistance and diabetes a normal part of aging?


Obviously, virtually all living things age and die. (“Virtually”, because a few living things appear not to age at all.) While aging is a natural process, so infectious and genetic diseases are natural processes too, and we’ve largely discovered how to deal with the first, and are working on the second. There’s no reason that aging can’t be delayed or even abolished; it’s not necessarily inevitable.

Some manifestations of aging are visible, such as grey hair and wrinkled skin, and don’t seem obviously related to lifestyle or health habits, so far as we know. Dysfunction on the cellular level is not visible, but takes place in aging.

Scientists often consider that in humans, aging causes obesity, muscle loss, and diabetes. For example, “Studies have shown that insulin resistance increases with age, independent of changes in total adiposity.” Yet the same study concluded its results by saying, “These results suggest that insulin resistance is more closely associated with abdominal adiposity than with age.”

Similarly, sarcopenia, or loss of muscle, is considered a part of aging. Yet exercise, especially resistance training, and higher dietary protein, robustly fight the loss of muscle, so sarcopenia can’t be entirely due to aging.

Fasting, calorie restriction, and aging

Valter Longo, the well-known USC scientist who has studied intermittent and prolonged fasting and their effects on aging, believes that fasting has been shown to have profound effects on aging. Yet, as I pointed out, his studies in humans leave something to be desired, since most of the people in his studies were overweight and/or sedentary. We don’t know how much of the benefits of fasting seen in these people are due to fighting aging or are due simply to better health.

Similarly, domestic lab animals have a tendency to obesity, since they eat highly refined, processed food and are confined to cages. In calorie restriction studies on these animals, much of the benefits to their health may be due merely to preventing them from becoming obese, and not due to a true anti-aging effect.


Scientists consider metformin, the most-prescribed anti-diabetes drug, and rapamycin, an immunosuppressant, to be the best leading candidates for drugs that will actually slow or prevent or even reverse aging. A clinical trial (a trial using humans) of metformin to see its effects on aging is currently underway.

Yet look at who the participants in this trial are: “older adults with impaired glucose tolerance”, that is, these people are pre-diabetic.

We know that type 2 diabetes is caused by, or closely associated with, obesity, dietary sugar and refined carbohydrates, and lack of exercise.

How many of the participants in the metformin clinical trial are obese and/or eat lots of garbage food and don’t exercise? My guess is a very large fraction of them.

Metformin is effective at treating diabetics; it decreases blood sugar and insulin. But if metformin helps the people in the clinical trial, it won’t tell us anything about aging. They’re not healthy, and nothing leads us to think that their ill health is caused by aging rather than bad food, obesity, and lack of exercise.

Metformin may not help people who are lean and healthy and eat good food.

The only way we know if an anti-aging treatment works is if it helps people already healthy.

Everyone is fat

Some 70% of the American people are overweight or obese, although I’ve argued that the figure is closer to 80% when body fat is taken into account. Excess body fat accelerates aging. So does muscle loss.

The causes of this sad state of affairs are several. One is that people don’t know what to do, and if they go to a doctor to ask, he or she doesn’t know either. “Eat less and move more” is terrible advice. Another reason is that even when they know, most people won’t do much about it. Too hard to give up sugar, much less lift weights.

Whatever the causes, aging isn’t synonymous with obesity, diabetes, and sarcopenia.


Scientists confuse aging with poor health. They overlap but aren’t the same. Until anti-aging treatments extend the lives of healthy animals and humans, we don’t know if they truly work.

PS: My new book, Best Supplements for Men, has a chapter on life extension and anti-aging.

PPS: Check out my Supplements Buying Guide for Men.

The Rogue 8-Fold Path

The Rogue 8-Fold Path:

  • Right Diet
  • Right Exercise
  • Right Sleep
  • Right Ambition
  • Right Mindset
  • Right Discipline
  • Right Livelihood
  • Right Social Ties

I give a brief explanation in the video below.


PS: Check out my new book, Best Supplements for Men.

PPS: Check out my Supplements Buying Guide for Men.

How Alcohol Causes Anxiety

It’s well-known that excessive drinking of alcohol can lead to next-day anxiety. That anxiety can in turn lead to the desire to drink more alcohol to ease it, leading to a cycle of excess alcohol and addiction. A study I read on this leads to speculate on how alcohol causes anxiety.

Binge drinking increases bacterial components in the bloodstream

The study is Acute Binge Drinking Increases Serum Endotoxin and Bacterial DNA Levels in Healthy Individuals.

Binge drinking, the most common form of alcohol consumption, is associated with increased mortality and morbidity; yet, its biological consequences are poorly defined. Previous studies demonstrated that chronic alcohol use results in increased gut permeability and increased serum endotoxin levels that contribute to many of the biological effects of chronic alcohol, including alcoholic liver disease. In this study, we evaluated the effects of acute binge drinking in healthy adults on serum endotoxin levels. We found that acute alcohol binge resulted in a rapid increase in serum endotoxin and 16S rDNA, a marker of bacterial translocation from the gut. Compared to men, women had higher blood alcohol and circulating endotoxin levels. In addition, alcohol binge caused a prolonged increase in acute phase protein levels in the systemic circulation. The biological significance of the in vivo endotoxin elevation was underscored by increased levels of inflammatory cytokines, TNFα and IL-6, and chemokine, MCP-1, measured in total blood after in vitro lipopolysaccharide stimulation. Our findings indicate that even a single alcohol binge results in increased serum endotoxin levels likely due to translocation of gut bacterial products and disturbs innate immune responses that can contribute to the deleterious effects of binge drinking.

The contents of the gut are not intended to be placed into the circulation. Normally, so-called tight junctions in the lining of the intestines keep bacterial contents inside the gut and out of the circulation, but binge drinking opens up the tight junctions and allows leakage of contents into the circulation.

In the study, healthy volunteers ingested “2 ml vodka 40% v/v ethanol/kg body weight in a total volume of 300 ml orange/strawberry juice”. Using myself as an example, at 73 kg body weight, that would be 146 ml, or (146/750) about 1/5 of a bottle of liquor, or about 5 ounces. That comes to just over 3 drinks which, while it was ingested at one sitting, isn’t really all that much.

Blood alcohol went to a maximum of about 85 mg/dl, or just over the legal driving limit (which used to be 100 mg/dl). Again, not all that high. The chart below shows how levels of bacterial DNA climbed, by about 60%. Levels of bacterial lipopolysaccharide (LPS), which is a seriously toxic product that consists of parts of the bacterial cell wall, rose to a similar degree.




These bacterial components that get into the bloodstream wreak havoc, increasing levels of inflammation and contributing to liver damage.

The connection between bacterial LPS and anxiety

In animal models, “Lipopolysaccharide (LPS), a component of gram-negative bacteria, is widely used to systematically stimulate the immune system and generate profound physiological and behavioural changes, also known as ‘sickness behaviour’ (e.g. anhedonia, lethargy, loss of appetite, anxiety, sleepiness).”

Inject a rat with LPS, and acts sick and displays signs of anxiety.

In healthy human volunteers, “LPS was found to produce increases in the concentrations of cytokines and CSs [corticosteroids], as well as inducing mild fever, anorexia, anxiety, depressed mood and memory impairment. The levels of anxiety, depression and cognitive impairment were positively correlated with the levels of circulating cytokines, a finding supporting yet again the involvement of cytokines in the mediation of the emotional and cognitive responses to illness.”

In humans, LPS produces depression and anxiety.

If binge-drinking alcohol produces increases in LPS in the blood, then that’s probably the cause of day-after, alcohol-induced anxiety.

And of course anxiety and depression go together. Binge-drinking could cause depression.

The authors of the first paper observe, “Mutant mice lacking genes related to immune function exhibit decreased alcohol consumption indicating immune signaling promotes alcohol consumption. Thus, it is tempting to speculate that LPS increase in the systemic circulation after an acute alcohol binge could promote the desire for alcohol consumption.”

In other words, the immune reaction to binge-drinking stimulates the need for more alcohol, leading to addiction.


To my mind, the fact that binge-drinking as few as 3.5 drinks promotes leaky gut and increases in LPS in the blood stream provides a clear mechanism as to why alcohol leads to anxiety. It’s completely related to well-founded observations in biological psychiatry that bacterial LPS is elevated in people with depression and anxiety, and that fixing leaky gut can help overcome these conditions. Same in chronic fatigue syndrome.

And yes, leaky gut is real.

PS: I devoted a chapter to the vagaries of drinking alcohol in my new book, Best Supplements for Men.

PPS: Check out my Supplements Buying Guide for Men.

Rapamycin Anti-Aging Medicine: An Interview with Alan S. Green, M.D.

Rapamycin, a drug used as an immunosuppressant in the treatment of organ transplant patients, may be the most potent life-extension drug currently available, and the practice of rapamycin anti-aging medicine is just getting started. Mikhail Blagosklonny, a doctor and scientist at the Roswell Park Cancer Institute in New York, has been the most notable and vocal advocate of rapamycin to extend human lifespan. While rapamycin has adverse side effects in humans who take it daily for immunosuppression, recent research has found that pulse dosing, perhaps once a week, may confer most of the anti-aging benefits without any adverse side effects.

Will rapamycin fight aging in humans and extend lifespan? Unfortunately, clinical trials of rapamycin for this purpose are unlikely to happen any time soon, but some people would like to find out. Among them was Alan S. Green, M.D., who practices medicine in New York state, and who, beginning in early 2016, began to take rapamycin himself, along with metformin, an angiotensin blocker, and aspirin.

At the age of 72, Dr. Green found himself suffering from old age:

I attended college on a tennis scholarship and ran a marathon in just under 4 hours at age 40. But by age 70 my main physical activity was reduced to walking my two Shiba Innu dogs in the park. Then by age 72, I experienced angina and shortness of breath on small hills. As a trained pathologist I accepted the reality that I was in rather poor shape. My fasting blood sugar was up, my creatinine blood level was elevated indicating renal insufficiency and I couldn’t fit into any of my pants. I then began trying to learn about aging. I discovered a story more extraordinary and improbable than anything I had ever encountered in my lifetime.

He began to take rapamycin on a weekly dosing schedule, along with the other drugs noted, and after only 4 months, he experienced vastly improved health.

Based upon empirical medicine principles, I decided rapamycin 6 mg once a week would be an  aggressive treatment and 3 mg once every 10 days would be a conservative treatment. I decided to go with aggressive treatment. January 2016, I began the rapamycin-based Koschei formula with intent to take it for one year; in what could euphemistically be called a “proof-of-concept” experiment.  I didn’t have to wait one year; by 4 months the results were miraculous. I lost 20 pounds,  my waist-line went from 38 inches to 33. I bought a pair of size 32 jeans and didn’t have to wear joggers no more. I could walk 5 miles a day and ride a bike up hills without any hint of angina. Creatinine went from elevated to normal and fasting blood sugar went down. I thought I was Lazarus back from the dead. It’s now over 1 year and I feel great. I’ve also had no mouth sores, the most common clinical side-effect. For me, rapamycin is the world’s greatest medicine. [My emphases.]

Dr. Green reports: “Subjective impression: Miraculous improvement in health; feeling old to feeling young.” 

Dr. Alan S. Green


Given all of this, and after reading through his website, I decided it would be a good idea to interview Dr. Green, and he graciously consented to it. This is a tremendous interview with Dr. Green, who appears to be the only physician in the world practicing anti-aging medicine with a rapamycin-based treatment regimen, arguably the most potent life-extension intervention currently known.

As a practicing physician, Dr. Green has translated the scientific research on anti-aging and life extension and put it to work on humans, and as such, he’s a true pioneer in medicine. I predict that the approach he uses will become more widespread, and quickly. While Silicon Valley startups and tech moguls reach for unproven and perhaps even phantom methods to fight aging, and are pouring lots of money into the effort, Dr. Green shows that potent anti-aging medicine is here now, and you don’t need to be a billionaire to afford it. (Are you listening, Peter Thiel?)

Following are my questions and Dr. Green’s answers.

P. D. Mangan: You said that earlier in life, you were physically active, having run a marathon at age 40. When you found yourself feeling the effects of aging at age 72, is there anything that prompted you to turn to rapamycin and other anti-aging drugs rather than trying to become more active again and/or changing diet? Did you feel that physical/dietary changes wouldn’t be adequate for the health problems you were facing?

Alan S. Green, M.D.:  My point was I had been in good shape with jogging and tennis so when I started going down hill it was very apparent. At about age 67 I stopped playing tennis due to slowness and fatigue. I tried to control increasing size of waist line with diet but without much success. However, I viewed all changes as normal aging which was the traditional medical view. It wasn’t until age 72 when I developed angina and SOB walking up small hills in the park with my 2 Shiba innu dogs, that I finally concluded that I had a progressive fatal disease and that disease was aging. As I didn’t know anything about aging, I had no reason to consider diet or exercise as a remedy. My plan was to study aging to determine if there was any treatment.


PDM: I’ve learned a great deal from Mikhail Blagosklonny myself, have read all of his aging theory papers, and believe his quasi-programmed theory of aging makes more sense than almost anything else out there. Yet there are many other theorists of aging. Why did Blagosklonny’s ideas resonate so much with you? Did you come across other theorists who weren’t as convincing?

ASG: I believe in science, not metaphysics so “theories” not supported by scientific facts mean nothing to me. The start of understanding aging is that rapamycin increases life span of all living things and mean life span of mice by 25%. Further study showed that rapamycin blocked almost all key steps in progression of atherosclerosis and rapamycin prevented development of Alzheimer’s disease. Furthermore, mTOR was the command and control of all cells of all living things. Blagosklonny had a theory which explained how reducing mTOR slowed aging and slowed diseases of aging, so this was very interesting theory as it dealt directly with mTOR. Blagosklonny also had an anti-aging treatment plan for reducing mTOR. I was impressed with Blagosklonny enough that his treatment plan was certainly worth a shot. After 4 months of the rapamycin based treatment, my body had undergone what I considered a miraculous change and I felt cured. Being cured was what resonated with me. Today I went for a 40 mile bike ride with a stiff headwind. I felt perfectly fine and when came home I took my dogs for walk in the park and those small hills which once caused angina now seemed like nothing more than Gopher mounds. So it is not the Blagosklonny theory which impressed me; but rather the results.


PDM: A very large number of Americans, perhaps as much as 80%, have some degree of insulin resistance, i.e. they’re not in optimal health, and around the same fraction are overweight or obese. Do you have an opinion as to what degree the diseases of aging, such as heart disease and cancer, may be due to these factors, and to what degree they are strictly caused by old age?

ASG: I believe aging is a bundle of many disease mechanisms; but the most important one in the 60-95 age range is elevated mTOR. I would estimate that in general 75% of aging and age related disease in this age group is due to elevated mTOR. Specifically with atherosclerotic cardiovascular disease it is probably closer to 90% and with cancer probably less than 50%.


PDM: Do you think that rapamycin treatment will become widespread in the near future? What are the obstacles, if any, to it becoming more widely adopted?

ASG:  Rapamycin may become more widespread; but probably not. The obstacle is lack of appropriate human trials. Rapamycin will never be an “on label” drug. Furthermore, rapamycin has been used by over a million people as a biologic poison in transplant medicine. It will be very difficult to overcome the bad name it has received in transplant medicine. Rapamycin is type-cast as a bad guy. Use of rapamycin once a day is harmful because it knocks out mTOR1 and mTOR2; but use once a week is safe because it only lowers mTOR1. The main obstacle is financial and not medical. Nobody has a financial incentive to promote rapamycin. But rapamycin could become more widespread, because Baby Boomers are very savvy and know how to use the internet to get information.


PDM: I note that of the drugs you advocate for anti-aging, metformin, aspirin, and ACE inhibitors/AR blockers are cheap, while rapamycin is more expensive. Does any other drug come close to rapamycin in efficacy or is it indispensable? Of the four drugs, what fraction of anti-aging effect is due to rapamycin in your estimation?

ASG: Rapamycin is only $3.50 for 1 mg if you buy it on line with a prescription from Canada; therefore monthly cost might come to $50-100 a month.

My rough guess of the relative value of each as anti-aging drug would be as follows: rapamycin, ACE inhibitor/AR blocker, metformin, aspirin: 75, 18, 6, 1.


PDM: Do you think that other, non-pharmacological anti-aging interventions, such as intermittent fasting or perhaps even intense exercise, are superfluous for someone on a drug regimen such as yours? If the drugs activate AMPK and inactivate mTOR, then would the physical interventions make any difference, given that they do that as well, and perhaps not as effectively?

ASG: I think physical activity is of great value. I cycled 1000K in May. I understand value of HIIT for people in their 40s; but for people my age, I think a few hours of exercise at moderate intensity is probably best. Humans are the premier long distance runners of the animal world. Running and walking can be too traumatic for joints in old people; but cycling is easy and safe as long as stay on bike paths and away from cars. The effect of using legs muscle at the cellular level is it increases AMPK which increases GLUT4 transport of sugar into muscle which reduces insulin resistance.

Caloric restriction is also of great value. Men should get their waist hip ratio down to 0.9 range. If you had a 32 inch waist when age 21, there is no reason you should not have a 32 inch waist line at age 75 and with rapamycin you can do it. After get rid of extra waistline fat; then I favor eating about 8% fewer calories than required; but without any additional weight loss

With all due respect to victims of the Holocaust, and not to minimize one of the greatest atrocities in human history, I cite the case of Yisrael Kristal. Yisrael is the oldest living man in the world and in good mental and physical health. In August 1944 at age 40 he went to Auschwitz concentration camp. In January 1945 he was rescued by the Russians and his weight was down to 80 pounds. He was probably just a few weeks away from death from starvation. He endured 6 months of starvation and hard labor. Only a small handful of men 40 years old were rescued from the Nazi concentration camps; so hard to say that mere coincidence that Yisrael Kristal is oldest living man in world. In a possible related study, mice fed rapamycin for 3 months in middle age went on to have a remarkable long extension of lifespan after rapamycin was stopped. The most senior mouse lived 1400 days which was stated to be the equivalent of 140 in human years. I mention this mouse study to show that what happened to Yisrael in 1944 could have an ongoing effect for the next 70 years.


PDM: Since I’m not a fan of statins myself, I note that you stopped taking one due to adverse side effects. What do you make of studies showing that higher total cholesterol is associated with longer life? Have you revised your opinion at all on whether it’s worthwhile to lower cholesterol or take a statin?

ASG:  I agree with your basic point that you don’t like surrogate markers. Lowering cholesterol doesn’t prove statins prevent heart attacks. However, I have seen studies showing statins lower all cause mortality. So I would use statins, if it did not cause problems for me.


PDM: You stated after following your anti-aging regimen for 14 months, “Subjective impression: Miraculous improvement in health; feeling old to feeling young.” I think that’s fantastic; why aren’t more people doing this? Do you know of any other physicians besides yourself that prescribe regimens like yours?

ASG: Anecdotal reports in medicine are always considered very unreliable and proving nothing. Aside from Blagosklonny, there are no anti-aging experts saying people should use rapamycin. If you showed my results to some anti-aging experts their response might be something like this: “Even taking all the results as true, it still proves nothing. It would require 30 years to show rapamycin increases lifespan or decreases age related disease and would need results in hundreds of persons for a statistical analysis. The results don’t even show rapamycin is a good fitness drug as subject also used diet and exercise which in themselves could account for all positive results.”

My interpretation is rapamycin is a miracle anti-aging drug; but some anti-aging experts would just poop-poop results as meaning nothing.

I know of no other physician who has a rapamycin based regimen like mine.


PDM: Did you have any trepidation about starting to take rapamycin, given that there’s so little human data on it for anti-aging?

ASG: I had great fear that rapamycin would not work. I wasn’t interested in something that would extend my lifespan. I wanted something that would reverse aging. I wanted to be restored to good health. I thought rapamycin based treatment might slow aging; but I never expected to feel young again. I consider aging to be the mother-of-all-disease; so while I certainly had fear, the fear was not about rapamycin.

I think one of the greatest days of my life was about 4 months into treatment when I suddenly had that “Holy shit” moment’ as in “Holy shit, this stuff actually works.”

When I say “Old” I mean you go for a walk in the park with your dogs and with a small hill you have angina, fatigue and shortness of breath and when I say “Young” I mean going for a 40 mile bike ride and feeling great.


PDM: Was your decision to take anti-aging drugs more or less sudden, i.e. did you give it any thought a few years earlier?

ASG: As soon as I had done enough research to know the score, there was no delay in starting treatment. I was very lucky in that by the year 2015 when I began my search for understanding of aging and treatment, there had been an explosion of scientific research and understanding of aging. By contrast, in the year 2005, nothing was known about aging, rapamycin, mTOR; it was all just gobbledygook.

From the start of research to the start of treatment was 8 months.


PDM: I was fascinated to learn about angiotensin disruption for anti-aging, which I’m not sure if I had heard of before, and also that it fits the growth vs longevity paradigm. (On second thought, I had heard of it, but I forgot. Must be the effects of age.) Do you think hypertension is a “normal” manifestation of aging and that everyone can expect to have it to some degree as they age?

ASG: The two best characterized systems which promote aging are the mTOR system and the angiotensin-renin system. Angiotensin II is the primary cause of hypertension; but angiotensin II also promotes atherosclerosis, damage to mitochondria and increase ROS in tissues. I think all older persons probably suffer from higher activity from angiotensin II than is healthy. So probably most old people had some degree of hypertension and they would benefit from being on angiotensin blocker/inhibitor (ARB/ACE). The important thing is to use one that crosses blood-brain barrier.


PDM: There exists a remarkable indirect correlation between insulin level and hypertension, heart disease, cancer, stroke, diabetes. What is relationship between insulin level and mTOR?

ASG: There is a direct correlation between insulin level and mTOR level in the cell. I believe that insulin level is the best surrogate test for mTOR level. So the chart showing very strong correlation between the 5 common diseases of aging and insulin level is not because insulin is bad per se; but that high insulin in blood indicates high mTOR activity in the cell.


PDM: Given that most of these drugs are cheap, and even generic rapamycin could come down in price, to what extent do you see major pharmaceutical companies as a hindrance to the adoption of this regimen? If they don’t promote it to physicians, since there isn’t enough money in it, will it catch on?

ASG: Our system is based on drugs being developed and promoted by Big Pharma. I don’t think Big Pharma is an obstacle; they just will not help. There is no way for anybody to make any money from rapamycin because it is a generic drug. So you are correct, very difficult for rapamycin to catch on.


PDM: Given that the use of these drugs could radically cut healthcare spending, do you see that as more of an obstacle, or an incentive, to its adoption?

ASG: Saving money is an incentive to the payors. It is not an incentive to the medical industry or to Big Pharma. So to be a real incentive need a different kind of health care system. You would need somebody in charge of entire system who could say need to save money by preventing diseases of aging and then that person would need the knowledge that such action was actually possible and then implement program to prevent diseases of aging.

In the system we now have, there is nobody to do that. There is nothing payors can do to implement preventive medicine and they certainly don’t know it is even possible.

I believe healthy old people could make a great contribution to society instead of being a financial burden. So the failure to have preventive of diseases of aging is a tragedy of the highest order.


PDM: Do you see any other interventions in your future or on the horizon? Or is your anti-aging regimen the current state of the art? Do you plan to keep practicing medicine indefinitely, now that you’ve solved your aging and health problems?

ASG: The future is here now. The focus on treatments of the future not yet available is a distraction from the very excellent treatments now available.

Blagosklonny provided the state of the art treatment in Koschei 2014 paper. In May 22, 2017 paper, “From rapalogs to anti-aging formula”, Blagosklonny updated treatment and I may include some of his new ideas in my office treatment plan.

I do plan to continue to practice medicine. Aging is an extraordinary complex disease and people should not be forced to fight aging on their own.


I thank Dr. Green for taking the time to answer my questions and for such a great interview. He’s a real pioneer in the application of anti-aging science to medical practice.

PS: I wrote an extensive section on supplements for longer life in my new book, Best Supplements for Men.

PPS: Check out my Supplements Buying Guide for Men.

Blood Pressure Drugs Extend Lifespan

Common and cheap blood pressure drugs extend lifespan in animals by inhibiting the renin-angiotensin system. This pathway for life extension is both different from other pathways, such as mTOR or the insulin/IGF-1 pathways, and intertwined with them.

Renin-Angiotensin System

Animals, including humans, finely control blood pressure through both hormones and the nervous system. Blood pressure control is very important, since loss of blood pressure can lead to shock and death, for instance in blood loss, or in extreme illness.

Two hormones, renin and angiotensin, regulate blood pressure. The kidneys secrete renin which, in case of low blood pressure, cleaves angiotensinogen to make the hormone angiotensin I, which is then converted by angiotensin converting enzyme into angiotensin II, a potent peptide which acts to constrict blood vessels in order to raise blood pressure. Angiotensin II also causes the secretion of yet another hormone, aldosterone, which in turn causes the kidneys to retain more sodium and water, which also raises blood pressure.

Hypertension, or high blood pressure, promotes cardiovascular disease, including heart attacks and stroke. Lowering high blood pressure is considered an important strategy in preventing heart disease and stroke.

Anti-hypertensive drugs have several different mechanisms, but for the purposes of this article, and seemingly most importantly for life extension, we’ll focus on two types of drugs that affect angiotensin, namely angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor (AR) blockers. There seems to be little difference in effectiveness between ACE inhibitors and AR blockers in terms of mortality, at least in certain classes of patients.

Blood pressure, aging, and life extension

It’s well known that blood pressure tends to rise with age.

Of course, as people get older, they get fatter and lose muscle, insulin resistance increases, and they become more sedentary, and those factors all affect blood pressure.

Yet aging itself seems to be a factor even absent these. Blood pressure rises with age in lab animals, for instance.

In mice, disruption of the angiotensin II receptor increases lifespan. Not only that, but the increase is large, as large as that caused by insulin receptor disruption. See chart below.

Knocking-out AT1A prolongs life span in the mouse. A Kaplan-Meier an...

The average lifespan of normal mice was 24 months, that of genetically disrupted angiotensin receptor knockout mice was 31 months, about a 26% increase. When all the wild-type animals had died, 85% of the knockout mice were still alive. Body weights and physical activity between the two groups were the same, so this was not an artifact of reduced food intake, i.e. calorie restriction. (Many life-extension treatments appear to work by inducing lower food intake.)

However, another study found that long-term angiotensin inhibition resulted in less fat tissue.

In rats, long-term angiotensin blockade exerts “a significant protective effect on the function and structure of the cardiovascular system in all treated animals.” Of interest, the animals were divided into 3 groups: control (no treatment), a group treated with an ACE inhibitor, and a group treated with an AR blocker. There was no difference between the 2 treatments, which “clearly indicates that most of the effects are exerted through AT1 receptors. An outstanding finding was the significant and similar prolongation of life span in both groups of treated animals compared with untreated control animals.” The average survival of the control group was 735 days, while the two treatment groups lived 892 and 877 days, respectively, a large effect.

ACE inhibitors even robustly extend lifespan in the worm C. elegans which surprisingly have a a molecule homologous to ACE.

In spontaneously hypertensive rats, ACE inhibition doubles the lifespan to that of normal rats. Maybe that should be expected; another way of saying this is that spontaneous hypertension halves lifespan. However, it does show the crucial importance of blood pressure.

In cell culture, resveratrol downregulates angiotensin receptor expression. Since resveratrol functions as a calorie restriction mimetic, this shows that yet another way that calorie restriction extends lifespan may be through its effect on angiotensin receptors.

Indeed, obesity increases the activity of the renin-angiotensin system. Weight loss in humans decreases expression and activity of the system.

Calorie restriction and angiotensin inhibition “display a number of converging effects, i.e. they delay the manifestations of hypertension, diabetes, nephropathy, cardiovascular disease, and cancer; increase body temperature; reduce body weight, plasma glucose, insulin, and insulin-like growth factor-1; ameliorate insulin sensitivity; lower protein, lipid, and DNA oxidation, and mitochondrial H2O2 production; and increase uncoupling protein-2 and sirtuin expression.”

So, can you get all the effects of calorie restriction just by inhibiting the angiotensin system? Could be, yes.

“…both animal and human evidence show that RAS blockade can prevent age-related structural and functional alterations in several organs, progression to the metabolic syndrome, the development of diabetes, hypertension and some of its consequences, cardiovascular changes, and cerebral and cognitive impairments. The latter conditions act as surrogate markers of the ageing process, and at the same time, they accelerate age-related structural and functional decay in various tissues.” (Above ref.)

Oddly enough, there’s an iron connection. Namely:

Blocking angiotensin is about much more than blood pressure. Patients treated with angiotensin blockers had quite a bit better survival than patients treated with beta blockers, even with both groups having the same reduction in blood pressure.

Another class of anti-aging drug

The 3 most powerful anti-aging drugs appear to be rapamycin, metformin (or the similar supplement, berberine), and aspirin. There are other drugs and supplements that promote life extension, such as resveratrol and curcumin, and it’s difficult to make direct comparisons as to which of these are better, or which combinations, etc., but the first 3 are generally accepted as having the most potential to extend human lifespan.

We might be able to add a fourth class of drugs to the list of powerful life-extension agents, namely those that affect and inhibit the renin-angiotensin system, i.e ACE inhibitors and AR blockers.

Both classes of these drugs are widely used to lower blood pressure. They’re also quite cheap, perhaps a few dollars a month for either. When taken in low doses, they seem to have few side effects, and as far as I can tell, doctors are not hesitant about prescribing them.

Of the drugs mentioned above, only rapamycin is expensive.

Alan S. Green, M.D., who practices rapamycin-based treatment of diseases of aging, uses ACE inhibitors as part of his anti-aging regimen, in addition to rapamycin, metformin, and aspirin.

I’ll be posting an interview with Dr. Green soon.

My new book, Best Supplements for Men, has an extensive section devoted to life extension supplements.

PS: Check out my Supplements Buying Guide for Men.

Video: Do I Take Testosterone?

For lots of ideas on how to boost your testosterone, get my new book, Best Supplements for Men.

PPS: Check out my Supplements Buying Guide for Men.

Berberine May Reduce Cardiovascular Risk

Berberine (which I wrote about here) is a herbal supplement obtained from a number of different plants, which Chinese medicine has used for perhaps thousands of years. Its physiological mechanism most resembles metformin, the world’s most prescribed diabetes drug. It lowers blood glucose, activates AMPK, and does a seemingly endless number of other beneficial things. And berberine may reduce cardiovascular risk.

Endothelial cells

Endothelial cells are those cells that line arteries and are very important for cardiovascular health. When the cells lining arteries don’t function well, this is known as endothelial dysfunction.

The vascular endothelium, which regulates the passage of macromolecules and circulating cells from blood to tissues, is a major target of oxidative stress, playing a critical role in the pathophysiology of several vascular diseases and disorders.

Vascular endothelial cells have a finite lifespan and can enter a state of senescence and promote atherosclerosis. Maintaining youthful and healthy endothelial cells in the lining of arteries is essential for cardiovascular health.

Older or senescent endothelial cells produce lower amounts of nitric oxide, the important signaling molecule that inititates the relaxation of blood vessels and keeps them youthful.

So how do we keep our arteries youthful?

Berberine increases endothelial progenitor cells

Berberine increases the production of nitric oxide, which in turn plays a key role in the regulation of endothelial progenitor cells (EPCs). These cells mature and replace older endothelial cells, ensuring the arteries stay flexible and youthful.

Researchers took a look at the effect of berberine on EPCs: Berberine-Induced Upregulation of Circulating Endothelial Progenitor Cells Is Related to Nitric Oxide Production in Healthy Subjects.

First, what I liked about this study. It was done in humans, so we know that this works and not just in rats or mice. Second, berberine is not well-absorbed into the circulation. I’ve seen a number of studies in which berberine was injected at high doses into rats or mice, and I doubt we can meaningfully extrapolate those results to humans taking oral doses. This study used healthy people taking berberine orally.

The subjects were 20 healthy people, average age 54, with no cardiovascular disease and taking no medication. They took 400 mg of berberine 3 times a day for 30 days. Then they looked at EPCs, as well as their activity, and the level of nitric oxide in the blood.

Berberine therapy resulted in a dramatic increase in EPCs. See chart below.

The number of EPCs rose 50%.

Results for proliferative, adhesive, and migratory activity of EPCs were similar.

Also, blood glucose, LDL cholesterol, and blood pressure all declined.

The researchers found that EPC numbers and activity were strongly correlated with increased nitric oxide in blood, so that may be how berberine works to promote EPCs.


As noted, EPCs are strongly and negatively correlated with cardiovascular risk. An article in the New England Journal of Medicine tells the story: Circulating Endothelial Progenitor Cells, Vascular Function, and Cardiovascular Risk.

“…endothelial progenitor cells may provide a circulating pool of cells that could form a cellular patch at the site of denuding injury or serve as a cellular reservoir to replace dysfunctional endothelium…

To test this hypothesis, we measured the activity of endothelial progenitor cells in relation to cardiovascular risk factors and endothelial function in a group of healthy volunteers. These subjects had no symptoms associated with atherosclerosis or active ischemia.”

For the result, see chart below.

“The nature and size of our study do not permit us to determine whether low levels of endothelial progenitor cells can accurately predict subsequent cardiovascular events… Establishing a definitive cause-and-effect relation requires studies in which the levels of endothelial progenitor cells are experimentally manipulated and the biologic or therapeutic effects assessed. Rather, we believe our data suggest that circulating endothelial progenitor cells have a role in vascular homeostasis. We further speculate, but cannot prove, that continuous risk-factor–induced injury may lead to the eventual depletion of circulating endothelial progenitor cells. Interestingly, recent studies in animals have suggested that the exhaustion of stem cells may be an important determinant of a number of age-related conditions. Future studies will therefore be needed to determine whether this postulated risk-factor–induced exhaustion of circulating endothelial progenitor cells is a factor in the pathogenesis of cardiovascular disease.”

While the effect of berberine appears important, we can only say that the number and activity of EPCs is associated with lower cardiovascular risk. That seems important enough. Berberine’s additional actions on blood glucose, LDL, and blood pressure certainly seem to substantiate that.

You can read a review of the metabolic and cardiovascular effects of berberine here.

PS: Berberine is just one of the supplements I discuss in my new book, Best Supplements for Men.

PPS: Check out my Supplements Buying Guide for Men.

A Walk in the Park

PS: If you want to learn more about the right supplements, check out my new book, Best Supplements for Men.

Grey Hair Reversal

I once asked whether there was a cure for grey (or gray) hair. There might be, because my hair is turning dark, or at least darker, and might be a case of grey hair reversal.

What occasioned that article was my posting the following pic some time ago:

Which in turn led a reader to comment that my hair was white. While I think of it as grey, it certainly is (was) white in sunlight.

However, my hair is now significantly darker. Check it out.


Admittedly, before and after comparisons aren’t great, and I still have plenty of grey hair. No one who saw me would say that I didn’t.

On the other hand, I have much darker hair than before. That’s not supposed to happen.

What’s going on?

Hair reflects health

Like the skin, hair is a marker for overall health and aging, so anti-aging interventions could, in theory, not only prevent grey hair but reverse it. The problem for the reversal of grey hair is whether the melanocytes, the cells that produce hair pigment, have permanently departed, or whether they can be revived. In the research I’ve read on this topic, no one seems to know.

Grey hair seems to be caused by excess hydrogen peroxide literally bleaching the hair, and this happens because of less catalase, the enzyme that neutralizes hydrogen peroxide, and greater oxidative stress from aging. If that’s the whole story on grey hair, then it seems that it could be reversed. There are indeed some cases in the scientific literature of people’s grey hair turning dark.

I attribute my darker hair to lowering my iron levels, which would lower the level of oxidative stress, including in hair follicles. But I admit that’s just a guess. My ferritin has gone from 137 to 55 at last check.

Aside from my usual anti-aging program, the only other thing I’ve added lately that I can think of is taking berberine, which could have an effect. My workouts and diet remain the same: lifting weights and a low-carbohydrate, whole food diet featuring plenty of meat, dairy, eggs, salads and vegetables, and virtually no processed foods.

So, what I’m saying is that if you commit to an anti-aging lifestyle, which is to say a healthy lifestyle, you may see some changes like grey hair turning dark(er).

Early grey hair runs in my family. My Dad had lots of grey hair in his early 40s.


My grey hair started in my 30s. I’m now 62.

I couldn’t guarantee this result for everyone, but it seems remarkable enough. As I said, that’s not supposed to happen.

After I wrote this, I made the following video, and in it I think you can actually see how much darker my hair has become.

PS: For more anti-aging tips, see my latest book, Best Supplements for Men.

PPS: Check out my Supplements Buying Guide for Men.

Why Older Men Should Lift Weights

Aging means loss of muscle. Men at the age of 80 have typically lost 50% of the muscle they had in youth. Let me emphasize – 50%. That sad statistic shows why strength training is crucial, and why older men should lift weights.

And listen up you younger men: muscle loss begins as early as your 30s, with 10% of your muscle disappearing each decade if you don’t do something about it.

Loss of muscle leads to frailty, lack of vitality, and disease, since muscle is an important determinant of insulin sensitivity. Do you want to go into older age with strength, vigor, and lust for life, or do you want to be weak, feel tired all the time, and feel like old age isn’t even worth the trouble?

Does aging cause muscle loss, or is aging just associated with it, being caused by something else, such as lack of activity? The short answer to that question, in my opinion, is that muscle loss and aging cause and feed on each other in a vicious cycle.

Older men respond robustly to weightlifting

Aging-related muscle loss is thought to be related to anabolic resistance, the condition in which aging muscle doesn’t respond to growth stimuli as well as does younger muscle. The two growth stimuli are dietary protein and strength training.

Muscle is a dynamic tissue, and breaks down and rebuilds regularly, in tune with daily rhythms of fasting and eating, and rest and training. The following diagram illustrates this.

Muscle protein breakdown (MPB) proceeds at the same magnitude in both younger and older people, but muscle protein synthesis (MPS) in older people is lower than in young people, and when this goes on for a long time, muscle loss results.

What can older men (and women) do about this? Lift weights.

The muscle synthetic response on older men remains robust, and they gain muscle and improve their metabolism.

In a study of older men doing high-intensity weight training, men aged 60 to 75, average age 64, trained for 16 weeks using heavy loads (85 to 90% of 1RM). Note that while the study calls the protocol “high-intensity”, it’s not what is normally meant by that term, which means going to failure and pushing muscles to their utmost. In this case, they’re referring to using heavy weights.

The results after less than 4 months of training:

  • Body fat dropped by 3 percentage points, from 24.5 to 21.6%, with no dietary intervention.
  • Muscle strength increased from 50 to 80%.
  • Aerobic capacity (VO2max) increased.
  • Lipid profiles improved; cholesterol/HDL ratio went from high to moderate risk.

The authors of the study made the following points:

  • Older men respond robustly to heavy resistance training, similarly to younger men.
  •  Peak aerobic and working capacities showed significant improvement.
  • The level of exercise intensity in older men needs reevaluation.
  • Heavy resistance training can be practiced by older men and is safe and healthy.

To my mind the most important point is the third: if you’re older, don’t be fooled by people telling you that walking a few times a week for a few miles a day is enough.

Get off your duff and lift weights.

We often hear that adults should aim for 150 minutes a week of moderate intensity aerobic activity. Examples of moderate activity include “brisk walking, swimming and mowing the lawn.” So according to this, walking for 30 minutes, 5 times a week, is sufficient.

But you’ll lose muscle by doing only that.

To be fair, health authorities increasingly recommend some strength training.

But using resistance bands, water paddles, or for most people, their own body weight, isn’t going to cut it. Every older person that’s capable of it should lift weights. Heavy weights.

Even with all the emphasis on aerobic capacity as a promoter of good health, lifting weights significantly improves aerobic capacity in older adults.

Adding more protein and cutting out some of the carbs, when combined with regular strength training, will produce outstanding results. (In the above studies, no dietary changes were made.)


Men lose muscle as they age, but they don’t lose the ability to increase it by lifting weights.

Exercise prescriptions for older men are inadequate. They need to do more than walk.

Lift weights and you’ll see large improvements in body composition, with less body fat and more muscle.

Functional ability will increase, but perhaps even more importantly, self-confidence and sense of well-being will shoot through the roof.

PS: To learn about how more muscle leads to better health and how to train for strength, get my book, Muscle Up.

My new book is Best Supplements for Men.




My Current Workout Routine

Here’s a brief run-through of my current workout routine. Maybe it would work for you too.

I’ll keep this short and hopefully informative. Here’s a video of me doing weighted dips just last week. See the chipped paint on that dip station – that’s my gym, I love it.

Awhile back I wrote about my high-intensity workout routine. Not much has changed; here are my A/B split workouts, which I do once every 3 days, along with a pic taken 2 days ago after my workout.

I occasionally do some jump rope on my off days, otherwise I just walk a couple miles.


PS: I get lots of help from supplements – maybe you could do the same, and my new book Best Supplements for Men shows how.

PPS: Check out my Supplements Buying Guide for Men.

The Truth About Soy

Soybeans are made into a number of food products, such as miso and tofu in Asia, but in the West, it’s increasingly become an ingredient in all kinds of foods, like veggie burgers. Food manufacturers add a soy product, textured vegetable protein, to many processed foods. Is soy good, bad, or indifferent? Here’s the truth about soy: the good, the bad, and the ugly.

The Good

Soy consumption is associated with a lower risk of cardiovascular disease, enough that the FDA decided that soy food manufacturers could make health claims for them. ” [T]he agency has concluded that soy protein included in a diet low in saturated fat and cholesterol may reduce the risk of CHD by lowering blood cholesterol levels.”

The FDA pronounced their judgment in 1999, but unfortunately the intervening years have not been kind to the data on soy, which turn out to have little effect on blood lipids and cholesterol.

Cholesterol itself doesn’t cause heart disease anyway, so the FDA’s reasoning in this case is spurious.

The good about soy isn’t really all that good.

The Bad

Soy contains phytoestrogens, which are molecules that mimic the action of estrogen. They’re a class of compounds known as endocrine disruptors, which affect the sex hormone systems of both men and women, and are of increasing concern in the environment. Endocrine disruptors are also found in food packaging, personal care products, store receipts, and plastics, and should be avoided.

If we should avoid environmental endocrine disruptors, it seems a really bad idea to be ingesting them in large quantities.

Soy contains large amounts of endocrine-disrupting phytoestrogens. See table below.

The amount of estrogens in soy makes the use of hormones in meat into a non-issue.

Some studies have found the effects on male hormones such as testosterone to be minor, others have found a larger effect. The larger point, however, is that because phytoestrogens bind and activate the estrogen receptor, they don’t need to change male hormones to have a feminizing effect.

Large amounts of soy can lead to a complete loss of manhood and gynecomastia (man boobs).

The Ugly

Phytoestrogens in soy can disrupt the endocrine system in fetuses and infants, leading to lifelong reproductive problems in both men and women, and can alter the developing brain.(Source.) Consumption of tofu is associated with decreased cognitive function in adults.

Soy simulates the growth of estrogen-dependent breast tumors in a dose-dependent manner, so soy products may cause cancer.

Men who consumed large amounts of soy had lower sperm counts. “In the multivariate-adjusted analyses, men in the highest category of soy food intake had 41 million sperm/ml less than men who did not consume soy foods.”

Soy suppresses thyroid function and is a goitrogen. As someone who’s had hypothyroidism, I can say that you really, really don’t want that to happen.

The Really Ugly

The really ugly part of soy is that Big Food puts it in everything, and as we saw above, the FDA approves of it, and so large numbers of people are consuming large amounts of soy. Could that be responsible for the general feminizing of men that so many have noted?

They even put it in baby food. Baby food, Mandrake.

Image result for soy baby formula


Textured vegetable protein (TVP) is a waste product of soy oil extraction, so of course they decided to put into food. The food company Archer Daniels Midland invented TVP in the 1960s, and if there’s one thing you don’t want to eat, it’s a food invented by a food manufacturer, especially only a few decades ago. Hydrolyzed vegetable protein is another product often made from soy and found in many processed foods.

Unbeknownst to most consumers, in addition to well recognized soy products such as soy milk, tofu and tempeh, soy is found in upwards of 60% of processed foods. Textured soy protein (50–70% soy protein) is a meat substitute found in hotdogs, hamburgers, sausages and other meat products while soy protein isolate (90% soy protein) is used to enrich energy bars, sports drinks, infant formula, cereals, granola bars, imitation dairy products, ice cream, cheese and even doughnuts. In addition, textured soy protein is used to fortify numerous products in the school breakfast and lunch programs as well as other federal assistance programs. Soy is a popular food additive because it is a cholesterol-free, vegetable protein rich in complex carbohydrates and unsaturated fats, high in fiber, and free of lactose. It also contains upwards of 100 or more phytoestrogens. [Source.]

The Deep Soy State may be metaphorical, but it’s a very good metaphor, with food companies and the government colluding to get it into all kinds of foods.

Avoiding soy and phytoestrogens

Soy and the phytoestrogens in them are widespread ingredients in processed foods, so avoiding soy is both a simple and sometimes difficult task: don’t eat processed foods. Eat whole, unprocessed or minimally processed foods like meat, dairy, eggs, fish, vegetables, and nuts.

I’ve got some more bad news too: beer contains phytoestrogens. It comes from hops, which contain a potent phytoestrogen, and which may be responsible for reported menstrual problems in female hop workers. “Hops have been shown to contain one of the most potent in vitro estrogenic substance known from the plant kingdom, (±)-8-prenylnaringenin.” (Source.) The new style craft beers contain more hops than ever, so they are probably best avoided.

Soybean oil does not contain phytoestrogens, but you shouldn’t consume it anyway. It’s toxic waste as far as I’m concerned, and can cause cancer and heart disease.


The good news is that if you make a concerted effort to avoid soy and other estrogenic substances, any hormonal or sexual health problems such as infertility or erectile dysfunction should return to normal in fairly short order, perhaps weeks to months, depending on initial severity.

So cast off your chains, you have nothing to lose but your man boobs.

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PPS: Check out my Supplements Buying Guide for Men.