Is Viagra the Most Potent Heart Disease Drug?

Erectile dysfunction (ED) is associated with heart disease, which is logical, since erections depend on the circulation of blood, and arteries must be in a healthy state for both erectile function and heart health. The relation between the two conditions allows us to ask, is Viagra the most potent heart disease drug?

Viagra and similar drugs are associated with vastly fewer heart disease deaths

A just-published study took a look at a large number of Swedish men, 43,145 to be exact,  7.1% of whom got treatment for ED. Then the researchers looked at who died, had a heart attack, or who had heart failure. “Association between treatment for erectile dysfunction and death or cardiovascular outcomes after myocardial infarction.”

Men who got treatment for ED with Viagra had a large reduction in both deaths and hospitalization for heart failure. Reduction in deaths was 33% overall, 40% for heart failure.

Importantly, reduction in death rates appears to be dose dependent.

Men who got 1 prescription for Viagra had 34% fewer deaths.
Men who got 2 to 5 prescriptions had 53% fewer deaths.
Men who got greater than 5 prescriptions had 81% fewer deaths.

Only men who got Viagra for ED had lower death rates. There was no association with death rates for those who got another form of treatment for ED, alprostadil.

What in the world is going on here? The answer can lead us to the true cause of heart disease.

Nitric oxide

Viagra (sildenafil), and the other drugs in this class, such as Cialis and Levitra, are inhibitors of an enzyme abbreviated PDE5, hence they’re called PDE5 inhibitors. They result in an increase in nitric oxide in endothelial cells, which form the lining of blood vessels. In turn, nitric oxide (NO) dilates blood vessels and is critically important in maintaining vascular health.

NO has been implicated in a number of cardiovascular diseases and virtually every risk factor for these appears to be associated with a reduction in endothelial generation of NO. Reduced basal NO synthesis or action leads to vasoconstriction, elevated blood pressure and thrombus formation… Appropriate pharmacological or molecular biological manipulation of the generation of NO will doubtless prove beneficial in such conditions.

The study on Viagra and heart disease deaths only shows association, not causation, and the researchers caution that men who took Viagra may have been in better health to begin with, although none of the men in the study had had a heart attack at the start of the study.

But we can see a mechanistic link between Viagra, which dilates blood vessels that allow erections, and less heart disease, due to better blood vessel function, lower blood pressure, and lower tendency to form blood clots.

Viagra blows statins out of the water

Statin drugs are used to lower cholesterol and allegedly prevent coronary artery disease.

In high-risk populations, that is, in people with existing coronary artery disease, a meta-analysis showed that statins had no statistically significant effect in decreasing death rates.

Earlier studies found a benefit to statins, but we need to keep in mind the biases in studies funded by pharmaceutical companies. After 2004, when full disclosure regulations came into effect, statins appear to have stopped working. That is, studies done before full disclosure found lost of benefit, afterwards they found little to no benefit.

Either way, Viagra showed a huge reduction in deaths, much greater than statins.

Nitric oxide and heart health

The working of the lining of blood vessels, or endothelial function, is critical for arterial health, and endothelial dysfunction is a marker of atherosclerotic disease.

Endothelial dysfunction is a systemic disorder and a key variable in the pathogenesis of atherosclerosis and its complications. Current evidence suggests that endothelial status is not determined solely by the individual risk factor burden but rather, may be regarded as an integrated index of all atherogenic and atheroprotective factors present in an individual, including known as well as yet-unknown variables and genetic predisposition. Endothelial dysfunction reflects a vascular phenotype prone to atherogenesis and may therefore serve as a marker of the inherent atherosclerotic risk in an individual.

Nitric oxide, as we saw above, is a crucial mediator of endothelial function.

Insulin resistance is strongly associated with heart disease. And insulin resistance causes endothelial dysfunction.

Given the huge reduction in death rates with Viagra as compared to statins, and assuming a mechanistic link between Viagra and the reduction, it sure looks like endothelial function, as mediated by nitric oxide, is far more important to heart disease than cholesterol.

How to increase nitric oxide and endothelial function

Besides Viagra, what else improves endothelial function through increases of nitric oxide.

Citrulline, a supplemental amino acid, treats erectile dysfunction and improves exercise performance. It does this through increasing nitric oxide signaling.

Vitamin D increases endothelial function.

Exercise increases flow-mediated dilation, the measure of endothelial function. “This may contribute to the benefit of regular exercise in preventing cardiovascular disease.” – Understatement of the year.

Iron massively decreases nitric oxide synthase activity, and iron chelators increase it.

For more on how to increase your health and lifespan, try a copy of Dumping Iron,  acclaimed by the world’s leading authority on iron and health, Leo Zacharski, M.D.

PS: Check out my Supplements Buying Guide for Men.

Control Your Mitochondria or They Will Control You

Mitochondria are small organelles within cells, popularly known as the powerhouses of the cell, since their main function is to burn energy. With a few exceptions, such as red blood cells, every cell in the body contains hundreds or thousands of mitochondria, and they are crucially important in aging. That’s why you must control your mitochondria or they will control you.

Aging mitochondria

Mitochondria are so important to aging that there’s an entire theory called the mitochondrial theory of aging.

As cells age, so do mitochondria, and they decline in capacity to make energy, generating reactive oxygen species (ROS, or free radicals), which cause self-damage as well as damage to the cells within which they reside.

Mitochondrial quality control is crucial to fighting aging.

Mitochondrial quality control

Perhaps the most crucial mitochondrial quality control process is autophagy, the cellular self-cleansing process that rids cells of junk. When mitochondria are subject to this process, it’s known as mitophagy. Mitochondria that are past their expiration date, that are inefficient and generating large amounts of free radicals, are sent through the meat grinder of autophagy, their constituents broken down and sent for recycling, and new mitochondria are built to replace them.

The decline in autophagy is one of the hallmarks of aging. An aging organism can no longer increase autophagy to the extent that it could when young. Autophagy is necessary because of the importance of maintaining clean cells. With aging, cells become cluttered and inefficient, and this is one of the crucial differences between young and old cells. Aging takes place most of all at the cellular level; aging cells mean an aging body. Maintenance of highly functional mitochondria is a characteristic of youth.

Insulin resistance is a characteristic of aging, and people with it have poorly functioning mitochondria.

Older people have lower exercise capacity and in general a lot less energy than young people. This is due in large part to declining mitochondrial function.

How to increase mitochondrial function

As you get older, and if you do nothing to intervene in the aging process, mitochondria decline in function and cause aging. In essence, if you don’t control your mitochondria, they will control you. Fortunately, there are a number of things you can do about this; most of them require some discipline.


Exercise robustly increases mitochondrial function. A new study found that high-intensity interval training robustly increased the ability of mitochondria to generate energy, 69% greater in older people, and 49% in younger. The older people had a greater deficit in function, hence they had a greater improvement.

Intensity is a crucial component of exercise in every way, but especially so regarding improvement in mitochondria.

The study found that resistance training did not improve mitochondrial function (though it did improve insulin sensitivity), but this is likely because of training that wasn’t intense enough. Other studies have found increases in mitochondrial proteins involved in energy production in resistance training. That’s one reason for strength training I recommend high-intensity training. Nonetheless, if you lift weights, it may be beneficial to add a component of high-intensity interval training.

Intermittent fasting

Nothing increases the process of autophagy more than going without food. Intermittent fasting increases the quality of mitochondria, partly through this mechanism.

The cellular and molecular effects of intermittent fasting are similar to those of regular exercise, which suggests that mechanisms are similar.

Resveratrol and other phytochemicals

Resveratrol increases lifespan in mice on a diabetes-inducing diet. One of the ways that it works is by increasing mitochondrial quantity and quality.

EGCG, from green tea extract, also improves mitochondrial quality.


The accumulation of iron causes mitochondria to become dysfunctional, and this is critical in aging. Controlling iron levels is critical to fighting aging.

Control your mitochondria or they will control you

Aging is characterized by a loss of mitochondria quality and quantity, and there’s every reason to think these are critical to the aging process.

A couch-potato life, with no hormetic stressors, leads to poor mitochondria, and subsequent aging and disease.

Therefore you must control your mitochondria or they will control you.


For more on how to control aging, the best few bucks you’ll ever spend are on my book, Stop the Clock.

PS: You can support this site by purchasing through my Supplements Buying Guide for Men.

Guest Post: How to Make the Most of Your Time

This is a guest post by Jennifer Landis, who writes at Mindfulness Mama. (See her previous guest post.) Jennifer is a health nut – which explains what she’s doing here at Rogue Health. When she pitched me this post, she said it was a bit “parenty”, which it is, but it’s all good.


Unexpected Ways to Make the Most of Your Time 

When you’re a parent, the amount of free time you have is pretty much non-existent. After all, you’re doing cooking, cleaning and laundry for more people — and the smaller that extra human is, the messier they tend to be!

You’re also on high alert pretty much round the clock, so even small tasks you used to do without thinking take at least twice as long because you’re constantly being interrupted — or at the very least, your mind isn’t fully on the job.

Five Ways to Get a Little Extra Time

This means your leisure time takes a big hit, and that could turn you into an extremely miserable person to be around. Instead of embracing martyrdom and turning into a monster, try these tips for getting a little more out of your day.

Just a little extra efficiency here and there can add up to a glorious couple hours of free time on the weekend — and maybe a little each day — if you play your cards right. Here’s how:


  1. Turn Tasks Into Togetherness Time 

Whether you see your kids all day or they have started school and won’t be home until mid-afternoon, you can still kill two birds with one stone in the time you spend with them. Once a day(ish), declare that it’s time to do a chore together — emptying the dishwasher, folding laundry, sweeping the floor, whatever. The job goes faster with help as long as you pick something age-appropriate, and you set the expectation that families pitch in together.

You can also have more in-depth conversations that you might think — working side by side somehow frees older kids up to start talking about things they’d never bring up at the dinner table.


  1. Limit Your Screen Time

For real, it’s time to talk about what a time suck Facebook is. It’s so tricky to get a handle on just how many minutes — or hours! — per day you waste on social media because you probably open up those apps for just a few minutes at a time. Maybe you’re waiting for the microwave to finish, and then suddenly your food got cold because you got sucked into a political debate.

Instead, give yourself a specific time frame for internet browsing and social media during the day — maybe 30 minutes in the morning and 30 minutes at night. When you compartmentalize, you’ll use those distracting screen a lot less and have more free time for something you really love.


  1. Maximize Your Time in the Car 

Whether you commute to work or just spend a lot of time playing chauffeur for your kids each afternoon, the time you spend behind the wheel — or worse, stuck in traffic — can seriously cut into your enjoyment of life. Try using that time to your advantage with some great apps that let you listen to your favorite book, learn a new language or even meditate — all hands free!

You can also record your daily to-do list or make phone calls with your Bluetooth to take care of little things while you’re stuck on the road.


  1. ABC: Always Be Carrying … a Book! 

You never know when you’re going to be stuck waiting in line for longer than you expected, so it’s a good idea to toss a book into your bag so you can pass the time productively. You can leverage this otherwise annoying time to enjoy yourself for a bit, or you can focus on learning a new skill.

Carry a journal instead, and you can get creative by writing your own material while you wait. Maximizing your time also means stealing some moments back for yourself, and this is easier to do when you pack appropriately.


  1. Learn to Say No to Things That Don’t Bring You Joy

If you’re feeling over-booked with committees and volunteer work in addition to everything else you do for your family, it’s time to start cutting back. You de-clutter your home to get rid of things you no longer need, right? You can also de-clutter your life to clear your schedule of activities and commitments that are making you crazy instead of fulfilled.

You only need to ask yourself one simple question to know if a new activity is something you should say yes to: Would you be glad to clear your Saturday to do it, right now? If not, it’s probably not worth adding to your schedule. Avoid a difficult conversation by emailing your polite regrets, and refuse to feel guilt by saying you’re going to spend time with your family instead — then do it!

By finding extra time in your day with just a few of these tips, you can breathe a little easier because you won’t be breathlessly running from task to task. Enjoy your extra time by doing something for yourself — even if it’s just a quick trip to the gym! — or by spending a relaxing afternoon with your family. You’ve definitely earned it!

PS: If you liked this article or my website in general, check out my books, Dumping Iron, Muscle Up, and Stop the Clock.

PPS: You can support this site by purchasing through my Supplements Buying Guide for Men.

The End of Cancer?

Cancer is the second leading cause of death in the U.S., and is one of the most dreaded diseases anywhere. It typically strikes older people more; some 90% of cancer is diagnosed in people over the age of 50, and incidence increases with age. Could we be looking at the end of cancer?

While many of the causes of cancer have been identified, the exact manner in which cancer starts and why it does so remains an open question in science. While the lay person may consider the origin of cancer to be of academic interest only, the way that cancer starts, and even precisely what cancer is, has great relevance to prevention and treatment. A new line of thought on cancer has emerged in recent years, backed by compelling evidence, that the prevalent theory of how cancer starts and what it is are wrong, at least in part.

This new way of looking at the problem is the metabolic theory of cancer.

Is cancer caused by genetic mutations?

The prevailing theory of cancer is that it’s caused by genetic mutations, which lead to uncontrolled growth, metastasis, and death. The Mayo Clinic flatly states, “Cancer is caused by changes (mutations) to the DNA within cells.” A scholarly review, The Hallmarks of Cancer, argues that the “enabling characteristic” for these hallmarks of cancer is “genome instability”, that is, the increased propensity of the cell’s genes to mutate.

But seemingly, there’s a paradoxically low rate of mutations together with a high rate of cancer. Even the authors of the review cited above state:

But mutation of specific genes is an inefficient process, reflecting the unceasing, fastidious maintenance of genomic integrity by a complex array of DNA monitoring and repair enzymes. These genome maintenance teams strive to ensure that DNA sequence information remains pristine… Yet cancers do appear at substantial frequency in the human population, causing some to argue that the genomes of tumor cells must acquire increased mutability in order for the process of tumor progression to reach completion in several decades time.

Mutations are rare, they say, because cells strive to repair their DNA, but cancer occurs frequently.

There are a number of other paradoxes of cancer.

The discovery that cancer cells collectively manifest millions of different types of gene mutations led to the idea that all cancers were different, or different in type, and required complex treatment.

But what if cancer cells all had a remarkable similarity, one that had nothing to do with genetic mutations?

The Warburg effect

Otto Warburg, who won the Nobel Prize for Physiology or Medicine in 1931, first proposed that cancer is due to a metabolic defect.

Just as there are many remote causes of plague, heat, insects, rats, but only one common cause, the plague bacillus, there are a great many remote causes of cancer-tar, rays, arsenic, pressure, urethane- but there is only one common cause into which all other causes of cancer merge, the irreversible injuring of respiration.

In most normal cells, energy is burned in the mitochondria in the presence of oxygen to produce ATP, the currency of energy. Cancer cells have a severely diminished, or no, capacity to do this. Instead, they burn glucose for energy in a process known as aerobic glycolysis. The mitochondria of cancer cells appear to be severely damaged, so the only way they can obtain energy is through this alternative and relatively inefficient method.

Cancer cells burn glucose, as opposed to the mixture of fat and glucose burned by normal cells. Furthermore, non-cancerous normal cells can use ketone bodies for energy, and most cancer cells cannot.

Cancer as a metabolic disease

If genetic mutations don’t cause cancer, what does?

Thomas Seyfried, the most well-known scientist in this area, postulates that cancer is a metabolic disease.

In Seyfried’s view, metabolic dysfunction in the mitochondria of cancer cells is the initial event in cancer formation. The result is genomic instability, leading to the gene mutations seen in cancer; but the mutations are not causal, the metabolic dysfunction is.

Cancer cells burn sugar as a result of their dysfunction.

Therefore, treatment partially consists of depriving cancer cells of glucose. One way to do that is to lower blood glucose levels by the ketogenic diet. In fact, Seyfried has advocated just this approach. It appears to be effective, though much more clinical research would need to be done.

2-deoxyglucose, a compound that is taken up by cells but which cannot be metabolized, and which essentially jams up the metabolic machinery, inhibits cancer cells in vitro. So it appears that depriving cancer cells of glucose, their main fuel, inhibits their growth and may kill them.

Is there any other way to jam the molecular machinery of cancer cells?

Inhibiting cancer metabolism

Enter Dr. Laurent Schwartz, French physician and oncologist, who has been working on this problem for many years and treats patients using the metabolic theory of cancer. (In addition to conventional treatment.)

Schwartz and colleagues have developed a compound called Metabloc, which consists of two over-the-counter (in the U.S. at least) supplements, hydroxycitrate and alpha lipoic acid. These two compounds interfere with the metabolism of cancer cells, but have little effect on the metabolism of normal cells.  Below is a chart showing various strengths of both compounds either alone or in combination against cancer cells in vitro. The highest concentrations of the combination, though still in the micromolar range, reduced cancer cell viability to zero, i.e. no surviving cells.

This treatment, in contrast to standard cancer treatment, is non-toxic, with few side effects.

In vivo, in mice, the combination works too, greatly inhibiting tumor growth. Interestingly, adding another common compound, capsaicin, the substance that gives hot chili peppers their heat, inhibited cancer cells even more. The addition of a fourth compound, a peptide drug called octreotide, further diminished cancer cell viability. Octreotide is a potent inhibitor of growth hormone.

Schwartz has published several papers on the effects in actual patients; the most recent (as far as I know) is “Combination of Metabolic Treatment of Aggressive Primary Brain Tumour and Multiple Metastases of the Brain”.

Background: The combination of hydroxycitrate and lipoic acid has been demonstrated by several laboratories to be effective in reducing murine cancer growth. In previous article in 2014, we reported the fate of 11 patients treated for metastatic cancer unresponsive to chemotherapy. As of today, 32 months after inclusion, five of these patients (45%) are still alive.

Patients and Methods: We report the cases of 12 patients with advanced brain tumor. They were all treated with conventional treatment and a combination of sodium R lipoate (800 mg bid), hydroxycitrate at 500 mg tid and low-dose naltrexone at 5 mg at bedtime. Eight patients had primary brain tumour (n=8 including five glioblastomas) four patients had multiple brain metastases.

Results and Discussion: The combination of conventional and metabolic treatment was well tolerated. Four out of five patients with gliobastoma are still alive and well. The longest follow-up is 7 years.The four patients with disease widely metastatic to the brain have experienced long-term survival. A randomized clinical trial of metabolic treatment associated with conventional treatment is warranted.

The conclusion of the paper states:

To our knowledge, this is the first attempt to treat cancer using a combination of molecules targeting abnormal cancer metabolism. None of these patients experienced major side effects of metabolic treatment. At this stage of development, not a single case proves the efficacy of treatment. But at the time of writing, most patients were alive and well several months after having been sent home to await their death. Several months of life without symptoms strongly suggests that targeting cancer metabolism may be a reasonable option in therapy of advanced brain cancer. The role of metabolic treatment and its association with existing therapy remains to be explored in well-conducted trials.

The end of cancer?

It’s obviously too soon to say whether this new treatment for cancer will be so much of a success that the treatment becomes widely accepted and used. Apparently, Dr. Schwartz is the only oncologist in the world who is using it. His new book is “Cancer: Un Traitement Simple et Non Toxique.”

The number of cancers is increasing and, despite what we hear about medical progress, mortality has not dropped since 1960 , especially for tumors of the pancreas, lungs, liver, brain …

And if, instead of merely seeking to destroy cancer cells with aggressive treatments, they were also rendered functional again? This approach can improve the effectiveness of chemotherapy and the survival of patients.

This is the conviction of Dr. Laurent Schwartz, shared by many scientists around the world. This brilliant physician and researcher in cancer has spent his career gathering evidence that the mechanisms that cause cells to multiply in an anarchic way are essentially related to a sugar burning problem .

In this book written for patients and caregivers, he proposes to normalize the metabolism of cancer cells by a combination of non-toxic and inexpensive foods and supplements, or even a diet low in carbohydrates.

This metabolic treatment has already benefited many patients.

I can only say that if I had cancer, I would definitely seek out the expertise of Laurent Schwartz. He appears to be little known in the U.S., but his latest book will be translated into English and published here. It’s also being translated into Spanish and Italian.


Dr. Laurent Schwartz

While Dr. Schwartz has patented Metabloc, the fact that it’s comprised of two OTC supplements means it’s cheap and that huge pharmaceutical industry profits can’t be made on this treatment. That’s an obstacle to it becoming more widely adopted, since cancer treatment is big business.

PS: If you liked this article or my website in general, check out my books, Dumping Iron, Muscle Up, and Stop the Clock.

PPS: You can support this site by purchasing through my Supplements Buying Guide for Men.

Is Alcohol an Anti-Aging Drug?

The consumption of alcohol has been shown, over and over again, to be associated with substantially lower death rates, especially from heart disease. Since aging is the biggest risk factor for the main chronic diseases of civilization, and alcohol lowers death rates, is alcohol an anti-aging drug?

Alcohol and lower death rates

There are grounds for skepticism in the association between alcohol and lower death rates. (I’ve been one of the skeptics.) For instance, people who have quit drinking, and are therefore non-drinkers, may have quit either because they were alcoholics or had other health problems, therefore their higher death rates would not entirely be due to non-drinking. Some studies have tried to get around this limitation by comparing drinkers only to lifelong teetotalers.

There are also confounders, such as IQ and social status. Contrary to what might be assumed, more intelligent people and those with higher socioeconomic status drink more, and IQ and SES are also associated with better health and longer life. Researchers can statistically adjust for these factors, but there may be others that they don’t see. There are ways of getting around this limitation too, as we’ll see.

In Spanish men, alcohol consumption was associated with much lower death rates from heart disease. What’s interesting here is that it’s not just moderate drinkers who have lower death rates from heart disease, hazard ratio 0.49 indicating less than half the risk. But high and very high consumers also had lower risk, at 0.46 and 0.50 respectively. (As there are scores or hundreds of similar studies on alcohol and death rates, I will cite merely this one.)

To get around the IQ and socioeconomic status effects, it helps to look at some particular group of people, and that’s what a study of British doctors did. As confirmation of the ex-drinker hypothesis, ex-drinkers had higher mortality than never-drinkers or current drinkers. But even when the drinking doctors were compared to the never-drinking doctors, they had 28% lower death rates from heart disease, 31% lower from respiratory disease, and 12% lower death rates overall.

It’s possible that IQ and social status effects are not completely eliminated in this study. Even among doctors, some are smarter and make more money than others. But it would seem to considerably narrow the IQ range under consideration, from say 110 to 150, instead of 75 to 150 in the entire population. The authors of this study conclude:

Although some of the apparently protective effect of alcohol against disease is artefactual, some of it is real.

In other words, studies like these show a mixture of factors, such as IQ, status, previous health, and so on, but one of the factors is that alcohol decreases death rates.

Why alcohol lowers death rates

Lots of theories have been floated as to why alcohol might lower death rates, especially from heart disease. But the following one really grabbed my attention. First, we need to look at one of the most prominent ideas in aging research: growth vs longevity.

Put bluntly, anything that promotes growth – after the age of maturity or reproductive onset – also promotes aging.

More mechanistically, anything that causes constitutive activation of mTOR (the mammalian target of rapamycin) promotes aging.

Food, obesity, anabolic steroids, growth hormone: all promote mTOR and thus promote aging.

Food restriction, resveratrol, rapamycin, metformin: all decrease mTOR activation, and thus promote longer life.

Add alcohol to the list of mTOR deactivators.

Alcohol mechanistically deactivates mTOR. These effects were seen in cultures and animals at a concentration of about 0.1% ethanol, which just barely above the legal driving limit for blood alcohol. In other words, this effect could be very real in real-life, actual drinkers, not just in a laboratory.

This effect might wholly explain lower death rates in drinkers. There are reasons to think that less mTOR activation will decrease both heart disease and cancer rates. While drinkers have higher risks of certain cancers, especially of the esophagus, which alcohol directly contacts, they may have lower risks of other forms of cancer, for instance non-Hodgkin’s lymphoma.

mTOR also regulates insulin sensitivity, so there’s another means by which alcohol could function as an anti-aging drug.

The mTOR effect is also consistent with alcohol inhibiting muscle growth. In other words, drinking could cut your gains. It seems doubtful that this has much of an effect in those who train hard and drink moderately, but it does seem to account for muscle wasting in alcoholics.

Is alcohol an anti-aging drug?

Despite my skepticism about the association between alcohol and better health, a lot of this research is compelling in my opinion. The mechanistic link with mTOR, which so tightly regulates aging, is another piece of evidence, and these effects seem to be compatible with the amount of alcohol drunk by real-world, moderate drinkers.

PS: If you liked this article or my website in general, check out my books, Dumping Iron, Muscle Up, and Stop the Clock.

PPS: You can support this site by purchasing through my Supplements Buying Guide for Men.

Fasting Cleans the Brain

Intermittent fasting, or going without food for some period of time, has many benefits. Fasting lowers the level of the hormone insulin, which then allows fat-burning to take place. Weight loss is one of the reasons that intermittent fasting has garnered so much attention of late. Another reason it’s so healthy is that fasting cleans the brain. Let me explain.

Food causes profound physiological effects

The body tightly controls energy use and storage. When we eat, the body responds with various hormonal and biochemical effects, among them an increase in the hormone insulin and activation of the growth mechanism mTOR (mammalian target of rapamycin). It does this so that food energy can go to the right places, whether storage or for immediate use, and so that the body can replenish itself by building new structures.

When this system goes awry, for instance by frequent eating (“grazing”) or by ingestion of lots of refined carbohydrates, the body preferentially stores more energy and obesity can result.

In contrast, not eating food also has profound effects, such as deactivation of mTOR, lowering of insulin, and activation of the energy-sensing network AMPK.

The most prominent and important effect of fasting is an increase in autophagy, the cellular self-cleansing process.

Autophagy and why it’s important for health and lifespan

Aging is the outcome of a contest between damage and repair.

Damage occurs for many reasons, but most importantly as a consequence of living and burning energy. While the analogy between an aging body and a used car isn’t perfect, in the respect of damage, they are similar. Using them wears them out.

The difference between a living thing (including a human) and an automobile is that the living thing is capable of repairing itself. It periodically breaks down pieces of its machinery that are past their expiration date and replaces them. For example, the average red blood cell lasts only 120 days before it’s removed and replaced by a new one.

Autophagy is the means by which the body removes misfolded and aging proteins, organelles such as mitochondria, and generally keeps up cellular housekeeping by removing and replacing damaged parts.

Eating food all but stops autophagy; fasting strongly increases it. With this it can be seen that autophagy is a cyclical process, rising and falling on a daily or even hourly basis. In humans, autophagy strongly increases with overnight fasting during sleep.

Autophagy also declines in aging; that is, a given stimulus produces less autophagy in an older than a younger animal.

Because of the decline in autophagy with age, damage accumulates. If we were to have the ability to strongly increase autophagy, much of the damage could be repaired.

All interventions that increase lifespan in lab animals also increase autophagy. This fact is critical. Animals that have been engineered to have low or no autophagy do not see an increase in lifespan with calorie restriction, rapamycin, resveratrol, reduced insulin signaling, anything. I’m not aware of a single exception.

Clearing damage from the brain

Fasting intermittently strongly increases autophagy. In normal animals including humans, going without food for a few hours increases this process; in aging animals, longer periods of fasting may be necessary.

While the effect of fasting on the liver, muscles, and other organs has been well-known, until recently it was thought that this did not occur in the brain.

But scientists have recently shown that short-term fasting induces profound neuronal autophagy. Mice that were fasted for 24 hours showed an increase in autophagy in the brain, and this effect increased after 48 hours of fasting. The authors of this study discuss its implications for human health:

Our observation that a brief period of food restriction can induce widespread upregulation of autophagy in CNS neurons may have clinical relevance. As noted above, disruption of autophagy can cause neurodegenerative disease, and the converse also may hold true: upregulation of autophagy may have a neuroprotective effect…  it has been suggested that intermittent fasting might improve neuronal function by means that are entirely independent of caloric intake, and may instead reflect an intrinsic neuronal response that is triggered by fasting… Food restriction is a simple, reliable, inexpensive and harmless alternative to drug ingestion and, therefore, we propose that short-term food restriction may represent an attractive alternative to the prophylaxis and treatment of diseases in which candidate drugs are currently being sought.

How long does one need to fast to elicit this effect? In this study, 24 hours sufficed to double the number of autophagic vacuoles in neurons, and 48 hours increased them another ~50%. However, 24 hours is a long time for a mouse, and a human could conceivably need longer.

But, 16 to 20 hours of fasting in a normally healthy human is enough to drop insulin greatly and as a consequence increase autophagy. Fasts like these are relatively easy, since your sleep time counts. If you don’t eat after dinner, say 6 P.M., and then don’t eat until noon the next day, you’ve just fasted 18 hours.


Intermittent fasting as an anti-aging strategy

Intermittent fasting as an anti-aging strategy is central to my book Stop the Clock.

Aging means a decline in autophagy and a consequent increase in molecular damage. By fasting intermittently and periodically, autophagy can be increased and molecular damage repaired.

The brain also might be repaired in this way, as this study shows.

PS: If you liked this article or my website in general, check out my books, Dumping Iron, Muscle Up, and Stop the Clock.

PPS: You can support this site by purchasing through my Supplements Buying Guide for Men.

Video: Geroprotectors

If you prefer the talking head version of my recent article on geroprotectors, here ya go.

Geroprotectors: Anti-Aging Molecules

Geroprotectors are molecules that have been shown to slow aging and/or extend lifespan in experimental animals. A group of mainly Russian scientists have collaborated on a website that lists all known geroprotectors: anti-aging molecules.

Many compounds are listed on the site, and we’ve discussed many of them here as well, but we’ll just look at a few of them here that have been tested in a couple of recent experiments. They are:

  • rapamycin
  • metformin
  • berberine
  • resveratrol
  • vitamin D3
  • aspirin
  • EGCG
  • n-acetylcysteine
  • caffeine

Screening geroprotectors in cell culture

The first study is Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling.

Activation of the mammalian target of rapamycin, or mTOR, is thought to be a very important pro-aging mechanism. It’s not surprising that this paper appeared in the journal Aging, of which Mikhail Blagosklonny is the editor, as he’s been one of the most prominent proponents of the involvement of constitutive mTOR activation in aging. Rumor has it that he’s started taking rapamycin himself.

DNA damage also increases in aging.

Both of these processes, mTOR activation and DNA damage, are decreased by calorie restriction, the potent life-extension intervention.

The scientists who did this research tested the first 6 compounds listed above in cell culture systems to elucidate whether they kept a lid on mTOR activation and DNA damage. A relatively simple system like a cell culture can be used to rapidly screen compounds for potential anti-aging effects. In this case, the compounds tested were all known to extend lifespan in one case of another, so the scientists wanted to see how they worked in cell culture with regard to the two processes.

Below is a chart of how these compounds affected DNA damage, using two different indicators.

In this system, aspirin is not listed as it had no effect. 2dG is deoxyglucose, a compound that inhibits glucose metabolism and extends lifespan in C. elegans, but that is toxic in rodents. 9Which is why I didn’t list it above.) All the compounds (except aspirin) were effective, with berberine and rapamycin being among the most effective.

Next, the scientists looked at the ratio of phosphorylated mTOR to mTOR. In this case, lower is better, meaning mTOR is less activated.

Here, metformin was the winner, followed by resveratrol and aspirin.

They also looked at the levels of reactive oxygen species (ROS), a measure of free radical damage in the cells, compared to control.

Here, aspirin was the clear winner, followed by berberine, resveratrol, and vitamin D.

Another recent study looked at the ability of berberine to suppress the conversion of cells into senescent cells. It did so, through deactivation of mTOR with subsequent lower levels of DNA damage.

Another study attempted to validate known geroprotectors using an in vitro model. The substances that passed were n-acetylcysteine, EGCG (from green tea) and myricetin, a plant flavonoid.

Each of these three compounds investigated on the pathway level covers a particular side of the senescence process and some of the effects are shared among compounds: EGCG and Myricetin both activate cAMP pathway; Myricetin and NAC inhibit pro-proliferative signaling via MAPK, p38, PAK and AKT signaling, whereas the effect of NAC on these pathways was stronger. The combination of these compounds with proper dosing may reveal synergistic effects and turn out to be even more beneficial than independent use.

Finally, a study, which I discussed in my book Stop the Clock, showed that screening compounds that protected mammalian neurons in culture from glucose toxicity yielded a number that extended lifespan in the worm C. elegans. The compounds were caffeine, ciclopirox olamine, tannic acid, acetaminophen, bacitracin, and baicalein. Caffeine is of course well-known; ciclopirox olamine is a known iron chelator and antifungal medication.

Taking geroprotectors

I take some of these compounds myself, as I wrote about recently. From those listed above, I currently take berberine, aspirin, vitamin D3, resveratrol, EGCG (green tea extract, occasionally), and I drink plenty of caffeine in the form of coffee, tea, and chocolate.

The doses I use are fairly low (except for caffeine), but that’s OK, since many of them act via hormesis, that is, low-level toxicity that promotes stress resistance. So you don’t need much. That being said, optimal doses of these for humans are unknown for the most part.

The cell culture and in vitro models used in the studies discussed above are very promising ways to test known anti-aging compounds and to screen for others. They allow researchers a much cheaper and faster way to test many compounds without a long, expensive experiment using many animals. These methods also show what these compounds are doing physiologically, elucidating their mechanisms of action.

⇒PS: If you liked this article or my website in general, you can return the favor by buying one of my books, Dumping Iron, Muscle Up, and Stop the Clock. Or one of the others, like Smash Chronic Fatigue, Top Ten Reasons We’re Fat, or Best Supplements for Men’s Health, Strength, and Virility.

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Or hit up my Patreon page.

High-Fat Diet Doesn’t Cause Obesity

I wrote the other day about the less-than-optimal control animals and humans used in fasting and calorie-restriction studies. Partly this is due to the bad food that most people eat, as well as the substandard lab food that rats and mice eat. A similar problem exists in other diet experiments on lab animals. Here I’ll show that a high-fat diet doesn’t cause obesity – in lab animals anyway.

High-fat lab diets

If you read much of the scientific literature, you’ll come across lots of studies using lab rats and mice that were fed “high-fat” diets. Usually they produce ghastly results, like obesity, diabetes, cancer, cognitive deficits, and so on. Then the mainstream media trumpets these as meaning that you are going to get sick and die if you eat a high-fat diet.

Just to pull one more or less at random, “High-Fat Diet Disrupts Behavioral and Molecular Circadian Rhythms in Mice“. Control mice ate the Harlan Teklad 7012 diet of standard lab chow. It’s 25% protein, 17% fat, and 58% carbohydrate. Importantly, it contains no sugar and has high-quality, natural ingredients.

The high-fat group ate Research Diet 12451. Here are the ingredients:

This diet is 35% carbohydrate, 20% protein, and 45% fat. It contains sucrose – table sugar – as 17% of calories, as well as soybean oil, maltodextrin, and casein.

High fat? It’s more like dessert for rodents.

That amount of sugar is comparable to what the typical obese and heart-disease-prone American eats. Soybean oil has a high omega-6 content. Maltodextrin is a simple carbohydrate that turns to maltose and then glucose when absorbed, spiking blood sugar and insulin. Casein supplies all the protein, whereas the standard lab chow has no animal protein.

Yes, of course animals eating this garbage get sick.

Healthy high-fat diets

In contrast, look at another paper: A high-fat, ketogenic diet induces a unique metabolic state in mice. The animals on the ketogenic diet had lower body weight, lower glucose and insulin, and higher AMPK activity, a pro-longevity mechanism. When animals were switched to this diet, they lost weight. All very healthy, yet it was a high-fat diet, with 95% fat, 5% protein, and 0% carbohydrate. A very high-fat diet.

One of the experimental arms in this experiment was on the Research Diet 12451, as illustrated above. They got fat and sick.

Conclusion: Don’t believe everything you read

The animals on the “high-fat” diet in the first study were in reality eating a high-sugar, moderate-fat diet. Very misleading, if you ask me.

The animals in the second study ate a very high fat, no carb and sugar diet, and were healthy.

So next time you read about a high-fat diet making animals sick, diabetic, obese, or whatever, you can’t take it at face value.

PS: Check out my books, Dumping Iron, Muscle Up, and Stop the Clock.

PPS: You can support this site by purchasing through my Supplements Buying Guide for Men.

My Latest Video: Fasting, Calorie Restriction, and Aging

I recorded this video a few days ago, but thought I’d post it here for those of you who haven’t seen it yet. I discuss the implications of my recent post on anti-aging studies and the use of morbid control subjects.

You can subscribe to Rogue Health and Fitness on YouTube. I plan to make more videos.

High-Intensity Interval Training Makes Fitness Fast

Ever since Dr. Kenneth Cooper introduced the concept of aerobics, we’ve been conditioned to believe that steady-state exercise at a moderate pace is the best, perhaps only, way to increase cardiorespiratory fitness. Jogging, treadmills, and the like, done for 30 minutes or more at a time, have been deemed best. So, lots of people have spent countless hours doing these things, but it increasingly looks like they spent lots more time than they need have. The question is, why are you still jogging? High-intensity interval training makes fitness fast, much faster than jogging or other aerobic exercise. It’s simply more efficient.

High-intensity interval training

High-intensity interval training (I wrote about it here), abbreviated HIIT (or HIT), uses the intensity of exercise as the most important variable. Instead of steady-state, moderate-intensity exercise, HIIT has you going all-out for brief periods of time, followed by a short rest period, then another brief, all-out bout, and so on. While the exercise done in HIIT is much more intense, it’s also much shorter in time.

It’s been known for some time that HIIT is effective at increasing fitness, but what we would like to know is how it compares to moderate-intensity, steady-state exercise in that regard. Does it increase fitness as much?

To answer that, a group led by Martin Gibala, the exercise physiologist whose name has become linked to high-intensity exercise, studied a group of young, sedentary men.

Half the men did sprint-cycle interval training, consisting of three 20-second all out bouts of stationary cycling, interspersed with two minutes of low-intensity cycling.

Half the men did moderate-intensity cycling at 70% of their maximum heart rate, for 45 minutes.

Both groups worked out 3 times a week for 12 weeks.

According to standard exercise dogma, the moderate-intensity cyclists should have improved their fitness more. After all, they were doing aerobics (“cardio”), the HIIT exercisers were doing mainly anaerobic training, and took a lot less time.


  1. Peak oxygen uptake, a direct measure of cardiorespiratory fitness, increased 19% in both groups.
  2. Insulin sensitivity increased similarly in both groups, 4.9 in HIIT, 5.0 in moderate-intensity (no significant difference).
  3. Muscle mitochondrial content increased similarly in both groups.

The high-intensity group worked out a total of one minute per session,  3 x 20 seconds, with a total time commitment of 10 minutes per session when warm-up and time between all-out bouts are included. The moderate-intensity group worked out 45 minutes, or 50 minutes with warm-up and cool-down periods.

No more time excuse

The number one reason people give for not exercising is lack of time. This study shows that in less than 30 minutes a week, you can get in great shape. The aerobic, moderate-intensity group spent 2.5 hours a week to get the same results.

If you make your warm-up and cool-down periods shorter, as well as the intervals between bouts, you could get in shape in probably 15 minutes a week.

It’s intense

High-intensity interval training is intense. You have to give it everything you’ve got in those 3, 20 second intervals. For that reason, some people find it unpleasant.

Personally, I don’t find it unpleasant at all. However, I do enjoy walking as a form of low-intensity exercise. if you want to, you could certainly do both. Just keep in mind that if you do both, walking doesn’t generate the kind of intensity that increases the 3 indices of fitness: peak oxygen uptake, insulin sensitivity, and muscle mitochondria. You need to get over a threshold of intensity before that happens.

Aerobics dogma overturned

This study, along with others of a similar nature, shows you don’t need long hours of exercise to increase cardiorespiratory fitness. I think it also shows that, just as with lifting weights, intensity is the most important exercise variable.

Not volume. Intensity.

Exercise intensity lies on a continuum, from low (walking) to middle (jogging) to high (high-intensity intervals). Getting more fit depends on exceeding an intensity that makes your body work harder than it’s used to.

If you exercise with low to medium intensity, and become fitter, the only ways to increase your fitness are a) increase the amount of time exercising, or b) increase the intensity. Most people choose an increase in time, and some who want to get very fit end up spending hours and hours a week exercising. That’s not necessary. In HIIT, you are always working at the threshold of your physiological ability. So long as you exert the utmost effort when you do it, you will always be getting fitter without an increase in exercise time.


If you do another form of exercise, such as lifting weights, you should be aware that if you combine it with HIIT, it could be easy to get into a state of overtraining. I can attest to this myself. HIIT workouts ideally ought to be treated as a separate workout, separated from another by at least a day. Too much exercise isn’t healthy and your enjoyment of the rest of your life will decline due to fatigue. Of course, the amount of training an individual can handle varies based on age, current condition, diet, sleep, and other factors.

The exercise of the future?

Ever since the concept of aerobics came about, we’ve been stuck in a paradigm that the only way to increase fitness and decrease the risk of disease, especially heart disease, is to exercise aerobically. Is it a coincidence that the rise of aerobics coincides with the rise of the obesity epidemic? I don’t think it is a coincidence, although obviously other factors are involved.

Now that we know that long hours of plodding are not necessary for fitness and for protection against heart attacks, HIIT could be the wave of the future.

I’ve already embraced it thoroughly – and I used to be a distance runner.

A chapter in my book Muscle Up describes high-intensity training and details a number of high-intensity routines.

PS: Check out my books, Dumping Iron, Muscle Up, and Stop the Clock.

PPS: You can support this site by purchasing through my Supplements Buying Guide for Men.

Anti-Aging Studies Are Seriously Compromised

Valter Longo, the noted scientist in aging research, has published a number of studies about fasting as an anti-aging measure. He’s developed a fasting-mimicking diet to be used for extended fasts, which I wrote about here. He and colleagues have a new study out, but the question in my mind now is, does the fasting-mimicking diet work? It may not be as effective as advertised, because anti-aging studies are seriously compromised, including this one.

Extended fasting

Intermittent fasting is the practice of going without food for some period of time. An intermittent fast would usually last a minimum of 16 hours, and extend to 24 hours, perhaps more. Definitions in these matters are not totally arbitrary, but are rather loose. Beyond 24 hours or so, a fast that extends into days, would not be an intermittent fast, but an extended fast.

Previous studies have found anti-aging effects, including immune system regeneration, with extended fasting. Keep in mind that when a mouse or rat is fasted for several days, that’s a very long time in human terms.

The current study looked at humans on a fasting-mimicking diet.

Fasting-mimicking diet

Extended fasts of several days can be difficult, if not physically then psychologically, and to get around the difficulty, Longo has developed a fasting-mimicking diet. (Discussed in my previous article.) The idea is that a low-calorie, low-fat, low-protein diet for 5 days will not raise insulin of IGF-1, and thus this diet effectively, or nearly enough, physiologically mimics complete fasting.

The current, just-published study is called “Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease“. A layman’s summary says:

Fasting: More than a fad

Mice that fast periodically are healthier, metabolically speaking. To explore whether fasting can help people as well, Wei et al. studied 71 people who either consumed a fasting-mimicking diet for 5 days each month for 3 months or maintained their normal diet for 3 months and then switched to the fasting schedule. The fasting-like diet reduced body weight and body fat, lowered blood pressure, and decreased the hormone IGF-1, which has been implicated in aging and disease. A post hoc analysis replicated these results and also showed that fasting decreased BMI, glucose, triglycerides, cholesterol, and C-reactive protein (a marker for inflammation). These effects were generally larger in the subjects who were at greater risk of disease at the start of the study. A larger study is needed to replicate these results, but they raise the possibility that fasting may be a practical road to a healthy metabolic system.

In sum, the participants decreased:

  • blood pressure
  • body weight and fat
  • IGF-1, the growth hormone implicated in aging
  • blood glucose
  • cholesterol
  • triglycerides
  • C-reactive protein

However, a significant caveat to the above is that changes in glucose, triglycerides, and C-reactive protein overall were not significant; an analysis revealed that changes occurred only in high-risk participants.

One would have to agree that these results look great, and if so, why do I question whether the diet worked?

The answer lies in the baseline values of the participants.

  • Only ~37% were of normal weight, with ~39% being overweight (BMI between 25 and 30), and ~24% being obese (BMI >30). The subjects were on average somewhat leaner than an average group of Americans, but not much.
  • Body fat: the paper gives body fat in terms of total volume, but lean body mass in terms of percent; doing a calculation reveals that the average body fat percent was about 34%. Even with the fact that over 60% of the participants were women, that’s a lot. They were fat.
  • What did they eat normally? No information is given, but the average American eats 20 teaspoons of sugar daily, and the diet of the average American is 50% carbohydrate.

My point is that the participants who ate the fasting-mimicking diet were fairly typical: they were overweight, had high body fat and low muscle mass, and most likely ate like the typical American with plenty of processed junk.

Of course if you drop their calorie intake and they eat less crap food, they’re going to have better health markers. That’s a given.


What about people who already eat well, with a carbohydrate percentage well under 50%, with no refined carbs or sugar or vegetable oil, no processed junk food, and who have low body fat and exercise regularly? Is the fasting-mimicking diet going to strongly decelerate your aging?

Not likely.

Calorie restriction may not even work

A similar phenomenon is at work in animal studies of calorie restriction, which is the most robust life-extension intervention known.

The food that scientists feed lab rats and mice is garbage, loaded with sugar and vegetable oil and toxic amounts of iron. Do you think eating less of that will extend their lives? Not surprisingly, the answer is yes.

Lab mice and rats that are used as controls in calorie restriction studies are metabolically morbid. With their garbage food, and kept in cages with little exercise, the average control rat or mouse becomes obese as they age.

So the question arises: does calorie restriction really extend lifespan by slowing aging, or do the animals just live longer because they don’t become obese or develop diabetes?

Calorie restriction does not appear to extend the lifespans of wild mice.

Below is a chart of the weight of (lab) rats throughout their lifespans. (From here.) Rats are fully mature, according to the same article, at 5 to 6 months. Do wild rats gain weight after maturity? That seems doubtful to me, and very old rats, assuming they survived long enough in the wild, would be likely to lose weight. But in the laboratory, they gain weight steadily throughout life, and that does not seem normal. They become metabolically morbid and overweight/obese.

Any intervention that prevents their weight gain will prolong their lives, but that does not mean it will prolong the lives of normal rats or humans.

Added: In “Impact of caloric restriction on health and survival in rhesus monkeys: the NIA study“, the authors discuss why the NIA monkeys did not show an increase in lifespan, while in another study, the WNPRC, they did. Answer: the control animals in WNPRC were fed junk diets with nearly 30% sucrose – yes, you read that right, the control animals got tons of table sugar.

A notable difference between the two studies is the composition of the monkey diets…. 

Fat content of the NIA study diet was derived from soy oil and the oils from the other natural ingredients (i.e. corn, wheat, and fish). Fish meal contains approximately 8–12% fat and is rich in omega-3 fatty acids. The WNPRC study dietary fat was derived from corn oil. [Corn oil is known to promote cancer.] Carbohydrate content was also strikingly different; although both diets have 57–61% carbohydrate by weight, the NIA study diet was comprised primarily of ground wheat and corn, while the WNPRC study diet contained corn starch and sucrose. Indeed, the WNPRC diet was 28.5% sucrose, while the NIA study diet was only 3.9% sucrose. This latter point may be particularly important as a diet high in sucrose can contribute to the incidence of type II diabetes.

Drosophila melanogaster, the fruit fly, is often used in studies of aging. Over a 3-year period of adaptation to laboratory conditions, they undergo a rapid loss of stress resistance. One might look at these as the fly equivalent of obese lab animals or humans. Studying aging in this population will give faulty data.

In my opinion, this is a scandal.

Conclusion: Aging studies need an overhaul

Fasting studies in humans and calorie restriction studies in animals both appear to suffer from control groups that are metabolically morbid. Sick people and animals.

The majority of Americans, about 80%, are not 100% healthy and suffer from chronic health problems to one degree or another. If a diet, a fast, or other regimen corrects some of those problems, that does not mean that it slows aging, only that the participants became less metabolically morbid.

If a calorie restriction regimen extended animals’ lives, much of the time that might be only because they were prevented from becoming obese. Wild mice may be living optimally for life extension already, and restricting their food in wild conditions may do nothing. What they need is protection from predators.

What’s needed are studies using metabolically healthy humans and animals at baseline, and then finding out whether a given intervention helps them. But good luck with that. Cost and convenience are huge factors in any scientific study. Labs don’t want to pay staff to come in to feed animals on weekends, for instance, and they want to use the cheapest, most convenient food.

Lab food contains toxic levels of iron, up to 10 times the requirement, and as animals age, their body iron stores increase dramatically, causing misfolding of proteins and oxidative stress and sarcopenia. Hey, maybe it’s the food? I’ve hammered on this topic, but expect it to go nowhere as usual.

I’ve lately become much more skeptical about studies in aging, and those are the reasons why.

PS: Here’s the talking head version in which I discuss the various fasting and CR experiments and what they mean for the science of aging.

PS: Check out my books, Dumping Iron, Muscle Up, and Stop the Clock.

PPS: You can support this site by purchasing through my Supplements Buying Guide for Men.

PPS: I was contacted by the new site and asked for a mention. Looks to be a very worthwhile site dedicated to the science of aging, and written by professionals.

Five Ways to Fight Depression

Depression is a physical sickness that manifests as a mental illness. We know this because of the physical signs and symptoms that accompany depression: fatigue, insomnia or hypersomnia, significant weight loss or gain, and others. It follows that treating the physical aspects of depression can alleviate the mental aspects. Here are five ways to fight depression.

Huge numbers of Americans take antidepressant meds, and they’re of dubious safety. Of people over the age of 12, 11% take antidepressants, and the rate is close to 1 in 4 middle-aged women.

I’m writing this because I heard that a friend’s relative, a young man, committed suicide. Sad, pointless, and it didn’t have to happen.

Quit eating crap food

A diet with a high glycemic index, that is, one that tends to raise blood glucose (sugar) levels – spikes them – is associated with depression. (See previous link.) So are diets heavy in processed food – characterized by sweetened desserts, fried food, processed meat, and refined grains. Sugar consumption is associated with depression.

All of that stuff is just crap food, and raises your risk of depression. If you are depressed, stop eating that stuff instanter. (And even if you aren’t and you value your health.)

Eat whole, unprocessed foods. If a factory came in between the farm and the food on your plate, don’t eat it. That means most of the food in the center aisles of the supermarket: the chips, sodas, fruit juices, frozen packaged dinners, pizza, ice cream, cakes and cookies… what else? I don’t even know anymore because it’s been so long since I’ve eaten any of it.

Exercise, especially weightlifting

People who exercise regularly are less likely to be depressed, and higher intensity exercise is more protective against depression than lower intensity. Intervention studies have shown that there’s an actual treatment effect, i.e. the association is not (only) due to depressed people lacking the mojo to get up and move around.

Furthermore, exercise appears to treat depression as strongly, or more so, than psychiatric drugs.

Exercise compares favorably to antidepressant medications as a first-line treatment for mild to moderate depression and has also been shown to improve depressive symptoms when used as an adjunct to medications.

Many more studies could be cited, but you can also ask anyone who exercises (such as me) what they feel like during and after exercise: on top of the world.

It’s said that three lines of thought are common to depression:

  1. I’m no good.
  2. The world is a bad place.
  3. The future is hopeless.

Exercise can’t make the world a better place, but as for numbers one and three, I assert that exercise can help immensely. When you feel good physically it’s more difficult to think that you’re no good, and the future looks better. Maybe the world will seem brighter too.

Now, why do I emphasize weightlifting as a good form of exercise to fight depression.

  1. It shares many effects with aerobic exercise, such as increasing aerobic fitness (VO2max), which is important for better mental and physical fitness.
  2. It’s an intense form of exercise, especially compared to, e.g., walking. Many of the increased benefits of lifting weights may in fact be due to nothing besides it being more difficult.
  3. Lifting weights improves body composition, i.e. the ratio of muscle mass to fat, and therefore makes you look and feel better. (Aerobic exercise has a poor record in this area.) Hard to feel bad about yourself when you look great, and better than most people around you.

But don’t neglect the cardiovascular aspect of your exercise, which means don’t sit in the gym for 5 minutes between sets looking at your phone or chatting with friends. Work. Out. For that I favor high-intensity lifting and high-intensity interval training.

Vitamin D and magnesium

Good nutrition in general is very useful against depression, but vitamin D and magnesium may be two of the most important nutrients in this case, since they both work against depression and many people are low in them.

Vitamin D deficiency is associated with depression. Supplementation with vitamin D improves depression.

Even among healthy adolescents, who could be expected to be outside in sunshine much more than healthy – much less unhealthy – adults, prevalence of vitamin D insufficiency is as high as 42%.

Magnesium deficiency is associated with depression and supplementing it can treat the illness.

Dose of vitamin D is related to many factors, such as body weight, latitude of residence, season, and skin color, therefore it’s impossible to make across-the-board dose recommendations. See here for a discussion of doses.

The RDA for magnesium is 420 mg for adult men, 320 for women.

Get a good night’s sleep

Depression is associated with insomnia, hypersomnia, and disruption of circadian rhythms. Paradoxically, whole or partial sleep deprivation for one night can relieve depression. Advancing the sleep phase (staying up later) can help.

There are all kinds of ways to improve your sleep, such as alcohol avoidance, melatonin, a completely dark bedroom, magnesium. One thing people like us should do is install light-reducing programs on our computers, tablets, and phones, such as f.lux and Twilight. Interestingly, my new Kindle Fire tablet came with a built-in color adapter, Blue Shade, so word’s getting out.


Light has profound effects on the brain. Light therapy treats depression as effectively as drugs. Most light therapy involves sitting before a bright light with wavelengths similar to the sun, for 30 to 60 minutes in the morning, usually upon awakening.

Or, you could cut out the middleman and get some sun in the morning. Make it a habit to get exercise in the sun, and don’t wear sunglasses. This is obviously more difficult in the winter and at certain latitudes, so the use of bright light may be in order.


Depression isn’t some mysterious thing that comes out of nowhere, but is connected to brain function. Improving dietary and other lifestyle inputs can improve the brain’s function and out a big dent in depression.

PS: Check out my books, Dumping Iron, Muscle Up, and Stop the Clock.

PPS: You can support this site by purchasing through my Supplements Buying Guide for Men.

Is Grass-Fed Beef Worth the Money?

In the recent post about best and worst protein supplements, a reader asked me whether I thought grass-fed whey was worth the money, and I answered in the negative. There’s a larger question: is grass-fed beef worth the money? Grass-fed anything?

Why grass-fed whey protein is not worth extra money

Grass-fed animals, cows in this case, produce meat and milk that has a different fatty acid profile from animals that are grain-fed. In particular, omega-6 fatty acids are lower, and omega-3 fatty acids are higher; this is a much more beneficial fatty acid profile than from grain-fed animals.

So, if it’s more beneficial for health, what’s the problem with grass-fed whey? Whey has virtually no fat in it; it’s pure protein. You end up paying a lot of extra money for no benefit.

It’s a typical health food scam, IMO.

Grass-fed beef

Grass-fed beef, as noted above, contains lower levels of omega-6 fatty acids. These are the same types of polyunsaturated fats found in vegetable oils and that raise inflammation. An unbalanced ratio of omega-6 to omega-3 may lie behind many chronic diseases; our paleolithic ancestors may have had a 1: 1 ratio; in the modern world, we may have 15:1 or higher. Decreasing omega-6 fats is definitely a good thing.

So why do I question whether grain-fed beef, with lower omega-6 fatty acids, is worth it? Don’t we want to be healthy?

To answer that, check out the graph I made, below. It shows the content of omega-6 fats in grass-fed beef,  grain-fed beef, and chicken. Data are from Self Nutrition Data.


The type of beef used in the chart is ground, 70% lean, per 100 grams (just under 1/4 pound) of meat. Grass-fed beef has about 28% less omega-6 than grain-fed. Chicken has a whopping 6 to 7-fold more than either of them.

Now let’s look at omega-3 fats, the beneficial fat that most people don’t get enough of. For comparison, I’ve added salmon to the graph.

Grass-fed beef has more omega-3 than grain-fed, but it’s dwarfed by salmon.

What can we conclude from this?

If you eat chicken with any frequency, say once a week, grass-fed beef will not decrease the amount of omega-6 fats that you consume. The chicken in your diet will overwhelm any decrease in omega-6 from eating grass-fed beef.

If you eat any salmon at all – and this is generally true for eating any type of fatty fish – you would get a far greater amount of omega-3 fats than from grass-fed beef.

Using the Pareto principle, that 20% of the inputs yield 80% of the benefits, you’d be better off giving up chicken and eating salmon regularly, say once or twice a week. Furthermore, a teaspoon of cod liver oil has about 1000 mg of omega-3 fats; since I don’t eat fish regularly, I supplement with fish oil.

If you eat no chicken – and importantly, eat nothing made with vegetable oil – and you eat fish regularly, and you have a lot of cash, then go ahead and buy the grass-fed beef. Otherwise, as I’ve shown above, you’d be better off making the other changes I noted.

Eating grass-fed beef is like a man with a pot belly trying to improve his attractiveness by buying a sports car. While a sports car improves his attractiveness, he’d be better off getting rid of his belly first before he goes and blows a bunch of money on a car.

Hormones and Antibiotics

Added: Some people object (here and on Twitter) that grass-fed beef contains less or no antibiotics and hormones.

Regarding antibiotics: Antibiotic residue testing in meat results in few positive samples. Upshot: antibiotics are rapidly metabolized, and animals must go through a withdrawal period before slaughter. Unacceptable levels of antibiotics are found in less than 1% of inspected meat.

Regarding hormones, most foods have much larger amounts of estrogens than beef. See table below – link.

To my mind, the same principles apply as for fatty acids. The value added from a much more expensive product isn’t worth it, not to me anyway.

PS: Check out my books, Dumping Iron, Muscle Up, and Stop the Clock.

PPS: You can support this site by purchasing through my Supplements Buying Guide for Men.

Big Animals Die Younger

A recurring theme in research on aging is that of growth vs longevity. In essence, they’re opposed: more growth means shorter life, and less growth means longer life. The activation of physiological mechanisms in growth promotes aging, and deactivating them promotes longevity. Big animals die younger.

Evidence in non-human animals

Between species, larger animals tend to live longer. Elephants live longer than mice, who live longer than flies and worms. Mikhail Blagosklonny, the noted scientist who studies aging, sums it up as “Big mice die young but large animals live longer“.

As the article says, within species, larger animals die younger. Small mice live longer than big mice, because they grow less.

Why do larger animals, between species, live longer? Larger animals have fewer predators and low rates of accidental death; therefore, natural selection has worked on them to evolve longer lives, with more robust anti-aging mechanisms. In contrast, if the average mouse is dead at two years of age from predation or other accidents of life, then there’s nothing for natural selection to work on.

Calorie restriction is the most robust life-extension intervention known to science. Animals live longer when their food is restricted. The causes of this are hotly debated, but one theory is that since food promotes growth, restricting food hinders growth and extends life. Even when animals are fully grown, food activates the growth mechanism and effectively shortens life.

Evidence in humans

There’s a lot of evidence that larger humans die younger.

Obesity by definition means higher than normal body fat and thus higher body weight. The adverse health effects of obesity are well known.

Even when body fat remains the same, however, larger size appears to mean shorter life.

Among professional baseball players, larger size was strongly correlated to a lower age at death. See graph below.

Note that BMI for all the baseball players is quite similar, so age at death was not related to being overweight, but to total body weight and height. Taller players died younger.

Among different ethnic groups in California, death rates correspond to their average body mass index, in order from lowest to highest: Asian Indian, Chinese, Japanese, Hispanic, White, African-American. (Hispanics actually weight the most of these groups, evidence for the Hispanic health paradox.)

Among Olympic athletes, those who set records at younger ages died younger. “Early and extraordinary peaks in physical performance come with a longevity cost“.

Life history theory postulates a trade-off between development and maintenance. This trade-off is observed when comparing life histories of different animal species. In humans, however, it is debated if variation in longevity is explained by differences in developmental traits. Observational studies found a trade-off between early and high fecundity and longevity in women. Development encompasses more than fecundity and also concerns growth and physical performance. Here, we show a life history trade-off between early and above average physical performance and longevity in male Olympic athletes. Athletes who peaked at an earlier age showed 17-percent increased mortality rates and athletes who ranked higher showed 11-percent increased mortality rates. Male athletes who had both an early and extraordinary peak performance suffered a 4.7-year longevity cost.  This is the first time a life history trade-off between physical performance and longevity has been found in humans. This finding deepens our understanding of early developmental influences on the variation of longevity in humans.

The authors say, “It is important to note that cocaine was available since the first Olympic games and could have played a role in the association.” I’ve never heard before of Olympic athletes using cocaine, but that would certainly shorten lives. I suppose it’s completely unknown how many athletes used it.

Basketball players, who are of course much taller than average, don’t seem to live very long. Anecdotally,

Within the past year, the NBA has seen a spate of deaths among some of its notable retired big men — among them Moses Malone, Darryl Dawkins and Anthony Mason, none older than 60.

And now Larry Bird admits, he doesn’t expect to live to a ripe old age.

Another piece of evidence: women live longer than men, and women are smaller.

Kitavans, Okinawans, and Cretans

The people of Kitava, Okinawa, and Crete are famous for better health and longer lives. Their diets and lifestyles have been extensively studied and have given rise to concepts like the Mediterranean and Okinawan diets, the Blue Zones, and the importance of religion and social ties for health and longevity.

What seems to have escaped many researchers is that these people are all small.

Kitavans show no evidence of heart disease or strokes and cancer appears to be rare. Young Kitavan men average 125 lbs (57 kg), and Kitavan men over the age of 60 average 107 lbs (49 kg). Kitavan women are also small. By the way, 80% of Kitavans smoke, yet appear to be in excellent health.

Okinawa has a high number of centenarians. The average male Okinawan centenarian weighs 97 lbs (44 kg); the average female centenarian weighs 81 lbs (36.7 kg). (ibid.)

The average man in Crete has a BMI of 22.8, the lowest of any surrounding Mediterranean communities, and they have the lowest death rate. “Cretans have 1/2 the all-cause and <1/20 coronary heart disease (CHD) mortality of larger northern Europeans.” (ibid.)

If size has such a large correlation to death rate, it makes me wonder how important the diets or other lifestyle factors of these people are. Maybe we’ve been looking at the wrong things, and all along it’s been their size that’s the most important. Of course, their diets affect how large they grow too.


Centenarians are on average short. In a group of Italian centenarians, average height was 156 cm, or 5’1.4″. “Mean values for height and weight of nonagenarians and centenarians were at the lower percentile values of the distributions reported for elderly American and European subjects…” Height was calculated using a formula based on knee height, so that spinal shrinkage did not influence results.

Okinawan centenarians are of “short stature”. In another group of centenarians, women were on average 2.5 cm (1 inch) shorter than controls, but men were not shorter.

It also appears to be trivially easy to find examples of long-lived short people. For example, just the other day the NY Times ran an article about Robert Marchand, the now-celebrated 105-year-old Frenchman who keeps breaking cycling records. It turns out that M. Marchand is 5’0″ tall, and weighs 115 lbs. Salustiano Sanchez, who once held the rank of world’s oldest man, and who died at age 112, was nicknamed “Shorty”.


So, there seems to be good evidence, both human and animal, that larger and/or taller humans and animals have shorter lives. Noted aging researcher Luigi Fontana has calculated that “risks of developing type 2 diabetes, cardiovascular disease, and several types of cancer” are lowest at a BMI of 21 to 22, and rise from there.

Why is there an inverse relation between growth and longevity?

One answer centers on mTOR, the cellular growth controller. When mTOR is activated after maturity, physiological reactions occur that promote aging. This is the “quasi-programmed” theory of aging. mTOR is necessary for growth and development, but continues in a mindless loop afterwards, accelerating aging.

Interventions that inhibit constitutive activation of mTOR are either good for health or extend lifespan:

Interventions and conditions that promote mTOR constitutive activation are detrimental to longevity:

  • obesity
  • growth hormone supplementation. Acromegaly, or excess growth hormone, results in a 2 to 3-fold higher death rate.
  • anabolic steroids
  • insulin resistance.

However, an attribute like height is under strong genetic control, so it’s safe to say that genes have a lot to do with the growth vs longevity effect.

On the other hand, heights have increased over the past two centuries. Italian conscripts increased in height by about 5 inches from 1854 to 1963, and current rates of height increase are from 10 to 30 mm a decade. That increase must be environmental, and could be due to better nutrition and fewer childhood diseases.

What to do about it

You can’t control your height, so what can you do about this association?

  1. Stay lean with a good, muscular body composition and low body fat.
  2. Use some of the interventions listed above, such as resveratrol, intermittent fasting, and dumping iron.

That’s about it. Having good body composition will ensure that you don’t have insulin resistance. Essentially, all of these things go together: insulin sensitivity, normal rhythms of autophagy, and good body composition. mTOR inhibits autophagy, the cellular self-cleansing process which is so critical to aging.

Beyond that, anti-aging treatments that inhibit mTOR are underway. You can already get metformin if you find the right doctor, although OTC berberine might be as good. Rapamycin is a promising anti-aging drug that’s being extensively studied, although it has its downsides. It seems possible that pulse dosing of rapamycin, perhaps once weekly, could have anti-aging effects without many of the downsides. Mikhail Blagosklonny believes that “rapamycin will become the cornerstone of anti-aging therapy in our life time”.

PS: Check out my books, Dumping Iron, Muscle Up, and Stop the Clock.

PPS: You can support this site by purchasing through my Supplements Buying Guide for Men.

Best and Worst Protein Supplements

As part of some research I’m doing for another project, I looked into protein supplements. For myself, I’ve always confined my choice of protein supplement to the best ones, and haven’t looked around a lot in general. I also asked some of Twitter peeps if they’d recommend candidates for the worst protein supplements. While this post is not meant to be a comprehensive guide, here’s a quick tour d’horizon of the best and worst protein supplements. I confined myself to ten of them.

Best Protein Supplements

These are not in any particular order.

  1. Immunocal. This whey protein supplement is clinically proven to raise glutathione, and therefore it’s good for people suffering from an illness that increases oxidative stress. (Most of them do.) Immunocal is non-denatured and unflavored. Downside is that it’s quite expensive. While if I were ill I’d be happy to spend the money on it, this product is more than what athletes and bodybuilders need; they can use a less expensive product without loss of effect.
  2. NutraBio Whey Protein Concentrate. I’ve long recommended this protein. Cold-processed, non-denatured, moderately priced. NutraBio has both flavored and unflavored types. The flavored contain artificial flavors and sweeteners, so avoid those if you’re concerned about them.
  3. Bulk Supplements Whey Protein. Unflavored, great quality, and inexpensive. This may be the best protein supplement for the money, at 20 bucks for a kilo.
  4. MyProtein IsoPro 97. This one gets high marks for purity and quality, according to my research. Probably a bit harder to find, but it’s available at Amazon
  5. Optimum Nutrition Gold Standard 100% Whey Protein Powder. This may be among the best of the big-selling brands. Artificially flavored/sweetened.
  6. Vega Sport ProteinI doubt if I have many vegans in my audience, but if you want a vegan protein option, here it is. The protein comes from  pea, pumpkin, organic sunflower seed, and alfalfa. There’s some interesting research that plant proteins can be as effective for muscle growth as animal-based protein if you get enough, or possibly more. This one has 30 g a serving, so it would likely do the job.


Worst Protein Supplements

Again, in no particular order.

    1. Muscle Milk. Lousy protein combo, spiked with glutamine, contains maltodextrin, corn fiber, fructose, sunflower and canola oil. Only 16 grams of protein per 150 calories serving. Just, no.
    2. Optimum Serious Mass. While two scoops has 50 grams of protein, it also has 1250 calories, maybe half of what a normally active, moderately sized man needs. This might be good if you’re a malnourished ICU patient, but even then there must be better choices. The mass you gain is likely to be fat. First ingredient is maltodextrin. Mass gainers make a lousy choice as a protein supplement.
    3. Odwalla Vanilla Protein Drink. Hipster protein. First two ingredients, soy milk and sugar. Enough said. A whopping 43 grams of sugar, or about 10 teaspoons. 370 calories. Good Lord, where do they come up with this stuff?
    4. Gatorade Whey Protein Recover Bar. 360 calories.   Look at the garbage ingredients: sugar, vegetable oil, nonfat dry milk, etc. Avoid. And avoid protein bars generally, even if you need the protein, although there may be a few good ones – I don’t know, I never eat them.


There must be thousands of protein supplements out there. If you want to supplement protein, you should look for a short list of ingredients with few of them artificial. For those seeking the highest purity, unflavored is best. Chocolate and other flavors are usually artificial, as are sweeteners. Others may contain vegetable oils, sugar, and unpronounceable artificial ingredients.

By the way, what do you eat for protein if you’re on the go and want something quick, but without the lousy ingredients in protein bars? keep a supply of hard-boiled eggs in your fridge. They’re 8 grams protein each, have lots of healthy fats, and are low calorie. Perfect.

This list is far from comprehensive and is just meant as a quick view of protein supplements. If readers have suggestions or, God forbid, criticism, I’d be happy to hear them.

PS: Check out my books, Dumping Iron, Muscle Up, and Stop the Clock.

PPS: You can support this site by purchasing through my Supplements Buying Guide for Men.