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 Geroscience.com 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.

Coffee, Whiskey, and Cigars Longevity Diet

It’s common for people who have lived a long time to divulge their “longevity secrets”, but in most cases they nor anyone else really knows what the answers to their long lives are. In some cases, centenarians attribute their long life to their vices. Could there be a coffee, whiskey, and cigars longevity diet? Or, as a wag put it: The Bureau of Alcohol, Tobacco, and Firearms – Longevity Edition.

Look at this man: 107-year-old U.S. veteran says he owes longevity to cigars, whiskey and ‘staying out of trouble’. Richard Overton, the veteran in question, is now 110. Here’s a National Geographic video about him. He’s the oldest living veteran of World War II.

I’m going to make the case here that Mr. Overton’s lifestyle has something to do with his long life.

How he lives

Here’s what I gathered from several articles and videos about Richard Overton:

  • He still drives – a Ford pickup
  • He owns a lot of guns
  • If he wakes up at 2 o’clock in the morning, he just gets up
  • He drinks up to 4 cups of coffee in the morning
  • He adds bourbon whiskey to his coffee
  • He smokes cigars, perhaps 10 a day.
  • He’s very active in his church
  • Has a 91-year-old girlfriend
  • He’s lean
  • He avoids stress – he’s easy going and says he’s stayed out of trouble

How his lifestyle contributes to his longevity

He’s lean and he fasts

I”m beginning to think that drinking coffee and whiskey and smoking cigars is healthier than eating a bowl of Honey Nut Cheerios with skim milk for breakfast. Not that the former is so great, but compare it to the alternative that most people have for breakfast.

By doing so, he’s not raising his blood sugar or contributing to insulin resistance. Coffee is also associated with better health and a longer life, and inhibits iron absorption.

By having only coffee and whiskey for breakfast, he may be practicing a form of intermittent fasting. At least, he doesn’t seem to be eating around the clock like almost everyone else these days.

Moderate alcohol drinking is associated with less heart disease.

He might be practicing hormesis by smoking cigars. Tobacco use is associated with much less Parkinson’s disease. He’s said that he doesn’t inhale; while cigar smoking is associated with higher death rates, much of that appears to be due to lung cancer, which is caused by inhaling smoke. While I’m not recommending cigar smoking, it doesn’t seem to have harmed Mr. Overton.

He’s not overweight. There aren’t too many fat centenarians.

He doesn’t sleep too much

Too much sleep, over 8.5 hours, is associated with higher mortality.

He’s active

He still drives and owns guns. While someone in better health could be expected to stay more active, being active also helps one stay in better health.

He goes to church

Being socially active and especially attending church is associated with longer life. He has a girlfriend and a family and lots of friends.

He avoids stress

Overton appears very easy-going. He’s said that after having bullets fly around him in the Pacific in World War II, nothing else could bother him.

He said that he’s stayed out of trouble. That could mean avoiding bad people and dangerous things, thus avoiding getting hurt in a crime or an accident. If you want to live a long time, that’s a necessity.


Undoubtedly, Mr. Overton is blessed with a great genetic makeup. But some of his lifestyle could contribute to his long life.

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.

Hormesis for Health and Longevity: A Guide

It’s obvious that people we refer to as couch potatoes have worse health than others, although these days the couch potatoes outnumber the others. The reason for their worse health is that they are not placing enough stress on their bodies, which adapt to a low-stress state. Then when a real stress comes along, they’re not prepared for it. The phenomenon called hormesis is one in which small doses of toxins or other stressors cause the increase in the body’s (or cell’s) stress defense mechanisms. Hormesis is robustly associated with good health and long life. Anyone wanting to take charge of his health should know about it, so here’s a guide to hormesis for health and longevity.

What hormesis is

Hormesis has been known, albeit in a vague way, for a long time. Famously, King Mithridates VI of Pontus allegedly took small doses of various poisons in order to fortify himself against real doses. Whether that’s true or not, it shows that people knew enough about how that works to concoct a legend about it.

Hormesis is the beneficial effect caused by low levels of potentially toxic agents. (Ref.) In essence, what doesn’t kill you makes you stronger, although that expression should be tempered by the fact that doses of a stress much less than that needed to kill you have beneficial, hormetic effects.

Many types of stressors can cause hormesis, for example:

  • exercise
  • phytochemicals (from plants)
  • radiation, both solar and other
  • heat and cold
  • alcohol
  • calorie restriction and fasting
  • toxic metals in some cases

Hormesis is characterized by a so-called J-shaped (sometimes U-shaped) curve, in which a small amount of a substance or stress results in better health than a zero amount. Increasing the dose increases the stress response up to a point, beyond which increasing doses worsen health.

Image result for hormesis u-shaped curve

This curve illustrates the concept. With increasing exposure, or dose, health risk decreases to a nadir of risk, after which it rises. At some point of increasing dose, the risk rises above that seen initially, at which point the dose can be truly said to be toxic and promoting ill health. Sometimes this curve is shown upside down, but the meaning is the same.

Hormesis activates biochemical stress defenses, most notably through the Nrf2 transcription factor that regulates the expression of antioxidant, protective mechanisms. Among these mechanisms are enzymes like catalase, superoxide dismutase, glutathione peroxidase, and the so-called phase 2 detoxifying enzymes.

A principle of hormesis is that of pre-conditioning. To use an example, if you train to run 10 miles, you become pre-conditioned, and if you had to run 15, you could do it. If you only trained for 1 mile, and then had to run 10, you would not be able to, or only with great difficulty and harm to your health.

The opposite of hormesis is, for lack of a better term, one that I’ve called the couch potato lifestyle, one in which the organism is never challenged. Then, when an untoward event or stress or toxin comes its way, it’s unprepared.

Activating stress response pathways via hormesis is essential for health and anti-aging.

Agents of hormesis


Probably the most familiar of hormetic agents is exercise. When you exercise, you consume more oxygen than usual to burn more energy, and this results in increased levels of free radicals (also known as reactive oxygen species, ROS).

…exercise-induced ROS production plays a role in the induction of antioxidants, DNA repair and protein degrading enzymes, resulting in decreases in the incidence of oxidative stress-related diseases and retardation of the aging process.


Phytochemicals are plant-derived molecules with beneficial health effects. They include phenols, flavonoids, and others.

While animals can defend themselves by fighting or fleeing, plants are literally rooted to the ground and thus can’t do that. It may come as a surprise that plants do not want to be eaten.

To defend themselves, plants use chemical warfare.

Many or most of the various phytochemicals that benefit human health are toxins, low doses of which upgrade stress defense mechanisms and prevent cancer and heart disease.  Dietary phytochemicals are likely responsible for the health benefits of fruits and vegetables.

Coffee, tea, chocolate, and red wine also have known health benefits; as these are all plant products, the polyphenols and other chemicals in them provide the benefits.

A short list of hormetic phytochemicals would include:

  • curcumin – from the spice turmeric
  • epigallocatechin gallate (EGCG) – from tea
  • chlorogenic acid – from coffee
  • resveratrol – from red wine
  • sulforaphane – from cruciferous vegetables like broccoli
  • chocolate flavonoids

Many of these compounds may also chelate iron, accounting for a great deal of their health benefits. Chocoalte appears to be a huge source of polyphenols, larger than red wine and green or black tea.


Solar radiation causes the production of vitamin D in the skin, but in addition, the radiation itself may be beneficial due to hormesis, and the same goes for other forms of radiation both cosmic and terrestrial.  Low dose radiation

  • upgrades cellular stress defense
  • activates DNA damage repair
  • prevents harm from high doses of radiation
  • stimulates removal of precancerous cells
  • suppresses inflammation and prevents inflammatory diseases
  • stimulates immunity
  • may slow aging

Nuclear shipyard workers appear to have lower cancer rates than others.  Radiation increased the lifespans of British radiologists. In airline pilots and crew, who are exposed to cosmic radiation, a “significant negative risk trend for all-cause mortality was seen with increasing dose [of radiation].” The health effects of many spas have been attributed to radiation.

Sunbathing is also associated with longer life, and sun avoidance has been compared to smoking a pack of cigarettes daily.

Cancer Mortality Rates by State Economic Area - Colon Cancer: White Male 1970-94

The map above (from SUNARC) shows colon cancer mortality in white men in the U.S., 1970-1994. Areas with lots of solar radiation had much lower death rates; the results for breast and ovarian cancer, as well as multiple sclerosis are similar.

How much radiation exposure is healthful, and how should you get it? I’m not sure anyone knows the answer. As it concerns solar radiation, sunburning should be avoided. I’ve seen reports of people wearing radioactive rocks around their necks; I wouldn’t be willing to do that though unless we had a much better understanding of doses needed as well as how much radiation the rocks emit.

Heat and Cold

Both heat and cold are stresses.

Sauna bathing is associated with greatly reduced cardiovascular and all-cause mortality. Note that in this study, they compared only frequency of sauna use, so that sauna bathers were compared only to other sauna bathers. It’s suggested that sauna bathing may be comparable to physical exercise in its effects.

Winter swimmers have higher levels of stress defense molecules, including glutathione, indicating that cold induces hormesis. Cold showers also have health benefits.


Alcohol functions as a low-dose toxin and initiates hormesis. Alcohol is robustly associated with lower death rates; however, much of the benefit comes from red wine, so in most cases, plant polyphenols play a greater role than alcohol itself in promoting health.

Calorie restriction and intermittent fasting

Calorie restriction and intermittent fasting are solid life-extension interventions, and they produce a stress.  They both promote hormesis.

Toxic metals

Please don’t try this at home, but very low doses of methylmercury greatly increased the hatching rate of mallard duck eggs, and it promotes hormesis in C. elegans.


Activating hormesis is robustly associated with better health and longer life. Most anti-aging and life-extending interventions work via hormesis.

The body contains robust anti-aging mechanisms, but they must be activated before they work. The couch potato lifestyle, which features lack of exercise and round-the-clock eating of junk food, is  anti-hormesis.

To slow aging and extend lifespan, use a broad program of hormesis using the factors above. That program would consist of exercise, consumption of phytochemicals, sun exposure, intermittent fasting, and heat and/or cold exposure.

PS: Check out my books, Dumping Iron, Muscle Up, and Stop the Clock. (Stop the Clock is most relevant for hormesis.)

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

Blood Donations, Blood Transfusions, and Iron

In the course of my book Dumping Iron, I discussed blood donations and some of their technicalities, specifically how they lower body iron stores.  In this short article I’ll discuss a few more aspects of blood donations, blood transfusions, and iron.

Transfusion of old, stored blood is harmful

When blood is donated, it is mixed with an anticoagulant and a preservative. The former is to keep the blood from clotting, the latter to preserve its shelf life. Currently, donated blood has an expiration date 42 days (6 weeks) from the day it’s drawn. Most of the blood gets transfused well before its expiration date, but some does not, and gets transfused in the last week of its shelf life and up to the expiration date. This is especially true of less common blood types (B negative, say), for which the supply is lower.

When blood is stored, it ages, essentially decomposes. The red blood cells (RBCs) do not all become decrepit simultaneously, since they have different ages when they are donated. An average RBC lives about 120 days inside the body, before it’s destroyed and replaced with a new one. Hence, when a donor gives blood, the RBCs have a range of ages, from 1 to 120 days. As the blood ages inside its container, some of the RBCs get quite old indeed, well over 120 days, and they decompose (lyse) or otherwise decay.

If a patient is transfused with blood that’s been stored for 6 weeks, bad things can happen.

Red blood cells stored 35 days or more are associated with adverse outcomes in high-risk patients. There’s actually been a ton of research on this topic, but as this study is recent, I’ll just focus on this one.

Clinical trials have shown that longer red blood cell (RBC) storage duration does not worsen outcomes; however, these studies included few RBCs near the end of the 42-day storage limit. We tested the hypothesis that these “oldest” RBCs are associated with adverse outcomes.

The study looked at 28,247 transfused patients given 129,483 units of blood (RBCs, not plasma or platelets). They found that units of blood older than 5 weeks, but not those younger, were associated with adverse events. Odds ratio for mortality with older units of blood was 1.40 in critically ill patients – that means they were 40% more likely to die than those given younger units of blood. There was no extra mortality in those not critically ill, but in older patients there was increased morbidity (sickness) – 22% more likely to become ill.

A recent editorial on this matter concludes that “current maximum storage durations should be carefully reevaluated.” In other words, we’re storing blood too long, and the storage length should probably be no more than 35 days. The problem is that blood shortages are always ongoing, and that would further restrict the blood supply.

Why are old units of blood harmful? The editorial answers that “those that received blood stored for six weeks showed several effects associated with increased harm, including disruption in iron handling, increased extravascular hemolysis, and the formation of circulating non-transferrin-bound iron.”

Old blood cells lyse (similar to exploding) or otherwise decompose, and they release iron into the unit of blood, which when transfused gives the patient a large dose of iron. Some of the cells decompose after transfusion, also releasing iron.

Iron is the reason that transfusion of old blood can harm people.

While this may not seem relevant, if you or a family member need a transfusion, maybe you could inquire about (or insist on) blood that’s younger than 5 weeks old. That might save some agony. Some doctors used to order transfusions of the youngest blood possible in certain cases, though I don’t know how common that practice is any longer.

Should the donation interval be longer?

Currently in the U.S., blood donors can give blood at 56 day (8 week) intervals. In my book, I mentioned that after a blood donation, the blood volume recovers quickly, possibly in 24 hours or less, as the body makes plasma to fill in the volume gap. But replacing the lost RBCs takes longer, hence the waiting period of 8 weeks until the next donation.

A recent study argues that this donation interval should be longer, due to iron requirements.

In conclusion, we provide detailed insights into changes and recovery in iron homeostasis over time until 180 days after blood donation in both regular and new whole blood donors. We conclude that for the vast majority of male donors, the donation interval of 56 days is too short to recover from donation-induced reduction in body iron stores. To stay on the safe side, we propose, as our expert opinion, that ferritin should be kept above 30 mg/L at all times. Based on our observations, this implies a baseline ferritin at each donation of at least 50 mg/L. Furthermore, we propose ferritin as the best parameter to assess personalized donation intervals because it (1) significantly decreases upon blood donation in the present study and (2) has been found to be associated with symptomatic ID in blood donors. Alternatively, and in the absence of point-of-care ferritin platforms, development of ID in donors may be prevented by (1) prolongation of donation intervals to 180 days in all donors as suggested by both the current and the REDS-III study and/or (2) (low) dose iron supplementation.

In a nutshell, they don’t want donors to become iron deficient, a laudable goal.  We know from the data in my book that two donations annually almost guarantee having a ferritin in the desirable, low normal range, so that agrees with the study’s conclusion of 180 days between donations.

However, if someone starts with a ferritin on the high side, say >300, which many people have, it could take a long time to lower it given twice a year donations.

The authors also want donors to have enough time to get their iron stores back to where they were before, the very thing we’re trying to prevent.

My conclusion from this is that, if you are a regular blood donor who donates more than twice a year, you should be cognizant of your current ferritin level, in order to avoid iron deficiency.

A problem with taking the authors’ suggestion to the conclusion of lengthening donation intervals is the same one as with old blood: it would shrink the blood supply, probably even more than a shorter shelf life would. So it seems unlikely to happen.

A large national study of ferritin testing in Canadian blood donors found:

Low-ferritin donors {ferritin <25 µg/L] represented 2.9% of first-time and reactivated (no donation in past 12 months) male donors, 32.2% of first-time and reactivated female donors, 41.6% of repeat male donors, and 65.1% of repeat female donors.

So, repeat donors were much more likely to have low ferritin, and especially the women. The study concluded:

The minimum hemoglobin level will be increased to 130 g/L for male donors [13 g/dl, that’s still a low number for men, below normal] and the minimum interdonation interval changed to 84 days (four donations yearly) for female donors based on iron deficiency risk groups.

If I’m reading that right, Canadian women can now donate only 4 times a year, instead of the previous 6 times. It also seems possible that many of the low-ferritin male donors would be found in the low hemoglobin group.

Previously, a minimum hemoglobin of 12.5 g/dl was required for both male and female donors, but just this past year, the American Red Cross raised the minimum for men to 13 g/dl. That should greatly ameliorate the problem of frequent male donors with iron deficiency. (I was also happy to see this statement from the Red Cross, “The Red Cross does not measure iron levels before blood donation. You can have a normal hemoglobin level and be accepted for blood donation, but still have a low iron level. The fingerstick that is done during your health history is a measure of your hemoglobin level.”)

Recovery of hemoglobin after donation

How long does it actually take to recover the RBCs, together with their hemoglobin, after a blood donation?  Some researchers took a look at that.

RESULTS: After donation of approximately 550 mL of whole blood, [Note: larger than the American donation of 450 ml] the lost amount of tHb of 75 ± 15 g (8.8 ± 1.9%) was recovered after a mean of 36 ± 11 days (range, 20-59 days).

CONCLUSIONS: The results of this study confirm the minimal, recommended donation intervals (56 days for men) as adequate when, for the first time, judged upon by tHb as a direct marker of hematologic recovery.

The following chart shows the percentage of subjects, all of them men, average age 30, by how long it took each one to recover all lost hemoglobin after a donation.

About one fourth of them recovered completely in less than 25 days, and half by 35 days. Almost all recovered by just about the time until they could donate again, 56 days.

The human body makes 200 billion red blood cells daily – that’s 2.3 million per second, requiring 2 x 10^15 iron atoms each second. Unfathomable really. But that process speeds up after blood donation. If someone really needs to, and they have adequate iron stores, the body can ramp up production of blood up to 8-fold.

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.

Major Bacterial Involvement in Rheumatoid Arthritis

In a couple of recent articles, we saw that bacteria and iron are accelerants and likely causes of aging, and that the resultant hypercoagulation can be targeted. Etherisia Pretorius (a South African as the name implies) and Douglas Kell (British), two of the authors of the papers which went into those articles, along with colleagues, have recently written about major bacterial involvement in rheumatoid arthritis. This paper is worth bringing to your attention for a couple of reasons at least: 1) it suggests new ways to treat this condition, which is notoriously progressive and refractory to treatment; 2) it shows the involvement of iron, once again proving that everything I write is correct.♠

What rheumatoid arthritis is

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation, and while it most notably affects the joints, it can damage many other parts of the body. Signs and symptoms include:

  • Tender, warm, swollen joints
  • Joint stiffness that is usually worse in the mornings and after inactivity
  • Fatigue, fever and weight loss

RA affects up to 1% of the population, and is about 3 times as common in women as in men.

The authors of this paper write:

We discuss how the exposure of genetically susceptible individuals to environmental factors (1) that can act as triggers (2), cause an immunological reaction, followed by an autoimmune response (3), can result in RA (4). We review a plethora of evidence, collectively referred to as Ebringer’s theory (5), that points to the environmental trigger as microbial (particularly from e.g. urinary tract infections) (6). We then look at the role of LPS from these microbes (7) in causing an imbalance between pro- and anti-inflammatory cytokines, followed by systemic inflammation, and the effect on the cardiovascular and hematological health of the RA patient (8) (see Figure 1). Finally, recognizing the lack of easy and accessible biomarkers, we suggest that in a truly precision medicine approach, hypercoagulability and also microparticle presence, as well as LPS and β-amyloid analysis could play an important role in tracking the progression of the disease.

Bacteria and iron

A high fraction of those with RA had an infection before diagnosis. One reason that women may have a higher rate of RA is because they have a higher rate of urinary tract infections, especially from the bacteria Proteus.

Once infected, antibodies formed against the bacteria can cross-react with human antigens, such as in joints, and cause inflammatory reactions.

How do these bacteria get inside the body? As we’ve previously discussed, body sites that are normally considered sterile, such as the blood, may have quite a lot of bacteria in them.

These bacteria come from the normal flora of the oral cavity and the gut, as well as from infections. Periodontitis is significantly associated with RA, and gut dysbiosis is frequently found in RA patients. Cardiovascular complications are also common in RA.

One of the keys here is that iron dysregulation allows the bacteria to grow.

We all get some bacteria inside us regularly, but the body’s natural immunity prevents them from growing and reproducing. One of the most important aspects of this natural immunity is iron withholding. Bacteria require iron to grow, as do all living things, and the body tightly holds on to iron to keep bacteria from procuring it for their own uses. Iron is at the center of an evolutionary arms race between animals and microorganisms.

In iron dysregulation, iron escapes from the proteins that hold it, mainly ferritin and transferrin. The free iron is then available for bacteria to use.

An important point is that the more iron in storage, that is, in ferritin, the more there is available to escape and become free iron. Lower body iron stores can mitigate this. This is shown by the fact that in hemochromatosis, or iron hereditary overload, physiological damage occurs, despite the fact that most of the iron is bound by ferritin.

In RA, iron dysregulation and bacterial growth cause hypercoagulation and other damage.

So, would dumping iron via phlebotomy (bloodletting) help treat RA? I couldn’t find a reference to the effect that it’s been tried. But hemochromatosis can masquerade as RA, and iron is found in the joints in RA and other joint diseases.

I’m guessing that someone with RA would not be allowed to donate blood, however. Therapeutic phlebotomy, under a doctor’s care, could be an option.

In addition, attention to gut issues and/or periodontal disease should be of benefit.


Rheumatoid arthritis, a potentially crippling and painful disease, has no known cause. But bacteria are definitely involved, and they are spurred on by excess and free iron.

PS: Check out my book, Dumping Iron, which explains much more about the connection of iron to disease.

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

The Simplest Health Plan: Cut Carbs, Lift Weights

I got into a small debate on Twitter with Brad Schoenfeld, a fitness expert who’s more than skeptical about low-carbohydrate eating. Despite the fact that low-carb diets outperform low-fat, calorie-restricted diets every time they’re put to the test, Schoenfeld thinks the evidence is lacking. Because diets are not matched for calories and protein. Anyway I thought that in this post I’d show how lifting weights and low-carb make for excellent health markers.

Lifestyle factors

I lift weights once every three days, doing a high-intensity program. I’ve been doing this for almost 7 years at this point, though I lifted weights when I was younger too.

I eat low-carb. A high-carb day for me is maybe 100 grams of carbs, and I do that maybe once a week. (Out at dinner at a Mexican place; even though I order the chicken, lots of chips and salsa and tortillas come with it.) The rest of the time, I eat less than 50 grams of carbs. I take supplements too. I also fast intermittently and dump iron.

I’m 61 years old, soon to be 62.

Fasting insulin and insulin resistance

My fasting insulin is 2.9. (Normal range: 2.6-24.9.) Basically you can’t get much better than that. Fasting insulin is one of the most important biomarkers of health, as it shows lack of insulin resistance.

Insulin resistance accelerates aging and disease like nobody’s business, and if there’s anything you want to avoid so that you don’t get the chronic diseases of aging, like cancer and heart disease, that’s it. Insulin resistance is commonly measured by HOMA-IR (Homeostatic Model Assessment of Insulin Resistance). Normal value for adults is <2.

My HOMA value: 0.8. Zero insulin resistance.

Triglyceride/HDL ratio

The ratio of triglycerides to HDL cholesterol is the most important item on a lipid panel. (See also the excellent article by George Henderson and Grant Schofield on the importance of the triglyceride/HDL ratio.)

My triglyceride/HDL ratio is 0.5. There are no normal ranges, but ideal is considered <2.0, dicey 2.0 to 4.0,  above 4.0, you need help; and above 6.0, prepare to die. (Just kidding, if it’s above 6.0, get to work.)

So, my triglyceride/HDL ratio is better than ideal.

My father had heart disease for many decades. Seeing this made me decide long ago that I never wanted it to happen to me. Looks like it won’t.

BMI and body fat

My BMI (body mass index) is just over 23. (Overweight is ≥25, obese ≥30.)

My body fat percent is about 12. That’s a guess, as I haven’t had it measured, and it could be higher. (If my guess isn’t good enough for you, oh well.) I’m not pro bodybuilder lean by a long shot, but I’m lean for a normal guy.


These stats are from just one person, so it doesn’t prove anything.

But, I eat delicious food, I never go hungry (other than a bit during fasting), and my biomarkers are better than perfect. All modesty aside, people compliment me on my appearance regularly.

So does it matter if the merits of a low-carbohydrate diet are not scientifically proven, with all the i’s dotted and t’s crossed? America is 80% overweight/obese, people normally lose weight easily on a low-carbohydrate diet, and we need a debate on its merits? Sheesh.

Granted, some portion of my excellent biomarkers are due to lifting weights. It’s not all diet.

But if people would just get off their backsides and lift some weights, while cutting the sugar and flour out of their diets, the obesity rate would drop like a stone. So would the rates of heart disease, diabetes, and cancer.



Eat a low-carbohydrate diet, lift weights, throw in some intermittent fasting if desired, and you’re golden. You won’t get heart disease, and you’ll look better than 95% of your peers.

Put more simply:

  1. Cut anything with flour and sugar
  2. Lift weights.

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 Supplement Stack

A young college football player who’s keen on staying in shape asked me over on Twitter if I had a list of my current supplements. Though I’ve written about most of them individually and in my supplements book, I don’t have a current list. My thoughts on some of these have changed over time, though not radically changed. So here’s my supplement stack as it now stands. These may not be right for everyone, as they depend on many factors, such as age, level of activity, goals, and how well you do in other areas, such as exercise, diet, and sleep. These are not recommendations, so please do your research and read our disclaimer.

Morning sup stack

In the morning, a coffee with a dash of cream is usually all I consume for the first few hours of the day, sometimes longer. With my coffee, I take:

  • IP6, ~500 mg. It’s in bulk so measurement isn’t precise.
  • resveratrol, ~100 mg. Ditto.
  • berberine, 500 mg
  • vitamin D, 5000 IU – not every day though, as I believe 5,000 IU could be pushing upper limits. Say 4-5 days a week, less in summer when I get some sunshine.
  • vitamin K, ~1 mg. I don’t believe in taking the 5 mg capsule, so I open it and pour a bit in my coffee, and make it last a week.
  • aspirin, 80 mg (“baby” size). Read my article about aspirin; it probably makes sense only for certain people over age 50.
  • fish oil, 1 tsp., 3 days a week. I use cod liver oil. This is another supplement you don’t want to overdo.


On a day when I do a 16-hour or longer fast, in addition to what I’ve already taken above, at mid-morning I may take

  • niacin, 250 mg. Increases autophagy during a fast. More than 250 mg causes me intense, uncomfortable flushing, so I limit it to this.

Mid-Day and Dinner

I often don’t remember these, and I don’t consider them critically important, so that doesn’t bother me. But when I do remember — maybe a couple times a week, I take

  • green tea extract, 400 mg. It has ~30 mg caffeine in it, so I don’t take it later than mid-day
  • curcumin, 500 mg. Not absorbed well at all unless with a high-fat meal.

Workout supplements

Once every three days I lift weights. On those days, after my workout I take:

  • whey protein, 20 grams.
  • creatine, 3-5 grams. I’ve become somewhat skeptical that creatine will help someone who already eats well. But it’s harmless at worst, and cheap, so… I take it.

Night stack

  • magnesium, 200 mg. Promotes relaxation.
  • lithium, 5 mg. Only a couple times a week maybe.


Despite what you’ve read above, I’m skeptical about excessive supplement need. For example, I don’t take a multivitamin, nor do I take any sort of “pre-workout blast” or Lord knows what else they’re selling out there. Everything I take has solid scientific backing for efficacy.

I’m also skeptical of those who say you don’t need supplements. Maybe you don’t need them, but what’s optimal is another story. Most of the supplements I take are fairly cheap and provide insurance and just maybe some edge.

Mangan’s Supplement Rule of Thumb: The more expensive a supplement is, the less likely you are to benefit from it. (Nicotinamide riboside, for example.)

If you wanted to narrow this down, which ones are the most important? I’d say most people could benefit from magnesium and the appropriate amount of vitamin D.

All the supplements discussed above are listed on my supplements buying guide page.

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.

Standard Dietary Advice Makes You Fat and Sick

Standard dietary advice, the advice given by dietitians, doctors, and the Dietary Guidelines for Americans, makes you fat and sick. It’s a combination of unsound science and compromises with the powerful food industry. The people who make and give dietary advice are fighting an intense rearguard action to avoid having to admit that they’ve been wrong all along.

Standard dietary advice is poison, and the medical establishment fully embraces it. It keeps them supplied with customers to whom they can prescribe expensive drugs and procedures.

Standard weight loss diet

Let’s look at a standard weight loss diet. Up to 80% of Americans are overweight/obese, so this is meant for them. (If you’re lean and healthy on what you’re already eating, you presumably don’t need advice.) WebMD has an article on losing weight without fad diets. (i tried for the more authoritative May Clinic diet, but they want you to buy their book to find out what it is. I assume this one is similar.) The WebMD diet advises:

  • Practice portion control. In other words, eat less. Brilliant, the same low-calorie strategy that’s been proven to fail for decades.
  • Eat a variety of foods, including “whole grains”. An extremely monotonous diet isn’t necessarily harmful at all; it depends on what’s in it. Whole grains are not necessary for health.
  • Eat more fruits and vegetables. How are you going to lose weight by eating more of something?
  • Eat often. My personal favorite. “Aim for five to six mini-meals per day. Space your meals every 3 to 4 hours.” Eating more often is completely unnatural and will likely actually make you gain weight.

Is there anything good about the standard weight loss diet? Yes, on the plus side they tell you to get rid of junk food like cookies, chips, crackers, and  ice cream, and to avoid soda and fruit juice.

The standard weight loss diet is ineffective, and that’s partly because it’s a compromise between what will cause weight loss and what people are willing to do.

Standard diabetic diet

Diabetes is a condition of high blood sugar caused by insulin resistance, and is strongly associated with obesity and/or excess body fat. Diet can make the difference between a return to health and a steady descent downward to kidney failure, amputations, infections, and death.

Here are some highlights of what the American Diabetes Association recommends for diabetics:

  • 3 meals and 2 snacks daily. Basically, eating every 4 hours or so.
  • High carbohydrate intake. They call it “moderate”, but it’s 45% of calories as carbohydrate. The average American eats 50% of his calories as carbs.
  • Low calories, i.e. the same failed low-calorie diet.

U.S. Dietary Guidelines

This is official government advice, vetted extensively by panels of doctors and scientists. Read the summary here.

The “Key Recommendations” state that grains and oils are part of a healthy diet, meaning presumably that if you don’t eat them, you will be unhealthy, which is worse than nonsense.

It allows up to 10% of daily calories as sugar.

It doesn’t allow normal (“full-fat”) dairy, one of the healthiest things you can eat; instead it insists on Frankenfoods, i.e. low-fat or fat-free dairy, and “fortified soy beverages”, a chemical concoction.

American physicians are fat too

Suppose you’re overweight/obese or have some kind of other health problem related to your weight. You go to your doctor to get some medical advice.

Chances are good your doctor is overweight or obese himself (or herself, increasingly), and can do little to help you.

A recent survey of U.S. primary care physicians found that 53% of them were overweight or obese. That means that they are either unwilling to keep themselves lean, or unable to do so.

Considering that physicians have very high levels of the personality trait of conscientiousness — otherwise they wouldn’t be in that occupation — how likely is it that thy’re unwilling to stay lean? Very low, I’d say.

That means that they don’t know how to stay lean. If they can’t even provide themselves with good advice, how will they do that for you?

The medical establishment embraces dietary nonsense

All of the above is fully within the mainstream of the medical establishment. Is their advice doing any good? With 80% of the population overweight or obese, diabetes becoming an epidemic, and no end in sight, the answer must be “no”.

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.

Young Blood, Aging, and Iron

The by-now famous experiments that have tied the circulations of young and old animals together, showing the rejuvenating effects of “young blood”, have also shown that the harmful effects of old blood may be greater than the rejuvenating effects of young blood. There’s something about old blood — likely many things — that cause a young animal to show signs of aging; I’ve speculated that two of the more important factors might be iron and bacterial lipopolysaccharides — or possibly the bacteria themselves. Here we’ll discuss the links among young blood, aging, and iron.

Of course, other elements in old blood differ in quantity from those in young blood, and scientists are studying a number of candidates that take the form the form of proteins, as Josh Mitteldorf discusses in his latest article.  (See my review of Josh’s book, Cracking the Aging Code.) One of the proteins under investigation is VCAM-1, for vascular cell adhesion molecule, the level of which increases in old blood.

Exposure of young animals to old blood increases the expression of VCAM-1.

Studies from our lab and others have recently shown that brain function – specifically neurogenesis, synaptic plasticity and cognitive function in the hippocampus, a key center for learning and memory– is inhibited in young mice connected to aged mice through heterochronic parabiosis or aged plasma intravenous injections….  BECs [brain endothelial cells] upregulate expression of vascular adhesion molecules as a result of increased systemic inflammatory signaling resulting from multiple diseases that afflict the CNS. We discovered that BEC-specific VCAM1 increases in the hippocampus during normal aging. Exposure of young BECs to an aged systemic environment induces BEC activation and upregulation of VCAM1 both in vitro and in vivo. Specifically, systemic injections of aged human blood into young immunodeficient (NSG) mice- acutely over 4 days or spread over 3 weeks- increased BEC-specific VCAM1 expression, increased brain inflammation as assessed by microglial activation, and inhibited hippocampal neurogenesis. Blocking VCAM1 signaling systemically with a neutralizing monoclonal antibody rescued neurogenesis and prevented aged plasma induced microglial activation. This study suggests preventing BEC-immune cell crosstalk through VCAM1 may be a therapeutic target for ameliorating aged blood induced decline in brain function. 

To decipher: old blood injected into young mice → brain inflammation and ↑VCAM-1 production. Blocking VCAM-1 with an antibody abolished this effect, showing that VCAM-1 is the culprit, or one of them, in brain inflammation.

But, what is it about old blood that causes an increase in VCAM-1 expression?

It may very well be iron. The addition of iron chelators to endothelial cell cultures reduces, in a dose- and time-dependent manner, the production of VCAM-1.

These data suggest that iron plays a critical role in TNFα mediated VCAM-1 induction in HDMEC [human dermal microvascular endothelial cells], and the target for iron effects may be IRF-1, NF-kB, and potentially chromatin remodeling.

Iron could be one of the main factors in old blood that causes inflammation and damage.

NF-kappa B is another molecule that’s been suggested as a pro-aging factor in old blood; it’s a master regulator of factors that increase inflammation, which is a key characteristic of aging.

Iron chelators block the increase in NF-kappa B.

These results demonstrate that the iron chelator effectively blocks NF-kappa B activation and coordinate TNF-alpha and IL-6 gene upregulation by HM [hepatic macrophages] in cholestatic liver injury or under in vitro lipopolysaccharide stimulation. These findings support a pivotal role for iron in activation of NF-kappa B and cytokine gene expression by HM in vitro and in vivo.

Iron satisfies a few other requirements for evidence of being involved in aging:

  1. Iron increases in aging.
  2. Iron promotes oxidative stress, a key characteristic of aging.
  3. Iron is implicated in diseases of aging, including heart disease, cancer, and Alzheimer’s.
  4. Iron promotes infections, which increase in aging.
  5. Iron promotes mTOR activation, thought to be critical in aging.

Here we have an element, iron, which looks to me like a prime candidate in aging promotion. Why aging researchers generally don’t see this, I don’t know, but possibly iron just isn’t a sexy topic. Or, I could be wrong, but obviously I doubt it.

I’ll just leave you with one other item of interest.

Restored Vulnerability of Cultured Endothelial Cells to High Glucose by Iron Replenishment. When endothelial cells are serially cultured, they lose their sensitivity to damage by high glucose, which is normally toxic. It turns out that serial culturing causes them to lose their iron, to a level only 10% that of normal. When the cells were incubated with iron, they took it up, their iron levels were restored to normal, and high glucose once again became toxic to 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.