Category Archives: Exercise

Peter Lakatos: Tips for Better Movement

The Hungarian edition of Perfect Health Diet is on sale! Jaffa Kiadó is the publisher, it can be purchased here, and this is the cover:

Hungarian cover

Peter Lakatos gets most of the credit for making the Hungarian edition happen. In addition to being a PHD fan, Peter is a StrongFirst Girya Master Instructor with Pavel Tsatsouline, Expert 2 Krav Maga instructor with Eyal Yanilov, blue belt Brazilian jiu jitsu practicioner with Carlson Gracie Jr., and a creator of Primal Move. Peter was born and lives in Budapest, Hungary.

Here are Peter’s tips for better movement.

Move More, but for the Right Reasons

Most training systems tell you to move more to become slimmer. And when you stop being slim, they ask you to move more. This advice is misdirected. Movement should not be thought of as a tool for creating a caloric deficit. Rather, movement should be regarded as a means to better health. Movement can make you slimmer, but only as a side effect of making you healthier.

If you move only to lose weight, and rely on movement for weight loss, you are in trouble. As David Whitley would say: you can’t out-train a doughnut.

The goal of movement should be better health and a more capable body. Movement reshapes your brain and makes you mentally, emotionally, and physically ready for almost any challenge.

We designed Primal Move to help people achieve this positive reshaping of brain and body. Here is a video which introduces Primal Move:

We noticed early on while creating Primal Move that we can easily get our students to move more or more intensely: all we had to do was add games. Games and play are seriously underrated in physical education. Today, we often see kids suffering from play deprivation. Yes, you read that correctly; I am not talking about sleep deprivation, but play deprivation.

Stuart M. Brown, whom we consider to be the world’s number one expert on play, studied several serial killers and found a shocking common pattern in their lives – they all had been deprived of play. According to Dr Brown, play deprivation can cause many cognitive disorders, and lack of play implies a lack of social skills. That does not mean that those who don’t play will become serial killers. But maybe they won’t become Mother Theresa either!

Improve Your Movement Quality

Moving better is where all things start. Now, better is of course hard to measure, but simply said – when things are getting easier you just learned how to make a certain movement more efficient. Moving better means moving with better coordination, better control, less mental, emotional and sometimes physical tension. Moving better means we have full access to the human body, and give us a great foundation for the next step, becaming stronger.

We created a full division in Primal Move focused on moving better, called the Fundamentals. Our Fundamentals division is based on the Functional Movement System of Gray Cook and Lee Burton, and we truly recommend visiting their website, Want to be super clever on human movements? Read Gray’s book, The Movement.

In Primal Move Fundamentals, we start and finish with a short but very valuable evaluation called the Primal Flow Evaluation. Yes, we want to know how well you move before we try to make you stronger or more fit.

We really believe the movement hierarchy should be based on the quality of movement. Establishing quality of movement first prepares you to load the movements with weight, repetition or speed. But don’t think you have to move like a ballet dancer. Just move well enough, so that additional strength will not distort your structure.

Now better movement gives a great feeling. Moving better and more fluidly builds your confidence. Can you remember a time when movement was painful – when you moved to play or even simply to take a book off the shelf, and knew before you did it that, “This is going to hurt,” and so you flinched and slowed your movement down. Maybe even just thinking about the movement made you stressed.

Moving better not only means you move well, but also that you learn movements faster because your movement literacy – the term was coined by Istvan Balyi, the famous Hungarian-Canadian sport expert – is wide enough that you will excel and enjoy almost any movement or game you attempt to practice.

Think about this – who is the last kid to get picked for football? Always the one who does not move well, does not kick well, the one who has problems on many levels with tha game. If you don’t get picked, you don’t practice. If you don’t practice, you don’t get better. If you don’t get better, you stop moving. If you stop moving, you get slower. Giving up on movement and play can lead to poor health and a greater likelihood of obesity and other health problems. Yes, there is a risk of a downward spiral with lifelong consequences.

Gaining Strength

Increasing strength is always a high payoff strategy. Being stronger makes everything easier. Yes, I know, we are so clever and original.

To get stronger you have many choices. Are you a minimalist? Keep to bodyweight exercises, play with leverage, and read Pavel Tsatsouline’s book, The Naked Warrior. Bodyweight movements made difficult with leverage are how gymnasts develop extremely strong and attractive bodies.

If you prefer to pick up heavy objects – and many claim this is the meaning of life – we recommend that you still consider minimalist solutions. Kettlebells and sandbags, plus a pull up bar, are a perfect set of equipment for building strength. Want to learn more about these? Visit and

Thanks Peter! For those who would like videos, here is a group doing Primal Move Fundamentals:

One thing I like about Primal Move is that they have developed movement exercises for those who are not physically able to perform the Fundamentals. This practice is called Primal Move Regeneration:

And for runners, here is Primal Move Velocity:

Physical Activity: Whence Its Healthfulness?

In our last post, Exercise: Is Less Better Than More?, I quoted four studies showing that light aerobic exercise, of the intensity of jogging at 10 or 11 minutes per mile, improved health up to a volume of about 30 minutes per day, but then the health benefits plateau. Light aerobic exercise seems to become unhealthy as the volume exceeds 50 minutes per day.

Today I’ll continue looking at low-level activity to try to clarify where the health benefits come from, so that we can better design a health-maximizing exercise program.

Sitting versus Standing

There seem to be negative health effects from even short periods – a few hours – of inactivity: sitting or lying down.

A recent systematic review, first-authored by TJ Saunders of Obesity Panacea, found that a single day of bed rest is sufficient to raise triglycerides, and that 2 hours of sitting increases insulin resistance and impairs glucose tolerance – moving the body closer to a diabetic phenotype. [1]

Research by Marc Hamilton found that sitting shuts down expression of lipoprotein lipase (LPL) in skeletal muscle, preventing muscle cells from importing fat. [2] A Science Daily article shows an interesting video based on this research. Here are blood samples after consumption of an identical meal eaten the same person; the left sample was taken after a meal eaten sitting down, the right sample after a meal eaten standing:

When sitting, dietary fats are taken up only by adipose tissue. When standing, they are taken up by muscle and adipose tissue both.

Time spent standing did more to push fat into muscle cells than vigorous daily exercise. This is significant because pushing nutrients into muscle cells promotes muscle growth. If you have trouble gaining muscle, maybe the problem is too much sitting, and what you need is not more intense workouts, but more frequent standing!

Sleep Is Good

Not all inactivity is bad, however. Sleep is highly beneficial.

Consequences of poor quality or insufficient sleep include:

  • Higher rates of cancer. [3]
  • Impaired immunity and vulnerability to infection. [4]
  • Higher rates of heart disease. [5]
  • Higher all-cause mortality. [6]
  • Faster cognitive decline with age. [7]
  • Shortening of telomeres. [8]
  • Higher rates of diabetes. [9]

One way to interpret this: Inactivity during the day is unequivocally bad, but inactivity at night may be a good thing.

This may be an indication that the benefits of activity come not through fitness, but through entrainment of circadian rhythms. To enhance circadian rhythms, we want daytime activity but night-time rest.

Activity at Work

If activity and exercise at work are good, it might seem a good thing to have an active job. Why not get paid for getting your exercise?

However, the data is not so clear. In comparisons of sedentary work with active work, usually the sedentary workers come out pretty well. For example:

  • In women, no relationship was found between occupational physical activity and heart disease risk. [10]
  • In the HUNT 2 study, people with metabolic syndrome were more likely to die of cardiovascular disease if their work included physical activity than if it was sedentary. [11]
  • In the Copenhagen City Heart Study, high occupational physical activity was associated with higher all-cause mortality. [12]

It seems that when it comes to routine physical activity, more is not better. Exercise is a stressor, and it’s easy to get too much. Being active for eight hours a day is too much.

How Much Activity is Optimal?

If we can easily get too much low-level activity, then what is the optimal amount?

I suggested in my last post that we don’t have an innate “activity reward” system in the brain because our hunter-gatherer ancestors got more exercise than they needed. If that’s true, then we can look to hunter-gatherers to see what constitutes enough activity.

So how much activity did hunter-gatherers get?

It’s been estimated that hunter-gatherers typically walk 5 miles a day, run 1 mile a day, and do various resistance-style carrying and lifting activities. For instance, anthropologist Kim Hill states:

The Ache hunted every day of the year if it didn’t rain. Recent GPS data I collected with them suggests that about 10 km (kilometers) per day is probably closer to their average distance covered during search. They might cover another 1-2 km per day in very rapid pursuit. Sometimes pursuits can be extremely strenuous and last more than an hour. Ache hunters often take an easy day after any particularly difficult day, and rainfall forces them to take a day or two a week with only an hour or two of exercise. Basically they do moderate days most of the time, and sometimes really hard days usually followed by a very easy day. The difficulty of the terrain is really what killed me (ducking under low branches and vines about once every 20 seconds all day long, and climbing over fallen trees, moving through tangled thorns etc.)

The Hiwi on the other hand only hunted about 2-3 days a week and often told me they wouldn’t go out on a particular day because they were “tired”. They would stay home and work on tools etc. Their travel was not as strenuous as among the Ache (they often canoed to the hunt site), and their pursuits were usually shorter. When I hunted with Machiguenga, Yora, Yanomamo Indians in the 1980s, my days were much, much easier than with the Ache. And virtually all these groups take an easy day after a particularly difficult one. [13]

So the Ache walked about 6 miles per day, ran about 1 mile; other groups did less, but all of them traversed more difficult terrain than modern walkers and runners. So it seems that 5 miles of walking and 1 mile of running per day on easy terrain might be a reasonable estimate for the optimal daily activity level.

Five miles is about 10,000 steps. A review of the evidence suggested that 7,000 to 11,000 steps per day achieves all the health benefits of walking. [14]

In a comment, Jason gave us a link to a Runner’s World article that contained figures from a recent paper [15]. These illustrate the plateauing of health benefits at a relatively low level of activity:

Above about 30 MET-hours per week of activity, corresponding to 2 hours per week (20 minutes per day) of running at 7 minutes per mile or 4 hours per week (40 minutes per day) of jogging at 10 minutes per mile, there are no health benefits to additional activity.

In other words, the benefits of exercise run out after running 3 miles or jogging 4 miles per day – not far from the hunter-gatherer activity level.

The shape of this curve is supportive of the idea that circadian rhythm enhancement, not fitness, is the cause of the health benefits of exercise. Levels of activity beyond running 20 minutes per day do increase fitness – every cross country or track team in the country trains at a higher level than this – but do not improve health; so health does not depend on fitness. It looks like we need a certain amount of activity to properly entrain our circadian rhythms – to tell our bodies that it is daytime, the time of activity – but once we’ve achieved that, we don’t need to do more.

Centenarians Don’t Over-Exercise

Dan Buettner, author of The Blue Zones: Lessons for Living Longer From the People Who’ve Lived the Longest, has said, “None of the longest-lived societies we studied exercise as we think of it.”

And, based on my readings of centenarian obituaries, it seems true that the longest-lived often don’t do a lot of exercise. A reader who has commented as “B.C.” emailed me a link to a New York Times story on Julia Koo, a centenarian who recently celebrated her 107th birthday in good health. Her secret to a long life: “No exercise, eat as much butter as you like and never look backwards.” [16]


It looks like if we want optimal health, at least four factors should influence our daily activity:

–          When it comes to vigorous activites like running, jogging, or lifting, we should do neither too much nor too little. A half hour of such activity per day may be optimal for health, an hour or more may do us more harm than good. Thus, occupations that require physical activity throughout the day may be health impairing.

–          Several hours per day of walking is probably beneficial.

–          The rest of the day should be restful, but not completely inactive. We should not go more than 20 minutes without standing.

–          There are reasons to believe that the benefits of activity may derive more from circadian rhythm entrainment than from fitness. If this is true, then it may be important to develop a routine that includes some activity every day, than it is to optimize fitness by a well designed high-intensity interval training and on-day/off-day protocol.

It really didn’t occur to me until we worked on the new edition of the book that circadian rhythms might be the reason for the health benefits of exercise. (We have more evidence in the book for this idea, including the observations that exercise in the day improves sleep quality at night, and that circadian rhythm disruption has similar health effects to sedentary living.) Since working through this research, I’ve become much more committed to doing something every day – but much less concerned about whether that activity is well designed to make me fit.


[1] Saunders TJ et al. Acute sedentary behaviour and markers of cardiometabolic risk: a systematic review of intervention studies. J Nutr Metab. 2012; 2012:712435.

[2] Hamilton MT et al. Role of low energy expenditure and sitting in obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Diabetes. 2007 Nov;56(11):2655-67.

[3] Nieto FJ et al. Sleep-disordered breathing and cancer mortality: results from the Wisconsin Sleep Cohort Study. Am J Respir Crit Care Med. 2012 Jul 15;186(2):190-4.

[4] Bollinger T et al. Sleep, immunity, and circadian clocks: a mechanistic model. Gerontology. 2010;56(6):574-80.

[5] Hoevenaar-Blom MP et al. Sleep duration and sleep quality in relation to 12-year cardiovascular disease incidence: the MORGEN study. Sleep. 2011 Nov 1;34(11):1487-92.

[6] Cappuccio FP et al. Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. Sleep. 2010 May;33(5):585-92.

[7] Altena E et al. Do sleep complaints contribute to age-related cognitive decline? Prog Brain Res. 2010;185:181-205.

[8] Barceló A et al. Telomere shortening in sleep apnea syndrome. Respir Med. 2010 Aug;104(8):1225-9.

[9] Botros N et al. Obstructive sleep apnea as a risk factor for type 2 diabetes. Am J Med. 2009 Dec;122(12):1122-7.

[10] Mozumdar A et al. Occupational physical activity and risk of coronary heart disease among active and non-active working-women of North Dakota: a Go Red North Dakota Study. Anthropol Anz. 2012;69(2):201-19.

[11] Moe B et al. Occupational physical activity, metabolic syndrome and risk of death from all causes and cardiovascular disease in the HUNT 2 cohort study. Occup Environ Med. 2012 Sep 28. [Epub ahead of print]

[12] Holtermann A et al. Occupational and leisure time physical activity: risk of all-cause mortality and myocardial infarction in the Copenhagen City Heart Study. A prospective cohort study. BMJ Open. 2012 Feb 13;2(1):e000556.

[13] O’Keefe JH et al. Exercise like a hunter-gatherer: a prescription for organic physical fitness. Prog Cardiovasc Dis. 2011 May-Jun;53(6):471-9.

[14] Tudor-Locke C et al. How many steps/day are enough? For older adults and special populations. Int J Behav Nutr Phys Act. 2011 Jul 28;8:80.

[15] Chomistek AK et al. Vigorous-intensity leisure-time physical activity and risk of major chronic disease in men. Med Sci Sports Exerc. 2012 Oct;44(10):1898-905.

[16] James Barron, “Lessons of 107 Birthdays: Don’t Exercise, Avoid Medicine and Never Look Back,” The New York Times, September 24, 2012,

Exercise: Is Less Better Than More?

NOTE: Shou-Ching and I will be traveling in Europe next week; she’ll be speaking at this meeting and we’ll take a few days vacation. Blogging will resume on October 2 or so.

A New York Times column, “For Weight Loss, Less Exercise May Be More,” got some attention this week. It was based on a recent study of the effects of exercise on weight loss.

The Danish study [1] found that exercise is helpful for weight loss – but only the first 30 minutes of light exercise per day. Additional exercise had no effect on body weight – in fact it even seemed to diminish weight loss. Those who jogged for 60 minutes a day lost five pounds, those who jogged for 30 minutes lost seven.

The subjects wore activity tracking devices – Actigraph GT1-M devices, which are an older model of these and similar to a Fitbit – which produced a surprising result. Those who exercised 30 minutes a day were seemingly energized by their exercise, as they became more active in their daily lives – more likely to take the stairs, for instance. Those who exercised 60 minutes a day, on the other hand, seemed to be worn down by their exercise, and became less active in daily life.

It seems that 30 minutes of exercise improved health but 60 minutes of exercise may have diminished well-being. When it comes to exercise, perhaps, less is more.

A Well-Supported Result

While the Danish study [1] was novel in looking at how weight loss and non-exercise activity respond to exercise, it is not the first study to show that light activity may be healthier than intense activity.

In the new Scribner edition of our book, we greatly expand the part which discusses how to optimize immunity and heal or prevent disease. The new edition discusses exercise. We found a number of recent studies showing that light daily activity is as good or better than intense activity for health:

  • A study of American runners found that those who ran between 1 and 20 miles per week at a jogger’s pace of 10 or 11 minutes per mile reduced their risk of dying as much as those who ran more than 20 miles a week or who ran faster. [2]
  • Another Danish study reported that Danes who exercised two or three times per week for a total of one to two and a half hours reduced mortality by 44% and extended their lifespans by 6.2 years for men and 5.6 years for women. Those who exercised either more or less had less benefit. [3]
  • A study of 416,175 Taiwanese adults found that an hour and a half of moderate exercise per week (13 minutes per day) reduced mortality by 14% and extended lifespan by 3 years. An additional 15 minutes per day reduced mortality by only another 4%. Benefits peaked at 50 minutes of exercise per day. [4]

These are intriguing results. What’s more intriguing is that it doesn’t seem to matter how fit the exerciser is. People gain substantial health benefits from light exercise, even if the activity never makes them fit.

An Evolutionary Argument for Not Over-Exercising

Thanks to Stephan Guyenet, we’ve been talking a lot about the reward system of the human brain. It evolved in order to make us want to do healthy things, like braving the stings of angry bees to get honey from hives concealed high in trees.

David recently linked to an interesting post suggesting that our Paleolithic ancestors may have done a lot of honey gathering, which reminds me of this movie about the Hadza and their honey seeking:

Why did we develop an attractive taste for sugar, and why does the brain reward us for carb consumption? Presumably because the Paleolithic diet was too low in carbs for optimal health, and evolution wanted to encourage Paleolithic hunter-gatherers to gather more honey.

But, however valuable carbs are, it’s not clear that they are as valuable as the extra six years of life we obtain from light daily exercise. Yet there’s no innate reward for exercise. Many people are quite content to live their whole lives as couch potatoes.

Why didn’t evolution reward exercise, if it is as valuable as carbs? Probably because Paleolithic humans almost invariably got more exercise than they needed. Perhaps our brain evolved to prevent our ancestors from over-exercising, and now our brain unfortunately rewards us for over-resting!


It looks like exercise is healthful, but most or all of the benefits come from a relatively small amount – the first 30 minutes per day.

Doing the research for the new edition of our book has led me to revise my ideas of why exercise is beneficial, and how we should exercise to optimize health. In my next post, I’ll discuss why I think light exercise is most healthful, the tension between healthfulness and fitness, what I think a health-oriented exercise program should look like, and how my personal exercise activity has changed.


[1] Rosenkilde M et al. Body fat loss and compensatory mechanisms in response to different doses of aerobic exercise–a randomized controlled trial in overweight sedentary males. Am J Physiol Regul Integr Comp Physiol. 2012 Sep;303(6):R571-9.

[2] Gretchen Reynolds, “Moderation as the Sweet Spot for Exercise,” New York Times, June 6, 2012,

[3] European Society of Cardiology (ESC) (2012, May 3). Regular jogging shows dramatic increase in life expectancy. ScienceDaily.

[4] Wen CP et al.  Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet. 2011 Oct 1;378(9798):1244-53.

Can Endurance Exercise Promote Cancer?

I got into a bit of trouble in the comments a few weeks back when I joked that Grete Waitz may have died from marathoning. Steve replied:

Paul, you said “… marathoning (from which Grete Waitz just died at 57)”

Gee. The news said cancer. How confident are you that she died “from” running marathons?

Of course, not confident at all. Maybe if she’d been a sprinter she would have died at 54. Maybe if Lance Armstrong had been a couch potato he would still have had testicular cancer metastasized to his brain and lung at age 25.

A few days ago I got an email. Two highly fit endurance athletes, both of whom have always tended to their health and been careful to eat “healthy” (i.e. vegetable and whole grain rich, meat and fat poor) diets, have contracted cancers in the prime of life and been given less than a year to live. My correspondent asked, “Why?”

Let’s look into this. Is it possible that endurance exercise, especially if combined with a high-carb diet, may promote cancer?

Oxidative Damage to DNA and Cancer

Human DNA is constantly being damaged and repaired. It’s been estimated that over the course of a cell cycle – that is, from the time a cell is formed to the time it divides into two daughter cells – a human cell develops 5,000 single-stranded DNA breaks due to oxidative damage from reactive oxygen species (ROS). The vast majority are repaired by the body’s DNA repair machinery. [1]

However, in typical human cells 0.1% or 5 are not successfully repaired; instead a corresponding break is created in the complementary DNA strand, resulting in a double-strand break. In people with Bloom syndrome, an inherited condition which creates a strong predisposition to cancer, fully 1% or 50 are not successfully repaired. [1]

The double-strand break leads to a re-arrangement or “translocation” of parts of the chromosome. Usually, this does not break the coding region for a protein, but it does break non-coding regions resulting in changes to gene expression.

These sorts of genetic changes are observed both in cancer and in aging. [1] In short, oxidative damage to DNA is considered a risk factor for cancer development.

Oxidative Damage to DNA Has Been Specifically Linked to Endurance Exercise

Diets and activities that increase oxidative stress – for instance, diets deficient in antioxidant minerals – can therefore increase cancer risk. And diets and activities that minimize oxidative stress can minimize cancer risk and facilitate recovery.

Endurance exercise generates oxidative stress. Marathon running “caused a large increase in the tissue content of oxidized glutathione (189%) at the expense of reduced glutathione (-18%).” [2]

Moreover, endurance exercise damages DNA:

Both a systemic inflammatory response as well as DNA damage has been observed following exhaustive endurance exercise….

Extremely demanding endurance exercise has been shown to induce both a systemic inflammatory response [15, 42, 53, 71] as well as DNA damage [21, 36, 58, 62, 80]….

Exercise-induced DNA damage in peripheral blood cells appear to be mainly a consequence of an increased production of reactive oxygen and nitrogen species (RONS) during and after vigorous aerobic exercise [58]. Besides oxidative stress, other factors such as metabolic, hormonal and thermal stress in addition to the ultra-structural damage of muscle tissue are characteristic responses to prolonged strenuous exercise, that can lead to the release of cytokines, acute phase proteins and to the activation or inhibition of certain lines of the cellular immune system [15, 29]. [3]

There seems to be a big difference between moderate exercise and exercise to exhaustion. Moderate exercise actually protects DNA by upregulating DNA repair:

Sato et al. showed that acute mild exercise as well as chronic moderate training does not result in DNA damage, but rather leads to an elevation in the sanitization system of DNA damage [66]. [3]

However, endurance exercise leads to increased DNA damage:

Increased levels of DNA strand breaks were observed after exhaustive treadmill running in subjects of different training status [22, 45]….

In conclusion, there is growing evidence that strenuous exercise can lead to DNA damage that with few exceptions [36] is predominantly observed not before 24 h after the resolution of exercise [21, 44, 45, 80]. [3]

In addition, strenuous endurance exercise induces hormonal and other changes which might promote cancer. An Ironman triathlon has significant effects on hormones and inflammatory markers, some of which persist for more than 19 days post-race:

Briefly, as described in details elsewhere [42], there were significant (P<0.001) increases in total leukocyte counts, MPO, PMN elastase, cortisol, CK activity, myoglobin, IL-6, IL-10 and hs-CRP, whereas testosterone significantly (P<0.001) decreased compared to pre-race. Except for cortisol, which decreased below pre-race values (P<0.001), these alterations persisted 1 d post-race (P<0.001, P<0.01 for IL-10). Five days post-race CK activity, myoglobin, IL-6 and hs-CRP had decreased, but were still significantly (P<0.001) elevated. Nineteen days post-race most parameters had returned to pre-race values, with the exception of MPO and PMN elastase, which had both significantly (P<0.001) decreased below pre-race concentrations, and myoglobin and hs-CRP, which were slightly, but significantly higher than pre-race [42]. [3]

In the opinion of the authors of this review, the biggest problem is production of reactive oxygen and nitrogen species (RONS) by damaged immune cells:

The most conclusive picture that emerges from the available data is that oxidative stress seems to be the main link between exercise-induced inflammation and DNA damage…. DNA damage in peripheral immuno-competent cells, indeed, most likely resulted from an increased generation of RONS due to initial systemic inflammatory responses or the delayed inflammatory processes in response to muscle damage (Fig. 1). [3]

What About High-Carb Diets?

Do high-carb diets contribute?

During strenuous exercise mitochondria produce oxidation products:

The mitochondrial electron transport system can trigger the formation of superoxide leading to increased production of H2O2 by superoxide dismutase [49], [50]. [4]

In a normal person at rest, about 1-2% of the oxygen utilized by mitochondria ends up in superoxide. [4]

Before we go further let’s take a brief detour into mitochondrial chemistry: specifically, something called the electron transport chain.

Here’s a stylized view:

Source: Wikipedia.

The main point for our purposes is that there are two points of entry into the chain, one that goes through complex I and one that bypasses it.

Glucose metabolism favors entry via complex I, while fatty acid metabolism is relatively more favorable to entry via complex II. Quantitatively, glucose metabolism produces 5 NADH molecules (entering at complex I) for every one succinate molecule (entering at complex II), while fatty acid metabolism produces only 2 NADH for every one succinate.

High-carb dieting tends to habituate the body to metabolism of glucose. Therefore, it increases utilization of complex I.

This is significant because complex I is vulnerable to production of excess oxidative stress under some circumstances.

In principle, every mitochondrial complex has the potential to operate cleanly with minimal production of superoxide. However, if mitochondrial function is in any way impaired, so that operation of a complex is inhibited, then ROS production can rise substantially.

If for some reason electrons cannot flow properly through the electron transport chain, then they leave as superoxide:

One factor which may sensitise cells to increased DNA damage is impaired mitochondrial function [74]…. Reduced electron flow through the mitochondrial respiratory chain, particularly through the inhibition of complex I or complex III, favours the enhanced production of superoxide and H2O2 [75]. Together, with the age-dependent increase in oxidative stress and decline in NAD+ and ATP content, we found a tendency to the reduction in the activity of the respiratory complexes with age in all organs. Sipos et al. (2003) showed that mitochondrial formation of H2O2 due to complex I inhibition is more clinically relevant than ROS production due to inhibition of complex III and IV in situ [76]. [4]

What exactly did Sipos et al. find?  They state:

ROS formation was not detected until complex III was inhibited by up to 71 +/- 4%, above that threshold inhibition, decrease in aconitase activity indicated an enhanced ROS generation. Similarly, threshold inhibition of complex IV caused an accelerated ROS production. By contrast, inactivation of complex I to a small extent (16 +/- 2%) resulted in a significant increase in ROS formation, and no clear threshold inhibition could be determined. [5]

Basically, superoxide can be generated in complexes I, III, and IV. However, in complexes III and IV, there is a high threshold of inhibition of electron transport before any superoxide is produced. In complex I, there is no threshold:  even very slight inhibition will generate ROS. This means that during practical living, the great majority of excess ROS is produced from complex I.

This means that high-carb dieting, which increases utilization of complex I, will tend to generate oxidative stress if there is any inhibition of complex I.

But in endurance exercise, there is inhibition of complex I. To name just one pathway, exercise increases levels of the hormone DHEA, and DHEA inhibits complex I. [6]

It looks like high-carb diets and endurance exercise may be a bad combination.

Are Whole Grains Especially Bad?

There may be specific problems with grain toxins. For instance, wheat germ agglutinin, a wheat toxin that is very effective at distributing itself through the body through transcytosis, is able to damage mitochondria:

WGA induced a loss of transmembrane potential, disruption of the inner mitochondria membrane, and release of cytochrome c and caspase-9 activation after 30 min of cell interaction. [7]

At high doses in test tubes this can lead to cell death. It’s conceivable that at physiological levels WGA damage to mitochondria might mildly inhibit complex I and increase oxidative stress.

Of course, any deficiency in antioxidant minerals zinc and copper, which dismutate superoxide to hydrogen peroxide which is then disposed of by glutathione peroxidase (a selenium containing enzyme), would increase oxidative stress. Wheat contains phytic acid which chelates minerals and reliance on wheat as a calorie source may impair antioxidant status.


I don’t want to exaggerate the risks of endurance sports. With the exception of melanoma [8], there isn’t a clear increase in cancer incidence among marathon runners. And if this post seemed a bit tortuous, it’s because there’s no simple “smoking gun” pathway connecting endurance exercise to cancer.

On the other hand, endurance exercise is probably not as healthy, in terms of cancer risk, as shorter-duration activities. Also, the risk may rise substantially on high-carb or wheat-based diets. There are at least a few plausible mechanisms, not all of which I’ve discussed here, that might connect endurance exercise on grain-based high-carb low-fat diets to cancer.


[1] Vilenchik MM, Knudson AG. Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12871-6.

[2] Cooper MB et al. The effect of marathon running on carnitine metabolism and on some aspects of muscle mitochondrial activities and antioxidant mechanisms. J Sports Sci. 1986 Autumn;4(2):79-87.

[3] Neubauer O et al. Exercise-induced DNA damage: is there a relationship with inflammatory responses? Exerc Immunol Rev. 2008;14:51-72.

[4] Braidy N et al. Age related changes in NAD+ metabolism oxidative stress and sirt1 activity in wistar rats. PLoS One. 2011 Apr 26;6(4):e19194.

[5] Sipos I et al. Quantitative relationship between inhibition of respiratory complexes and formation of reactive oxygen species in isolated nerve terminals. J Neurochem. 2003 Jan;84(1):112-8.

[6] Safiulina D et al. Dehydroepiandrosterone inhibits complex I of the mitochondrial respiratory chain and is neurotoxic in vitro and in vivo at high concentrations. Toxicol Sci. 2006 Oct;93(2):348-56.

[7] Gastman B et al. A novel apoptotic pathway as defined by lectin cellular initiation. Biochem Biophys Res Commun. 2004 Mar 26;316(1):263-71.

[8] Ambros-Rudolph CM et al. Malignant melanoma in marathon runners. Arch Dermatol. 2006 Nov;142(11):1471-4.