Standard Calorie Restricted Diet May Lead to Cancer and Death

Researchers at Colorado State University recently completed a review of the limited amount of science around yo-yo dieting (scientists call it weight cycling) and cancer risk. What’s interesting is that, although consistent caloric restriction has been shown to reduce cancer risk, it appears that yo-yo dieting might increase risk of certain cancers.[1]

Weight Cycling and Cancer: Weighing the Evidence of Intermittent Caloric Restriction and Cancer Risk.

Overweight and obese individuals frequently restrict caloric intake to lose weight. The resultant weight loss, however, typically is followed by an equal or greater weight gain, a phenomenon called weight cycling. Most attention to weight cycling has focused on identifying its detrimental effects, but preclinical experiments indicating that intermittent caloric restriction or fasting can reduce cancer risk have raised interest in potential benefits of weight cycling. Although hypothesized adverse effects of weight cycling on energy metabolism remain largely unsubstantiated, there also is a lack of epidemiological evidence that intentional weight loss followed by regain of weight affects chronic-disease risk. In the limited studies of weight cycling and cancer, no independent effect on post-menopausal breast cancer but a modest enhancement of risk for renal cell carcinoma, endometrial cancer, and non-Hodgkin’s lymphoma have been reported. An effect of either intermittent caloric restriction or fasting in protecting against cancer is not supported by the majority of rodent carcinogenesis experiments. Collectively, the data argue against weight cycling and indicate that the objective of energy balance-based approaches to reduce cancer risk should be to strive to prevent adult weight gain and maintain body weight within the normal range defined by body mass index.

Previous research has shown a relationship between yo-yo dieting and morbidity and mortality, although the underlying causes are not known. It’s also shown that the prevalence of yo-yo dieting is high.[2]

Of course, adherents to the calorie counting paradigm will, as they always do, blame dieters for their diet’s failure. They will claim that this is caused by a “lack of willpower,” but now they rely on flawed, Oprah-inspired pop psychology to explain it. “You’re too stressed,” “You had a miserable childhood,” “Your life sucks, boo hoo,” etc. They won’t consider the well-established causes of their unsustainable, grain-based diet’s failure. Instead, they’ll look far and wide for vague, untestable answers in order to abstain from a much needed critical look at their own flawed nutritional theory.

In another recent study of dieters 63% of study participants engaged in yo-yo dieting.[3] If most dieters fall prey to yo-yo dieting, can’t we conclude that a standard calorie restricted diet is more likely to wreck your health, give you cancer, or kill you, then help you? When will the medical establishment stop blaming its patients and wake up to this?

There is a better way.


1. Thompson HJ, McTiernan A. Weight Cycling and Cancer: Weighing the Evidence of Intermittent Caloric Restriction and Cancer Risk. Cancer Prev Res (Phila). 2011 Oct 7. [Epub ahead of print] PubMed PMID: 21982873.

2. Brownell KD, Rodin J. Medical, metabolic, and psychological effects of weight cycling. Arch Intern Med. 1994 Jun 27;154(12):1325-30. Review. PubMed PMID: 8002684.

3. Osborn RL, Forys KL, Psota TL, Sbrocco T. Yo-yo dieting in African American women: weight cycling and health. Ethn Dis. 2011 Summer;21(3):274-80. PubMed PMID: 21942158.

The Fitness Laffer Curve

In economics, The Laffer Curve is a visual representation of economist Art Laffer’s theory about the relationship between government tax rates and tax revenues. He thought that there is point at which increasing tax rates begin to negatively affect revenues due to removing the capital from the markets that would have otherwise been generating more taxable profits and incomes, as well as reducing the financial incentives for production. Tax rates that are low and rates that are very high both result in a sub-maximal return for the government. There is a rate somewhere in between that balances these effects, and produces a maximum tax revenue. His idea was famously illustrated this way.

Tangent: I find it curious that market liberals tend to use this idea to bolster their arguments while Keynesians have demonized Laffer. The goal of the Laffer Curve is to maximize government revenue at whatever cost to private markets. Seems to me to be a more of a tool for those seeking to raise taxes than to lower them, but I digress.

As I’ve written before, the same relationship exists between exercise fitness and human health, so I have modified the graph for our purposes. Let’s call it the Fitness Laffer Curve.

We know about the benefits of exercise fitness for human health and we also know that extreme endurance exercise can result in permanent heart damage and other negative outcomes. Somewhere in between is an optimal level of activity that results in the highest increase in health.

The Captivity of History

Most of us in the Paleo community have come to view civilization as separating us from the environment we were made for, but, in his opus, Coming home to the Pliestocene, Paul Shepard takes it a step further. He indicts history itself as a denativizing force. I’ve barely started reading the book, but it’s been fascinating so far.

A repeated question of our time is, “How do we become native to this place?” History cannot answer this question, for history itself is the great denativizing process, the great deracinator. Historical time is invested in change, novelty, and escape from the renewing stability and continuity of the great natural cycles that ground us to place and the greater community of life on earth. As Norman O. Brown writes: “Man, the disconnected animal, unconsciously seeking the life proper to his species, is man in history: repression and the repetition-compulsion generate historical time. Repression transforms the timeless instinctual compulsion to repeat into the forward-moving dialectic of neurosis which is history.”

Rice Alters Human Gene Expression

There’s been a lot of goodwill towards rice lately among the more open-minded bloggers in the Paleo community. Sure, it’s a Neolithic food, but there hasn’t been much of a case against occasionally consuming white rice for people with normal metabolic function. Removing the bran from rice (to create the white variety) removes the antinutrients too. So it may not be especially nutritious, but if you’re an athlete looking to retain or gain muscle mass, it’s a safe source of carbs.

Or so we thought.

A new study shows that very small pieces of rice RNA (microRNA) can enter the blood stream, then bind to recepters in the liver that normally work to reduce LDL cholesterol, resulting in an increase in plasma levels of LDL cholesterol.

Uh oh!

OK calm down. Before demonizing rice we’ll want to understand whether it affects small, dense LDL or large, boyant LDL, and we’ll need someone who understands biochemistry to interpret the study to get a clearer picture of it’s significance. Maybe the effect is small or counteracted by other properties of the food. Who knows? Not me, this is way above my pay grade. But it’s pretty interesting none the less that bits of rice RNA can enter the bloodstream and alter human gene expression.

The authors also suggest that microRNA may be considered as a new class of bioactive chemicals in food like vitamins, minerals, or phytosterols. Fascinating.

Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA.

Our previous studies have demonstrated that stable microRNAs (miRNAs) in mammalian serum and plasma are actively secreted from tissues and cells and can serve as a novel class of biomarkers for diseases, and act as signaling molecules in intercellular communication. Here, we report the surprising finding that exogenous plant miRNAs are present in the sera and tissues of various animals and that these exogenous plant miRNAs are primarily acquired orally, through food intake. MIR168a is abundant in rice and is one of the most highly enriched exogenous plant miRNAs in the sera of Chinese subjects. Functional studies in vitro and in vivo demonstrated that MIR168a could bind to the human/mouse low-density lipoprotein receptor adapter protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1 expression in liver, and consequently decrease LDL removal from mouse plasma. These findings demonstrate that exogenous plant miRNAs in food can regulate the expression of target genes in mammals.


1. Zhang L, Hou D, Chen X, Li D, Zhu L, Zhang Y, Li J, Bian Z, Liang X, Cai X, Yin Y, Wang C, Zhang T, Zhu D, Zhang D, Xu J, Chen Q, Ba Y, Liu J, Wang Q, Chen J, Wang J, Wang M, Zhang Q, Zhang J, Zen K, Zhang CY. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res. 2011 Sep 20. doi: 10.1038/cr.2011.158. [Epub ahead of print] PubMed PMID: 21931358.

Cycling Intensity is Important for Longevity, Not Duration

A new study from Denmark shows that cycling intensity has a strong relationship with life expectancy and cycling duration appears to have little, if any.[1]

Here’s study’s data on intensity and duration’s association with life expectancy:

And the data for each group showing the stronger association intensity has with reducing risk of death:

The high intensity cycling group had the lowest risk of all-cause mortality and an increase of 4-5 years of life expectancy compared to the low intensity group, and the difference was highest in risk of CHD related death.

The difference in all-cause mortality from increasing cycling duration was small or non-existant among all groups.

The authors were careful to state that, although intensity has a stronger relationship, we don’t really know what is the optimal duration, if it exists at all. But it appears that less than 30 minutes of cycling was enough to drop the high intensity group’s risk of death from coronary heart disease to less than a fifth of the low intensity group (the largest difference in the study). Interestingly, risk of death from CHD among the high intensity group crept upwards among those cycling more than an hour per day, but stil remained lower than the low and average intensity groups. The average intensity group saw a smaller difference of less than half the risk of death from CHD while also cycling less than 30 minutes a day when compared to the low intensity group.


I want to say “I told you so,” but let’s remember this is an observational study that isn’t powerful enough to show cause (however, it appears that they did do their best to adjust for differences between the groups). This does provides evidence that high intensity cycling longer than an hour per day may not be as dangerous as we thought, although not optimal. I doubt they were anywhere near the amount of training that professionals engage in though. Still, it certainly does add to the growing body of evidence that short, intense cycling is best way to train for health and longevity. Remember this study the next time you’re thinking about heading out for a fast 50!


1. Schnohr P, Marott JL, Jensen JS, Jensen GB. Intensity versus duration of cycling, impact on all-cause and coronary heart disease mortality: the Copenhagen City Heart Study. Eur J Cardiovasc Prev Rehabil. 2011 Feb 21. [Epub ahead of print] PubMed PMID: 21450618.

Today’s Hill Repeat Ride Report

I went out for a hill repeat workout today. There is a nice wide creek valley about five minutes from a park where I like to base my rides. I rode down into the valley, put the bike in the small crank and 2nd easiest gear then hit the hill. First time wasn’t too bad. I made it progressively more difficult by shifting into a more challenging gear on each of the next two climbs. It wasn’t as hard a workout as I expected, so I think I need to find a longer hill. This one appears to be about 50 feet in the steep section I used for the repeats.

I meant to snap a photo of the hill from the base. Next time. Here’s the ride’s elevation map:

I was out for about 25 minutes and did 412 ft. of climbing. My heart rate peaked at 92% of my max (I’d like to get that higher).

A workout like this is intentionally short and intense, but I don’t feel exhausted like I would have from a multi-hour ride, and it was fun! Don’t be scared of hill repeats. On a short ride like this it’s not nearly as hard as you might expect. Remember the benefits of this style of riding.

Postscript: I’m working on a followup to my previous post on longevity. Should be out later this week.

Life Expectancy of Endurance Athletes

A new study claims that Tour de France cyclists add an average 8 years to their life span through extreme endurance training, and that people engaged in such activity should have no fear that they could be doing damage to their health.[1] Hmm. Pretty big statements for an epidemiological study. Let’s dig in.

Here’s the abstract:

Increased Average Longevity among the “Tour de France” Cyclists.

It is widely held among the general population and even among health professionals that moderate exercise is a healthy practice but long term high intensity exercise is not. The specific amount of physical activity necessary for good health remains unclear. To date, longevity studies of elite athletes have been relatively sparse and the results are somewhat conflicting. The Tour de France is among the most gruelling sport events in the world, during which highly trained professional cyclists undertake high intensity exercise for a full 3 weeks. Consequently we set out to determine the longevity of the participants in the Tour de France, compared with that of the general population. We studied the longevity of 834 cyclists from France (n=465), Italy (n=196) and Belgium (n=173) who rode the Tour de France between the years 1930 and 1964. Dates of birth and death of the cyclists were obtained on December 31 (st) 2007. We calculated the percentage of survivors for each age and compared them with the values for the pooled general population of France, Italy and Belgium for the appropriate age cohorts. We found a very significant increase in average longevity (17%) of the cyclists when compared with the general population. The age at which 50% of the general population died was 73.5 vs. 81.5 years in Tour de France participants. Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners. Our findings underpin the importance of exercising without the fear that becoming exhausted might be bad for one’s health.

And here’s why it’s wrong:

The study compared professional cyclists to the general population, only controlling for country of origin and age. So the pro’s were compared to a group in which some members suffered from known causes of reduced life span like: genetic disease, poverty, smoking, obesity, sedentary lifestyles, and oh yeah, WORLD WAR II, without controlling for any of them.

Were the pro cyclists conscripted at the same rate as the general population? Given the popularity of competitive cycling in France, Belgium, and Italy, I would suspect that even if they were, these men were kept from the front lines. Their data did not include cause of death.

Did they come from similar socio-economic backgrounds? Today’s pro’s usually come from fairly well-off families rather the poor families. You can’t say the same thing about the general population, and poverty is known to reduce life span.[2]

I could go on, but you get the idea: The study was so poorly-controlled that its breathtakingly over-reaching conclusions are totally unsupported. Even if we assume their data is sound, they simply cannot conclude that pro cycling caused the increase in life span. Doing so is the cardinal sin of epidemiology. Correlation does not imply causation. It’s only a clue to look closer with more powerful studies that most often find no causal link, only a coincidence and one or more confounding variables.

They acknowledged some of these factors as limitations of their study (but not the deadliest war in human history). Yet, despite already published studies that clearly show heart damage in marathon runners they confidently concluded:

In our opinion, physicians, health professionals and general population should not hold the impression that strenuous exercise and/or high-level aerobic competitive sports have deleterious effects, are bad for one’s health, and shorten life.

I’d add that using poorly-controlled, observational data to recommend extreme endurance exercise–even beyond the point of exhaustion–is not only unsupported by the data, it’s irresponsible.

Other Longevity Studies

Several observational studies have looked at similar data and reached a wide range of conclusions. They have suggested several factors as possible causes of the increase in life span, including: the sports themselves, genetic selection of elite athletes, active and healthy lifestyles of athletes, lower rates of smoking, less alcohol consumption, lower body weight, lower overall blood pressure, and lower risk of ischemic heart disease caused by any of the previously listed factors.[3-7]

So which is it? Did the sports cause longer life span or was it another factor or combination of factors? Observational studies are simply incapable of determining this. They can only show association. That’s why a well done observational study concludes only that a correlation exists and modestly offers several possible causes, if any.

Evidence Against Endurance Sports

Endurance athletes, especially marathon runners, have been the subject of recent studies designed to observe the effects of endurance sports on the heart. Nearly all of them have shown acute damage, and some have shown long-term damage correlated to degree of participation in endurance sports.

Several studies have shown damage to the heart in lifelong endurance athletes, including myocardial fibrosis (thickening of the heart values) that can lead to heart failure.[8,9] An enlarged heart was once thought to be a temporary adaptation to endurance athletics, but at least one study has found the syndrome can persist decades after retirement from professional cycling.[10] Marathon running is now well-correlated with an increased risk of heart attack caused by atherosclerosis.[11] Even completing a single marathon can result in temporary heart damage.[12] The evidence is steadily mounting that too much endurance exercise pushes the heart too far beyond it’s evolved capability and leads to disease.[13]

Another thing to consider is the low bone mineral density most endurance athletes suffer from.[14-16] A frail skeleton in advancing age is a precursor to breaking bones from a fall, and that can lead to death among the elderly.[17]

There is an interesting line of research, still in early stages, that shows that glucose may speed up the aging process in worms and yeasts. In one study, lifespan was reduced by 20%. This metabolic pathway may have been conserved through evolution in humans. The diet of a typical endurance athlete is loaded with sugar in order to sustain enormous efforts hour after hour. It’s too early to say, but it’s possible that this diet has a negative effect on life span. An author of one of the studies was convinced enough to have removed all sugar and starch from her diet.[18,19]

Evolutionary Perspectives

The prevailing notion in the Paleo community is that humans rarely pushed their cardiovascular systems to the extremes that professional cycling and other endurance sports demand. Hunting was a matter of stalking prey (mostly walking quietly), then sprinting in for the kill. Since these extreme endurance events are evolutionarily novel, human genes are likely poorly adapted to them, making them detrimental to human health. This consistent with the new clinical evidence that lifelong marathon running and competitive cycling results in heart damage.[20]

On the the other hand, proponents of endurance running claim that persistence hunting observed in hunter gatherer populations and several anatomical features unique to humans suggest that we are well adapted to endurance exercise. Humans are the only mammals that sweat in the heat, are relatively hairless, and are bipedal. These factors allow us run more efficiently in hot weather than other species. Using these advantages, we can pursue prey over long distances during the hottest part of the day until it suffers from heat exhaustion and is killed. This idea is known as the Endurance Running Hypothesis, and is advocated by biologists Daniel E. Lieberman and Dennis M. Bramble.[21,22]

I think this point of view has some problems. It’s likely that hairlessness and sweating were adaptations to hot climates, but to claim they were adaptions to a specific behavior in such climates seems a bit overreaching. These traits gave the humans that had them an advantage in nearly every activity carried out in the heat, not just in persistence hunting. Also, running for miles in hot weather seems like a pretty inefficient way of hunting. The hunter(s) would have to expend an enormous amount of energy for each hunt, including those that were unsuccessful. Ambush hunting or scavenging would have been more calorically efficient, producing selection pressure against persistence hunting. Many anthropologists have challenged the Endurance Running Hypothesis, stating that archaeological and ethnographic data do not support it.[23] Still, one cannot ignore the fact that no species has nearly the same capacity for endurance running as humans and that some hunter gatherer groups traditionally practiced persistence hunting in Africa and North America.[24]

Below, David Attenborough narrates a modern day persistence hunt by the San, a hunter gatherer group in Southern Africa that carries the oldest existing human DNA.

An Evolutionarily Consistent Theory

On one hand we have some rather problematic observational studies that show higher life span among professional cyclists and endurance athletes. On the other hand, we have observational studies showing clear evidence of heart damage in lifelong marathon runners and professional cyclists. Evolutionary arguments seem to support the notion that extreme endurance exercise is novel to humans, but how can we explain the epidemiology? We can simply ignore them for being poorly-controlled studies, or we can suggest a confounding variable: genetics.

A study published March 2011 in PLos ONE suggests that genetics may be a factor in increased lifespans among endurance athletes.[25] Here’s the abstract. The complete paper is available at PLoS ONE and it’s worth reading in its entirety.

Are ‘Endurance’ Alleles ‘Survival’ Alleles? Insights from theACTN3 R577X Polymorphism

Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching ≥100 years of age). Owing to its effects on muscle structure/function, a potential candidate is the Arg(R)577Ter(X) polymorphism (rs1815739) in ACTN3, the structural gene encoding the skeletal muscle protein α-actinin-3. We compared the ACTN3 R577X genotype/allele frequencies between the following groups of ethnically-matched (Spanish) individuals: centenarians (cases, n = 64; 57 female; age range: 100-108 years), young healthy controls (n = 283, 67 females, 216 males; 21±2 years), and humans who are at the two end-points of exercise capacity phenotypes, i.e. muscle endurance (50 male professional road cyclists) and muscle power (63 male jumpers/sprinters). Although there were no differences in genotype/allele frequencies between centenarians (RR:28.8%; RX:47.5%; XX:23.7%), and controls (RR:31.8%; RX:49.8%; XX:18.4%) or endurance athletes (RR:28.0%; RX:46%; XX:26.0%), we observed a significantly higher frequency of the X allele (P = 0.019) and XX genotype (P = 0.011) in centenarians compared with power athletes (RR:47.6%; RX:36.5%;XX:15.9%). Notably, the frequency of the null XX (α-actinin-3 deficient) genotype in centenarians was the highest ever reported in non-athletic Caucasian populations. In conclusion, despite there were no significant differences with the younger, control population, overall the ACTN3 genotype of centenarians resembles that of world-class elite endurance athletes and differs from that of elite power athletes. Our preliminary data would suggest a certain ‘survival’ advantage brought about by α-actinin-3 deficiency and the ‘endurance’/oxidative muscle phenotype that is commonly associated with this condition.

In other words, elite endurance athletes may be endowed with genes that predispose them to incredible feats of endurance and also exceptionally high life span. Their genes are the primary factor in determining their life span. This unique genetic profile is also common in centenarians, so perhaps we should be wondering why endurance athletes rarely live past 80 years of life, and not decades longer. If that is the case, it would appear that endurance sports do in fact negatively impact life expectancy. This theory is consistent with the longevity studies, the evidence showing negative health outcomes, and the evolutionary perspective that humans may not be well-adapted to endurance exercise. A lot more study is needed before the theory is confirmed, but it does tie everything together nicely.


What should we do with all this conflicting data and theory? Observational studies show higher life span among endurance athletes, but it could be due to genetic or other factors, and new clinical studies show detrimental cardiovascular effects from endurance exercise. Still, we can’t wait for better studies or new insights to guide us, we live in the world now and must decide on a course of action now. I suggest we exercise a little epistemic modesty and admit that we can’t say for sure what the effect of extreme endurance sports are on human life expectancy. In this case, I think we should follow the examples we can observe in nature that hint at the evolutionary appropriateness of endurance exercise. While some hunter gatherers engage in persistence hunting, most do not, and evidence that it occurred in the past is has been contended.

The honest answer right now is that we don’t know how extreme endurance exercise affects life span, but there are not-yet-established scientific and evolutionary reasons to believe humans aren’t optimally adapted to it, and the observed increase in endurance athlete life span is due to genetic differences, not the effect of endurance exercise. Therefore, I think the best course of action is to avoid extreme endurance exercise, and if you do engage in it, limit it’s frequency to protect your heart. Also be aware that it may cause still unknown health problems due to its evolutionary discordance (a hint of unwelcome unknown unknowns).

Postscript on Cycling Folklore

You may have heard the claim that professional cyclists life spans are shortened on average by 15 years. Tim Moore made this claim in his book French Revolutions: Cycling the Tour de France.[26] (Read the excerpt on Google Books) I could not find his source for that claim, he did not respond to my tweet (his only contact method) asking for evidence, nor could I find a study that supports it, which leads me to believe that this claim might be a bit of cycling folklore. It’s been repeated in The New Statesman and other media outlets. He might counter that new doping methods and drugs caused a more recent decline in pro cyclist life span that would not appear in studies with subjects from previous generations. Maybe it’s true, but studies available at the time didn’t support it.


1. Sanchis-Gomar F, Olaso-Gonzalez G, Corella D, Gomez-Cabrera MC, Vina J. Increased Average Longevity among the “Tour de France” Cyclists. Int J Sports Med. 2011 Aug;32(8):644-7. Epub 2011 May 26. PubMed PMID: 21618162.

2. Fiscella K, Franks P. Individual income, income inequality, health, and mortality: what are the relationships? Health Serv Res. 2000 Apr;35(1 Pt 2):307-18. PubMed PMID: 10778817; PubMed Central PMCID: PMC1089103.

3. Teramoto M, Bungum TJ. Mortality and longevity of elite athletes. J Sci Med Sport. 2010 Jul;13(4):410-6. Epub 2009 Jul 1. Review. PubMed PMID: 19574095.

4. Karvonen MJ, Klemola H, Virkajärvi J, Kekkonen A. Longevity of endurance skiers. Med Sci Sports. 1974 Spring;6(1):49-51. PubMed PMID: 4826692.

5. Sarna S, Kaprio J, Kujala UM, Koskenvuo M. Health status of former elite athletes. The Finnish experience. Aging (Milano). 1997 Feb-Apr;9(1-2):35-41. PubMed PMID: 9177584.

6. Sarna S, Sahi T, Koskenvuo M, Kaprio J. Increased life expectancy of world class male athletes. Med Sci Sports Exerc. 1993 Feb;25(2):237-44. PubMed PMID: 8450727.

7. Kujala UM, Tikkanen HO, Sarna S, Pukkala E, Kaprio J, Koskenvuo M. Disease-specific mortality among elite athletes. JAMA. 2001 Jan 3;285(1):44-5. PubMed PMID: 11150106.

8. Wilson M, O’Hanlon R, Prasad S, Deighan A, Macmillan P, Oxborough D, Godfrey R, Smith G, Maceira A, Sharma S, George K, Whyte G. Diverse patterns of myocardial fibrosis in lifelong, veteran endurance athletes. J Appl Physiol. 2011 Jun;110(6):1622-6. Epub 2011 Feb 17. PubMed PMID: 21330616; PubMed Central PMCID: PMC3119133.

9. Breuckmann F, Möhlenkamp S, Nassenstein K, Lehmann N, Ladd S, Schmermund A, Sievers B, Schlosser T, Jöckel KH, Heusch G, Erbel R, Barkhausen J. Myocardial late gadolinium enhancement: prevalence, pattern, and prognostic relevance in marathon runners. Radiology. 2009 Apr;251(1):50-7. PubMed PMID: 19332846.

10. Luthi P, Zuber M, Ritter M, Oechslin EN, Jenni R, Seifert B, Baldesberger S, Attenhofer Jost CH. Echocardiographic findings in former professional cyclists after long-term deconditioning of more than 30 years. Eur J Echocardiogr. 2008 Mar;9(2):261-7. PubMed PMID: 17470417.

11. Möhlenkamp S, Lehmann N, Breuckmann F, Bröcker-Preuss M, Nassenstein K, Halle M, Budde T, Mann K, Barkhausen J, Heusch G, Jöckel KH, Erbel R; Marathon Study Investigators; Heinz Nixdorf Recall Study Investigators. Running: the risk of coronary events : Prevalence and prognostic relevance of coronary atherosclerosis in marathon runners. Eur Heart J. 2008 Aug;29(15):1903-10. Epub 2008 Apr 21. PubMed PMID: 18426850.

12. Neilan TG, Januzzi JL, Lee-Lewandrowski E, Ton-Nu TT, Yoerger DM, Jassal DS, Lewandrowski KB, Siegel AJ, Marshall JE, Douglas PS, Lawlor D, Picard MH, Wood MJ. Myocardial injury and ventricular dysfunction related to training levels among nonelite participants in the Boston marathon.Circulation. 2006 Nov 28;114(22):2325-33. Epub 2006 Nov 13. PubMed PMID: 17101848.

13. La Gerche A, Prior DL, Heidbüchel H. Strenuous endurance exercise: is more better for everyone? Our genes won’t tell us. Br J Sports Med. 2011 Mar;45(3):162-4. Epub 2010 Dec 27. PubMed PMID: 21187292.

14. Smathers AM, Bemben MG, Bemben DA. Bone density comparisons in male competitive road cyclists and untrained controls. Med Sci Sports Exerc. 2009 Feb;41(2):290-6. PubMed PMID: 19127198.

15. Medelli J, Lounana J, Menuet JJ, Shabani M, Cordero-MacIntyre Z. Is osteopenia a health risk in professional cyclists? J Clin Densitom. 2009 Jan-Mar;12(1):28-34. Epub 2008 Oct 1. PubMed PMID: 18835799.

16. Campion F, Nevill AM, Karlsson MK, Lounana J, Shabani M, Fardellone P, Medelli J. Bone status in professional cyclists. Int J Sports Med. 2010 Jul;31(7):511-5. Epub 2010 Apr 29. PubMed PMID: 20432201.

17. Topinková E. Aging, disability and frailty. Ann Nutr Metab. 2008;52 Suppl 1:6-11. Epub 2008 Mar 7. Review. PubMed PMID: 18382070.

18. Lee SJ, Murphy CT, Kenyon C. Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression. Cell Metab. 2009 Nov;10(5):379-91. PubMed PMID: 19883616; PubMed Central PMCID: PMC2887095.

19. Ruckenstuhl C, Carmona-Gutierrez D, Madeo F. The sweet taste of death: glucose triggers apoptosis during yeast chronological aging. Aging (Albany NY). 2010 Oct;2(10):643-9. Review. PubMed PMID: 21076182; PubMed Central PMCID: PMC2993794.

20. O’Keefe JH, Vogel R, Lavie CJ, Cordain L. Achieving hunter-gatherer fitness in the 21(st) century: back to the future. Am J Med. 2010 Dec;123(12):1082-6. Epub 2010 Sep 16. Review. PubMed PMID: 20843503.

21. Bramble DM, Lieberman DE. Endurance running and the evolution of Homo. Nature. 2004 Nov 18;432(7015):345-52. PubMed PMID: 15549097.

22. Liebenberg L. The relevance of persistence hunting to human evolution. J Hum Evol. 2008 Dec;55(6):1156-9. Epub 2008 Aug 29. PubMed PMID: 18760825.

23. Pickering TR, Bunn HT. The endurance running hypothesis and hunting and scavenging in savanna-woodlands. J Hum Evol. 2007 Oct;53(4):434-8. Epub 2007 Aug 27. PubMed PMID: 17720224.

24. Liebenberg L. Persistence Hunting by Modern Hunter-Gatherers. Current Anthropology. 2006; 47:6.

25. Fiuza-Luces C, Ruiz JR, Rodríguez-Romo G, Santiago C, Gómez-Gallego F, Yvert T, Cano-Nieto A, Garatachea N, Morán M, Lucia A. Are ‘endurance’ alleles ‘survival’ alleles? Insights from the ACTN3 R577X polymorphism. PLoS One. 2011 Mar 3;6(3):e17558. PubMed PMID: 21407828; PubMed Central PMCID: PMC3048287.

26. Moore T. French Revolutions, Cycling The Tour De France. Griffin, 2003. Web.