Human Genomics Didn’t Fail, The Paradigm Did

At the turn of the century one of the most exciting areas of medical research was the Human Genome Project, a massive scientific undertaking that successfully mapped the entire human genome in 2003. The hope was that by conducting large association studies, researchers could identify the genes that cause various diseases such as cancer, diabetes, heart disease, etc. Once the troublesome gene was identified, pharmacalogical interventions could be developed to reduce or stop the expression of the disease gene, which would end or reverse the progression of the disease.

Unfortunately, very little came from these association studies. Only a few genes were linked to specific diseases, and these proved to only create a predisposition to the disease, not a definite trigger. So far genes can only explain about 5-10% of cancer risk, 10% for type 2 diabetes,[1] and 5% for parkinson’s disease. The “failure” of these studies has lead to the widespread opinion that the study of human genomics has been fruitless.

I see things differently. The fact that these studies found few associations shows that the causes of these diseases are more than likely environmental, not biologically predetermined. That is, certain lifestyles are the most likely underlying causes. We don’t need to worry about “fixing” a “broken” biology. Human beings are not broken by default. I am more and more convinced that the strongest factors in determining disease risk are an industrial, Neolithic diet and a sedentary lifestyle. We only need to leave behind our bad habits.

We don’t need new “miracle” drugs to come along and save us from ourselves. We need to give up the modern, culturally-reinforced behaviors that underly diseases of civilization. That’s something we can do now, on our own, without the need of decades-long research projects and billion dollar, blockbuster drugs.

References

1. Herder C, Roden M. Genetics of type 2 diabetes: pathophysiologic and clinical relevance. Eur J Clin Invest. 2011 Jun;41(6):679-92. doi: 10.1111/j.1365-2362.2010.02454.x. Epub 2010 Dec 30. Review. PubMed PMID: 21198561.

Why We’re Sick in One Picture

Want to see everything that is wrong with conventional diet and exercise regimens and the causes of ever-increasing chronic disease in one photo? Here it is. (Hat tip: Reddit)

It goes like this:

Eat a processed, high carbohydrate, grain-based diet that makes you fat and hungry,[1] and results in chronic disease.[2] Try to remedy the situation by doing “cardio” exercise like jogging which over-stresses your heart[3] and saturates your body with the stress hormone cortisol. Finally, double down on this failed strategy by blaming meat for your declining health and adopt an extremely high carbohydrate, unnatural[4] Vegan diet that requires endless pill-popping and results in malnutrition and heart disease.[5,6]

Thumbs up!

Why do we do this to ourselves? There are much better paths to optimal health.

References

1. Ludwig DS, Majzoub JA, Al-Zahrani A, Dallal GE, Blanco I, Roberts SB. High glycemic index foods, overeating, and obesity. Pediatrics. 1999 Mar;103(3):E26. PubMed PMID: 10049982.

2. Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O’Keefe JH, Brand-Miller J. Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr. 2005 Feb;81(2):341-54. Review. PubMed PMID: 15699220.

3. 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.

4. Milton K. The critical role played by animal source foods in human (Homo) evolution. J Nutr. 2003 Nov;133(11 Suppl 2):3886S-3892S. Review. PubMed PMID: 14672286.

5. Shinwell ED, Gorodischer R. Totally vegetarian diets and infant nutrition. Pediatrics. 1982 Oct;70(4):582-6. PubMed PMID: 6812012.

6. Ingenbleek Y, McCully KS. Vegetarianism produces subclinical malnutrition, hyperhomocysteinemia and atherogenesis. Nutrition. 2011 Aug 26. [Epub ahead of print] PubMed PMID: 21872435.

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.

References

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.

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.

Thoughts

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!

References

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.

Why Do You Ride? Health and Longevity or Maximum Cycling Fitness

My main problem with cycling is the major emphasis on cycling fitness rather than health and longevity. Let’s face it, the large majority of cyclists aren’t competitive professionals. Nor do we want to be. We ride for fun and to improve and maintain our health. But the emphasis on improving speed, distance, power output, and other measures of fitness create this disconnect. These things are important to winning races. They are not especially important to improving health and living a long time. In fact, they may actually be working against it.

Do you care about your VO2 max or lactic threshold? Me either. What I do care about is reducing my likelihood of suffering from the diseases of civilization (cancer, heart disease, diabetes, i.e. diseases that were extremely rare in our pre-agricultural past), keeping body fat low while retaining muscle mass, and having fun. Will endless, Puritanical struggling to improving your cycling fitness help achieve these goals? I doubt it, but before we get to that, let’s talk about the Paleo lifestyle.

Paleo is a lifestyle that improves health and compresses the morbidity of the end of life through approximating the environment in which human genes evolved. This is accomplished through modifying diet and exercise to better match the diet and exercise of our ancient ancestors from the Paleolithic Period, where the overwhelming majority of human evolution occurred. Present your genes with the environment (including the food and exercise) they expect, and they will reward you with optimal health. Think of a wild animal in captivity in a zoo. It will get sick, get fat, get depressed, fail to reproduce or it’s off-spring won’t survive infancy, but all of the effects of captivity are reversed when it’s returned to the wild. We are animals and modern life is the “zoo” deterring us from the environment to which we are adapted. We can approximate a return to the wild to achieve optimal health, leaving behind modern food and physical stresses to which human genes are poorly adapted. That’s Paleo in a nutshell.

Does cycling fit into this perspective? Like most questions, the answer is “it depends,” but assuming we’re considering the type of cycling that cycling culture encourages, the answer is definitely “no.”

The end result of training for cycling fitness instead of health.

I’m talking about cycling long distances, at consistently high heart rates, while consuming a steady stream of high-sugar drinks and foods. There is nothing in our ancestral past that would suggest that our genes are adapted to exercising this way. This type of exercise goes by the pejorative “chronic cardio” within the Paleo community, and for good reason.

Beyond the evolutionary argument, there is emerging science that suggests that lifelong endurance cycling is bad for your heart,[1,2] your bones,[3-5] your muscles,[6] and potentially increases your risk of cancer.[7] Abusing sugary “sports drinks” and foods might lead to metabolic derangement (then diabetes), and there are some scientific clues that sugar consumption might be one of the causes of aging.[8,9] Beyond that, a fragile skeleton and low muscle mass are well-established harbingers of an early grave.[10-12]

Is that worth shaving 30 seconds off your 40k time trial time? It is for some, and to each his own. The point I want to make is that the perception that endurance athletes are a model for optimal human health is flat wrong. Just ask this one. Some love cycling enough to make this sacrifice. Some are competitive professionals who’ve dedicated their lives to it. For them, this trade-off in health is OK. But most of us don’t want to go down that road. We want to maximize health and longevity, and we want to include cycling to do it. To do this we must recognize that cycling fitness and health are not always directly related.

That’s why I created this blog. To explore evolutionarily-informed cycling and health, and to challenge the dominant fitness-maximizing paradigm in cycling that, I believe, comes at the expense of health.

References

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. Knechtle B, Baumann B, Wirth A, Knechtle P, Rosemann T. Male ironman triathletes lose skeletal muscle mass. Asia Pac J Clin Nutr. 2010;19(1):91-7. PubMed PMID: 20199992.

7. Reichhold S, Neubauer O, Bulmer AC, Knasmüller S, Wagner KH. Endurance exercise and DNA stability: is there a link to duration and intensity? Mutat Res. 2009 Jul-Aug;682(1):28-38. Epub 2009 Feb 20. Review. PubMed PMID: 19699460.

8. 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.

9. 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.

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

11. Sirola J, Kröger H. Similarities in acquired factors related to postmenopausal osteoporosis and sarcopenia. J Osteoporos. 2011;2011:536735. Epub 2011 Aug 28. PubMed PMID: 21904688.

12. Ensrud KE, Ewing SK, Taylor BC, Fink HA, Stone KL, Cauley JA, Tracy JK, Hochberg MC, Rodondi N, Cawthon PM; for the Study of Osteoporotic Fractures Research Group. Frailty and risk of falls, fracture, and mortality in older women: the study of osteoporotic fractures. J Gerontol A Biol Sci Med Sci. 2007 Jul;62(7):744-51. PubMed PMID: 17634322.