Gene-ial or Dan-Gene-rous? Better Make Sure You Are Made For Every Other Day Fasting, If You Don't Want to Ruin Your Glucose + Lipid Metabolism and Become Viscerally Obese

Yes! I freely admit that I do have a problem with the subliminal "binge and starve" of the popular every other day fast, because it paves the not so royal road to binge eating disorders.
Only 2 years ago, there was hardly anyone but the followers of Martin Berkhan's "Lean Gains" regimen who knew what intermittent fasting would be. Ironically, now that mainstream is catching on, the hype within the fitness community is slowly abating  - maybe part of the reason is that it's no longer "cool" enough now that your fat neighbor does it ;-).

It goes without saying that the mainstream version comes without an obligatory exercise component and - what's probably even worse - in the absence of macronutrient, let alone food prescriptions that would make sure that the every other day fasts that are becoming increasingly popular these days become "binge and starve" protocols.

The every other day fast, a gateway to eating disorders?

I could probably write a whole article about the potential of feast and fast strategies to function as a gateway to binge-eating disorders, but I know that most of you will discard that by stating: "Pah, that's happening only to the psychologically labile person who can't control his-/herself"... I will argue against that in another article, but I want to let you know here and now, that you could hardly be more off.
Did you know that eggs can improve the lipid profile of most of us?
Stay calm! In view of the fact that rodents in the wild-type control group, who had fully functional LDL receptors did not show a similar negative response to the well-meant dietary intervention, the results of the study at hand are hopefully irrelevant for most of you. If you do have friends and relatives with inexplicably high cholesterol levels, you would however be ill-advised to encourage them to battle their problems with every other day fasting.
Anyway... What this article is actually about is a paper from the British Journal of Nutrition. It was written by Dorighello et al. and has been published online ahead of print. The corresponding study was designed to test the hypothesis that alternate day fasting, which has previously been shown ... 
  • to decrease established metabolic risk factors of CVD and diabetes in human subjects and rodents (Varady. 2007),
  • to reduce the production of liver mitochondrial reactive oxygen in mice (Caro. 2008), and 
  • to increases the lifespan of rodents (Martin. 2006)
would ameliorate tissue mitochondrial oxidative stress and glucose intolerancr in LDL-receptor knockout mice. The LDL-receptor negative mouse is a common, or rather the scientific model of familial high cholesterol (these are the people who are put on a statin the very moment, they enter their doctor's office).

What the scientists expected and what they found were two pair of shoes

I guess you don't have to be a rocket scientists to see what the data in Figure 1 is telling us: In spite of a 20% reduction in energy intake (over the whole week), the rodents in the Dorighello study did not benefit from their every other day fasting regimen (EODF)
Figure 1: Changes in lipid and blood glucose levels (relative to control on ad libitum diet; left) and carcass composition in % of total weight (right; data based on Dorighello. 2013)
Accordingly, the Brazilian scientists who had expected that the fasting induced energy restriction, (-20%), alone, should ameliorate the metabolic disturbances in LDL-receptor knockout mice, and reduce their susceptibility to atherosclerosis, had to acknowledge that their clever every other day fasting regimen can have unexpected and, in the last consequence, eventually fatal effects on the heart health of the laboratory mice:
  • Epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68 %, respectively.
  • Pasma levels of leptin were 50 % higher in the EODF mice than in the ad libitum-fed mice.
  • EODF mice showed increased plasma levels of cholesterol -  total cholesterol (37 %), VLDL-cholesterol (195 %) and LDL-cholesterol (50 %). 
  • The glucose homeostasis of the "EODF mice" also disturbed. The scientists observed a +40 % increase in glycemia and a +50% increase in insulinaemia. In short, the mice became glucose intolerant and insulin resistant.
  • The significant increases in systemic inflammatory markers, TNF-a and C-reactive protein, only topped the list of negative side effects of the every other day fast off.
Overall this lead to a 3-fold increase in spontaneous atherosclerosis development, an effect of which it cannot be said often enough that it was observed exclusively in the LDL-receptor negative mice.
Practically speaking... In spite of the fact that the main take home message of the study at hand may be relevant only for those who harbor a certain genetic disposition, I do not recommend a zero calorie every other day fast to anyone - irrespective of whether he or she does or doesn't have LDL receptors  ;-)
If you are not aware of cases of familiar hyper-cholesteraemia and want to improve your lipid metabolism by fasting and eating clean, I suggest you re-read my previous article about the "Two Day High-Protein, Low-Carb Fast" and try this, or a classic intermittent fasting routine with a 6-8h feeding window to shed some body fat and get in better metabolic shape.
So what does this mean? The results of the study at hand are exemplary of something regular SuppVersity readers have encountered a dozen of times, already. A fact that vindicates the often-heard, but rarely understood notion that "we are all different". As the study at  hand clearly shows, our gene's and their consequences on our physiology determine not just what we should eat, but also when we shoult eat it. 

You got to be wary, though! Contrary to what you may read in some shiny magazines and on banners on the Internet, the often advertized "gene type diet" is not even on the horizon, yet.

Yes, we can (theoretically) identify each and every gene in our bodies, but in contrast to a general LDL receptor dysfunction, many of the more subtle genetic differences are as of yet totally unknown. Any list of foods, or, as this study shows, suggest food frequency rules you may get are up to know about as accurate as the names of the man or woman of your dreams you will get if you follow the friendly advice the music television advertisement gives you and "send an SMS with the keyword 'love' and your name" to a random number. Even for the well-studied APO-E polymorphisms, scientists are time and again surprised to find that their results are not in line with data from previous studies. Contemporary accepted implications, such as "people whose apolipoproteins belong to the APO-E4 class will do more harm than good if they consume larg(er) amounts of fish oil" could thus be as flawed as the idea that only fat can make you fat - likewise the result of premature conclusions that seemed logical in view of the contemporarily available, highly insufficient data, by the way.

References:
  • Caro P, Gómez J, López-Torres M, Sánchez I, Naudi A, Portero-Otín M, Pamplona R, Barja G. Effect of every other day feeding on mitochondrial free radical production and oxidative stress in mouse liver. Rejuvenation Res. 2008 Jun;11(3):621-9.
  • Martin B, Mattson MP, Maudsley S. Caloric restriction and intermittent fasting: two potential diets for successful brain aging. Ageing Res Rev. 2006 Aug;5(3):332-53.
  • Varady KA, Hellerstein MK. Alternate-day fasting and chronic disease prevention: a review of human and animal trials. Am J Clin Nutr. 2007 Jul;86(1):7-13. Review.
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