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.

Two Days A Week High Protein, Low Carb Fast Cuts >10% of Body Fat in 4 Months And Improves Insulin and Leptin Sensitivity More Than Chronic -25% Energy Restriction

I wonder if she just found out that sheddin 10% body fat can be as easy as doing two "protein modified fasts" per week!?

It has been some time since the last interesting study on Intermittent Fasting has found its way into the SuppVersity news; and I have to admit that the protocol of the study I am about to discuss today does not really qualify as "intermittent fasting" in the "lean gains" sense.

Still, the latest study from the University Hospital of South Manchester NHS Foundation Trust comes with a couple of very interesting results... the only downside is that the subjects were "the usual" ones, namely obese sick people:  115 women with a family history of breast cancer (aged 20 and 69 years). This is problematic, because the same fast during which the obese person draws on his or her fat stores to "survive" can sent the lean sub 10% body fat athlete into a catabolic low energy state and have his blood sugar drop to hypoglycemic levels, when he or she returns to eating ad libitum after the 2 fasting days.

Will intermittent fasting shrink your bust?

Sorry, I just could not resist to use focus on this question of paramount importance. Why? Well the study at hand is the first to actually investigate the negative effects of fasting on your cup size ;-) All jokes aside, this is obviously not a non-sense or cosmetic measure.

As I already mentioned in the introduction, the subjects had a history of breast cancer and in view of the association between breast cancer risk and bra cup size in US women aged <42 (Swanson. 1996) -

• 26% increased risk for cup size B
• 23% increased risk for cup size C
• 95% increased risk for cup size D*

- it does appear to make at least some sense to measure the effect the diet had on bust size, as well (* note: the data was calculated for normal weight women).

Figure 1: Change in body composition in response to dietary energy restriction (-25%; DER) and 2-day per week fasting with calorie (IFC) and carbohydrate (IFCA) restriction on the two fasting days (Harvie. 2013)

So, if you are concerned about losing fat in the wrong places (don't that it may decrease your breast cancer risk to shed superfluous fat on your chest, ladies) the data in figure 1 will probably comfort you. It does after all confirm that the additional loss of abdominal fat (as evidenced by the reduction in waist circumference) is more pronounced than the additional 1-2% reduction in bust size the women in the two intermittent fasting groups, IFC and IFCA experienced.

Details on the protocol:  Diet composition

Side effects? What is interesting and something I have not seen before in a study is an evaluation of differences in side effects and nutrient sufficiency:

• feeling cold (3% DER)
• decreased energy (5% IFC & DER)
• constipation (8% IFC, 3% DER)
• headaches (5% IFC, 3% IFCA)
• bad breath (5% IFC, 3% IFCA)
• light-headed (3% IFC)
• lack of concentration (3% DER)
• mood swings (3% IFC & DER)
• thinking about food 24/7 (8% IFC, 3% IFCA & DER)

Interestingly the different pre-occupation with food did not impact the hunger scores. The only thing the scientists observed was a minimal difference in hunger scores on fasting day 1 in the IFC vs. IFCA group.

Of the usual low-carb diet deficiencies in Mg, Fe, Zn, Ca, vitamins A and D and fibre, the multi compensated everything but the scarcity of magnesium (Mg), zinc (Zn) and selenium (Se) in the IFC group.

The dietary energy restriction (DER) and the intermittent fasting carbohydrate restricted (IFC) groups were isocaloric and contained only 75% of the calculated energy requirements of the women. Contrary to the women in the DER group who consumed a diet with a macronutrient ratio of 25/45/30% protein / carb / fat, the subjects in the IFC group were however

"asked to restrict energy and carbohydrate on two consecutive days each week (70 % energy restriction and 40 g carbohydrate) and to consume a euenergetic Mediterranean-type diet that met their estimated energy requirements for the remaining 5 d of the week."

The restricted IFC diet the subjects consumed on those "fasting days" provided between 625kcal/day and 680kcal/day and included approximately

• 250 g of protein foods including lean meat, fish, eggs, tofu, textured vegetable protein, 
• three servings of low-fat dairy foods (e.g. 195 ml semi skimmed milk, 150 g low-fat yoghurt, 30 g low-fat cheese), 
• four portions of low-carbohydrate vegetables and 
• one portion of low-carbohydrate fruit, 
• at least 1170 ml of other low-energy fluids, and 
• an over-the-counter multivitamin and mineral supplement providing the RDA for vitamins and typically 20 – 50 % for minerals on restricted days.

Lastly, the subjects in the IFCA protocol followed the exact same rulez, but were allowed to consume "unlimited lean meat, fish, eggs, tofu, MUFA and PUFA on restricted days." In addition, the saturated fat content of both intermittent diets was limited to 10% and alcohol consumption was discouraged, but not prohibited.

Addendum: In view of the fact that the question arose several times both here in the comments and on facebook, I want to point out that the 250g of protein foods are not identical to 250g of protein. They will rather contribute max. 50-90g of protein and will thus not go beyond the dietary constraints of 625kcal. Apropos, other than one commenter suspected the weekly caloric deficit was indeed identical in the DER and the IFC group. Let's to the math with simplified figures: Baseline intake 2,000kcal - 25% => 7x400kcal = 2,800kcal deficit in the DER group vs. 2x (2000kcal-600kcal) = 2,800kcal on the two consecutive low carb fasting days in the IFC group.

"And what about the 'health effects'?"

It we take a look at the serum markers, it's actually quite surprising that there were no significant improvements in HbA1c, blood glucose, IL-6, TNF-alpha, adiponectin, cholesterol and triglycerides. After all, this is what we almost expect with any type of fat loss.

Figure 2: Changes in blood glucose and insulin resistance, as well as leptin levels after 3 month on the respective diets and another month on "weight maintenance" when 68% of the ICF & ICFA subjects stuck to their protocol (Harvie. 2013)

The comparatively high fat loss in the IFC and ICFA groups (-12% and -11% over the three months of dieting) did yet result in significant improvement in insulin sensitivity and had a much more pronounced effect on the leptin levels, which is - in the case of overweight individuals - a good thing, as it signifies a reduction in "leptin resistance".

Altough they were allowed to, the IFCA subjects (middle bar) did not eat much more protein and fat than their peers in the IFC group.

Bottom line: Overall the results of the study at hand leave no doubt that a carbohydrate restricted 5:2 day (5 days you eat normal, 2 days you fast) high protein fasting strategy is a very effective means to shed body fat and increase your insulin sensitivity - for the overweight individual (!).

In that, it's worth mentioning that you do not even have to force yourself to abstain from foods altogether on the two fasting days: It's actually sufficient to cut the carbs by 43 % (which was the effective reduction in the IFC & IFCA groups compared with 23 % for the DER group) as long as you are not into fatty foods and don't compensate for that by overconsuming protein and fats... yep, you heard me right, there is NO MAGIC in low carb dieting that would allow you to eat as much protein and fat as you want and still lose weight. The subjects in the IFCA who were allowed to do so added no more than 10g of extra protein and 15g of fat to your ~600kcal allowance on the fasting days.

Now, I am not sure how realistic it is that everyone will do the same as the subjects in the IFCA group and refrain from overeating on eggs, sausages of even Quest protein bars and all the other delicious(ly convenient) ready made "low carb foods" that are flooding the market these days. If you are a trainer or nutritionist, I would thus suggest you don't tell them they allowed to eat "as much as they want as long as it contains no carbs" ;-)

References: 

• Harvie M, Wright C, Pegington M, McMullan D, Mitchell E, Martin B, Cutler RG, Evans G, Whiteside S, Maudsley S, Camandola S, Wang R, Carlson OD, Egan JM, Mattson MP, Howell A. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br J Nutr. 2013 Apr 16:1-14. [Epub ahead of print]
• Swanson CA, Coates RJ, Schoenberg JB, Malone KE, Gammon MD, Stanford JL, Shorr IJ, Potischman NA, Brinton LA. Body size and breast cancer risk among women under age 45 years. Am J Epidemiol. 1996 Apr 1;143(7):698-706.