Differential Effect of Alternate-Day Fasting Versus Daily Calorie Restriction on Insulin Resistance

ByCrossFitSeptember 23, 2019

The standard treatment for obesity is moderate, chronic calorie restriction. Recent research has suggested more severe, time-restricted dietary changes — for example, intermittent or alternate-day fasting — may cause greater metabolic improvements alongside similar weight loss. This study compared alternate-day fasting (ADF) to continuous calorie restriction (CR) in insulin-resistant subjects.

The trial had a two-phase design. For the first six months, subjects consumed 25% fewer calories than they expended to induce weight loss. For the next six months, they consumed the same number of calories they expended to maintain weight.

Fifty-three overweight or obese, insulin-resistant subjects were randomized to one of three dietary patterns. The ADF group alternated between “fast” days and “feast” days; during the weight-loss period, they were instructed to consume 25% and 125% of energy expenditure, respectively, and during the weight-maintenance period, 50% and 150%. The CR group consumed the same number of calories on all days — 75% and 100% in the weight-loss and weight-maintenance phases, respectively. Thus, total prescribed calories were the same between the two groups.

Study staff prepared and provided all meals for the first three months of the study. Subjects received nutritional counseling for the remaining time.

As shown in Figure 2 below, both groups lost similar amounts of weight: 8-10% over the first six months, with some regain over the remaining six months. The diets also led to similar changes in BMI and fat mass.

These diets differed dramatically, however, in their impact on fasting insulin levels and HOMA-IR (a measure of insulin resistance). ADF induced a 44% reduction in fasting insulin and a 48% reduction in HOMA-IR over six months, both of which decreased further by 12 months. Conversely, CR led to only small changes in fasting insulin and HOMA-IR over six months, and these reductions effectively disappeared by 12 months. Neither diet led to significant changes in lipid or inflammatory markers.

The changes associated with ADF were seen despite poor compliance with the diet. During the weight-loss phase, ADF subjects were instructed to consume 399 calories per day but actually consumed 1,049 on average; during the weight-maintenance phase, they actually consumed 1,175 on a prescription of 799. This suggests compliance with ADF may be challenging, an observation reinforced by the fact that six out of 17 ADF subjects dropped out before completing the 12-month diet. It also indicates, however, that less severe caloric restriction — down to only 50% of energy expenditure — is sufficient to drive significant metabolic improvements.

This small study demonstrates that periodic, severe caloric restriction induces greater metabolic improvements than continuous, moderate caloric restriction, despite causing similar weight loss. In other words, it indicates fasting has unique metabolic benefits. Future research could contribute to a more precise understanding of the benefits of fasting by answering some of the following questions:

  • What is the impact of ADF when properly followed? How can adherence to ADF be improved?
  • How does ADF compare to time-restricted feeding, intermittent fasting, periodic multiday fasting, and similar regimens?
  • How does fasting affect markers of liver health and fatty liver disease?
  • How does fasting affect subjects who are already diabetic? How do these effects compare to those caused by a ketogenic diet or carbohydrate restriction?
  • Do more severe fasts lead to improvements in lipid and inflammatory markers?

Addressing these and other questions will help develop an understanding of how fasting can be best applied toward specific outcomes. The current data alone suggests fasting deserves serious consideration as an alternative to conventional weight-loss prescriptions.

Comments on Differential Effect of Alternate-Day Fasting Versus Daily Calorie Restriction on Insulin Resistance


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Guy Savage
September 24th, 2019 at 8:45 am
Commented on: Differential Effect of Alternate-Day Fasting Versus Daily Calorie Restriction on Insulin Resistance

Its ironic that with all the data they don't appear to boil down what they actually fed the trial participants. If you look at the conflicts of interest Krista A. Varady was paid out author fees for her The Every Other Day Diet book content and involvement. On the face of it the study is a clinical trial to promote her book hypothesis.

I've not read her book, but from the abstracts it describes that in her proposition, you can continue to eat everything you "love" just calorically restricted and every other day. If that is the case, it doesn't address the fundamental issue of bad nutrition, and the myriad of problems caused by quality food that humans have no business eating. Essentially that approach continues to normalise the problem; the Standard American Diet or Standard Western Diet.

Dr's Jason Fung and Dr Ben Bikman, Ivor Cummings, Professor Seyfried (and dozens of others) on the other hand deal with this, don't restrict calories (except Seyfried for Cancer treatment) and gets people off grains, carbs and seed oils and into a ketogenic macro. When you eat enough animal based protein and fat and keep carbs below 50-30g a day, the body becomes fat adapted and provides feedback which regulates appetite. Add a 6-8 hour compressed eating window and it becomes even easier (16/8 or 18/6). This up-regulates Mitochondrial Uncoupling Protein (MUP) so fat cells liberate stored lipid energy to generate heat just for the sake of it.

Fasting (24-72 hours), prolonged cold exposure and high intensity load bearing exercise like CrossFit, all supercharge MUP production (along with human growth hormone), and stimulate cells to make more mitochondria to burn more lipids, to make more ATP. The same process also protects against lean mass loss as long as you remain over 5-7% body fat.

However caloric restriction and a nutrient profile that develops an insulin spike does the opposite.

While this study is interesting, it withholds its true potential because of bias. To "prove" a hypothesis, that was developed in a book to counteract the effects of a bad diet, without actually fixing the bad diet, is bad science.

In practice ADF is a whole lot easier and way more productive, when you accept that you must first fix what you are putting into your body; so when you are at your target weight, you stay there.

Personally, I always train at least 12-18 hours fasted and having done everything from paleo to strict ketogenics, I have now settled on a zero carb carnivore diet at around 35% calories from protein and 65% fat. My blood work is epic, my bone density is in the 95th percentile for age as is muscle mass. I also successfully train during fast days and even through an annual 2 week fast.

CF L1 Trainer

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Dmitry Andryukhin
September 24th, 2019 at 7:53 am
Commented on: Differential Effect of Alternate-Day Fasting Versus Daily Calorie Restriction on Insulin Resistance

This an amazing post. thx for bringing this up here I have finally some data to talk sense into my parents to start fast.

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