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The Nutrition Examination Research Digest (NERD) aims to provide rigorous, unbiased analysis of the latest and most important nutrition and supplementation studies. Click here to subscribe or login if already a subscriber .

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Quoth the insulin hypothesis, “Nevermore”

We previously covered the first highly-controlled trial on ketogenic diets and weight loss, and this is the much-anticipated and longer follow-up trial. Does the ketogenic diet truly provide a weight loss advantage?

Study under review: Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men

Introduction

Adversarial collaboration is when researchers who hold conflicting opinions gather to conduct experiments that will help to resolve or reduce their differences. The present study was a product of this process. The Nutrition Science Initiative (NuSI), co-founded by Gary Taubes (champion of the carbohydrate-insulin hypothesis of obesity), assembled a team of experts to run a clinical trial designed to answer the question: Will very-low-carbohydrate ketogenic diets lead to greater energy expenditure, and thus fat loss, when compared to a high carbohydrate diet?

Ketogenic diets usually take the form of severely restricted carbohydrate intakes, usually down to around 5% of total calories. Taubes has hypothesized that whenever someone goes on a diet, they “will remove the most fattening carbohydrates from the diet and some portion of total carbohydrates as well. And if we lose fat, this will almost assuredly be the reason why” (Why We Get Fat, p. 144-47). Prior research conducted by Dr. Kevin Hall, lead researcher of the study under review, has not supported this hypothesis. When investigating mechanisms of fat loss, Dr. Hall’s pilot study showed that a reduction in carbohydrate was not necessary for fat loss nor was any metabolic advantage (i.e. increased metabolism) for fat loss seen when insulin secretion was reduced by 22% while on a low-carb diet. That trial (covered in our blog post and in NERD #11, Volume 2) had some limitations, though, such as its short 6-day duration. The present study aims to expand on this research, by conducting a two-month trial that compares a high-carbohydrate to a ketogenic diet.

As there are different versions of the carbohydrate-insulin hypothesis of obesity, it’s important to clarify which one is being tested. The hypothesis being examined here proposes the following: carbohydrate in the diet elevates insulin secretion, which suppresses the release of stored body fat and drives circulating fat to be stored. A decrease of circulating fatty acids leaves less total energy available for use by organs like the heart, liver, and muscles, which can lead to a decline in energy expenditure and promote hormonal signaling, resulting in increased food intake[1]. Thus, it is posited that the development of obesity is a consequence of carbohydrate-induced insulin production driving fat into storage, preventing it from being oxidized for energy.

It would then stand to reason that reducing the amount of carbohydrate consumed, while keeping variables such as total calories and protein intakes constant, should result in a drop of insulin secretion, causing a cascade reaction that would allow for increased energy expenditure and increased fat loss. The competing calories in, calories out (CICO) hypothesis maintains that exchanging carbohydrate for fat will not notably affect body fat levels nor energy expenditure. This study was designed to test which of these hypotheses might be true.

A team of researchers, recruited by the Nutrition Science Initiative (NuSI), conducted a study to test the carbohydrate-insulin hypothesis of obesity. This hypothesis states that the development of obesity is brought about through elevated insulin, caused by too much carbohydrate in the diet, driving fat into storage and preventing it from being oxidized for energy.

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