Yale Researchers Find Keto Diet Can Be Healthful or Harmful, Depending on the Timing

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According to a study by Yale researchers, while a ketogenic diet may provide health benefits in the short term, it can lead to negative effects in mice after approximately a week.

A ketogenic diet — which provides 99% of calories from fat and only 1% from carbohydrates — produces health benefits in the short term, but negative effects after about a week, Yale researchers found in a study of mice.

The results offer early indications that the keto diet could, over limited time periods, improve human health by lowering diabetes risk and inflammation. They also represent an important first step toward possible clinical trials in humans.

The keto diet has become increasingly popular as celebrities, including Gwyneth Paltrow, Lebron James, and Kim Kardashian, have touted it as a weight-loss regimen.

In the Yale study, published in the January 20, 2020, issue of Nature Metabolism, researchers found that the positive and negative effects of the diet both relate to immune cells called gamma delta T-cells, tissue-protective cells that lower diabetes risk and inflammation.

A keto diet tricks the body into burning fat, said lead author Vishwa Deep Dixit of the Yale School of Medicine. When the body’s glucose level is reduced due to the diet’s low carbohydrate content, the body acts as if it is in a starvation state — although it is not — and begins burning fats instead of carbohydrates. This process in turn yields chemicals called ketone bodies as an alternative source of fuel. When the body burns ketone bodies, tissue-protective gamma delta T-cells expand throughout the body.

This reduces diabetes risk and inflammation, and improves the body’s metabolism, said Dixit, the Waldemar Von Zedtwitz Professor of Comparative Medicine and of Immunobiology. After a week on the keto diet, he said, mice show a reduction in blood sugar levels and inflammation.

But when the body is in this “starving-not-starving” mode, fat storage is also happening simultaneously with fat breakdown, the researchers found. When mice continue to eat the high-fat, low-carb diet beyond one week, Dixit said, they consume more fat than they can burn, and develop diabetes and obesity.

“They lose the protective gamma delta T-cells in the fat,” he said.

Long-term clinical studies in humans are still necessary to validate the anecdotal claims of keto’s health benefits.

“Before such a diet can be prescribed, a large clinical trial in controlled conditions is necessary to understand the mechanism behind metabolic and immunological benefits or any potential harm to individuals who are overweight and pre-diabetic,” Dixit said.

There are good reasons to pursue further study: According to the Centers for Disease Control, approximately 84 million American adults — or more than one out of three — have prediabetes (increased blood sugar levels), putting them at higher risk of developing type 2 diabetes, heart disease, and stroke. More than 90% of people with this condition don’t know they have it.

“Obesity and type 2 diabetes are lifestyle diseases,” Dixit said. “Diet allows people a way to be in control.”

With the latest findings, researchers now better understand the mechanisms at work in bodies sustained on the keto diet, and why the diet may bring health benefits over limited time periods.

“Our findings highlight the interplay between metabolism and the immune system, and how it coordinates maintenance of healthy tissue function,” said Emily Goldberg, the postdoctoral fellow in comparative medicine who discovered that the keto diet expands gamma-delta T cells in mice.

If the ideal length of the diet for health benefits in humans is a subject for later studies, Dixit said, discovering that keto is better in small doses is good news, he said: “Who wants to be on a diet forever?”

Reference: “Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue” by Emily L. Goldberg, Irina Shchukina, Jennifer L. Asher, Sviatoslav Sidorov, Maxim N. Artyomov and Vishwa Deep Dixit, 20 January 2020, Nature Metabolism.
DOI: 10.1038/s42255-019-0160-6

The research was funded in part by grants from the National Institutes of Health.

8 Comments on "Yale Researchers Find Keto Diet Can Be Healthful or Harmful, Depending on the Timing"

  1. What drivel! No ketogenic diet has 99% of calories from fat and 1% from carbs. Zero calories from protein?

    • The actual published paper (as opposed to this SciTech briefing) states that the diet used was
      5% carbohydrate
      15% protein
      80% fat

  2. Well thats interesting, i’ve been on a keto lifestyle for over two years now, and I get complete bloodwork tests every three months. According to my results everything is perfect, that is for a 21 yr old ( so says my Doc ) and I’m almost 70. It would be good if these “experts” who do research would actually get what the breakdown of the keto diet consists of, and not their incorrect assumptions. ( That fact alone shows that nobody could seriously take their work and research as correct ).
    To make statements that the Keto diet and lifestyle is somewhat limiting is almost laughable, although if you are used to such “healthy foods” like doughnuts, fries, candy, soda / fizzy drinks, processed foods etc etc, I suppose it might be
    I myself find that lots of any fresh meats, fish, cheese, green veggies, berry fruits and even very low carb breads and the like are just fine.
    I also imagine that although I lost 66lbs with ease, and now do bodybuilding with the “newly” found spare energy, that also has also nothing to do keto….

  3. This research is a waste of money, Some study I read used a whitening agent found in flour and other processed ingredients to create dishes in rats. Easy absurd. I’ve been doing keto for 5 years on and off. I have not developed diabetes coming on/off of it for 5 years.There are so many people doing this diet. Bodybuilders also use it for competitions to drop water weight. Where’s a bodybuilder with diabetes? The only issue I would think is sustainability. Keto does get very monotonous and requires cooking for yourself. Other issues would be performance depending on training styles (intensity wise).

  4. I’ve found keto dieting very useful to lose weight. However, I am not sure how healthy it is in the long term. I hope they do more research on this but I like the idea in general as it rings true about what people used to eat in the past, especially in winters when no fruits were available.

  5. I always go on low fat keto which is safer (avoid cheeses, oils) to lose weight dramatically the start of the year for two months. Majority of my calories is from protein. The only major fat I have is of 2 dinners a week of beef steak with fat trimming, but counter it with 2 lean white fish and 3 chicken breast for remainder. I found it is the easiest way to lose weight.. you dont even need to exercise in order to lose weight plus you have so much more energy after the first few weeks going through it. You will have major sugar cravings, fatigue, headaches at the start but things will turn around quickly and you will end up burning fat like crazy even while sleeping. I tend to switch to Paleo after this to sustain myself also avoiding dairy products in the process…

  6. Thanks for your valuable resources keep sharing the information like this…

  7. The actual published paper (as opposed to this SciTech briefing) states that the diet used was
    5% carbohydrate
    15% protein
    80% fat

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