The ketogenic diet may not work for women

Scientists at UC Riverside are studying how popular keto diets and intermittent fasting work at the molecular level and whether both sexes benefit equally.

The idea behind the keto diet is that low levels of carbohydrates and very high levels of fats and proteins will force the body to use fat as fuel, leading to weight loss. There are legions of people who swear by it and countless companies produce food designed for these people.

Woman eating meat

Intermittent fasting works on a similar principle, restricting food to a small window of time during the day. During the hours without food, the body depletes its sugar reserves and burns fat. Fat becomes ketone bodies that the brain can use as fuel.

Despite their popularity, scientists have not yet identified the genes or proteins that allow diets to work, if at all.

“The metabolic shift between sugar and fat – it’s amazing that we still don’t understand. But if we do, we can tell you if keto is right for you,” said UCR biochemist Sarah Radi.

A new $ 2 million grant from the National Institutes of Health will allow Radi and cell biology professor Frances Sladek to investigate this change. They think they already have an idea of ​​how it might work.

The key is probably a protein called HNF4 that is found at high levels in the liver. It is a transcription factor, which converts DNA into RNA, which is then converted into new proteins, and comes in two forms, P1 or P2.

The UCR-led team originally investigated P2 as a pro-cancer protein. They found no link to cancer, but they did find that mice with high levels of P2 in the liver also had different genes for metabolism.

They also learned that P2 appears in greater numbers later in the day, which could explain why mice did not gain as much weight if the time they ate was restricted, even if the mice ate too much.

Radi suspects that an energy-sensitive enzyme could cause the switch between P1 and P2, which could allow the process of burning fat to gain energy. “That’s what we’re trying to prove,” he said.

In this study, special attention will be paid to the ways in which male and female mice respond to keto and intermittent fasting diets. Some research suggests that there are differences.

“Keto doesn’t seem to work so well for women, because we metabolize fat differently and have different genes turned on and off in response to fasting,” Sladek said. “But we really don’t know why or how, that’s what we’re hoping to learn.”

Whether the diet is effective for either sex, researchers warn against taking any diet to the extreme. It is unclear whether all fat is metabolized by a ketogenic or fasting diet, or whether a large portion only builds up in the body. Standard Japanese diets contain 20% fat, American diets average 35%, and ketogenic diets can contain up to 70 or 80%, which is likely to be an unsustainably high amount.

“If you eat a lot of fat, it will eventually make you fat. If you eat too much of anything, it will make you fat, including carrots,” Sladek said. “Ultimately, the most important thing is how much you eat, what you eat and the time of day you eat.”

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