Results from the study demonstrated that the high-fat and keto diets promoted obesity, with the weight of mice on these diets doubling over the 16 weeks of the study. Mice on the control diet increased weight by around 10% — a normal rate for mice of that age — despite all mice in the study consuming roughly the same number of calories. In addition, the high-fat and keto diets impaired glucose tolerance and compromised liver function. Liver damage and elevated levels of blood sugar were observed after only two weeks of both diets.
Mice on the keto diet also developed elevated levels of triglycerides — a risk factor for heart disease and stroke — and showed increased levels of systemic inflammation. Additionally, they developed fat deposits in the liver and expressed genes associated with inflammation and liver scarring.
“The keto diet was very damaging to the livers and overall health of mice with regular weights,” Singh said, explaining that the body can utilize fat for energy, but there are metabolic consequences associated with the increase in fat processing. “People who hear about the keto diet’s reputation for weight reduction may be tempted to try it themselves. What this research says is — don’t! This diet should only be considered when properly supervised by a physician and/or dietician.”
Whole grains and carbohydrates
In comparison, mice on the high-carbohydrate diet did not continuously gain weight nor experience liver damage like those on the high-fat diets. Singh emphasized that a highly processed, carbohydrate-heavy diet is not inherently healthy, but it did less damage to the liver than the high-fat diets.
Mice on the whole-grain rich chow diet gained the least weight and demonstrated the best health indicators.
“A whole-grain-based diet is always a win — for mice or people,” Singh said.
The potential of fiber
In a separate experiment in the study involving mice with obesity, the high-fat and keto diets also led to further weight gain. However, when the keto diet was supplemented with fiber — a condition not tested in mice with normal weights — mice with obesity maintained more stable weight and better health indicators in several areas compared to mice on the high-fat diet or the keto diet without extra fiber.
The researchers also found that fiber supplementation did not hinder ketogenesis in mice who ate the keto diet. This is important, Singh said, because the keto diet is used for managing specific medical conditions, like epilepsy.
“Incorporating dietary fibers into the keto diet may reduce gastrointestinal complications associated with very high-fat diets while maintaining the therapeutic benefits of ketogenesis for patients,” Singh said.
Dietary choices are complex, but that does not make them equivalent
The important thing to remember, Singh said, is that diet is complex, and there is no one-size-fits-all solution.
“Over time, researchers have learned a lot about what is healthy or unhealthy based on an individual's health status, but there is no single dietary magic bullet for weight loss or any other metabolic health concern,” Singh said. “Anyone who experiences health problems or is concerned about their diet should talk to their physician or a registered dietician to develop a plan, based on research, that fits their specific needs and life circumstances.”
Penn State contributors to this research include Anthony Koehle III, research technologist; Sangshan Tian, doctoral student in nutritional sciences; Loi Nguyen Jr., former undergraduate research assistant and research technician; Gopi Yalavarthi, doctoral student in nutritional sciences; Fuhua Hao, postdoctoral scholar in veterinary and biomedical sciences; Sumudu Rajakaruna, postdoctoral research associate in nutritional sciences; Andrew Patterson, Tombros Early Career Professor, professor of molecular toxicology and of biochemistry and molecular biology; and Rita Castro, associate teaching professor of nutritional sciences. Other contributors include Devendra Paudel of Johns Hopkins Bloomberg School of Public Health; Chloé Robert and Benoit Chassaing of Université Paris Cité in France; and Inês V da Silva of Universidade de Lisboa in Portugal.