Recent research has shed light on the effects of high-fat and ketogenic diets, revealing significant concerns for health and weight management. In a controlled study, mice subjected to these diets experienced a startling weight increase, with their body weight doubling over a 16-week period. In contrast, mice adhering to a standard control diet gained only about 10% of their body weight—consistent with normal growth—despite similar caloric intake across all subjects. Notably, the high-fat and ketogenic diets led to impaired glucose tolerance and liver dysfunction, with signs of liver damage and elevated blood sugar levels becoming evident as early as two weeks into the study.
The ketogenic diet in particular resulted in heightened triglyceride levels, which are recognized as risk factors for heart disease and stroke, alongside increased systemic inflammation. Additionally, the mice developed fatty liver deposits and exhibited gene expression linked to inflammation and liver scarring.
“The keto diet was very damaging to the livers and overall health of mice with regular weights,” Singh commented. He highlighted the body’s capability to use fat for energy but cautioned about the metabolic ramifications of increased fat consumption. “While people may be drawn to the keto diet due to its weight-loss reputation, this research advises against it. Such diets should only be pursued under the careful oversight of a physician or dietitian.”
Whole grains and carbohydrates
In comparison, mice on a high-carbohydrate diet did not exhibit continuous weight gain or liver damage, unlike their counterparts on high-fat diets. Singh stressed that while a heavily processed carbohydrate-rich diet is not ideally healthy, it ultimately caused less harm to the liver than the high-fat options. Remarkably, mice fed a diet rich in whole grains experienced the least weight gain and showcased the most favorable health markers.
“A whole-grain-based diet is always beneficial—for mice or humans,” Singh stated.
The potential of fiber
In another phase of the study involving mice with obesity, the detrimental effects of high-fat and ketogenic diets became even more pronounced. However, when fiber was added to the ketogenic diet—a variable not tested with normal-weight mice—obese mice maintained more stable weight and demonstrated better health indicators compared to those on either the high-fat diet or the keto diet without fiber.
The researchers also observed that fiber supplementation did not disrupt ketogenesis in mice following the ketogenic diet. This finding is significant, as Singh noted, because the ketogenic diet is often used for managing specific medical conditions, including epilepsy.
“Adding dietary fibers to the ketogenic framework may alleviate gastrointestinal issues traditionally associated with extremely high-fat diets while preserving the therapeutic benefits of ketogenesis for patients,” Singh explained.
Dietary choices are complex, but that does not make them equivalent
As Singh pointed out, it’s essential to recognize that diet is intricate, and no universal solution applies to everyone.
“Over time, researchers have made significant strides in understanding what constitutes a healthy or unhealthy diet based on individual health conditions. However, there is no single dietary magic bullet for weight loss or resolving metabolic health issues,” Singh emphasized. “Anyone with health concerns about their diet should consult their physician or a registered dietitian to develop a tailored plan based on research that aligns with their specific needs and 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 and professor of molecular toxicology and of biochemistry and molecular biology; and Rita Castro, associate teaching professor of nutritional sciences. Other contributors include Devendra Paudel from Johns Hopkins Bloomberg School of Public Health; Chloé Robert and Benoit Chassaing from Université Paris Cité in France; and Inês V da Silva from Universidade de Lisboa in Portugal.
