Recently, much attention has been drawn to the perils of excessive carbohydrate intake. While a high-carb diet can indeed be detrimental, overconsumption of fats might precipitate even graver health issues, according to a study on mice conducted by scientists from the Department of Nutritional Sciences at Penn State University.
In findings published in the Journal of Nutrition, the researchers assessed how diets varying in their fat-to-carbohydrate ratio impacted metabolic wellbeing and liver function in mice over time. Their conclusion was that, generally, high-fat diets inflicted greater harm than high-carbohydrate diets, though the incorporation of fiber appeared capable of mitigating adverse effects under certain circumstances.
Mice were fed one of four feeding regimes—high-carbohydrate, high-fat, ketogenic, or a standard whole-grain-rich chow serving as the control group—for the experiment. In mice with normal body mass, the keto diet led to weight gain, impaired glucose assimilation, dysregulated lipid profiles, and increased hepatic inflammation and fat accumulation. The high-fat diet also resulted in weight gain alongside other health complications not seen in the high-carbohydrate group. Overall, the mice maintained on the standard chow exhibited the superior health outcomes.
“There are vast metabolic differences between humans and mice, yet this investigation offers relevant insights for people,” commented study co-author Vishal Singh. “Most individuals are aware of the importance of a balanced diet, but some are drawn to very high-fat diets—the keto diet, for instance—for weight loss purposes. This research signals tangible liver damage that could arise from the improper implementation of such diets.”
Across all experimental diets examined, the protein content was consistently held constant at 18% of total calories; variations were exclusively in the fat and carbohydrate proportions. The high-fat diet consisted of 42% carbohydrates and 40% fat, the high-carbohydrate diet featured 70% carbohydrates and 11% fat, and the ketogenic diet comprised 1% carbohydrates and 81% fat.
The fats predominant in these diets were saturated fats, a category typically solid at room temperature. The American Heart Association advises that saturated fats should constitute 6% or less of a human’s total caloric intake.
The carbohydrates utilized in these food plans were largely refined, meaning they came from processed sources, including white flour and added sugars. Scientific literature frequently links refined carbohydrates to metabolic disruptions and other negative physical and mental health ramifications.
These test diets were benchmarked against the whole-grain-rich chow, which is the standard fare for laboratory mice. This control diet contained 29% protein, 57.5% carbohydrates, and 13.5% fat.
Throughout the 16-week study period, the scientists tracked blood sugar levels and a comprehensive battery of liver function and health indicators regularly. Additional measurements were taken once the experimental feeding ceased.
“Our goal was to ascertain the effects of altering the carbohydrate-to-fat balance on health status over 16 weeks of dietary adherence,” stated Umesh Goanand, a co-author from Penn State University.
Ketogenic diets—commonly termed keto diets—virtually eliminate carbohydrate intake. This induces a metabolic state known as ketosis, where the body shifts to utilizing fat for fuel instead of glucose, its usual energy source.
The study’s outcomes revealed that both high-fat and ketogenic diets contributed significantly to obesity, with mice on these regimens doubling their body weight over the 16 weeks. Mice on the control diet gained about 10% in weight—a normal finding for mice of that age—despite all subjects consuming roughly equivalent amounts of calories. Furthermore, the high-fat and keto diets resulted in poorer glucose tolerance and impaired liver function. Liver damage indicators and elevated blood sugar levels were apparent as early as two weeks into both diets.
Mice consuming the keto diet also displayed increased triglyceride levels—a risk factor for cardiovascular disease and stroke—alongside heightened systemic inflammation. Moreover, they developed hepatic fat deposits and showed increased expression of genes linked to liver inflammation and scarring.
“The keto diet proved significantly detrimental to the liver and overall health of the normal-weight mice,” Singh observed, explaining that while the body can use fat for energy, the heightened reliance on fat metabolism carries metabolic consequences. “Individuals hearing about the keto diet’s reputation for weight loss might be tempted to try it themselves. However, this study suggests a warning—beware! This diet should only be undertaken with proper medical professional and/or dietitian supervision.”
In contrast to the high-carbohydrate group, mice on the high-fat regimen did not exhibit sustained weight gain or the degree of liver injury seen in the keto-fed mice. Singh emphasized that while a diet rich in processed carbs is not inherently healthy, it imposed less liver burden than the high-fat approach.
The mice fed the whole-grain-rich diet gained the least weight and demonstrated the best overall health metrics.
“A whole-grain based diet is consistently beneficial—for mice and for humans alike,” noted Singh.
In a secondary experiment involving obese mice, both the high-fat and keto diets led to further increases in weight. However, when the ketogenic diet was supplemented with fiber—a condition not tested on the normal-weight mice—the obese mice maintained more stable weight and better health markers in several areas compared to those on the high-fat or standard keto diets without added fiber.
The investigators also found that adding dietary fiber did not impede ketogenesis in the mice adhering to the keto plan. This is significant, Singh mentioned, because the keto diet is employed to manage certain conditions, such as epilepsy.
“Incorporating dietary fiber into a ketogenic regimen could alleviate the gastrointestinal side effects associated with very high-fat diets while preserving the therapeutic advantages of ketogenesis for patients,” Singh elaborated.
It remains crucial to remember, Singh pointed out, that diet is a multifaceted issue, and there is no single solution for everyone.
“Over time, researchers have learned a great deal about what is healthful versus harmful depending on an individual’s current health status, but no single dietary magic bullet exists for weight loss or resolving other metabolic concerns,” Singh stated. “Anyone experiencing health issues or worried about their nutrition should consult with their physician or a registered dietitian to establish a research-backed plan tailored to their specific requirements and life circumstances.”
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