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Gender-Specific Reactions to Keto Diet: Insights from UT Health San Antonio

A recent investigation conducted by researchers at The University of Texas Health Science at San Antonio (UT Health San Antonio) has uncovered intriguing findings regarding the effects of a ketogenic diet, particularly in how it influences males and females differently. Researchers have suggested that estrogen might provide protective benefits, potentially mitigating some of the adverse effects of this popular low-carbohydrate, high-fat dietary regimen.

Study Background

Published on August 26, 2025, in the journal Cell Reports, this study examined the physiological responses of male and female mice on a ketogenic diet. The keto diet has grown in popularity across North America and Europe due to its potential benefits in managing Type 2 diabetes and controlling seizures in individuals with epilepsy. Despite its benefits for weight loss and some health markers, the study emphasizes that the outcomes may significantly depend on variables such as metabolic rate and, crucially, gender.

Key Findings

The research revealed that male mice, but not female mice, exhibited an accumulation of cells in various organs that expressed markers of cellular senescence when subjected to a ketogenic diet. Cellular senescence is a condition where cells lose their ability to divide and function, contributing to both age-related decline and various health problems.

According to Dr. David Gius, MD, PhD, the lead author and assistant dean for research at UT Health San Antonio, these findings imply that sex-specific differences in response to a ketogenic diet could have significant clinical implications. He stated, "These results suggest that sex specificity alters the effects of a ketogenic diet."

In the study, male mice also displayed increased oxidative stress levels—an indicator of cellular damage—contrasting with the female counterparts, which did not show similar reactions when placed on a keto diet.

The Role of Estrogen

One of the most compelling aspects of the study is the role of estrogen in potentially counteracting these negative effects. Administration of estrogen to male mice on a ketogenic diet was seen to prevent increases in both cellular senescence and oxidative stress. Conversely, when female mice received tamoxifen, a drug that blocks estrogen receptors, they exhibited similar increases in oxidative stress levels to those previously observed in male mice.

This led researchers to conclude that estrogen plays a critical role in mediating the effects of ketogenic diets, with a noticeable protective influence in females that appears to be absent in males.

Implications for Further Research

These findings underscore the need for further exploration into how gender impacts dietary responses. Historically, much research has relied on male subjects, often assuming that females would yield inconsistent results due to hormonal fluctuations tied to their menstrual cycles. However, this study calls that assumption into question and suggests that the responses of female subjects could provide a fuller understanding of dietary impacts.

Conclusion

As the popularity of the ketogenic diet continues to rise, this research prompts health professionals and individuals considering this dietary approach to reflect on the inherent differences in how men and women may metabolically respond to such diets. This pioneering study by UT Health San Antonio highlights the necessity for tailored dietary recommendations, taking into consideration not just personal health goals but also biological sex as a critical factor.

For additional insights, visit UTHealthSA.org and connect with their extensive resources across various social media platforms.