Keto and Sex Differences: Why Men and Women Respond Differently to a Ketogenic Diet
A 2025 study from University of Utah Health published in Science Advances found a striking sex difference in the metabolic consequences of long-term ketogenic dieting: male mice developed severe fatty liver, while female mice showed no significant fat accumulation in the liver. Both sexes showed elevated blood lipids and disrupted blood sugar regulation, but the protective effect in females is hypothesized to involve estrogen's role in fat oxidation and insulin sensitivity. This finding adds to a growing body of research suggesting that keto's effects on metabolism differ meaningfully between men and women, with implications for post-menopausal women, men with pre-existing liver risk, and anyone considering keto as a long-term lifestyle rather than a short-term intervention.
The University of Utah keto study: sex-specific metabolic effects
Researchers at University of Utah Health placed mice on a long-term ketogenic diet lasting more than nine months and tracked detailed metabolic outcomes. In male mice, the extended keto diet caused severe hepatic steatosis (fatty liver) and impaired liver function. Female mice following the same protocol showed no significant liver fat accumulation. Both male and female mice developed elevated triglycerides and disrupted blood sugar control within two to three months. When carbohydrates were reintroduced, blood glucose remained dangerously elevated for extended periods. The researchers noted that the underlying mechanism for the sex difference in liver fat remained unclear at the time of publication and is a subject for ongoing investigation. The findings were published in Science Advances in 2025 and reported widely by ScienceDaily in January 2026.
Hormonal factors that may drive sex differences on keto
Oestrogen has well-documented metabolic effects, including promotion of fat oxidation, enhanced insulin sensitivity, and a protective role against hepatic fat accumulation. Researchers hypothesise that oestrogen may help protect against the liver fat deposition seen in male animals on long-term keto. Post-menopausal women, who have lower oestrogen levels, may face different keto outcomes than pre-menopausal women, though direct trial data on this subgroup remain limited. Testosterone, conversely, may influence how the liver responds to high-fat, low-carbohydrate diets, potentially contributing to the more pronounced lipid dysregulation seen in male subjects.
Body composition and weight loss differences between sexes
Previous research has found that men and women tend to lose weight at different rates on keto and tend to lose it from different body compartments. Men often show faster initial weight loss on keto, largely due to greater glycogen depletion and a higher baseline metabolic rate. Women may lose weight more slowly at first but often show more sustained fat loss over longer periods. Studies also suggest that women on keto are more likely to report menstrual cycle changes, particularly at the start of the diet, which may relate to the hormonal sensitivity of the hypothalamic-pituitary-ovarian axis to rapid carbohydrate restriction and caloric deficit.
Keto and muscle: different implications for men and women
Men and women differ in baseline muscle mass, anabolic hormone profiles, and rates of muscle protein synthesis, all of which interact with the metabolic state induced by keto. Research on resistance-trained men suggests keto can maintain muscle mass with adequate protein intake, but may blunt strength gains compared to higher-carbohydrate protocols. Women on keto in resistance training contexts have shown similar patterns, though studies are fewer and smaller. Both sexes benefit from maintaining protein intake above 1.6 grams per kilogram of body weight when combining keto with resistance training to preserve muscle.
What this means for personalising keto by sex
The emerging evidence on sex-specific keto responses supports a more personalised approach to ketogenic dieting. Men with a family history of liver disease or who have pre-existing fatty liver should monitor liver function markers if pursuing long-term keto and discuss the risks with their physician. Women considering keto should be aware of potential hormonal effects, particularly around the menstrual cycle, and pre-menopausal women experiencing cycle disruptions on keto may need to adjust protein and total caloric intake. Both men and women benefit from working with a registered dietitian rather than using generic keto templates, particularly for long-term protocols.
FAQ
Does keto work better for men or women?
The answer depends on the outcome measured. Men often lose weight faster initially on keto, but a <a href="https://www.science.org/doi/10.1126/sciadv.adx2752">2025 study</a> found they are more susceptible to keto-induced fatty liver than women. Women may experience hormonal effects on their menstrual cycle but appear metabolically protected against liver fat accumulation. Neither sex has a universally better outcome on keto; individual responses vary significantly.
Can keto cause fatty liver in men?
A <a href="https://www.science.org/doi/10.1126/sciadv.adx2752">2025 study from University of Utah Health</a> found that male mice on a long-term ketogenic diet developed severe hepatic steatosis (fatty liver), while female mice did not show the same effect. Whether this directly translates to men is not yet established, but it suggests that men with pre-existing liver conditions or metabolic risk factors should monitor liver health on long-term keto.
Does keto affect women's hormones?
Keto can affect women's hormonal profiles, particularly at the start of the diet. Rapid carbohydrate restriction and caloric deficit can disrupt the hypothalamic-pituitary-ovarian axis, leading to menstrual irregularities in some pre-menopausal women. These effects are often temporary and may resolve as the body adapts. Women with a history of hormonal conditions should consult a physician before starting keto.