Jesse Cochran, a senior at the University of Iowa and research assistant in the E. Dale Abel Laboratory, where the study was conducted, and his colleagues were originally studying how the keto diet fares as a treatment for heart failure in mice. But they soon realized that female and male mice were responding differently to the low-carb, high-fat diet. “We went back and repeated the experiments to evaluate the reproducibility of this response,” says Cochran, the lead investigator. “Again, we found that in contrast to male mice, female mice did not lose weight in response to the ketogenic diet.” In their experiment, they fed male and female mice either a control diet or a keto diet. By calories, the control diet consisted of 24 percent protein, 16 percent fat, and 60 percent carbohydrates, whereas the keto diet was 93 percent fat, 5 percent protein, and 2 percent carbohydrates. After 15 weeks of following the randomized diets, male mice experienced significant fat loss and female mice did not. The female mice also experienced impaired blood sugar control. RELATED: Can the Keto Diet Help Prevent or Manage Heart Disease?
What the Findings Suggest About How Keto May Affect Weight in Humans
The findings were presented at the Endocrine Society’s 101st annual meeting and expo on March 24, 2019, in New Orleans. But the results have yet to be published in a peer-reviewed journal or replicated in humans. “This is a starting place but doesn’t merit making any decisions about your own diet,” says Robert Santos-Prowse, RDN, who practices at an inpatient rehab facility in Tennessee and is the author of The Cyclical Ketogenic Diet. “The results don’t tell us much about how humans would respond to a ketogenic diet. The translation is not always one to one.” Santos-Prowse was not involved in the current study. Additionally, the caloric makeup of the diet implemented in the study doesn’t translate to what humans most often eat when they follow the diet, Cochran says. Study authors chose to employ a diet with 5 percent protein because previous data on mice, which was published in October 2015 in Diabetologia, found that the weight loss properties of keto may only be present when the diet is composed of 5 percent protein or less. Humans on the keto diet commonly eat a diet that is 75 percent fat, 20 percent protein, and 5 percent carbohydrates. He also notes that the age range analyzed doesn’t align to the age at which humans often go on the diet. “The diet was commenced at the age of 3 to 4 weeks, which corresponds to teens or adolescents,” Cochran says. “For a more applicable context, it might be necessary to start the diet at a later age corresponding to adulthood.” RELATED: What Are the Benefits and Risks of the Keto Diet?
Could Estrogen Play a Role in Weight Loss?
The team then explored the role of estrogen (a hormone vital for sexual and reproductive development in females) by removing the ovaries of female mice. Yet again, the mice were randomized to either a control or a keto diet. Female mice on the keto diet that had their ovaries removed lost weight and fat mass, “which may partially be attributed to estrogen,” the authors write in their abstract. However, those mice still experienced impaired blood sugar control. Despite the male mice losing weight on the keto diet, researchers found that they exhibited signs of nonalcoholic fatty liver disease. This is when too much fat gets stored in the liver, and it can potentially lead to cirrhosis, which is severe liver damage, or liver cancer. RELATED: 11 Keto Diet Dangers You Need to Know
Why More Studies Are Needed on the Weight Loss Results of Keto
Future studies building on the team’s research should seek to identify the exact signaling pathways that mediate the weight loss response to keto diets and how sex hormones play a role, Cochran says. Long-term research on the health effects of keto is currently lacking. For now, consult your healthcare team before trying any extreme fad diet, including keto. “Regardless of sex, patients should embark on these diets only under direct medical supervision and in consultation with a dietitian nutritionist,” he cautions.
