- Ketogenic diets promote short-term weight loss, but the precise mechanisms behind the metabolic changes are still unknown.
- New research in mice and humans suggests that the ketogenic diet may protect against obesity by increasing specific bile acids and decreasing calorie absorption in the intestines.
- The long-term health effects of the ketogenic diet are unclear, and experts recommend plant-based diets, such as the Mediterranean diet, which promote a more favorable diversity of the gut microbiome.
The ketogenic diet is a low-carb eating plan that has been widely tested as a weight loss tool. Yet, it is unclear exactly how it works to reduce body weight.
Some suggest that gut bacteria and their byproducts may play a role in the beneficial metabolic effects of a ketogenic diet. However, the specific bacteria or byproducts involved are not yet well understood.
Now, a new study published in
These bile acids, namely taurodeoxycholic acid and tauroursodeoxycholic acid, may protect against obesity by decreasing the absorption of calories in the intestines. This could lead to a decrease in body weight and fasting blood glucose.
Distinguishing their work from classic animal studies, the researchers took additional steps to determine whether these results could apply to humans.
They documented similar associations between bile acids and metabolic traits in two human studies, adding to the potential importance of their findings.
This multi-method research highlights a specific interaction between the host and the gut microbiome that could explain how the ketogenic diet reduces body weight and fasting blood glucose in rodents and humans.
Researchers studied the effects of a ketogenic diet on blood levels of bioactive proteins.
They found that consuming a ketogenic diet significantly altered these metabolites, while also significantly reducing body weight and fasting blood sugar.
Further analysis showed that 22 specific metabolites increased, while 18 decreased with the ketogenic diet.
When researchers tested another 7-week dietary intervention involving supplementation with the amino acid methionine, it reversed the declines in body weight and fasting caused by the ketogenic diet. It also reduced six specific bile acids linked to changes in weight and glucose.
Treating mice with four of these bile acids revealed that two of them – taurodeoxycholic acid and tauroursodeoxycholic acid – significantly reduced body weight and blood sugar and improved glucose tolerance. This was true whether the mice were on a regular diet or a ketogenic diet supplemented with methionine.
Other bile acids detected were not affected by dietary changes and showed no association with body weight or fasting blood glucose.
Through a series of additional experiments, the researchers showed that consuming a ketogenic diet increased blood levels of taurodeoxycholic acid and tauroursodeoxycholic acid in mice while decreasing their body weight and fasting blood sugar.
The researchers who conducted the current study sought to determine whether their results obtained on mice were potentially applicable to humans.
They conducted an observational study, measuring bile acids in blood and stool samples from 416 healthy participants aged 20 to 60 years.
They also looked at data from a previously published low-carb report.
Consistent with their findings in mice, lower blood levels of specific bile acids in humans were significantly associated with higher body mass index (BMI) and fasting blood sugar levels.
They also found specific gut bacteria genes linked to BMI and fasting blood sugar. The low-carb diet appeared to significantly reduce these genes, and these changes were linked to BMI, fasting blood sugar, and bile acid levels.
In this study, it was shown that increasing the levels of certain bile acids (taurideoxycholic acid and tauroursodeoxycholic acid) led to decreased body weight and fasting blood glucose in mice. Similar associations have been observed in humans.
The study authors explain that the ketogenic diet reduces levels of a specific gut bacteria called Lactobacillus murinus ASF361, which produces an enzyme called bile salt hydrolase.
Lower levels of this bacteria or reductions in bile salt hydrolase increase levels of the two bile acids mentioned, taurodeoxycholic acid and tauroursodeoxycholic acid.
These increased bile acids, in turn, reduce calorie absorption by interfering with the expression of a gene encoding a protein called carbonic anhydrase 1 in the intestines, which may be linked to obesity.
According to the study, reduced calorie intake leads to weight loss and lower fasting blood sugar levels.
The researchers propose this mechanism of bile acid regulation because it is consistent with their findings in animals and humans. They acknowledge, however, that due to the lack of evidence, other potential explanations cannot be ruled out.
Today’s Medical News I spoke with Alyssa Simpson, RDN, CGN, CLT, a registered dietitian, certified gastrointestinal nutritionist, and owner of Nutrition Resolution in Phoenix, AZ, who was not involved in the study.
She commented that the research suggests a potential new mechanism for ketogenic diet weight loss that extends to include calorie absorption, influenced by changes in bile acids.
However, she does not generally recommend the ketogenic diet to patients, questioning its long-term sustainability and health implications due to its restrictive nature.
Simpson explained that:
“Although effective for weight loss (short term), there are concerns about the ketogenic diet due to its impact on the gut microbiome, leading to reduced diversity and altered bile acids, which may have a potential impact on long-term health.”
She noted that previous research suggests that high-fat, no-carb diets reduce microbiome diversity in a way that can decrease the production of beneficial antioxidants and
“This study confirms the impact of the ketogenic diet on the reduction of microbial diversity, highlighting selective changes,” she said.
Eliza Whitaker, MS, RDN, a registered dietitian and medical nutrition consultant at Dietitian Insights, who was also not involved in the study, agreed that the results should be interpreted with caution.
She noted limitations of the study, such as including only male mice, despite known variations in male and female bile acid profiles in humans.
Notably, Whitaker noted that “the results differ from previous studies that have suggested that higher-fat diets may impact the gut microbiome in ways that could
Simpson and Whitaker both recommend diets more consistently associated with better long-term health, including the Mediterranean and DASH diets.
Compared to a ketogenic diet, these diets “more reliably promote microbiome diversity through a variety of plant foods and provide essential nutrients, (which) may better support overall well-being,” Simpson concluded.