Recent research has revealed that ketogenic diets may be effective against multiple sclerosis (MS) in murine models. This study, published in Cell Reports, highlights the significance of the gut microbiome in the diet's therapeutic effects.

The Keto Connection to Autoimmune Diseases

The ketogenic diet is characterized by a high-fat, low-carbohydrate composition, where the majority of daily calorie intake is derived from fats, with minimal contribution from carbohydrates. This dietary approach has been associated with weight loss and increased cholesterol levels, raising concerns about its long-term health implications [2]. Nevertheless, the potential benefits of ketogenic diets for individuals with autoimmune diseases, including MS, have come under investigation [3] [4].

In this study, the researchers specifically targeted experimental autoimmune encephalomyelitis (EAE) mice, a model frequently used to study MS due to its similarity to human pathology. The scientists aimed to determine whether a ketogenic diet could help protect these animals from the onset of EAE.

Findings: Reduced Incidence and Severity of Symptoms

The research indicated that mice placed on a ketogenic diet—composed of approximately 90.5% fat, 0% carbohydrates, and 9.5% protein—were significantly more resistant to EAE compared to those fed a high-fat diet that was less ketogenic (75% fat, 15% carbohydrates, and 10% protein). The keto-fed mice exhibited both a lower incidence of the disease and milder symptoms, which correlated with an improved immune profile.

However, when the same experiment was conducted on mice with depleted gut microbiota, the protective effects of the ketogenic diet were not observed, indicating that gut bacteria play a critical role in mediating the benefits of this diet.

From Ketosis to Ketone Supplements

Ketogenic diets work by altering the body's energy metabolism. When glucose is scarce, the body shifts to burning fat through a process called beta-oxidation, producing ketone bodies that serve as alternative energy sources. One critical ketone body is beta-hydroxybutyrate (βHB).

The study explored whether direct supplementation with βHB could replicate the effects of ketogenic diets. Mice on a high-fat diet supplemented with a ketone ester showed similar resistance to EAE as those on a ketogenic diet, suggesting that βHB supplementation could be a viable alternative to a full ketogenic diet for managing autoimmune disorders.

“The implications of our findings are profound, as they suggest that supplementation with a single bioactive molecule like βHB could offer a more manageable therapeutic alternative than the strict regimen imposed by a ketogenic diet.” – Dr. Peter Turnbaugh

Gut Microbiome: The Key Player

Interestingly, while the liver primarily produces βHB under a ketogenic diet, the beneficial effects of both ketogenic diets and ketone ester supplementation for MS seem to operate through βHB production in intestinal epithelial cells. Mice genetically modified to prevent βHB production in the gut failed to gain the protective benefits against MS, underscoring the role of the gut microbiome.

Researchers identified Lactobacillus murinus, a beneficial bacterium, and its metabolite indole lactic acid (ILA) as vital contributors to this protective effect. ILA has demonstrated an ability to reduce autoimmune responses by inhibiting the pro-inflammatory cytokine IL-17, which is associated with autoimmune diseases. Treatment with ILA and the introduction of _L. murinus_ into the gut flora of MS mice alleviated symptoms, affirming that enhancing ILA production via βHB can impart protective effects.

Future Implications and Considerations

The authors express hope that their findings will advance therapeutic options for patients with multiple sclerosis, potentially leading to more tolerable alternatives to restrictive diets. This could significantly impact patient compliance and health outcomes in the management of autoimmune conditions.

Literature Cited

Reference Study Details
[1] Alexander, M., et al. (n.d.). A diet-dependent host metabolite shapes the gut microbiota to protect from autoimmunity. Cell Reports.
[2] Burén, J., et al. (2021). A ketogenic low-carbohydrate high-fat diet increases LDL cholesterol in healthy, young women: a randomized controlled feeding trial. Nutrients, 13(3), 814.
[3] Pinto, A., et al. (2018). Anti-oxidant and anti-inflammatory activity of a ketogenic diet: new perspectives for neuroprotection in Alzheimer’s disease. Antioxidants, 7(5), 63.
[4] Brenton, J. N., et al. (2019). Pilot study of a ketogenic diet in relapsing-remitting MS. Neurology: Neuroimmunology & Neuroinflammation, 6(4), e565.

[5] Lifespan.io