• Investigating the Role of the Ketogenic Diet in the Prevention and Treatment of Colorectal Cancer: A Narrative Review
  • Parvin Babaei,1 Vajihe Ghalenoei,2 Narges Salavati,3 Hiva Azami,4,*
    1. MSc Pediatric Nursing Student, Student Research Committee, School of Nursing and Midwifery, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
    2. BSc Graduate in Nursing, Faculty of Medical Sciences, Islamic Azad University of Birjand, South Khorasan, Iran
    3. Student research committee, Shoushtar faculty of medical sciences, Shoushtar, Iran
    4. Department of Medical Emergencies, School of Nursing and Midwifery, Hamadan University of Medical Sciences, Hamadan, Iran


  • Introduction: Colorectal cancer (CRC), ranked as the third most common cancer globally with a high incidence and mortality rate, poses a significant public health challenge. Unhealthy dietary patterns and lifestyle are among the top risk factors. Consequently, finding effective strategies for CRC prevention and treatment is a major concern. Recent research has explored the potential efficacy of the ketogenic diet (KD) in the fight against CRC. The KD, which is high in fat and very low in carbohydrates, fundamentally shifts the body's metabolism to produce ketone bodies. This metabolic switch can specifically target cancer cells, as they are often glucose-dependent. This paper aims to evaluate the effectiveness of the ketogenic diet in CRC prevention and therapy, decipher its link with molecular mechanisms, and determine its influence on the gut microbiome.
  • Methods: This article is a narrative review of published research. It involved a comprehensive search using advanced features with Boolean operators (AND/OR) and a combination of MeSH and non-MeSH keywords. The primary search terms in English and Persian were: "colorectal cancer," "ketogenic diet," "beta-hydroxybutyrate," "microbiome," and "nutritional interventions." The search was conducted in several databases: PubMed, Scopus, Web of Science, and Google Scholar (as a search engine), and nationally in SID and Magiran. The initial search found 23 studies. Nine studies were selected for inclusion and further analysis based on criteria that included original research articles (quantitative, qualitative, or mixed-methods) published within the last 5 years (2020-2025) in Persian or English with free full-text access. Exclusion criteria were systematic reviews, meta-analyses, grey literature, and duplicate or irrelevant articles.
  • Results: The ketogenic diet (KD) and its primary metabolite, β-hydroxybutyrate (BHB), have shown significant anti-cancer effects in preclinical models of CRC. Studies indicate that KD suppresses tumor growth by reducing colon tumor burden in mouse models of CRC and inducing apoptosis in cancer cells. These effects are partially mediated by changes in the gut microbiome, specifically by increasing the population of bacteria that produce stearic acid, which has anti-tumor properties. Furthermore, BHB inhibits tumor growth by activating the Hcar2-Hopx signaling pathway, which reduces the proliferation of intestinal crypt cells; a mechanism that has also been confirmed in human models. Additionally, KD helps inhibit cancer progression by suppressing the function of Lgr5+ stem cells in intestinal crypts and reducing inflammation (e.g., by decreasing IL-17 production).
  • Conclusion: This study demonstrates that the ketogenic diet and its metabolites, particularly beta-hydroxybutyrate (BHB), have significant potential in the prevention and treatment of colorectal cancer through multiple mechanisms. These findings open new avenues for therapeutic interventions based on dietary strategies and ketone supplements. The results of this review are consistent with similar research exploring the role of diet and metabolism in cancer control. However, the majority of the current evidence is derived from preclinical studies (animal and laboratory models), which limits its direct generalizability to humans. The practical applications of these findings could include providing a basis for developing complementary dietary strategies or using ketone supplements as new therapeutic approaches for CRC patients. These approaches hold promise and may have fewer side effects compared to conventional treatments. To definitively confirm these effects and determine their efficacy and safety in humans, future research should include well-designed, randomized, controlled clinical trials with large sample sizes. Further research is also needed to determine the optimal dose and duration of the ketogenic diet or ketone supplements for CRC treatment and to more accurately identify patients who would respond to this type of therapy.
  • Keywords: Colorectal cancer, Ketogenic diet, Beta-hydroxybutyrate, Microbiome, Nutritional interventions