Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities

Abstract

Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet program. The ketogenic diet (KD) has recently emerged as a metabolic therapy in cancer treatment, targeting cancer cell metabolism rather than a conventional dietary approach. The ketogenic diet (KD), a high-fat and very-low-carbohydrate with adequate amounts of protein, has shown antitumor effects by reducing energy supplies to cells. This low energy supply inhibits tumor growth, explaining the ketogenic diet's therapeutic mechanisms in cancer treatment. This review highlights the crucial mechanisms that explain the ketogenic diet's potential antitumor effects, which probably produces an unfavorable metabolic environment for cancer cells and can be used as a promising adjuvant in cancer therapy. Studies discussed in this review provide a solid background for researchers and physicians to design new combination therapies based on KD and conventional therapies.

Keywords: alternative cancer therapies; anticancer diet; calories restriction; targeting cancer metabolism.

Figure 1

Scheme of cell behavior during ketogenic diet; (a) normal cell feeding with KD, lower level of glucose prevents glycolysis pathway, increases ketone body level as a result of fatty acid oxidation, thus enhancing level of acetyl-CoA in mitochondria to compensate for the ATP needing (b) cancer cell feeding with KD, and abolishes glycolysis. Additionally, the mitochondria are dysfunctional so the cell cannot produce ATP; thus, KD prevents cancer cell proliferation.

Figure 2

Ketogenic diet mechanism of action as a cancer therapy, (→), activation; (┬), inhibition; MMP-9, matrix metalloproteinases-9; TNF-α, tumor necrosis factor alpha; HDAC, histone deacetylases; PKM2, pyruvate kinase M2; AMP-K, AMP-activated protein kinase; IL-1B, interleukin 1 beta; IF-γ, interferon gamma; NF-kB, nuclear factor kappa B.