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.

Iron Regulates Cellular Proliferation by Enhancing the Expression of Glucose Transporter GLUT3 in the Liver

“…Ketone BHB inhibits the proliferation and viability of cancer cells but has no effect on healthy fibroblasts [44][45][46]. Here, we found that BHB treatment in HepG2 cells reversed the FAC-induced GLUT3 upregulation in a dose-dependent manner using RT-PCR, immunostaining, and Western blot (Figure 5A-C).…”

Iron Regulates Cellular Proliferation by Enhancing the Expression of Glucose Transporter GLUT3 in the Liver

“…Ketone BHB inhibits the proliferation and viability of cancer cells but has no effect on healthy fibroblasts [44][45][46]. Here, we found that BHB treatment in HepG2 cells reversed the FAC-induced GLUT3 upregulation in a dose-dependent manner using RT-PCR, immunostaining, and Western blot (Figure 5A-C).…”

Effects of the ketogenic diet on skin—potential benefits and risks

“…There is preliminary evidence that it may benefit individuals with autism spectrum disorder (ASD) ( 79 ). Numerous scientific studies also confirm the beneficial effects of KD in treating certain types of cancer ( 39 , 80 , 81 ). The key anti-cancer mechanism of KD is carbohydrate reduction, which leads to lower glucose levels and slower proliferation of cancer cells ( 39 , 82 ).…”

“…Numerous scientific studies also confirm the beneficial effects of KD in treating certain types of cancer ( 39 , 80 , 81 ). The key anti-cancer mechanism of KD is carbohydrate reduction, which leads to lower glucose levels and slower proliferation of cancer cells ( 39 , 82 ). KD is also used in glucose transporter 1 (GLUT1) deficiency syndrome to provide an alternative source of energy for the brain in conditions of impaired glucose access ( 83 ).…”

Lifestyle-Based Approaches to Cancer Prevention and Treatment: Diet, Physical Activity, and Integrative Strategies

“…It achieves this by downregulating interleukin-1β (IL-1β) expression in bone-marrow-derived macrophages and promoting the expression of mitochondrial uncoupling protein 2, thereby protecting against oxidative stress and supporting increased longevity [ 57 ]. Additionally, reduced levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), have been observed with KD, suggesting its potential to enhance cancer treatment outcomes through its anti-inflammatory actions [ 58 ].…”

Iron Regulates Cellular Proliferation by Enhancing the Expression of Glucose Transporter GLUT3 in the Liver

“…Ketone BHB inhibits the proliferation and viability of cancer cells but has no effect on healthy fibroblasts [44][45][46]. Here, we found that BHB treatment in HepG2 cells reversed the FAC-induced GLUT3 upregulation in a dose-dependent manner using RT-PCR, immunostaining, and Western blot (Figure 5A-C).…”

Effects of the ketogenic diet on skin—potential benefits and risks

“…There is preliminary evidence that it may benefit individuals with autism spectrum disorder (ASD) ( 79 ). Numerous scientific studies also confirm the beneficial effects of KD in treating certain types of cancer ( 39 , 80 , 81 ). The key anti-cancer mechanism of KD is carbohydrate reduction, which leads to lower glucose levels and slower proliferation of cancer cells ( 39 , 82 ).…”

“…Numerous scientific studies also confirm the beneficial effects of KD in treating certain types of cancer ( 39 , 80 , 81 ). The key anti-cancer mechanism of KD is carbohydrate reduction, which leads to lower glucose levels and slower proliferation of cancer cells ( 39 , 82 ). KD is also used in glucose transporter 1 (GLUT1) deficiency syndrome to provide an alternative source of energy for the brain in conditions of impaired glucose access ( 83 ).…”

Lifestyle-Based Approaches to Cancer Prevention and Treatment: Diet, Physical Activity, and Integrative Strategies

“…It achieves this by downregulating interleukin-1β (IL-1β) expression in bone-marrow-derived macrophages and promoting the expression of mitochondrial uncoupling protein 2, thereby protecting against oxidative stress and supporting increased longevity [ 57 ]. Additionally, reduced levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), have been observed with KD, suggesting its potential to enhance cancer treatment outcomes through its anti-inflammatory actions [ 58 ].…”

Iron Regulates Cellular Proliferation by Enhancing the Expression of Glucose Transporter GLUT3 in the Liver

“…Ketone BHB inhibits the proliferation and viability of cancer cells but has no effect on healthy fibroblasts [44][45][46]. Here, we found that BHB treatment in HepG2 cells reversed the FAC-induced GLUT3 upregulation in a dose-dependent manner using RT-PCR, immunostaining, and Western blot (Figure 5A-C).…”

Effects of the ketogenic diet on skin—potential benefits and risks

“…There is preliminary evidence that it may benefit individuals with autism spectrum disorder (ASD) ( 79 ). Numerous scientific studies also confirm the beneficial effects of KD in treating certain types of cancer ( 39 , 80 , 81 ). The key anti-cancer mechanism of KD is carbohydrate reduction, which leads to lower glucose levels and slower proliferation of cancer cells ( 39 , 82 ).…”

“…Numerous scientific studies also confirm the beneficial effects of KD in treating certain types of cancer ( 39 , 80 , 81 ). The key anti-cancer mechanism of KD is carbohydrate reduction, which leads to lower glucose levels and slower proliferation of cancer cells ( 39 , 82 ). KD is also used in glucose transporter 1 (GLUT1) deficiency syndrome to provide an alternative source of energy for the brain in conditions of impaired glucose access ( 83 ).…”

Lifestyle-Based Approaches to Cancer Prevention and Treatment: Diet, Physical Activity, and Integrative Strategies

“…It achieves this by downregulating interleukin-1β (IL-1β) expression in bone-marrow-derived macrophages and promoting the expression of mitochondrial uncoupling protein 2, thereby protecting against oxidative stress and supporting increased longevity [ 57 ]. Additionally, reduced levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), have been observed with KD, suggesting its potential to enhance cancer treatment outcomes through its anti-inflammatory actions [ 58 ].…”