Impact of ketogenic diets on breast cancer

By Pooja Toshniwal PahariaReviewed by Lily Ramsey, LLMOct 17 2023

In a recent review published in Nutrients, researchers explored the therapeutic potential of the ketogenic diet (KD) for breast cancer (BC).

Study: Ketogenic Diet and Breast Cancer: Recent Findings and Therapeutic Approaches. Image Credit: Boontoom Sae-Kor/Shutterstock.com

Background

BC, the most common cancer in women, is greatly influenced by dietary patterns. The ketogenic diet (KD), characterized by a high fat and low carbohydrate intake, has received interest as a potential treatment.

However, the benefits of KD on BC are unknown, and most research has concentrated on Mediterranean diets as preventative or therapeutic methods.

About the review

In the present review, researchers comprehensively reviewed existing data on the association between the ketogenic diet and breast cancer.

The review included preclinical animal studies, randomized controlled trials, case-control studies, cohort studies, and clinical studies published in Scopus, PubMed/MedLine, Cochrane Library, Google Scholar, and Web of Science databases exploring the role of KD in managing breast cancers.

Studies not published in English, editorials, commentaries, and those not fully accessible were excluded.

Association between breast cancer and diet

Breast cancer (BC) incidence has been connected to dietary changes and the introduction of ultra-processed food items, notably animal-based nutrition. Adiposity and energy homeostasis are important risk factors for BC. Recent research has shed more light on the impact of dietary variables on certain types of breast cancer, like estrogen receptor-negative (ER-ve) BC.

Hypercaloric diets, which include processed and red meats, fatty foods, and carbohydrates, raise BC risk by increasing circulating estrogen levels, inflammatory cytokines, and insulin-like growth factor 1 (IGF-1) linked to BC.

Healthy food habits, on the other hand, such as vegetables and fruits high in fiber, vitamins, and omega-3 fatty acids, improve health by lowering deoxyribonucleic acid (DNA) damage and chronic inflammation.

The Women's Intervention Nutrition Study (WINS) showed that women who received nutritional treatments reduced their fat intake from 29% to 20%. After a five-year follow-up, patients who received dietary therapies had a 24% increase in relapse-free time interval compared to controls.

Non-starchy veggies may lower luminal B (ER) breast cancer incidence, but carotenoid-dense foods and calcium-rich diets may reduce BC risk among premenopausal and postmenopausal females. A healthy diet rich in nutrients such as polyphenols, folates, and vitamins can help lower BC risk.

The PREDIMED trial found that Mediterranean diets and extra-virgin-type olive oil (EVOO) can potentially help prevent breast cancer.

EVOO contains monounsaturated-type fatty acids such as oleic acid and squalene, and polyphenols such as oleuropein, oleocanthal, lignans, and hydroxytyrosol, all of which are beneficial to human health.

Patients' outcomes, cardiometabolic indices, and quality of life have all been proven to improve with low-glycemic index diets, notably the Mediterranean diet.

Effects of the ketogenic diet on breast cancer

The "Warburg Effect" is a phenomenon in which cancer cells use glycolysis to create lactate and energy. This mechanism is linked to tumor cell proliferation and growth.

In recent times, researchers have made efforts to develop a dietary plan that might serve as an adjunct to oncolytic therapy. Numerous studies have demonstrated that KDs can alter tumor cell metabolism and, in certain situations, prevent tumor development.

Reduced carbohydrate consumption lowers circulating blood sugar levels, which diminishes insulin-like growth receptor signaling and circulating insulin levels related to cancer genesis and development. The KD also has a significant impact on tumor cell mitochondrial metabolism.

The KD generates a rise in ketone bodies and a decrease in glucose levels in tumor cells with malfunctioning mitochondria, which are not utilized for energy generation, allowing cancer cells to thrive and survive.

KD can inhibit cancer-promoting pathways such as the phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) signaling and adenine triphosphate (ATP) production in functionally impaired mitochondria.

BHB promotes nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene transcription and the formation of glutathione, which detoxifies cells from reactive oxygen species (ROS). Furthermore, BHB suppresses the actions of histone deacetylases (HDACs), limiting cancer cell growth and survival.

Another characteristic of cancer cells is ROS elevation, caused by microenvironmental instability and mitochondrial malfunction.

Glutathione and Nrf2 regulate ROS levels. Preclinical investigations in mice fed with KD revealed a rise in circulating glutathione and activated Nrf2, the transcription factor that regulates antioxidant gene expression and detoxifying enzyme levels.

Emerging data indicates that a ketogenic diet may have anticancer features such as slowing tumor development, protecting disease-free cells from radiation and chemotherapy damage, amplifying chemotherapy's harmful effects on tumor cells, and reducing inflammation. KDs might be an effective anticancer approach as a nutritional intervention.

Conclusion

Based on the review findings, in breast cancer (BC), the ketogenic diet (KD) has been found to reduce tumor development and increase treatment response. The ketogenic diet (KD), a high-fat, low-carbohydrate diet, switches the body's metabolism from glucose to ketone, causing metabolic stress on cancer cells and moderating inflammation and oxidative stress.

However, substantial clinical trials are missing, and there are still worries regarding the safety and long-term implications of ketosis.

Long-term side effects include unwanted metabolic alterations, higher blood lipid levels, hepatic steatosis, kidney stones, hypoproteinemia, and co-enzyme deficiencies.