The relationship between nutrition and health has been a topic of interest for centuries. In recent decades, scientific research has uncovered important insights into how our diets can affect cancer risk, treatment, and survivorship. As cancer and metabolic disorders like obesity rise, there's growing awareness of nutrition's pervasive effect. Dietary intake is linked to multiple pathways involved in carcinogenesis and tumor progression.
Understanding the Diets
With the rise in cancer and metabolic disorders such as obesity, there has been increasing awareness of the pervasive effect of nutrition. In recent years, two popular diets, the plant-based diet and the ketogenic diet, have been the subject of much discussion regarding their potential roles in cancer prevention and treatment.
Plant-Based Diet
A plant-based diet emphasizes whole, unrefined, or minimally refined plant foods. It prioritizes nutrient-dense plant foods while minimizing processed foods, oils, and animal products. This approach focuses on micronutrient density rather than fixed macronutrient proportions. It is a minimally processed diet that is low in fat and moderate to high in unrefined carbohydrates. A whole foods, plant-based diet means that the majority (at least 80% to 90%) of the food should be unprocessed plant-based foods - things like legumes, fruits, vegetables, seeds, whole grains, and nuts.
Keto Diet
The keto (or ketogenic) diet involves severely cutting carb consumption while increasing fat intake to switch the body into ketosis, a metabolic state that allows the body to burn fat for fuel instead of carbohydrates. The KD challenges the dogma that meat intake should be reduced and reverses the dietary macronutrient profile with fat and protein as major macronutrients instead of carbohydrates. The KD aims to promote the production of ketone bodies from fatty acids, typically through very low carbohydrate (approximately 5% calories), high fat (approximately 75% calories), and moderate protein (approximately 20% calories) intake. Most calories in a KD are obtained from meat, dairy, fish, oils, and eggs, with some nuts, seeds, and nonstarchy vegetables. These calculations typically translate to fewer than 40 g of carbohydrates per day compared with the standard Western-style diet (>250 g/day).
Scientific Evidence: Plant-Based vs. Keto for Cancer
A July 2020 review published in JAMA Oncology evaluated a plant-based diet vs. keto diet for cancer reduction. An analysis of data on both diets showed that there’s more support for plant-based diets as opposed to the keto diet as part of a lifestyle that’s associated with reduced cancer risk. Consumption of a plant-enriched diet is associated with reduced cancer incidence and is recommended by dietary guidelines for cancer prevention. Currently available data support plant-based diets as opposed to KD as part of a lifestyle associated with reduced cancer risk. The results of this review suggest that the collective evidence supports plant-enriched diets vs KD for the reduction of cancer risk and the improvement of metabolic disorders in survivors.
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Plant-Based Diets and Cancer Prevention
In the prevention setting, plant-based diets are consistently associated with a reduced cancer incidence; seminal large epidemiologic studies include the Adventist Health Study-2, EPIC Oxford and Oxford Vegetarian Cohort and NutriNet-Santé. To our knowledge, long-term epidemiologic evidence for a KD is not available, but participants with diets low in plant foods had an increased cancer incidence in these studies. Furthermore, 2meta-analyses showed thatLCDs are associated with higher mortality, especially for those whose diets favored animal-derived protein and fat. Low protein intake (<10% calories) has been associated with a 4-fold reduction in cancer mortality compared with high protein intake (>20% calories) in adults aged 50 to 65 years in the National Health and Nutrition Examination Survey III study. Consistent with these data and many other studies, the American Institute of Cancer Research/World Cancer Research Fund and the American Cancer Society recommend a diet comprising primarily whole plant-based foods and limited sugary drinks, highly processed foods, refined grains, and red and processed meats based on cumulative generalizable evidence for cancer. The World Cancer Research Fund also summarized the evidence for individual cancers.
Keto Diets and Cancer
While some studies in mice show that the keto diet is useful in very specific tumor types, such as a specific type of breast cancer with mutations in the PIK3CA gene, ongoing research is investigating whether this is true for humans with this type of breast cancer. Limited preclinical data suggest that KD may enhance the effects of specific cancer treatments and/or have tumor subtype-specific effects. For example, KDs induced tumor growth retardation in models in which anti-PD-1 treatment alone or in combination with anti-cytotoxic T-lymphocyte associated protein 4 failed to reduce tumor growth via alterations in the gut microbiome. Pre-clinical data in BRAF V600E-expressing melanoma suggested that a KD upregulated 3-hydroxy-3-methylglutaryl coenzyme A lyase (a key enzyme in ketogenesis), which raised levels of acetoacetate that then activated MEK1 and fueled tumor growth.
Potential Mechanisms of Action
Nutrition may play a substantial role in cancer prevention and treatment via multiple mechanisms. Although there are considerable differences in the KD and WFPBD, there are some common mechanisms by which they may be associated with a decrease in cancer risk.
Insulin Levels
Insulin and some of the most prevalent genomic alterations in human cancers (such as PIK3CA variations and PTEN loss) activate the phosphoinositide 3-kinase (PI3K) signaling cascade. This pathway regulates cellular metabolism as well as cell survival and proliferation. Thus, high insulin levels can promote and sustain tumor growth. A WFPBD is associated with decreased fasting plasma insulin concentrations and improved insulin sensitivity. Decrease d insulin levels have also been reported in KD clinical trials, although some preclinical studies showed contrary findings, suggesting increased insulin resistance.
Fiber and the Gut Microbiome
In patients with melanoma who were treated with checkpoint inhibitors, patients with sufficient dietary fiber intake ([H11350]20 g per day) and no probiotic use had higher odds of responding to treatment with programmed cell death 1 (PD-1) inhibitors as well as a longer progression-freesurvival.These findings were confirmed in preclinical animal models, and mice that received a low-fiber diet or probiotics had a lower frequency of interferon γ-positive cytotoxic T cells in the tumor microenvironment and an impaired response to anti-PD-1 therapy. A preclinical model with anti-cytotoxic T-lymphocyte associated protein 4 inhibitors showed contrasting results. Similar positive effects of fiber have been observed in the setting of colon cancer prevention. Given higher rates of colon cancer in African American individuals compared with African individuals living in rural areas, 20 healthy African American individuals and 20 African individuals from rural areas were administered a 2-week dietswitch(high-fiber, low-fat,AfricanstyledietadministeredtoAfrican American individuals and a high-fat, low-fiber, Western stylediet to African individuals from rural areas).
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Phytochemicals and Short-Chain Fatty Acids
Plant foods contain phytochemicals, such as flavonoids, that have anti cancer properties; therefore, they are more abundant in a WFPBD than a KD. Some of the beneficial anticancer effects of both diets were associated with an increase in short-chainfattyacids(SCFAs)bydifferent mechanisms. Conversely, KDs were associated with increased blood ketone body levels(mainlyβ-hydroxybutyrate[βHB]), aSCFA.AlthoughβHB also has HDAC inhibitory effects, butyrate is a stronger HDAC inhibitor. There is conflicting evidence as to whether βHB has anticancer effects vs proinflammatory and tumor proliferative effects in in vitro and in vivo models. The discrepant findings may be because of a βHB paradox.
Challenges and Future Directions
Nutrition trials with cancer-specific primary objectives often require large sample sizes and long intervention periods to see changes, especially given that long-term adherence to dietary changes during clinical trials is difficult. Other challenges with nutrition studies in oncology include differences inintervention duration, lack of standardization of macronutrient content, conflation of weight loss effect vs nutrient intake effect, and suboptimal adherence. For example, if ketosis is not achieved, a KD essentially amounts to carbohydrate restriction. Plant-based KDs are a potential alternative, with benefits from both dietary patterns.This approach may be difficult to sustain given the limited number of high-fat plant foods.
Expert Opinions
Experts at Memorial Sloan Kettering Cancer Center (MSK) are at the forefront of this research. Hematologic oncologist Urvi Shah cares for people with plasma cell disorders, including multiple myeloma. Medical oncologist Neil Iyengar treats people with breast cancer. Both conduct research aimed at understanding the interplay between nutrition and cancer.
Dr. Shah: Our review of the evidence supports a plant-based diet for reducing cancer risk compared with a ketogenic diet. All three found that people eating more plants and less animal protein had less cancer overall. That’s consistent with other large studies and included in the guidelines by the American Institute of Cancer Research and American Cancer Society, which all recommend diets that incorporate high amounts of plant-based food.
Dr. Iyengar: Currently, there is no evidence to suggest that a specific diet by itself can treat cancer. There is preliminary evidence to suggest that certain dietary patterns can help make some cancer treatments work better or reduce side effects.
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