Cancer remains a formidable global health challenge, marked by high morbidity and mortality rates. While conventional treatments like chemotherapy, surgery, and radiation play a crucial role in cancer management, they often come with debilitating side effects. This has led to increased interest in complementary approaches, particularly the role of diet and nutrition in cancer prevention and treatment. Emerging research suggests that dietary interventions, such as fasting and specific dietary components, may influence cancer development, progression, and treatment outcomes. This article delves into the current scientific evidence surrounding the potential of diet to impact cancer, exploring the mechanisms involved, clinical studies, and the importance of personalized nutrition in cancer care.
The Role of Fasting in Cancer Treatment
Fasting, defined as the voluntary abstention from all or specific foods, has a long history rooted in religious and cultural traditions. In recent years, scientists have begun to explore the potential of fasting, particularly intermittent fasting (IF), as a complementary strategy in cancer treatment. IF involves alternating between periods of fasting, with either no food or significant calorie restriction, and periods of unrestricted eating. Common variations of IF include alternate-day fasting, short-term IF (16-8 hours of daily fasting), prolonged IF, and whole-day fasting with a specific frequency per week.
Emerging evidence suggests that fasting could play a key role in cancer treatment by fostering conditions that limit cancer cells' adaptability, survival, and growth. Fasting could increase the effectiveness of cancer treatments and limit adverse events. Yet, we lack an integrated mechanistic model for how these two complicated systems interact, limiting our ability to understand, prevent, and treat cancer using fasting. Normal cells are protected from chemotherapeutic assaults by changes in circulating hormones and metabolites, resulting in decreased cell differentiation and activity in the metabolism.
Mechanisms of Fasting on Cancer Cells
Fasting induces several metabolic and hormonal changes that may impact cancer cells. These changes include:
- Reduced Glucose and Insulin Levels: Fasting suppresses glucose, IGF1, and insulin levels. To fulfill the body's fuel demands during fasting, metabolic stress causes insulin levels to drop and glucagon levels to rise, increasing the breakdown of liver glycogen reserves (into glucose) and triglycerides (into glycerol and free fatty acids).
- Increased Ketone Body Production: The brain progressively adjusts using the ketone bodies in addition to glucose to satisfy its energy requirements, while other tissues use fatty acids for energy. Gluconeogenesis is fueled by ketone bodies created in the liver from fatty acids, fat‐derived glycerol, and amino acids during the ketogenic state. Furthermore, β‐hydroxybutyrate, a ketone body, works as an endogenous histone deacetylase inhibitor.
- Activation of Autophagy: Fasting has been demonstrated to have significant restorative benefits through molecular mechanisms, such as enhanced autophagy and sirtuin activity. Fasting activates the autophagic process, which induces cell death through a variety of mechanisms. It also suppresses CD73 and CD39 expression and causes extracellular ATP accumulation, which inhibits Treg cells and the M2 phenotype while activating CD8+ cytotoxic T cells. Fasting also inhibits hemoxygenase 1. It accelerates cellular death and activates CD8+ cytotoxic T lymphocytes, which drive the apoptosis cycle once again. Both procarcinogenic and anticarcinogenic mechanisms have been connected to autophagy, which regulates oncogenes and tumor suppressor genes and has a complicated relationship with cancer.
- Increased Oxidative Stress in Cancer Cells: By lowering glucose intake and boosting fatty acid oxidation, fasting can induce a transition from aerobic glycolysis to mitochondrial oxidative phosphorylation in cancerous cells, resulting in increased ROS. Fasting causes cancer cells to release oxidative phosphorylation (OXPHOS) through aerobic glycolysis, which leads to an increase in reactive oxygen species (ROS), p53 activation, DNA damage, and cell death in response to chemotherapy. The combined impact of increased ROS and decreased antioxidant defense increases oxidative stress in cancerous cells and enhances chemotherapeutic action.
- Immune System Modulation: Fasting causes cancer cells to release oxidative phosphorylation (OXPHOS) through aerobic glycolysis, which leads to an increase in reactive oxygen species (ROS), p53 activation, DNA damage, and cell death in response to chemotherapy.
These metabolic and hormonal shifts create an environment that is less favorable for cancer cell growth and survival while potentially enhancing the effectiveness of conventional cancer treatments.
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Clinical Evidence of Fasting in Cancer Treatment
Clinical studies have been carried out to measure the relevance of various modalities of intermittent fasting on metabolic and hormonal endpoints correlated to cancer development and prognosis, given their practicality and the beneficial weight reduction effect in overweight/obese people.
Fasting may have aided in the healing process of chemotherapy‐induced DNA damage. Those patients fasted for 36 h before treatment and 24 h thereafter, having a total of 350 calories per day. Within 8 days of chemotherapy, no substantial weight loss was recorded, although there was an improvement in quality of life and weariness. Although clinical evidence is limited, several studies are under way in the advanced cancer scenario. Several studies posit that prolonged periodic fasting may be acceptable, viable, and able to potentiate the chemoradiotherapy and TKIs, triggering anticancer immunity and curbing chemo-related hazards and tumorigenesis in certain cancer patients undergoing chemotherapy. In particular, extended periodic fasting would presumably have slight effectiveness against existing cancers if it used alone without any adjunct treatments.
For instance, intermittent fasting clinical trials for metastatic prostate cancer (NCT02710721), early breast cancer patients (NCT05023967) and metastatic breast cancer (NCT04708860), gynecological cancers (NCT03162289), breast cancer survivors (NCT04330339, NCT04691999, NCT04560439), head and neck cancer (NCT05083416), prostate cancer survivors (NCT04288336), colon cancer survivors (NCT04345978, NCT05114798), obesity‐related malignant neoplasm, chronic lymphocytic leukemia/small lymphocytic lymphoma survivors (NCT04626843), gliomas survivors (NCT04461938, NCT02286167), melanoma (NCT04387084), childhood cancer survivors (NCT03523377), and non‐small cell lung cancer (NCT03700437, NCT03151161, NCT02066038) are currently underway.
Cautions and Considerations
While fasting shows promise as a complementary cancer treatment, it is crucial to approach it with caution and under the guidance of healthcare professionals. Patients who are frail or malnourished or who are in danger of malnutrition should not be included in fasting clinical trials, and patients’ overall physical and mental health ought to be closely monitored during the clinical research studies. The advantages of fasting will be maximized while patients are protected from malnutrition with this multimodal dietary strategy.
Dietary Components and Cancer Risk
Beyond fasting, the overall composition of the diet plays a significant role in cancer risk and prevention. It has been estimated that 30-40 percent of all cancers can be prevented by lifestyle and dietary measures alone.
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Foods That Increase Cancer Risk
- Obesity and Overeating: Eating too much food is one of the main risk factors for cancer. Sixty-four percent of the adult population is overweight or obese. It was estimated in a recent study, from a prospective cancer prevention cohort, that overweight and obesity accounted for 14 percent of all cancer deaths in men and 20 percent of those in women. Significant positive associations were found between obesity and higher death rates for the following cancers: esophagus, colon and rectum, liver, gallbladder, pancreas, kidney, stomach (in men), prostate, breast, uterus, cervix, and ovary.
- Refined Sugar and Carbohydrates: Refined sugar is a high energy, low nutrient food - junk food. "Unrefined" sugar (honey, evaporated cane juice, etc) is also very concentrated and is likely to contribute to the same problems as refined sugar. Concentrated sugars and refined flour products make up a large portion of the carbohydrate intake in the average American diet. Elevated fasting glucose, fasting insulin, 2 hour levels of glucose and insulin after an oral glucose challenge, and larger waist circumference were associated with a higher risk of colorectal cancer. In multiple studies diabetes has been linked with increased risk of colorectal cancer, endometrial cancer, and pancreatic cancer. It is clear that severe dysregulation of glucose metabolism is a risk factor for cancer.
- Low Fiber Intake: Unrefined plant foods typically have an abundance of fiber. Dairy products, eggs, and meat all have this in common - they contain no fiber. Refined grain products also have most of the dietary fiber removed from them. So, a diet high in animal products and refined grains is low in fiber.
- Red and Processed Meat: Red meat has been implicated in colon and rectal cancer. A recent meta-analysis also found red meat, and processed meat, to be significantly associated with colorectal cancer.
- Imbalance of Omega-3 and Omega-6 Fats: Omega 3 fats (alpha-linolenic acid, EPA, DHA) have been shown in animal studies to be protect from cancer, while omega 6 fats (linoleic acid, arachidonic acid) have been found to be cancer promoting fats.
Protective Dietary Factors
- Calorie Restriction with Optimal Nutrition (CRON): The basic idea is to eat a reduced amount of food (about 70-80 percent of the amount required to maintain "normal" body weight) while still consuming all of the necessary amounts of vitamins, minerals, and other necessary nutrients. The only restriction is the total amount of energy (calories) that is consumed.
- Flaxseed: Flax seed provides all of the nutrients from this small brown or golden hard-coated seed. It is an excellent source of dietary fiber, omega 3 fat (as alpha-linolenic acid), and lignans. Ground flax seeds have been studied for its effect on cancer. The lignan fraction containing secoisolariciresinol diglycoside (SDG) and the flax seed also reduced metastasis.
- Fruits and Vegetables: One of the most important messages of modern nutrition research is that a diet rich in fruits and vegetables protects against cancer. For most cancers, people in the lower quartile (1/4 of the population) who ate the least amount of fruits and vegetables had about twice the risk of cancer compared to those who in the upper quartile who ate the most fruits and vegetables. Vegetables, and particularly raw vegetables, were found to be protective; 85% of the studies that queried raw vegetable consumption found a protective effect. Allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes also had a fairly consistent protective effect.
- Cruciferous Vegetables: Allium and cruciferous vegetables are especially beneficial, with broccoli sprouts being the densest source of sulforophane.
- Protective Nutrients: Protective elements in a cancer prevention diet include selenium, folic acid, vitamin B-12, vitamin D, chlorophyll, and antioxidants such as the carotenoids (α-carotene, β-carotene, lycopene, lutein, cryptoxanthin).
The Microbiome and Cancer
The microbiome is a community of bacteria, viruses, fungi and other microbial cells living harmoniously within us and driving our metabolism and immune function. When there is dysfunction in the microbiome we start to experience excessive inflammation, which can promote cancer development.
The microbiome is influenced by your immune system, your diet, your lifestyle and the vitamins and minerals that you take. When you eat, everything that you don’t digest gets digested by the microbiome. The microbiome breaks down fiber and antioxidant micronutrients from fruits, vegetables, and whole grains and these post-biotics circulate to the cells and organs of the body.
Studies have proven you can enhance your immunity by changing your diet.
Personalized Nutrition in Cancer Care
Dr. Heber said recommending the same diet for every person with cancer would be impractical. Many variables go into a patient’s diet, such as how many calories they burn per day, how much protein they need, and if there are allergies to certain foods. The type of cancer and the stage of the cancer also matter when it comes to nutrition.
There should generally be adequate protein and colorful fruits and vegetables because they carry antioxidants and fiber that help support the immune system and the gastrointestinal tract.
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Addressing Common Misconceptions
Some people suggest that following specific diets or avoiding certain foods will help to treat or even cure cancer, but there is no credible evidence to support this claim. There is no special diet that can “cure cancer” and there is little evidence that following a strict diet will have any added benefit.