The question of what individuals with cancer should consume is often mired in confusion. While a diet rich in cancer-fighting, antioxidant-rich vegetables, low-fat protein sources, whole grains, nuts, seeds, and colorful fresh fruits is often recommended, the advice shifts dramatically when chemotherapy-induced weight loss occurs. Patients are then encouraged to consume whatever they can tolerate, including sweetened energy drinks, carbohydrate-rich comfort foods, and even high-sugar solutions administered intravenously. This article delves into the "deadly diet combo theory," exploring the intricate relationship between nutrition, cancer, and the immune system, while touching upon various dietary strategies and their potential impact on cancer treatment.
The Glucose-Cancer Connection
A significant connection exists between high blood sugar (hyperglycemia), diabetes, and cancer. Tumors heavily depend on glucose for survival, a principle utilized in PET scans to detect tumors. High blood glucose levels raise insulin, stimulating cancer cells to absorb and utilize more glucose, facilitating their nourishment. Furthermore, elevated blood glucose increases levels of Insulin-like Growth Factor I (IGF-I), which promotes tumor cell growth by activating the PI3K/Akt/HIF-1alpha pathway, encouraging cell multiplication, survival, and angiogenesis.
Regardless of cancer type, grade, stage, or mutations, a hallmark of all cancer cells is damaged mitochondria, which prefer glucose and glutamine for fuel. This metabolic inflexibility presents a potential vulnerability. Healthy cells with healthy mitochondria can adapt to various fuel sources, but cancer cells struggle to burn fat efficiently due to their impaired respiration.
Dietary Energy Restriction (DER) and Ketogenesis
Dietary energy restriction, sufficient to lower blood glucose, can reduce insulin and IGF-1 levels, thereby quieting tumor-driving genes and pathways. Glucagon stimulates fat burning, increasing ketones and fatty acids in the blood. Cancer cells cannot ferment ketone bodies and fatty acids, making them an unsuitable fuel source. Glucose restriction stresses cancer cells, while most healthy cells can efficiently utilize fatty acids and ketones for energy.
Glucagon also maintains blood sugar levels by initiating gluconeogenesis in the liver, allowing the body to produce necessary glucose from proteins and fats, negating the need for carbohydrate consumption. The brain can burn ketones, gradually shifting from glucose to ketone metabolism under low-glucose conditions.
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Both cancer cells and healthy cells possess GLUT-1, a glucose transporter that facilitates glucose uptake from the bloodstream. Under low-glucose conditions, healthy cells increase GLUT-1 transporters to optimize glucose absorption. However, cancer cells, being less adaptable, cannot increase GLUT-1 levels and may even experience a decrease, further impairing their glucose uptake.
Burning ketones for energy instead of glucose reduces the production of reactive oxygen species (ROS), minimizing oxidative damage associated with chronic diseases. This metabolic shift from carbohydrate to fat burning can potentially lower the risk of various chronic conditions. Ketogenic diets, which promote ketone production, are considered neuroprotective, protecting brain cells from damage and exhibiting anti-inflammatory properties.
The Role of Glutamine
Most cancer cells thrive on a combination of glucose and the amino acid glutamine. However, some cancer cells can survive without glucose, efficiently utilizing glutamine as a primary fuel source. Dr. Seyfried recommends a low-calorie ketogenic diet consisting of approximately 80% fat and 20% protein and carbohydrate to force cells to burn fat for energy. This diet provides sufficient protein for cellular function without excess amino acids like glutamine.
The goal is to shift the body's metabolism from glucose to ketone utilization. Fat molecules break down into fatty acids (convertible to ketones) and glycerol (convertible to glucose). While carbohydrates are most effective at raising blood sugar, proteins can also contribute via gluconeogenesis.
Practical Considerations for Ketogenic Diets
Individuals following strict ketogenic diets for seizure control or cancer management must meticulously weigh and measure food intake and monitor blood sugar and ketone levels daily using specialized meters. Dr. Seyfried suggests maintaining blood sugar levels between 55-65 mg/dL and ketone levels above 4.0 mM. This can be achieved through fasting (water only) for 3-5 days or by limiting carbohydrate intake to less than 12 grams per day and protein intake to 0.8-1.2 grams per kg body weight per day. Caloric intake should be fine-tuned based on daily test results, considering individual metabolic differences.
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Surgical debulking may be more effective after a few weeks on the ketogenic diet, if time permits. Medications, particularly diuretics, insulin, and blood sugar-lowering drugs, need close monitoring by a physician due to the diet's potential impact on dosages. Steroid medications like dexamethasone can interfere with the diet's effectiveness by raising blood sugar.
Designing a nutritionally adequate ketogenic diet requires expertise, and guidance from experienced professionals is recommended.
Immunotherapy and Diet
Over the past decade, there has been a noticeable increase in clinical research integrating immunotherapy, diet, and supplementation in cancer therapy. The cancer immunotherapy landscape is driven by innovative strategies, including therapeutic monoclonal antibodies, immune checkpoint inhibitors (ICIs), cancer vaccines, and adoptive cell transfer techniques. These approaches range from overall immune system activation to precise, targeted actions.
ICIs, a significant subgroup of monoclonal antibodies, target immune checkpoint proteins that regulate T-cell activation. Resistance to ICIs can be intrinsic, related to tumor cell alterations, or extrinsic, influenced by factors like the tumor microenvironment, host characteristics, and diet.
The Role of Diet in Immune Cell Functioning
Obesity and metabolic disorders disrupt macrophage activation, leading to harmful inflammation. Macrophage responses are regulated by classical (M1) and alternative (M2) activation programs. Chronic inflammation, influenced by diet, can impact cancer development. Studies indicate that a vegetables-rich diet is linked to a reduced inflammatory profile. The dietary composition of fatty acids influences cytokine production.
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The Dietary Inflammatory Index (DII) was created to classify foods negatively affecting the body’s inflammatory processes. Incorporating foods with lower DII scores, such as fruits, vegetables, whole grains, lean proteins, healthy fats, and specific spices, can effectively reduce systemic inflammation and mitigate the risk of cancer development. Diets rich in omega-3 fatty acids and high-fiber content have been linked to improved outcomes in cancer patients undergoing immunotherapy.
Dietary and Nutritional Strategies to Enhance Immunotherapy Effectiveness
Consuming fibrous foods as prebiotics in the gut influences mucosal immune functions, reducing the risk of enteric inflammation by elevating anti-inflammatory cytokines and decreasing proinflammatory cytokines and the systemic immune response. Undigested food can be converted into short-chain fatty acids (SCFAs), like butyrate, which the gut absorbs, alleviating inflammatory disorders by boosting T-regulatory cell (Treg) numbers and reducing IFN-γ levels. A fiber-rich diet proves beneficial when using ICIs, likely due to the increased SCFAs that stimulate immune cell differentiation and function.
The ketogenic diet (KD) involves obtaining the majority of energy from fat rather than carbohydrates. A KD has been observed to lower glucose levels, thereby reducing lactate production by glycolytic cancer cells. KD has been found to increase the CD4 + T-cell population and decrease Tregs in animals compared to controls. KD has emerged as a potential adjuvant in cancer immunotherapy, positively impacting ICI responsiveness.
3-Hydroxybutyrate, the principal ketone body, has been shown to induce T-cell-dependent tumor growth retardation in aggressive tumor models. This antineoplastic effect prevents immune checkpoint blockade-linked PD-L1 upregulation on myeloid cells, promoting the expansion of CXCR3 + T cells, and induces gut microbiota compositional changes.
While some anticancer immunotherapies benefit from very low carb or ketogenic diets, high-fat diets may worsen therapy outcomes. A patient’s nutritional state, especially their fat intake, significantly affects how they respond to anticancer therapy.
Metabolic Confusion
Metabolic confusion, also known as calorie-shifting or calorie cycling, involves alternating calorie intake between higher and lower amounts. This strategy aims to prevent the body from slowing down its metabolism in response to long-term caloric restriction. However, research on its effectiveness is mixed.
Some studies suggest it may offer an alternative for individuals who struggle with consistent caloric restriction, while others find no significant difference between calorie shifting and calorie restriction in terms of weight loss and maintenance. Metabolic confusion may be more about adherence than metabolism.
While metabolic confusion offers flexibility, it's crucial to consider potential downsides, such as the risk of dramatically affecting blood sugar levels in individuals with diabetes. Additionally, focusing solely on calorie counts without considering food quality can lead to nutrient deficiencies and increased consumption of ultra-processed foods.
The GAPS Diet
The Gut and Psychology Syndrome (GAPS) diet is an elimination diet created by Dr. Natasha Campbell-McBride, theorizing that a leaky gut causes several conditions that affect the brain, such as autism spectrum disorder (ASD). The GAPS protocol is designed to help heal and seal the gut wall, prevent toxins from entering the bloodstream, and lower “toxicity” in the body. However, research on the effectiveness of the GAPS diet is limited.
The GAPS diet is a very restrictive protocol that requires cutting out many nutritious foods for long periods of time. It also provides little guidance on how to ensure your diet contains all the nutrients you need. Because of this, the GAPS diet may increase the risk of malnutrition. This is especially true for children who are growing fast and need a lot of nutrients, since the diet is very restrictive.