The ketogenic diet (KD), characterized by high fat and very low carbohydrate intake, has gained popularity for weight loss and potential health benefits. Originally used to manage epilepsy in children, its application in cancer therapy has become a topic of increasing interest. While some studies suggest potential benefits such as slowed tumor growth and improved response to chemotherapy, others raise concerns about promoting metastasis. This article explores the complexities of the ketogenic diet in the context of cancer, examining its potential benefits, associated risks, and important considerations for cancer patients.
Historical Context and Mechanisms of the Ketogenic Diet
As early as 500 BC, fasting was recognized as an effective treatment for various medical ailments. In 1910, Guelpa and Marie proposed fasting as an antiepilepsy treatment. Woodyatt noted in 1921 that starvation or high-fat, low-carbohydrate diets in individuals without significant medical comorbidities led to the production of acetone and β-hydroxybutyrate, energy sources produced by the liver in the absence of glucose. The term "ketogenic diet" was later coined by Wilder and Peterman, who formulated the fat-to-carbohydrate ratio still used today, consisting of 1 g protein per kg of body weight in children and 10 to 15 g carbohydrates daily, with fat making up the remainder of calories.
The ketogenic diet mimics the fasting state, where the body responds to the lack of glucose by producing ketones for energy. Normally, the body breaks down carbohydrates into glucose to fuel our cells. With high carbohydrate and glucose intake, the pancreas increasingly secretes more insulin, which promotes the interaction of growth hormone receptors and growth hormones to produce insulin-like growth factor 1 (IGF-1) in the liver, promoting cell growth and proliferation, which can be detrimental to patients with cancer. In KDs, the 4:1 ratio of high fat to low carbohydrates mimics the metabolic effects of starvation. These diets slow cancer by inhibiting insulin/IGF and downstream intracellular signaling pathways, such as phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR). Ketogenic diets also amplify adenosine monophosphate-activated protein kinase (AMPK), which inhibits aerobic glycolysis and suppresses tumor proliferation, invasion, and migration.
Potential Benefits of the Ketogenic Diet in Cancer Therapy
Slowing Tumor Growth
Previous research has suggested that the ketogenic diet may slow tumor growth. Braunstein noted in 1922 that glucose disappeared from the urine of patients with diabetes after a cancer diagnosis, suggesting that glucose is recruited to cancerous areas where it is consumed at higher than normal rates. Nobel laureate Otto Warburg later found that cancer cells thrive on glycolysis, producing high lactate levels even in the presence of abundant oxygen. The resulting tumor dependence on glucose can be exploited with KD use.
A recent clinical trial found that patients with breast cancer who followed a ketogenic diet for 12 weeks had a better response to chemotherapy, such as reduced tumor size and downstaging, compared to those in a control diet group. Ho and colleagues found that a low carbohydrate, high protein diet slows tumor growth and prevents cancer initiation. A possible explanation is that healthy tissue nutrition selectively delays tumor growth, while cancer cells are deprived of nutrition (carbohydrates).
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Improved Response to Chemotherapy
Both intermittent fasting and the keto diet have shown some benefit to patients going through chemotherapy, such as a reduction in some drug toxicity and improved quality of life.
Metabolic Effects
When glucose is scarce, the body senses the need to make an alternative form of energy for cells. The liver then produces ketones and fatty acids, which provide for normal cells but do not benefit cancer cells. Cancer cells have dysfunctional mitochondria and possibly electron transport chain defects, which disrupt normal adenosine triphosphate (ATP) production from the mitochondria. Excess lactate production, which is part of the Warburg effect, compensates for ATP production defects caused by dysfunctional mitochondrial oxidative phosphorylation. Overexpression of glucose transporters 1 and 3 (Glut-1, Glut-3) also occurs in many cancers and corresponds to the degree of glucose uptake in aggressive tumors, as seen on positron emission tomography (PET). Overexpression of hexokinase, the rate-limiting enzyme of glycolysis, further drives production of pyruvate and lactate, which cause reactive oxygen species damage.
Risks and Concerns Associated with the Ketogenic Diet in Cancer
Increased Risk of Tumor Metastasis
A new study by researchers at the Herbert Irving Comprehensive Cancer Center (HICCC) found that the ketogenic diet may increase the risk of tumor metastasis. In a mouse model of breast cancer, mice fed with a ketogenic diet experienced significantly more lung metastases compared to those on a control diet. In vivo luminescence imaging of lung tumors (metastasized from breast cancer) in mouse models, comparing the keto diet (right image) and the control (left image).
The researchers found that the ketogenic diet-induced metastasis is dependent on a protein called BACH1. When knocking out BACH1 in breast cancer cells, later injected into mice, those cells lost the metastatic boost normally induced by the ketogenic diet. "The cancer cells detect that this place deprived of glucose is not nutritionally comfortable, so they want to escape. They don’t want to stay in the wrong place,” Gu says. The researchers are currently exploring the possibility of using compounds that suppress BACH1 to block metastasis.
Nutritional Deficiencies and Side Effects
Adhering to a keto diet can be challenging and may be particularly so for cancer patients, many of whom may be enduring side effects from treatment. Entering a state of ketosis requires following a strict diet-plan, comprised of high fat foods such as bacon, heavy cream, and butter, while simultaneously restricting other categories of food, such as starchy vegetables like sweet potatoes, whole grains, and certain fruits. This dramatic change in eating habits can lead to nausea and digestive upset in addition to unintentional weight loss and increased risk of malnutrition.
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It may be difficult for keto-dieters to meet their energy and protein needs, and the diet may cause long-term issues, including kidney damage, higher cholesterol levels, unintentional weight loss, bone loss, and certain vitamin and mineral deficiencies. There are concerns about providing protein to patients who are at risk for renal problems.
Weight Loss and Cachexia
Dieting is of concern to cancer patients worried about additional weight loss. The standard diet is made up predominantly of carbohydrates and is high in caloric value. A therapeutic weight plateau should follow initial weight loss with KD, in contrast to pathologic rapid weight loss in non-KD patients.
Keto Meal Plan for Cancer Patients
The keto meal plan for cancer patients is designed to support overall health with nutrient-rich, low-carb, high-fat foods. It focuses on meals that are easy to digest and nourishing for individuals undergoing cancer treatment. This plan takes into account the specific dietary needs of cancer patients, offering a keto approach that’s gentle yet effective. It’s about providing strength and comfort through food during a challenging time. The keto diet for cancer patients emphasizes low-carb, high-fat foods that may help manage energy levels and reduce inflammation during treatment. This guide is a valuable resource for integrating ketogenic eating into a cancer care regimen, focusing on meals that nurture and strengthen. It also includes easy keto meals for cancer patients, designed to be both simple to prepare and gentle on the digestive system.
Foods to eat:
- Non-Starchy Vegetables: Leafy greens, broccoli, cauliflower, and asparagus.
- Healthy Fats: Avocado, olive oil, coconut oil, and fatty fish for omega-3s.
- Lean Proteins: Chicken, turkey, fish, and tofu for protein needs.
- Low-Sugar Berries: Strawberries, blueberries, and raspberries in moderation.
- Fermented Foods: Yogurt, sauerkraut, and kimchi for gut health.
- Bone Broth: Nutrient-rich broth for hydration and minerals.
- Nuts and Seeds: Almonds, walnuts, and flaxseeds for healthy fats.
- Herbs and Spices: Turmeric, ginger, and garlic for anti-inflammatory properties.
Foods not to eat:
- High-Sugar Foods: Minimize intake of sugary items to control blood sugar levels.
- Processed Meats: Limit processed and cured meats with additives.
- Processed Foods: Avoid highly processed and refined foods.
- Excessive Dairy: Limit dairy intake and choose low-sugar options.
- High-Carb Foods: Minimize consumption of high-carb items for ketosis.
- Alcohol: Consume alcohol in moderation, if at all.
- Artificial Additives: Avoid artificial colors, flavors, and preservatives.
- Vegetable Oils: Opt for healthy fats like olive oil over vegetable oils.
Grocery list:
- Dairy & eggs
- Fresh grocery
- Meats
- Fish & seafood
- Plant based
- Dry goods
- Spices & sauces
Eggs, spinach, and mushrooms are staples that can be bought in bulk. Olive oil, salmon, and mixed greens are often cheaper when purchased in larger quantities. Avocado, lemon, and chicken breast can be more economical in bulk. Broccoli, cauliflower, and full-fat Greek yogurt are also more affordable in larger sizes.
Clinical Evidence and Trials
Fine and colleagues conducted a 4-week feasibility study of the low-carbohydrate modified Atkins KD (≤ 20 g of carbohydrates daily) in PET-positive advanced cancer patients with solid tumors. There was a correlation between insulin levels and ketosis but not IGF. Stable disease or partial remission (measured standardized uptake value) on PET-CT correlated with 3-fold higher ketosis (but not weight loss or reduced caloric intake) relative to patients with progressive disease.
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In the ERGO trial, Rieger and colleagues studied 20 relapsed glioblastoma patients who were on KD supplemented with plant oils. Calories were unlimited. The primary endpoint was percentage of patients who discontinued the diet. Mean weight loss was significant, but quality of life (QOL) was maintained. The investigators also studied the effects of KD alone or combined with bevacizumab in a mouse glioblastoma model.
In a pilot study, Schmidt and colleagues provided KD plus oil-protein shakes as snacks to 7 of 16 patients with a variety of advanced metastatic cancers. Mean weight loss was statistically significant, blood lipid or cholesterol levels remained stable, some QOL measures improved, and there were no severe AEs.
Schwartz and colleagues reviewed the cases of 32 glioma patients treated with energy restricted KDs -5 from case reports, 19 from a clinical trial by Rieger and colleagues, and 8 from Champ. They also reported on 2 of their own glioma cases treated with the energy-restricted KD and studied tissues for expression of key ketolytic enzymes.
The VA Pittsburgh Healthcare System safety that trial enrolled 17 patients, 11 of whom were evaluated. Mean weight loss was significant, and weight loss of ≥ 10% was noted in responders (stable or improved disease) compared with nonresponders. Three patients dieted longer than 16 weeks (survival, 80-116 weeks).
Duke University has initiated a randomized study (NCT00932672) of the Atkins diet and androgen deprivation therapy for patients with prostate cancer. Tel Aviv Sourasky Medical Center in Israel is recruiting previously treated chemoradiation patients with high-grade glial tumors for an open-label study (NCT01092247) of the efficacy of KD in preventing tumor growth and recurrence. St. Joseph’s Hospital and Medical Center (Phoenix, AZ) is recruiting newly diagnosed glioblastoma patients for a phase 1/2 prospective trial (NCT02046187) involving upfront resection followed by KD with radiotherapy and concurrent temozolomide, followed by adjuvant temozolomide chemotherapy. The primary endpoint is number of patients with AEs and the secondary endpoints are overall survival, time to progression, and QOL.