Background: The use of a high-calorie, high-carbohydrate, low-fat diet is currently the standard of nutrition for most cancer patients. However this diet may not be the best approach for slowing cancer growth. Increased fluorodeoxyglucose (18F-FDG) uptake seen in many aggressive tumors compared with noncancerous tissue suggests that cancer cells preferentially utilize glucose through glycolysis, and a low carbohydrate ketogenic diet may starve the tumor of its energy supply. Clinical data on the safety and feasibility of the ketogenic diet in advanced cancer patients are sparse with most data existing in animal studies and minimal human data.
Methods: We recruited 17 patients with advanced or metastatic solid tumors who declined or failed chemotherapy and offered them participation in this study. After a 2-day screening period, we instructed them on the modified Atkins style ketogenic diet, allowing 20 to 40 grams of carbohydrates per day, and provided advice on grocery shopping and menu planning with regular clinic visits beginning at baseline for 4 consecutive weekly visits followed by a visit every 4 weeks until a maximum of 16 weeks or premature termination. Physical exams and serum blood testing, including serum ketone (beta-hydroxybutyrate) measurements, plus quality of life (QOL) measurements were collected during these visits. We monitored for adverse effects (AEs) and collected data on feasibility, diet tolerability, and tumor response, using positron emission tomography/computed tomography scans at baseline, 4, 8, and 16 weeks.
Results: Eleven patients (aged 65 ± 11.7 years, weight 203 ± 4.98 lb proceeded with the trial, dieting between 4 to 16 weeks. The mean number of previous treatment failures was 1.7 ± .97. Tumor histology was diverse: 6 had adenocarcinoma (bile duct, prostate, colon, pancreas, lung), 4 had squamous cell carcinoma (lung, parotid, glottis), 2 had brain tumors (glioblastoma, astrocytoma), 1 had papillary carcinoma (thyroid), 1 had hepatocellular carcinoma, and 3 had melanomas. Six of 17 failed the screening process. At the end of the trial, patients demonstrated significant decrease in body weight and body mass index. No significant AEs were noted. Serum lipid profiles were not affected, and hematologic parameters remained stable. Patients who continued on the diet for 4 weeks or more (n = 6) experienced a trend in improved well-being and symptomatology, and at end of their trial, participation had no statistically significant deterioration in QOL. We saw no significant deterioration in social (P = .179), physical (P = .225), emotional (P = .313), financial difficulties (P = .347), cognitive (P = .195) and role functioning scores (P = .859) as well as in fatigue (P = 1.00), insomnia (P = .798), appetite (P = .269), constipation (P = .343), diarrhea (P = .347), and pain (P = .262) scores. At 4 weeks, 6 patients (54.5%) had stable disease. By 8 weeks, 5 patients (45.4%) had stable disease. At that point, 1 was withdrawn due to grade 3 weight loss, and 4 continued until 16 weeks. At 16 weeks, all 4 patients (36%) had stable or improved disease at the end of their trial participation. After completing the 16-week trial period, 4 patients opted to continue the ketogenic diet and were followed long term. Out of the 4 long-term patients, 1 (melanoma) died after 80 weeks; 1 (melanoma) resumed chemotherapy and remains alive with stable disease at 92 weeks of follow-up; 1 (lung cancer) died, stopped dieting and died after 40 weeks; and 1 (melanoma) remains free of disease at 70 weeks’ follow-up.
Conclusions: A modified ketogenic diet is safe and tolerable, in advanced cancer patients. Quality of life remained stable, and a trend toward improved symptom and functioning scores was observed. Tumor stabilization and prolongation of expected lifespans were observed in selected patients. Future randomized studies using the ketogenic diet in lieu of or in combination with standard chemotherapy is warranted.
