Modified Atkins diet in advanced malignancies - final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System

Abstract

BackgroundDysfunctional mitochondrial processes limit malignant cells ability to use energy from fatty acids and ketones. Animal studies using ketogenic diets for cancer show encouraging results. We tested the diet’s safety and feasibility in cancer patients across a broad variety of solid tumors.MethodsWe recruited 17 advanced cancer patients who were not on chemotherapy. They consumed 20 to 40 g of carbohydrates daily with evaluations performed weekly until week 4, then every 4 weeks until 16 weeks. Quality of life questionnaires monitored for tolerability and compliance. Positron emission/computerized tomography was ordered at baseline, 4,8 and 16 weeks. Student t-testing evaluated differences between baseline and last visit scores for quality of life, weight, body mass index, and serum parameters. Correlations between weight loss and serum ketones, glucose, lipids and creatinine were done. Two-tailed unpaired t-testing of the mean weight loss compared responders against non-responders.ResultsEleven out of seventeen enrolled patients were evaluable. Mean age was 65+/- 11.7 years, weight 203 +/- 4.98 lbs. (92 ± 2.3 kgs.) and previous treatment failures was 1.7, +/- 0.97. All lost significant weight with hematologic, biochemical and lipid tests remaining stable. Quality of life scores slightly improved. At 4,8 and 16 weeks, six (54.5 %), five (45.4 %) and four (36 %) patients were stable or improved. We observed no correlations between serum glucose, ketones or lipids. Clinical response did not correlate with ketosis or glycemia. Responders (stable disease or partial responders) lost statistically more weight than non-responders. Dietary compliance was difficult. Only three patients continued dieting past 16 weeks. Out of these, two patients developed brain metastases and were on steroids. They survived 80 and 116 weeks respectively. The third patient underwent residual tumor resection and has no disease at 131 weeks.ConclusionsModified Atkins diets are safe and feasible in advanced cancer. Quality of life was preserved. Patients who lost at least 10 % of their body weight responded the best. Steroid intake affected optimal ketone and glucose levels. Despite this, survival improved in some melanoma and lung cancer patients. Further studies are recommended.Trial registrationClinicaltrials.gov NCT01716468. Registered on September 18, 2012

A systematic review of the use of ketogenic diets in adult patients with cancer

“…Seven studies reported on changes in blood lipids. Four studies did not observe any significant changes in triglycerides, cholesterol, high‐density lipoprotein and low‐density lipoprotein . One study reported a significant drop in low‐density lipoprotein and high‐density lipoprotein .…”

“…All studies investigated the effect of oral KD; however, there was considerable variation in how the diet was delivered. Three studies followed a traditional KD with a 4 : 1 or 3 : 1 fat (F) to carbohydrate CHO) + protein (P) kg m –2 (F : CHO + P) , two studies used a ratio of F : CHO + P between 0.7 : 1 and 1.8 : 1 , three studies used a modified Atkins diet (20–40 g day −1 CHO) , two studies used a low glycaemic index diet (<70 g day −1 CHO) and one study used a Paleolithic KD with a F : P ratio of 2 : 1 .…”

“…We included three early-phase single-arm clinical trials (28)(29)(30) , three prospective cohort studies (31)(32)(33) , one retrospective review (34) and four case reports (6,(35)(36)(37) . Only two studies were designed to compare intervention and control groups: one retrospective review (34) and one prospective study (33) .…”

“…In three studies, the cancer stage ranged from an early to a more advanced stage (6,28,36) . Five studies involved participants with brain cancer (30,(33)(34)(35)37) , one study involved rectal cancer (6) and five studies had participants with mixed cancer sites (28,29,31,32,36) . The duration of intervention ranged from 2.4 to 134.7 weeks.…”

“…(meta-analysis) (n = 0) studies used a modified Atkins diet (20-40 g day À1 CHO) (29,34,35) , two studies used a low glycaemic index diet (<70 g day À1 CHO) (30,31) and one study used a Paleolithic KD with a F : P ratio of 2 : 1 (6) . All studies encouraged participants to eat to satiety; however, only two studies reported on energy and macronutrient intake (32,36) .…”