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

Jocelyn L Tan-Shalaby,Dana Genovese,Andrew D Liman,Vida A Passero,Krystal Edinger,Jennifer Carrick,Rashmikant B Shah

doi:10.1186/s12986-016-0113-y

Jocelyn L Tan-Shalaby, Dana Genovese + Show 5 more

Open Access

https://doi.org/10.1186/s12986-016-0113-y

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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

Highlights

Dysfunctional mitochondrial processes limit malignant cells ability to use energy from fatty acids and ketones
Aerobic fermentation was considered a compensatory response to an underlying deficiency in oxidative phosphorylation that could arise from any number of deficiencies in the structure, function or number of mitochondria [11]
We investigated quality of life parameters and used a modified Atkins diet as the standard diet for this trial

Summary

Introduction

Dysfunctional mitochondrial processes limit malignant cells ability to use energy from fatty acids and ketones. Emerging evidence indicates that ketogenic diets can have therapeutic potential for a broad range of cancers in preclinical animal models and in patients [1,2,3,4,5,6]. Warburg first showed that aerobic fermentation (lactate production in the presence of oxygen) was a hallmark feature of many cancers [9]. This unusual metabolism of tumor cells later became known as the Warburg effect [10]. KDs could put tumor cells under metabolic stress in lowering the availability of glucose and in elevating blood ketone bodies that require functional mitochondria for metabolism [13, 14]

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