Current Research
Compared with normal mice, tumor-bearing mice placed on a low-carbohydrate diet had lower glucose, insulin, and lactic acid levels. 4 An in vivo microdialysis study of patients with head and neck cancers found decreased lactic acid levels in the tumor tissues after a 4-day KD. 13 Most early studies and case reports involving KD in cancer focused on brain tumors. 11,14-16 Human clinical studies on this diet in cancer care were limited to small, nonrandomized, brief trials (4-12 weeks) or single case studies (Table). 11,17-20
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. 17 In the ERGO trial, Rieger and colleagues studied 20 relapsed glioblastoma patients who were on KD supplemented with plant oils. 18 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 this mouse study, KD alone had no effect; however, it increased median survival from 52 to 58 days (P < .05) with bevacizumab.
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. 19 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. 18,20,21 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. Prolonged remission was noted from 4 months to more than 5 years in these case reports. 20
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). One of these patients was alive at 121 weeks. 22
The safety and feasibility data suggest that cancer patients can tolerate KD use. Investigators should consider combining the KD approach with standard treatment modalities, including chemotherapy and radiation.
Already investigators have conducted in vitro studies of the effect of gene expression of ketolytic and glycolytic enzymes within tumor tissue on KD response. Tumors expressing mutations in key mitochondrial oxidative phosphorylation enzymes were more likely to respond to KD use than were tumors without mutations. 16,23
