Effect of a ketogenic diet on the clear cell renal cell carcinoma cell growth
Clear cell renal cell carcinoma (ccRCC) is characterized by a metabolic feature : an energy production by aerobic glycolysis at the expense of oxydative phosphorylation . Ketogneic diet (KD), which consists of high fat and low carbohydrate intakes, could bring required energy substrates to healthy cells while depriving tumor cells of glucose.
We study the effect of ketogenic diet on a ccRCC cell line : ACHN. Fifteen CD-1 nude mice received a sub-cutaneous xenograft of ACHN cells, and were then split into 3 feeding groups and fed either a standard diet (SD group, n=5), a 2:1 ketogneic diet (KD 2:1 group, n=5) or a 4:1 ketogenic diet (KD 4:1 group, n=5) ad libitum. Tumor growth, blood glucose and blood ketone levels were measured weekly for 8 weeks.
Ketosis was quickly reached. The mean blood ketone level was 0,86 mmol/L in SD group, 1,07 mmol/L in KD 2:1 group and 1,21 mmol/L in KD 4:1 group (p) (Fig.1). The mean 8-week tumor growth was 351% in SD group, 65% in KD 2:1 group and 66% in KD 4:1 group (p=0,01) (Fig.2). There was no difference in weight increase between the 3 groups.
This study showed that ketogenic diet can slow ccRCC tumor growth in a mouse model, without any difference of result between 2:1 or 4:1 KD. These outcomes have to be verified in other cell lines, and signalling pathways need to be understood by transcriptomic and metabolomic analyses, before starting clinical trials.
Funding:  The Cancer Genome Atlas Research Network, “Comprehensive molecular characterization of clear cell renal cell carcinoma,” Nature, vol. 499, no. 7456, pp. 43–49, Jul. 2013.