Calorie restriction, but not a ketogenic diet, inhibits the growth of tumours in a mouse model of pancreatic cancer, found a study in Nature.
Although both dietary interventions are thought to alter tumour growth, the latest study indicates that calorie restriction limits growth by altering lipid levels in tumours. Low glycaemic diets, such as calorie restriction and a ketogenic diet, minimise spikes in blood sugar and insulin levels, an effect that is linked to the inhibition of tumour growth in some animal models. Whether other metabolic changes associated with these diets might affect tumour growth is less well understood.
Matthew Vander Heiden and colleagues from Massachusetts Institute of Technology, Cambridge, studied the effects of calorie restriction and a ketogenic diet in a pancreatic cancer mouse model, and found that only calorie restriction causes inhibition of tumour growth.
Calorie restriction, but not a ketogenic diet, lowers lipid levels in plasma and tumours, and reduces the activity of an enzyme that is required for cancers to adapt to low-lipid environments, which leads to an imbalance in unsaturated and saturated fats. Although a ketogenic diet also impairs the activity of this enzyme, this diet increases lipid availability and thereby maintains unsaturated/saturated fat ratios that favour tumour growth.
In addition to the mouse experiments, the authors evaluated associations between dietary patterns and survival time among 1,165 patients with pancreatic cancer. The preliminary findings suggest that diets higher in fat and lower in carbohydrates might be associated with longer survival times. However, low glycaemic diets are not suitable for all patients with cancer, the authors note; they can be difficult to maintain and tolerate, and weight loss may affect treatment options.
Further investigations into how diet can influence metabolic changes that affect tumour growth may guide strategies to incorporate the use of diets or treatments that mimic these effects into established cancer treatment approaches, the authors conclude.
Low glycaemic diets alter lipid metabolism to influence tumour growth
Evan C. Lien, Anna M. Westermark, Yin Zhang, Chen Yuan, Zhaoqi Li, Allison N. Lau, Kiera M. Sapp, Brian M. Wolpin & Matthew G. Vander Heiden
Published in Nature on 20 October 2021
Dietary interventions can change metabolite levels in the tumour microenvironment, which might then affect cancer cell metabolism to alter tumour growth. Although caloric restriction (CR) and a ketogenic diet (KD) are often thought to limit tumour progression by lowering blood glucose and insulin levels, we found that only CR inhibits the growth of select tumour allografts in mice, suggesting that other mechanisms contribute to tumour growth inhibition.
A change in nutrient availability observed with CR, but not with KD, is lower lipid levels in the plasma and tumours. Upregulation of stearoyl-CoA desaturase (SCD), which synthesises monounsaturated fatty acids, is required for cancer cells to proliferate in a lipid-depleted environment, and CR also impairs tumour SCD activity to cause an imbalance between unsaturated and saturated fatty acids to slow tumour growth. Enforcing cancer cell SCD expression or raising circulating lipid levels through a higher-fat CR diet confers resistance to the effects of CR.
By contrast, although KD also impairs tumour SCD activity, KD-driven increases in lipid availability maintain the unsaturated to saturated fatty acid ratios in tumours, and changing the KD fat composition to increase tumour saturated fatty acid levels cooperates with decreased tumour SCD activity to slow tumour growth.
These data suggest that diet-induced mismatches between tumour fatty acid desaturation activity and the availability of specific fatty acid species determine whether low glycaemic diets impair tumour growth.
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