Is there a role for carbohydrate restriction in the treatment and prevention of cancer?

Rainer J Klement and Ulrike Kammerer

Nutrition & Metabolism 2011, 8:75 doi:10.1186/1743-7075-8-75

Published: 26 October 2011

Abstract

Over the last years, evidence has accumulated suggesting that by systematically reducing the amount of dietary carbohydrates (CHOs) one could suppress, or at least delay, the emergence of cancer, and that proliferation of already existing tumor cells could be slowed down. This hypothesis is supported by the association between modern chronic diseases like the metabolic syndrome and the risk of developing or dying from cancer. CHOs or glucose, to which more complex carbohydrates are ultimately digested, can have direct and indirect effects on tumor cell proliferation: first, contrary to normal cells, most malignant cells depend on steady glucose availability in the blood for their energy and biomass generating demands and are not able to metabolize significant amounts of fatty acids or ketone bodies due to mitochondrial dysfunction. Second, high insulin and insulin-like growth factor (IGF)-1 levels resulting from chronic ingestion of CHO-rich Western diet meals can directly promote tumor cell proliferation via the insulin/IGF-1 signaling pathway. Third, ketone bodies that are elevated when insulin and blood glucose levels are low, have been found to negatively affect proliferation of different malignant cells in vitro or not to be usable by tumor cells for metabolic demands, and a multitude of mouse models have shown anti-tumorigenic properties of very low-CHO ketogenic diets. In addition, many cancer patients exhibit an altered glucose metabolim characterized by insulin resistance and may profit from an increased protein and fat intake. In this review, we address the possible beneficial effects of low CHO diets on cancer prevention and treatment. Emphasis will be placed on the role of insulin and IGF-1 signaling in tumorigenesis as well as altered dietary needs of cancer patients.

Conclusions

We summarize our main findings from the literature regarding the role of dietary CHO

restriction in cancer development and outcome.

(i) Most, if not all, tumor cells have a high demand on glucose compared to benign

cells of the same tissue and conduct glycolysis even in the presence of oxygen (the

Warburg effect). In addition, many cancer cells express insulin receptors (IRs) and

show hyperactivation of the IGF1R-IR pathway. Evidence exists that chronically

elevated blood glucose, insulin and IGF1 levels facilitate tumorigenesis and

worsen the outcome in cancer patients.

(ii) The involvement of the glucose-insulin axis may also explain the association of

the metabolic syndrome with an increased risk for several cancers. CHO restriction

has already been shown to exert favorable effects in patients with the metabolicsyndrome. Epidemiological and anthropological studies indicate that restricting

dietary CHOs could be beneficial in decreasing cancer risk.

(iii) Many cancer patients, in particular those with advanced stages of the disease,

exhibit altered whole-body metabolism marked by increased plasma levels of

inflammatory molecules, impaired glycogen synthesis, increased proteolysis and

increased fat utilization in muscle tissue, increased lipolysis in adipose tissue and

increased gluconeogenesis by the liver. High fat, low CHO diets aim at accounting

for these metabolic alterations. Studies conducted so far have shown that such

diets are safe and likely beneficial, in particular for advanced stage cancer patients.

(iv) CHO restriction mimics the metabolic state of calorie restriction or – in the case of

KDs – fasting. The beneficial effects of calorie restriction and fasting on cancer

risk and progression are well established. CHO restriction thus opens the

possibility to target the same underlying mechanisms without the side-effects of

hunger and weight loss.

(v) Some laboratory studies indicate a direct anti-tumor potential of ketone bodies.

During the past years, a multitude of mouse studies indeed proved anti-tumor

effects of KDs for various tumor types, and a few case reports and pre-clinical

studies obtained promising results in cancer patients as well. Several registered

clinical trials are going to investigate the case for a KD as a supportive therapeutic

option in oncology.