Recently I read a very interesting publication named “Is There a Role for Carbohydrate Restriction in the Treatment and Prevention of Cancer?” This article originally was published in Nutrition and Metabolism in 2011 and can be found at http://www.medscape.com/viewarticle/757713_6 . The authors of the article are Rainer J. Klement (Department of Radiation Oncology, University hospital of Würzburg, D-97080 Würzburg, Germany) and Ulrike Kämmerer (Department of Obstetrics and Gynaecology, University hospital of Würzburg, D-97080 Würzburg, Germany).
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/IGF1 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 antitumorigenic properties of very low CHO ketogenic diets. In addition, many cancer patients exhibit an altered glucose metabolism 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 IGF1 signaling in tumorigenesis as well as altered dietary needs of cancer patients.
When defining the factors of a healthy lifestyle that aims at preventing a disease like cancer, a logical approach is to compare individuals that get the disease with those that don’t. Cancer, which might be considered a disease of civilization, has consistently been reported to be very rare among uncivilized hunter-gatherer societies. This observation makes sense from an evolutionary perspective from which it is reasonable to assume that the lifestyle factors that protect our genome against tumorigenesis have been selected for early in the history of the genus homo when humans lived as hunter-gatherers. In particular, the time since the neolithic revolution, which meant the transition from foraging and nomadism to agriculture and settlement, spans a fraction less than 1% of human history. Thus, the switch from the “caveman’s diet” consisting of fat, meat and only occasionally roots, berries and other sources of carbohydrate (CHO) to a nutrition dominated by easily digestible CHOs derived mainly from grains as staple food would have occurred too recently to induce major adoptions in our genes encoding the metabolic pathways. This is even more the case for the changes that occurred over the past 100 years, in particular the switch from labor in the field to a sedentary lifestyle and an increase in the consumption of easily digestible CHOs with high glycemic indices (GIs), leading to diseases of civilization that are strongly associated with the so-called Western way of life. Despite a large heterogeneity in regional occupation, modern hunter-gatherers share certain lifestyle factors that are not frequently met in Westernized societies, including regular physical activity, sun exposure, sufficient sleep, low chronic stress and the lack of foods that would also not have been available to our pre-neolithic ancestors. While there is already compelling evidence for the beneficial roles of regular physical activity and sufficient vitamin D in the prevention and treatment of cancer, the influence of the altered nutritional patterns in the Western diet is less clearly defined.
The scientist summarize their main findings from the literature regarding the role of dietary CHO restriction in cancer development and outcome.
- 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.
- 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 metabolic syndrome. Epidemiological and anthropological studies indicate that restricting dietary CHOs could be beneficial in decreasing cancer risk.
- 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.
- 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.
- Some laboratory studies indicate a direct antitumor 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.