Abstract and Introduction
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.[1–4] 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.
Modern Hunter-gatherers' Diet
Data from 229 hunter-gatherer societies included in the revised Ethnographic Atlas indicate that hunter-gatherer diets differ from typical Western ones in basically two aspects: first, a strong reliance on animal foods (45–65% of energy or E%) and second, the consumption of low- GI plant foods such as vegetables, fruits, seeds and nuts. This is consistent with stable isotope studies of human fossils.[8,9] As a consequence, the amount and type of carbohydrates in the typical western diet differ markedly from the ones that our genes adapted to. In particular, Cordain and colleagues estimated that modern hunter-gatherers derived about 22–40 E% from CHOs and 19–30 E% from protein, which is lower and higher, respectively, than recommended by Western food agencies. Recently, Ströhle & Hahn confirmed that the energy derived from CHOs - despite being dependent upon geographic latitude and ecological environment - in modern hunter-gatherers is markedly lower than in Westernized societies. High CHO intake, in particular in the form of sugar and other high GI foods, has been linked to modern diseases like metabolic syndrome, Alzheimer's disease,[12,13] cataract and macula degeneration[14–16] and gout. Intriguingly, with the possible exception of Alzheimer's disease, the occurrence and prognosis of cancer seems positively associated with both the prevalence of these diseases[19–28] and the GI and glycemic load (GL) of the diet;[29–32] this implies a possible role of high CHO intake in cancer as well.
In this review, we are going to present some arguments that support the hypothesis that lowering the amount of CHOs in the diet can have direct beneficial effects on the prevention and treatment of malignant diseases. The main focus will be on very low CHO, ketogenic diets as an effective supportive therapy option for cancer patients.
Nutr Metab. 2011;8(75) © 2011 BioMed Central, Ltd.