Is There a Role for Carbohydrate Restriction in the Treatment and Prevention of Cancer?

Rainer J Klement; Ulrike Kämmerer

Disclosures

Nutr Metab. 2011;8(75) 

In This Article

Is There a Role for Carbohydrate Restriction in the Prevention of Cancer?

"Prevention of cancer" can refer to either the inhibition of carcinogenesis per se or - once that cells made the transition to malignancy - the sufficient delay of tumor growth, so that it remains undetected and asymptomatic during a subject's lifespan. There is evidence that even modest CHO restriction may influence both of these mechanisms positively through various pathways. The IGF1R-IR pathway has already been discussed: once a potentially carcinogenic somatic mutation has occurred, the probability for carcinogenesis of a cell that is borderline between apoptosis and malignancy might be raised by high levels of insulin and IGF1 in the microenvironment. Once a cell became malignant, high insulin and IGF1 levels might accelerate proliferation and progression towards a more aggressive, glycolytic phenotype. In rats treated with the carcinogen N-methyl-Nnitrosourea, it has been shown that lowering the CHO content of the diet from 60 E% to 40 E% with a simultaneous increase in protein was sufficient to lower postprandial insulin levels as well as decrease the appearance rate of tumors from (18.2 ± 1.3)%/wk to (12.9 ± 1.4)%/wk (p < 0.05), however with no statistically significant effect on tumor latency and weight measured after 10 wk.[143] Similarly, a recent study reported that NOP mice, which normally have a 70 - 80% chance of developing breast cancer over their lifetime due to genetic mutations, stayed tumor-free at 1 year of age when their calories from CHO were limited to 15%, while almost half of those on a 55% CHO diet developed tumors.[131] Notably, only 3 out of 11 mice in the 15% CHO group died with having a tumor compared to 7 out of 10 in the 55% CHO group; at death, significantly lower plasma insulin levels had been measured for the low CHO group. These results support the epidemiological[25,29,31,32] and in vitro [81,144] findings that high CHO diets, in particular those including high GI foods, promote mammary tumorigenesis via the sustained action of insulin.

Lower insulin levels may further increase the chance of intermittent ketosis, in particular if CHO restriction is combined with exercise, calorie restriction or intermittent fasting. Seyfried and Shelton[40] pointed out the possibility of ketone bodies to help in cancer prevention through their ability to protect the mitochondria from inflammation and ROS. Being more satiating than low-fat diets,[145,146] a low CHO diet would make it easier to avoid caloric overconsumption or to implement intermittent fasting as an additional lifestyle change.[147]

Avoidance of Chronic Inflammation

Another potential benefit of low CHO diets might lie in their influence upon inflammatory processes that take place within various tissues. Inflammation is a wellestablished driver of early tumorigenesis and accompanies most, if not all cancers.[148] Chronic, 'smouldering' inflammation can both cause and develop along with neoplasia. There is evidence that chronic intake of easily digestible CHOs is able to promote such an inflammatory state in leukocytes and endothelial cells.[94] In obese individuals[149] and healthy subjects who underwent eccentric exercise training,[150] the inflammatory state was further augmented postprandially through a high CHO intake, but not through high-fat, low CHO meals in the latter study. Maybe more importantly, even moderate CHO restriction has been shown to effectively target several important markers of atherosclerosis and type II diabetes, both of which are associated with chronic inflammation.[151–157] Forsythe et al. showed that in overweight individuals with dyslipidemia a very low CHO diet had a more favorable effect than a low fat diet in reducing several markers of inflammation.[158] Given these findings, it can be hypothesized that a diet with a low GL positively affects cancer risk through reducing postprandial hyperglycemia and the associated inflammatory response.

In this context, it is important to note that a low CHO diet offers further possibilities to target inflammation through omission or inclusion of certain foods. Usually, CHO restriction is not only limited to avoiding sugar and other high-GI foods, but also to a reduced intake of grains. Grains can induce inflammation in susceptible individuals due to their content of omega-6 fatty acids, lectins and gluten.[159,160] In particular gluten might play a key role in the pathogenesis of auto-immune and inflammatory disorders and some malignant diseases. In the small intestine, gluten triggers the release of zonulin, a protein that regulates the tight junctions between epithelial cells and therefore intestinal, but also blood-brain barrier function. Recent evidence suggests that overstimulation of zonulin in susceptible individuals could dysregulate intercellular communication promoting tumorigenesis at specific organ sites.[161]

Paleolithic-type diets, that by definition exclude grain products, have been shown to improve glycemic control and cardiovascular risk factors more effectively than typically recommended low-fat diets rich in whole grains.[162] These diets are not necessarily very low CHO diets, but focus on replacing high-GI modern foods with fruits and vegetables, in this way reducing the total GL. This brings us back to our initial perception of cancer as a disease of civilization that has been rare among hunter-gatherer societies until they adopted the Western lifestyle. Although there are certainly many factors contributing to this phenomenon, the evidence presented in this review suggests that reduction of the high CHO intake that accounts for typically > 50 E% in the Western diet may play its own important role in cancer prevention and outcome.

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