Abstract
Ketogenic diets are low carbohydrate (CHO), high fat diets that are currently very popular for weight loss. Since cancer cells typically consume far more glucose than normal cells, low CHO diets are currently being considered as possible therapeutic regimens to manage cancer. However, our understanding of the safety and efficacy of such CHO-restricted diets in the prevention and treatment of cancer is still in its infancy. In this perspective we provide an overview of the current state of knowledge regarding the use of low CHO diets in the prevention and treatment of cancer. We also highlight the gaps in our knowledge regarding the potential usefulness of low CHO diets in cancer. While pre-clinical rodent studies have provided convincing evidence that CHO restriction may be effective in reducing cancer growth, there has not been sufficient attention given to the effect of these low CHO diets, that are often high in fats and low in soluble fiber, on inflammation. This is important, given that different fats have distinct effects on inflammation. As well, we demonstrate that short chain fatty acids, which are produced via the fermentation of fiber by our gut microbiome, have more anti-inflammatory properties than β-hydroxybutyrate, a ketone body produced during nutritional ketosis that is touted to have anti-inflammatory activity. Since chronic inflammation is strongly associated with cancer formation, defining the type of fats in low CHO diets may contribute to our understanding of whether these diets may work simply by reducing glucose bioavailability, or via modulation of inflammatory responses.
Highlights
Low carbohydrate (CHO) diets restrict CHO intake while increasing fat and/or protein
We provide an overview of the current state of knowledge regarding the safety and efficacy of low CHO diets for cancer prevention and treatment
There is a need to evaluate the effect of different fatty acids in low CHO and ketogenic diets on inflammatory status, since this may help formulate a more optimal diet plan that facilitates weight loss, and acts to reduce inflammation
Summary
Low carbohydrate (CHO) diets restrict CHO intake while increasing fat and/or protein. A more extensive list of publications reporting the efficacy of CHO restrictive diets or ketogenic diets in slowing tumor growth in rodent model systems can be found in a recent review by Weber et al [24] Despite these promising results, there are other studies demonstrating that low CHO, high fat diets promote cancer progression [36]. They are metabolized for ATP generation more readily than longer chain fatty acids [43] From these studies we demonstrated that while CHO restriction alone was sufficient to reduce NNK-induced lung nodule formation, partial substitution of the fats typically consumed in a Western diet with fish oil produced a far more robust reduction in lung nodule formation [41]. Increased fat intake may stimulate bile acid secretion, required to emulsify fat and promote intestinal absorption, and this bile acid may be recycled in the liver to generate a secondary bile acid
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