Effects of Short-Chain and Saturated Long-Chain Fatty Acids on Tumor Growth - In Vitro and Experimental in Vivo Effects

Current nutritional recommendations for patients having a malignancy tend to take into account that the metabolism of energy-yielding substrates is lipid-based, and that glucose utilization is severely impaired. Fat should thus be the preferred energy substrate. However, in order to determine which types of fat are either advisable or should be avoided, it is necessary to consider data from nutrient pharmacology. In the present review article, the effects of short-chain as well as saturated long-chain fatty acids on tumor growth are outlined. Short-chain fatty acids, in particular butyrate, interfere with tumor growth by both inhibiting proliferation and promoting cell differentiation and also apoptosis. In addition, angiogenesis, invasion and metastasis are reduced. These effects were consistently observed not only in many tumor cell lines, but also in vivo. They are mediated by an altered expression of regulatory proteins and caspases and are probably due to an inhibition of histone deacetylation. Since the half-life of butyrate is only about 6 minutes, tributyrin (glycerol tributyrate) may be used instead. Furthermore, butyrate becomes available from the bacterial fermentation of dietary fiber, e.g. of pectin in the gut. Saturated long-chain fatty acids, especially palmitate and stearate also decrease the proliferation rate of malignant cells and induce apoptosis, thus retarding tumor growth. An inhibition of both glycolysis and fatty acid synthesis in malignancies may be the predominant mechanisms of these effects. Saturated long-chain fatty acids such as palmitate and stearate are found particularly in milk, butter and several other dietary fats.