A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model

Abstract

Summary A comparison has been made between the ability of long-chain triglycerides (LCT) and mediumchain triglycerides (MCT) to prevent weight loss induced by the cachexia-inducing colon adenocarcinoma (MAC16) and to reduce tumour size. There was no difference in calorie consumption or nitrogen intake between the various groups. When compared with a normal control high carbohydrate, low fat diet, animals fed MCT showed a reduced weight loss and a marked reduction in tumour size. In contrast neither weight loss nor tumour size differed significantly from the controls in animals fed the LCT diet. An elevated plasma level of 3-hydroxybuturate was found only in the animals fed the MCT diets. Administration of LCT caused an increase in the plasma level of FFA, which was not observed in the MCT group. These results suggest that diets containing MCT would provide the best ketogenic regime to reverse the weight loss in cancer cachexia with a concomitant reduction in tumour size.Weight loss is a common feature of many neoplastic diseases (De Wys, 1986) and appears to be independent of the tumour burden and often precedes clinical diagnosis. The end result of the continuing decline in nutritional status is the clinical syndrome of cancer cachexia. Patients with weight loss have a poorer response to chemotherapy and a shorter survival time than those without weight loss (De Wys et al., 1980).We have utilized the MAC 16 adenocarcinoma of the mouse colon as an experimental model of human cachexia, where weight loss arises from the metabolic effects of the tumour on the host (Bibby et al., 1987). Animals bearing the MAC16 tumour show weight loss at small tumour burdens (less than 1% of the host weight) and without a reduction in either food or water intake. Weight loss is characterized by a progressive loss of both body fat and muscle dry weight, which increases in direct proportion to the tumour burden (Beck & Tisdale, 1987). Although there is extensive mobilization of body fat reserves ketosis does not occur (Bibby et al., 1987). Ketonuria has also been shown not to occur in cancer patients . Since ketone bodies are believed to play an important role in the regulation of lean body mass during starvation we and others (Tisdale, 1982;Magee et al., 1979;Williamson & Matthaei, 1981) have suggested that a high fat/low carbohydrate ketogenic diet should also preserve lean body mass during cancer cachexia, and would not be expected to be utilized by a poorly vascularized tumour, which would depend primarily on glucose as an energy source. In addition 3-hydroxybutyrate has recently been shown to inhibit the lipolytic and proteolytic factors produced by the MAC16 tumour and which may be responsible for the cachexia (Beck & Tisdale, 1987). Such an approach has been vindicated since mice bearing the MAC16 tumour fed a diet in which up to 80% of the energy was supplied as medium-chain triglycerides (MCT) show a reduction in both the extent of weight loss and tumour weight . A ketogenic diet containing 70% MCT and supplemented with D-3-...

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“…While the diet had no effect on rats bearing the Walker 256 sarcoma [120], it decreased the cachectic weight loss in proportion to its fat content in mice bearing the mousespecific colon carcinoma MAC16 [121]. For the latter, they further proved an anti-cachectic effect of a ketogenic diet in which the MCTs were replaced with long chain triglycerides (LCTs), although to a somewhat lesser extent [122]. Contrary to LCTs, MCTs do not require transport in chylomicrones, but readily reach the liver where they are metabolized to yield high amounts of ketone bodies.…”