Metabolic effects of arginine on malignant and non malignant tissues
In the only human study to date arginine supplementation stimulated tumour protein synthesis in patients with breast cancer. However, it is not known if these stimulatory effects of arginine are limited to breast cancer, and the mechanisms of its action are not well understood. Moreover it would be important to find out whether the action of arginine is selective for malignant tissues or if it can affect normal, healthy tissues. The first study investigated the effect of arginine supplements for 3 days on nitrogen balance and on the liver synthesis rate of albumin in healthy volunteers. The addition of arginine to the diet produced a remarkable nitrogen retention over the three days. No changes in the albumin synthesis rates were detected between the two dietary periods. No effects were observed on the protein synthesis, RNA content or transcriptional efficiency in a variety of the tissues when adult rats were supplemented with arginine for three days. In vitro studies using a human breast tumour cell line (MCF-7) showed that arginine is an essential nutrient for the proliferation of breast tumour cells. Neither the direct precursor for polyamine synthesis, ornithine, nor the polyamine putrescine could replace arginine for growth. Only citrulline could completely substitute arginine for protein synthesis and growth. The arginine:nitric oxide pathways did not seem involved in the stimulatory effects of arginine. The main reason for the high arginine requirement was found to be the production of the enzyme arginase. The final study investigated the in vivo effects of arginine supplements on human tumours. Arginine supplementation did not affect the tumour protein synthesis rates in patients with head and neck tumours, suggesting that not all human tumours are stimulated by arginine.