Grant Abstract: Metabolic Implications of Dietary Arginine Supplements

Grant Number: 1R55CA065502-01A2
PI Name: Peter Garlick
Project Title: Metabolic Implications of Dietary Arginine Supplements

Abstract: Dietary supplements of L-arginine have heen shown tO have a variety of potentially beneficial effects in animals and humans, including enhancement of the immune system, wound healing, recovery from surgery, and Inhibition of tumor growth. Consequently, arginine supplements have heen suggested for infection, trauma and cancer, as well as for a number of other conditions. However, the evidence of tumor inhibition obtained from cancer bearing animnls is paradoxical, with some studies indicating a stimulation rather than an inhibition of tumor growth by arginine. The only study to date in humans showed an enhancement of tumor protein synthesis and Ki67 expression when arginine supplements (3Ogid for 3d) were given to patients with breast cancer. In contrast, preliminary data from patients with head and neck cancer showed that arginine did not stimulate the tumor, suggesting that the effects of arginine supplements might be tumor type specific. Arginine supplements might therefore be used to advantage in some cancer patients to improve recovery from surgery, immunity and wound healing, but this surgery, immunity and wound healing, but this requires additional Knowledge of arginine's effects on human tumors other than those of the breast, as well as its effect on normal tissues. It is therefore proposed to investigate how arginine supplements influence protein synthesis rates and cell proliferation markers (Ki67 and proliferating cell nuclear antigen) in different malignant tumors and healthy tissues of surgical patients. Arginine supplements will be taken for three days and tissues will be sampled at surgery after injection of [2H5]phenyialanine. In a second experiment, tumors will he disaggregated and separate measurements made on malignant and tumor infiltrating cells, to examine whether it is the cancer or the host defences that are stimulated by arginine. A third experiment will test the assumption that the increase m tumor protein synthesis and cell proliferation resulting from arginine supplementation truly indicates a stimulation of tumor growth. In anir)l models of cancer, changes in tumor growth resulting from vaiiiations in dietary arginine intake will be correlated with changes in protein synthesis and cell proliferation. The ensuing knowledge will fill an existing void on the metabolic effects of dietary argliiine supplements on human tissues, and will provide information which is crucial if we are to realize the therapeutic potential of arginine, yet avoid harmful side effects.

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