OBJECTIVE: To determine the efficacy of glycine propionyl-L-carnitine (GPLC) to decrease lipid peroxidation, elevate nitric oxide, and improve blood lipid profiles in human subjects. METHODS: Thirty untrained, normolipidemic subjects performed eight weeks of supervised aerobic exercise while supplementing GPLC at one of two doses (1 or 3 grams daily of PLC + glycine) or placebo, following random assignment in a double-blind manner. Fasting blood samples were analyzed at rest for malondialdehyde, nitric oxide, and lipids before and after the intervention. RESULTS: Malondialdehyde was decreased (p<0.05) from pre- to post-intervention with 1 g GPLC (1.08+/-0.24 vs. 0.69+/-0.25 micromol.L (-1)) and 3 g GPLC (0.94+/-0.18 vs. 0.66+/-0.17 micromol.L (-1)), but did not change statistically (p>0.05) with placebo (1.12+/-0.21 vs. 1.03+/-0.23 micromol.L (-1)). Nitric oxide was increased (p<0.05) from pre- to post-intervention with 3 g GPLC (21.34+/-2.27 vs. 29.46+/-3.61 micromol.L (-1)), but did not change statistically (p>0.05) with 1 g GPLC (23.22+/-4.13 vs. 26.24+/-4.32 micromol.L (-1)) or placebo (24.31+/-3.90 vs. 26.14+/-4.11 micromol.L (-1)). No main effects or interaction effects were noted for blood lipids (p>0.05). CONCLUSION: GPLC supplementation combined with eight weeks of aerobic exercise decreases lipid peroxidation and elevates nitric oxide, but does not further improve blood lipid profiles in normolipidemic subjects.