Alpha-lipoic acid has been found to enhance glucose uptake into skeletal muscle in animal models. Studies have also found that the co-ingestion of carbohydrate along with creatine increases muscle creatine uptake by a process related to insulin-stimulated glucose disposal. The purpose of this study was to determine the effect of alpha-lipoic acid on human skeletal muscle creatine uptake by directly measuring intramuscular concentrations of creatine, phosphocreatine, and adenosine triphosphate when creatine monohydrate was co-ingested with alpha-lipoic acid. Muscle biopsies were acquired from the vastus lateralis m. of 16 male subjects (18-32 y) before and after the experimental intervention. After the initial biopsy, subjects ingested 20 g x d(-1) of creatine monohydrate, 20 g x d(-1) of creatine monohydrate + 100 g x d(-1) of sucrose, or 20 g x d(-1) of creatine monohydrate + 100 g x d(-1) of sucrose + 1000 mg x d(-1) of alpha-lipoic acid for 5 days. Subjects refrained from exercise and consumed the same balanced diet for 7 days. Body weight increased by 2.1% following the nutritional intervention, with no differences between the groups. There was a significant increase in total creatine concentration following creatine supplementation, with the group ingesting alpha-lipoic acid showing a significantly greater increase (p < .05) in phosphocreatine (87.6 --> 106.2 mmol x kg(-1) dry mass [dm]) and total creatine (137.8 --> 156.8 mmol x kg(-1) dm). These findings indicate that co-ingestion of alpha-lipoic acid with creatine and a small amount of sucrose can enhance muscle total creatine content as compared to the ingestion of creatine and sucrose or creatine alone.