Alpha-lipoic acid and L-acetyl carnitine are two nutritional supplements that have received increasing attention as potential neuroprotective interventions in neurodegenerative and other disease states. Alpha-lipoic acid/L-acetyl carnitine had been demonstrated to improve learning in aged beagles over 2 months of administration, and showed a trend to improve cognitive function in a mouse model of Alzheimer's disease (human apoE4 transgene). Moreover, alpha-lipoic acid/L-acetyl carnitine was neuroprotective in a mouse model of Parkinson's disease (rotenone-induced parkinsonism), with effects including decreased oxidative stress, and increased mitochondrial biogenesis. In fibroblasts derived from individuals with Alzheimer's disease, alpha-lipoic acid/L-acetyl carnitine reduced increased levels of oxidative stress. In healthy men exposed to intensive exercise, alpha-lipoic acid provided antioxidant effects systemically (decreased peroxidation). L-acetyl carnitine improved neuroimaging correlates of cerebral blood flow in 30 subjects with dementia. These nutritional supplements have been safe and well-tolerated, and they have been tested in age groups including children, up to the elderly. Alpha-lipoic acid had been successfully administered over an extended period in an open-label trial in Alzheimer's disease. Importantly, it appeared that the effects of alpha-lipoic acid and L-acetyl carnitine when administered together were significantly augmented (100-1000 times), as opposed to when administered separately. This therefore provided a strong rationale to test the two in combination.