Singapore researchers have discovered that lipoic acid does not cross the blood brain barrier in rats.

In an effort to determine whether lipoic acid, which has in the past shown to affect brain tissue, might have some activity relevant to treating Alzheimer’s disease, the researchers administered LA to rats and measured its presence in their brains. LA was only found in trace amounts, indicating that it does not readily cross the blood brain barrier, and furthermore that LA’s effect on the brain must therefore be mediated by other factors, possibly due to its capacity to reactivate other circulating antioxidants.

Here’s the abstract:

Distribution study of orally administered lipoic acid in rat brain
tissues.

Brain Res. 2008 Nov 19; PMID: 19046949

Chng HT, New LS, Neo AH, Goh CW, Browne ER, Chan EC.

Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, 117543 Singapore.

Lipoic acid (LA), an essential cofactor for mitochondrial enzymes and a natural antioxidant, has been explored for the treatment of Alzheimer’s disease. However, lipoic acid distribution in brain has not been investigated via oral dosing in human subjects or animals. Therefore, we aim to investigate the distribution of orally administered LA from systemic circulation into rat brain tissues and understand the transport efficiency of lipoic acid across the blood- brain barrier. Brain and blood samples were obtained from male Lister Hooded rats at pre-defined time points after single and chronic oral dosing of LA at 50 mg/kg. Levels of LA were determined using liquid chromatography tandem mass spectrometry. An equilibrium dialysis method was employed to elucidate LA protein binding in brain and blood tissues. Basal endogenous levels of LA in control rats were found to fluctuate between 0.005 and 0.267 microM in blood and 0-0.024 microM in brain after correction for residual blood volume. Pharmacokinetic profiling demonstrated rapid biphasic elimination of LA in blood and poor distribution into various brain regions with levels ranging from 0.0009 to 0.0072 microM. The in vitro and in vivo LA brain:blood partition ratios were 0.1 and -0.01, respectively. Our results demonstrate for the first time that LA does not cross the blood-brain barrier readily and suggest that the antioxidant effect of LA in brain may not be due to its direct effect in the central nervous system.