Antioxidant combination prevents memory and learning deficits

Combination of N-acetylcysteine, α-lipoic acid and α-tocopherol substantially prevents the brain synaptosomal alterations and memory and learning deficits of aged rats


Brain aging alters intrasynaptosomal Na+ and K+ concentrations in rats.
Aging alters rat brain synaptosomal membrane potential.
Intrasynaptosomal Ca2 + under basal incubation is raised in aged brain.
Antioxidant supplementation ameliorates the age-related synaptosomal changes.
Antioxidant supplementation partially prevents age-dependent learning deficits.


This study has compared several synaptosomal parameters in three groups of rats: young (46 months), aged (22–24 months) and antioxidant supplemented aged rats (antioxidant supplementation given with the diet as a combination of N-acetylcysteine, α-lipoic acid and α-tocopherol from 18 months onwards till 22–24 months). The synaptosomes from aged rat brain, in comparison to those of young animals, exhibit an increased membrane potential with altered contents of Na+ and K+ under basal incubation condition and in the presence of depolarizing agents. The intrasynaptosomal Ca2 + is also higher in aged than in young rat. These age-dependent changes in synaptosomal parameters are prevented markedly in the antioxidant supplemented group. When examined on T-maze, the aged animals are noticeably impaired in learning and memory functions, but the deficit is remarkably prevented in the antioxidant supplemented aged animals. It is suggested that the synaptosomal alterations partly contribute to the cognitive deficits of aged animals, and both are rescued by long-term antioxidant supplementation.

N-acetylcysteine has been mentioned many times on this blog (as well as in my book – see sidebar); tocopherol is a form of vitamin E, and alpha lipoic acid has similar properties as NAC: it raises glutathione levels and protects mitochondria. The three in combination prevent deterioration in the brains of aged rats, and of course there’s no reason they won’t do the same in humans.

Personally it looks to me like the combination of alpha lipoic and NAC is superfluous; either one or the other would probably do. Vitamin E should be supplemented with care, in other words, don’t over do it, and a combination of mixed natural tocopherols would be far better than synthetic, racemic alpha tocopherol.


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