Known as the UNIVERSAL antioxidant (given that it’s both water- and lipid- soluble), this antioxidant is present in virtually every type of living cell in the human body as it is manufactured in mitochondria. After initial synthesis, ALA is covalently bonded through lysyl residues to various enzyme complexes in order to facilitate important redox reactions.
Systemically, ALA and its reduced counterpart dihydrolipoic acid (DHLA) possess a wide range of antioxidant and anti-inflammatory properties including: the scavenging of ROS, metal chelation, repairment of oxidative damage, and the regeneration of endogenous antioxidants such as vitamin E and glutathione. Consequently, these characteristics have potential to be used therapeutically to treat various conditions.
Is ALA the Universal Skin Care Dud?
Ironically however, for such a universal compound, there is a serious deficit in the amount of research supporting the topical use of ALA. Compared to the water-soluble only L-ascorbic acid, the difference between the two’s collection of supporting research is rather vast. Lacking in both in vitro AND in vivo documentation, the only (mildly) meaningful study is one that involved comparing a 5% ALA cream against a placebo. While the study was double-blinded and randomized, the results weren’t too impressive. The single skin attribute that exhibited a statistically significant change (~10%) was skin roughness. But honestly, that’s it?!
As if ALA needed more bashing, in a study published in the Journal of Investigative Dermatology (the most prestigious and impacting PEER-REVIEWED dermatological journal), the Skinceuticals-associated team of physicians at Duke University tested the efficacy of 5% ALA against 15% L-ascorbic acid (vitamin C) and 1% D-alpha-tocopherol (vitamin E). (I only mention the journal and the school because there are obvious conflicts of interests). The in vivo study revealed that while the Skinceuticals formulation (vitamins C and E) provided significant protection against UVB-induced damage (measured by erythema and sunburn cells), the Perricone MD formulation (ALA) had no effect. And even though vitamins C, E, and ALA are “network” antioxidants (ALA regenerates vitamin E; vitamin E regenerates vitamin C), the addition of 5% ALA to the other formulation did not increase performance. Talk about a letdown!
Even More Derping
The authors suggest that the reasons why ALA isn’t effective as a topical antioxidant, is due to the following:
- ALA’s antioxidant potential is at least partially dependent on its conversion to its more potent, but unstable conjugate: DHLA. While both dihydrolipoamide dehydrogenase and glutathione reductase can reduce ALA to DHLA, the two reactions are very inefficient and occur slowly. Furthermore, it is unclear whether or not ALA, whose free “unbound” form has little presence in living tissue, can even access the mitochondrial compartment (cristae)—the location of physiologically-relevant “bound” ALA, in order to perhaps reinforce the endogenous supply of ALA.
- When ALA is oxidized after reacting with a free radical, its one-electron oxidation product is strongly pro-oxidant, and is capable and likely to cause free radical damage to surrounding cellular and tissue components, including other antioxidant systems. So even if ALA has some clinical potential as an antioxidant, its destructive tendencies may partially negate the overall influence. In comparison, the ascorbyl (vitamin C) radical, has a relatively low pro-oxidant potential that tends to react with itself, rather than attacking neighboring compounds.
- When ALA is administered systemically, it remains in plasma for only 30 or so minutes. After that, it is rapidly cleared by the liver. A similar clearance may also occur after percutaneous absorption, though it is unlikely that a significant concentration of topical ALA will penetrate into the bloodstream, making this “reason” less relevant.
Alpha Lipoic Acid Summary
Overall, while ALA may be both water- and lipid-soluble, and is ubiquitously present in its enzymatically-bound form, the benefits of including and depending on ALA to provide significant antioxidant protection, are few if any. Therefore, it is not recommended to incorporate too many ALA-containing products into your routine. There are plenty of other multi-tasking antioxidants that actually deserve your attention.