Alpha lipoic acid (ALA) is a cell-signalling nutrient that is a powerful activator of Nrf2.5 In combination with acetyl-l-carnitine, coenzyme Q10 and melatonin, ALA demonstrates activation of antioxidant gene expression, up-regulation of energy metabolism and mitochondrial biogenesis, and the maintenance of the structural integrity of the mitochondria.6 As well, a 2013 human cell culture study demonstrated that ALA increased the expression of the genes encoding detoxification processes in cells exposed to paraquot toxicity (paraquot is a poisonous herbicide that is linked to Parkinson’s disease).
Translocation of Nrf2 from the cytoplasm to the nucleus, where it activates a battery of antioxidant genes, is promoted by ALA administration. In studies investigating the anti-inflammatory effects of ALA, researchers found that it can attenuate the inflammatory responses in cardiac dysfunction and lung injury through Nrf2 activation, and it can directly suppress the activities of NF-kΒ, the signalling molecule that controls the body’s inflammatory cascade.7;8 ALA’s ability to concurrently induce Nrf2 activation and NF-kB suppression may prove effective as a future treatment for vascular disease, hypertension, and systemic inflammation.9
In combination with coenzyme Q10, ALA has been shown to provide a four-fold increase in tissue Nrf2 levels.10 As a chemopreventive agent, ALA can also attenuate the loss of glutathione (GSH) synthesis caused by age-associated loss of gene expression. As the body’s principal endogenous antioxidant, GSH status is critical to the health of the cell and loss of GSH will dramatically increase the level of oxidative damage. Animal-model studies show that ALA can increase both Nrf2 and GSH levels in aging rats, providing enhanced antioxidant protection and detoxification support.
Overall, these findings highlight ALA’s role as a critical cell-signalling molecule on several fronts: it is capable of up-regulating the synthesis of the cellular GSH; it induces the activation of Nrf2; it protects mitochondrial function; it induces mitochondrial biogenesis; and it attenuates inflammation by down-regulating the activity of NF-kΒ.
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