A new protective mechanism for Alpha Lipoic Acid

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Melissa Peterson ● 2 min read

Recent experimental research shows alpha-lipoic acid (ALA) may have new protein targets within the mitochondria that are crucial for energy supply. The newly discovered mechanism suggests ALA supplementation to be an effective strategy for mitochondrial function in chronic inflammatory states. 

ALA has diverse antioxidant and anti-inflammatory functions. It is also a cofactor for key mitochondrial enzymes involved in glucose metabolism and energy production, and may be essential for energy metabolism. 

Previous animal research showed that ALA supplementation increased mitochondrial capacity, partially restored mitochondrial enzyme activity and increased ATP production, when in the presence of inflammatory induced nitrous oxide (NO). Other research also shows small molecular S-nitosothiols, which act as reservoirs and donors for NO, down-regulate mitochondrial function.[1,2]
NO is a soluble and highly diffusible gas generated by a wide variety of cells and required for endothelium-derived smooth muscle relaxation. NO regulates protein function through a process called S-nitrosylation and it is believed this process is important for key metabolic pathways. 

However, excess NO, produced in inflammatory states, is toxic to cells and, when unregulated, increases reactive nitrogen species (RNS) causing nitrosative stress. This type of stress can affect cell function and increase the potential of pathological processes, especially in endothelial cells, and may diminish oxidative phosphorylation and mitochondrial energy production. 

Due to the previous findings, researchers decided to test the theory that diminished mitochondrial enzyme function central to energy production, due to nitrosative stress, can be alleviated with ALA supplementation through S-nitrosylation regulation.[1]
The results showed NO adversely affected the function of a complex III enzyme in the electron transport chain and a subunit of alpha-ketoglutarate dehydrogenase complex (KDC), an important enzyme in the Krebs cycle. When ALA was introduced, it significantly reduced S-nitrosylation in both of these mitochondrial enzyme complexes and effectively restored mitochondrial enzyme activities inhibited by excess NO, while significantly increasing ATP production. 

The regulatory functions of ALA may now include altering protein S-nitrosylation and regulating the expression of some proteins affected by S-nitrosylation mechanisms. Glutathione (GSH) levels were also analysed and it is proposed that this new mechanism of ALA may be through the regulation of GSH, as this antioxidant protects mitochondrial complexes from NO-induced damage. 

The researchers concluded that the studies shed light on a new mechanism of antioxidant activity of ALA and suggest a strategy for the treatment of diseases in which chronic inflammation is involved. This is particularly important for conditions such as atherosclerosis and type 2 diabetes. 


  1. Hiller S, DeKroon R, Hamlett ED, et al. Alpha-lipoic acid supplementation protects enzymes from damage by nitrosative and oxidative stress. Biochimica et Biophysica Acta 2016;1860(1 Pt A):36-45. [Abstract
  2. Richardson G, Benjamin N. Potential therapeutic uses for s-nitrosothiols. Clin Sci (Lond) 2002;102(1):99-105. [Abstract]


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Melissa Peterson has been a writer and educator in the health and medical science fields for over 15 years. Naturopathically trained, Melissa also has postgraduate qualifications in literature research and reviewing. Her business, Words On Therapy, provides many services to industry including technical articles, white papers, blogs, SEO content, copywriting and research collation.