Alpha-lipoic acid (ALA) is a molecule found in the mitochondria that acts as a cofactor for some enzymatic reactions related to cellular energy production and glucose metabolism. ALA is synthesized in the human body, but not in quantities that are large enough to meet the energy needs of the cell. ALA can be obtained from fruits and vegetables, such as spinach, broccoli, brussels sprouts, and tomatoes. Dietary sources of ALA exist as the R enantiomeric or structural form, which has been shown to have increased bioavailability and a better pharmacokinetic profile than the S enantiomer. ALA is involved in many roles in the human body, including glucose and lipid metabolism and it supports health during oxidative stress. ALA has also been shown to provide support in the presence of diabetic polyneuropathy (DPN).

ALA is perhaps most well-known for its role in the support of glucose metabolism. In addition to its role as a cofactor in metabolic pathways related to glucose, ALA has also been shown to augment the activity of certain proteins from insulin signaling pathways in preclinical studies, including the insulin receptor substrate 1, phosphatidylinositide 3 kinase, and protein kinase B. It also exhibits activity related to signaling molecules in the insulin and insulin-like growth factor-1 pathways.

Beyond blood sugar support, ALA has been shown to modulate the activity of certain pro-inflammatory cytokines, such as nuclear factor kappa B. It can scavenge reactive oxygen species (ROS), provide some metal chelating activity, and restore endogenous antioxidants, such as glutathione. ALA may also support health in the presence of neuropathic symptoms.

A double-blind, placebo-controlled, clinical trial assessed the efficacy of oral supplementation with 600 mg to 1,800 mg of ALA in diabetic individuals with DPN for 6 weeks. At the end of the treatment period, improvements in neuropathic symptoms and neural deficits were observed. Other similar clinical trials have also demonstrated improvements in symptoms related to DPN.

Due to its role in supporting the body’s response to inflammation and oxidative stress, ALA may also support cognitive function and brain health. ALA has also been shown to increase levels of the norepinephrine and dopamine neurotransmitters in the brain. A systematic review evaluated the current literature regarding ALA supplementation in the presence of certain psychiatric and neurological disorders. Although there were reports of positive trial outcomes related to multiple sclerosis, traumatic brain injury, and the prevention of certain neurodegenerative disease progression, this branch of research is still relatively new and many trials were too small for broad conclusions. However, preliminary results provide hope for future, larger studies to be conducted.

ALA is a versatile compound with many roles in the human body. R-alpha-lipoic acid is the enantiomer that exists in nature and has been shown to have a higher bioavailability than its S-enantiomeric form. ALA sourced from diet or supplementation, or both, may provide support for healthy glucose and lipid metabolism, cellular health, and a healthy response to oxidative stress.

By Colleen Ambrose, ND, MAT