Alpha lipoic acid (ALA) is an endogenous cofactor found in cells. It can be obtained from a variety of foods in the diet. ALA is sometimes referred to as a “universal antioxidant” because it is both water- and fat-soluble and can neutralize free radicals ⁽²⁶⁾. It is marketed as a dietary supplement for this reason, and is also used as adjuvant therapy for neuropathy and to improve glycemic control. Preclinical studies show that ALA plays a crucial role in energy production, and exerts antioxidant and apoptotic effects ^{(1) (2) (3)}.

Studies on ALA in humans have been conducted across various populations. Preliminary data suggest long-term supplementation may help preserve walking ability in patients with secondary progressive multiple sclerosis, especially those with less disability at baseline ⁽²⁷⁾. Studies of intravenous and oral forms suggest improved insulin sensitivity, vasodilation, and neuropathy symptoms in diabetic patients ^{(5) (6) (7) (21) (28)}, although earlier studies to determine its role in reversing neuropathies ^(8) (9) and liver disease ^(10) (11) produced mixed results. Data from a double-blind RCT suggest short-term ALA supplementation can be beneficial for idiopathic pain without altering glycemia in patients with normal levels ⁽⁴⁵⁾, but another trial did not find it helpful for fibromyalgia ⁽⁴⁶⁾.

In women with gestational diabetes, oral ALA may improve liver function and glucose metabolism ⁽²⁹⁾. Meta-analyses also suggest ALA supplementation may reduce inflammatory mediators such as CRP, IL-6, TNF-α, and improve some glucose and lipid parameters ^{(30) (31) (32) (33) (34)}, but confirming studies are needed. In other preliminary studies, ALA induced mild weight loss and waist circumference reduction in overweight or obese subjects ⁽²³⁾. Long-term use of R-ALA, which has increased bioavailability, produced modest weight loss in overweight/obese adults without significant reductions in triglyceride levels ⁽⁴⁷⁾.

In postoperative settings, ALA helped improve wound healing and scarring in women undergoing cesarean section ⁽³⁵⁾, and reduced pain after carpal tunnel decompression ⁽²⁴⁾. In patients with atrial fibrillation, it reduced serum markers of inflammation but not AF recurrence after ablative treatment ⁽²⁵⁾.

Although current data suggest protective effects of antioxidants against Alzheimer’s disease, such effects were not found with a combination of coenzyme Q, vitamin C, vitamin E, and ALA ⁽²⁰⁾. And even though preclinical studies of ALA demonstrate antioxidant properties with efficacy in neurodegenerative models, oral ALA was ineffective in patients with geographic atrophy from advanced macular degeneration ⁽⁴⁸⁾.

High doses of ALA can cause hypoglycemic symptoms ⁽⁴⁾ and other serious conditions. ALA may also antagonize the effects of chemotherapy and radiation therapy because of its antioxidant properties.