Alpha lipoic acid

What alpha-lipoic acid does in your body

Alpha-lipoic acid (ALA) is an organosulfur compound produced naturally in human cells. It is both water- and fat-soluble, which means it can reach tissues that most antioxidants cannot, including the brain. Your body makes small amounts of ALA in the mitochondria, where it functions as a cofactor for the pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase enzyme complexes. These enzymes sit at the center of cellular energy production. Without them, glucose cannot be efficiently converted into ATP.

ALA exists in two mirror-image forms: R-lipoic acid (the naturally occurring form) and S-lipoic acid (a synthetic byproduct). Most supplements contain a 50/50 racemic mix of both. Pharmacokinetic studies show the R-form has roughly 40-50% higher peak plasma concentrations than the S-form after oral dosing ^[1]. This matters because R-lipoic acid is the form your mitochondria actually use.

The antioxidant recycler

ALA's most distinctive property is its ability to regenerate other spent antioxidants. When vitamin C, vitamin E, or glutathione neutralize a free radical, they become oxidized and temporarily inactive. ALA can restore them to their active forms, effectively multiplying the body's total antioxidant capacity. A 2007 review found that ALA supplementation in aged rats elevated mitochondrial glutathione levels, restored electron transport chain activity, and reduced markers of lipid peroxidation and DNA oxidative damage ^[2].

ALA also crosses the blood-brain barrier, a feat most antioxidants can't manage. This gives it potential relevance for neurodegenerative conditions where oxidative damage accumulates in brain tissue.

Clinical evidence: where it works

Diabetic neuropathy

The strongest clinical data for ALA comes from diabetic peripheral neuropathy research. A 2023 meta-analysis of 10 randomized controlled trials (1,242 patients) found that oral ALA at 600 mg/day significantly reduced neuropathy symptom scores compared to placebo, with a dose-dependent response ^[3]. A separate 2024 network meta-analysis confirmed these findings, reporting that ALA at 600 mg/day lowered total symptom scores by 1.05 points versus control ^[4]. The mechanism appears to involve reduced oxidative stress in peripheral nerves and improved microcirculation.

Blood sugar regulation and insulin sensitivity

A meta-analysis of 41 studies found that ALA supplementation improved glycemic biomarkers and reduced inflammatory markers in metabolically compromised populations ^[5]. The effect on fasting glucose and HbA1c is modest but consistent across trials. People taking blood sugar-lowering medications should discuss ALA with their doctor, as the combined effect can cause hypoglycemia.

Body weight

A 2020 dose-response meta-analysis of randomized placebo-controlled trials found that ALA supplementation significantly reduced body weight and BMI compared to placebo, though the average weight loss was small (around 1.27 kg) ^[6]. This is likely too modest to justify ALA as a standalone weight loss intervention, but it may contribute to broader metabolic improvement.

Heavy metal chelation

ALA and its reduced form (dihydrolipoic acid, DHLA) can bind certain toxic metals including mercury, arsenic, lead, and cadmium. A 2024 review found that ALA mitigated aluminum and arsenic toxicity in animal models and reduced blood lead levels in treated rats ^[7]. Human evidence for metal chelation remains limited, and ALA should not replace established chelation protocols. However, its dual role as antioxidant and mild chelator makes it an interesting adjunct in environmental toxicology research.

Dosage and practical considerations

Clinical trials typically use 300-600 mg/day for general antioxidant support and up to 1,200-1,800 mg/day for diabetic neuropathy. Take ALA on an empty stomach, as food reduces absorption by roughly 30%. If you can find a stabilized R-lipoic acid product, it offers better bioavailability than the standard racemic form. High doses above 600 mg may cause mild gastrointestinal discomfort in some people. ALA can also interfere with biotin absorption at high doses over several weeks, so consider supplementing biotin separately during extended use ^[1].