How does Alpha-lipoic acid (ALA) help?

How Alpha-Lipoic Acid (ALA) Helps

Alpha-lipoic acid is most definitively beneficial for diabetic neuropathy, with the American Diabetes Association recommending 600 mg once daily for symptom relief, while its cardiovascular benefits remain uncertain and should not replace proven therapies. 1

Primary Established Benefit: Diabetic Neuropathy

The strongest evidence supports ALA for treating diabetic peripheral neuropathy. 1 The American Diabetes Association specifically recommends oral dosing of 600 mg once daily, which shows efficacy equivalent to intravenous infusions. 1

Mechanism in Neuropathy

• ALA delays or reverses peripheral diabetic neuropathy through multiple antioxidant properties, increasing reduced glutathione levels (an important endogenous antioxidant). 2
• It prevents neuronal lipid peroxidation and addresses endoneurial microvascular damage and hypoxia caused by nitric oxide inactivation from increased oxygen free radical activity. 2
• Clinical trials demonstrate that 600 mg ALA improves neuropathic deficits by preventing glycation processes and nerve hypoxia. 2

Antioxidant Properties: The "Antioxidant of Antioxidants"

ALA functions as a uniquely powerful antioxidant system through its oxidized (ALA) and reduced (DHLA) forms. 3

Key Antioxidant Characteristics

• The ALA/DHLA combination represents an ideal antioxidant because it can quench radicals, chelate metals (particularly iron and copper), is amphiphilic, and has no major adverse effects. 3, 4
• It directly terminates free radicals, chelates transition metal ions, increases cytosolic glutathione and vitamin C levels, and prevents toxicities associated with their loss. 4
• ALA modulates various oxidative stress pathways, making it applicable in conditions where the oxidant-antioxidant balance is disrupted, such as neurodegenerative disorders. 3

Metabolic Effects in Diabetes

ALA improves insulin sensitivity, though oral administration shows only marginal effects compared to intravenous infusion. 5

• Intravenous infusion of ALA increases insulin-mediated glucose disposal in patients with type 2 diabetes. 5
• ALA functions naturally as a co-enzyme in the pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase mitochondrial enzyme complexes. 5
• It improves glycemic control and effectively mitigates toxicities associated with heavy metal poisoning. 4

Cardiovascular Disease: Limited and Uncertain Evidence

For cardiovascular disease, the evidence is contradictory and weak, with most high-quality studies showing no significant benefit. 6

Evidence Against Cardiovascular Benefit

• The most recent meta-analysis by Abdelhamid et al. in 2020 found no effect of ALA on CHD mortality or events in randomized controlled trials. 6
• Most cohort studies do not find association of ALA intake or its biomarkers with coronary heart disease. 6
• Meta-analyses generally conclude there is a lack of or weak significant association between ALA and cardiovascular outcomes. 6

Limited Potential Benefit

• ALA may have protective effects only in individuals with very low intake of long-chain omega-3 PUFA (< 100 or < 175 mg/d), where it could participate in restoring higher concentrations through elongation and desaturation. 6
• Some meta-analyses showed modest reductions in fatal CHD (RR 0.85; 95% CI 0.75,0.96) but not total CHD. 6

Critical Clinical Caveat

For patients with established cardiovascular disease, ALA should not replace guideline-directed medical therapy including antiplatelet agents, statins, ACE inhibitors, and revascularization when indicated, as recommended by the American College of Cardiology. 7

Additional Potential Applications

ALA shows promise in other oxidative stress-related conditions, though evidence is less robust than for diabetic neuropathy. 3, 8

• Clinical studies suggest ALA may be useful in cardiovascular diseases and nerve discomforts beyond diabetic neuropathy. 3
• Its unique pharmacological actions, coupled with relatively low toxicity, have led to trials in diseases associated with increased oxidative stress, inflammation, and metal overload. 8
• ALA can be considered alone or in combination with other functional substances for conditions where oxidant-antioxidant balance is disrupted. 3

Practical Dosing and Safety

• The established therapeutic dose is 600 mg once daily orally for diabetic neuropathy. 1
• ALA has relatively low toxicity and no major adverse effects. 3, 8
• Oral administration has limitations compared to intravenous infusion for some applications. 5