7 Benefits and Side Effects of Alpha Lipoic Acid (Plus 10 Safety Precautions)

Alpha lipoic acid first caught my attention because of its unusual history. German physicians originally used it to treat acute poisoning from death cap mushrooms. By the 1980s, researchers had discovered something more interesting: it functions as a powerful antioxidant that works in both fat-soluble and water-soluble environments. That dual capability is quite rare among antioxidants.

Dr. Lester Packer, a well-known antioxidant researcher, described alpha lipoic acid as an “ideal” antioxidant in his book The Antioxidant Miracle. I should note that such enthusiastic claims warrant scrutiny. Let me walk through what the clinical evidence actually supports.

What is Alpha Lipoic Acid?

The discovery of alpha lipoic acid dates back to 1937 when scientists Snell and colleagues noticed that certain bacteria required a specific compound from potato extract to grow. A few years later, researchers isolated this growth factor and identified it as alpha lipoic acid.

What makes alpha lipoic acid interesting from a biochemical standpoint is its role in energy production. It acts as a cofactor for enzymes involved in glycolysis and the citric acid cycle within mitochondria. Your cells literally use it to convert food into energy.

Beyond energy metabolism, alpha lipoic acid has several proposed functions as an antioxidant:

1. Scavenging reactive oxygen species directly
2. Regenerating other antioxidants including vitamin C, vitamin E, and glutathione
3. Chelating metal ions that might otherwise catalyse oxidative damage
4. Repairing oxidised proteins
5. Regulating gene transcription and inflammatory pathways, including inhibition of nuclear factor kappa B

I find the antioxidant recycling function particularly noteworthy. Most antioxidants get “used up” when they neutralise free radicals, but alpha lipoic acid can help regenerate them.

What Does the Research Show?

1. Blood Lipid Regulation

Dyslipidaemia (abnormal blood fat levels) increases risk for obesity, insulin resistance, and cardiovascular disease. Risk factors include smoking, sedentary lifestyle, and diets high in saturated or trans fats.

A 2018 systematic review and meta-analysis examined 11 controlled clinical trials with 452 adult participants. The researchers found that alpha lipoic acid supplementation significantly reduced serum triglycerides, total cholesterol, and LDL cholesterol. However, it did not affect HDL (the “good” cholesterol). 1

Interestingly, the subgroup analysis revealed that effects were strongest in participants with a BMI above 30 kg/m² and when daily doses exceeded 600 mg. This suggests alpha lipoic acid may be most useful for those with obesity-related lipid problems.

My interpretation: The evidence for blood lipid benefits exists but comes with caveats. The studies included had considerable variation, so I would not rely on alpha lipoic acid as a primary treatment for high cholesterol.

2. Blood Sugar Control

Type 2 diabetes involves insufficient insulin sensitivity and impaired glucose uptake by tissues. Common symptoms include frequent urination, excessive thirst, and unintended weight loss.

A 2020 systematic review and meta-analysis pooled data from 28 placebo-controlled trials with 1,016 participants. Alpha lipoic acid supplementation significantly reduced serum insulin levels and insulin resistance (measured by HOMA-IR). However, it did not significantly affect fasting glucose or HbA1c (the marker of long-term blood sugar control). 2

The proposed mechanism involves stimulation of AMPK activity in skeletal muscle and adipose tissue, which improves insulin receptor signalling.

My interpretation: Alpha lipoic acid appears to improve insulin sensitivity without dramatically lowering blood sugar itself. For people with diabetic bladder dysfunction or other diabetes-related complications, this could be relevant as an adjunct therapy, though it should not replace standard diabetes management.

3. Blood Pressure

Hypertension is defined as systolic blood pressure at or above 140 mmHg or diastolic at or above 90 mmHg. Elevated blood pressure increases stroke and coronary heart disease risk.

A 2019 meta-analysis of 7 randomised controlled trials with 478 participants examined lipoic acid supplementation at doses from 300 to 1,800 mg daily for 8 to 20 weeks. The analysis found modest blood pressure lowering effects, particularly in subjects with blood pressure slightly above normal (below 130/80 mmHg). 3

My interpretation: The blood pressure effect appears real but modest. I would not expect alpha lipoic acid to replace blood pressure medication, but it might offer some support for those in the “pre-hypertension” range.

4. Diabetic Peripheral Neuropathy

This is where alpha lipoic acid has perhaps its strongest evidence base. Diabetic peripheral neuropathy affects a substantial proportion of people with diabetes and can cause tingling, burning, pain, and numbness, typically worse at night. Left untreated, it increases risk of foot ulcers and amputation.

A 2018 systematic review and meta-analysis examined 20 randomised controlled trials involving 1,894 patients with diabetic peripheral neuropathy. When alpha lipoic acid was combined with epalrestat (a medication used for neuropathy), the combination significantly improved nerve conduction velocity compared to either treatment alone. 4

The Mayo Clinic notes that alpha lipoic acid has been used in Germany for years to treat diabetic neuropathy, though they caution that more research is needed. 5

My interpretation: Of all the proposed uses for alpha lipoic acid, diabetic neuropathy has the most convincing evidence. The fact that it has a track record in German clinical practice adds to my confidence, though I recognise this does not constitute rigorous proof.

5. Inflammatory Markers

Chronic low-grade inflammation underlies many metabolic diseases including type 2 diabetes, atherosclerosis, and endothelial dysfunction.

A 2018 systematic review and meta-analysis examined 18 randomised controlled trials with 912 participants. Oral lipoic acid significantly reduced C-reactive protein (CRP), interleukin-6 (IL-6), and tumour necrosis factor alpha (TNF-α) in patients with metabolic syndrome and related conditions. 6

Reduced inflammation may partly explain the benefits seen in other conditions. For people with inflammatory bladder conditions like interstitial cystitis or painful bladder syndrome, the anti-inflammatory properties could theoretically be relevant, though I have not found studies specifically examining this.

My interpretation: The anti-inflammatory effect appears consistent across multiple studies, which gives me more confidence than some of the other proposed benefits.

6. Weight Loss

Obesity affects over 2 billion people globally. Even modest weight loss of 5-10% can improve metabolic health markers.

A 2017 meta-analysis of 12 placebo-controlled clinical trials found that alpha lipoic acid supplementation produced a small but statistically significant reduction in body weight (-0.69 kg) and BMI (-0.38 kg/m²). There was no significant effect on waist circumference. 7

The subgroup analysis found weight loss was most pronounced in those who used it for less than 10 weeks, at doses under 600 mg daily, and in overweight (not obese) individuals.

My interpretation: I would describe the weight loss effect as statistically significant but clinically modest. Losing less than a kilogram is unlikely to be noticeable for most people. Alpha lipoic acid is not a weight loss supplement in any meaningful sense.

7. Burning Mouth Syndrome

Burning mouth syndrome causes chronic burning sensations in the mouth without visible lesions. It primarily affects menopausal women and may have psychological, hormonal, or neurological components.

A randomised, double-blind, placebo-controlled trial of 60 patients found that oral lipoic acid (800 mg daily for 8 weeks) did not significantly improve symptoms compared to placebo. 8

My interpretation: Despite some earlier positive reports, this well-designed trial suggests alpha lipoic acid may not help burning mouth syndrome. I would not recommend it for this purpose.

Food Sources of Alpha Lipoic Acid

Alpha lipoic acid occurs naturally in foods, bound to the amino acid lysine. Food sources include:

• Organ meats (particularly liver and kidney)
• Red meat
• Spinach
• Broccoli
• Tomatoes

Your body also produces small amounts of alpha lipoic acid through conversion of octanoic acid and cysteine in mitochondria. The amounts from food and endogenous synthesis are considerably lower than supplement doses used in clinical trials.

Dosage Considerations

Most clinical trials have used doses between 100 and 600 mg daily. The evidence suggests this range is generally safe, though optimal dosing varies by condition:

• General antioxidant support: 100-300 mg daily
• Diabetic neuropathy: 600 mg daily (the most studied dose)
• Blood sugar support: 300-600 mg daily

Absorption is better on an empty stomach. People with diabetic complications or cognitive concerns may need higher doses, which warrants discussion with a healthcare provider.

Choosing Between Different Forms

Two forms of alpha lipoic acid exist: the natural R-form and the synthetic S-form. Most supplements contain a 50/50 mixture (called “alpha lipoic acid”), while some contain pure R-lipoic acid.

Research suggests R-lipoic acid achieves higher blood concentrations than the S-form. One study found blood levels were roughly double with the R-form compared to the S-form. 9

A newer form called sodium R-lipoic acid (NaRLA) reportedly achieves even higher blood concentrations by solving stability problems with pure R-lipoic acid. 10

Whether these differences translate to better clinical outcomes remains uncertain. The R-form costs more, and most clinical evidence comes from studies using the mixed alpha lipoic acid form.

Side Effects

At appropriate doses, alpha lipoic acid is generally well tolerated. Reported side effects include:

• Skin reactions (rash, hives, itching)
• Gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhoea)
• Dizziness
• Strong-smelling urine

Side effects appear more common at higher doses (1,200-1,800 mg daily). 11

Safety Precautions

Based on case reports and theoretical concerns, the following precautions apply:

1. Children: One case report described refractory seizures in a child who ingested an unknown dose. Keep supplements away from children. 12

2. Liver disease: A case of acute cholestatic hepatitis was reported in a man with diabetes and kidney disease taking 600 mg daily. Those with existing liver problems should exercise caution. 13

3. Iron levels: High-dose lipoic acid may reduce iron absorption, though iron deficiency anaemia has not been reported in humans. 14

4. Biotin interaction: Alpha lipoic acid and biotin have similar chemical structures and may compete for cellular transport, potentially increasing biotin requirements.

5. Pregnancy and breastfeeding: Safety has not been established. Avoid use.

6. Kidney or liver impairment: Use with caution due to limited safety data.

7. Surgery: Stop use 2 weeks before surgery due to potential effects on blood sugar control.

8. Thyroid medications: May interfere with thyroid hormone effectiveness.

9. Cancer chemotherapy: Antioxidants may theoretically reduce the effectiveness of certain chemotherapy drugs. Discuss with your oncologist.

10. Diabetes medications: Alpha lipoic acid may enhance blood sugar lowering effects, increasing hypoglycaemia risk. Monitor blood sugar closely if combining with insulin or oral diabetes medications such as glimepiride, glyburide, pioglitazone, rosiglitazone, or glipizide.

The Bottom Line

Alpha lipoic acid has reasonable evidence supporting several health applications, with diabetic peripheral neuropathy being the strongest. Its effects on blood lipids, insulin sensitivity, and inflammation appear real but modest. I would not describe it as a miracle antioxidant, but it may have a role as an adjunct therapy for specific conditions.

If you are considering alpha lipoic acid for diabetes-related concerns, particularly neuropathy, the evidence is reasonable enough to discuss with your doctor. For weight loss or general “antioxidant protection,” the evidence is weaker, and expectations should be tempered accordingly.

References

1. Mousavi SM, et al. The effect of alpha-lipoic acid supplementation on lipid profile: A systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Syndr. 2019;13(1):506-511. PubMed

2. Akbari M, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis. Metabolism. 2020;112:154351. PubMed

3. Mohammadi V, et al. The effect of alpha-lipoic acid supplementation on blood pressure: A systematic review and meta-analysis of randomized controlled trials. Clin Nutr ESPEN. 2019;30:78-84. PubMed

4. Jiang DQ, et al. Efficacy of alpha-lipoic acid combined with epalrestat for diabetic peripheral neuropathy: A systematic review and meta-analysis. J Clin Pharm Ther. 2018;43(5):647-656. PMC

5. Mayo Clinic. Alpha-lipoic acid. Mayo Clinic

6. Akbari M, et al. The effects of alpha-lipoic acid supplementation on inflammatory markers among patients with metabolic syndrome: A systematic review and meta-analysis. Nutr Metab. 2018;15:39. PMC

7. Kucukgoncu S, et al. Alpha-lipoic acid (ALA) as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials. Obes Rev. 2017;18(5):594-601. PubMed

8. Lopez-Jornet P, et al. Efficacy of alpha lipoic acid in burning mouth syndrome: a randomized, placebo-controlled, double-blind study. Oral Dis. 2009;15(6):404-408. PubMed

9. Hermann R, et al. Enantioselective pharmacokinetics and bioavailability of different racemic alpha-lipoic acid formulations. Eur J Pharm Sci. 1996;4(3):167-174. PubMed

10. Carlson DA, et al. The plasma pharmacokinetics of R-(+)-lipoic acid administered as sodium R-(+)-lipoate. Altern Med Rev. 2007;12(4):343-351. PubMed

11. Ziegler D, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy. Diabetes Care. 2006;29(11):2365-2370. PubMed

12. Emir DF, et al. Alpha-lipoic acid intoxication, treatment and outcome. Clin Toxicol. 2015;53(8):796. PubMed

13. Rizos CV, et al. The hepatotoxicity of alpha-lipoic acid. Exp Clin Endocrinol Diabetes. 2011;119(6):327-328. PubMed

14. Suh JH, et al. R-alpha-lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues. Antioxid Redox Signal. 2004;6(5):827-835. PubMed