Alpha-lipoic acid is considered generally well tolerated in many studies, but that does not make it risk-free. However, it has dose-dependent side effects, rare but serious reactions and drug interactions. The editors have collected what you should know before considering use.
Overall tolerability
Alpha-lipoic acid is one of the supplements with a relatively well-studied safety profile, thanks primarily to medical research. In clinical trials for diabetic polyneuropathy, thousands of patients received ALA for weeks, months, and even years.
NATHAN 1 studied 600 mg of ALA daily for four years in people with diabetic polyneuropathy. Serious adverse events were reported in 38.1% of the ALA group and 28.0% of the placebo group. Not every event was attributed to treatment, but the source’s statement that the groups did not differ was incorrect. Shorter studies and the Ziegler et al. (2004) analysis reported generally favorable tolerability under their study conditions.
At the same time, the SYDNEY 2 study clearly showed dose dependence: at 600 mg per day, the frequency of side effects was close to placebo, while at 1200 and 1800 mg, nausea, vomiting, and dizziness occurred more often. This trial-specific balance of benefit and tolerability is not a universal dosing recommendation.
For athletes and people taking ALA supplements, the bottom line is simple: the risk of side effects increases with dose, and the benefits of high doses in healthy people are unproven.
Digestion, skin and other frequent reactions
The most common adverse effects of ALA are gastrointestinal: nausea, heartburn, abdominal discomfort, less commonly vomiting and diarrhea. They occur more often with high doses and taking on an empty stomach, which is also recommended for better absorption.
The second group is skin reactions: rash, itching, urticaria. In a study by Koh et al (2011) where obese participants took up to 1800 mg/day, pruritus and rash were more common than in the placebo group.
Some people note a specific smell of urine when taking ALA, which is associated with the excretion of sulfur-containing metabolites. It is unpleasant, but not dangerous.
| Side effect | Frequency | Contributing factors |
|---|---|---|
| Nausea, heartburn, abdominal pain | The most frequent | Dose, taking on an empty stomach |
| Rash, itching, urticaria | Infrequent | Individual sensitivity, high doses |
| Dizziness, headache | Infrequent | High doses |
| Odor of urine | It happens | Metabolism of sulfur-containing compounds |
| Hypoglycemia | Rare | Taking sugar-lowering drugs, autoimmune mechanism |
Injection site reactions and rare allergic reactions have also been reported with intravenous administration in medical facilities, but this is less relevant for oral supplements.
Hypoglycemia and insulin autoimmune syndrome
The most serious, albeit rare, side effect of ALA is related to blood glucose levels. Because ALA can increase the uptake of glucose by cells, it is theoretically possible for people taking insulin or hypoglycemic pills to get too low in sugar.
A separate mechanism is insulin autoimmune syndrome, or Hirata's disease. This is a condition in which the immune system forms antibodies against its own insulin. The antibodies first bind insulin and then release it unpredictably, causing episodes of hypoglycemia, often hours after a meal.
This syndrome has long been known in Japan and other Asian countries in connection with taking drugs containing sulfhydryl groups. Gullo et al (2014) described a case series in Europeans taking ALA and linked susceptibility to certain genetic variants of the HLA system.
Possible hypoglycemia symptoms include sweating, shaking, intense hunger, palpitations, confusion and weakness. Stop ALA and seek medical assessment if these occur. Severe confusion, seizures, fainting or inability to swallow require emergency help; do not give food or drink to someone who cannot swallow safely.
Drug interactions
The main interactions of ALA are related to its influence on glucose metabolism and the ability to bind metals. The following are situations that require attention:
- hypoglycemic drugs and insulin — increased glucose reduction is possible, more frequent monitoring is required;
- iron, magnesium, calcium preparations — ALA can bind metal ions, so the doses should be separated in time;
- thyroid hormones — some sources mention a possible effect on their metabolism, so patients with thyroid gland diseases should consult their doctor;
- chemotherapy — the use of antioxidants during cancer treatment should be discussed with the oncologist.
The instructions for thioctic acid drugs also note that regular alcohol consumption reduces the effectiveness of treatment and is a risk factor for nerve damage, so it is recommended to abstain from alcohol while taking it.
There is not enough data on the safety of ALA during pregnancy and breastfeeding, so taking it without medical indications is not recommended during these periods. ALA supplements are not given to children without a doctor's prescription.
If you take any prescription medications, tell your doctor about ALA just as you would any other supplement. This is especially important for people with diabetes.
How to reduce the risk of side effects
Most adverse reactions to ALA are mild and resolve after dose reduction or discontinuation. However, they can be largely prevented by following a few rules.
Avoid interpreting trial doses as a general supplement recommendation. The source discusses 300–600 mg daily as studied amounts, while higher amounts more often cause gastrointestinal or skin reactions. A lower dose cannot guarantee prevention of insulin autoimmune syndrome; whether to use ALA at all requires an assessment of benefit and risk.
Secondly, if taking on an empty stomach causes discomfort in the stomach, you can divide the daily amount into two parts or take ALA with a small snack, understanding that absorption will decrease a little.
Third, people with diabetes, thyroid disease, and those taking many medications should only start taking after consulting a doctor and with glucose control. Any unexplained episodes of weakness, sweating or confusion is a reason to immediately measure sugar and consult a doctor.
Editorial conclusions
Many participants tolerate ALA in clinical trials, but neither a 600 mg dose nor a history of use establishes safety for everyone. The NATHAN 1 serious-adverse-event findings and rare autoimmune hypoglycemia need to be considered.
The most frequent side effects — nausea, heartburn, skin rashes — are dose-dependent. A rare but serious complication is hypoglycemia, particularly within the insulin autoimmune syndrome in genetically predisposed individuals.
People with diabetes, thyroid diseases, pregnant women and those taking sugar-lowering drugs need special care.
We also recommend our articles on what alpha lipoic acid is and how it works, its evidence base for athletes, and antioxidants in sports nutrition.
References
- Ziegler D, Ametov A, Barinov A, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006;29(11):2365–2370.
- Ziegler D, Low PA, Litchy WJ, et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011;34(9):2054–2060.
- Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Diabet Med. 2004;21(2):114–121.
- Koh EH, Lee WJ, Lee SA, et al. Effects of alpha-lipoic acid on body weight in obese subjects. Am J Med. 2011;124(1):85.e1–85.e8.
- Gullo D, Evans JL, Sortino G, Goldfine ID, Vigneri R. Insulin autoimmune syndrome (Hirata disease) in European Caucasians taking α-lipoic acid. Clin Endocrinol (Oxf). 2014;81(2):204–209.
- Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009;1790(10):1149–1160.
