Alpha-Lipoic Acid: Benefits and Research

21 December 2024, by SANUSq Research team
13 min reading time

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Alpha-lipoic acid turns up on almost every list of "anti-ageing antioxidants". Behind the buzzword is a real molecule with interesting properties, but the alpha lipoic acid benefits that research actually supports are narrower than the marketing suggests. Here is what it is, where the evidence is strongest, and where it pays to stay cautious.

Written by SANUSq Research Team | Medically reviewed by Dr Ajay Kumar, MD
Published: 21 December 2024 | Updated: 21 December 2024

What is alpha-lipoic acid?

Alpha-lipoic acid (ALA), also called thioctic acid, is a compound your body makes for itself in small amounts and that is also found in food. It works inside the mitochondria, the parts of the cell that turn nutrients into usable energy, where it acts as a helper (a cofactor) for key enzymes in energy metabolism.

Unusually, it dissolves in both water and fat, so it can work in almost every part of the cell.

It exists in two mirror-image forms. The R form is the one the body makes and is generally thought to be the more biologically active. The S form comes from chemical synthesis. Most supplements contain a 50:50 mix of the two, sometimes labelled "racemic".

In a review of how alpha-lipoic acid works, Shay et al. (2009) describe it as a compound that scavenges free radicals, binds metals and helps restore glutathione levels inside cells, which otherwise tend to fall with age. The authors note that its effects in cell and animal studies go beyond a simple antioxidant role, and that much of this work has still to be confirmed in people.

An antioxidant that recycles other antioxidants

What sets alpha-lipoic acid apart is that it doesn't just neutralise free radicals itself. It also helps regenerate other antioxidants, including vitamin C, vitamin E and glutathione, so they can go back to work. That is why it is sometimes called an "antioxidant of antioxidants": it supports the cell's whole defence network rather than a single link in the chain.

An early and widely cited review by Packer et al. (1995) set out how alpha-lipoic acid and its reduced form react with several types of reactive oxygen species and interact with vitamin C and glutathione, which may in turn recycle vitamin E. The authors also pointed out that, under some conditions, the reduced form can act as a pro-oxidant, a reminder that "antioxidant" is not a simple label.

It is this cluster of properties, rather than one dramatic effect, that explains the scientific interest in the molecule, and a good deal of hope the evidence hasn't yet borne out.

Alpha lipoic acid benefits: what the neuropathy research shows

The most substantial body of research concerns diabetic neuropathy: nerve damage, often felt as tingling, burning, numbness or pain in the feet and legs, that can develop in people with diabetes. Raised blood sugar over long periods increases oxidative stress, which gradually harms small nerves, hence the interest in an antioxidant.

It is important to be clear about the setting. These studies were carried out in people with diagnosed diabetes, under medical supervision, often with alpha-lipoic acid given by intravenous drip. That is a very different thing from taking an over-the-counter supplement on your own.

A meta-analysis by Ziegler et al. (2004) pooled four randomised, placebo-controlled trials in 1,258 people with diabetes and symptomatic polyneuropathy. After three weeks of 600 mg a day given intravenously, symptoms such as pain, burning and numbness had improved more than with placebo, and some measures of nerve function were also better. Adverse events were no more common than with placebo.

One of those trials, the SYDNEY trial reported by Ametov et al. (2003), randomised 120 people with diabetic neuropathy to intravenous alpha-lipoic acid or placebo for 14 treatments. Sensory symptom scores improved by an average of 5.7 points with alpha-lipoic acid, compared with 1.8 points with placebo.

In the SYDNEY 2 trial, Ziegler et al. (2006) gave 181 people with diabetic neuropathy 600, 1,200 or 1,800 mg of oral alpha-lipoic acid, or placebo, for five weeks. Symptom scores fell by about half in all three alpha-lipoic acid groups, compared with about a third on placebo. Nausea, vomiting and dizziness became more common as the dose rose, and the authors judged 600 mg once a day to offer the best balance.

Why the picture is more mixed than it first looks

A systematic review by Han et al. (2012) pooled 15 randomised trials of intravenous alpha-lipoic acid (300–600 mg a day for two to four weeks) and found improvements in nerve conduction speed and symptoms. However, the authors cautioned that most of the included studies were of poor methodological quality, so the evidence may not be strong.

A Cochrane review by Baicus et al. (2024) looked only at trials lasting at least six months, including 816 participants in three studies. It concluded that alpha-lipoic acid probably has little or no effect on neuropathy symptoms at six months, and may have little or no effect on nerve impairment, although a meaningful benefit could not be ruled out. All three studies were judged at high risk of bias because many participants dropped out.

Put simply: alpha-lipoic acid has shown short-term improvements in neuropathy symptoms in medically supervised trials, while the case for long-term benefit is still uncertain. If you have diabetes and notice tingling, burning or numbness, see your doctor. Nerve symptoms need proper assessment, and good blood sugar control, foot care and prescribed medicines remain the foundation. A supplement is not a substitute for any of them.

What about blood sugar, weight and anti-ageing?

Blood sugar. Some studies suggest a modest effect on insulin sensitivity, but that doesn't make it a diabetes treatment.

A meta-analysis by Mahmoudi-Nezhad et al. (2021), covering 28 studies and just over 1,000 adults, found that alpha-lipoic acid supplementation was associated with small reductions in insulin levels and in a marker of insulin resistance (HOMA-IR). There was no change in fasting glucose or HbA1c, the long-term blood sugar measure doctors use most. Results varied with dose, study length, the participants' health and study quality.

Weight.

Pooling 10 randomised, placebo-controlled trials, Kucukgoncu et al. (2017) found that people taking alpha-lipoic acid lost on average about 1.3 kg more than those on placebo over the short term. The authors described the effect as small and called for longer studies.

Neither effect comes close to what a balanced diet and regular activity can do.

Anti-ageing and skin. Its antioxidant role and use in skin creams have built an appealing "anti-ageing" story, but solid evidence that it slows ageing in healthy people is lacking.

Other early lines of research

Researchers have also looked at alpha-lipoic acid in relation to brain function, liver health, migraine and other complications of diabetes. So far the signals are preliminary: small studies, inconsistent results and uneven methods. In health research, the gap between "studied" and "shown" matters a great deal.

What is alpha lipoic acid found in?

Small amounts occur naturally in food. Commonly cited sources include:

Organ meats such as liver and kidney.
Red meat.
Vegetables such as spinach and broccoli.
Yeast.

The amounts in food are far lower than the doses used in clinical studies, which rely on concentrated forms. For most people, a varied diet together with what the body makes itself covers everyday needs.

Choosing an alpha lipoic acid supplement: forms and absorption

Two practical points come up often. The first is the form. Most products contain the R/S mix, while "R-lipoic acid" products contain only the form the body makes. The second is absorption. Alpha-lipoic acid is generally better absorbed on an empty stomach, and levels in the blood fall again fairly quickly. That helps explain why studies looking for clear effects sometimes used an intravenous drip.

Quality and dosage vary widely between products, so if you are considering one, choose a transparent manufacturer and follow the label.

Safety and precautions

Alpha-lipoic acid is usually well tolerated at common doses, though nausea and other digestive upsets can occur, especially at higher doses. A few cautions are worth knowing:

Diabetes medication. Because it may lower blood sugar, it could add to the effect of insulin or other glucose-lowering medicines and raise the risk of low blood sugar (hypoglycaemia). Don't start it without talking to your doctor, and never use it in place of prescribed treatment.
Insulin autoimmune syndrome. In rare cases, alpha-lipoic acid has been linked to a condition in which the body makes antibodies against its own insulin, causing repeated episodes of low blood sugar, even in people without diabetes. Genetics appears to play a part.
Other medicines and health conditions. Check with your doctor or pharmacist before taking it if you take any regular medication, have a long-term health condition, or are pregnant or breastfeeding.

Gullo et al. (2014) described six European patients who developed insulin autoimmune syndrome, with spontaneous episodes of low blood sugar, 30 to 120 days after starting 600 mg a day of lipoic acid. None was using insulin. Hypoglycaemic episodes became less frequent once lipoic acid was stopped, and most of the patients carried a particular gene variant thought to increase susceptibility.

If you develop shakiness, sweating, confusion or unusual hunger while taking alpha-lipoic acid, stop taking it and seek medical advice promptly.

The bottom line

Alpha-lipoic acid is a genuine antioxidant with an unusual ability to help recycle others. Its most researched use is for the symptoms of diabetic neuropathy in a medical setting, where short-term trials have been positive but longer-term evidence is uncertain. Beyond that, most claims remain research questions. For a healthy person, a varied diet and a healthy lifestyle do far more than any supplement. For someone with diabetes, medical care and blood sugar control come first, and no supplement replaces them.

Frequently asked questions

What is alpha-lipoic acid used for?

It is an antioxidant the body makes itself, involved in energy production and able to help regenerate other antioxidants such as vitamins C and E and glutathione. Its best-researched use is for the symptoms of diabetic neuropathy, under medical supervision.

Is alpha-lipoic acid really anti-ageing?

That is an attractive shortcut with little evidence behind it. There is no solid proof that it slows ageing in healthy people.

Can alpha-lipoic acid help with diabetes?

Medically supervised trials have shown short-term improvements in the symptoms of diabetic neuropathy, although longer studies are less clear. It is not a treatment for diabetes and doesn't replace medication or blood sugar control. Because it may lower blood sugar, talk to your doctor before trying it.

Should I take an alpha-lipoic acid supplement?

For most healthy people, a varied diet is enough. Taking a supplement is a decision best made with a healthcare professional, particularly because of its possible effect on blood sugar.

What are the side effects of alpha-lipoic acid?

It is generally well tolerated, though nausea and digestive upset can occur, especially at higher doses. It may lower blood sugar, and in rare cases it has been linked to insulin autoimmune syndrome. Take care if you have diabetes, take regular medication, or are pregnant or breastfeeding.

How are alpha-lipoic acid and glutathione linked?

Alpha-lipoic acid helps restore glutathione, one of the main antioxidants the cell makes for itself. Both belong to the same antioxidant network, but they are different molecules with different uses and levels of evidence.

References

Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochimica et Biophysica Acta. 2009;1790(10):1149–1160. PMID 19664690
Packer L, Witt EH, Tritschler HJ. alpha-Lipoic acid as a biological antioxidant. Free Radical Biology and Medicine. 1995;19(2):227–250. PMID 7649494
Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Diabetic Medicine. 2004;21(2):114–121. PMID 14984445
Ametov AS, Barinov A, Dyck PJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 2003;26(3):770–776. PMID 12610036
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. PMID 17065669
Han T, Bai J, Liu W, Hu Y. A systematic review and meta-analysis of α-lipoic acid in the treatment of diabetic peripheral neuropathy. European Journal of Endocrinology. 2012;167(4):465–471. PMID 22837391
Baicus C, Purcarea A, von Elm E, Delcea C, Furtunescu FL. Alpha-lipoic acid for diabetic peripheral neuropathy. Cochrane Database of Systematic Reviews. 2024;1(1):CD012967. PMID 38205823
Mahmoudi-Nezhad M, Vajdi M, Farhangi MA. An updated systematic review and dose-response meta-analysis of the effects of α-lipoic acid supplementation on glycemic markers in adults. Nutrition. 2021;82:111041. PMID 33199187
Kucukgoncu S, Zhou E, Lucas KB, Tek C. Alpha-lipoic acid (ALA) as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials. Obesity Reviews. 2017;18(5):594–601. PMID 28295905
Gullo D, Evans JL, Sortino G, Goldfine ID, Vigneri R. Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking α-lipoic acid. Clinical Endocrinology. 2014;81(2):204–209. PMID 24111525

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