Lipoic acid is a natural antioxidant and anti-inflammatory compound with a suite of potential health benefits. Read on to learn more about how this essential nutrient helps increase your wellbeing and how you can add more of it to your diet.
What is Lipoic Acid?
Some call it the “universal antioxidant” .
ALA is considered an essential fatty acid, meaning that the human body needs it but cannot produce it on its own. The NIH recommends between 1.1 g (for women) and 1.6 g (for men) of ALA per day, with somewhat higher requirements (1.3 – 1.4 g) for pregnant and breastfeeding women .
List of Important Functions for Lipoic Acid:
- Lipoic acid acts as a powerful antioxidant both inside and outside of the cells [1, 2].
- Lipoic acid scavenges several reactive oxygen species (ROS) .
- Lipoic acid helps to regenerate both fat and water-soluble antioxidant vitamins (such as vitamins C and E) [2, 1].
- Lipoic acid improves sugar and fat metabolism .
- Lipoic acid is an essential cofactor for mitochondrial respiratory enzymes that improves mitochondrial function . Lipoic acid exerts a “rejuvenating” impact on mitochondria by protecting them against the higher levels of ROS they produce during the aging process .
- Lipoic acid also has anti-inflammatory action, independently of its antioxidant activity .
Production of Lipoic Acid in the Human Body
A healthy body makes enough lipoic acid to supply its energy requirements; therefore, there is no daily requirement for this supplement. However, several medical conditions appear to be accompanied by low levels of lipoic acid – specifically, diabetes, liver cirrhosis, and heart disease .
In parts of Europe, lipoic acid is approved for the treatment of diabetic neuropathy. It has been shown to enhance insulin sensitivity, improve microcirculation in the limbs, and reduce neuropathic symptoms [1, 7].
Also, lipoic acid produced in the body decreases with age, which could increase free radical-induced damage. Lipoic acid supplementation in animal models have also prolonged lifespan and prevented neurological damage .
Health Benefits of Lipoic Acid
While alpha-lipoic acid is generally accepted to be a healthy component of our diets, the FDA has not approved it as a supplement for any medical purpose or health claim. Talk to your doctor before supplementing with ALA.
1) Skin Health
Hyperbaric oxygen therapy is used as a treatment for wounds that won’t heal as a result of diabetes or radiation injury. Lipoic acid accelerated wound repair in patients affected by chronic wounds undergoing hyperbaric oxygen (HBO) therapy [8, 9, 10].
Skin Damage & Aging
Topical lipoic acid also reversed skin damage caused by cigarette smoke .
Lipoic acid appears to have possible beneficial effects in the prevention of diabetes. In some countries, it is approved as part of a treatment plan for diabetic patients .
In type 2 diabetic patients, lipoic acid improved metabolic indices and erectile dysfunction. Lipoic acid supplementation reduced BMI, HbA1C, total cholesterol, HDL-cholesterol and triglycerides .
Lipoic acid has drawn considerable attention as an antioxidant for use in managing diabetic complications such as retinopathy, neuropathy and other vascular diseases .
In Europe, alpha-lipoic acid is approved for the treatment of diabetic neuropathy (nerve damages due to high blood sugar in diabetics). It is believed to enhance insulin sensitivity, improve microcirculation and reduce neuropathic symptoms [1, 7].
Studies show that lipoic acid improves these nerve damage symptoms such as stabbing and burning pain, asleep numbness, and prickling sensations [24, 25, 26, 27]. Lipoic acid also improves the function of motor nerves and reduced blood glucose .
Lipoic acid is a well-tolerated and effective long-term intervention for diabetic neuropathy. In mild-to-moderate cases, lipoic acid supplementation for four years improved symptoms and prevented progression of neuropathic impairments .
In type 1 diabetic patients with autonomic diabetic neuropathy (damages to the nerve that control vital functions of the autonomic nervous system, such as blood pressure and heart rate), lipoic acid improved systolic blood pressure, dizziness, instability upon standing, leg edema and erectile dysfunction .
In diabetics, lipoic acid also improved cardiac autonomic neuropathy .
People with impaired glucose metabolism often have blood vessel damage and impaired blood vessel function. Lipoic acid can improve blood vessel function by decreasing oxygen-derived free radicals .
In adolescents with type 1 diabetes, lipoic acid improved blood vessel function .
In children and adolescents with asymptomatic type 1 diabetes, lipoic acid improved left ventricular (heart chamber that pumps the blood throughout the body) function, suggesting that it may help prevent cardiomyopathy (damage to the heart muscles) .
In aged type 2 diabetes complicated with acute brain infarction (tissue death from blood clots), lipoic acid significantly reduced the patient’s oxidative stress, blood glucose and cholesterol levels .
Elevated asymmetric dimethylarginine (ADMA) concentrations predict cardiovascular events in patients with type 2 diabetes. In patients with T2D, lipoic acid reduced ADMA .
In patients with type 2 diabetes, lipoic acid increased vasodilatation (widening of blood vessels) in response to ACh .
3) Antioxidant Activity
4) Weight Management
In healthy overweight/obese women on a calorie-restricted diet, those who were given lipoic acid supplements lost a little more weight than those who didn’t. The authors concluded that ALA could be a helpful addition to a weight loss program, but that ALA by itself won’t trigger weight loss .
Even without dieting, lipoic acid can improve glucose and fat metabolism. As a result, more of the sugars and fats in foods will be broken down and used for energy instead of being stored as fat. This will also cause the consumer to feel the need to eat less .
In obese patients with type 2 diabetes, people given lipoic acid lost significantly more weight and had lower triglyceride levels .
Overall, lipoic acid may have a role in managing weight, but its effect may not be strong enough to make a big difference on its own. Talk to your doctor about incorporating ALA supplements or ALA-rich foods into your weight loss strategies.
Potential Benefits Under Investigation
ALA is currently under investigation for many other potential benefits, but none have produced the same kind of clinical evidence as the benefits discussed above.
Many of these potential effects have only been studied in cell or animal studies, which may not apply at all to human health. Alternately, they may have human studies that produced mixed or contradictory results. We include them here because we think it’s interesting to see where the research is headed. Talk to your doctor about ALA supplementation or other strategies to manage your health.
5) Brain Health & Neurological Disorders
In all, lipoic acid has produced promising results in various neurological disorders, but further research is still required in order to determine the role of ALA in human brain health and whether it can be used in any therapies.
In rats, lipoic acid given immediately after stroke restored damaged neurons and promoted long-term functional recovery through enhanced anti-inflammatory and antioxidant actions .
Another study in rats showed that lipoic acid reduced brain damage and increased survival rate after a stroke .
When lipoic acid was given daily to patients with AD (receiving a standard treatment with cholinesterase inhibitors), their cognitive symptoms appeared to stabilize. The patients did not improve, but their disease progressed much more slowly .
In another study, in AD patients with dementia, lipoic acid slowed down the progression of the disease .
Levels of acetylcholine (Ach) are significantly decreased in Alzheimer’s. Many of the drugs that are currently used to treat this disease work to increase Ach levels. In rats, it was shown that lipoic acid raises the level of acetylcholine (Ach) and choline acetyltransferase (ChAT, an enzyme that increases available acetylcholine levels) and decreased the activity of acetylcholinesterase (AchE) in the brain .
Parkinson’s disease is described as a disease with reduced dopamine function and loss neurons in the brain due to misfolded proteins, poor autophagy, increased oxidative stress and inflammation, and mitochondria dysfunction .
In a mouse model of Parkinson’s disease, lipoic acid improves motor dysfunction, protects against dopaminergic neurons loss, and decreases α-synuclein accumulation in the substantia nigra area of the brain. Further, lipoic acid inhibits the activation of nuclear factor-κB (NF-κB) and decreases proinflammatory molecules .
Lipoic acid reduces neuronal death in laboratory models of Parkinson’s disease .
Side Effects of Antipsychotics
Weight gain and other metabolic disturbances are major side effects of atypical antipsychotic drugs (AAPDs). In schizophrenia patients using AAPDs, lipoic acid reduced BMI (weight to height ratio) and total cholesterol levels .
Lipoic acid also promoted weight loss and reduced abdominal fat in overweight and clinically stable schizophrenia patients. Moreover, lipoic acid was well tolerated throughout the 12-week study .
Lipoic acid also improved metabolic risk factors in Schizophrenia patients. A study showed that lipoic acid increased adiponectin and decreased fasting glucose and aspartate aminotransferase (AST, a liver enzyme) .
In a Russian study, lipoic acid reduced relapse frequency in multiple sclerosis patients and decreased corticosteroid use . Effects were further magnified by adding other antioxidants to the regimen.
Lipoic acid suppressed the symptoms of MS in a mouse model .
6) Exercise Recovery
Further clinical studies are required to determine whether ALA supplements improve exercise recovery in humans.
By increasing blood total antioxidant capacity, lipoic acid protected DNA and fatty acids from oxidative stress due to exercise .
Lipoic acid appeared to shift the internal chemistry of cells, promoting the regeneration of injured muscles. In physically active males, lipoic acid significantly elevates H2O2 but reduced NO generation before or after exercise. Lipoic acid increases IL-6 and IL-10 levels at 20 min after exercise and decreases IL-1β and TNF-α before and after exercise .
7) Decreases Inflammation
A diet rich in lipoic acid could reduce markers of inflammation over time, but more studies on the effect of supplements are required.
Abnormal inflammatory responses contribute to diseases such as diabetes, Alzheimer’s disease and multiple sclerosis . Lipoic acid was shown to have an anti-inflammatory effect in subjects with multiple sclerosis , metabolic syndrome , and diabetes .
Lipoic acid can reduce inflammatory markers in subjects with organ transplants .
8) Heart Health
Dietary lipoic acid may help support heart health, but more research into the effects of supplements on the human heart is required.
Many studies suggest the potential role of lipoic acid in the prevention and treatment of atherosclerosis (hardening of the arteries) and related cardiovascular disease .
Lipoic acid improves blood vessel structure and function [1, 6]. Lipoic promotes anti-inflammatory and antithrombotic (blood clot-reducing) pathways and increases nitric oxide-mediated vasodilatation (blood vessel widening) .
Lipoic acid may also decrease atherosclerotic plaque burden .
One study indicates that lipoic acid may increase the atherogenicity of LDL, but when it’s combined with exercise, this atherogenic effect is abolished .
Lipoic acid may have a beneficial effect in preventing the development of hypertension (elevated blood pressure) by lowering the level of inflammatory cytokines in the blood, thus preventing pathological changes to blood vessel cells and normalizing changes in blood pressure .
In multiple clinical trials, lipoic acid inhibited the overproduction of endothelin I, the main vasoconstrictor (narrower of blood vessels) . Furthermore, lipoic acid significantly increased the synthesis of NO, the main vasodilator (widener of blood vessels) .
Lipoic acid may improve the function of the cells making up the blood vessel walls .
However, clinical studies have also shown that lipoic acid is not very effective in lowering blood pressure on its own. Its effectiveness at reducing blood pressure is limited without the use of other strategies .
9) Metabolic Syndrome
People who eat a diet rich in ALA seem to be less likely to develop the markers of metabolic syndrome, but the relationship is unclear and more human research is required.
In patients with metabolic syndrome, lipoic acid improved blood vessel cell function and reduced proinflammatory markers .
In obese subjects with impaired glucose tolerance, lipoic acid improved insulin sensitivity and decreased free fatty acids, triglycerides, total cholesterol, and LDL cholesterol. Lipoic acid also decreased proinflammatory markers and increased adiponectin .
10) Eye Health
Further research will be required to determine the role of lipoic acid in human eye health.
Oxidative stress increases with aging and conditions such as diabetes, and it can have detrimental effects on vision. According to a few studies, lipoic acid may help by counteracting oxidative stress in the eyes.
In one study, lipoic acid improved vision and other symptoms in 45 patients with glaucoma .
Lipoic acid also improved the vision-related quality of life in patients with age-related macular degeneration (AMD) .
Lipoic acid reduced retinal cell death in mice with retinitis pigmentosa, an inherited, degenerative eye disease .
Migraines are poorly understood, and much more research will be needed to determine the role of lipoic acid in their prevention and treatment.
In patients with migraines, lipoic acid has the ability to reduce the frequency, duration, and intensity of migraines .
Lipoic acid improved the effectiveness of the migraine drug topiramate. The combination of lipoic acid and topiramate was significantly more effective at decreasing the frequency and duration of migraines than the drug alone. In addition, lipoic acid helped reduced topiramate-related side effects .
While lipoic acid is not as effective as conventional painkillers, it may reduce the quantity of pharmaceutical drugs required to manage pain. Much more research will be required to determine its role in pain management.
Lipoic acid improved the quality of life in patients with neuropathies. A significant reduction was observed in a number of pain parameters, such as intensity, burning, unpleasantness and superficial pain .
Lipoic acid reduced the postoperative incidence of pain in patients with carpal tunnel syndrome .
Lipoic acid decreased sciatic pain caused by a herniated disc. Patients on lipoic acid reported a decreased need for analgesia .
Lipoic acid administered together with gamma-linolenic acid (GLA) reduced symptoms and functional impairment in patients with carpal tunnel syndrome .
13) Ulcers and IBD
There have, as of yet, been no studies on the effect of ALA in humans with ulcers or IBD.
In rats, lipoic acid protected against alcohol-induced stomach ulcers .
Other studies also showed that lipoic acid effectively attenuates ulcerative colitis in mice [92, 93]. However, in one study in mice with mild ulcerative colitis, lipoic acid actually increased oxidative damage to the colon and liver .
14) Sperm Quality
While promising, these results are limited to a single study which has not yet been repeated. Much more research will be required to determine the effect of ALA on male fertility. However, eating a healthy, ALA-rich diet wouldn’t hurt.
In a study of 44 infertile men, 600 mg of lipoic acid significantly increased total sperm count, sperm concentration, and motility levels after 12 weeks .
15) High-Risk Pregnancies
More human studies will be required to determine the full extent of ALA’s role in pregnancy and birth. While ALA-rich foods should be safe, talk to your doctor before supplementing with lipoic acid if you are expecting.
In high-risk pregnancies, lipoic acid may facilitate the return to normal pregnancy conditions and improve the condition of both the mother and the fetus . Additionally, smaller numbers of miscarriages were recorded with lipoic acid supplementation .
Lipoic acid decreases inflammation in women with gestational diabetes .
Lipoic acid reduced cervical inflammation after a preterm labor episode .
16) Bone Health
Again, while eating a healthy diet rich in ALA probably won’t hurt, more studies are required to fully flesh out the role of lipoic acid in bone health.
In postmenopausal women with osteopenia (low bone density), lipoic acid slightly increased bone mineral density (BMD) .
In female rats with osteopenia, lipoic acid not only stopped the bone resorption but stimulated its formation .
Lipoic acid decreased inflammation and ameliorated cartilage degeneration in rats with osteoarthritis .
While these results may seem promising, they have not been repeated in human trials. Many ALA-rich foods are generally considered healthy, but it’s important to talk to your doctor if you think you’ve been exposed to heavy metals or other toxic compounds.
Lipoic acid protected against Cd-induced oxidative stress and kidney cell death in rats .
Lipoic acid attenuated liver damage caused by copper nanoparticles in rats .
In rats, administration of lipoic acid together with zinc and calcium ameliorated lead (Pb) toxicity and decreased lead body burden to near-normal. Lipoic acid does this by preventing the accumulation of lead within the blood and tissues .
Other Toxic Compounds
Dimethylnitrosamine (DMN) is a waste product of several industrial processes. Lipoic acid reduces kidney damage caused by this chemical in male mice .
Lipoic acid protected against polychlorinated biphenyl (PCB)-induced testicular toxicity in male rats .
Lipoic acid reduced methylmercury-induced brain injury in rats .
Lipoic acid attenuated antimycin A-induced cell toxicity .
18) Cancer Research
These early studies indicate that lipoic acid is suitable for further study in cancer research. They are not grounds to recommend ALA supplements to cancer patients. Many compounds seem to have “anti-cancer effects” in cell studies, but fail to do anything against cancer in animals or humans.
Cell-based and animal model studies have suggested that lipoic acid may inhibit the initiation and promotion stages of cancer .
19) Longevity Research
Longevity research is contentious and controversial, and the extent to which lifespan can be extended with diet and supplements is unknown. Furthermore, ALA has not been correlated with longevity in humans. However, many ALA-rich foods are part of a healthy diet, and lipoic acid consumption may be linked to lifespan in this way.
A study showed that while lower doses of lipoic acid increased the total lifespan in mice, high doses decreased it .
It is well known that dietary restriction extends lifespan. When mice were first exposed to dietary restrictions and then allowed to feed as desired, the beneficial effect of dietary restriction was abolished. However, when mice were supplemented with lipoic acid in the second phase, the beneficial effect of dietary restriction on longevity was maintained .
Lipoic acid may improve longevity by:
- Fighting free radicals. Aging and reduced longevity are due in part to the action of free radicals. Lipoic acid is effective in protecting against the damage caused by free radicals .
- Rejuvenating mitochondria. Feeding old rats with acetyl carnitine and lipoic acid for a few weeks restored mitochondrial function and lowered oxidants to the level of young rats .
- Increasing telomerase. Lipoic acid may increase telomerase , thereby increasing telomere length and reversing the aging process.
20) Topics of Future Research
Because of its antioxidant and anti-inflammatory effects, lipoic acid is currently being investigated in the context of a variety of health conditions.
Note that many of these conditions only have a single study available, meaning that the evidence is nowhere near the vicinity of sufficient to recommend ALA for patients.
Some of the conditions are listed below.
- Hypothyroidism: In patients with subclinical hypothyroidism, lipoic acid improved endothelial function, by decreasing oxygen-derived free radicals .
- HIV infection: In human immunodeficiency virus (HIV)-infected subjects with a history of unresponsiveness to highly active antiretroviral treatment, lipoic acid increased glutathione levels and enhanced or stabilized lymphocyte proliferation .
- Cystinuria: Lipoic acid inhibited cystine stone formation in mice .
- Liver Surgery: Lipoic acid reduced ischemia/reperfusion injury of the liver in humans undergoing liver surgery .
- Heart Surgery: In patients with coronary heart disease and those planned for coronary artery bypass graft operation, lipoic acid significantly decreased inflammation when blood is removed from the body (extracorporeal circulation) .
- High-fructose corn syrup caused pancreatic damage: Lipoic acid ameliorated metabolic changes and pancreatic lesions .
- Peripheral Artery Disease: 3 months of lipoic acid supplementation improved walking tolerance and delayed pain onset in peripheral arterial disease .
- Acute Coronary Syndrome: Lipoic acid ameliorated oxidative stress in patients with confirmed acute coronary syndrome (ACS) .
- Takotsubo syndrome: Takotsubo syndrome is a form of stress-induced heart muscle damage. Lipoic acid improved the innervation of adrenergic nerve cells in the hearts of patients with Takotsubo syndrome .
- Heart Failure: Lipoic acid prevented heart cell death [6, 6], prevented progressive heart remodeling, and improved heart function in animal studies .
- Olfactory Loss: Infections of the upper respiratory tract sometimes result in the loss of the sense of smell. Lipoic acid improves olfactory function .
- Idiopathic dysgeusia: In patients with idiopathic dysgeusia, an altered perception of taste, lipoic acid was associated with significant symptomatic improvements .
- Sickle Cell Disease: In patients with sickle cell disease, lipoic acid protected a subset of patients from oxidative damage to fat and proteins .
- Polycystic ovary syndrome: A combination of lipoic acid and d-chiro-inositol (DCI) improved clinical and metabolic health in women with polycystic ovary syndrome . Supplementation of myoinositol and lipoic acid improved reproductive outcome and metabolic profiles in PCOS women undergoing in vitro fertilization .
- Chronic Spinal Cord Injury: In men with chronic spinal cord injury, lipoic acid reduced fasting blood sugar, body weight, BMI, waist circumference and blood pressure. Lipoic acid also decreased food intake .
Lipoic Acid Mechanisms
Antioxidants and antioxidant enzymes:
- Increased glutathione (GSH) [20, 6, 49, 92]
- Increases superoxide dismutase (SOD) [69, 33, 6, 92]
- Increases catalase (CAT) 
- Increases Nrf-2 
Markers of oxidative stress:
- Decreases malondialdehyde (MDA) [20, 33, 49, 92]
- Decreases myeloperoxidase (MPO) 
- Decreases troponin-I levels 
- Decreases Nox4 and p22phox (CYBA) 
- Reduces both Th1 and Th2 cytokines 
- Decreases TNF-α [62, 20, 6, 56, 142, 104]
- Decreases IL-2 , IL-4 [56, 143], IL-1β  and IL-17 
- Can increase , but mostly decreases IL-6 [56, 65, 142]
- Increases IL-10 
- Decreases CRP 
- Decreases NO [62, 20, 92], but can also increase NO 
- Decreases iNOS 
- Suppresses NK cell activation 
- Decreases TGF-beta [20, 143]
- Decreases IFNγ [56, 143]
- Decreases NF-κB [6, 104]
- Decreases MMP-2 [20, 56] and MMP-9 [58, 56]
- Decreases ICAM-1 [58, 56, 143, 142] and VCAM-1 
- Decreases MCP-1 (CCL2) [56, 142] and RANTES (CCL5) 
- Increases heme oxygenase (HO-1, HMOX1) 
- Activates AMPK [144, 145]
- Modestly reduced nonesterified fatty acids (NEFA) 
- Increases LDL receptor (LDL-R) 
- Decreases PPARγ , C/EBPα, and C/EBPβ 
- Increases SIRT1 
- Increases PDK4 
- Increases PPARβ (PPARD) 
- Increases acetylcholine (ACh) and choline acetyltransferase (ChAT) and decreases acetylcholinesterase (AChE) in the hippocampus 
- Increases VGlut1 
Cells and mitochondria:
- Increases Bcl-2 
- Decreases Bax, caspase-3 and caspase-9 activity 
- Increases PGC-1α (PPARGC1A), TERT 
Sources of Lipoic Acid
- Plant oils 
- Fish and seafood 
- Nuts and seeds 
- Vegetables (spinach, broccoli, tomato) 
- Meat (kidney, liver, heart) 
Available supplements come in doses of lipoic acid between 600 – 1,800 mg daily . Studies show that increased dosage is also followed by increased side effects.
Oral lipoic acid has a limited bioavailability of about 30% . Studies show that there is significant inter-subject variability in peak blood lipoic acid concentrations, due to individual differences in gut absorption .
Potential Risks and Side Effects
Urticaria and itching are the most common adverse events, but they are generally mild and go away on their own .
Lipoic acid is also associated with a dose-dependent increase in nausea, vomiting, and vertigo . Higher doses of 1,200 mg and 1,800 mg have more frequent adverse effects . An oral dose of 600 mg once daily appears to provide the optimum risk-to-benefit ratio .
This is particularly the case in the elderly population, where 600 mg dose was well tolerated, but higher doses caused intolerable flushing and intolerable upper gastrointestinal side effects. However, subjects taking gastrointestinal prophylaxis medications had no upper gastrointestinal side effects .
Lipoic acid (possible overdose) may cause refractory convulsions in children .
One study in mice suggests that prophylactic and abundant intake of lipoic acid causes fatty liver and liver injury . There is one recorded case of lipoic acid causing acute cholestatic hepatitis in humans . It may be prudent to monitor cholesterol and liver enzymes with long-term lipoic acid supplementation.
Finally, in rats, it was shown that lipoic acid reduces the absorption of iron. Lipoic acid supplementation could potentially trigger iron deficiency anemia . No such events have been reported in humans though.
Talk to your doctor before supplementing with ALA to avoid adverse events and unexpected interactions.