Lipoic acid is a natural antioxidant and anti-inflammatory fatty acid with a suite of essential functions, from vitamin metabolism to mitochondrial respiration. Read on to learn more about how this compound works and how to add more of it to your diet.
What is Lipoic Acid?
Some call it the “universal antioxidant” .
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) [1, 2].
- 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, 6].
Also, lipoic acid produced in the body decreases with age, which could increase free radical-induced damage. Lipoic acid supplementation in animal models has also prolonged lifespan and prevented neurological damage .
Ongoing Speculative 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 .
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 , 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) [28, 5, 29, 30].
- Increases superoxide dismutase (SOD) [31, 32, 5, 30].
- Increases catalase (CAT) .
- Increases Nrf-2 .
Markers of oxidative stress:
- Decreases malondialdehyde (MDA) [28, 32, 29, 30].
- Decreases myeloperoxidase (MPO) .
- Decreases troponin-I levels .
- Decreases Nox4 and p22phox (CYBA) .
- Reduces both Th1 and Th2 cytokines .
- Decreases TNF-α [36, 28, 5, 35, 37, 34].
- Decreases IL-2 , IL-4 [35, 38], IL-1β  and IL-17 .
- Can increase , but mostly decreases IL-6 [35, 39, 37].
- Increases IL-10 .
- Decreases CRP .
- Decreases NO [36, 28, 30], but can also increase NO .
- Decreases iNOS .
- Suppresses NK cell activation .
- Decreases TGF-beta [28, 38].
- Decreases IFNγ [35, 38].
- Decreases NF-κB [5, 34].
- Decreases MMP-2 [28, 35] and MMP-9 [41, 35].
- Decreases ICAM-1 [41, 35, 38, 37] and VCAM-1 .
- Decreases MCP-1 (CCL2) [35, 37] and RANTES (CCL5) .
- Increases heme oxygenase (HO-1, HMOX1) .
- Activates AMPK [42, 43].
- 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
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.
Alpha lipoic acid (ALA) is an antioxidant fatty acid with many essential functions in the human body. Notably, it helps regulate antioxidant vitamins (like vitamins E and C) and assists in mitochondrial respiration.
Lipoic acid is also the topic of a great deal of early speculative research. Some researchers believe that it may play a role in suppressing cancer in the early stages, for example, but this has only been demonstrated in cell studies. Limited clinical research also indicates that lipoic acid supplementation may prove useful as a complementary approach to conventional treatments for a number of conditions. As always, talk to your doctor if you think supplements could help you reach your health goals.
The most common adverse side effects of lipoic acid supplements include itching, nausea, vomiting, and vertigo.