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What is Alpha-Lipoic Acid (ALA)? + Dosage & Side Effects

Written by Biljana Novkovic, PhD | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Biljana Novkovic, PhD | Last updated:

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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?

Lipoic acid (LA), also known as alpha-lipoic acid (ALA), R-lipoic acid, or thioctic acid, is a disulfide-containing compound [1], found inside every cell of the body [2].

Some call it the “universal antioxidant” [3].

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) [1].
  • 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 [2].
  • Lipoic acid is an essential cofactor for mitochondrial respiratory enzymes that improves mitochondrial function [4]. Lipoic acid exerts a “rejuvenating” impact on mitochondria by protecting them against the higher levels of ROS they produce during the aging process [5].
  • Lipoic acid also has anti-inflammatory action, independently of its antioxidant activity [3].

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 [2].

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 [3].

Lipoic acid is an antioxidant compound found inside every cell. It is essential for many enzymatic reactions, and it is essential for the normal function of the human body.

Antioxidant Activity

Lipoic acid neutralizes free radicals and associated oxidative cellular damage [7, 8].

Lipoic acid scavenges several reactive oxygen species (ROS) [1].

Lipoic acid also helps regenerate antioxidant vitamins C and E [1, 2].

In addition, lipoic acid promotes the activity of other antioxidants such as glutathione and coenzyme Q10, which are two essential anti-aging health-promoting compounds [9].

Lipoic acid increases tissue GSH levels, which otherwise decline with age, by restoring glutathione peroxidase activity [5].

Ongoing Speculative Research

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 [10].

ALA has also been studied for its potential effects on lung and breast cancer cells [11, 12].

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 [13].
  • 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 [14].
  • Cystinuria: Lipoic acid inhibited cystine stone formation in mice [15].
  • Liver Surgery: Lipoic acid reduced ischemia/reperfusion injury of the liver in humans undergoing liver surgery [16].
  • 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) [17].
  • High-fructose corn syrup caused pancreatic damage: Lipoic acid ameliorated metabolic changes and pancreatic lesions [18].
  • Peripheral Artery Disease: 3 months of lipoic acid supplementation improved walking tolerance and delayed pain onset in peripheral arterial disease [19].
  • Acute Coronary Syndrome: Lipoic acid ameliorated oxidative stress in patients with confirmed acute coronary syndrome (ACS) [20].
  • 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 [21].
  • Heart Failure: Lipoic acid prevented heart cell death [5], prevented progressive heart remodeling, and improved heart function in animal studies [5].
  • Olfactory Loss: Infections of the upper respiratory tract sometimes result in the loss of the sense of smell. Lipoic acid improves olfactory function [22].
  • Idiopathic dysgeusia: In patients with idiopathic dysgeusia, an altered perception of taste, lipoic acid was associated with significant symptomatic improvements [23].
  • Sickle Cell Disease: In patients with sickle cell disease, lipoic acid protected a subset of patients from oxidative damage to fat and proteins [24].
  • Polycystic ovary syndrome: A combination of lipoic acid and d-chiro-inositol (DCI) improved clinical and metabolic health in women with polycystic ovary syndrome [25]. Supplementation of myoinositol and lipoic acid improved reproductive outcome and metabolic profiles in PCOS women undergoing in vitro fertilization [26].
  • 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 [27].

Lipoic Acid Mechanisms

Antioxidants and antioxidant enzymes:

Markers of oxidative stress:

Inflammation:

Fat metabolism:

Cardiovascular system:

Brain function:

Cells and mitochondria:

Sources of Lipoic Acid

Dietary

  • Vegetables (spinach, broccoli, tomato) [47].
  • Meat (kidney, liver, heart) [47].

Supplemental Doses

Available supplements come in doses of lipoic acid between 600 – 1,800 mg daily [9]. Studies show that increased dosage is also followed by increased side effects.

Oral lipoic acid has a limited bioavailability of about 30% [48]. Studies show that there is significant inter-subject variability in peak blood lipoic acid concentrations, due to individual differences in gut absorption [49].

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 [4].

Lipoic acid is also associated with a dose-dependent increase in nausea, vomiting, and vertigo [50]. Higher doses of 1,200 mg and 1,800 mg have more frequent adverse effects [51]. An oral dose of 600 mg once daily appears to provide the optimum risk-to-benefit ratio [50].

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 [52].

Lipoic acid (possible overdose) may cause refractory convulsions in children [53].

One study in mice suggests that prophylactic and abundant intake of lipoic acid causes fatty liver and liver injury [54]. There is one recorded case of lipoic acid causing acute cholestatic hepatitis in humans [55]. 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 [56]. No such events have been reported in humans though.

Talk to your doctor before supplementing with ALA to avoid adverse events and unexpected interactions.

The most common side effects of lipoic acid supplementation is itching, while some people also experience nausea, vomiting, and vertigo.

Further Reading

Takeaway

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.

About the Author

Biljana Novkovic

Biljana Novkovic

PhD
Biljana received her PhD from Hokkaido University.
Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science and health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

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