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Alpha-Lipoic Acid

Nutrient Name: Alpha-lipoic acid.
Synonyms: Alpha lipoic acid, ALA, acetate replacing factor, biletan, lipoic acid, lipoicin, thioctacid, thioctan, thioctic acid.
Related Substance: Alpha-dihydrolipoic acid (DHLA); dihydrolipate.

Summary Table
nutrient description

Chemistry and Forms

1,2-Dithiolane-3-pentanoic acid; 1,2-dithiolane-3-valeric acid; 6,8-thioctic acid; alpha-lipoic acid; 5-(1,2-dithiolan-3-yl) valeric acid.

Physiology and Function

Known by many names, alpha-lipoic acid (ALA) is a naturally occurring, fat-soluble and water-soluble, vitamin-like antioxidant and enzyme cofactor. It is involved in antioxidant protection and cell damage prevention, energy production and blood sugar regulation, growth stimulation and regulation of gene transcription, detoxification, and toxic metal chelation. Although the enzyme pathway for its de novo synthesis has not been fully elucidated, cysteine appears to be the source of sulfur, and octanoate serves as the intermediate precursor for the 8-carbon fatty acid. ALA is readily converted into dihydrolipoic acid (DHLA), its reduced form, in many tissues of the body. ALA is not required in the diet and therefore is not considered a true vitamin, because it can be synthesized by humans, as well as plants and other animals.

Lipoic acid was first isolated in 1951 by Reed and co-workers, in the course of research on “potato growth factor” in lactic acid bacteria, as a catalytic agent associated with pyruvate dehydrogenase; it serves as a coenzyme in the Krebs cycle and functions in the same manner as many B-complex vitamins. Lipoamide, the protein-bound form of the naturally occurring isomer R-alpha-lipoic acid, where it is covalently attached through the carboxylic acid to lysine residues, is a required cofactor for several multienzyme complexes that catalyze energy metabolism reactions within mitochondria. The pyruvate dehydrogenase complex and the alpha-ketoglutarate dehydrogenase complex both catalyze reactions within the citric acid cycle. The alpha-ketoacid dehydrogenase complex catalyzes the metabolism of leucine, isoleucine, and valine, the three branched-chain amino acids. ALA also increases glucose transport and improves heart rate variability. Biliary excretion, electrochemically inactive degradation products, and complete utilization of ALA appear to be the primary substrate in the endogenous metabolism. Urinary excretion of ALA and its main metabolites does not play a significant role in ALA elimination.

Alpha-lipoic acid is a carboxy acid with two sulfur atoms that can be oxidized or reduced and thus, along with glutathione, is one of the thiol antioxidants. Lester Packer, PhD, of the University of California–Berkeley, and others demonstrated the potent antioxidant activity of ALA and described it as the “universal,” “ideal,” and “metabolic” antioxidant because of its unique ability to neutralize free radicals in both lipophilic and hydrophilic environments and operate effectively throughout all tissues, including the brain. The low molecular weight and lipophilicity of ALA also enables it to cross the blood-brain barrier and may contribute to its protective effects on brain and neural tissue. ALA directly supports the liver in its detoxifying functions and plays an important role enhancing the activity of the body’s systemic “antioxidant network.” ALA and dihydrolipoic acid (DHLA), also known as dihydrolipoate, both act as powerful antioxidants, protecting against oxidative damage by interacting with potentially damaging reactive oxygen and nitrogen species. In particular, the two forms work together to quench peroxynitrite radicals, an especially destructive class of free radicals consisting of both oxygen and nitrogen, which are known to play a role in the pathophysiology of chronic inflammation, atherosclerosis, lung disease, and neurological disorders. DHLA also enhances the uptake of cysteine by cells to enable increased glutathione synthesis and support intracellular glutathione levels. Furthermore, ALA and DHLA facilitate the synergistic relationship among antioxidants by regenerating ascorbic acid from dehydroascorbic acid, indirectly regenerating vitamin E, and reducing the oxidized forms of vitamin C, glutathione, and coenzyme Q10 to extend their metabolic life spans. Both ALA and DHLA may also chelate free metal ions, such as iron, copper, and arsenic, and prevent them from generating highly reactive free radicals that induce oxidative damage. Lastly, ALA (and DHLA) may play a role in repair of oxidative damage.

Alpha-lipoic acid also regulates signal transduction of nuclear factor kappa B (NF-κB), a transcription factor protein that binds to DNA and affects the rate of transcription of certain genes, with NF-κB-binding sites. By inhibiting the activation of NF-κB, ALA may influence a wide range of pathological processes, including inflammation, atherosclerosis, diabetes, hypertension, glaucoma, cancer, and acquired immunodeficiency syndrome (AIDS).

nutrient in clinical practice

Known or Potential Therapeutic Uses

Alpha-lipoic acid has been used clinically to protect against oxidative stress, to enhance mitochondrial function, to support healthy liver and neurological function, and to reduce the cellular effects of aging. In a clinical trial investigating in vivo antioxidant activity of ALA in healthy humans, Marangon et al. 1 found that a 4-month course of 600 mg/day significantly decreased several biomarkers of oxidative stress compared to baseline. Pharmacokinetic studies of oral ALA suggest that it might be most effectively administered in divided doses throughout the day, rather than in a single daily dose, because it is rapidly absorbed, rapidly metabolized, and rapidly cleared from plasma and tissues.

Historical/Ethnomedicine Precedent

Alpha-lipoic acid has not been used historically as an isolated nutrient.

Possible Uses

Age-related macular degeneration, Alzheimer’s disease (dementia), Amanita poisoning, antioxidant support, cancer, cataracts, cellular oxidative damage, diabetic polyneuropathy, glaucoma, hepatitis C, human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) support, insulin resistance, ischemia-reperfusion injury, metal chelation, neuralgias, surgical recovery, type 2 diabetes mellitus.

Deficiency Symptoms

De novo synthesis generally prevents ALA deficiency, which has not been described per se. Nevertheless, the destruction of its cofactor form may play an important role in numerous pathophysiological processes. For example, individuals with primary biliary cirrhosis may have circulating antibodies to lipoamide-containing enzyme subunits. 2 Likewise, arsenic can render ALA inactive in arsenic toxicity by forming a complex with ALA in dehydrogenase enzymes. 3

Dietary Sources

Limited quantitative information is available regarding ALA content in various food sources, and research into the relationship of dietary sources to circulating free ALA is in preliminary stages. Most dietary ALA is derived from lipoamide-containing enzymes and delivered as lipoyllysine (i.e., bound to lysine), which digestive enzymes may not effectively cleave. 3

Foods that contain mitochondria, especially red meat, are believed to provide the highest levels of alpha-lipoic acid. Other animal sources include heart, liver, kidney, and skeletal muscle (i.e., red meat). Broccoli, spinach, tomatoes, and potatoes are rich plant sources of lipoyllysine, with yeast, peas, brussels sprouts, and rice bran having lower amounts. 4

Nutrient Preparations Available

The R-isomer of alpha-lipoic acid is the form synthesized naturally and is the only form that functions as a cofactor for mitochondrial enzymes; it is currently commercially available. Previously, ALA was exclusively available as a 50/50 racemic mixture of the two optical isomers, R-alpha-lipoic acid and S-alpha-lipoic acid, as rendered by conventional chemical synthesis. R-ALA has greater bioavailability than S-ALA when administered orally and is reduced within the mitochondria to DHLA 28 times more rapidly, hypothetically providing significantly greater antioxidant activity. 5

Dosage Forms Available


Dosage Range


Dietary: Alpha-lipoic acid is created in the human body and thus is not an essential nutrient. Consequently, humans are usually not deficient in ALA.

Supplemental/Maintenance: 20 to 50 mg/day.

Pharmacological/Therapeutic: 50 to 400 mg/day.

The amount of ALA used in research has ranged from 150 to 600 mg per day, with 600 mg/day being used to treat diabetic neuropathies and 150 mg/day for glaucoma.

Toxic: No upper limit (UL) dose has been established.

safety profile


Alpha-lipoic acid has been well tolerated and is considered to be extremely safe in the dosages typically used in clinical settings (e.g., 600 mg/day). When administered under medical supervision to patients with diabetic neuropathy, oral doses as high as 1200 mg/day (600 mg twice daily) for 2 years and 1800 mg/day (600 mg three times daily) for 3 weeks produced no adverse effects. No cases of toxicity from ALA overdose in humans have been published or otherwise reported. Nevertheless, no long-term studies have yet systematically evaluated the safety of ALA in healthy adults.

Nutrient Adverse Effects

General Adverse Effects

Skin rash (occasional).

Pregnancy and Nursing

There are no reports of adverse reactions. However, because no studies have confirmed the safety or documented any dangers of using ALA during pregnancy, nutraceutical intake should be avoided by pregnant or lactating women until safety has been demonstrated.


Use of ALA and other antioxidants is controversial during radiation therapy and some forms of chemotherapy.

Precautions and Warnings

Theoretically, as discussed later, orally administered ALA might enhance the effects of insulin and oral hypoglycemic agents and induce hypoglycemia.

interactions review

Strategic Considerations

Although research into the biological activity of alpha-lipoic acid has been underway for more than 40 years, scientific knowledge of its potential role in clinical medicine has only recently begun emerging in a comprehensive and cohesive picture. The significant antioxidant activity of ALA and alpha-dihydrolipoic acid (DHLA), as well as other modes of biological activity, presents numerous apparent, and many as-yet undiscovered, opportunities for concomitant use with conventional medications, in both the prevention and the reduction of drug adverse effects, as well as through collaborative implementation of integrative strategies and by invoking beneficial or supportive interactions within the context of professional management. Even though R-ALA is the naturally occurring form and has superior pharmacokinetic characteristics, almost all human clinical trials of ALA administration have been performed using racemic ALA. 6 Furthermore, continued research into ALA’s relative role in antioxidant networks will undoubtedly reveal deeper implications for its physiological functions and clinical applications. Thus, more refined research design is warranted to enable advancement of clinical knowledge concerning the therapeutic use and efficacy of alpha-lipoic acid.

nutrient-drug interactions
Cisplatin and Related Platinum Chemotherapy Compounds
Gentamicin, Amikacin, and Related Aminoglycoside Antibiotics
Irbesartan and Related Angiotensin II Receptor Antagonists
Oral Hypoglycemic Agents and Insulin
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Anesthesia, General
Cyclophosphamide and Vincristine
Doxorubicin and Related Anthracycline Chemotherapy

Evidence: Doxorubicin (Adriamycin, Rubex).

Extrapolated, based on similar properties: Daunorubicin (Cerubidine), epirubicin (Ellence, Pharmorubicin), idarubicin (Idamycin, Zavedos), Mitoxantrone (Novantrone, Onkotrone).

Similar properties but evidence lacking for extrapolation: Daunorubicin, liposomal (DaunoXome); doxorubicin, pegylated liposomal (Caelyx, Doxil, Myocet).

The cardiotoxicity of doxorubicin can be of rapid onset and can endure for decades, often absent cardiac complaints. In a longitudinal assessment of cardiac function in 22 patients treated with anthracycline for osteogenic sarcoma or malignant fibrous histiocytoma, Brouwer et al. 23 found systolic dysfunction in more than a quarter of the patients and diastolic dysfunction in nearly half after two decades (median, 22 years). Moreover, cardiac dysfunction was progressive, as measured at 9, 14, and 22 years. Numerous animal studies have demonstrated ALA’s ability to ameliorate myocardial toxicity, nephrotoxicity, and other effects of lipid peroxidation induced by doxorubicin. 24-29 If, as suggested, ALA provides a significant protective effect against toxicity induced by doxorubicin, it may therefore improve the therapeutic index of doxorubicin. Further research in well-designed human trials is warranted to confirm the efficacy of ALA as an adjuvant therapy within a comprehensive approach to chemotherapeutics and to develop clinical guidelines for such integrative therapeutics within oncological care.

Levothyroxine, Thyroid
herb-nutrient interactions
Coenzyme Q10
Omega-3 Fatty Acids (Fish Oil)
Selenium and Milk Thistle (Silybum marianum)
Vitamin B 1 (Thiamine)
Vitamin E
Vitamin K
Citations and Reference Literature
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