Alpha Lipoic Acid

Alpha-lipoic acid (ALA) is a natural compound that helps cells make energy. Although a popular "anti-aging" supplement, animal research suggests that ALA can have either good or bad effects on brain health and lifespan. The evidence from human research is very limited and similarly mixed. ALA supplements are generally regarded as safe.

EFFICACY
Possibly
with   Very limited  evidence
SAFETY WHEN
USED AS DIRECTED
Very likely
with   Moderate  evidence

ALA is made by our cells and helps convert sugar into energy. ALA acts as an antioxidant in laboratory experiments on isolated cells, helping to protect against free radical and inflammatory damage (1, 2). Whether ALA functions as an antioxidant in the human body remains unclear.

Did You Know? Before discovering its essential role in helping cells make energy, ALA was known as "potato growth factor" because it was first isolated from potatoes and helped bacteria to grow.

ALA is naturally produced in plant and animal cells, especially in organs such as the heart, liver and kidneys, as well as leafy greens.

ALA is available as a supplement in capsule form. When ALA is commercially synthesized, two "mirror image" forms are produced, which are referred to as R-lipoic acid (R-LA) and S-lipoic acid (S-LA). R-LA is the form that is naturally produced by animal and plant cells and is more easily used by cells than S-LA (3). Although supplements contain either pure R-LA or equally proportioned mixes of R- and S-LA, it is unclear if one supplement type is more effective.

Laboratory research suggests that ALA may act as an antioxidant, scavenging free radicals and preventing inflammation and damage of brain cells in conditions like stroke, multiple sclerosis, Alzheimer's disease, and dementia.

Most evidence for brain protection comes from experiments in isolated cells and laboratory animals. In mice, ALA treatment before a stroke reduced the amount of brain damage by 35-40%, as well as improved brain function and recovery (4). Another study in rats found that after traumatic brain injury, ALA enhanced healing by reducing cell death and scar tissue formation, while increasing blood vessel formation and blood flow to the damaged area (5). However, these results have yet to be replicated in humans.

Possibly protects against dementia, based on very limited evidence. In animal and test tube experiments, ALA can reduce the formation of Alzheimer's disease plaques and increase the production of acetylcholine, an important signaling molecule that is impaired in Alzheimer's disease (6). However, we don't yet know whether ALA can prevent dementia or age-related cognitive decline in humans. An upcoming clinical trial will explore whether an omega-3-ALA vitamin cocktail could help prevent Alzheimer's disease (NCT01780974).

Controversial value to Alzheimer's patients, due to mixed evidence. Human research on ALA in mild cognitive impairment (MCI) and Alzheimer's has been limited with mixed results. In the largest clinical trial to-date, Alzheimer's patients' cognitive function was worsened, not improved, by 16 weeks of treatment with an antioxidant cocktail of ALA (900mg), vitamin E and Vitamin C. The supplements did reduce evidence of oxidative stress in the brain by 19%, but that did not appear to help the patients (7). In a smaller but longer clinical trial, patients with Alzheimer's disease did benefit from supplementation with a combination of 600mg of ALA with omega-3 fatty acids. Specifically, the patients receiving the supplement had less cognitive and functional decline over the course of one year compared to the group that received placebo (8).

In a mouse model of Alzheimer's disease, a combination of ALA and regular exercise improved certain aspects of learning and memory compared to sedentary mice (9). Another study found that 2 weeks of ALA treatment improved learning and memory and reduced oxidative stress in very old mice (10).

Unlikely, based on very limited evidence. Although ALA is a popular anti-aging supplement, the evidence that it extends lifespan is mixed. Experimental results from fruit flies and worms suggest that ALA extends lifespan (11, 12), but these results have not been reliably replicated in mammals. One study in mice showed that ALA supplementation extended lifespan in mice that had undergone a period of caloric restriction, but it blocked the lifespan extension effects of dietary restriction when it was taken before starting the diet (13). However, another study found that ALA daily supplementation shortened lifespan in older mice by 18% (10).

Very likely safe based on moderate evidence. Evidence from human trials suggests that alpha-lipoic acid is generally safe for healthy individuals, with one clinical trial reporting occasional minor stomach discomfort at high doses (8).

Because of its potential function as an antioxidant, ALA may reduce the effectiveness of chemotherapy or radiation therapy in cancer patients (14, 15). Always talk to your oncologist about any dietary supplements you take and how they may affect your treatment.

There are no official recommended doses for ALA supplements, but clinical trials have used doses ranging from 20-1800 mg a day for up to a year without reporting serious side effects.

Due to its potential antioxidant and anti-inflammatory functions, ALA is being considered as a potential therapy for a number of disorders. An upcoming clinical trial will further explore the possible benefits of an omega 3 fatty acids+ALA vitamin cocktail in Alzheimer's disease prevention (NCT01780974). Currently, clinical trials are underway to determine whether ALA by itself or in combination with other compounds can be effective for treating or preventing conditions such as heart disease (NCT00765310), thyroid cancer (NCT01396733), multiple sclerosis (NCT01188811), and obesity (NCT01138774).  More information about planned and on-going clinical trials can be found at clinicaltrials.gov (U.S.) and at clinicaltrialsregister.eu (Europe).

  • WebMD offers information on alpha lipoic acid dosing and safety.
  • The FDA gives an overview on dietary supplements, their regulation and safety.
  1. Packer, L., Tritschler, H. J. & Wessel, K. (1997) Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic Biol Med 22: 359-378.
  2. Smith, A. R., Shenvi, S. V., Widlansky, M., Suh, J. H. & Hagen, T. M. (2004) Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem 11: 1135-1146.
  3. Breithaupt-Grogler, K., Niebch, G., Schneider, E., Erb, K., Hermann, R., Blume, H. H., Schug, B. S. & Belz, G. G. (1999) Dose-proportionality of oral thioctic acid--coincidence of assessments via pooled plasma and individual data. Eur J Pharm Sci 8: 57-65.
  4. Clark, W. M., Rinker, L. G., Lessov, N. S., Lowery, S. L. & Cipolla, M. J. (2001) Efficacy of antioxidant therapies in transient focal ischemia in mice. Stroke 32: 1000-1004.
  5. Rocamonde, B., Paradells, S., Barcia, J. M., Barcia, C., Garcia Verdugo, J. M., Miranda, M., Romero Gomez, F. J. & Soria, J. M. (2012) Neuroprotection of lipoic acid treatment promotes angiogenesis and reduces the glial scar formation after brain injury. Neuroscience 224: 102-115.
  6. Holmquist, L., Stuchbury, G., Berbaum, K., Muscat, S., Young, S., Hager, K., Engel, J. & Munch, G. (2007) Lipoic acid as a novel treatment for Alzheimer's disease and related dementias. Pharmacol. Ther. 113: 154-164.
  7. Galasko, D. R., Peskind, E., Clark, C. M., Quinn, J. F., Ringman, J. M., Jicha, G. A., Cotman, C., Cottrell, B., Montine, T. J. et al. (2012) Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 69: 836-841.
  8. Shinto, L., Quinn, J., Montine, T., Dodge, H. H., Woodward, W., Baldauf-Wagner, S., Waichunas, D., Bumgarner, L., Bourdette, D. et al. (2014) A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer's disease. J Alzheimers Dis 38: 111-120.
  9. Cho, J. Y., Um, H. S., Kang, E. B., Cho, I. H., Kim, C. H., Cho, J. S. & Hwang, D. Y. (2010) The combination of exercise training and alpha-lipoic acid treatment has therapeutic effects on the pathogenic phenotypes of Alzheimer's disease in NSE/APPsw-transgenic mice. Int. J Mol Med 25: 337-346.
  10. Farr, S. A., Price, T. O., Banks, W. A., Ercal, N. & Morley, J. E. (2012) Effect of alpha-lipoic acid on memory, oxidation, and lifespan in SAMP8 mice. J Alzheimers Dis 32: 447-455.
  11. Bauer, J. H., Goupil, S., Garber, G. B. & Helfand, S. L. (2004) An accelerated assay for the identification of lifespan-extending interventions in Drosophila melanogaster. Proc Natl Acad Sci U. S. A 101: 12980-12985.
  12. Benedetti, M. G., Foster, A. L., Vantipalli, M. C., White, M. P., Sampayo, J. N., Gill, M. S., Olsen, A. & Lithgow, G. J. (2008) Compounds that confer thermal stress resistance and extended lifespan. Exp Gerontol 43: 882-891.
  13. Merry, B. J., Kirk, A. J. & Goyns, M. H. (2008) Dietary lipoic acid supplementation can mimic or block the effect of dietary restriction on life span. Mech Ageing Dev 129: 341-348.
  14. Melli, G., Taiana, M., Camozzi, F., Triolo, D., Podini, P., Quattrini, A., Taroni, F. & Lauria, G. (2008) Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy. Exp Neurol 214: 276-284.
  15. Dovinova, I., Novotny, L., Rauko, P. & Kvasnicka, P. (1999) Combined effect of lipoic acid and doxorubicin in murine leukemia. Neoplasma 46: 237-241.

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