Who Found Alpha-Lipoic Acid, and Why a Liver Factor Became a Mitochondria Story
Alpha-lipoic acid began as a microbial growth factor that Reed's group traced to liver, then became a cofactor for mitochondrial enzymes. This history covers the 1951 crystals, the German trials, the R-form studies and how research doses compare with label doses.
The history of alpha-lipoic acid starts with a microbial growth factor and ends inside the mitochondria of nearly every cell. In his own account, Lester Reed says he inherited a project on an "acetate-replacing factor" in the spring of 1949. Esmond Snell and associates had started that research at the University of Wisconsin and continued it at the University of Texas. Reed's group found that liver was a rich source of the factor ([Reed, JBC 2001](https://www.jbc.org/article/S0021-9258%2820%2974076-7/fulltext)). ## Liver residue, 6-pound batches, and 10 tons for 30 milligrams Reed reports obtaining the first pale yellow crystals, about 3 milligrams, on or about March 15, 1951. The material his lab used was liver residue, not fresh liver. Pharmaceutical companies were processing pork and beef liver into extracts for pernicious anemia, and the residue left over was dried and sold as an animal feed supplement. Reed arranged to get that residue from Eli Lilly and Co., and Lilly later scaled the method up to 250-pound batches. By Reed's estimate, about 10 tons of liver residue went into roughly 30 milligrams of crystalline compound. The team published the crystal work in [Science](https://pubmed.ncbi.nlm.nih.gov/14854913/) that year. The structure came next. Reed's account describes lipoic acid as a cyclic disulfide. The correct form, 6,8-dithiooctanoic acid, was established by synthesis at Lederle Laboratories, where E. L. R. Stokstad and associates made dl-lipoic acid. ## A cofactor for the enzymes that burn fuel in mitochondria Lipoic acid serves as a cofactor for the pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes. Reed's account places both complexes in mitochondria and describes the lipoyl group as attached to the enzyme by a flexible arm, which he proposed lets the group move among the active sites in a "swinging arm" mechanism ([Reed, JBC 2001](https://www.jbc.org/article/S0021-9258%2820%2974076-7/fulltext)). A 2017 review calls lipoic acid an essential cofactor for mitochondrial 2-ketoacid dehydrogenase complexes ([DOI](https://doi.org/10.1074/jbc.TM117.000259)). The same complexes pass electrons to NAD+, the coenzyme covered in our [NAD longevity guide](/health/nad-longevity-complete-guide). For the wider mitochondrial picture, see our [mitochondrial health guide](/health/mitochondrial-health-complete-guide), and for the other mitochondrial cofactor, see our [CoQ10 ingredient page](/ingredients/coq10-coenzyme-q10). ## What the German trials measured, and what they did not A 2002 review of mercury toxicity says in its background that alpha-lipoic acid has been used in Germany as an approved treatment for diabetic polyneuropathy for 40 years ([PubMed](https://pubmed.ncbi.nlm.nih.gov/12495372/)). The sources reviewed here do not document approvals in other countries, so none are named. ALADIN, a three-week trial published in 1995, was run by a team in Düsseldorf and enrolled 328 people with non-insulin-dependent diabetes and symptomatic peripheral neuropathy. They received intravenous alpha-lipoic acid at 1,200, 600 or 100 mg a day, or placebo. The 600 mg group had a larger drop in symptom scores than placebo (p < 0.001), and adverse events were 18.2% at 600 mg and 20.7% on placebo ([DOI](https://doi.org/10.1007/BF00400603)). ALADIN III, a seven-month trial, enrolled 509 outpatients. The active arm received 600 mg intravenously for three weeks, then 600 mg three times a day by mouth for six months. Symptom scores did not separate the groups by the end, and the authors wrote that the treatment had no effect on neuropathic symptoms distinguishable from placebo to a clinically meaningful degree, possibly because of rising variability between centers. The same trial reported a favorable effect on neuropathic deficits ([DOI](https://doi.org/10.2337/diacare.22.8.1296)). A 2004 meta-analysis of four of these trials, covering 1,258 patients, reported a 24.1% relative difference in favor of alpha-lipoic acid on symptom scores after three weeks of intravenous treatment. Responder rates were 52.7% on alpha-lipoic acid and 36.9% on placebo. The authors searched the database of a German drug company, VIATRIS GmbH, to find the trials, a detail readers should weigh when judging the pooled result ([DOI](https://doi.org/10.1111/j.1464-5491.2004.01109.x)). ## The R form and the racemic mix The racemic form is a 1:1 mix of R and S forms, as a 2020 crossover trial describes it ([DOI](https://doi.org/10.1002/jcph.1605)). A 2019 review reports that the R enantiomer shows better pharmacokinetic parameters than the S form, including higher bioavailability, and puts the bioavailability of ALA at about 30% ([DOI](https://doi.org/10.3390/biom9080356)). In that 2020 trial, 20 people with progressive multiple sclerosis took 600 mg of R-lipoic acid in one period and 1,200 mg of the racemic mix in another. Blood levels were bioequivalent, and reports of each gastrointestinal side effect were lower on the R form, 31 versus 60. ## Does the label dose match the research dose? The gap between research doses and label doses is wide. The ALADIN trials used 600 mg a day, and the R-form trial used 600 mg of R-lipoic acid. Those are the amounts the trials measured, so they are the reference point for any label comparison. Mt. Angel Vitamins sells [CoQ10 100 mg Plus Alpha Lipoic Acid](https://mtangelvitamins.com/products/coq10-alpha-lipoic-acid?utm_source=learn_hub&utm_medium=content&utm_campaign=blog_post&utm_content=history-of-alpha-lipoic-acid-from-liver-to-mitochondria), one capsule a day with 100 mg of CoQ10, 100 mg of lecithin and 5 mg of alpha-lipoic acid. A 60-capsule bottle is $25.99, about 43 cents a day (live price checked October 22, 2026). At 5 mg, the alpha-lipoic acid in that capsule is a small fraction of the amount the trials used, so the capsule is a different product from the one those studies tested. Reed's own account counts the work in pounds: about 6 pounds of liver residue at a time in his lab, 250-pound batches at Lilly, and roughly 10 tons behind about 30 milligrams of crystals. The milligram figure on a label uses the same unit, but the unit alone does not tell you what a trial tested. ## Next reads - [Mitochondrial health complete guide](/health/mitochondrial-health-complete-guide): the pillar for the pathway this history follows. - [History of iron supplements and the ferritin test](/blog/history/history-of-iron-supplements-and-the-ferritin-test): another origin story in this series, this one about a mineral. ### Related reading - [coenzyme Q10 from beef heart mitochondria to supplements](/blog/history/history-of-coq10-from-beef-heart-to-ubiquinone) - [vitamin E from fertility factor to tocopherol](/blog/history/history-of-vitamin-e-from-fertility-factor-to-tocopherol)