Acetyl-L-CarnitineALCAR / ALC · 4 claims

Pooled across randomised trials, ALCAR reduced pain on the visual analogue scale by 1.47 points (95% CI 1.06–1.87, p<0.00001) in diabetic peripheral neuropathic pain. Effect was similar whether given orally (MD 1.15, 95% CI 0.33–1.96) or as an intramuscular-oral sequence (MD 1.19, 95% CI 0.34–2.04).

No severe adverse events were reported, and total adverse event rates matched control. Common complaints were pain, headache, paraesthesia, hyperesthesia, retching, biliary colic and gastrointestinal upset.

The meta-analysis carries a correction. A trial listed as “Onofrj, 1995” should not have been included, and corrected forest plots were issued. Cochrane, reviewing the same territory, judged that trials provided little or no information on functional impairment, sensory testing and symptoms — a notably more conservative read.

• MetaLi S, Li Q, Li Y, Li L, Tian H, Sun X. Acetyl-L-carnitine in the treatment of peripheral neuropathic pain: systematic review and meta-analysis of RCTs PLoS One 2015 · correction at doi 10.1371/journal.pone.0129991
• RevAcetyl-L-carnitine for the treatment of diabetic peripheral neuropathy Cochrane review · substantially more conservative conclusion

In non-diabetic peripheral neuropathic pain the pooled reduction was 0.71 points on VAS (95% CI −0.01 to 1.43, p=0.05) — half the diabetic effect, and the interval includes no effect at all.

This is a clean illustration of why claims need splitting by population. Same supplement, same outcome measure, same analysis: convincing in one group, borderline in the other. A page that reports only “ALCAR reduces nerve pain” has thrown away the part that determines whether it applies to the reader.

• MetaLi S, et al. Subgroup analysis, diabetic vs non-diabetic PNP PLoS One 2015 · diabetic MD 1.47 vs non-diabetic MD 0.71

A 2003 meta-analysis pooled 21 double-blind trials covering 1,204 adults on 1.5–3.0 g/day for 3 to 12 months, and reported a modest but statistically significant benefit in mild cognitive impairment and mild Alzheimer's disease.

The independent critical assessment is unusually blunt. The DARE reviewers noted the conclusions rest on pooling treatment effects measured by various different instruments and “may not, therefore, be reliable,” and that the clinical importance of the statistically significant findings was not clear.

Funding flag. The literature search included the internal publication data bank of Sigma-Tau, the manufacturer. Disclosed, not disqualifying, and worth knowing.

• MetaMontgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind RCTs of acetyl-L-carnitine vs placebo in mild cognitive impairment and mild Alzheimer's disease Int Clin Psychopharmacol 2003;18(2):61-71 · PMID 12598816 · DARE critical abstract

A placebo-controlled trial found that ALCAR significantly worsened chemotherapy-induced peripheral neuropathy. This is the mirror image of the diabetic neuropathy result: same supplement, same broad symptom, opposite direction.

It is also the one genuinely actionable warning on this page. Anyone reasoning from “ALCAR helps nerve pain” to “ALCAR will help my chemotherapy nerve pain” is reasoning toward the documented harm.

• RCTHershman DL, et al. Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy Effect ran in the direction of harm