Acetyl-L-Carnitine (ALCAR)

Cognition: Montgomery et al. (Int Clin Psychopharmacol, 2003; PMID 12598816) pooled double-blind trials in mild cognitive impairment and mild Alzheimer's disease and found benefit; the two largest trials, Thal et al. (Neurology, 1996; PMID 8797468; 431 adults, 3 g/day, one year) and Thal et al. (Neurology, 2000; PMID 10994000; 229 adults with early-onset Alzheimer's disease, 3 g/day, one year), were null on their primary endpoints, and Hudson et al. (Cochrane Database Syst Rev, 2003; PMID 12804452) found no benefit on objective cognitive measures. Pennisi et al. (Nutrients, 2020; PMID 32408706) is a narrative review and itself calls the role in dementia still under debate. No trial tested healthy older adults. Neuropathy: Li et al. (PLoS One, 2015; PMID 25751285) pooled peripheral neuropathic pain trials (self-reported pain, not cognition) and found benefit at 2 to 3 g/day, while stating that most of the pooled trials were funded by the manufacturer of the acetyl-L-carnitine tested and naming a potential commercial bias; Sima et al. (Diabetes Care, 2005; PMID 15616239) is one of those diabetic neuropathy trials; Rolim et al. (Cochrane Database Syst Rev, 2019; PMID 31201734) rated the evidence very low certainty and found no benefit at 1,500 mg/day or less. Harm: Hershman et al. (J Clin Oncol, 2013; PMID 23733756), 409 women receiving taxane chemotherapy, found 3 g/day made neuropathy worse, and the two-year follow-up (Hershman et al., J Natl Cancer Inst, 2018; PMID 29361042) found the worsening persisted; this trial was funded by the National Cancer Institute and the Medical Research Council. Grade C: positive older pooled data against the two largest trials null, on clinician-rated and self-reported endpoints.