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Choline chloride

Intravenous choline in patients on intravenous nutrition

Most of this work comes from one group led by Alan Buchman, at Baylor College of Medicine and later Northwestern University.

• In 4 patients with low plasma free choline after years of intravenous nutrition (Buchman 1995), choline chloride added to the nutrition solution for 6 weeks raised plasma free choline into the normal range within a week and resolved fatty liver on CT; fatty liver returned in one patient 10 weeks after choline was stopped (PMID: 7590654).
• Buchman 2001 was a randomized trial in 15 patients. Patients received their usual nutrition (8 patients) or nutrition with 2 g of choline chloride added (7 patients) for 24 weeks; liver density on CT improved from week 4, ALT fell, and fatty liver returned 10 weeks after choline was stopped (PMID: 11531217).
• In a pilot trial in 11 patients (Buchman 2001), choline-supplemented nutrition improved delayed visual recall over 24 weeks (p=0.028), with borderline changes on two other tests and no significant change on the remaining tests (PMID: 11190987).
• THRIVE-3, a phase 2b/3 trial of choline chloride for injection against placebo, planned for 129 adolescents and adults with intestinal failure on long-term parenteral support and sponsored by Protara Therapeutics, started on 10 December 2025 and was recruiting when checked on 27 October 2026 (ClinicalTrials.gov NCT06910943).

Oral choline in healthy people

In a double-blind crossover study of 13 men, oral choline (the study gave 50 mg/kg) raised plasma choline but did not change physical or cognitive performance after exhausting load-carriage exercise (PMID: 12502178).

Acetyl-L-carnitine

Dementia and mild cognitive impairment

• A 2003 meta-analysis pooled double-blind trials of 3 to 12 months in mild cognitive impairment and mild Alzheimer's disease and found a small advantage over placebo (summary effect size 0.20, 95 percent confidence interval 0.11 to 0.30) (PMID: 12598816).
• In Thal 1996, a 1-year trial in 431 people with Alzheimer's disease, patients on acetyl-L-carnitine and on placebo declined at the same rate on both primary measures; a post hoc analysis suggested slower decline in patients aged 65 or younger (PMID: 8797468).
• Thal 2000 ran for 1 year in 229 people with early-onset Alzheimer's disease. The trial set up to test that subgroup found no slowing of decline on the primary measures (PMID: 10994000).
• In a 2003 Cochrane review of 11 trials, benefit appeared only on clinical global impression at 12 and 24 weeks, there was no evidence of benefit on objective measures, and the reviewers found no evidence to recommend routine clinical use (PMID: 12804452).

Depression

A 2018 meta-analysis of 12 randomized trials with 791 participants pooled the 9 trials that had a placebo or no-treatment group and found lower depressive symptom scores with acetyl-L-carnitine, with high heterogeneity between trials (PMID: 29076953).

Neuropathy

• Two 52-week trials in 1,257 people with diabetic neuropathy found improved vibration perception and sural nerve fiber counts, with less pain in one trial and in the pooled group on the higher dose, while nerve conduction did not improve (PMID: 15616239).
• A 2015 meta-analysis of 4 neuropathic pain trials (523 patients) found lower pain scores than with placebo, with similar effects in trials that began with injections into muscle and in oral-only trials (PMID: 25751285).
• In women having taxane chemotherapy, acetyl-L-carnitine worsened nerve damage (PMID: 23733756).

Injection studies

In Italy, acetyl-L-carnitine has been marketed as an injection that is often given into muscle (PMID: 20661677). In 18 patients with cirrhosis and hepatic encephalopathy, a single 0.5 g intravenous dose shortened the latency of a visual-evoked brain response 30 minutes later (PMID: 16445703), and in a 48-patient trial in hepatic coma, intravenous acetyl-L-carnitine added to branched-chain amino acids lowered blood ammonia more than the amino acids alone (PMID: 19357525).

L-carnosine

Human studies

• In a 2026 meta-analysis of 13 studies, five randomized trials found no significant difference between L-carnosine and placebo on most cognitive measures; pooling three trials from one research team found that anserine with carnosine improved delayed story recall, and the authors rated the strength of evidence as low (PMID: 42123986).
• In 39 healthy older adults at the University of Tokyo (Hisatsune 2016), a 3:1 anserine and carnosine supplement preserved delayed verbal recall over 3 months compared with placebo (p=0.0128) (PMID: 26682691).
• A 2025 pharmacokinetic study in 16 healthy volunteers found that oral carnosine peaked in plasma within the first hour and was barely detectable after 4 hours; in 5 of them, brain carnosine measured by magnetic resonance spectroscopy rose at 1 hour and was back to baseline by 5 hours (PMID: 40647235).

Animal and laboratory studies

Preclinical studies report antioxidant, anti-inflammatory and anti-aggregation activity and protective effects in animal models of Alzheimer's disease (PMID: 33806459). In the laboratory, carnosine added to human plasma was broken down with a half-life of about 1.2 minutes (PMID: 37081019).

Acetyl-L-carnitine

In the SWOG S0715 trial, 409 women having taxane chemotherapy for breast cancer took acetyl-L-carnitine (the trial gave 3,000 mg a day) or placebo for 24 weeks; nerve damage scores (chemotherapy-induced peripheral neuropathy) were worse with acetyl-L-carnitine at 24 weeks, and grade 3 to 4 neurotoxicity occurred in 8 women on acetyl-L-carnitine and 1 on placebo (PMID: 23733756). The difference persisted over two years of follow-up (PMID: 29361042). In a 1-year trial in 431 people with Alzheimer's disease, the authors described acetyl-L-carnitine as very well tolerated (PMID: 8797468), and a Cochrane review of 11 dementia trials found no significant difference in adverse events between acetyl-L-carnitine and placebo (PMID: 12804452). A pooled analysis of neuropathic pain trials listed pain, headache, paresthesia (tingling), hyperesthesia (heightened skin sensitivity), biliary colic, digestive complaints and retching as the common adverse events, with total adverse event rates similar in the acetyl-L-carnitine and control groups (PMID: 25751285).

L-carnosine

In a dose-escalation study in 16 healthy volunteers, the authors judged single oral doses of up to 10 g of carnosine well tolerated, although 3 of the 15 volunteers who took 10 g had side effects (PMID: 40647235). After 15 g, 10 of the 13 volunteers who took that dose (77 percent) had side effects, most often headache, nausea and tingling, and 4 weeks of 5 g twice a day caused no adverse events in the 4 people who took it (PMID: 40647235). A PubMed search found no human study of L-carnosine injected into a vein or muscle; the one human injection study found used L-carnosine mixed into a hyaluronic acid skin filler in 13 patients (PMID: 34378075).

Choline chloride

The intravenous choline chloride studies in patients on long-term intravenous nutrition enrolled 4 to 15 patients, and their abstracts do not describe adverse events (PMID: 7590654, PMID: 11531217). The phase 2b/3 THRIVE-3 trial lists adverse events and changes in the QTc interval on the electrocardiogram among its outcomes and had posted no results when its record was checked on 27 October 2026 (ClinicalTrials.gov NCT06910943).

Injection warnings for a related compound

No FDA label exists for an injectable form of choline chloride, acetyl-L-carnitine or L-carnosine. The FDA label for injectable levocarnitine (L-carnitine) reports serious hypersensitivity reactions such as anaphylaxis, laryngeal edema and bronchospasm, mostly in dialysis patients and some within minutes of intravenous dosing, and seizures with oral or intravenous use (Carnitor label, FDA, version of 20 November 2023). Acetyl-L-carnitine is partly converted to L-carnitine in the body (PMID: 2591464).