Acetyl L-carnitine

Evidence from meta-analyses of randomized controlled trials suggests that ALCAR might slow cognitive decline, especially in patients with mild cognitive impairment (MCI) or the early stages of Alzheimer’s disease. However, the size of this effect is not likely to be large, and possibly not noticeable. Our search identified:

• 2 meta-analyses of randomized controlled trials in patients with MCI and/or Alzheimer's disease
• 2 clinical trials in elderly patients with fatigue
• Multiple small randomized controlled trials of ALCAR in MCI and/or Alzheimer's patients
• 2 observational studies of serum and cerebral spinal fluid (CSF) levels of carnitine
• 0 observational studies on the prevention of Alzheimer’s disease
• Many preclinical animal studies

ALCAR may improve cognitive function in elderly adults with fatigue based on two clinical trials from the same researchers [3][4], but no studies show that ALCAR can prevent Alzheimer's disease. Two studies reported that carnitine levels may decline in individuals as they progress to MCI and Alzheimer's disease [5][6].

Preclinical studies suggest many ways that ALCAR may benefit the brain. It may help to improve memory and mitochondrial function, especially in elderly animals [7][8][9]. Evidence also suggests that it may raise the levels of nerve growth factor and increase the activity of acetylcholine, a neurotransmitter that is critical to healthy brain function and is substantially lost in Alzheimer's disease [2].

APOE4 Carriers:

Little evidence exists on how carnitine treatment affects APOE4 positive or negative patients. One study reported that levels of l-carnitine in spinal fluid were lower in Alzheimer's patients without an APOE4 gene allele compared to patients with mild cognitive impairment [5]. One preclinical study in mice reported that ALCAR and alpha lipoic acid treatment improved spatial and temporal memory tests but only in mice with APOE4 [10]. For more information on what the APOE4 gene allele means for your health, read our APOE4 information page.

For Dementia Patients

Despite some promise from early clinical trials, a meta-analysis of clinical trials concluded that ALCAR supplements are unlikely to provide a clinically meaningful benefit on the cognitive, behavioral, or functional abilities of Alzheimer's patients [1]. For patients with less severe cognitive problems, specifically mild cognitive impairment or early-stage Alzheimer's disease, the clinical trial evidence is slightly more positive but also less reliable [11].

ALCAR is generally considered safe at doses up to 2–3 grams/day and has been used safely in clinical trials for up to 12 months. Some side effects noted in clinical trials include diarrhea, nausea, and vomiting [1]. Carnitine can inhibit thyroid hormone activity, so those seeking treatment for hypothyroidism should not take any form of carnitine supplement [12]. In addition, some research suggests that certain gut bacteria can convert carnitine to a substance called trimethylamine-N-oxide (TMAO), which may be associated with an increased risk of cardiovascular disease. However, this not well understood and needs more research [13].

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

ALCAR is a common, over-the-counter supplement. Trials in Alzheimer's disease patients and elderly individuals with fatigue have generally used 2–3 grams/day for six months to one year. There are many natural sources of carnitine, such as red meat, fish, poultry, and some dairy products, but obtaining the doses used in previous clinical trials requires taking a dietary supplement.

For more information, visit the NIH's health information fact sheet.

More information on carnitine supplementation can be found at Drugs.com.

1. Hudson S, Tabet N (2003) Acetyl-L-carnitine for dementia. The Cochrane database of systematic reviews, CD003158.
2. Jones LL, McDonald DA, Borum PR (2010) Acylcarnitines: role in brain. Progress in lipid research 49, 61-75.
3. Malaguarnera M, Cammalleri L, Gargante MP et al. (2007) L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. The American journal of clinical nutrition 86, 1738-1744.
4. Malaguarnera M, Gargante MP, Cristaldi E et al. (2008) Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue. Archives of gerontology and geriatrics 46, 181-190.
5. Lodeiro M, Ibanez C, Cifuentes A et al. (2014) Decreased cerebrospinal fluid levels of L-carnitine in non-apolipoprotein E4 carriers at early stages of Alzheimer's disease. Journal of Alzheimer's disease : JAD 41, 223-232.
6. Cristofano A, Sapere N, La Marca G et al. (2016) Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia. PloS one 11, e0155694.
7. Hagen TM, Ingersoll RT, Wehr CM et al. (1998) Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proceedings of the National Academy of Sciences of the United States of America 95, 9562-9566.
8. Barnes CA, Markowska AL, Ingram DK et al. (1990) Acetyl-1-carnitine. 2: Effects on learning and memory performance of aged rats in simple and complex mazes. Neurobiology of aging 11, 499-506.
9. Snigdha S, de Rivera C, Milgram NW et al. (2016) Effect of mitochondrial cofactors and antioxidants supplementation on cognition in the aged canine. Neurobiology of aging 37, 171-178.
10. Shenk JC, Liu J, Fischbach K et al. (2009) The effect of acetyl-L-carnitine and R-alpha-lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer's disease. Journal of the neurological sciences 283, 199-206.
11. Montgomery SA, Thal LJ, Amrein R (2003) Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. International clinical psychopharmacology 18, 61-71.
12. Benvenga S, Amato A, Calvani M et al. (2004) Effects of carnitine on thyroid hormone action. Annals of the New York Academy of Sciences 1033, 158-167.
13. Koeth RA, Wang Z, Levison BS et al. (2013) Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature medicine 19, 576-585.