L-carnitine is an ultra-versatile under-utilized superstar in the tool bag of the integrative healthcare provider. The goal of this review is to reacquaint readers with this safe, effective, and cost-effective intervention. A quick search of PubMed revealed 65 meta-analytic and systematic reviews of this agent. A selection of these will be presented below.
L-carnitine serves as a transporter of free fatty acids greater than 14 carbons in length to be shuttled into the inner mitochondrial matrix where they enter the beta oxidation pathway. L-carnitine is present in greatest concentration in skeletal and cardiac muscle, yet is found in all mammalian tissue (Reynolds 1996, Thorne 2002). It is synthesized in the liver, kidneys, and brain from the amino acids lysine and methionine. Oral bioavailability is approximately 15% (Reynolds 1996, Thorne 2002). Commercially there are several forms of carnitine available, yet acetyl-L-carnitine is the preferred form by most clinicians, as it has been suggested only the acetyl form crosses the blood brain barrier.
Metabolic Effects
Muller and colleagues (2002) conducted the definitive study establishing that oral L-carnitine supplementation achieves the outcome of increasing the relative proportion of energy derived from fat. Ten subjects in crossover fashion with washout were administered L-carnitine or placebo at 3 g per day for 10 days. Subjects were then administered C13 labeled palmitate, and breath samples were collected every 15 minutes for 15 hours. C13 exhalation averaged 5.12% after 10 days supplementation with placebo. C13 exhalation averaged 7% after supplementation with L-carnitine. The authors conclude “this is the first investigation to conclusively demonstrate that oral L-carnitine supplementation results in an increase in long chain fatty acid oxidation in vivo in subjects without L-carnitine deficiency”.
A meta analysis of nine studies (N=911) concluded that participants randomized to carnitine lost significantly more weight and demonstrated significantly greater reductions in BMI (Pooyandjoo 2016). Xu and colleagues (2017) showed significant benefit of L-carnitine on insulin resistance, yet highlighted that the impact on insulin resistance was not significant until nine months of carnitine intervention. A meta analysis of four studies concluded L-carnitine lowers fasting blood glucose yet does not impact HbA1C (Vidal-Casariego 2013). A meta analysis of 55 studies, and a second meta analysis of 67 studies, concluded that L-carnitine administration reduces total cholesterol, LDL-cholesterol, and triglyceride, while increasing levels of HDL-cholesterol (Askarpour 2019, Fathizadeh 2019). A meta analysis of seven studies further showed L-carnitine administered orally, yet not intravenously, significantly reduces lipoprotein (a) levels (Serban 2016). Meta analysis of 13 studies showed that L-carnitine significantly reduces circulating levels of CRP, and slightly yet significantly reduces TNF-alpha and IL-6 (Haghighatdoost 2019). A meta analysis of 16 studies showed L-carnitine lowers ALT, AST, and GGT. The effect does not occur in normal weight or healthy participants (Askarpour 2020).
Secondary Coronary Prevention
A meta analysis of 13 studies (N=3629) of L-carnitine post MI concluded administration of L-carnitine achieved a 27% reduction in all-cause death, a 65% reduction in ventricular arrhythmia, and a 40% reduction in the development of angina (DiNicolantonio 2013). A meta analysis of 17 studies of L-carnitine for heart failure concluded significant impact for overall efficacy, left ventricular ejection fraction, stroke volume, cardiac output, and the E/A ratio (a marker of left ventricle function). Furthermore, L-carnitine lowered circulating levels of BNP (brain natriuretic peptide), NT-proBNP. L-carnitine also improved left ventricular end systolic dimension, left ventricular end diastolic diameter, and left ventricular end systolic volume (Song 2017).
Mental Health
A meta analysis of 12 studies (N=791) concluded L-carnitine significantly reduces depressive symptoms. Three RCTs compared L-carnitine to antidepressants and found similar efficacy while delivering significantly fewer adverse effects (Veronese 2018).
Neurodegeneration
A meta analysis of 21 studies of at least three months duration among individuals with dementia or Alzheimer’s showed L-carnitine supplementation significantly improved the Clinical Global Impression of Change. Benefit was noted for clinical scales and psychometric testing (Montgomery 2003).
Peripheral Neuropathy
A meta analysis of four RCTs evaluated the impact of L-carnitine on peripheral neuropathic pain. L- carnitine significantly reduced visual analogue scale scores (VAS). L-carnitine was found to be more effective for diabetic neuropathic pain than non-diabetic neuropathic pain (Li 2015).
Male Fertility
A meta analysis evaluated 28 studies of multiple natural medicines for improving sperm parameters. Specific to L-carnitine, the authors concluded significant benefit for sperm total motility, sperm progressive motility, and sperm morphology. L-carnitine was the only agent assessed that impacted sperm progressive motility (Salas-Huetos 2018).
Hepatic encephalopathy
A meta analysis of nine studies (N=779) evaluated L-carnitine administration among individuals with hepatic encephalopathy. L-carnitine administration significantly reduced blood ammonia levels, blood bilirubin, AST, BUN, and creatinine. The intervention also increased circulating levels of albumin (Abbasnezhad 2019).
Performance enhancement
While no meta analysis was available on this topic, a well-developed body of literature has demonstrated L- carnitine to benefit a wide array of outcomes related to athletic performance. My favorite such intervention used MRI to demonstrate faster recovery following squat exercise (Volek 2002).
Discussion
L-carnitine is cost-effective and safe. All reviewed meta analyses in this review suggested adverse events were no different from placebo. Some individuals will report mild GI distress. The clinical applications of this versatile substance are growing at an exponential rate. In seemingly any arena the agent is studied, it proves itself to be of important impact. Prior to compiling this review, acetyl-L-carnitine was a common prescription in private practice for secondary coronary prevention, neurodegeneration, male fertility, and for elite athletes. Since compiling this review, L-carnitine will be considered in settings of diabetes, dyslipidemia, and liver disease.
References:
Abbasnezhad A, et al. J Gastroenterol Hepatol. 2019;34(12):2062-2070.
Askarpour M., et al. Arch Med Res. 2020;51(1):82-94.
Askarpour M. et al., Nutr Metab Cardiovasc Dis. 2019;29(11):1151-1167.
DiNicolantonio, J.J., et al. Mayo Clin Proc. 2013;88(6):544-551.
Fathizadeh, H., et al. Curr Pharm Des. 2019;25(30):3266-3281.
Haghighatdoost F., et al. Eur J Clin Pharmacol. 2019;75(8):1037-1046.
Li S., et al. PLoS One. 2015;10(3):e0119479.
Montgomery, S.A., et al. Int Clin Psychopharmacol. 2003;18(2):61-71.
Müller, D.M., et al. Metabolism. 2002;51(11):1389-1391.
Pooyandjoo, M., et al. Obes Rev. 2016;17(10):970-976.
Reynolds, J.E.F et al. Martindale The Extra Phamacopoeia. 31st ed. Royal Pharmaceutical Society of Great Britain 1996, London England.
Salas-Huetos, A., et al. Adv Nutr. 2018;9(6):833-848.
Serban MC., et al Sci Rep. 2016;6:19188.
Song X., et al. Biomed Res Int. 2017;2017:6274854.
Vidal-Casariego, A., et al. Exp Clin Endocrinol Diabetes. 2013;121(4):234-238.
Volek, J.S., et al. Am J Physiol Endocrinol Metab. 2002;282(2):E474-E482.
Xu, Y., et al. Adv Clin Exp Med. 2017;26(2):333-338.
