Carnitine is a non-essential amino acid with a key role in energy metabolism control. Treatment with the acetyl form acetyl-L-carnitine has been suggested to be effective against fatigue in a variety of chronic neurological diseases, chronic fatigue syndrome, and chemotherapy-induced fatigue. A randomized, double-blind human study showed a trend of improvement in fatigue with use of actyl-L-carnitine1. Another showed the efficacy and safety of acetyl-L-carnitine (1 g twice daily) to be superior to those of amantadine (100 mg twice daily), one of the drugs most widely used to treat MS-related fatigue 2.

      An animal study demonstrated the antioxidant, anti-apoptotic and immune modulatory effects of acetyl-L-carnitine as an add-on therapy with dexamethasone for treatment of a relapsing-remitting (RR) EAE 3. These findings suggest use of acetyl-L-carnitine as an additive treatment during long-term use of dexamethasone in MS.

      Acetyl-L-carnitine is a supplemental form, but natural L-carnitine can be found primarily in animal foods such as milk, meat, poultry, and fish. It is important to note that overconsumption of L-carnitine – especially from high-fat sources – with betaine and choline leads to excess conversion to harmful trimethylamine N-oxide (TMAO) in conditions of dysbiosis4,5. TMAO has been linked to inflammation, cardiovascular disease, and neurodegenerative disorders5,6. Fortunately, this can be curtailed by consumption of cruciferous vegetables and other key dietary improvements 5.

      While L-carnitine is a normal component of human breastmilk and has been explored scientifically in the contexts of both pregnancy and nursing7,8, acetyl-L-carnitine itself has not been thusly studied. During pregnancy, supplementation with 500 mg/day of L-carnitine has been observed to reverse the decline in the nutrient’s levels that can occur naturally during this time9, while 500 mg three times per day can reverse an existing deficiency in the expectant mother10. Of note, an animal study suggested that maternal L-carnitine supplementation (1.5 mM in drinking water) may improve brain health in offspring who would otherwise be at neurological risk due to cigarette smoke exposed mothers 11.

References

1. Ledinek AH, Sajko MC, Rot U. Evaluating the effects of amantadin, modafinil and acetyl-L-carnitine on fatigue in multiple sclerosis–result of a pilot randomized, blind study. Clin Neurol Neurosurg. Dec 2013;115 Suppl 1:S86-9. doi:10.1016/j.clineuro.2013.09.029

2. Tomassini V, Pozzilli C, Onesti E, et al. Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial. J Neurol Sci. Mar 15 2004;218(1-2):103-8. doi:10.1016/j.jns.2003.11.005

3. Zidan A, Hedya SE, Elfeky DM, Abdin AA. The possible anti-apoptotic and antioxidant effects of acetyl l-carnitine as an add-on therapy on a relapsing-remitting model of experimental autoimmune encephalomyelitis in rats. Biomed Pharmacother. Jul 2018;103:1302-1311. doi:10.1016/j.biopha.2018.04.173

4. Hosseinkhani F, Heinken A, Thiele I, Lindenburg PW, Harms AC, Hankemeier T. The contribution of gut bacterial metabolites in the human immune signaling pathway of non-communicable diseases. Gut Microbes. Jan-Dec 2021;13(1):1-22. doi:10.1080/19490976.2021.1882927

5. Janeiro MH, Ramirez MJ, Milagro FI, Martinez JA, Solas M. Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target. Nutrients. Oct 1 2018;10(10)doi:10.3390/nu10101398

6. Manolis AA, Manolis TA, Melita H, Manolis AS. Gut Microbiota and Cardiovascular Disease: Symbiosis Versus Dysbiosis. Curr Med Chem. Dec 12 2021;doi:10.2174/0929867328666211213112949

7. Manta-Vogli PD, Schulpis KH, Dotsikas Y, Loukas YL. The significant role of carnitine and fatty acids during pregnancy, lactation and perinatal period. Nutritional support in specific groups of pregnant women. Clin Nutr. Aug 2020;39(8):2337-2346. doi:10.1016/j.clnu.2019.10.025

8. Levocarnitine. Drugs and Lactation Database (LactMed(R)). 2006.

9. Keller U, van der Wal C, Seliger G, Scheler C, Ropke F, Eder K. Carnitine status of pregnant women: effect of carnitine supplementation and correlation between iron status and plasma carnitine concentration. Eur J Clin Nutr. Sep 2009;63(9):1098-105. doi:10.1038/ejcn.2009.36

10. de Bruyn A, Jacquemyn Y, Kinget K, Eyskens F. Carnitine Deficiency and Pregnancy. Case Rep Obstet Gynecol. 2015;2015:101468. doi:10.1155/2015/101468

11. Chan YL, Saad S, Al-Odat I, et al. Maternal L-Carnitine Supplementation Improves Brain Health in Offspring from Cigarette Smoke Exposed Mothers. Front Mol Neurosci. 2017;10:33. doi:10.3389/fnmol.2017.00033