ACETYL L-CARNITINE

BACKGROUND

Ingredient Type: Amino Acid

Also Known As: Acetylcarnitine, L-carnitine

Acetyl-L-Carnitine (ALC) is an amino acid that is naturally produced in the body from L-carnitine. As ALC is a mitochondrial metabolite, it acts by facilitating the movement of fatty acids into the mitochondria for energy. It is noted to increase general metabolic activity, support the nervous system, and cognitive function (1).

TRADITIONAL USES

ALC was initially discovered in 1905 as a significant component of tissues found in the animal and plant kingdoms. In 1952, a study assessed the efficacy of ALC on the growth of the mealworm, Tenebrio molitor. According to the study, the mealworms could not use fat stores when in the starved state. During this time, two scientists Friedman and Fraenkel noted in their research that carnitine stimulated fatty acid oxidation in the liver, which led to the discovery that carnitine functioned in transporting activated long-chain fatty acids into the mitochondria for energy production (4).

From this time, science has expanded its knowledge and understanding of this amino acid and subsequently has recognized many other benefits for dietary or supplemental ALC support. Although exogenous supplementation is an alternative for those seeking to increase their levels through ALC supplements, those with no dietary restrictions can obtain a significant source of ALC from meats (2).

WHAT DOES SCIENCE TELL US?

Acetyl-L-Carnitine Possibly Supports Energy Production:

Two studies were conducted to assess the levels of L-carnitine in the body and its association with Chronic Fatigue Syndrome (CFS). Being that carnitine is an essential amino acid for mitochondrial energy production, it was proposed that patients experiencing CFS would likely have lower levels of L-carnitine. The first study consisted of treating 30 CFS patients in a crossover design comparing L-carnitine and amantadine, one of the more well-known medications for managing fatigue in multiple sclerosis patients. Each medication was given for two months, with a 2-week washout period between each medication/supplement. Of the 15 patients who completed the study, it was found that L-carnitine provided statistically significant improvements in the 12 of 18 measured parameters (6).

The second study assessed 35 patients, 27 females, and 8 males, with clinically diagnosed Chronic Fatigue Syndrome.  From this study, it was concluded that CFS patients have statistically significantly lower serum levels of total carnitine, free carnitine, and acylcarnitine levels. The researchers also noted a significant correlation between serum levels of total and free carnitine and clinical symptomology. The consistent findings amongst the patients with CFS may be indicative of mitochondrial dysfunction, potentially contributing to the cause of the patients’ fatigue (5).

Acetyl-L-Carnitine Possibly Supports Cognitive Function:

Cognitive function is largely a problem with those suffering from liver conditions, whether acute or chronic. In this study, 120 patients were randomly assigned to either a treatment group for 60 days with L-carnitine or placebo (2 g twice a day). The results suggested a protective effect of the L-carnitine in ammonia-precipitated encephalopathy in cirrhotic patients. L-carnitine, inducing ureagenesis, is proposed to help decrease the blood and brain ammonia levels by converting it to more neutral and expellable urea, which is not known to damage tissues as elevated levels of ammonia does. In this study, a significant therapeutic effect of L-carnitine was also observed in the NCT-A, which is an accepted and reliable psychometric test assessing the mental function of cirrhotic patients with hepatic encephalopathy (9).

With L-carnitine’s pivotal role in fatty acid oxidation and energy metabolism, it is presumed that much of the support and health of cognitive function is directly related to L-carnitine’s ability to enhance blood flow, oxygen supply, and nutrient delivery to the necessary tissues and cells. It is the benefits of the metabolic processes which L-carnitine is involved in that not only supports physical but mental fatigue and stamina as well (7).

Acetyl-L-Carnitine Might Support Heart Health:

A research group performed studies on the biochemical and clinical aspects of cardiogenic shock and the effects of supra-physiological doses of L-carnitine on the conditions of oxidative damage due to acute cellular hypoxia. In their open study, 27 patients hospitalized in a shock condition were followed for the entire duration while in the intensive care unit. The resulting study data revealed a significantly positive trend for L-carnitine patients regarding their survival rate from the cardiogenic shock state. The researchers attributed the improvement of the patients’ metabolic acidosis to the L-carnitine supplementation (12,13).

Another study examined the efficacy of long-term L-carnitine supplementation for the treatment of heart failure caused by dilated cardiomyopathy. Seventy patients were studied who had moderate to severe heart failure caused by dilated cardiomyopathy. Following a stability period of 3 months, patients were randomly assigned to receive either supplementation of L-carnitine (2 g/day orally) or a placebo. At baseline, there was not noted statistical significance between the two test groups. Baseline measurements were taken along with long-term incremental measurements assessing the following clinical and hemodynamic parameters: ejection fraction, Weber classification, maximal time of cardiopulmonary exercise test, peak VO2 consumption, arterial and pulmonary blood pressure, and cardiac output. The assessed results following a mean of 33.7 months revealed that the patient survival rate was significantly favorable in the L-carnitine group vs. the placebo group. At the time of analysis, there were six deaths in the placebo group, whereas there was only one death in the L-carnitine group (14).

In a third, double-blind placebo-controlled study, the effects of oral L-carnitine administration were assessed on patients with suspected acute myocardial infarctions over 28 days. A total of 101 patients were evaluated with 51 patients in the L-carnitine group and 50 patients in the placebo group. The baseline cardiac markers were comparable between both test groups. Following the completion of the study, it was assessed that the infarct size, as noted by the levels of cardiac enzymes, showed to be significantly reduced in the L-carnitine group as compared to the placebo group. Additionally, it was noted that serum aspartate transaminase and lipid peroxidase levels showed significant decreases within the L-carnitine group as well. “Total cardiac events, including cardiac deaths and nonfatal infarction, were 15.6% in the L-carnitine group vs. 26% in the placebo group.” It was assessed based on the results that L-carnitine supplementation may have protective benefits for patients suspected with acute myocardial infarction within the first 28 days following the incident (15).

Acetyl-L-Carnitine Might Support a Healthy Weight:

A recent review on the effects of L-carnitine supplementation in recovery found beneficial effects on the recovery process following exercise, enhancement of athletic capacities such as maximum oxygen consumption, and higher power output, along with alleviating muscle injury and reducing markers of cellular damage and free radical formation accompanied with muscle soreness. L-carnitine was found to play a vital role in fatty acid oxidation and energy metabolism. It is recognized that the highly energetic processes as exercise and recovery are supported much in response to the enhanced blood flow, oxygen supply, and nutrient delivery in response to the presence of adequate levels of L-carnitine. Previous, as well as current studies, point to the efficacy of L-carnitine supplementation in support of increased muscle mass accompanied by decreases in body weight and reduced physical and mental fatigue (7).

Another recent review and meta-analysis of 9 randomized studies examined the effect of carnitine on adult weight loss. Results from the meta-analysis of the noted trials revealed that those who received the L-carnitine supplementation lost significantly more weight and showed a decrease in body mass index compared to the control groups (8).

Acetyl-L-Carnitine Possibly Supports Healthy Nerves:

In a small study, seven diabetic patients with painful diabetic neuropathy (DN), seven diabetic patients without DN, and seven healthy controls were assessed for the efficacy of L-carnitine in the treatment of diabetic neuropathy along with its effect on levels of the endogenous peptide B-endorphin. Blood sample values were assessed to determine basal B-endorphin levels along with a base pain assessment as measured by electroneuromyography. A 30mg/kg intravenous bolus injection of L-carnitine was then administered. Results found an acute rise in the B-endorphin levels 3 hours following the administration, but pain scores did not change during this time. The improvement in pain, however, was noted in diabetic patients with DN after 15 days post-L-carnitine administration. It was noted that diabetic patients have lower levels of B-endorphins vs. the non-diabetic population. Although there was no significant change in the levels of B-endorphins, treatment with L-carnitine was effective in treating diabetic related neuropathy (11).

Acetyl-L-Carnitine Possibly Supports Healthy Blood Sugar Levels:

A study was conducted to evaluate the effects of L-carnitine on insulin-mediated glucose uptake and oxidation in type II diabetic patients in comparison to a healthy control group. In this study, 15 patients with type II diabetes and 20 healthy individuals underwent a 2-hour euglycemic hyperinsulinemic clamp with a simultaneous, constant infusion of L-carnitine or a saline solution. To determine the efficacy of the supplemental infusion, respiratory gas exchange was measured along with plasma glucose, insulin, non-esterified fatty acids, and lactate levels. Additionally, urinary nitrogen excretion was measured to evaluate protein oxidation. Based on the results of the study, it was noted that glucose uptake was increased significantly with the L-carnitine supplemented group vs. the saline solution control group. Glucose oxidation was seen to have increased only in the diabetic group, along with decreased plasma lactate levels during the L-carnitine infusion vs. the saline solution infusion. It was concluded, based on the results that L-carnitine significantly improved insulin sensitivity in insulin-resistant diabetics. At the same time, healthy subjects experienced a significant effect on whole-body insulin-mediated glucose uptake (10).

SAFETY

Interactions:

There are a few drug interactions that negatively impact L-carnitine metabolism or decrease the availability of the biologically active form of L-carnitine in the body. Please remember to consult your healthcare professional before supplementation L-carnitine to avoid unnecessary interactions or side-effects.

Anticonvulsant medications such as phenobarbital, valproic acid, phenytoin, and carbamazepine have a lowering effect on serum carnitine concentrations. In a study of 471 patients treated for convulsions with the noted anticonvulsants, carnitine serum levels in all treatment groups noted a reduction between 6 – 64% (17).

In another study, ten children receiving pivampicillin for eight days were assessed for carnitine levels based on analyzed fatty acid and carbohydrate oxidation. From this study, it was analyzed that the antibiotic pivampicillin negatively impacted carnitine metabolism, as was noted in the inhibition of fatty acid oxidation during treatment (18).

As noted in previous studies, L-carnitine supplementation can aid with the conversion of ammonia to urea, a more neutral and easily excretable form, less toxic to the body. In a study of 230 patients with cystic acne who were on isotretinoin therapy, symptoms were assessed to demine the link between carnitine deficiency and the presence of symptoms such as myalgia, weakness, and hypotension. The results indicated that there was a direct correlation between increased liver enzymes and lipids and decreased carnitine plasma levels. The treatment group supplemented with L-carnitine had a reduction in their myalgias while the placebo group continued symptom complaints. It was concluded that L-carnitine supplementation helps prevent elevated liver and lipid enzymes commonly associated with certain drug-associated side-effects (19).

Side-Effects:

Acetyl-L-Carnitine side effects, if any, are particularly mild. Doses of approximately 3 g/day and above can cause nausea, abdominal cramps, diarrhea, and vomiting (16). Ensure proper absorption by utilizing L-carnitine, not the racemic mixture of (D/L-carnitine) as the D-form is not a biologically active form and can hinder the utilization of the active L-form (2).

REFERENCES

1. Acetyl-L-Carnitine/a-Lipoic Acid Supplements. https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/carnliposupp_508.pdf Accessed 25 June 2019.
2. L-Carnitine. http://www.altmedrev.com/archive/publications/10/1/42.pdf Accessed 25 June 2019.
3. Ramsay RR. A Brief History of Carnitine and its Presence in the CNS. In: Teelken A., Korf J. Neurochemistry. 1997; 1039-1045.
4. Freidman S, Fraenkel G. Reversible Enzymatic Acetylation of Carnitine.  Arch. Biochem. Biophys. 1955;59(2): 491-501. doi: 10.1016/0003-9861(55)90515-4.
5. Plioplys AV, Plioplys S. Serum Levels of Carnitine in Chronic Fatigue Syndrome: Clinical Correlates. Neuropsychobiology. 1995; 32:132-138.
6. Plioplys AV, Plioplys S. Amantadine and L-Carnitine Treatment of Chronic Fatigue Syndrome. Neuropsychobiology. 1997; 35:16-23. doi: 10.1159/000119325.
7. Fielding R, Riede L, Lugo JP, Bellamine A. L-Carnitine Supplementation in Recovery after Exercise. Nutrients. 2018;10(3): 349.
8. Pooyandjoo M, Nouhi M, Shab-Bidar S, Djafarian K, Olyaeemanesh A. The Effect of L-Carnitine on Weight Loss in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Obes. Rev. 2016;17(10):970-6. DOI: 10.1111/obr.12436.
9. Malaguarnera M, Pistone G, Astuto M, et al. L-Carnitine in the Treatment of Mild or Moderate Hepatic Encephalopathy. Dig Dis. 2003; 21:271-275. DOI: 10.1159/000073347.
10. Mingrone G, Greco AV, Capristo E, et al. L-Carnitine Improves Glucose Disposal in Type-2 Diabetic Patients. J Am. Coll Nutr. 1999; 18:77-82. doi: 10.1080/07315724.1999.10718830.
11. Cakir N, Yetkin I, Karakoc A, et al. L-carnitine in the Treatment of Painful Diabetic Neuropathy and It’s Effect on Plasma Beta-Endorphin Levels. Curr Ther Res Clin Exp. 2000; 61:871-876.
12. Corbucci GG, Lettieri B. Cardiogenic Shock and L-Carnitine: Clinical Data and Therapeutic Perspectives. Int J Clin Pharmacol Res. 1991; 11:283-293.
13. Corbucci GG, Loche F. L-Carnitine in Cardiogenic Shock Therapy: Pharmacodynamic Aspects and Clinical Data. Int J Clin Pharmacol Res. 1993; 13:87-91.
14. Rizos I. Three-Year Survival of Patients with Heart Failure Caused by Dilated Cardiomyopathy and L-Carnitine Administration. Am Heart J. 2000;139: S120-A123.
15. Singh RB, Niaz MA, Agarwal P, Beegum R, Rastogi SS, Sachan DS. A Randomized, Double-Blind, Placebo-Controlled Trial of L-Carnitine in Suspected Acute Myocardial Infarction. Postgrad Med J. 1996;72(843):45-50.
16. Carnitine: Lessons from One Hundred Years of Research. Ann NY Academy Sci. 2004; 1033:9-11.
17. Hug G, McGraw CA, Bates SR, Landrigan EA. Reduction of Serum Carnitine Concentrations During Anti-Convulsant Therapy with Phenobarbital, Valproic Acid, Phenytoin and Carbamazepine in Children. J Pediatr. 1991; 119:799-802.
18. Melegh B, Pap M, Molnar D, et al. Carnitine Administration Ameliorates the Changes in Energy Metabolism Caused by Short-Term Pivampicillin Medication. Eur J Pediatr. 1997; 156:795-799.
19. Georgala S, Schulpis KH, Georgala C, Michas T. L-Carnitine Supplementation in Patients with Cystic Acne on Isotretinoin Therapy. J Eur Acad Dermatol Venereol. 1999; 13:205-209.