Acetyl L-carnitine (ALCAR)

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Information on nutritional supplements people with ALS have been taking

Wikipedia page

Acetyl-L-carnitine or ALCAR, is an acetylated form of L-carnitine. It is naturally produced by the body, although it is often taken as a dietary supplement. ALCAR is broken down in the blood by plasma esterases to carnitine which is used by the body to transport fatty acids into the mitochondria for breakdown.

Acetyl- L-carnitine’s transport of the important metabolic factor Acetyl CoA into the mitochondria increases energy production. Similar in structure to acetylcholine, it also stimulates acetylcholine production and enhances cellular membrane health.

Effects on ALS[edit]

There are anecdotal observations of low ALCAR levels in ALS patients (see the discussion thread), but so far no systematic study has been made about the issue. In an August 2013 Phase II double-blinded study [1], ALCAR showed signs of slowing down progression of ALS in human patients between 40-70 years and on Riluzole. Dosage was 3 g/day for 48 weeks.

Bioavailability of oral ALCAR decreases with increased dose [2], so it is more effective to take several small doses at a few hours' intervals. Insulin helps drive carnitine into the muscles [3]. Choline appears to help carnitine economy by reducing excretion and promoting uptake by the muscles (see: ). A couple grams of choline daily is another good adjunct to oral carnitine supplementation. In addition to the synergism of choline (and lecithin), two additional studies support the strategy of combining ALCAR & alpha lipoic acid and in conjunction with CoQ10. [4], [5]

One study [6] demonstrated that ALCAR protects brain cells against glutamate-induced and ammonia-induced toxicity. Another [7] showed that it protects against temporary cerebral ischemia (no blood flow) by maintaining the cell's energy cycle.

ALCAR may facilitate nerve regeneration after nerve injury. [8] It increases nerve growth factor levels in the central nervous system of aged rats. [9]

It has been concluded to have a great potential for the treatment of diabetic neuropathy. [10]

Regulated pathways[edit]

ALCAR upregulates VDAC1 gates in rat brain mitochondria. [11] It raises ATP levels [12] and promotes acetylcholine production [source needed].

Choline acetyltransferase and ALS[edit]

In a 1989 study on four autopsied ALS patients and four controls, the average ChAT activity, expressed on a dry weight basis, of 58 ALS neurons was lower than that of 67 control neurons. The large, well-preserved neurons at the early nonadvanced stage had markedly lower ChAT activities than control neurons. [13]

Discussion threads on the ALSTDI forum[edit]

Low Acetyl-L-Carnitine levels and ALS - Huge piece of the puzzle?

In a human PD model, ALCAR and Alpha Lipoic acid combined worked in 100 to 1000 times smaller concentrations than individually.


Acetyl-L-carnitine has been shown to improve mitochondrial function (Carta 1993; Virmani 2002; Jin 2008). Acetyl-L-carnitine appears to increase the growth and repair of neurons (Wilson 2010; Kokkalis 2009) while protecting neurons from high levels of glutamate when combined with lipoic acid (Babu 2009). Acetyl-L-carnitine also protects neuron cell cultures from excitotoxicity, one of the putative mechanisms of disease in ALS (Bigini 2002). Acetyl-L-carnitine has also been found to reduce neuromuscular degeneration and increase life span in animal models of ALS (Kira 2006). In one animal study, the effects of acetyl-L-carnitine were increased when administered in conjunction with lipoic acid (Hagen 2002).

L-carnitine: no follow-up?

L-Carnitine without the acyl group may be better at targeting muscles and NMJ:s and has better bioavailability, whereas Acetyl L-carnitine is able to cross the blood-CNS-boundary and reach glia and neurons.

Pubmed link collection at Studies on ALS[edit]

Studies on ALS: ALCAR

Where to get it[edit] (capsules) (powder)


  1. Beghi et al.: Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for ALS. Amyotroph Lateral Scler Frontotemporal Degener 2013;14:397-405. PMID: 23421600. DOI. Our objective was to assess the effects of acetyl-L-carnitine (ALC) with riluzole on disability and mortality of amyotrophic lateral sclerosis (ALS). Definite/probable ALS patients, 40-70 years of age, duration 6-24 months, self-sufficient (i.e. able to swallow, cut food/handle utensils, and walk), and with forced vital capacity (FVC) > 80% entered a pilot double-blind, placebo-controlled, parallel group trial and were followed for 48 weeks. ALC or placebo 3 g/day was added to riluzole 100 mg/day. Primary endpoint: number of patients no longer self-sufficient. Secondary endpoints: changes in ALSFRS-R, MRC, FVC and McGill Quality of Life (QoL) scores. Analysis was made in the intention-to-treat (ITT) and per-protocol (PP) population, completers and completers/compliers (i.e. taking > 75% of study drug). Forty-two patients received ALC and 40 placebo. In the ITT population, 34 (80.9%) patients receiving ALC and 39 (97.5%) receiving placebo became non-self-sufficient (p = 0.0296). In the PP analysis, percentages were 84.4 and 100.0% (p = 0.0538), respectively. Mean ALSFRS-R scores at 48 weeks were 33.6 (SD 10.4) and 27.6 (9.9) (p = 0.0388), respectively, and mean FVC scores 90.3 (32.6) and 58.6 (31.2) (p = 0.0158), respectively. Median survival was 45 months (ALC) and 22 months (placebo) (p = 0.0176). MRC, QoL and adverse events were similar. In conclusion, ALC may be effective, well-tolerated and safe in ALS. A pivotal phase III trial is needed.
  2. Harper et al.: Pharmacokinetics of intravenous and oral bolus doses of L-carnitine in healthy subjects. Eur. J. Clin. Pharmacol. 1988;35:555-62. PMID: 3234464. The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 g and 6 g has been investigated in 6 healthy subjects on a low carnitine diet. Carnitine was more rapidly eliminated from plasma after the higher dose. Comparing the 2-g and 6-g doses, the t1/2 beta of the elimination phase (beta) was 6.5 h vs 3.9 h, the elimination constant was 0.40 vs 0.50 h-1 and the plasma carnitine clearance was 5.4 vs 6.1 1 x h-1 (p less than 0.025), thus showing dose-related elimination. Saturable kinetics was not found in the range of doses given. The apparent volumes of distribution after the two doses were not significantly different and they were of the same order as the total body water. Urinary recoveries after the 2-g and 6-g doses were 70% and 82% during the first 24 h, respectively. Following the two oral dosing, there was no significant difference in AUCs of plasma carnitine. Urinary recoveries were 8% and 4% for the 2-g and 6-g doses during the first 24 h. The oral bioavailability of the 2-g dose was 16% and of the 6 h dose 5%. The results suggest that the mucosal absorption of carnitine is already saturated at the 2-g dose.
  3. Stephens et al.: Insulin stimulates L-carnitine accumulation in human skeletal muscle. FASEB J. 2006;20:377-9. PMID: 16368715. DOI. Increasing skeletal muscle carnitine content may alleviate the decline in muscle fat oxidation seen during intense exercise. Studies to date, however, have failed to increase muscle carnitine content, in healthy humans, by dietary or intravenous L-carnitine administration. We hypothesized that insulin could augment Na+-dependent skeletal muscle carnitine transport. On two randomized visits, eight healthy men underwent 5 h of intravenous L-carnitine infusion with serum insulin maintained at fasting (7.4+/-0.4 mIU*l(-1)) or physiologically high (149.2+/-6.9 mIU*l(-1)) concentrations. The combination of hypercarnitinemia (approximately 500 micromol*l(-1)) and hyperinsulinemia increased muscle total carnitine (TC) content from 22.0 +/- 0.9 to 24.7 +/- 1.4 mmol*(kg dm)(-1) (P<0.05) and was associated with a 2.3 +/- 0.3-fold increase in carnitine transporter protein (OCTN2) mRNA expression (P<0.05). Hypercarnitinemia in the presence of a fasting insulin concentration had no effect on either of these parameters. This study demonstrates that insulin can acutely increase muscle TC content in humans during hypercarnitinemia, which is associated with an increase in OCTN2 transcription. These novel findings may be of importance to the regulation of muscle fat oxidation during exercise, particularly in obesity and type 2 diabetes where it is known to be impaired.
  4. Di Donato et al.: Systemic carnitine deficiency due to lack of electron transfer flavoprotein:ubiquinone oxidoreductase. Neurology 1986;36:957-63. PMID: 3714057. A child with myopathy and systemic carnitine deficiency died at age 8 years in an acute metabolic attack. He had glutaric aciduria type II, and his cultured fibroblasts contained normal activity of four different acyl CoA dehydrogenases, but there was deficiency of electron transfer flavoprotein:ubiquinone oxidoreductase (ETF-QO). This enzyme is thought to reduce coenzyme Q in the respiratory chain, funneling reducing equivalents from seven flavoproteins in the beta-oxidation of acyl CoAs. There was massive urinary excretion of the short-chain acylcarnitines that accumulated in mitochondria as a result of the ETF-QO defect. Carnitine therefore acts as a buffer for excessive accumulation of intramitochondrial acyl CoAs, and defective beta-oxidation can cause carnitine insufficiency.
  5. Schönheit et al.: Effect of alpha-lipoic acid and dihydrolipoic acid on ischemia/reperfusion injury of the heart and heart mitochondria. Biochim. Biophys. Acta 1995;1271:335-42. PMID: 7605800. The aim of the present study was to evaluate a possible interference of alpha-lipoic acid (LA) or its reduced form (dithiol dihydrolipoic acid = DHLA) in the cardiac ischemia/reperfusion injury both at the level of the intact organ and at the subcellular level of mitochondria. In order to follow the effect of LA on the ischemia/reperfusion injury of the heart the isolated perfused organ was subjected to total global ischemia and reperfusion in the presence and absence of different concentrations of LA. Treatment with 0.5 microM LA improved the recovery of hemodynamic parameters; electrophysiological parameters were not influenced. However, application of 10 microM LA to rat hearts further impaired the recovery of hemodynamic functions and prolonged the duration of severe rhythm disturbances in comparison to reperfusion of control hearts. Treatment of isolated mitochondria with any concentration of DHLA could not prevent the impairment of respiratory-linked energy conservation caused by the exposure of mitochondria to 'reperfusion' conditions. However, DHLA was effective in decreasing the formation and the existence of mitochondrial superoxide radicals (O2.-). Apart from its direct O(2.-)-scavenging activities DHLA was also found to control mitochondrial O2.- formation indirectly by regulating redox-cycling ubiquinone. It is suggested that impairment of this mitochondrial O2.- generator mitigates postischemic oxidative stress which in turn reduces damage to hemodynamic heart function.
  6. Rao & Qureshi: Reduction in the MK-801 binding sites of the NMDA sub-type of glutamate receptor in a mouse model of congenital hyperammonemia: prevention by acetyl-L-carnitine. Neuropharmacology 1999;38:383-94. PMID: 10219976. Our earlier studies on the pharmacotherapeutic effects of acetyl-L-carnitine (ALCAR), in sparse-fur (spf) mutant mice with X linked ornithine transcarbamylase deficiency, have shown a restoration of cerebral ATP, depleted by congenital hyperammonemia and hyperglutaminemia. The reduced cortical glutamate and increased quinolinate may cause a down-regulation of the N-methyl-D-aspartate (NMDA) receptors, observed by us in adult spf mice. We have now studied the kinetics of [3H]-MK-801 binding to NMDA receptors in spf mice of different ages to see the effect of chronic hyperammonemia on the glutamate neurotransmission. We have also studied the Ca2+-dependent and independent (4-aminopyridine (AP) and veratridine-mediated) release of glutamate and the uptake of [3H]-glutamate in synaptosomes isolated from mutant spf mice and normal CD-1 controls. All these studies were done with and without ALCAR treatment (4 mmol/kg wt i.p. daily for 2 weeks), to see if its effect on ATP repletion could correct the glutamate neurotransmitter abnormalities. Our results indicate a normal MK-801 binding in 12-day-old spf mice but a significant reduction immediately after weaning (21 day), continuing into the adult stage. The Ca2+-independent release of endogenous glutamate from synaptosomes was significantly elevated at 35 days, while the uptake of glutamate into synaptosomes was significantly reduced in spf mice. ALCAR treatment significantly enhanced the MK-801 binding, neutralized the increased glutamate release and restored the glutamate uptake into synaptosomes of spf mice. These studies point out that: (a) the developmental abnormalities of the NMDA sub-type of glutamate receptor in spf mice could be due to the effect of sustained hyperammonemia, causing a persistent release of excess glutamate and inhibition of the ATP-dependent glutamate transport, (b) the modulatory effects of ALCAR on the NMDA binding sites could be through a repletion of ATP, required by the transporters to efficiently remove extracellular glutamate.
  7. Calvani & Arrigoni-Martelli: Attenuation by acetyl-L-carnitine of neurological damage and biochemical derangement following brain ischemia and reperfusion. Int J Tissue React 1999;21:1-6. PMID: 10463134. Alterations in brain metabolism after ischemia and reperfusion are described herein. Several roles played by carnitine and acetylcarnitine can be of particular relevance in counteracting these brain metabolism alterations. The effects of acetylcarnitine in several experimental models of brain ischemia in rats are described. The data obtained show that acetylcarnitine can have significant clinical neuroprotective effects when administered shortly after the onset of focal or global cerebral ischemia. In the canine cardiac arrest model, acetylcarnitine improved the postischemic neurological outcome and tissue levels of lactate and pyruvate were normalized. A trend toward reversal of pyruvate dehydrogenase inhibition in acetylcarnitine-treated dogs was also observed. The immediate postischemic administration of acetylcarnitine prevents free radical-mediated protein oxidation in the frontal cortex of dogs submitted to cardiac arrest and resuscitation. The transfer of the acetyl group to coenzyme A (CoA) to form acetyl-CoA as the primary source of energy is a plausible mechanism of action of acetylcarnitine.
  8. Fernandez et al.: Motonuclear changes after cranial nerve injury and regeneration. Arch Ital Biol 1997;135:343-51. PMID: 9270896. Little is known about the mechanisms at play in nerve regeneration after nerve injury. Personal studies are reported regarding motonuclear changes after regeneration of injured cranial nerves, in particular of the facial and oculomotor nerves, as well as the influence that the natural molecule acetyl-L-carnitine (ALC) has on post-axotomy cranial nerve motoneuron degeneration after facial and vagus nerve lesions. Adult and newborn animal models were used. Massive motoneuron response after nerve section and reconstruction was observed in the motonuclei of all nerves studied. ALC showed to have significant neuroprotective effects on the degeneration of axotomized motoneurons. Complex quantitative, morphological and somatotopic nuclear changes occurred that sustain new hypotheses regarding the capacities of motoneurons to regenerate and the possibilities of new neuron proliferation. The particularities of such observations are described and discussed.
  9. Taglialatela et al.: Acetyl-L-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats. Exp. Gerontol. 1994;29:55-66. PMID: 8187841. The hypothesis that some neurodegenerative events associated with ageing of the central nervous system (CNS) may be due to a lack of neurotrophic support to neurons is suggestive of a possible reparative pharmacological strategy intended to enhance the activity of endogenous neurotrophic agents. Here we report that treatment with acetyl-l-carnitine (ALCAR), a substance which has been shown to prevent some impairments of the aged CNS in experimental animals as well as in patients, is able to increase the levels and utilization of nerve growth factor (NGF) in the CNS of old rats. The stimulation of NGF levels in the CNS can be attained when ALCAR is given either for long or short periods to senescent animals of various ages, thus indicating a direct effect of the substance on the NGF system which is independent of the actual degenerative stage of the neurons. Furthermore, long-term treatment with ALCAR completely prevents the loss of choline acetyltransferase (ChAT) activity in the CNS of aged rats, suggesting that ALCAR may rescue cholinergic pathways from age-associated degeneration due to lack of retrogradely transported NGF.
  10. Nakamura et al.: Polyol pathway hyperactivity is closely related to carnitine deficiency in the pathogenesis of diabetic neuropathy of streptozotocin-diabetic rats. J. Pharmacol. Exp. Ther. 1998;287:897-902. PMID: 9864270. To investigate the relationship between polyol pathway hyperactivity and altered carnitine metabolism in the pathogenesis of diabetic neuropathy, the effects of an aldose reductase inhibitor, [5-(3-thienyl) tetrazol-1-yl]acetic acid (TAT), and a carnitine analog, acetyl-L-carnitine (ALC), on neural functions and biochemistry and hemodynamic factors were compared in streptozotocin-diabetic rats. Significantly delayed motor nerve conduction velocity, decreased R-R interval variation, reduced sciatic nerve blood flow and decreased erythrocyte 2, 3-diphosphoglycerate concentrations in diabetic rats were all ameliorated by treatment with TAT (administered with rat chow containing 0.05% TAT, approximately 50 mg/kg/day) or ALC (by gavage, 300 mg/kg/day) for 4 weeks. Platelet hyperaggregation activity in diabetic rats was diminished by TAT but not by ALC. TAT decreased sorbitol accumulation and prevented not only myo-inositol depletion but also free-carnitine deficiency in diabetic nerves. On the other hand, ALC also increased the myo-inositol as well as the free-carnitine content without affecting the sorbitol content. These observations suggest that there is a close relationship between increased polyol pathway activity and carnitine deficiency in the development of diabetic neuropathy and that an aldose reductase inhibitor, TAT, and a carnitine analog, ALC, have therapeutic potential for the treatment of diabetic neuropathy.
  11. Traina et al.: Acetyl-L-carnitine up-regulates expression of voltage-dependent anion channel in the rat brain. Neurochem. Int. 2006;48:673-8. PMID: 16527372. DOI. Acetyl-L-carnitine (ALC) exerts unique neuroprotective, neuromodulatory, and neurotrophic properties, which play an important role in counteracting various pathological processes, and have antioxidative properties, protecting cells against lipid peroxidation. In this study, suppression subtractive hybridization (SSH) method was applied for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts after treatment of rats with ALC. The technique generates an equalized representation of differentially expressed genes irrespective of their relative abundance and it is based on the construction of forward and reverse cDNA libraries that allow the identification of the genes that are regulated after ALC treatment. In the present paper, we report the identification of the gene of mitochondrial voltage-dependent anion channel (VDAC) protein which is positively modulated by the ALC treatment. VDAC is a small pore-forming protein of the mitochondrial outer membrane. It represents an interesting tool for Ca(2+) homeostasis, and it plays a central role in apoptosis. In addition, VDAC seems to have a relevant role in the synaptic plasticity.
  12. Chan & Shea: Effects of dietary supplementation with N-acetyl cysteine, acetyl-L-carnitine and S-adenosyl methionine on cognitive performance and aggression in normal mice and mice expressing human ApoE4. Neuromolecular Med. 2007;9:264-9. PMID: 17914184. In addition to cognitive impairment, behavioral changes such as aggressive behavior, depression, and psychosis accompany Alzheimer's Disease. Such symptoms may arise due to imbalances in neurotransmitters rather than overt neurodegeneration. Herein, we demonstrate that combined administration of N-acetyl cysteine (an antioxidant and glutathione precursor that protects against A beta neurotoxicity), acetyl-L-carnitine (which raises ATP levels, protects mitochondria, and buffers A beta neurotoxicity), and S-adenosylmethionine (which facilitates glutathione usage and maintains acetylcholine levels) enhanced or maintain cognitive function, and attenuated or prevented aggression, in mouse models of aging and neurodegeneration. Enhancement of cognitive function was rapidly reversed upon withdrawal of the formulation and restored following additional rounds supplementation. Behavioral abnormalities correlated with a decline in acetylcholine, which was also prevented by this nutriceutical combination, suggesting that neurotransmitter imbalance may contribute to their manifestation. Treatment with this nutriceutical combination was able to compensate for lack of dietary folate and vitamin E, coupled with administration of dietary iron as a pro-oxidant (which collectively increase homocysteine and oxidative damage to brain tissue), indicating that it provided antioxidant neuroprotection. Maintenance of neurotransmitter levels and prevention of oxidative damage underscore the efficacy of a therapeutic approach that utilizes a combination of neuroprotective agents.
  13. Kato &: Choline acetyltransferase activities in single spinal motor neurons from patients with amyotrophic lateral sclerosis. J. Neurochem. 1989;52:636-40. PMID: 2911033. Activities of choline acetyltransferase (ChAT) were microassayed in individual cell bodies of motor neurons, isolated from freeze-dried sections after autopsy of lumbar spinal cords from four patients with sporadic amyotrophic lateral sclerosis (ALS) and four control patients with nonneurological diseases. Numerous large neurons were found in the anterior horn at the early degeneration stage of ALS, but the cell bodies atrophied and decreased in number at the late advanced stage. The small, atrophied neurons were very fragile and were easily destroyed during the isolation procedure with a microknife. The average activity, expressed on a dry weight basis, of 58 ALS neurons was lower than that of 67 control neurons. The large, well-preserved neurons at the early nonadvanced stage had markedly lower ChAT activities than control neurons. The specific activity gradually increased with the progress of atrophy but did not return to the control level.