Editing Acetyl L-carnitine (ALCAR)

[[Information on nutritional supplements people with ALS have been taking]]

[https://en.wikipedia.org/wiki/Acetylcarnitine 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 ==

There are anecdotal observations of low ALCAR levels in ALS patients (see the [http://www.alstdi.org/forum/yaf_postst53060_low-acetyllcarnitine-levels-and-alshuge-piece-of-the-puzzle.aspx discussion thread]), but so far no systematic study has been made about the issue. In an August 2013 Phase II double-blinded study {{#pmid:23421600|beghi2013}}, 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 {{#pmid:3234464|harper1988}}, so it is more effective to take several small doses at a few hours' intervals. Insulin helps drive carnitine into the muscles {{#pmid:16368715|stephens2006}}. Choline appears to help carnitine economy by reducing excretion and promoting uptake by the muscles (see: http://examine.com/supplements/L-Carnitine ). A couple grams of choline daily is another good adjunct to oral carnitine supplementation. In addition to the synergism of choline (and lecithin), two additironal studies support the strategy of combining ALCAR & alpha lipoic acid and in conjunction with CoQ10. {{#pmid:3714057|didonato1986}}, {{#pmid:7605800|schonheit1995}}

One study {{#pmid:10219976|rao1999}} demonstrated that ALCAR protects brain cells against glutamate-induced and ammonia-induced toxicity. Another {{#pmid:10463134|calvani1999}} 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. {{#pmid:9270896|fernandez1997}} It increases nerve growth factor levels in the central nervous system of aged rats. {{#pmid:8187841|taglialatela}} 

It has been concluded to have a great potential for the treatment of diabetic neuropathy. {{#pmid:9864270|nakamura1998}}

=== Regulated pathways ===

ALCAR upregulates VDAC1 gates in rat brain mitochondria. {{#pmid:16527372|traina2006}} It raises ATP levels {{#pmid:17914184|chan2007}} and promotes acetylcholine production [source needed].

=== Choline acetyltransferase and ALS ===
err
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. {{#pmid:2911033|kato1989}}





== Discussion threads on the ALSTDI forum ==

[http://www.alstdi.org/forum/yaf_postst53060_low-acetyllcarnitine-levels-and-alshuge-piece-of-the-puzzle.aspx  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.

[http://www.alstdi.org/forum/yaf_postst54116_acetyllcarnitine.aspx Acetyl-L-carnitine]
:''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).''

[http://www.alstdi.org/forum/yaf_postst52472_lcarnitine-no-followup.aspx 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 ==

[http://alsanesthetics.org/research/solving-the-puzzle/potential-therapeutics-foci-of-intervention/82-alcar Studies on ALS: ALCAR]


== Where to get it ==

[http://www.amazon.co.uk/gp/product/B0017OFR6A amazon.co.uk (capsules)]

[http://www.amazon.co.uk/gp/product/B0041HPZ6M amazon.co.uk (powder)]


== References ==



[12]
<bibtex>
@article{Traina2006,
abstract = {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.},
author = {Traina, Giovanna and Bernardi, Rodolfo and Rizzo, Milena and Calvani, Menotti and Durante, Mauro and Brunelli, Marcello},
doi = {10.1016/j.neuint.2005.11.005},
issn = {0197-0186},
journal = {Neurochemistry international},
keywords = {Acetylcarnitine,Acetylcarnitine: metabolism,Acetylcarnitine: pharmacology,Animals,Apoptosis,Apoptosis: drug effects,Apoptosis: physiology,Brain,Brain: drug effects,Brain: metabolism,Calcium Signaling,Calcium Signaling: drug effects,Calcium Signaling: physiology,DNA Fingerprinting,Gene Expression Regulation,Gene Expression Regulation: drug effects,Gene Expression Regulation: physiology,Gene Library,Male,Mitochondria,Mitochondria: drug effects,Mitochondria: metabolism,Mitochondrial Membranes,Mitochondrial Membranes: drug effects,Mitochondrial Membranes: metabolism,Neuronal Plasticity,Neuronal Plasticity: drug effects,Neuronal Plasticity: physiology,Nootropic Agents,Nootropic Agents: metabolism,Nootropic Agents: pharmacology,RNA, Messenger,RNA, Messenger: drug effects,RNA, Messenger: metabolism,Rats,Rats, Wistar,Up-Regulation,Up-Regulation: drug effects,Up-Regulation: physiology,Voltage-Dependent Anion Channel 1,Voltage-Dependent Anion Channel 1: genetics},
mendeley-groups = {alcar},
month = jun,
number = {8},
pages = {673--8},
pmid = {16527372},
title = {{Acetyl-L-carnitine up-regulates expression of voltage-dependent anion channel in the rat brain.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16527372},
volume = {48},
year = {2006}
}
</bibtex>

[13]
<bibtex>
@article{Chan2007,
abstract = {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.},
author = {Chan, Amy and Shea, Thomas B},
issn = {1535-1084},
journal = {Neuromolecular medicine},
keywords = {Acetylcarnitine,Acetylcarnitine: pharmacology,Acetylcysteine,Acetylcysteine: pharmacology,Aggression,Aggression: drug effects,Animals,Apolipoprotein E4,Apolipoprotein E4: genetics,Apolipoprotein E4: metabolism,Cognition,Cognition: drug effects,Dietary Supplements,Humans,Mice,Mice, Transgenic,Oxidation-Reduction,S-Adenosylmethionine,S-Adenosylmethionine: pharmacology},
mendeley-groups = {alcar},
month = jan,
number = {3},
pages = {264--9},
pmid = {17914184},
title = {{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.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17914184},
volume = {9},
year = {2007}
}
</bibtex>

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