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’s (ALCAR) 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 [1], ALCAR showed signs of slowing down progression in human patients between 40-70 years and on Riluzole. Dosage was 3 g/day for 48 weeks.


== 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?]


== 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]


== References ==


[1]
<bibtex>@article{Beghi2013,
abstract = {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.},
author = {Beghi, Ettore and Pupillo, Elisabetta and Bonito, Virginio and Buzzi, Paolo and Caponnetto, Claudia and Chi\`{o}, Adriano and Corbo, Massimo and Giannini, Fabio and Inghilleri, Maurizio and Bella, Vincenzo La and Logroscino, Giancarlo and Lorusso, Lorenzo and Lunetta, Christian and Mazzini, Letizia and Messina, Paolo and Mora, Gabriele and Perini, Michele and Quadrelli, Maria Lidia and Silani, Vincenzo and Simone, Isabella L and Tremolizzo, Lucio},
doi = {10.3109/21678421.2013.764568},
issn = {2167-9223},
journal = {Amyotrophic lateral sclerosis \& frontotemporal degeneration},
keywords = {Acetylcarnitine,Acetylcarnitine: therapeutic use,Adult,Aged,Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: drug therapy,Disease Progression,Double-Blind Method,Drug Therapy, Combination,Excitatory Amino Acid Antagonists,Excitatory Amino Acid Antagonists: therapeutic use,Female,Humans,Male,Middle Aged,Nootropic Agents,Nootropic Agents: therapeutic use,Pilot Projects,Quality of Life,Riluzole,Riluzole: therapeutic use,Treatment Outcome,Vital Capacity},
month = sep,
number = {5-6},
pages = {397--405},
pmid = {23421600},
title = {{Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for ALS.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23421600},
volume = {14},
year = {2013}
}
</bibtex>
@@ Line 3: / Line 3: @@
 [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 (ALCAR) 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.
-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.
+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 [1], ALCAR showed signs of slowing down progression 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 additional 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}}
-Serum levels of L-carnitine are lower in patients with ALS in comparison to healthy people. Also, the lower serum level of L-carnitine is associated with the higher severity of the disease. {{#pmid:34119273|sarraf2021}}
-=== 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 ===
-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)]
@@ Line 56: / Line 24: @@
-[[Category:Supplement data pages]]
+[1]
+<bibtex>@article{Beghi2013,
+abstract = {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.},
+author = {Beghi, Ettore and Pupillo, Elisabetta and Bonito, Virginio and Buzzi, Paolo and Caponnetto, Claudia and Chi\`{o}, Adriano and Corbo, Massimo and Giannini, Fabio and Inghilleri, Maurizio and Bella, Vincenzo La and Logroscino, Giancarlo and Lorusso, Lorenzo and Lunetta, Christian and Mazzini, Letizia and Messina, Paolo and Mora, Gabriele and Perini, Michele and Quadrelli, Maria Lidia and Silani, Vincenzo and Simone, Isabella L and Tremolizzo, Lucio},
+doi = {10.3109/21678421.2013.764568},
+issn = {2167-9223},
+journal = {Amyotrophic lateral sclerosis \& frontotemporal degeneration},
+keywords = {Acetylcarnitine,Acetylcarnitine: therapeutic use,Adult,Aged,Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: drug therapy,Disease Progression,Double-Blind Method,Drug Therapy, Combination,Excitatory Amino Acid Antagonists,Excitatory Amino Acid Antagonists: therapeutic use,Female,Humans,Male,Middle Aged,Nootropic Agents,Nootropic Agents: therapeutic use,Pilot Projects,Quality of Life,Riluzole,Riluzole: therapeutic use,Treatment Outcome,Vital Capacity},
+month = sep,
+number = {5-6},
+pages = {397--405},
+pmid = {23421600},
+title = {{Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for ALS.}},
+url = {http://www.ncbi.nlm.nih.gov/pubmed/23421600},
+volume = {14},
+year = {2013}
+}
+</bibtex>