Absorption, Distribution and Excretion
Acetylcarnitine supplements are absorbed in a similar manner to L-carnitine. Acetylcarnitine is also excreted in a similar manner to L-carnitine. Both are excreted via the kidneys and involve renal tubular secretion. In mammals, the carnitine pool consists of non-esterified L-carnitine and various acylcarnitine esters. Among these esters, acetyl-L-carnitine is the most important in terms of quantity and function. The maintenance of carnitine homeostasis depends on dietary absorption, a moderate rate of synthesis, and efficient renal reabsorption. Dietary L-carnitine is absorbed via active and passive transport across the intestinal cell membrane. The bioavailability of dietary L-carnitine is 54-87%, depending on the amount of L-carnitine in the diet. The absorption of L-carnitine dietary supplements (0.5-6 grams) is primarily passive; the bioavailability is 14-18% of the dose. Most of the unabsorbed L-carnitine is degraded by microorganisms in the large intestine. Circulating L-carnitine is distributed in two kinetically defined compartments: one large and slow-turnover compartment (presumably muscle), and the other relatively small and fast-turnover compartment (presumably liver, kidneys, and other tissues). At normal dietary L-carnitine intake, the systemic turnover time in the human body is 38–119 hours. In vitro studies show that acetyl-L-carnitine undergoes partial hydrolysis within intestinal cells during absorption. In vivo studies show that daily oral administration of 2 g of acetyl-L-carnitine supplementation increased the concentration of circulating acetyl-L-carnitine by 43%, indicating that at least some of the absorption of acetyl-L-carnitine is not hydrolyzed. Following a single intravenous injection (0.5 g), acetyl-L-carnitine is rapidly hydrolyzed, but not completely; the concentrations of both acetyl-L-carnitine and L-carnitine return to baseline levels within 12 hours. At normal circulating L-carnitine concentrations, the kidneys reabsorb L-carnitine efficiently (90–99% of filtration load; clearance 1–3 mL/min), but exhibit saturation kinetics. Therefore, with increasing circulating L-carnitine concentrations (e.g., after high-dose intravenous or oral L-carnitine), reabsorption efficiency decreases and clearance increases, leading to a rapid decline in circulating L-carnitine concentrations back to baseline levels. The elimination kinetics of acetyl-L-carnitine are similar to those of L-carnitine. Evidence suggests that both L-carnitine and acetyl-L-carnitine are secreted via the renal tubules. Future research should investigate supplemental dosage, changes and maintenance of tissue concentrations of L-carnitine and acetyl-L-carnitine, and the correlation between metabolic and functional changes and outcomes. Acetyl-L-carnitine (ALC), a physiological component of the L-carnitine family, has been proposed for the treatment of Alzheimer's disease at pharmacologically appropriate doses. Due to the long-term nature of this disease, this study investigated the pharmacokinetics of acetyl-L-carnitine using multiple routes of administration in 11 patients with Alzheimer's disease. The study design included a 3-day baseline observation period, a sham treatment group with repeated blood sampling, a treatment group receiving 30 mg/kg (corrected) acetyl-L-carnitine intravenously for 10 consecutive days (with plasma pharmacokinetic studies conducted on day 7), and a treatment group receiving 1.5 g (corrected) acetyl-L-carnitine orally daily for 50 consecutive days (divided into three doses). Total acid-soluble L-carnitine, L-carnitine, and acetyl-L-carnitine in plasma and cerebrospinal fluid were determined using enantioselective radioenzyme assay. The concentration of short-chain L-carnitine esters was calculated as the difference between total L-carnitine and free L-carnitine. Plasma concentrations of the L-carnitine family components remained unchanged during the three-day baseline period and were unaffected during the sham treatment. Following intravenous bolus administration, plasma concentrations exhibited a biphasic curve with mean half-lives of 0.073 hours and 1.73 hours, respectively. At the end of oral treatment, plasma concentrations of acetyl-L-carnitine and short-chain L-carnitine esters were significantly higher than during the lead-in period. Cerebrospinal fluid concentrations parallel plasma concentrations, indicating that acetyl-L-carnitine readily crosses the blood-brain barrier. This study investigated the pharmacokinetics of acetyl-L-carnitine hydrochloride (calculated as internal salt) administered intravenously to six healthy volunteers (half male and half female). Plasma concentrations of acetyl-L-carnitine (A), L-carnitine (B), and total acid-soluble L-carnitine fractions, as well as urinary excretion, were assessed from 24 hours before administration to 48 hours after administration. Following administration, plasma concentrations of acetyl-L-carnitine (A) rapidly increased, then decreased, returning to baseline levels within 12 hours. Conversely, plasma concentrations of acetyl-L-carnitine (B) increased more slowly, peaking within 30–60 minutes, and then decreasing to baseline levels within 24 hours. Most of the injected acetyl-L-carnitine was excreted in the urine as B and A within 24 hours after administration. Within 12 hours post-injection, the mean renal clearance rates of both A and B were higher than baseline, suggesting the presence of a saturable tubular reabsorption process that may offset the significant changes in plasma L-carnitine concentration patterns. /Acetyl-L-carnitine hydrochloride/
L-carnitine and its short-chain, medium-chain, and long-chain acyl esters constitute the L-carnitine family. These compounds maintain a homeostatic equilibrium in vivo, the maintenance and restoration of which depend on dynamic exchange between L-carnitine and its esters (catalyzed by carnitine acyltransferase) and tubular reabsorption processes with different thresholds. The interactions of these compounds with albumin and plasma proteins in rats, dogs, and humans were carefully investigated using ultrafiltration and gel filtration techniques. The results showed that L-carnitine and its short-chain esters, namely acetyl-L-carnitine and propionyl-L-carnitine, do not interact with albumin or plasma proteins; the interaction of capryloyl-L-carnitine is low (12-30%) but still measurable; while palmitoyl-L-carnitine, a molecule with detergent activity, binds completely to albumin and plasma proteins. For more complete data on the absorption, distribution, and excretion of acetyl-L-carnitine (8 types), please visit the HSDB record page.

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Metabolism/Metabolites
L-carnitine participates in a reversible transesterification reaction in which the acyl group is transferred from coenzyme A to the hydroxyl group of L-carnitine…acetyl-L-carnitine…is biosynthesized in this manner.
Acetyl-L-carnitine (ALC) is a trimethylated ester of the amino acid L-carnitine, synthesized by enzymes in the human brain, liver, and kidneys. ALC transferase.
…Experimental studies have shown that in rats and humans, the kidneys can synthesize acetyl-L-carnitine from L-carnitine and acetoacetic acid or β-hydroxybutyrate…

Interactions
A study of 56 infertile men found that the combination of L-carnitine and acetyl-L-carnitine significantly improved sperm motility. In mouse models of aging and neurodegenerative diseases, the combined use of N-acetylcysteine (an antioxidant and glutathione precursor that counteracts Aβ neurotoxicity), acetyl-L-carnitine (which increases ATP levels, protects mitochondria, and buffers Aβ neurotoxicity), and S-adenosylmethionine (which promotes glutathione utilization and maintains acetylcholine levels) enhanced or maintained cognitive function and reduced or prevented aggressive behavior. The enhancement of cognitive function was rapidly reversed upon discontinuation of the supplement and recovered upon resupplementation. Behavioral abnormalities are associated with decreased acetylcholine levels, and this combination of nutritional supplements prevents this decline, suggesting that neurotransmitter imbalances may be one of the causes of these abnormal behaviors. This nutritional supplement combination compensates for dietary deficiencies in folic acid and vitamin E, while supplementing dietary iron as a pro-oxidant (these two factors together increase homocysteine levels and exacerbate oxidative damage in brain tissue), indicating its antioxidant neuroprotective effects. ...
HIV infection itself and antiretroviral drugs can both lead to oxidative stress and mitochondrial dysfunction. ...This study evaluated the effects of zidovudine, stavudine, and didanoxin on U937 and CEM cell lines. All of these drugs induced apoptosis and increased intracellular hydrogen peroxide levels, but did not increase superoxide anion levels. The addition of acetyl-L-carnitine (ALC) prevented the pro-oxidative effects of the tested drugs. Certain HIV-infected populations, especially those receiving high-intensity antiretroviral therapy, have insufficient acetyl-L-carnitine (ALC) levels, and ALC supplementation has been shown to have positive effects. These data suggest that one of the effects may be a direct antioxidant effect.
Beagles aged 7.6 to 8.8 years were supplemented twice daily with alpha-lipoic acid (LA) and acetyl-L-carnitine (ALC) for approximately two months. Compared to a control group receiving a placebo of methylcellulose, beagles supplemented with LA and ALC showed significantly lower error rates when reaching learning standards in two landmark discrimination tasks. Testing began after a 5-day adaptation period. These dogs also underwent a variable-delay version of a previously learned spatial memory task; results were not significant. The improved performance of the LA+ALC-supplemented dogs in the landmark tasks demonstrates the effectiveness of this supplement in improving discrimination ability and egocentric spatial learning. Studies have shown that long-term use of LA and ALC may effectively mitigate age-related cognitive decline by slowing mitochondrial deterioration and cellular aging.
For more (complete) data on interactions of acetyl-L-carnitine (9 types), please visit the HSDB records page.

Serhiyenko VA, Serhiyenko AA. Cardiac autonomic neuropathy: Risk factors, diagnosis and treatment. World J Diabetes. 2018 Jan 15;9(1):1-24. doi: 10.4239/wjd.v9.i1.1. Review.

Therapeutic Uses
L-carnitine, acetyl-L-carnitine, and/or propionyl-L-carnitine can be used as replacement therapy to restore normal carnitine concentrations and/or a normal ratio of non-esterified to esterified carnitine…
/EXPL THER/…A recent meta-analysis of 21 double-blind clinical trials of acetyl-L-carnitine for mild cognitive impairment and mild Alzheimer's disease showed significantly superior efficacy compared to placebo. A meta-analysis of 4 clinical trials of L-carnitine for diabetic neuropathy showed significantly superior efficacy compared to placebo.
/EXPL THER/An open-label crossover study included 24 elderly patients hospitalized for depression. Patients were divided into low and high groups according to the modified Hamilton Depression Rating Scale for the Elderly. The study period was 2 months. Half of the patients received acetyl-L-carnitine for 1 month and then switched to placebo (Group A); the other half received placebo first and then switched to acetyl-L-carnitine (Group B). Statistical evaluation included two aspects: parametric analysis of variance was performed on the four subgroups (A1, A2, B1, and B2), and the percentage changes in scores before and after treatment were analyzed in groups A and B. The results showed that acetyl-L-carnitine treatment was significantly effective in the A1/B1, A2/B2, A1, B1, and B2 subgroups. Notably, depressive tendencies were significantly improved in most groups, while the effects on general somatic symptoms, anxiety, fatigue, and sleep disturbances were minimal. Clinical evaluation, based on the percentage changes in scores before and after treatment, clearly confirmed that acetyl-L-carnitine was particularly effective in patients with more severe clinical symptoms. At the dosage and regimen used, the drug did not cause any side effects.
/EXPL THER/ ... Two multicenter clinical trials in patients with type 1 or type 2 diabetes found that acetyl-L-carnitine treatment… significantly relieved neuropathic pain and improved vibration sensation in patients with diabetic neuropathy. This therapy was most effective in patients with shorter disease duration of type 2 diabetes. For more complete data on the therapeutic uses of acetyl-L-carnitine (22 in total), please visit the HSDB record page.

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Pharmacodynamics
The complete physiological effects of acetyl-L-carnitine are still under investigation. Currently, acetyl-L-carnitine has been found to have positive effects on mental fatigue, neurodegenerative diseases, cognitive function, peripheral neuropathy, and sperm motility. Specifically, a study in HIV-infected individuals showed that patients supplemented with acetylcarnitine experienced increased CD4 cell counts, reduced lymphocyte apoptosis, improved polyneuropathy and cardiovascular damage, and decreased blood triglyceride and TNF-α levels. Another study suggests that acetylcarnitine may increase glucose utilization in patients with type 2 diabetes by enhancing the activity of glycogen synthase.

203.24

203.115

3040-38-8

Acetyl-L-carnitine hydrochloride; 5080-50-2; Acetyl-L-carnitine-d9; 203805-90-7

7045767

White to off-white solid powder

145°C

Originated from animals: Homo sapiens

-4.15

0

4

5

14

214

1

CC(O[C@@H](C[N+](C)(C)C)CC([O-])=O)=O

RDHQFKQIGNGIED-MRVPVSSYSA-N

InChI=1S/C9H17NO4/c1-7(11)14-8(5-9(12)13)6-10(2,3)4/h8H,5-6H2,1-4H3/t8-/m1/s1

(3R)-3-Acetyloxy-4-(trimethylazaniumyl)butanoate

Acetyl-L-carnitine Acetyl L carnitine ALCAR L-Acetylcarnitine L-O-Acetylcarnitine LAC

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: ~100 mg/mL (~492.0 mM; with ultrasonication)
DMSO: ~14.3 mg/mL (~70.3 mM; with ultrasonication and warming by heating to 60°C)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (12.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (12.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well.

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 (Please use freshly prepared in vivo formulations for optimal results.)