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Acetyl-L-Carnitine: Clinical Applications

Acetyl-l-carnitine (ALC) has been researched or used for a wide variety of health problems.

Peripheral neuropathy (secondary to trauma)
Diabetic peripheral neuropathy
HIV-related peripheral neuropathy
Alzheimer's disease
HIV infection and immune function
Cerebral hypoxia and ischemic reperfusion injury
Cardiovascular disease
Male infertility
Peyronie's disease
Cerebral ataxia
ADHD - attention deficit disorder
Down's syndrome
Facial paralysis
Pulmonary tuberculosis
Cognitive deficit due to alcoholism
Chronic fatigue syndrome
Parkinson's disease

Peripheral Neuropathy Secondary to Trauma

Over 300,000 cases of peripheral nerve trauma occur each year in Europe alone. Even with the best microsurgical nerve repair, normal sensation is rarely restored. Thus, peripheral nerve trauma is a major cause of morbidity and carries a high cost to healthcare. There is no effective treatment for peripheral nerve trauma apart from surgery (5). However, recent research in animals strongly suggests ALC can prevent and even reverse nerve death associated with trauma. Following unilateral sciatic nerve division, animals received parenteral ALC, saline, or no treatment. Results: Neuron loss was 21% for both sham and no treatment groups. Neuron loss was almost completely inhibited (0% and 2% loss ALC groups) after 2 weeks with ALC treatment. After 2 months, neuron loss was 35% without treatment and –4% with ALC (6).

While prevention of neuron loss is of great benefit, an effective neuro-regenerative treatment would be invaluable. A similar study was undertaken to determine whether ALC treatment could not only prevent neuron death, but also aid in regeneration. In this experiment, nerve tissue grafts were done 2 months after sciatic nerve dissection. Results: ALC significantly increased the growth of both nerve fibers and Schwann cells when compared with no treatment. Dramatic regeneration into the distal stump occurred, with an over 20 fold increase, compared with no treatment. The latter finding is essential for new nerve fibers to reach target sensory or motor organs. ALC has the potential to be the first effective preventative and regenerative treatment for all kinds of peripheral nerve trauma including injuries and surgeries (7).

Diabetic Peripheral Neuropathy

Peripheral neuropathy associated with diabetes mellitus (DM) affects almost 1/3 of patients (8). Experimental animal models show a disruption in carnitine metabolism and increased nerve conduction with acetyl-l-carnitine treatment (9, 10). In addition to two smaller studies showing significant improvement with intramuscular (IM) ALC injections (11, 12), a more recent randomized double blinded placebo controlled trial with 333 patients was conducted. Patients were treated with ALC 1,000 mg/day intramuscularly for 10 days, followed by oral ALC at 2,000 mg/day for 1 year. Nerve condition velocity dramatically increased by several fold in the ALC group compared with placebo. Acetyl-l-carnitinetreatment also significantly decreased painful neuropathies by 39% from baseline scores. The authors of the study concluded that ALC was a promising treatment for diabetic neuropathy (13).

HIV-Related Peripheral Neuropathy

Peripheral neuropathy is the one of the most common and debilitating conditions seen among HIV-infected individuals. While distal neuropathy may manifest secondary to viral infection, the majority of cases result from the mitochondrial toxicity of anti-retroviral medications (14). In one study, HIV+ patients with neurotoxic medication-induced neuropathy had significantly lower levels of acetyl-l-carnitine compared to controls. In 75% of patients levels were below the lowest limit measured in controls. Interestingly, there was no difference in levels of total carnitine when compared to controls. Thus, the authors suggest medication interference with the acetylation of carnitine (15). Another study did not find these differences (16). However, studies have also found significantly decreased carnitine levels in HIV+ patients’ tissues and cells, while serum levels were normal (17,18).

Improvement in painful distal neuropathy has been seen with IM and IV treatment with acetyl-l-carnitine. After 3 weeks 10 out of 16 patients reported clinical improvement (19). In a small open trial of four patients with grade 3 and 4 painful distal neuropathies, oral ALC 1.5 g was given twice daily for 6 months. Patients reported significant improvement in clinical symptoms and biopsies confirmed significant restoration of cutaneous innervation (20).

Alzheimer's Disease

Alzheimer's disease is the most common cause of dementia and the fourth leading cause of death in the elderly in the United States (21). Since acetyl-l-carnitine acts as a precursor to acetylcholine, increases NGF levels in the hippocampus, NGF receptor synthesis, and has been shown to improve cognitive deficits in aged rats, several studies have investigated the effect of this nutrient in patients suffering with Alzheimer's disease. Clinical trials have universally found ALC to slow the progression of cognitive deficits in patients with Alzheimer's disease. While not all studies have been equally positive, several small studies up to 1 year in duration have shown significantly less progression in several areas such as verbal fluency, verbal memory, short term memory, reaction time, timed attention, personal recognition and others measures (22,23,24,25). Patients were treated with 2 to 3 grams of ALC daily in these trials. In one long-term double blind controlled trial, 130 AD patients were treated with oral ALC or placebo for 1 year. While disease progression occurred in both groups, ALC treated patients showed slower declines for all 14 outcome measures assessed. Better compliance was associated with greater drug benefit (26). In two more recent, year long trials, benefits were found in younger patients - less than 65 years. Disease progression is typically more rapid in those afflicted at an early age (21,27).

HIV Infection and Immune Function

Acetyl-l-carnitineis perhaps the single most important supplemental nutrient for persons infected with HIV. ALC has shown benefit with regard to two essential aspects of this disease: 1) Immunologic changes resulting from HIV infection 2) Morbidity and toxicity of treatment with Nucleoside Reverse Transcriptase Inhibitors (NRTIs).

The association between elevated lymphocyte apoptosis and the decline of CD4 cells has been repeatedly observed with HIV infection (28, 29, 30). Long term non-progessors who remain healthy in spite of active HIV infection, have a low degree of apotosis compared with those progressing to AIDS (28, 31). Several studies have shown that high dose supplementation with ALC (3g/day) and LC (6g/day) significantly reduces CD4 apotosis, even in the presence of high viral titers (32, 33, 34, 35, 36, 37, 38). In one trial, 11 asymptomatic HIV+ men were treated with ALC (3g/day) for 4 months. ALC treatment lead to a strongly significant decrease in apototic CD4 cells. Elevated cell ceramide (an endogenous mediator of apotosis) levels decreased significantly with ALC treatment. In addition, baseline serum free IGF-1 levels dramatically increased with ALC treatment (19.1 vs.170 ng/ml) (33). IGF-1 is known to reduce cellular apotosis. Its stimulation may be another mechanism by which ALC exerts its anti-apototic effect. Other studies have additionally found significant increases in CD4 cells (34) and increased CD4 cell proliferation after treatment with carnitines (37, 38).


Several studies have looked at the effect of acetyl-l-carnitine on depression in elderly patients (39, 40, 41, 42, 43, 44). In a trial of 24 geriatric patients hospitalized for depression, ALC was found to be a highly effective treatment compared to placebo, particularly for patients with the most severe clinical symptoms (42). Bella et al. looked at the effects of ALC in 66 senile patients with diagnosed dysthymic disturbances. ALC treatment (3g/day p.o.) was found to significantly reduce all measures of depression and increase quality of life (41). A more recent preliminary study found elevated brain levels of phosphomonoesters (PME) in depressed elderly patients. ALC treatment significantly reduced depression scores with concomitant normalization of brain PME (39). Thus, it appears that one of the ways that ALC exerts its antidepressive effects is via normalization of the brain’s phospholipid metabolism. Others have found normalization of inappropriate cortisol levels (45), a common disruption found in patients with depression (46).

Cerebral Hypoxia and Ischemia Reperfusion Injury

A number of human clinical trials have demonstrated significant benefit as a result of treatment with acetyl-l-carnitine in cases of cerebral ischemia, stroke, and ischemia reperfusion injury. Patients (n=20) having suffered a stroke in the prior 6 months received a single 1.5g IV bolus of ALC or placebo. SPEC tomography showed increased blood flow to ischemic areas, ipsilateral and contralateral brain hemispheres, only in the ALC treated group (47). A similar study of 10 patients with brain ischemia showed increased blood flood to affected hemispheres and areas of lowest perfusion after treatment with ALC (48). With superior blood flow, improved cognitive function would be anticipated. Indeed, patients with cerebral circulatory insufficiency had significant improvements in memory, number and word tasks, response to simple stimuli and maze tests only after treatment with ALC and not placebo (49).

Patients undergoing vascular surgery suffer the effects of acute hypoxia and resulting reperfusion injury. ALC treatment powerfully attenuated the cellular damage, which occurred in untreated patients in both the brain and skeletal muscle during aortic pulmonary bypass and aortic iliac surgeries respectively. (50, 51). While ALC does not inhibit the infiltration of granulocyctes that occurs with ischemia reperfusion injury, it did significantly suppress their production of superoxide anions (O2-) which are responsible for lipid peroxidation and cell death.

It appears that in addition to its neuro-protective and neuro-regenerative effects, ALC can protect both nervous and muscular tissues by improving blood flow and reducing free radical damage that occurs during ischemia reprerfusion injuries. ALC may be of benefit in any condition where reduced oxygenation and or blood flow can lead to damage or decreased function.

Cardiovascular Disease

Several human studies have documented broad cardiovascular benefits of l-carnitine and propionyl-l-carnitine (PLC) (52, 53, 54). While little human research has examined the cardiovascular effects of acetyl-l-carnitine specifically, animal research suggests that the benefits obtained with LC and PLC are likely to be found with ALC as well. Animal experiments have repeatedly demonstrated that ALC treatment restores cardiolipin levels and mitochondrial function in aged hearts, to that of young animals (55, 56, 57). In one human trial, after 1 year of supplementation with ALC, diabetic patients had no loss in myocardial sympathetic nervous function, compared with deterioration in the placebo group (58).

Male Infertility

The concentration of carnitines in seminal plasma is 10 times greater than that of blood plasma (59). Acetyl-l-carnitine is the major carnitine ester in seminal plasma and spermatazoa. ALC composes 40-80% of total carnitine found in seminal plasma and spermatazoa (59, 61). Several studies have found an association between ALC concentration and sperm motility (59, 60, 61, 62). The ALC/LC ratio of spermatazoa with low motility was 1.77 compared with 4.7 in samples that were highly motile (61). Patients (n=20) with oligoasthenospermia (low sperm counts with decreased motility) were given ALC 4g/day for 60 days. While sperm density was unchanged, progressive motility increased significantly in 12 patients, by a mean of 2.7 fold. Motility returned to baseline 4 months after stopping ALC. There were 5 pregnancies during treatment and another 2 during the 4 months after discontinuation of ALC therapy (63). ALC may be an effective non-toxic treatment for infertility due to low motility sperm.

Peyronie's Disease

Acetyl-l-carnitine 1g b.i.d. p.o. for 3 months was significantly more effective than tamoxifen in acute and early chronic stages of Peyronie’s disease. ALC was significantly more effective in reducing pain and inhibiting disease progression. ALC reduced penile curvature significantly, while tamoxifen did not. Both treatments reduced plaque size. Tamoxifen induced numerous side effects whereas ALC did not (64.). In a trial of advanced or resistant Peyronie’s disease, either oral tamoxifen or PLC (2g/d) were combined with intraplaque verapamil. Only the PLC group had significantly reduced penile curvature, plaque size, cavernosal artery end-diastolic velocity, disease progression and the need for surgery. In addition, this treatment increased the International Index of Erectile Function score and resistivity index of the cavernosal arteries. The authors concluded that PLC plus intraplaque verapamil can be considered the treatment of choice in advanced and resistant Peyronie’s disease (65).


Intravenous acetyl-l-carnitine significantly increased glucose tissue uptake in type II diabetic patients. There was no significant difference in effect between the high and low dosages (5mg/kg bolus plus 0.025 to 1.0mg/kg constant infusion) (66).

Cerebral Ataxia

In a double blind placebo cross over trial, patients with Friedrich's ataxia (FA) (n=11) or idiopathic late onset cerebellar ataxia (ILOCA) (n=13) were treated with acetyl-l-carnitine. Treatment slowed disease progression in both groups. Coordination was significantly improved in patients with ILOCA at 6 months. There was a significant decrease in peripheral signs for patients with ILOCA. Muscle tone showed significant improvement at 6 months in the treated FA group (67).

ADHD - Attention Deficit Hyperactivity Disorder

Both acetyl-l-carnitine and l-carnitine have been studied for the treatment of hyperactivity. Hyperactivity affects nearly all young males with fragile X syndrome, the most common cause of inherited mental retardation. Stimulant drugs lack efficacy and can decrease attention span. In a preliminary trial, 17 fragile X boys were treated with ALC over 1 year. Treatment lead to a significant decrease in hyperactive behavior as assessed by the Conners Abbreviated Parent-Teacher Questionnaire (68). In another trial, otherwise healthy boys with ADHD were treated with LC 100mg/kg for 8 or 16 weeks. Compared with placebo, treatment significantly decreased attention problems and aggressive behavior in 13/24 boys with ADHD. On the request of parents, 20 boys continued LC for 6 months. Parents and teachers reported normal behavior in 19/20 boys at the end of this period (69)

Down's Syndrome

Acetyl-l-carnitine treatment for 90 days lead to significant improvements of visual memory and attention, both in absolute terms and in comparison with the other groups. The authors suggest ALC’s effect may be a consequence of counteracting the cholinergic deficit found in Down’s Syndrome (70).

Factial Paralysis

Otherwise healthy patients with idiopathic facial paralysis were treated with 3g/day of acetyl-l-carnitine for 1 month, plus 50 mg of methylprednisolone for 14 days. An earlier functional recovery of facial nerves was found in treated patients when compared with placebo (71).

Pulmonary Tuberculosis

Patients with active pulmonary tuberculosis were treated with either acetyl-l-carnitine 2g/day for 30 days or placebo. Antibacterial activity was increased or unchanged in the ALC group, while it decreased in the placebo group. The authors suggest that host immune response can be selectively modified by ALC (72).

Cognitive Deficit due to Alcoholism

Alcoholics abstinent for at least 1 month were treated with acetyl-l-carnitine 2g/day or placebo for 90 days. Treatment with ALC lead to significant improvement on measures of long term and logical memory, as well as a simple drawing test, when compared with placebo (73).

Chronic Fatigue Syndrome (CFS)

Serum levels of carnitine esters are decreased in both Japanese and Swedish patients with CFS (74, 75). Cerebral uptake of acetyl-l-carnitine is significantly reduced in patients suffering from CFS. Brain areas of decreased uptake are responsible for motivation, concentration and memory, which may be related to the fatigued state (75). Patients with CFS were treated with either LC or amantadine for 8 weeks. LC lead to significant clinical improvement in 12/18 patients. Amantadine had no effect (76). Cancer patients with non-anemic chemotherapy induced fatigue were treated with LC 4g/day for 7 days. Fatigue was amelorated in 45 of 50 patients after 1 week (77).


Hypothalmic amenorrhea (HA) is the most common cause of amenorrhea (78). Twenty HA patients were treated with acetyl-l-carnitine (2 g/day p.o.). Menstruation resumed within 3 and 6 month of treatment in 10 of 20 woman. LH, estradiol and prolactin levels significantly increased only in hypogonadotropic woman (79).

Parkinson's Disease

Sleep disorders are common in PD, as almost two thirds of patients report them (80). PD patients (n=20) received either 1g or 2g acetyl-l-carnitine daily for seven days. Both doses had beneficial effects on abnormal sleep parameters in PD patients (81).

To order Acetyl-L-Carnitine by phone, please call toll-free 877-347-8600.



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