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While acetyl-L-carnitine (ALCAR) appears to have a number of positive benefits, treating dementia is not one of them. Quite a large number of studies have been done including a large 431-patient study which found no overall benefit versus placebo. Some authors and many websites selling ALCAR claim that these studies show effectiveness, but that's just not true. In fact the studies, on the whole, prove an ineffectiveness for dementia. Whether it might help prevent progression to dementia is another issue and has not been adequately studied, but there some favorable evidence in that direction. Fortunately, ALCAR has positive research studies for quite a few conditions: ADHD, chronic fatigue, depression, depression in the elderly, diabetic neuropathy, erectile dysfunction, retroviral neuropathy, neuropathy from cancer drugs, fatigue in multiple sclerosis, macular degeneration, Peyronie's disease, and male infertility. None of these are well proven, but the research looks very promising. Since ALCAR is probably interchangeable with L-carnitine and propionyl carnitine, adding all of the research together makes these findings more reliable and probably mean that ALCAR helps the heart as well. Of course, if I have angina or heart failure, I'd take L-carnitine instead, just to be on the safe side. I do recommend ALCAR to patients with the above diseases in view of its low cost, very low level of side-effects, and many positive studies. There still is a need for more research, because each illness has only a few studies at most. Patient acceptance has been good. ADHD: Helped Children with Fragile X ADHD in Small Study: In a DB PC study of L-acetylcarnitine for the treatment of hyperactive behavior in 17 children with fragile X syndrome ADHD, 1 year of carnitine was reported as helpful. Torrioli MG, Vernacotola S, et al. Am J Med Genet. 1999 Dec 3;87(4):366-8 and Rev Neurol. 2001 Oct;33 Suppl 1:S65-70. ADHD: Acetyl- l-Carnitine Reduced Impulsive Behavior in Adolescent Rats: Chronic ALC helped an animal model of human hyperactivity and has no stimulant effect. Methylphenidate was also successful in the same study. The authors conclude it may help ADHD children. Adriani W, et al, Rome, Italy. Psychopharmacology (Berl). 2004 Nov;176(3-4):296-304. Epub 2004 May ADHD: Acetyl-L-Carnitine Helped Rats with Anoxic Brain Damage at Birth and Hyperactivity: Transient hyperactivity at P20-P45 postnatal days and permanent spatial memory deficits were shown by anoxic rats. A chronic ALC treatment (50 mg/kg/d injected intraperitoneally from P2, after anoxia, to P60) significantly reduced the transient increase in sniffing, rearing and locomotor activity of anoxic rats. Still more improved was the spatial memory performances in a maze at P30-P40 and in a water maze at P50-P60. No behavioral changes were seen in ALC-treated animals that received sham-exposure at birth. Authors suggest ALC may help the treatment of children who suffer anoxia at birth. Effect of acetyl-L-carnitine on hyperactivity and spatial memory deficits of rats exposed to neonatal anoxia. Dell'Anna E, Iuvone L, et al. University of Udine, Italy. Neurosci Lett. 1997 Feb 28;223(3):201-5. Ed: Hyperactivity is also transient during human life, peaking in childhood. Chronic Fatigue Syndrome: Carnitines Appear to Help: In a 24-week open, but randomized study of 30 chronic fatigue patients given 2 g/day of acetyl-L-carnitine, 2 g/day of propionyl-L-carnitine, or the combination, considerable improvement was reported in 59% of acetylcarnitine, 63% propionylcarnitine and 37% for the combo. Acetylcarnitine significantly improved mental fatigue (p =.015) and propionylcarnitine improved general fatigue (p =.004). Attention concentration improved in all groups, whereas pain complaints did not. Two weeks after treatment was stopped, a worsening of fatigue was experienced by 52%, 50%, and 37%, respectively. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Vermeulen RC, Scholte HR., Amsterdam, Netherlands. Psychosom Med. 2004 Mar-Apr;66(2):276-82 Depression: Acetyl-L-Carnitine Promoted for Elderly Depression: In a very poor, very small open trial of just two mildly depressed elderly men, Univ of Pittsburgh researchers suggest that ALCAR helps depression because elevated phosphomonoesters in the pre-frontal lobes decreased in both after 12 weeks of treatment and the decrease correlated with a decrease in HAM-D depression scores. 31P-MRS study of acetyl-L-carnitine treatment in geriatric depression: preliminary results. Pettegrew JW, Levine J, Gershon S, Stanley JA, Servan-Schreiber D, Panchalingam K, McClure RJ. Bipolar Disord. 2002 Feb;4(1):61-6; Pettegrew also claims that DB PC research shows that ALC helps both Major Depressive Disorder and Alzheimer's disease. Mol Psychiatry. 2000 Nov;5(6):616-32. Ed: Pettegrew goes far beyond what his research shows. Still, I think that ALCAR may prove to be of value for mild cognitive impairment and depression in the elderly and even depression with severe fatigue in younger adults. In view of its low cost and very few side-effects, I think it is fine to try out. If you improve, that's not proof that it helped. You need a much larger study to prove cause-effect. But if you improve, I would keep taking it. I have been prescribing it to patients, a number of whom have reported feeling better after starting it.
Depression: Acetyl-L-Carnitine Helped Chronic Depression: In a 12-week DB PC study of 204 patients with dysthymia, long-lasting depression, acetyl-L-carnitine (ALCAR) 500 mg b.i.d. did as well as the atypical antipsychotic amisulpride 50 mg b.i.d. with patients in both groups showing considerable improvement. A double-blind, randomised, controlled clinical trial of acetyl-l-carnitine vs. amisulpride in the treatment of dysthymia. Zanardi R, et al. Vita-Salute University San Raffaele, Milan, Italy. Eur Neuropsychopharmacol 2005 Nov 25. Ed: Amisulpride has been shown better than placebo in at least 3 double-blind studies (Int Clin Psychopharm 2002 Dec) and better than sertraline in one study. I have used carnitine for depressed patients with marked fatigue with some patient satisfaction. This study used a surprisingly low dose and still got excellent benefit. Depression in Elderly Helped by ALCAR: In a small cross-over study of 24 elderly admitted because of depression, ALCAR for 1 month was "highly effective" for depression, but general somatic symptoms as well as anxiety, asthenia and sleep disturbances didn’t improve. L-acetylcarnitine in depressed elderly subjects. A cross-over study vs placebo. Tempesta E, Casella L, et al., Catholic University of the Sacred Heart, Rome, Italy. Drugs Exp Clin Res. 1987;13(7):417-23. Depression In Elderly: Acetyl-L-Carnitine Helped: Only two small DB PC studies are listed on PubMed of ALC for depression. Both were done in Italy, one at a VA hospital of 28 patients 70-80 years old with depression (300.40 DSM-IIIR) with 500 mg three times a day and one at a lesser university, Univ. of Catania of 60 senile dysthymic patients for 60 days with 3 g/day. Evaluation of the effects of L-acetylcarnitine on senile patients suffering from depression. Garzya G, Corallo D, Fiore A, Lecciso G, Petrelli G, Zotti C. Drugs Exp Clin Res. 1990;16(2):101-6; Effect of acetyl-L-carnitine on geriatric patients suffering from dysthymic disorders. Bella R, Biondi R, Raffaele R, Pennisi G. Int J Clin Pharmacol Res. 1990;10(6):355-60. Ed: While these studies are both double-blind, I would be very reluctant to treat patients on the basis of these studies along. But if the patient also had another indication, the depression would increase my recommendation to the patient to give it a try.
Down's Syndrome: No Help: In a 6-month DB PC study of 40 patients, no benefit occurred. Res Dev Disabil 2006 Apr 16
Eye: Macular Degeneration: Carnitine-CoQ10 Combo May Help: Mitochondria and peroxisomes of the retinal pigment epithelium may play a central role in causing age-related macular degeneration (AMD). 14 adults with early AMD were treated with acetyl-L-carnitine (ALC), polyunsaturated fatty acids (PUFAs), coenzyme Q10 (CoQ10) and vitamin E, while 14 others were treated with vitamin E only. In the treated group, all the visual functions showed slight improvement which was evident after 3 months of treatment and remained nearly stationary for 24 months. The control group showed slow worsening although the difference never became statistically significant due to the small number of patients involved. Mitotropic compounds for the treatment of age-related macular degeneration. The metabolic approach and a pilot study. Feher J, Papale A, Mannino G, Gualdi L, Balacco Gabrieli C. University of Rome La Sapienza. Ophthalmologica. 2003 Sep-Oct;217(5):351-7 Eye: Age-Related Macular Degeneration Helped: In a 12-month DB PC study of 106 adults with early AMD,those given a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10 has improves in visual field mean defects, visual acuity, foveal sensitivity, and fundus alterations for AMD. In the treated group only 2% deteriorated vs. 17% for placebo (p = 0.006, odds ratio: 10.93). Decrease in drusen-covered area of treated eyes was also statistically significant. Feher J et al. University of Rome 'La Sapienza', Italy. Ophthalmologica. 2005 May-Jun;219(3):154-66 Fatigue in Multiple Sclerosis: Acetyl L-Carnitine Better than Amantidine: Acetyl L-carnitine (ALCAR) has been shown to improve fatigue in patients with chronic fatigue syndrome. In a 36-patient DB crossover study of 3 months each of amantadine (100 mg twice daily) or ALCAR (1 g twice daily). Beck Depression Inventory didn’t change. Six withdrew because of adverse reactions (5 amantadine and 1 ALCAR). ALCAR was better for the Fatigue Severity Scale (p = 0.039). Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial. Tomassini V, Pozzilli C, Onesti E, Pasqualetti P, Marinelli F, Pisani A, Fieschi C., University of Rome, Italy. J Neurol Sci. 2004 Mar 15;218(1-2):103-8 Nerve Regrowth: ALCAR Helps Severed Rat Nerves: Two months after unilateral sciatic nerve division 1 cm nerve graft repairs were performed (n=5), and treatment with 50 mg/kg/day ALCAR was used for 6 weeks. ALCAR treatment increased nerve fiber growth (total area 264% increase, P<0.001), and Schwann cells (total area 111% increase, P<0.05), when compared to no treatment. Regeneration into the distal stump was greatly enhanced (total area 2,242% increase, P=0.008). Pharmacological enhancement of peripheral nerve regeneration in the rat by systemic acetyl-L-carnitine treatment. McKay Hart A, Wiberg M, Terenghi G. Royal Free and University College Medical School, London, UK. Neurosci Lett. 2002 Dec 16;334(3):181-5 Neuropathy from Cancer Drugs: Acetyl-l-carnitine (1 g tid) for 8 weeks was given to 25 patients with neuropathy grade 3 during paclitaxel or cisplatin therapy, or grade 2 persisting for at least three months after discontinuing the drugs. All patients except one reported symptomatic relief, and only two described grade 1 nausea. The sensory neuropathy grade improved in 15 of 25 (60%), and motor neuropathy in 11 of 14 patients (79%). Total neuropathy score (TNS) that included neurophysiological measures improved in 23 (92%). Amelioration of sensory amplitude and conduction velocity (sural and peroneal nerves) was measured in 22 and 21 patients, respectively. Symptomatic improvement persisted in 12 of 13 evaluable patients at median 13 months after ALC. In view of its effect in improving established paclitaxel- and cisplatin-neuropathy, the authors recommend ALC testing in preventing progression or revert symptoms during neurotoxic chemotherapy. Symptomatic and neurophysiological responses of paclitaxel- or cisplatin-induced neuropathy to oral acetyl-l-carnitine. Bianchi G, et al. Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. Eur J Cancer. 2005 Jul 19 Neuropathy in Diabetes: Acetyl-L-Carnitine Helps in Large Study: In a large English 333-patient 1-year DB PC study 2000 mg/d ALC, peripheral nerve function improved and leg pain diminished. Acetyl-L-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. De Grandis D, Minardi C. Drugs R D. 2002;3(4):223-31
Neuropathy: Diabetics Helps by Acetyl-l-Carnitine in Two Huge Studies: ALC 500 and 1,000 mg/day three times a day, significant improvements in sural nerve fiber numbers and regenerating nerve fiber clusters occurred with active treatment. Nerve conduction velocities and amplitudes did not improve, but vibration perception improved in both studies. Pain as the most bothersome symptom showed significant improvement in one study and in the combined cohort taking 1,000 mg ALC. Acetyl-L-Carnitine Improves Pain, Nerve Regeneration, and Vibratory Perception in Patients With Chronic Diabetic Neuropathy: An analysis of two randomized placebo-controlled trials. Sima AA, Calvani M, et al, Wayne State University Diabetes Care. 2005 Jan;28(1):89-94 Neuropathy: Antiretroviral Toxic Neuropathy Helped: ALCAR (1500 mg twice daily) for up to 33 months in an open study of 21 HIV-positive patients with established antiretroviral toxic neuropathy (ATN). Skin biopsies showed that after 6 month's treatment, small sensory fibers increased (epidermis 100%, P = 0.006; dermis 133%, P < 0.05) by more than that for all fiber types (epidermis 16%, P = 0.04; dermis 49%, P < 0.05; sweat glands 60%, P < 0.001) or for sympathetic fibers (sweat glands 41%, P < 0.0003). Compared with controls, epidermal, dermal and sweat gland innervation reached 92%, 80% and 69%, respectively, after 6 month's treatment. Innervation improvements continued (epidermis and dermis) or stabilized (sweat glands) after 24 month's treatment. Neuropathic grade improved in 76% of patients and remained unchanged in 19%. HIV RNA load, CD4 and CD8 cell counts did not alter significantly throughout the study. Acetyl-l-carnitine: a pathogenesis based treatment for HIV-associated antiretroviral toxic neuropathy. Hart AM, Wilson AD, Montovani C, Smith C, Johnson M, Terenghi G, Youle M. London, UK. AIDS. 2004 Jul 23;18(11):1549-6 Neurotoxicity: Acetyl-L-Carnitine Might Help Cancer Drug Neurotoxicity in Rats: ALC in rat studies suggest it may help with neurotoxicity due to paclitaxel and cisplatin. Clin Cancer Res. 2003 Nov 15;9(15):5756-67
Peyronie's Disease: Acetyl-L-Carnitine Helped: In a randomized study of 48 men with Peyronie's disease, ALC 2000 mg/d did better than tamoxifen at reducing penile curvature, plaque size, disease progression, and penile pain with fewer side-effects. Italy. Acetyl-L-carnitine vs tamoxifen in the oral therapy of Peyronie's disease: a preliminary report. Biagiotti G, Cavallini G. BJU Int. 2001 Jul;88(1):63-7 Sex Dysfunction, Depression, Fatigue in Aging Males: Carnitines a Little Better Than Testosterone: In a 120-patient 6-month DB PC study of men average age 66, testosterone undecanoate 160 mg/day, or propionyl-L-carnitine 2 g/day plus acetyl-L-carnitine 2 g/day or placebo was given. Testosterone and carnitines significantly improved the peak systolic velocity, end-diastolic velocity, resistive index, nocturnal penile tumescence, International Index of Erectile Function score, Depression Melancholia score, and fatigue score. Carnitines were more active in improving nocturnal penile tumescence and erectile function. Testosterone increased prostate volume and free and total testosterone levels and lowered serum luteinizing hormone; carnitines did not. No drug significantly modified prostate-specific antigen or prolactin. Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Cavallini G, Caracciolo S, Vitali G, Modenini F, Biagiotti G. Bologna, Italy. Urology. 2004 Apr;63(4):641-6. Ed: Testosterone carries the risk of increasing prostate cancer and heart disease. Carnitines decrease heart disease. Sperm Motility Helped: In a 6-month DB PC study of 60 infertile men, l-carnitine (2 g/d) and l-acetyl-carnitine (1 g/d) found that combined treatment was effective in increasing sperm motility, especially in groups with lower baseline levels. A placebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia. Lenzi A, Sgro P, Salacone P, Paoli D, Gilio B, Lombardo F, Santulli M, Agarwal A, Gandini L. University of Rome-La Sapienza, Rome, Italy. Fertil Steril. 2004 Jun;81(6):1578-84 Sperm Motility Helped More by LAC and Combined LAC + LC than LC Alone: In a 6-month DB PC study of 60 infertile men with idiopathic asthenozoospermia of LC 3 g/d, LAC 3 g/d, a combination of LC 2 g/d and LAC 1 g/d, or placebo, sperm cell motility (total and forward) increased in patients to whom LAC was administered both alone or in combination with LC; combined LC + LAC therapy led to a significant improvement of straight progressive velocity after 3 months. The total oxyradical scavenging capacity of the semen toward hydroxyl and peroxyl radicals also increased and was positively correlated with the improvement of kinetic features. Patients with lower baseline values of motility and total oxyradical scavenging capacity of the seminal fluid had a significantly higher probability of responding to the treatment. Balercia G, et al. Polytechnic University of Marche, Ancona, Italy. . Fertil Steril. 2005 Sep;84(3):662-71. Juvenon: Acetyl-L-Carnitine + Alpha Lipoic Helped "Biomarkers" in Elderly Sedentary Men: A very small DB PC crossover 17-week study of 18 "healthy" but sedentary men 60-71 years of age with a four week washout between the acetyl-l-carnitine 500 mg with alpha lipoic acid 200 mg b.i.d. vs. placebo found no clear benefit to the supplement for fitness. After a 45 minute exercise test, 8 of 9 biomarkers for "cellular health and oxidative stress" favored the supplement: ammonia, beta-carotene, glutamine, glutathione, malondialdehyde, total antioxidant status (TAS), vitamin C, and vitamin E-gamma tocopherol. biomarkers for cellular health and oxidative stress: ammonia, beta-carotene, glutamine, glutathione, malondialdehyde, total antioxidant status (TAS), vitamin C, vitamin E-alpha tocopherol. Vitamin E-gamma tocopherol did not. Fitness, strength, and weight were not helped by the supplement. The total scores for the majority on the Psychological General Well-Being Index were said to be significantly better. Although the study was done by the Dept of Kinesiology of San Francisco State University in 2001, it has still not been published in a refereed scientific journal as of Oct. 2004. The study was apparently financed by the manufacturer, Bruce Ames of Juvenon. The combination was promoted in a puff piece in Reader's Digest, Nov. 2003 entitled, "The New Pill That Can End Aging." and a similar puff piece in Discover Magazine, Oct. 2003, in which Ames is called "controversial." The Juvenon website is full of anecdotal testimonies. www.juvenon.com. Ed: The research looks very poor for Juvenon being able to "end aging." Alpha lipoic has been found to work for peripheral neuropathy but at higher doses than recommended by Juvenon. While claims of other benefits for alpha lipoic are made, the research is simply not there. Acetyl-L-Carnitine has been well researched for Alzheimer's in far larger studies than the one done for Juvenon with no real evidence of benefit, although it may help the earlier mild cognitive impairment which precedes Alzheimer's. The acetyl-L-carnitine might help depression in the elderly, but the evidence is old and skimpy. As for biomarkers, who cares. We want evidence of real health benefits. Juvenon a Waste of Money: Juvenon costs $40/month for 1 g acetyl-L-carnitine, 400 mg alpha-lipoic acid (ALA) and 200 mcg of biotin per day (www.juvenon.com). While 1 g/day might be enough ALCAR, no human disease research has ever been done with Juvenon. Almost all studies done with ALCAR use 2-4 g/day. Buying 1 kilo at a time from dextersportscience.com, the cost for 2 g/day would be $8 per month instead of $80/month for Juvenon. As of November, 2004, there is absolutely no published human research showing that the addition of ALA or biotin adds anything to the benefit of ALCAR alone although these could also be purchased individually at a much lower total cost than Juvenon. Animal Studies Anxiety Helped in Rat Study: I accidentally deleted the article, but ALCAR was of benefit in a rat study of anxiety. Brain Areas of Rats Helped by ALCAR: ALCAR treatment began when the rats were adults (16 months) and continued for 6 months was able to counteract the age-dependent decrease in nerve cell number primarily in the temporal and occipital cortical areas, in the archicortex and hippocampus. Age-dependent nerve cell loss in the brain of Sprague-Dawley rats: effect of long term acetyl-L-carnitine treatment. Napoleone P, Ferrante F, Ghirardi O, Ramacci MT, Amenta F. Universita 'La Sapienza', Rome, Italy. Arch Gerontol Geriatr. 1990 Mar-Apr;10(2):173-85 Brain Recovery After 10 minute Arrest Better with Immediate ALCAR than with 30 Minute Delay: A 30-min delay in ALCAR administration following restoration of spontaneous circulation from 10 min cardiac arrest impairs the ability of this drug to promote neurologic recovery despite apparent normalization of brain lactate levels, while if given with no delay, it promotes neurologic recovery. Rosenthal RE, et al. University of Maryland. Neurosci Lett. 2005 Apr 18;378(2):82-7. Thomas E. Radecki, M.D., J.D. modern-psychiatry.com
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