A Cure for Erectile Dysfunction: ALC/ALA
Acetyl-L-Carnitine & Alpha Lipoic Acid Therapy)

(Notes in purple type are the personal observations of the author of this website.
I have no economic ties to the marketers of the amino acid and antioxidant, ALC & ALA, nor any other personal interest in promoting this therapy.
Big Pharmaceutical USA has no patent on these products, so the only press coverage ALC/ALA therapy receives is within the printed pages of medical journals, and in the hype on vitamin/supplement hawkers' web pages.
I have installed this web page as a public service to those who might benefit as we did from this little known therapy.)

Because this therapy typically takes months to work, and because a high dose is required to bring about big improvements, we recommend starting out at a dose of  at least 3000 mgs Acetyl L-Carnitine (ALC) and 1200 mg Alpha Lipoic Acid (ALA) per day right from the start.  4000mgs ALC/1600mgs ALA  would be the best dose to start on and stay on for the best chance of maximum results.  We were content with slow progress but many men are not likely to be, and for them, the slowly graduating doses my husband took would probably spell wasted money.     

There is no anecdotal or clinical evidence on record of any man with serious erectile impairment seeing substantial sexual benefits at a (continuous) daily dose below 3 grams ALC/ 1200 mgs ALA. 

We recommend to any man who has invested time and money in 4-6 mos at a minimum dose of 3000mg(3gms)ALC/1200 mg ALA and has still not seen any positive changes (if this should happen) to try one last month or even a few extra weeks of a higher dose of 4-5gms ALC/1600mgs-2000mgs ALA before giving up. Since ALC/ALA levels would be already built up in your body it should take but a short time to find out if a higher dose might have made the difference.  There are accounts of a single extra gram making all the difference.

It is highly recommended to take these meds with food or milk and have tums handy.  The ALA in particular can cause heartburn when combined with an empty stomach.  Splitting the daily dose into 2 or more doses seems easier also. 

ALC/ALC works by repairing neural pathways through action on a cellular level, and in turn exerts a positive cardiovascular effect.  Thus it works well on men whose ED (erectile dysfunction) is related to nerve damage resulting from diabetes, aging, spinal damage, etc.  It is unlikely that men whose ED is psychological in origin or exists as a side effect of another medicine (high blood pressure or antidepressant medicines for example) would benefit from ALC/ALA therapy. 

This therapy is not being hyped like viagra because no US pharmaceutical co stands to make a bundle on it.  These substances are under the jurisdiction of the "supplement" industry and can be purchased over-the-counter.
Some places that we and others have found to purchase ALC/ALA at reasonable prices: http://www.americannutrition.com/Natures_Purest/natures_purest.htm
Acetyl L-carnitine 500mg 120 Vcaps & Alpha Lipoic Acid 200mg 120 Vcaps
Package Deal for $24.95
(It is a bit hard to find on the page - look for CN02&04 in Item # column)
$21.99 for 60 capsules (500 mg of acetyl L-carnitine/200 mg of alpha lipoic acid)
($15.00 with GNC gold card) These can also be purchased at GNC stores also.
$45.99 for 240 capsules (500 mg of acetyl L-carnitine/200 mg of alpha lipoic acid)
http://www.vitaminshoppe.com/browse/sku_detail.jhtml?SkuID=236086&BrandName=Source+Naturals&BrandId=15& BreadCrumbType=Shop&SkuName=Acetyl+L-Carnitine+%26+Alpha+Lipoic
$13.99 for 60 tabs of combination ALC/ALA 650 mgs each
Dr. Trust Acetyl L-Carnitine 500mg 180 Caps $29.99
Dr. Trust Alpha Lipoic Acid 300mg 120 Caps $11.99
Time-Release version of ALA
Jarrow: manufactures a time-release version of ALA
Alpha lipoic sustain 300mg (60 Tabs)
JR-005Retail price: $27.95Sale price: $20.97
These places sell ALC and ALA in Bulk Powder Form, as well as Capsules
Acetyl L Carnitine 100 grams of powdered ALC for $9.00
Alpha Lipoic Acid 50 grams pure powder, $10.50
153-0188 Acetyl-L-Carnitine Powder, 3 oz. $19.99
234-0017 Pure ALA, 300mg, 180 capsules $23.99

Caution: Those with seizure disorders should only use acetyl-L-carnitine under medical advisement and supervision. Visit ALC/ALA index page for details of possible side effects.

Our experience:

My husband (age 60) saw significant improvement in 4 months (in erectile ability and force of ejaculation - both of which were nearly non-existent in the months prior to going on this regimen) at these dosages:
1500 mg Acetyl L-Carnitine (ALC) per day (one 500mg capsule of Acetyl L-Carnitine 3 times daily)
600 mg Alpha Lipoic Acid (ALA) per day (one 200mg capsule of Alpha Lipoic Acid 3 times daily)
taken with food or milk.
His erections, however, were not sufficient for penetration and we were limited to oral sex for 6 months.

No further improvements were noted over the next 2 months, and after 6 months on the above regimen, he increased the dose to 2000 mg Acetyl L-Carnitine (ALC) and 800 mg Alpha Lipoic Acid (ALA) daily. 
Two or 3 months into the increased dose therapy he was able, w/ help of a constriction ring, to sustain an erection sufficient to penetrate and complete intercourse. 

The improvements took another upward turn when he increased his daily dose to 3000 mg (3gms) ALC and 1200 mg ALA. His nocturnal and spontaneous waking erections returned, slowly at first, growing more pronounced as the months passed. Penetrative sex with the aid of a constriction device became a much more frequent occurance.

My husband was so encouraged by all these positive gains that he raised the daily dose to  4000mgs ALC/1600mgs ALA, and a short time later to his current dose of 5000mgs ALC/2000mg ALA per day.
His libido has increased, his erections have become hard enough to have completely normal sex without the need of a constriction ring, he has had some of the longest lasting orgasms/ejaculations on record in my memory, on one occasion was able to manage a second orgasm, and has initiated sex with increasing frequency.  

To sum up, my husband is now completely cured of ED (erectile dysfunction) and his libido has taken a backwards leap 20 yrs into the past.  We have recaptured the kind of spontaneous sex life that we enjoyed in our much younger years.

Of course he must continue to take ALC/ALA on a permanent basis, but given the benefits of these substances to aging cardiovascular systems, liver, kidneys, and cognitive function it is well worth the effort and expense.  Neural pathways are governed by a series of chemical events which clearly were lacking in some way to cause the damage in the first place. The cellular action of ALC/ALA is a continuous process that counteracts the effects of aging, and is not completely understood. If it is stopped, the deleterious effects of aging continue.

At age 55 I am also taking ALC/ALA.  The anti-aging effects on all our major organs and processes are as much a concern, although not as immediate, as was the ED issue. I am giving ALC/ALA to several of our older animals as well, in the expectation that it will slow their ongoing age-related deteriorating renal function.

Ten of the 11 other men (from 3 internet forums) that we now know of (in addition to my husband and the 60 test subjects in the two clinical trials below) who have followed this therapy at proper dose levels continuously have reported extremely encouraging results and vastly improved sexual function. The 11th man has unfortunately experienced no improvement. Our conjecture is that his erectile problems may exist as a side effect of a blood pressure medicine taken for benign prostate enlargement and thus cannot be alleviated by the cellular repairs of ALC/ALA. A problem in predicting whether or not ALC/ALA will work is that the cause of ED is often not known and may be due to multiple factors. We hope that more couples and/or single men will be able to benefit as we have.

Below follows some of the research on Carnitine's beneficial effects on sexual dysfunction. Many more studies of Carnitine's effect on cardiovascular disease, liver and kidney disease, obstructive lung disease, and other serious health problems have shown promising results.

Acetyl-L-Carnitine (ALC) is an esterified form of l-carnitine.  Propionyl-L-Carnitine (PLC) is another l-carnitine ester.  Since the latter is not readily available in this country, my husband takes ALC only; in the same dosage as the combined dosage (of ALC & PLC) that the men in the clinical study (below) were given.

The esterified forms have proven to work better than "plain" l-carnitine in other studies. Esters are referred to as "delivery versions" so presumably they enter the body ready to go to work.

Evidence exists that Acetyl-L-Carnitine (ALC) should be combined with Alpha Lipoic Acid (ALA) to prevent damage from "free radicals" which are a by-product of Acetyl-L-Carnitine's action on cells.
(See research study below - 3/4 down page)

Human Trial Concludes L-Carnitine Better Than Testosterone in Treating Erectile Dysfunction and Depression in Males

Journal of Urology, April, 2004   Italy

The April 2004 issue of the journal Urology published the findings of Italian researchers that the amino acid carnitine was more active than testosterone in improving symptoms of aging in men, such as sexual dysfunction and depression, associated with the decline of androgenic hormones. One thing though - participants received over 4 grams of L-Carnitine which is a bunch.

One hundred and twenty men between the ages of 60 and 74 with symptoms of low testosterone were randomized to receive daily doses of:

160 milligrams orally administered TESTOSTERONE UNDECANOATE,
for a six month period. Prostate-specific antigen, prostate volume, nocturnal penile tumescence, total and free testosterone, prolactin, luteinizing hormone, erectile function scores, depression, fatigue and other parameters were assessed before treatment, at three months, and after the treatment period.

Erectile function, sexual desire, sexual satisfaction and nocturnal penile tumescence increased over the course of the study in the group receiving
TESTOSTERONE as well as the group receiving CARNITINE. In addition, the group receiving CARNITINE experienced an increase in orgasm and general sexual well-being. Erectile function and nocturnal penile tumescence were significantly more improved in this group than in those receiving TESTOSTERONE While both treatments lowered depression scores, CARNITINE'S effect was greater.

Predictably, treatment with
TESTOSTERONE increased serum total and free testosterone and decreased luteinizing hormone levels, but CARNITINE'S effect on these hormones was not significant. Treatment with CARNITINE was not associated with an increase in prostate volume as was TESTOSTERONE treatment after six months. PSA levels did not increase in any of the groups.

Fatigue was likewise improved in both groups. As one negative effect, the men taking
TESTOSTERONE developed enlargement of their prostates, which did not occur in the CARNITINE group. Although both TESTOSTERONE and CARNITINE improved symptoms of male aging, there was overall superior benefit to CARNITINE with no real side effects.

CARNITINE is an essential nutrient. It has vitamin-like qualities. It is considered essential in helping to transport fatty acids into mitochondria (the power plants of the cells). A deficiency in carnitine can therefore result in an overall reduction in energy production by the cells. It is well-known that individuals can become carnitine-deficient for a number of reasons. L-carnitine, aside from being an incredible anti-aging nutrient, also has shown benefit for multiple medical conditions, including cardiovascular disease such as angina and congestive heart failure, liver and kidney disease, obstructive lung disease, and many others. L- carnitine has actually even shown benefit in AIDS patients. Although it is unusual to see physicians prescribing vitamins in the hospital, Acetyl l-Carnitine is routinely prescribed by kidney specialists for their patients, since the kidney is a major site of carnitine synthesis.

Although tissue carnitine levels have been found to be positively associated with sex hormone levels, the findings of this study show that the compound's action is not strictly linked to sex hormone blood levels. Carnitine's mechanism of action against reactive oxygen species (ROS) is different than conventional anti-ROS compounds tried for conditions associated with male aging, which may help explain its effectiveness

Urology. 2004 Apr;63(4):641-6. 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. Andrological Operative Unit, Headquarters of Societa Italiana di Studi di Medicina della Riproduzione, Bologna, Italy. Publication Types: Clinical Trial, Randomized Controlled Trial


Carnitine improves Viagra's potency in diabetics

A “Brief Communication” published in the September 2004 issue of the journal Current Medical Research Opinions (volume 20, no 9) reported that the addition of proprionyl-L-carnitine to treatment with sildenafil (Viagra) boosted efficacy of the drug in diabetic men who had previously experienced a low response. Sildenafil is a popular drug used to treat erectile dysfunction, a common complication of diabetes as well as other conditions such as aging. 

Readers of the April 19, 2004 issue of Life Extension Update may recall that a combination of proprionyl-L-carnitine and acetyl-L-carnitine improved symptoms of sexual dysfunction in aging men comparable to improvements achieved with testosterone treatment. In addition, carnitine increased reported sexual well-being to a degree greater than that provided by testosterone. 

For the current investigation, researchers in Rome studied forty type 1 and type 2 diabetic patients with erectile dysfunction that was unresponsive to treatment with sildenafil. Twenty men were randomized to receive two grams proprionyl-L-carnitine per day plus 50 milligrams sildenafil twice per week, while the remaining men received sildenafil alone for six months. Erectile function questionnaires and event logs were used to evaluate the treatments' effects. 

The researchers found that scores for achieving as well as maintaining an erection were significantly improved in the group receiving both carnitine and sildenafil compared to the group receiving the drug alone. Improved erections were reported by 68 percent of the group receiving carnitine compared to 23 percent of the men who did not receive it, and successful intercourse attempts were reported by 76 percent of the carnitine/sildenafil group, compared to 34 percent of the men who received only the drug.  

The known beneficial effect of carnitine on the cardiovascular system may be in part related to increased vasodilation and enhanced blood flow, effects which would simultaneously benefit erectile function. As sildenafil elicits its benefits though similar mechanisms, the researchers hypothesized that the combination of proprionyl-L-carnitine and sildenafil may provide greater effects of this nature than either compound given by itself. They suggest that the combination may offer a new approach for treating diabetic men with erectile dysfunction.


Preliminary observations on the use of propionyl-L-carnitine in combination with sildenafil in patients with erectile dysfunction and diabetes. 

Gentile V, Vicini P, Prigiotti G, Koverech A, Di Silverio F.
Department of Urology U Bracci, University La Sapienza, Rome, Italy. 

PURPOSE: To investigate the efficacy and tolerability of oral propionyl-L-carnitine (PLC) plus sildenafil in men with erectile dysfunction (ED) and diabetes unresponsive to sildenafil monotherapy. MATERIALS AND METHODS: Patients with medically documented ED of organic or mixed aetiology and diabetes (type 1 and 2) were randomised to receive oral PLC (2 g/day) plus sildenafil (50 mg twice weekly) (20 patients, Group 1) or sildenafil alone (20 patients, Group 2), in a double-blind, fixed-dose study. All patients had been previously treated unsuccessfully with a minimum of eight administrations of sildenafil. Efficacy was evaluated using the International Index of Erectile Function (IIEF) questionnaire: total score, subscores for questions 3 (Q3; achieving an erection) and 4 (Q4; maintaining an erection) and global efficacy question (GEQ: 'Has treatment improved your erections?'). Patients Event Logs were also used. RESULTS: After 24 weeks of treatment, mean scores for IIEF Q3 and Q4 had improved significantly in patients of Group 1 (4.25 +/- 0.63 and 3.95 +/- 1.0) compared with Group 2 (2.9 +/- 0.71 and 2.7 +/- 0.96) (p < 0.01). Moreover, the percentage of patients with improved erections (GEQ 68% vs. 23%) and successful intercourse attempts (76% vs. 34%) was significantly increased in Group 1 compared with Group 2 (p < 0.01). Fourteen (70%) patients in Group 1 and four (20%) in Group 2 reported an increase in mean IIEF EF domain score of > or = 4 (p < 0.01). Treatments were well tolerated and no patient discontinued study medication. Two patients in Group 1 reported mild gastric pain.CONCLUSIONS: Salvage therapy with PLC plus sildenafil was more effective than sildenafil in the treatment of ED in patients with diabetes refractory to sildenafil monotherapy. 

PMID: 15383186 [PubMed - in process] 

Improved pallesthetic sensitivity of pudendal nerve in impotent diabetic patients treated with acetyl-L-carnitine
Acta Urologica Italica (Italy), 1996, 10/3 (185-187)

Neurogenic impotence in diabetic patients seems to be largely associated with abnormal sensory nerve conduction of pudendal nerve afferent pathways. This condition accounts for a hypoactivity in the mechanisms of erection reflex and has been described as sensory-deficit impotence. Our study investigates the pharmacological action of acetyl-L-carnitine (ALC) in the treatment of this neurological disorder. Penile biothesiometry was applied to two groups of diabetic patients, whose impotence was principally neurogenic, in order to assess their vibration perception threshold variables. The groups were treated with ALC (1,500 mg/day) and placebo, respectively. The results obtained show a significant improvement in dorsal nerve somatosensory conduction in patients treated with ALC.

 Acetyl-L-carnitine corrects the altered peripheral nerve function of experimental diabetes 

Acetyl-L-carnitine (ALC) has been shown to facilitate the repair of transacted sciatic nerves. The effect of ALC (50 mg/kg/d) on the diminished nerve conduction velocity (NCV) of rats with streptozotocin (STZ)-induced hyperglycemia of 3 weeks' duration was evaluated. The aldose reductase inhibitor, sorbinil, which is reported to normalize the impaired NCV associated with experimental diabetes, was used as a positive control. Aldose reductase inhibitors are thought to have an effect by decreasing peripheral nerve sorbitol content and increasing nerve myo-inositol. Treatment of STZ- diabetic rats with either ALC or sorbinil resulted in normal NCV. Sorbinil treatment was associated with normalized sciatic nerve sorbitol and myo- inositol; ALC treatment did not reduce the elevated sorbitol levels, but sciatic nerve myo-inositol content was no different from nondiabetic levels. Both ALC and sorbinil treatment of STZ-diabetic rats were associated with a reduction in the elevated malondialdehyde (MDA) content of diabetic sciatic news, indicating reduced lipid peroxidation. The beneficial effects of sorbinil and ALC on the altered peripheral nerve function associated with diabetes were similar, but their effects on the polyol pathway (frequently implicated in the pathogenesis of peripheral neuropathy) were different. 

Metabolism: Clinical and Experimental (USA), 1995, 44/5 (677-680) 



Acetyl-L-Carnitine is the acetyl ester of L-carnitine. It occurs naturally in animal products. Chemically, acetyl-L-carnitine is known as beta-acetoxy-gamma-N, N, N-trimethylaminobutyrate. Acetyl-L-carnitine is also known as acetyl-carnitine, L-acetycarnitine, acetylcarnitine, acetyl levocarnitine, ALC and ALCAR. Acetyl-L-carnitine is a delivery form for both L-carnitine and acetyl groups.

Supplemental acetyl-L-carnitine may have neuroprotective activity. In addition, it, like L-carnitine, may have cardioprotective activity and may beneficially affect cardiac function. It may enhance sperm motiliy. Acetyl-L-carnitine may also have cytoprotective, antioxidant and anti-apoptotic activity.

Acetyl-L-carnitine is a delivery form for L-carnitine and acetyl groups. The functions of L-carnitine include transport of long-chain fatty acids across the mitochondrial membranes into the mitochondria (wherein their metabolism produces bioenergy) and transport of small-chain and medium-chain fatty acids out of the mitochondria in order to, among other things, maintain normal coenzyme A levels in these organelles. It may also have antioxidant activity. The acetyl component of acetyl-L-carnitine provides for the formation of the neurotransmitter acetylcholine. Abnormal acetylcholine metabolism in the brain, leading to acetylcholine deficits in certain brain regions, is thought to be associated with age-related dementias, including Alzheimer's disease. Acetyl-L-carnitine has been found to decrease glycation of lens proteins in vitro. It is thought to do so by acetylating certain lens proteins called crystallins. In so doing it protects them from glycation-mediated damage. Many biochemical changes occur during the aging process. These include decreased cardiolipin synthesis in the heart and impaired mitochondrial function. Cardiolipin is a key phospholipid necessary for mitochondrial transport processes in the heart. Mitochondria are vital for the production of cellular energy. Experiments in aged rats have shown that acetyl-L-carnitine supplementation leads to improved mitochondrial function and increased cardiolipin production. Acetyl-L-carnitine serves as a readily accessible energy pool for use in both activation of respiration and motility in human spermatozoa.

The pharmacokinetics of acetyl-L-carnitine are similar to L-carnitine (see L-carnitine). There is speculation that it is better absorbed than L-carnitine, but this has not yet been established.

Acetyl-L-carnitine has recently demonstrated some efficacy as a possible neuroprotective agent and may be indicated for use in strokes, Alzheimer's disease, Down's syndrome and for the management of various neuropathies. It may also have anti-aging properties. Research regarding acetyl-L-carnitine's possible beneficial effect on sperm motility is early-stage but promising.

Several studies have now demonstrated some positive effects of acetyl-L-carnitine supplementation in Alzheimer's patients especially with regard to tasks involving attention and concentration. In a double-blind, parallel design, placebo-controlled pilot study of 30 patients whose mild-to-moderate dementias were believed to be symptoms of Alzheimer's disease, there were significant, positive results as measured by some of the neuropsychological tests used in the study. In another early double-blind, placebo-controlled study of 130 patients with clinical diagnoses of Alzheimer's disease, a slower rate of deterioration was observed in 13 of 14 outcome measures at the end of this one-year study. Some of these measures reached statistical significance, including measures of logical intelligence, long-term verbal memory and selective attention. More recent studies continue to show beneficial effects in Alzheimer's disease. Younger patients seem to benefit most. It has been suggested that cognitive function may be improved in subjects with Alzheimer's disease by acetyl-L-carnitine's hypothesized ability to inhibit apoptosis of cerebral nerve cells.

Significant improvement in visual memory and attention in Down's syndrome subjects treated with acetyl-L-carnitine has also been reported.

These researchers hypothesized that acetyl-L-carnitine's positive actions in both Alzheimer's disease and Down's syndrome result from its direct and indirect cholinomimetic effects. There is also preliminary evidence that acetyl-L-carnitine can slow mental decline in the elderly who are not afflicted with dementias. Neuroprotective effects of acetyl-L-carnitine have been reported after stroke in both animal models and in humans. Cerebral blood flow reportedly improves in acetyl-L-carnitine treated subjects with cerebrovascular disease.

Peripheral nerve function has been improved with the use of acetyl-L-carnitine in experimental diabetes.

There is also early clinical evidence that acetyl-L-carnitine may be helpful in various peripheral neuropathies, and it has been suggested that this supplement might be helpful in alleviating the neurotoxicity associated with the nucleoside analogues used in the treatment of AIDS. This latter hypothesis has yet to be tested.

There is some evidence in animal work that acetyl-L-carnitine might have anti-aging effects. Mitochondrial function and ambulatory activity were assessed in a study of old rats fed acetyl-L-carnitine. Ambulatory activity was significantly increased in the old rats, and an examination of liver cells in the treated animals showed a significant reversal of age-associated decline of mitochondrial membrane potential. Cardiolipin, which declines with age, was significantly restored.

Finally, acetyl-L-carnitine has been reported to increase sperm motility in vitro, and in one human trial, 4 grams daily of this substance given to 20 oligoasthenospermic men, produced increased progressive sperm motility which was associated with a greater number of pregnancies.

None Known.

Because of lack of long-term safety studies, acetyl-L-carnitine is not advised for pregnant women or nursing mothers. Those with seizure disorders should only use acetyl-L-carnitine under medical advisement and supervision.

Mild gastrointestinal symptoms may occur in those taking acetyl-L-carnitine supplements. These include nausea, vomiting, abdominal cramps and diarrhea.
Increased agitation has been reported in some with Alzheimer's disease when taking oral acetyl-L-carnitine. In those with seizure disorders, an increase in seizure frequency and/or severity has been reported in some taking this substance. The incidence of this in this population is low.

Therapy with the nucleoside analogues didanosine (ddI), zalcitabine (ddC) and stavudine (d4T) may lead to decreased acetyl-L-carnitine levels.
Therapy with valproic acid and the pivalic acid-containing antibiotics may lead to secondary L-carnitine deficiencies (see L-carnitine).

There are no reports of overdosage.

Typical doses of supplemental acetyl-L-carnitine are 500 milligrams to 2 grams daily in divided doses.

Brooks JO 3d, Yesavage JA, Carta A, Bravi D. Acetyl-L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled trial using the trilinear approach. Int Psychogeriatr. 1998; 10:193-203. Chuang WW, Lin WW, Lamb DJ, Lipshultz LI. Effect of acetylcarnitine on sperm motility. J Urol. 2000; 163(4 Suppl):Abstract1324. Famularo G, Morreti S, Marcellini S, et al. Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogues. AIDS. 1997; 11:185-190. Gorini A, D'Angelo A, Villa RF. Action of L-acetylcarnitine on different cerebral mitochondrial populations from cerebral cortex. Neurochem Res. 1998; 23:1485-1491. Hagen TM, Ingersoll RT, Wehr CM, et al. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proc Natl Acad Sci USA. 1998; 95:9562-9566. Hagen TM, Wehr CM, Ames BN. Mitochondrial decay in aging. Reversal through supplementation of acetyl-L-carnitine and N-tert-butyl-alpha-phenyl-nitrone. Ann NY Acad Sci. 1998; 854,214-223. Lolic MM, Fiskum G, Rosenthal RE. Neuroprotective effects of acetyl-L-carnitine after stroke in rats. Ann Emerg Med. 1997; 29:758-765. Moncada ML, Vicari E, Cimino C, et al. Effect of acetylcarnitine treatment in oligoasthenospermic patients. Acta Eur Fertil. 1992: 23:221-224. Onofrj M, Fulgente T, Melchiadona D, et al. L- acetylcarnitine as a new therapeutic approach for peripheral neuropathies with pain. Int J Clin Pharmacol Res. 1995; 15:9-15. Pettegrew JW, Klunke WE, Panchalingam K. Clinical and biochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiol Aging. 1995; 16:1-4. Piovesan P, Quatrini G, Pacifici L, et al. Acetyl-L-carnitine restores choline acetyltransferase activity in the hippocampus of rats with partial unilateral fimbria-fornix transection. Int J Dev Neurosci. 1995; 13:13-19. Salvioli G, Neri M. L-acetylcarnitine treatment of mental decline in the elderly. Drugs Exp Clin Res. 1994; 20:169-176. Sano M, Bell K, Cote L, et al. Double-blind parallel pilot study of acetyl levocarnitine in patients with Alzheimer's disease. Arch Neurol. 1992; 49:1137-1141. Thal LJ, Carta A, Clarke WR, et al. A one year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. Neurology. 1996; 47:705-711. White HL, Scates PW. Acetyl-L-carnitine as a precursor of acetylcholine. Neurochem Res. 1990; 15:597-601.



"Oxygen is a double-edged sword," says Tory Hagen. "We need it to live and it’s essential to cell function. But oxygen can be converted into what we call reactive radical oxygen species, or free radicals."

Bruce Ames and Tory Hagen have long had an interest in mitochondria as they relate to aging. They were intrigued by Italian research showing that acetyl-L-carnitine improved mitochondrial activity in older rats [5].

When Ames and Hagen tried the same experiment, there was a problem [1]. The carnitine did improve mitochondrial health. But it also appeared to increase the level of free radicals. So, they decided to pair it with alpha-lipoic acid.

In one of the studies, Hagen, Ames and colleagues compared old rats to young rats, all fed acetyl-L-carnitine in their water and alpha-lipoic acid in their chow [2].

"We significantly reversed the decline in overall activity typical of aged rats to what you see in a middle-aged to young adult rat 7 to 10 months of age," Hagen says. "This is equivalent to making a 75- to 80-year-old person act middle-aged. We've only shown short-term effects, but the results give us the rationale for looking at these things long term."

(Another note: these researchers clearly had a financial interest in patenting a combination of the two compounds, but then most research is financed by economically motivated pharmaceutical cos. Their credentials in any case are legitimate. http://lpi.oregonstate.edu/staff/hagenbio.html )

Acetyl-L-carnitine and alpha-lipoic acid ( Alpha Lipoic Acid )

The interest started when researchers in the Linus Pauling Institute at Oregon State University and the University of California at Berkeley found that they improved both the activity, energy level and cognitive function of old rats.

"After just a month, older rats whose diet was supplemented with these two compounds were about twice as active as our control rats, which remained largely inactive," says Tory Hagen, an assistant professor in Oregon State University's Linus Pauling Institute.

"With the two supplements together, these old rats got up and did the Macarena," says Bruce Ames, a professor of biochemistry at the University of California at Berkeley. "The brain looks better, they are full of energy — everything we looked at looks more like a young animal."

There are scores of different theories about aging. Some believe that aging is due to the normal wear and tear resulting from daily living. Others think that it's the result of a pre-programmed genetic plan, a process that begins at birth and continues until your "biological clock" runs down.

Ames falls in the wear and tear camp. He thinks that aging is at least partly due to a process called oxidative stress.

One particularly vulnerable area appears to be the mitochondria (pronounced my-toe-kon-dree-a).

Your body is made up of millions of tiny cells. Think of each cell like a miniature city. Inside each city, you'll find the power stations of the cell. They're called mitochondria. Of the oxygen consumed by an average cell, the mitochondria use most of it to help turn food into energy.

Unfortunately, mitochondria also appear to have a major design flaw — they leak electron electricity. This, in turn, leads to an increase in the production of free radicals.

The antioxidant defenses of your body are usually adequate to prevent substantial tissue damage. However, an overproduction of free radicals (caused, for example, by intense exercise) or a drop in the level of the antioxidant defenses will lead to an imbalance between free radical generation and antioxidant protection.

This imbalance is known as oxidative stress.

Mitochondria are right in the neighborhood of the free radicals they just created. This means they're often the first victims.

It's ironic that the thing we most need to live — oxygen — is the very thing contributing to aging and some of the other problems associated with it, such as cancer and heart disease.

"Oxygen is a double-edged sword," says Tory Hagen. "We need it to live and it’s essential to cell function. But oxygen can be converted into what we call reactive radical oxygen species, or free radicals."

Bruce Ames and Tory Hagen have long had an interest in mitochondria as they relate to aging. They were intrigued by Italian research showing that acetyl-L-carnitine improved mitochondrial activity in older rats.

When Ames and Hagen tried the same experiment, there was a problem [1]. The carnitine did improve mitochondrial health. But it also appeared to increase the level of free radicals. So, they decided to pair it with alpha-lipoic acid.

In one of the studies, Hagen, Ames and colleagues compared old rats to young rats, all fed acetyl-L-carnitine in their water and alpha-lipoic acid in their chow [2]. "We significantly reversed the decline in overall activity typical of aged rats to what you see in a middle-aged to young adult rat 7 to 10 months of age," Hagen says. "This is equivalent to making a 75- to 80-year-old person act middle-aged. We've only shown short-term effects, but the results give us the rationale for looking at these things long term."

Supplementation has also been shown to improve both spatial and temporal memory. Pictures of brain cells show less decay in old rats fed a supplemented diet [3]. "It appears that some compounds, including carnitine and lipoic acid, can mask the metabolic problems caused by cellular aging and the natural oxidative process," Hagen says. "If we can better understand the process of aging and how to influence it, we may be able to give people a way to maintain human health for as long as possible."

The University of California have patented the use of acetyl-L-carnitine and alpha-lipoic acid as a way of "enhancing metabolism and alleviating oxidative stress."

Juvenon, a company founded by Ames and Hagen, has licensed the patent from the university. Their first product — Juvenon Energy Formula — contains both alpha-lipoic acid and acetyl-L-carnitine.

Of course, the big problem is the lack of reliable research to show that these compounds benefit humans in the same way as rats.

Under certain circumstances, large doses of the popular antioxidants vitamin C and CoQ10 have been shown to increase oxidative stress. Whether alpha-lipoic acid and carnitine have any negative effects is a question that can only be answered by more human research.

Aging is a complex process. Different tissues may have fundamentally different mechanisms underlying their maintenance and repair. And most scientists believe that mitochondrial health is only one cog in the aging wheel.

Ames acknowledges he has not discovered the Fountain of Youth. But he does lay claim to a Fountain of Middle Age. "I don't want to over-hype it," he cautions. "If you're an old rat, it looks very good. But we still have to wait for the results from the human trials. There's every reason to think it's going to work in people. I'm very optimistic."

1. Hagen, T.M., Ingersoll, R.T., Wehr, C.M., Lykkesfeldt, J., Vinarsky, V., Bartholomew, J.C., Song, M.H., & Ames, B.N. (1998). Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proceedings of the National Academy of Sciences, 95, 9562-9566 2. Hagen, T.M., Liu, J., Lykkesfeldt, J., Wehr, C.M., Ingersoll, R.T., Vinarsky, V., Bartholomew, J.C., & Ames, B.N. (2002). Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proceedings of the National Academy of Sciences, 99, 1870-1875 3. Liu, J., Head, E., Gharib, A.M., Yuan, W., Ingersoll, R.T., Hagen, T.M., Cotman, C.W., & Ames, B.N. (2002). Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid Proceedings of the National Academy of Sciences, 99, 2356-2361 4. Liu, J., Killilea, D.W., & Ames, B.N. (2002). Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. Proceedings of the National Academy of Sciences, 99, 1876-1881 5. Paradies, G., Ruggiero, F.M., Petrosillo, G., Gadaleta, M.N., & Quagliariello, E. (1995). Carnitine-acylcarnitine translocase activity in cardiac mitochondria from aged rats: the effect of acetyl-L-carnitine. Mechanisms of Ageing and Development, 84, 103-112

Additional research writeup:
Alpha Lipoic Acid: prevention of damage from "free radicals"
known to sometimes result from the actions of Acetyl L-Carnitine.
source: http://www.pjonline.com/pdf/articles/pj_20030426_combined.pdf

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