Acetyl L-Carnitine Goes to Your Brain

Mental fatigue, in particular, is improved by this energy-metabolism nutrient 
By Dr. Edward R. Rosick

Doctor, I’m tired." Of all the complaints I hear from my patients, fatigue has to rank in the top three (the other two are headaches and musculoskeletal disorders). Complaints of fatigue cut across age and gender lines, with 20-year-old jocks complaining as much as little old ladies. It seems that in 2004 America, just about everyone is tired much of the time.

When you stop and think about it, though, is it any wonder that almost all of us feel unduly tired at one time or another? Study after study has shown that, as a nation, we’re chronically sleep-deprived—for one thing, we watch too much late-night TV, at the expense of the precious ZZZs that are so vital to our good health. And during the day, Americans are by far the hardest-working people in the industrialized world. While our counterparts in Europe, e.g., take six-week summer vacations as the norm, most of us feel guilty when we take more than a week off. Between never-ending bills, high taxes, and trying to get the best of everything for our children, we don’t have time to rest—and without rest, fatigue isn’t far behind.

Yet even with the relentless demands of our hectic lives, most of us manage to slog through the day without feeling terrible. There are some people, however, in whom fatigue is more than just a nuisance—it’s a literal, chronic disease called chronic fatigue syndrome, or CFS.

CFS—Many Symptoms, No Definitive Cause

CFS is a relatively common disease, affecting an estimated 522 women and 291 men per 100,000 people in the United States.1 In addition to feeling an overwhelming sense of constant fatigue, many patients with CFS suffer from headaches, joint and muscle aches, depression, and gastrointestinal disturbances. CFS can strike a person after suffering from a significant viral infection, such as influenza or mononucleosis, but it can also strike suddenly, out of the blue. Once settled in, it can last and last, and it’s not uncommon for people to complain of CFS symptoms for years.

Because some people exhibit the first symptoms of CFS after a viral infection, medical researchers have tried to link this debilitating disease with the Epstein-Barr virus, a common cause of mononucleosis. Recent studies, however, have not borne out this viral link. The fact is that there is still no definitive cause for CFS—no viral, bacterial, or other infectious agent, no particular autoimmune disorder, and no laboratory test that can show without a doubt what causes this troubling, and often debilitating, disease.

CFS—No Definitive Treatment Either

Because there’s no definable cause for CFS, some in mainstream medicine have expressed doubt that it’s a true disease. Yet for the many women and men who suffer from CFS, it is all too real. Even more disheartening is the fact that, despite years of research, medical science can offer no significant treatment (let alone a cure) for CFS. Consequently, many physicians treat CFS piecemeal—that is, they treat the various symptoms (muscle aches, headache, depression, etc.) with separate remedies, such as NSAIDs and antidepressants. While such remedies often have positive results, they generally do nothing to alleviate the debilitating fatigue that lies at the heart of this syndrome.

Exercise Helps Combat the Fatigue

As a practitioner of integrative medicine, I find that many patients referred to me have vague or problematic complaints (such as CFS) for which my conventionally trained colleagues have little training or, in the HMO-dominated world, no time. Yet time to take a detailed history, time to do a through physical, and time to decide what lab tests are appropriate are the very keys to making the proper diagnosis.

Although CFS patients often have normal lab values, they have serious complaints. A common one is muscle tenderness, which tends to exacerbate their fatigue and reinforce their reluctance to do much of anything. Yet getting up and doing some exercise is one of the few conventional ways in which CFS patients can alleviate their fatigue, muscle aches, and even depression. A recent randomized, controlled study in Australia showed that CFS patients (age range 16–74) benefited significantly from twice-daily moderate exercise regimens.2 When compared with those who underwent relaxation/flexibility therapy, those who exercised had statistically greater improvements in their work capacity, systolic blood pressure, and depression.

Supplements May Help Too

Since oxidative stress has been postulated to be a contributing factor to CFS,3 I also educate my patients with this problem to make sure that, in addition to exercise, they get optimal amounts of antioxidant nutrients, such as N-acetylcysteine, alpha-lipoic acid, Ginkgo biloba, and bilberry (Vaccinium myrtillus), which have been shown to be effective in some small studies. Patients with significant signs of fatigue should also take a daily supplement containing vitamins A, C, and E. Adaptogenic herbs, such as Rhodiola rosea, can often help patients with CFS, fibromyalgia, and other conditions in which they are extremely fatigued.

Last but certainly not least, acetyl-L-carnitine, a supplement that has been shown to be safe and effective in treating various neurological disorders, may prove to be an effective weapon in the battle against CFS.

Acetyl-L-Carnitine—An Energy Booster, and More

Acetyl-L-carnitine is a natural derivative of L-carnitine, an amino acid found in red meat and dairy products and in all cells of the human body. L-Carnitine’s most vital role in our bodies is to facilitate the transport of fatty acids into and out of mitochondria, the tiny organelles that act as the biochemical “powerhouses” in our cells; it thus helps to maintain optimal cellular energy production. Acetyl L-carnitine molecules function as a delivery system across cell membranes for their two principal components: L-carnitine molecules and acetyl groups; the latter are vital for chemical reactions involved in numerous cellular metabolic processes.

After 24 weeks, 59% of the 
ALC group reported an improved 
condition. After 2 more weeks with 
no supplements, 52% of them 
reported a worsening of 
their condition.

By facilitating energy metabolism through its delivery of L-carnitine, acetyl L-carnitine (ALC) acts as a stimulant that improves energy, alertness, and mood. ALC has also been shown to be of benefit in curbing age-related cognitive decline, and it has been found to be helpful in treating Alzheimer’s disease.4 In addition, ALC has a neuroprotective effect (e.g., in diabetes, for which there is evidence that it helps to inhibit various peripheral neuropathies), and it helps protect our eyes from age-related degeneration. Furthermore, ALC can function as an antioxidant. For all these reasons, many integrative medical practitioners recommend ALC for a variety of ailments.

ALC Can Help in Multiple Sclerosis

When people think of multiple sclerosis (MS), they usually think first of the debilitating neuromuscular symptoms caused by this terrible disease. However, fatigue is also one of the hallmarks of MS, and a new study has shown that acetyl L-carnitine may be a useful and safe supplement to combat MS-induced fatigue.1

In a randomized, double-blind, crossover trial in Italy that compared the efficacy of ALC with that of amantadine (a commonly used prescription drug to treat MS fatigue), 36 patients (67% female, average age 44) were treated for 3 months with either amantadine (100 mg twice daily) or ALC (1 g twice daily). The patients then stopped taking ALC or amantadine for 3 months, after which they switched to the opposite treatment for another 3 months.

A significant majority (70%) of the patients taking ALC reported improvement in their levels of fatigue, versus 43% of those taking amantadine. Based on the data obtained, the researchers calculated that 29% of the ALC patients were clinically improved, versus 21% of the amantadine patients. They concluded, “The results of this study showed that ALCAR [ALC] is well tolerated by patients with MS and is more effective than amantadine in the treatment of MS-related fatigue.”

  1. Tomassini V, Pozzilli C, Onesti E, et al. Comparison of the effects of acetyl-L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomized, double-blind, crossover trial. J Neuro Sci 2004;218:103-8.

Dutch Study Evaluates ALC for CFS

Because fatigue is the hallmark of CFS, it seems logical to suppose that ALC, which can improve cellular energy levels, may be of benefit. A recent study conducted in the Netherlands and published in the journal Psychosomatic Medicine examined the effects of ALC and the very similar compound propionyl L-carnitine (PLC) in 90 CFS patients (77% female, average age 39) over a 24-week period.5 The patients were divided into three groups of 30 each: (1) the ALC group received 2 g/day of ALC; (2) the PLC group received 2 g/day of PLC; and (3) the ALC + PLC group received 2 g/day of ALC plus 2 g/day of PLC.

The study was conducted not in the preferred double-blind, placebo-controlled manner, but rather in the less rigorous “open label” manner, in which both the doctors and the patients knew who was getting what. The lack of placebo control is unfortunate because it means that the potentially potent placebo effect could not be ruled out. And the lack of double-blinding opens the possibility of bias—not from the patients, who probably had no preconceived ideas about either compound, but from the researchers (as they themselves admitted, with commendable candor). Despite the poor methodology, however, the study is worth consideration.

Evidence Centers on Patients’ Subjective Experience

Because CFS is an entirely subjective disorder, i.e., there are no objective criteria for verifying its presence or severity, the researchers had to rely on the subjective experience of the patients in assessing their own condition, which they did at the outset of the study and again after 8, 16, and 24 weeks. The primary basis for the evaluation was a concept called the clinical global impression of change (CGIC), which relies on the patient’s answer to the question, “Do you sense a change in your condition compared with the time at which the treatment began?” The answers may range from “very much worse” to “very much better.”

To gain more detailed information on the patients’ condition, the researchers administered questionnaires designed to evaluate fatigue and pain, as well as a psychological test of attention concentration. For fatigue—the “main event,” so to speak—they used the Multidimensional Fatigue Inventory (MFI-20), which assesses three aspects of fatigue: general, determined by generalized reports of fatigue (“I feel tired”); physical, determined by the physical sensation of tiredness; and mental, determined by cognitive symptoms (“I have problems concentrating because I’m fatigued”).6

ALC Improves Overall Score and Mental Fatigue

After 24 weeks, the CGIC scores for two of the groups showed significant improvement: 59% of the ALC group reported an improved condition, and 63% of the PLC group were improved; in the combined ALC + PLC group, only 37% were improved (indicating yet again that more is not always better). After 2 more weeks with no supplements, 52% of the ALC group reported a worsening of their condition, while 50% in the PLC group and 40% in the combined group reported a worsening; no patients reported any improvement.

Based on the MFI-20 questionnaire, the patients taking ALC reported statistically significant improvement in mental fatigue, while those taking PLC or the combined ALC + PLC showed significant improvements in general fatigue; there were no significant improvements in physical fatigue. There were also no improvements in the patients’ subjective evaluation of pain. All three groups did, however, demonstrate significant improvements in their tests of attention concentration.

The Brain Appears to Prefer ALC

At first glance, it might seem strange that two compounds that are as similar as ALC and PLC should show significantly different effects (in some respects) on the symptoms of CFS. The authors postulate that the different effects might be explained by different mechanisms of transport of these compounds from the blood into various tissues of the body. In their study, it appeared that ALC had a greater effect on the central nervous system, whereas PLC had a more peripheral effect. This is consistent, they say, with other human studies suggesting that ALC is preferentially taken up by the brain, and PLC is preferentially taken up by the heart.

Take Heart—ALC May Help

In my practice I’ve seen enough patients with similar complaints regarding chronic fatigue to believe that CFS is a disease as real as cancer or diabetes. Although the lack of a cure is frustrating, people with this disease should take heart that there are some safe, natural supplements, such as acetyl L-carnitine, that may help lift their fatigue and allow them to participate more fully in the many activities of daily life.


  1. Jason LA, Richman JA, Rademaker AW, et al. A community-based study of chronic fatigue syndrome. Arch Int Med 1999;159:2129-37.
  2. Wallman KE, Morton AR, Goodman C, et al. Randomized controlled trial of graded exercise in chronic fatigue syndrome. Med J Austral 2004; 180(9):444-8.
  3. Logan AC, Wong C. Chronic fatigue syndrome: oxidative stress and dietary modifications. Alt Med Rev 2001;6(5):450-9.
  4. Pettegrew JW, Klunke WE, Panchalingam K. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer’s disease. Neurobiol Aging 1995;16:1-4.
  5. Vermeulen RCW, Scholte HR. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Psychosom Med2004;66:276-82.
  6. Smets EMA, Garssen B, Bonke B, De Haes JCJM. The multidimensional fatigue inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychol Res 1995;39(5):315-25.
Dr. Rosick is an attending physician and clinical assistant professor of medicine at Pennsylvania State University, where he specializes in preventive and alternative medicine. He also holds a master’s degree in healthcare administration.