How a Mitochondrial Booster Became an Antidepressant

Acetyl0 L-carnitine (ALCAR) is best known as an energy supplement and mitochondrial booster the but folks in this  fibromyalgia clinical trial were looking for more than increased energy; they were looking for relief from pain and depression as well. They pinned ALCAR not as an energy booster per se, but as a central nervous system protectant – and they had good reason to do so.

Clin Exp Rheumatol. 2015 Mar-Apr;33(1 Suppl 88):82-5. Epub 2015 Mar 18. A randomised controlled trial comparing duloxetine and acetyl L-carnitine in fibromyalgia patients: preliminary data. Leombruni P1, Miniotti M1, Colonna F1, Sica C1, Castelli L2, Bruzzone M3, Parisi S3, Fusaro E3, Sarzi-Puttini P4, Atzeni F5, Torta RG1.

Acetyl L-carnitine

Acetyl- L-carnitine’s (ALCAR) transport of the important metabolic factor Acetyl CoA into the mitochondria increases energy production. Similar in structure to acetylcholine, it also stimulates acetylcholine production and enhances cellular membrane health.

acetyl L-carnitine depression

Acetyl L-carnitine can access the brain. It’s greatest effects may lie in central nervous system disorders

Central Nervous System: It’s where it does all this that is key. By enhancing energy stores and maintaining membrane fluidity in neurons it may reduce neuronal death. By reducing glutamate levels and oxidative stress in the brain it appears to reduce central nervous system excitotoxicity.  Either way it appears to have neuroprotective factors.  It’s been and is being studied in a variety of nervous system disorders.

Larger clinical trials are needed, but a 2014 review suggested that acetyl-L-carnitine may be able to  alleviate depression.  Acetyl-L-carnitine reduced hyperactivity and improved social functioning in two trials of ADHD patients with Fragile X Syndrome.

A trial featuring hepatitis patients taking interferon may have the most relevance for chronic fatigue syndrome (ME/CFS).  Acetyl-L-carnitine significantly improved both biological parameters (including viremia), as well as many physical factors (physical and mental fatigue, pain, physical functioning and vitality). Miller’s basal ganglia studies suggest ME/CFS patients and hepatitis patients receiving interferon have similar types of brain dysfunction. They suggest inflammation/oxidative stress induced basal ganglia damage may be causing fatigue in both groups.

Peripheral Nervous System – Acetyl-L-carnitine may also improve peripheral nerve functioning – a possibly important factor given the high incidence of small fiber neuropathy in FM (approx. 40%).  Six months of ALC supplementation (1,500 mgs/2 x’s daily) significantly increased sensory nerve density and reduced neuropathic pain in HIV patients with retroviral drug-induced nerve damage.   A recent meta-analysis suggests acetyl-L-carnitine has moderate pain-reducing effects in peripheral neuropathy.


This Italian study randomized 65 female FM patients to either duloxetine (Cymbalta), an FDA-approved treatment for fibromyalgia, or 500 mgs. of acetyl-L-carnitine (three times a day) for three months. Fibromyalgia impact, pain and mood symptoms were assessed at several points during the trial.

acetyl l carnitine improves functioning in fibromyalgia

Acetyl L-carnitine as as effective as Cymbalta in improving depression, well-being and physical functioning

Both treatments produced significant improvements in depression, overall well-being, and physical functioning. Duloxetine improved pain. In contrast to earlier findings in FM and other disorders, ALCAR did not. Anxiety was not significantly improved in either group.

Serious side-effects appeared to be significantly reduced in the ALCAR group compared to the Cymbalta group. (Side-effects prompted almost twenty-five percent of FM patients to drop out of one study.)

Reduced Synergy = Reduced Results?

No studies suggest acetyl L-carnitine has other than moderate effects in disease. Moderate effects in many chronic diseases, however, can present a significant step forward.

Studies may also be under-estimating acetyl L-carnitine’s potential effects by using it in isolation..  Jon Kaiser of the aptly named Synergy trial asserts acetyl L-carnitine is much more effective when taken with alpha lipoic acid (ALA) and n-acetylcysteine (NAC). That formulation was effective in boosting the immune functioning of HIV/AIDS patients, but was not as successful in people with chronic fatigue syndrome. Kaiser found that adding other nutrients plus a stimulant (either caffeine or methylphenidate) was much more effective in ME/CFS.

Acetyl-L-carnitine in combination with other nutrients (folate, alpha-tocopherol, B12, S-adenosyl methionine, N-acetyl cysteine) improved some cognitive functions in an Alzheimer’s trial.

Wrap Up

Acetyl-L-carnitine’s  ability to go toe to toe with an FDA approved antidepressant in the areas of mood, well-being and physical functioning in FM was impressive. Its inability to move the needle on pain was a bit surprising given study evidence it can do so in peripheral neuropathy. No studies to my knowledge, however, have determined how much of a contribution the small fiber neuropathy in FM makes to pain levels in that disorder.

It should be noted, though, that Cymbalta is not particularly effective. The number of FM patients needed to treat in order for one to have a fifty percent improvement in pain is seven (@ 120 mgs/day).

The study may also have underestimated the effects ALCAR can have when given in conjunction with other nutrients.  Kaiser, for instance, asserts ALCAR is much more effective when used with alpha lipoic acid and NAC.

Acetyl L-carnitine - nervous system protectant

Acetyl L-carnitine may be able to improve central and peripheral nervous system functioning

The lack of a placebo control group made it impossible to tease out placebo effects from treatment effects.  Numerous studies suggest ALCAR’s ability to increase energy reserves in neurons and maintain cell membrane health and reduce oxidative stress  could have positive effects on both central nervous system and peripheral nervous system functioning.

Can a mitochondrial enhancer like ALCAR replace an antidepressant and pain reliever like Cymbalta? The evidence at this point is too sparse to say so. ALCAR has not received the large-scale trials Cymbalta has in fibromyalgia. Given it’s few side effects and ease of purchase, however, this study and others suggest it may be worth a shot in pain, neurological and mood disorders.

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