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’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.
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.
- Unrewarding Reward: The Basal Ganglia, Inflammation and Fatigue In Chronic Fatigue Syndromeasal Ganglia
- Dopamine, the Basal Ganglia and Chronic Fatigue Syndrome #II – Treatments
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.
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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.
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.
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.
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.
- Inquiry of the Day: Were you ever prescribed antidepressants for ME/CFS or fibromyalgia and, if so, how did it go. Take the poll on Health Rising’s Forums and tell us here.
- Share your experience with Cymbalta or acetyl L-carnitine in the Review section of Health Rising’s new ME/CFS, FM and Chronic Pain Forums.
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Thanks very much for this, Cort. Another valuable contribution. It is helpful motivation to hear of effectiveness confirmed by trial results. For me, just knowing that there is good evidence that ALCAR and ALA protect neurons makes me seriously want to do it. Especially now with the Stanford evidence of neuronal damage.
Cort deserves special honors for his unflagging and astonishing outpouring of intelligent help for us all.
Thank you 🙂
Have used all three of these vitamins and it had no effect whatsoever on my FM. Have some relief from Cymbalta with no side effects.
Acetyl L-carnitine Never Helped me at all. Was on it for 3 months no effect at all. The Only thing that helps me is Gabapentin & Cymbalta. Endep for sleep . I feel that fibro is caused by some virus because when i take Antibiotics the pain level goes right down.
More research is needed along the lines of a virus….
in your case then more research into bacteria 😉 borrelia or a mycoplasma are a few of the usual suspects
I have the same results w antibiotics I noticed when I’m on them my pain is reduced. However antibiotics do not treat viruses they treat infections ( bacteria) so then it could not be a virus. It would have to be some kinda infection. 🙁
Here is a website that discusses this: http://www.chronicprostatitis.com/antibiotics-are-anti-inflammatory-agents/
We are all different. I stopped my Cipro for acute sinusitis three days early after it activated my fibro to an unbelievable level. Went back to usual bad level in a day or two.
Soph, just like you I seem to have some success whenever I am put on antibiotics for “suspected” infections. The antibiotics always have varying degrees of improvement but the improvement is short lived. Just recently my primary care doctor pointed out to me that antibiotics, to varying degrees, have anti-inflammatory properties. This had never occurred to me. I am sure many already knew this, but I did not. It could be that my short lived “improvements” with the antibiotics were due to reduced inflammation and had nothing to do with a virus?
that was Mark 😉 and too bad one can’t be on abx forever then ;/ do you know your reaction to just anti-inflammatories (NSAID’s like Ibuprofin)?
Soph, thanks for pointing that out and giving Mark the credit. I have never used NSAID’s much. I know they can be hard on the body if used regularly so I just never have. I don’t need them for pain as the Gabapentin takes care of my neurological pain.
Acetyl L-carnitine also did nothing for me and just like you the only thing that has given me relief for pain has been Gabapentin. Gabapentin has been a god-send for my pain.
I’m getting good results from Synergy’s Energy package which continues a bunch of co factors.
I have been waiting for you to give a personal update on this. Ritalin is the only drug my doctor has offered to prescribe. I assume I could get the nutritional supplement, KPAX, on my own? My fear has always been that if it gives you more energy will it then make you crash with PEM. You make me want to put my toe back in the water!
Cort, What is Synergy’s Energy package?
caused my vision to blur
Since severe pain is the most prominent symptoms of my FM, ALCAR does not sound help, tho I appreciate the article and research. The unfortunate reality is that, while we dispute the accuracy or reporting of some Big Parma efforts, their products have been through a number of trials and target salient symptoms. They do help some people
Hi Cort. Very interesting and insightful article. Thanks! I so wish I could try this, but for many of us whose level of income has been severly affected by our illness, these supplements are prohibitively expensive at the recommended dosage. It really is unfortunate.
I have tried 500mg once a day, which didn’t help at all. But both recommendations here (500mg three times a day or 1,500mg twice a day) are way out of my reach financially.
FWIW, Swanson’s sells ALC very inexpensively under their own label.
Thanks for the info, Ellen. Their price really is reasonable. I am in South Africa however, so will have to find out if they ship to us and what the shipping costs would be.
I initially took ProHealth’s acetyl l-carnitine/alpha lipoic acid supplement in 2006 for cognitive support with a small improvement in symptoms. After reading (where now, I could not say & am too weak to search) that ALCAR could be weight-dependent for dosing (& being obese), I increased my intake eventually to 4000mg. The improvement in pain (& cognitive symptoms to some extent) was gradual. I didn’t fully appreciate just how well it was working until I ran out once a couple of years later and within a week — good god! The pain was back. My legs especially felt like I had constant shin splints. To be sure over those couple of years all of my pain had increased so that we had to increase my other pain meds too (which made knowing what is doing what much more difficult…unless you, say, run out of one of them…). But I’ve now had several experiences of running out of ALCAR (the, uh, cognitive improvement was not profound) and within a week the same phenomenon occurs. Needless to say, I work hard not to run out.
I would note that I was not a responder to Cymbalta (we did two trials a few years apart). I also have both FMS and moderately severe ME/CFS (roughly a 15 on Bruce Campbell’s functional scale).
Swanson Vitamins is also my supplement source. FWIW, if you are in the US and on Food Stamps and/or in HUD housing, you can — via a prescription from your doctor — get almost fully reimbursed for out-of-pocket medical expenses in the form of additional Food Stamps (with $196 being the max amount possible) and reduced rent. Speak to your case worker and/or building manager.
Hello, Very interesting study. I have access to carnitine tartrate. I ve read somewhere that its not the same but I Dont know if that was based on evidence. Ive taken ALA twice (50 mg) and it knocked me out immediately. I had to go to bed. Is that possible or just a coincidence? Thanks
I have tried ALC and ALA together and found that it helps me. Not sure to what extent, but definitely an improvement in pain and brain fog. But, I don’t have CFS specifically, though I have had Lyme and do have FM. I am definitely going to continue taking it as it seems to reduce late-onset soreness and pain after physical activity. Cymbalta didn’t work for me. I take low dose Elavil instead.
I was in the clinical trial with Kpax & Ritalin and for me it was a disaster. I spent a month in misery, hoping for some magic to happen, dreading every time it was time to take the meds.
I withdrew from the trial after a month, and a short time later found out I have mast cell activation disorder. I think the Kpax was fine, I think I was allergic or highly sensitive to the Ritalin.
Wow – sorry to hear that. I wonder if MAST is a counter-indication for it. Did the diagnosis help you with treatment?
Teri I can’t be sure it was the K- Pax given the usual ups and downs, but I too felt horrible while on the 8 pill protocol. I’m currently taking 2 pills a day to use it up as a general supplement along with the Ritalin – no change for better or worse….
I know I’m late to the discussion but I wanted to throw in my 2 cents.
A month ago I went to Bermuda and in order to survive the trip (also have CFS) I doubled my mito supports. I felt great while there, and for the first time in my life I wasn’t the first person who needed to stop and rest. I attributed it to a much lower altitude (I live at 1100 feet). I maintained the doubled dose for a week after my holiday to give my body a chance to catch up and heal. I was back on my normal dose for a week and noticed that I needed to take the full amount of my pain killer (Nabilone) when for the last few weeks I had been taking less than half of what I could. I remembered reading something about ALCAR and fibro pain and so I doubled only the ALCAR, taking 500mg with breakfast and another at lunch. Within days my pain lessened. By the end of the week, I’m taking 1/3 of the pain killer that I could. I’m going to keep this up and may eventually go up to 1500 mg of ALCAR a day. I’d love to go off of the Nabilone because I’d like to be able to drive again. I have no idea how it affects my driving reflexes but I do know that it’s not exactly legal to drive with as technically I’m under the influence.
Note that my attempts with antidepressants to treat insomnia, CFS and FM have been epic failures as I don’t tolerate them at all and have had allergic reactions to some.
Can you list exactly what your “mito support?” Your said you doubled it, but never said what “it” is. Maybe I am just having trouble following, but it would be helpful if you listed the the supplements and amounts and then the amount you changed up.Thanks.
I generally take 5g of d-ribose, 500mg ALCAR, 200mg of CoQ10 and 10mg of sublingual NADh. For me it’s been a magical combination. It took me from bed bound and completely dependent to being able to bathe, dress, and prepare food for myself, I can now do laundry if I pace, I do most of the cleaning in my house and have recently started cutting the lawn again. I will be asking my primary care provider for Carnitor (prescription form of ALCAR) next time I see her. My pharmacist says it’s close enough and it makes a difference for me because my partner has medical benefits and it should be covered.
I have tried these in various combinations before taking only 2 or 3 at one time, and for me it doesn’t work nearly as well as taking all 4 together.
you know what would sériously enhance those mito’s; getting the bugs out of them!
I’m just gonna repeat this like a broken record until someone will listen or éven will be my guinea piglet 😉
ALCAR seems protective for ketamine induced damage in model where zebrafish used. Something to do with beta oxidation and fatty acids and ATP.
I have been taking acetyl-L-Carnitine for several years now. I stupidly stopped for several months and am paying a step price. I never knew about this research. I can testify to the improved energy and memory function with the use. And I have only ever taken partial doses. From now on I will take the full amount. My fatigue is really bad and I wish I had never quit taking it.
Diana – do you think you feel worse than before you started taking it – or is it that it’s just so crummy going back to your original state after feeling better?
Good luck with it!