Acetyl L-carnitine and Depression

There is much to learn about optimizing your brain health. Here is another article from the research arm of Designs for Health, a science-based company for nutrition-based answers for your health.

The modified amino acid carnitine is probably best known for its role in facilitating fat burning, via the carnitine palmitoyl and carnitine-acyl transferase enzymes that help shuttle fatty acids into the mitochondria. Because of this role in beta-oxidation (the literal process of fat burning), acetyl L-carnitine (ALCAR) has been studied for boosting fat loss. ALCAR has other therapeutic applications, however—ones not immediately obvious when looking only at its role in fat metabolism.

Therapeutic Applications of ALCAR

Acetyl L-carnitine, a methylated form of the amino acid carnitine, is synthesized from lysine in the human brain, liver, and kidney. The building block, L-carnitine, is also found in meat, poultry, fish, and dairy. (In fact, the name carnitine comes from its having been first isolated in meat.) Very small amounts occur naturally in plant foods, but animal foods are the predominant sources of carnitine. Owing to adequate endogenous synthesis (about 0.16 to 0.48 mg/kg of body weight/day), overt deficiencies are rare, even in strict vegetarians and vegans.

A little-known potential role for ALCAR has to do with brightening a dark mental outlook, rather than battling the bulge. Evidence suggests ALCAR might be beneficial for individuals with depression. A systematic review and meta-analysis of ALCAR supplementation for treatment of depressive symptoms found that, compared to placebo, ALCAR resulted in significant improvement in symptoms, and in trials where ALCAR was compared to antidepressant medication, ALCAR showed similar efficacy to the drugs, but were associated with significantly fewer adverse effects. These findings echoed those of an earlier review of randomized controlled trials that concluded ALCAR was superior to placebo with regard to improving depressive symptoms, and was equally effective as fluoxetine and amisulpride in treatment of dysthymic disorder. (Amisulpride is an antipsychotic drug also used to treat dysthymia.)

In a double-blind, placebo-controlled RCT comparing ALCAR to amisulpride, there was no significant difference in symptom improvement between ALCAR (500mg b.i.d.) or amisulpride (50 mg u.i.d.) at 12 weeks, but notably, ALCAR was better tolerated, which the authors suggested is clinically relevant since dysthymia often requires prolonged treatment.

Depression is a common malady in the elderly. ALCAR has shown significant promise for this patient population. A small study of older subjects (age 60-80) with dysthymia found that compared to placebo, ALCAR supplementation (3g/day) resulted in significant reduction in the severity of depressive symptoms and improvements in quality of life measurements. Other research supports this finding, even when a lower dose of ALCAR is used (1500mg/day).

The precise mechanisms by which ALCAR promotes improvement in depressive and dysthymic symptoms aren’t fully understood. It was recently found that ALCAR serves as an acetyl group donor, which supports additional functions that go beyond its role in energy metabolism. Both oral and intravenous administration of ALCAR have been shown to raise cerebrospinal fluid levels of ALCAR, indicating that the compound readily crosses the blood-brain barrier, a key feature of a compound we would look to for helping with mood disorders. It’s believed that the effects are modulated at least in part by epigenetic regulation of type 2 metabotropic glutamate (mGlu2) receptors.

An additional mechanism might be related to increases in brain derived neurotrophic factor (BDNF). It was shown in rats that ALCAR partially restored hippocampal and prefrontal cortex levels of BDNF. Notably, there was rapid onset of improved depressive symptoms (within 3 days) and the beneficial effects persisted for 2 weeks after ALCAR withdrawal. The rapid onset of benefit seen in rats was demonstrated in elderly human subjects with dysthymic disorder in a double-blind RCT comparing ALCAR to fluoxetine. The study found that results obtained with ALCAR and fluoxetine “were equivalent,” except that clinical response to ALCAR was observed within just one week, while fluoxetine took two weeks. Researchers have noted that this may be of special relevance because of the sometimes substantial lag time before clinical benefits are noticed with conventional antidepressants.

ALCAR modulates various neurotransmitter systems, including the gabaergic, dopaminergic, and cholinergic systems, which could play a role in its effects on depressive symptoms. It also increases acetyl-CoA levels and choline acetyltransferase activity, which has led to investigation of ALCAR for dementia, but findings here have mostly been disappointing.

Other non-traditional uses for ALCAR that are being explored include treatment of peripheral neuropathic pain, diabetic peripheral neuropathy, chemotherapy-induced neuropathy, fibromyalgia (pain and depressive symptoms, in particular), and even carpal tunnel syndrome. It’s heartening that a compound that’s relatively inexpensive and so readily available could be of benefit for issues that lack truly effective management strategies.

To learn more about neurobiology and optimizing brain health, see my article series about the Neurobiological Approach to Oneness.

Veronese N1, Stubbs B, Solmi M, Ajnakina O, Carvalho AF, Maggi S. “Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis”. Psychosom Med. 2018 Feb/Mar;80(2):154-159. doi: 10.1097/PSY.0000000000000537.

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