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Some TLC from ALC in depression

Acetyl-L-carnitine can pass through the blood-brain barrier more easily than L-carnitine. This meta-analysis takes a look at whether it can help with depression.

Study under review: Acetyl-l-carnitine Supplementation and the Treatment for Depressive Symptoms: A Systematic Review and Meta-analysis.

Introduction

Depressive symptoms and associated mood disorders, such as dysthymia (persistent mild depression) and major depressive disorder, are becoming more common, affecting over 322 million people worldwide in 2015 and increasing by 18.2%[1] from 2005 to 2015. Depression is associated with comorbidities[2], such as obesity[3], cardiovascular disease[4], irritable bowel syndrome[5], and pain conditions (migraines[6], fibromyalgia[7], etc.), as well as a reduced quality of life[8], and overall mortality[9]. Depression doesn’t just influence health and disability. The economic impact of depression is substantial[10] and could be easily outweighed[11] by upscaling effective treatment coverage, especially considering the potential health benefits and productivity boost. Although estimated to be higher[12] in females and adults of working age, depressive symptoms are prevalent in both sexes and all age groups[1].

Depressive disorders are hard to diagnose and treatment can be quite individual, leading to limited effectiveness[13], although several options are available. Pharmacotherapy may sometimes be unhelpful[14], as patients tend to try various medications before finding an effective antidepressant (or combination of antidepressants), and the severity of side effects[15] can be specific to the individual. Moreover, antidepressants have been associated with[16] falls, cardiovascular disease, and mortality. Psychotherapy is generally trusted more than medication, although it is not always[17] more effective. Physical activity reduces symptoms[18] of mild and moderate depression, with comparable treatment results to the two former options. This keeps the market for alternative treatments wide open.

While there are several risk factors associated with depression risk, some nutrients[19], especially fats[20] and their metabolism, have been inversely associated with depression. Contemporary research indicates that the link between increases in fatty acid intake and metabolism and a lower risk of depression may in part be attributable to L-carnitine[21], a conditionally essential nutrient (it can be synthesized by the body, but during conditions of stress or disease, synthesis can be inadequate and it must be obtained from the diet). L-carnitine’s primary function[22] is the transport of fats into the mitochondria for their breakdown into energy. Dietary carnitine intake, primarily found in food from fatty diets[23] and animal sources, correlates[24] with plasma carnitine concentrations. Women tend to have lower[25] plasma carnitine levels regardless of dietary intake, aligning with depressive symptom statistics[12].

A specific modified version of the molecule, acetyl-L-carnitine[26] (ALC), can pass through the blood-brain barrier[27] more easily and seems to have more prominent anti-depressive effects, potentially attributable to[28] modulation of brain energy and fat metabolism, neuroprotective factors, and connectedness and communication of neurons. Some of the possible effects of ALC in the brain are summarized in Figure 1.

A recent review[29] suggests that ALC seems to be equally effective as antidepressants and equally tolerable to placebo, but observes that there are many potential mechanisms and calls for more clinical trial data with advanced methodology. In view of the many potential mechanisms and inconsistent results as far as efficacy is concerned, the authors of this study decided to conduct a systematic review and meta-analysis to clarify these concerns.

Depressive symptoms are common and take a large toll on worldwide health and productivity. Some aspects of nutrition, especially fats and their metabolism, are being explored for their role in depression. Carnitine, a compound found in animal foods and primarily responsible for transporting fats to mitochondria for breakdown into energy, has been found to be inversely associated with depression. A natural metabolite of L-carnitine, acetyl-L-carnitine (ALC), shows some promise as a natural, well-tolerated antidepressant, but the ideal dosage, duration of supplementation, and resulting influence are still a subject of ongoing research. The authors of the study at hand designed a systematic review and meta-analysis to examine and quantify its efficacy.

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