Depression Linked to Shortage of a Single Naturally Occurring Chemical

But don't go trying to treat it with supplements.

Intermountain Medical Center

Approximately one-third of people with major depression don’t experience relief from existing methods of treatment. It affects 3.2 million patients in the United States alone, which is why researchers are urgently trying to find depression-linked molecules in the brain to target with new drugs. On Monday, scientists revealed the identity of one particularly promising biomarker, a molecule named acetyl-L-carnitine.

Acetyl-L-carnitine, or ALC, is naturally produced in the body and aids in the metabolism of food into energy. In the new Proceedings of the National Academy of Sciences paper, researchers reveal people with depression have lower levels of ALC in their blood. This link was previously established in animal studies, but this paper is the first to indicate that it exists in humans, too.

However, study co-author and Stanford University professor Dr. Natalie Rasgon tells Inverse that this discovery does not mean that people with depression should go buy ALC supplements, which are widely available online. These supplements, which aren’t approved by the FDA, are used by consumers to treat a variety of maladies ranging from age-related cognitive decline to erectile dysfunction. Just because depression is linked to decreased ALC doesn’t mean it can be fixed by supplementing the body with more of it.

As the research stands, we simply don’t know whether these supplements help with depression. Advocating for their use, she warns, could “just derail the potential efficacy of a drug if we can find it in controlled studies.”

“This is a supplement, but the substance which was tested is not a supplement; it’s an endogenous molecule,” says Rasgon. “At this point, we want to be very careful in specifying what we’ve achieved: We have found a new biomarker for depression, and it has significant potential for finding a new molecular target for drugs.”

Acetyl-L-carnitine prevents excessive firing of excitatory nerve cells in the brain.


Rasgon and her co-authors found the biomarker by collecting medical and personal details, blood samples, and clinical assessments from people, ranging from 20 to 70 years old, who had been diagnosed with depression. Out of all the participants, 28 had moderate depression, and 43 had severe depression.

It was obvious after comparing the blood samples of the depressed participants to those of 45 “demographically matched healthy people” that the depressed people had substantially lower ALC blood levels, regardless of age or gender.

The lowest ALC levels were observed in the blood of people who experienced the most severe symptoms, who underwent the onset of depression earlier in life, and those who hadn’t had luck with treatments. Importantly, the team also found that ALC levels were lower in the sample of participants who reported to the researchers a childhood history of neglect, abuse, and poverty — a correlation that Rasgon says highlights the ill effects of experiencing adversity during one’s developmental years.

“We’ve known that people who experienced childhood adversity subsequently experience worse overall health, cognitive performance, and are at risk for depression when they reach mid-life,” says Rasgon. “This study mechanistically addresses the link between adversity and depression because of the low ALC levels. This is speculative, but it could decrease the body’s capacity to tolerate stress.”

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