Naturally produced in the body, acetyl-L-carnitine is also widely available in drugstores, supermarkets, and health food catalogs as a nutritional supplement. People with severe or treatment-resistant depression, or whose bouts of depression began earlier in life, have particularly low blood levels of the substance.

The findings, which appear in the Proceedings of the National Academy of Sciences, build on extensive animal research. They mark the first rigorous indication that the link between acetyl-L-carnitine levels and depression may apply to people, too.

They also point the way to a new class of antidepressants that could be freer of side effects and faster-acting than those in use today, and that may help patients for whom existing treatments don’t work or have stopped working.

Trying to understand depression

Natalie Rasgon, professor of psychiatry and behavioral sciences at Stanford University, describes the findings as “an exciting addition to our understanding of the mechanisms of depressive illness.”

“As a clinical psychiatrist, I have treated many people with this disorder in my practice,” she says.

Depression, also called major depressive disorder or clinical depression, is the most prevalent mood disorder in the United States and the world, affecting 8-10 percent of the general population at any given time, with every fourth person likely to experience the condition over the course of a lifetime.

“It’s the No. 1 reason for absenteeism at work, and one of the leading causes of suicide,” Rasgon says. “Worse, current pharmacological treatments are effective for only about 50 percent of the people for whom they’re prescribed. And they have numerous side effects, often decreasing long term compliance.”

“In rodent experiments… a deficiency of acetyl-L-carnitine was associated with depression-like behavior,” McEwen says. Oral or intravenous administration of acetyl-L-carnitine reversed the animals’ symptoms and restored their normal behavior, he says.

In those studies, the animals responded to acetyl-L-carnitine supplementation within a few days. Current antidepressants, in contrast, typically take two to four weeks to kick in—in animal experiments as well as among patients.

Animal studies by Carla Nasca, a postdoctoral scholar in McEwen’s lab, suggest that acetyl-L-carnitine, a crucial mediator of fat metabolism and energy production throughout the body, plays a special role in the brain, where it works at least in part by preventing the excessive firing of excitatory nerve cells in brain regions called the hippocampus and frontal cortex.

Rasgon cautions against rushing to the store to pick up a bottle of acetyl-L-carnitine and self-medicating for depression.

The new study, which Nasca also initiated, recruited 20- to 70-year-old men and women who had been diagnosed with depression and, amid episodes of acute depression, had been admitted to either Weill Cornell Medicine or Mount Sinai School of Medicine, both in New York City, for treatment.

These participants went through screening via a detailed questionnaire and clinical assessment, plus blood samples and medical histories. Twenty-eight of them were judged to have moderate depression, and 43 had severe depression.

In comparing their blood samples with those of 45 demographically matched healthy people, the depressed patients’ acetyl-L-carnitine blood levels were found to be substantially lower. These findings held true for both men and women, regardless of age.

A word of caution

Further analysis showed that the lowest levels occurred among participants whose symptoms were most severe, whose medical histories indicated they were resistant to previous treatments, or whose onset of the disorder occurred early in life.

New clues to genetics of depression are ‘game-changing’
Acetyl-L-carnitine levels were also lower among those patients reporting a childhood history of abuse, neglect, poverty, or exposure to violence.

These patients, who collectively account for 25-30 percent of all people with major depression disorder, are precisely the ones most in need of effective pharmacological interventions, says Rasgon, who performed the bulk of the advanced data analysis for the study.

But she cautions against rushing to the store to pick up a bottle of acetyl-L-carnitine and self-medicating for depression.

“We have many previous examples of how nutritional supplements widely available over the counter and unregulated by the Food and Drug Administration—for example, omega-3 fatty acids or various herbal substances—are touted as panaceas for you-name-it, and then don’t pan out,” she says.

Big questions remain, she adds. “We’ve identified an important new biomarker of major depression disorder. We didn’t test whether supplementing with that substance could actually improve patients’ symptoms. What’s the appropriate dose, frequency, duration? We need to answer many questions before proceeding with recommendations, yet. This is the first step toward developing that knowledge, which will require large-scale, carefully controlled clinical trials.”

Additional researchers from Rockefeller University; Weill Cornell Medical College; the Icahn School of Medicine at Mount Sinai; Duke University; and the Karolinska Institute in Stockholm, Sweden also contributed to the work.

Stanford University shares in a multi-institutional agreement concerning intellectual property resulting from this research. The Hope for Depression Research Foundation, the Pritzker Neuropsychiatric Disorders Research Consortium, and the Robertson Foundation funded the study. Stanford’s psychiatry and behavioral sciences department also supported the work.

Read the original article on futurity.org.

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