Study of Leucine to Improve Brain Function and Depression Symptoms in Middle-Aged Adults

What this Trial Is About

Researchers are investigating the effects of a 6-week leucine challenge on brain chemistry, connectivity, and behavior in middle-aged adults with major depression. The study focuses on symptoms like loss of pleasure and slowed movements, which may indicate harder-to-treat depression and increased dementia risk. It explores how inflammation and the kynurenine pathway might contribute to depression by producing brain-toxic substances. Leucine, a nutrient, may block these toxins and improve brain function, but its effects in humans are not yet known. Participants will be randomly assigned to receive either L-leucine or L-lysine supplements daily for 6 weeks. L-leucine is given at 4.31 grams per day and aims to inhibit harmful kynurenine uptake in the brain, while L-lysine at 6 grams per day serves as an active comparator to control for general protein synthesis effects. Both supplements are taken orally. The study uses a triple-blind design to compare these two groups. During the study, participants will undergo brain scans and assessments at baseline, week 1, and week 6 to measure changes in glutamate levels, brain connectivity, effort, anhedonia, and psychomotor slowing. Blood tests and questionnaires will monitor inflammation and depression severity. Safety and adherence will be tracked throughout, with the total participation lasting 6 weeks. This research could help understand how inflammation affects depression and explore new treatment avenues.

Leucine in Midlife Depression