Depression has been linked to a significant burden of disease, loss of life, and decreased efficacy of treatment for its comorbidities. Empirical evidence has mounted over the past several decades supporting health benefits from vinegar ingestion, including improvements in blood glucose management, blood cholesterol levels, and inflammation indicators. To date, there have not been any studies in human populations that explore the potential relationship between daily vinegar ingestion and changes in depression indicators and blood metabolomics. This blinded, randomized controlled trial examined the impact of twice-daily vinegar ingestion on mental health measures in healthy young adults recruited from a metropolitan setting. Participants (n=28; aged 25.8±7.0 y; body mass index [BMI] >23 kg/m2) were stratified by age, gender, and BMI and randomly assigned to the liquid (VIN) or pill (CON) groups. VIN participants ingested 2 tablespoons of red wine vinegar (~1550 mg acetic acid; Pompeian Inc., Appendix J) diluted in 8-12 ounces of water, consumed with food at mealtimes twice daily (total ~3100mg acetic acid daily). CON participants consumed 1 vinegar pill daily (22.5 mg acetic acid; Spring Valley, Appendix J). The study lasted four weeks, and anthropometric measurements were conducted in a fasted state at weeks 0 and 4. Study adherence varied slightly (90±17% and 100±14% for VIN and CON respectively, p=0.084); hence, adherence was controlled for in all subsequent analyses. Changes in L-tryptophan (p=0.777, η2=0.003), peripheral serotonin levels (p=0.348, η2=0.035), GABA (p=0.403, η2=0.028), and gut-mediated short-chain fatty acids acetic acid (p=0.355, η2=0.034), and propionic acid (p=0.383, η2=0.031), did not differ significantly between VIN and CON groups respectively with the exception of isobutyric acid (p=0.0374, q=0.0473). However, Patient Health Questionnaire (PHQ-9) depression scores improved significantly for VIN participants in comparison to CON participants (-0.5±1.3 vs. +0.7±2.4 cm [p=0.026] and -0.4±0.7 vs. +0.3±1.0% [p=0.045]. Although these differences between groups are modest, which would be expected given the short study duration, changes were not driven by pharmacological or lifestyle interventions, suggesting the benefits of vinegar ingestion on mental health symptomology and the blood metabolome.