Daily Vinegar Ingestion Improves Depression and Enhances Niacin Metabolism in Overweight Adults: A Randomized Controlled Trial

Abstract

Depressive disorders are the most prevalent mental health conditions in the world. The commonly prescribed antidepressant medications can have serious side effects, and their efficacy varies widely. Thus, simple, effective adjunct therapies are needed. Vinegar, a fermented acetic acid solution, is emerging as a healthful dietary supplement linked to favorable outcomes for blood glucose management, heart disease risk, and adiposity reduction, and a recent report suggests vinegar may improve symptoms of depression. This randomized controlled study examined the 4-week change in scores for the Center for Epidemiological Studies Depression (CES-D) questionnaire and the Patient Health Questionnaire (PHQ-9) in healthy overweight adults ingesting 2.95 g acetic acid (4 tablespoons vinegar) vs. 0.025 g acetic acid (one vinegar pill) daily. A secondary objective explored possible underlying mechanisms using metabolomics analyses. At week 4, mean CES-D scores fell 26% and 5% for VIN and CON participants respectively, a non-significant difference between groups, and mean PHQ-9 scores fell 42% and 18% for VIN and CON participants (p = 0.036). Metabolomics analyses revealed increased nicotinamide concentrations and upregulation of the NAD+ salvage pathway for VIN participants compared to controls, metabolic alterations previously linked to improved mood. Thus, daily vinegar ingestion over four weeks improved self-reported depression symptomology in healthy overweight adults, and enhancements in niacin metabolism may factor into this improvement.

Keywords: acetic acid; depression; metabolomics; nicotinamide; vinegar.

Figure 1

Consort Flowchart.

Figure 2

Boxplots for metabolites with significant group x time interactions between VIN and CON participants: isobutyric acid, niacinamide, and L-isoleucine.

Figure 3

Metabolic pathway enrichment map: the horizontal coordinate is the enrichment significance p-value and the vertical coordinate is the KEGG pathway. Displayed are the 25 most important enzymatic pathways differentiating between groups, with colored side bar displaying the relative metabolite concentration in each group. Data analyzed between groups after calculating T2/T1 (post/pre). The first nine pathways listed had significant predicted changes (p < 0.05).

Figure 4

(A) PLS-DA Score Plot of Pathway Enrichment Analysis performed using all surveyed metabolites mapped to canonical KEGG pathways. Dots represent change in metabolic activity between groups across time points; size of dot represents the size of the pathway; darker colors (ranging from white to dark red) represent higher hits. (B) KEGG IDs referenced in pathway diagram. Key metabolite names are noted. Highlighted boxes represent up-regulated compounds. NAD+ salvage pathway noted with green arrows.

Figure 5

Acetate induced AMPK signaling to promote NAD+ cycling to nicotinamide. Activation of the SIRTS and PARPs occurs which function in mitochondrial energetics and neuronal protection.