Limited Changes in Red Blood Cell Parameters After Probiotic Supplementation in Depressive Individuals: Insights from a Secondary Analysis of the PRO-DEMET Randomized Controlled Trial

Background: Depression often coexists with anemia, potentially sharing common pathways, highlighting the need for treatments addressing both conditions simultaneously. This study evaluated the effect of probiotics on red blood cell (RBC) parameters in adults with depressive disorder. We hypothesized that probiotics would positively influence RBC parameters, potentially modulated by baseline inflammation or dietary intake, with improved RBC function correlating with better antidepressant outcomes. Methods: This secondary analysis of a two-arm, randomized, double-blind, controlled trial involved 116 adults with depressive disorder. Participants received a probiotic formulation containing Lactobacillus helveticus Rosell (R)-52 and Bifidobacterium longum Rosell (R)-175 or a placebo for 60 days. Data from 97 subjects were analyzed for RBC parameters, including hemoglobin (HGB), RBC count, hematocrit (HCT), mean corpuscular volume (MCV), mean hemoglobin concentration (MCH), mean corpuscular hemoglobin concentration (MCHC), and RBC distribution width (RDW). Results: Probiotic supplementation did not result in significant changes in RBC parameters compared to the placebo. However, probiotics may help stabilize HGB, HCT, MCH, and MCHC levels, potentially preventing fluctuations observed in the placebo group. Conclusions: While probiotics showed potential benefits for depressive symptoms, significant changes in RBC parameters were not observed. Larger studies are needed to clarify the mechanisms and clinical implications.