Vitamin D and probiotic co-supplementation affects mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome Original paper

What was studied?

This randomized, double-blinded, placebo-controlled clinical trial investigated the effects of co-supplementation with vitamin D and probiotics on mental health, hormonal profiles, inflammatory markers, and oxidative stress in women with polycystic ovary syndrome (PCOS). The study tested whether the combination of these two interventions could provide synergistic benefits in a population known to have both systemic inflammation and frequent vitamin D deficiency. The researchers hypothesized that probiotic-driven microbiota modulation and vitamin D’s immunomodulatory properties could jointly improve both mental and metabolic health in PCOS.

Who was studied?

Sixty women with PCOS, aged 18–40 years and with body mass index (BMI) between 17 and 34 kg/m², participated in the study. All subjects were insulin-resistant (HOMA-IR between 1.4–4) and had not been receiving prior vitamin D or probiotic supplementation. They were randomized into two groups: one received 50,000 IU of vitamin D every two weeks plus 8 × 10⁹ CFU/day of a probiotic blend containing Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum for 12 weeks, while the control group received matching placebos.

What were the most important findings?

Vitamin D and probiotic co-supplementation resulted in statistically significant reductions in depression, anxiety, and stress scores, indicating improved mental health. There were also significant improvements in hormonal parameters, particularly a reduction in total testosterone and hirsutism, which are hallmark features of PCOS-related hyperandrogenism. Inflammatory and oxidative stress markers showed marked improvement as well: high-sensitivity C-reactive protein (hs-CRP) and malondialdehyde (MDA) decreased, while total antioxidant capacity (TAC) and glutathione (GSH) levels increased.

From a microbiome perspective, the inclusion of multiple Lactobacillus and Bifidobacterium strains supports known major microbial associations (MMAs) relevant to metabolic and hormonal balance. These strains are associated with improved gut barrier function, increased short-chain fatty acid (SCFA) production—especially butyrate—and reduced translocation of lipopolysaccharide (LPS), which contributes to systemic inflammation. Enhanced expression of vitamin D receptors (VDR) by probiotics could further amplify these effects, facilitating vitamin D’s role in reducing oxidative stress and modulating immune response.

What are the implications of this study?

This trial provides compelling evidence that co-supplementation with vitamin D and probiotics can significantly improve mental health, reduce androgen levels, and counteract systemic inflammation and oxidative stress in women with PCOS. These findings are particularly relevant for clinicians exploring microbiome-modifying interventions in PCOS treatment. By targeting both neuroendocrine and metabolic pathways, the combination of vitamin D and probiotics appears to act via the gut-brain-endocrine axis—a crucial interface in PCOS pathophysiology. The results suggest that routine screening for vitamin D deficiency and addressing gut dysbiosis with targeted probiotics could become integral parts of comprehensive PCOS management. Importantly, this synergistic therapy may reduce the need for multiple pharmacologic agents and improve patient adherence and outcomes. Future research should evaluate long-term effects and perform microbiome sequencing to validate microbial shifts and functional changes driving these clinical benefits.