The Effects of Vitamin D-K-Calcium Co-Supplementation on Endocrine, Inflammation, and Oxidative Stress Biomarkers in Vitamin D-Deficient Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

The current study was conducted to assess the effects of vitamin D-K-calcium co-supplementation on endocrine, inflammation, and oxidative stress biomarkers in vitamin D-deficient women with polycystic ovary syndrome (PCOS). This randomized double-blind, placebo-controlled trial was performed on 60 vitamin D-deficient women diagnosed with PCOS aged 18-40 years old. Participants were randomly allocated into 2 groups to intake either 200 IU vitamin D, 90 μg vitamin K plus, 500 mg calcium supplements (n=30), or placebo (n=30) twice a day for 8 weeks. Endocrine, inflammation, and oxidative stress biomarkers were quantified at the beginning and the end of the study. After 8 weeks of intervention, compared with the placebo, vitamin D-K-calcium co-supplementation resulted in a significant reduction in serum-free testosterone (- 2.1±1.6 vs.+0.1±1.0 pg/ml, p<0.001) and dehydroepiandrosterone sulfate (DHEAS) levels (- 0.8±1.0 vs.-0.1±0.5 μg/ml, p=0.006). In addition, a significant increase in plasma total antioxidant capacity (TAC) (+ 75.7±126.1 vs.-80.4±242.8 mmol/l, p=0.005) and a significant difference in plasma malondialdehyde (MDA) concentrations (+ 0.03±0.6 vs.+1.4±2.4 μmol/l, p=0.005) was observed following the supplementation with vitamin D-K-calcium compared with the placebo. A trend toward a greater decrease in luteinizing hormone was observed in vitamin D-K-calcium co-supplement group compared to placebo group (- 7.0 vs.-1.2 IU/l, p=0.09). We did not find any significant effect of vitamin D-K-calcium co-supplementation on prolactin, follicle-stimulating hormone, 17-OH progesterone, inflammatory markers, and glutathione levels. Overall, vitamin D-K-calcium co-supplementation for 8 weeks among vitamin D-deficient women with PCOS had beneficial effects on serum DHEAS, free testosterone, plasma TAC, and MDA levels.

Metabolic alterations in multiple sclerosis and the impact of vitamin D supplementation

“…This is consistent with current knowledge about the molecular effects of vitamin D on related pathways, such as the Nrf2 antioxidant pathway, which leads to activation of the glutathione-S-transferase A2 enzyme, and the antiaging protein Klotho (27,28). This is also consistent with the relationship between vitamin D deficiency and elevated markers of oxidative stress and the reduction of markers of oxidative stress with vitamin D supplementation in multiple populations (12,13,29).…”

“…In other populations, vitamin D supplementation reduces markers of oxidative stress and also positively affects many other metabolic markers (12,13). Whether MS patients display a similar change in oxidative stress after vitamin D supplementation is not known.…”

The effect of Vitamin D supplementation on hormonal and glycaemic profile of patients with PCOS: A meta-analysis of randomised trials

“…Nine studies were included in the present meta‐analysis which investigated the impact of vitamin D supplementation in 647 patients . The actual number of patients that were randomised in the various treatment groups is available in Table .…”

Immunophenotypic Profiles in Polycystic Ovary Syndrome

“…Furthermore, vitamin D's anti-inflammatory impact on human pathophysiology is well-accepted [100]. A current meta-analysis of randomized controlled trials concluded that vitamin D supplementation to women with PCOS results in an improvement in hsCRP, malondialdehyde, and total antioxidant capacity [95,96]; serum total testosterone and androstenedione levels were reportedly lowered in vitamin D-calcium cosupplement group as compared to the control group [101], in response to upregulated insulin receptor genes [102]. However, vitamin D does not affect the symptoms of hyperandrogenism [103].…”