Effect of 6-Month Vitamin D Supplementation on Plasma Matrix Gla Protein in Older Adults

Abstract

Vitamin D supplementation has been widely promoted to restore 25-hydroxyvitamin D concentrations; however, experimental evidence suggests a nutrient interaction with vitamin K. We assessed the effects of 1200 IU vitamin D3 per day versus placebo for six months on vitamin K status in a randomized, double-blind, placebo-controlled trial with participants aged 60–80 years with depressive symptoms and ≥1 functional limitation for a secondary analysis. Stored baseline and six-month follow-up blood samples were available for 131 participants (n = 65 placebo vs. n = 66 vitamin D supplementation). We measured dephosphorylated uncarboxylated matrix gla protein (MGP) (dp-ucMGP) concentrations—a marker of vitamin K deficiency. Mean age was 68 years, and 89 participants (68%) were women. Vitamin K antagonists were used by 16 participants and multivitamin supplements by 50 participants. No differences in change between intervention and placebo were found (−38.5 ± 389 vs. 4.5 ± 127 (pmol/L), p = 0.562). When excluding vitamin K antagonist users and multivitamin users, dp-ucMGP at follow-up was significantly higher in the vitamin D group (n = 40) compared to placebo (n = 30), with a difference of 92.8 (5.7, 180) pmol/L, adjusting for baseline dp-ucMGP and sex. In conclusion, vitamin D supplementation for six months did not affect vitamin K status; however, among participants without vitamin K antagonist or multivitamin use, vitamin D supplementation influenced dp-ucMGP concentrations.

The Relationship between Dietary Vitamin K and Depressive Symptoms in Late Adulthood: A Cross-Sectional Analysis from a Large Cohort Study

“…Finally, another important finding of our research is that vitamin K was associated with depressive symptoms, only in people not taking vitamin D supplementation. While a recent paper suggest that vitamin D supplementation might lower vitamin K status [40], in our study, vitamin D supplementation seems to attenuate the negative effect of a low vitamin K intake. Nevertheless, in our study, another limitation is the lack of measurement of the uncarboxylated fraction of osteocalcin and matrix gla protein, markers of vitamin K status, which could better account for the real effect of vitamin K on depression and bone health.…”

Combined low vitamin D and K status amplifies mortality risk: a prospective study

“…Similar observations were found among kidney transplant recipients with higher dp-ucMGP concentrations among people on vitamin D therapy 1281 vs 974 pmol/L among non-users [ 13 ]. Also in a randomized-controlled trial, vitamin D supplementation for 6 months increased inactive dp-ucMGP compared to placebo in older adults without vitamin K antagonist or multi-vitamin use [ 32 ]. The use of vitamin D supplements has increased tremendously over the last decade and, therefore, more research is needed to investigate whether monotherapy of vitamin D can worsen vitamin K status in various populations.…”

Post hoc analysis of a randomised controlled trial: effect of vitamin D supplementation on circulating levels of desmosine in COPD

“…Administration of vitamin D may have the potential to induce relative vitamin K deficiency through this mechanism [20]. Recent studies indeed show that vitamin D supplementation reduces vitamin K status [23,24]. Survival is strongly reduced in kidney transplant recipients who are treated with active vitamin D with low versus high vitamin K status, which is most likely caused by calcifying effects of vitamin D on blood vessels unopposed by sufficient MGP that has been activated by vitamin K [24].…”