Investigating the Effects and Mechanisms of Combined Vitamin D and K Supplementation in Postmenopausal Women: An Up-to-Date Comprehensive Review of Clinical Studies

Abstract

Aging is a complex process and a significant risk factor for chronic diseases. Menopause, a component of aging in women, is associated with several important cardiometabolic conditions including metabolic syndrome, osteoporosis, and cardiovascular diseases. Menopausal women could benefit from preventative strategies that may decrease morbidity and mortality and improve their quality of life. Vitamins D and K are essential nutrients required for bone health, immune function, and reducing cardiovascular risks, yet their synergistic effect is less understood in aging women. This is the first comprehensive review to summarize the evidence found in randomized clinical trials of the beneficial effects of vitamin D and K co-treatment in postmenopausal women. In our literature search across key electronic databases such as Cochrane, PubMed, and Ovid, we identified 31 pertinent studies. Overall, significant findings indicate that the combined intake of vitamins D and K may positively affect cardiovascular and bone health in postmenopausal women, emphasizing the importance of maintaining a healthy diet rich in vegetables and fermented dairy products. Given the challenges in obtaining all necessary nutrients solely through the diet, vitamin D and K supplements are recommended for postmenopausal women to promote healthy aging and well-being.

Keywords: age-related diseases; aging; bone health; cardiovascular health; nutrients; osteoporosis; trials; vitamins.

Figure 1

Flow chart illustrating the process of selecting studies.

Figure 2

Chemical structures of vitamin D.

Figure 3

Chemical structures of naturally occurring vitamin K.

Figure 4

The impact of vitD and K on VC and CVD (AGEs—advanced glycation end products; BMP-2—bone morphogenetic protein 2; CVD—cardiovascular disease; dp-cMGP—dephosphorylated–carboxylated matrix Gla protein; dp-ucMGP—dephosphorylated–uncarboxylated matrix Gla protein; Gla—γ-carboxylated glutamic acid; IL—interleukin; NF-kB—nuclear factor kappa-light-chain enhancer of activated B cells; p-cMGP—phosphorylated-carboxylated matrix Gla protein; RAGE—receptor for advanced glycation end products; TNF-α—tumor necrosis factor-alpha; VC—vascular calcification; VitD—vitamin D; VitK—vitamin K; VSMC—vascular smooth muscular cells; ↑—increase; ↓—decrease).

Figure 5

The impact of vitamins D and K on bone mineralization (Akt—protein kinase B; ALP—alkaline phosphatase; BMD—bone mineral density; BMP-2—bone morphogenetic protein 2; cOC—carboxylated osteocalcin; IκB—inhibitor of nuclear factor kappa B; NFATc1—nuclear factor of activated T-cells 1; NF-kB—Nuclear factor kappa-light-chain enhancer of activated B cells; OPG—osteoprotegerin; PI3K—Phosphatidylinositide-3-kinase; RANKL—the receptor activator of NF-κB ligand; RUNX2—runt-related transcription factor 2; ucOC—undercarboxylated osteocalcin; VDR—vitamin D receptor; VitD—vitamin D; VitK—vitamin K; ↑—increase; ↓—decrease).