topicVitamin K2 Supplementation Bone Health Randomized Trial
claimThe same vascular calcification that stiffens large arteries and elevates cardiovascular risk also compromises the cerebral microvasculature that sustains neuronal metabolism, and reflects a systemic mishandling of calcium that is associated with depletion of the skeletal reservoir [,].
evidence level3
citationFang Shih-Chin (2026)
sourceBeyond Bone Health: Exploring the “Heart–Brain–Bone” Axis Modulated by Lipid-Soluble Nutrients (Omega-3, Vitamin D3, and Vitamin K2)
topicVitamin K2 Supplementation Bone Health Randomized Trial
claimFirst, we set out the review methodology, including the search strategy, eligibility criteria, and the explicit framework used to grade the strength of evidence ().
evidence level3
citationFang Shih-Chin (2026)
sourceBeyond Bone Health: Exploring the “Heart–Brain–Bone” Axis Modulated by Lipid-Soluble Nutrients (Omega-3, Vitamin D3, and Vitamin K2)
topicVitamin K2 Supplementation Bone Health Randomized Trial
claimThird, we critically appraise the clinical trial evidence, explicitly distinguishing mechanistic, observational, and randomized data and presenting positive, neutral, and null findings alongside one another; delineate the controversies and unresolved questions that temper any therapeutic claim; and identify the populations in which supplementation is most plausibly warranted (,and).
evidence level3
citationFang Shih-Chin (2026)
sourceBeyond Bone Health: Exploring the “Heart–Brain–Bone” Axis Modulated by Lipid-Soluble Nutrients (Omega-3, Vitamin D3, and Vitamin K2)
topicVitamin K2 Supplementation Bone Health Randomized Trial
claimPopulation aging is among the most consequential epidemiological transitions of the twenty-first century, and it is accompanied by a parallel rise in chronic, degenerative, non-communicable diseases.
evidence level3
citationFang Shih-Chin (2026)
sourceBeyond Bone Health: Exploring the “Heart–Brain–Bone” Axis Modulated by Lipid-Soluble Nutrients (Omega-3, Vitamin D3, and Vitamin K2)
topicVitamin K2 Supplementation Bone Health Randomized Trial
claimVitamin D deficiency has been consistently associated with adverse outcomes, including increased susceptibility to cancers, diabetes, hypertension, and cardiovascular disease [,].
evidence level3
citationD’Elia Saverio (2025)
sourceModulation of Cardiometabolic Risk by Vitamin D and K2: Simple Supplementation or Real Drug? Uncovering the Pharmacological Properties
topicVitamin K2 Supplementation Bone Health Randomized Trial
claimEpidemiological studies further indicate that populations in regions with higher sun exposure exhibit lower prevalence of deficiency and reduced mortality from chronic disease [,].
evidence level3
citationD’Elia Saverio (2025)
sourceModulation of Cardiometabolic Risk by Vitamin D and K2: Simple Supplementation or Real Drug? Uncovering the Pharmacological Properties
topicVitamin K2 Supplementation Bone Health Randomized Trial
claimThese findings are reinforced by recent large-scale analyses: for example, a 2023 study in Clinical Nutrition involving nearly 410,000 UK Biobank participants reported that individuals with severe deficiency (<30 nmol/L) had a 10% increased risk of atherosclerotic cardiovascular disease and up to 35% higher risk of cardiovascular mortality [].
evidence level3
citationD’Elia Saverio (2025)
sourceModulation of Cardiometabolic Risk by Vitamin D and K2: Simple Supplementation or Real Drug? Uncovering the Pharmacological Properties
topicVitamin K2 Supplementation Bone Health Randomized Trial
claim1 2 3 4 5 6 7 6 Vitamin D, a pleiotropic secosteroid, exerts physiological effects far beyond its classical roles in calcium homeostasis and skeletal health [].
evidence level3
citationD’Elia Saverio (2025)
sourceModulation of Cardiometabolic Risk by Vitamin D and K2: Simple Supplementation or Real Drug? Uncovering the Pharmacological Properties