Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial
What this study found
Daily 5 mg vitamin K1 did not prevent age-related bone loss at the lumbar spine or total hip over 2 years. Lumbar spine BMD changed by -1.28% with vitamin K1 versus -1.22% with placebo (p = 0.84), and total hip BMD changed by -0.69% versus -0.88% (p = 0.51). Vitamin K1 markedly increased serum vitamin K1 and reduced undercarboxylated osteocalcin, but did not clearly reduce bone resorption. Clinical fractures were fewer in the vitamin K1 group (9 vs 20 at 2 years; HR 0.41, 95% CI 0.15 to 1.18, p = 0.08; HR 0.45, 95% CI 0.20 to 0.98, p = 0.04 at 4 years), and cancers were also fewer (3 vs 12;…
- Study & population
- Single-center randomized, placebo-controlled trial in postmenopausal women with osteopenia in Toronto, Canada.
- Intervention
- Vitamin K1 (phylloquinone) was given orally at 5 mg daily for 2 years, with extension of follow-up to 4 years for early enrollees.
- Key limitation
- The trial was not powered for fracture or cancer outcomes, so those apparent benefits are uncertain.
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Open PDFOriginal abstract
Background Vitamin K has been widely promoted as a supplement for decreasing bone loss in postmenopausal women, but the long-term benefits and potential harms are unknown. This study was conducted to determine whether daily high-dose vitamin K1 supplementation safely reduces bone loss, bone turnover, and fractures. Methods and Findings This single-center study was designed as a 2-y randomized, placebo-controlled, double-blind trial, extended for earlier participants for up to an additional 2 y because of interest in long-term safety and fractures. A total of 440 postmenopausal women with osteopenia were randomized to either 5 mg of vitamin K1 or placebo daily. Primary outcomes were changes in BMD at the lumbar spine and total hip at 2 y. Secondary outcomes included changes in BMD at other sites and other time points, bone turnover markers, height, fractures, adverse effects, and health-related quality of life. This study has a power of 90% to detect 3% differences in BMD between the two groups. The women in this study were vitamin D replete, with a mean serum 25-hydroxyvitamin D level of 77 nmol/l at baseline. Over 2 y, BMD decreased by −1.28% and −1.22% (p = 0.84) (difference of −0.06%; 95% confidence interval [CI] −0.67% to 0.54%) at the lumbar spine and −0.69% and −0.88% (p = 0.51) (difference of 0.19%; 95% CI −0.37% to 0.75%) at the total hip in the vitamin K and placebo groups, respectively. There were no significant differences in changes in BMD at any site between the two groups over the 2- to 4-y period. Daily vitamin K1 supplementation increased serum vitamin K1 levels by 10-fold, and decreased the percentage of undercarboxylated osteocalcin and total osteocalcin levels (bone formation marker). However, C-telopeptide levels (bone resorption marker) were not significantly different between the two groups. Fewer women in the vitamin K group had clinical fractures (nine versus 20, p = 0.04) and fewer had cancers (three versus 12, p = 0.02). Vitamin K supplements were well-tolerated over the 4-y period. There were no significant differences in adverse effects or health-related quality of life between the two groups. The study was not powered to examine fractures or cancers, and their numbers were small. Conclusions Daily 5 mg of vitamin K1 supplementation for 2 to 4 y does not protect against age-related decline in BMD, but may protect against fractures and cancers in postmenopausal women with osteopenia. More studies are needed to further examine the effect of vitamin K on fractures and cancers. Trial registration: ClinicalTrials.gov (#NCT00150969) and Current Controlled Trials (#ISRCTN61708241)