Vitamin K Supplementation in Postmenopausal Women With Osteopenia (ECKO Trial): A Randomized Controlled Trial

PLoS Med. 2008 Oct 14;5(10):e196. doi: 10.1371/journal.pmed.0050196.

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).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Density / drug effects*
  • Bone Diseases, Metabolic / blood
  • Bone Diseases, Metabolic / drug therapy*
  • Bone Diseases, Metabolic / metabolism
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Fractures, Bone / prevention & control
  • Humans
  • Middle Aged
  • Osteocalcin / metabolism
  • Osteoporosis, Postmenopausal / prevention & control
  • Postmenopause*
  • Treatment Outcome
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin K / administration & dosage
  • Vitamin K / blood
  • Vitamin K / therapeutic use*
  • Vitamin K 1 / administration & dosage
  • Vitamin K 1 / blood
  • Vitamin K 1 / therapeutic use
  • Vitamin K 2 / administration & dosage
  • Vitamin K 2 / blood
  • Vitamin K 2 / therapeutic use
  • Vitamins / administration & dosage
  • Vitamins / therapeutic use

Substances

  • Vitamins
  • Osteocalcin
  • Vitamin K 2
  • Vitamin K
  • Vitamin D
  • Vitamin K 1
  • 25-hydroxyvitamin D

Associated data

  • ISRCTN/ISRCTN61708241
  • ClinicalTrials.gov/NCT00150969