Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial

• Published in: PLoS medicine 2008-10, Vol.5 (10), p.e196-12
• Main Authors: Cheung, Angela M, Tile, Lianne, Lee, Yuna, Tomlinson, George, Hawker, Gillian, Scher, Judy, Hu, Hanxian, Vieth, Reinhold, Thompson, Lilian, Jamal, Sophie, Josse, Robert
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Bone density; Bone Density - drug effects; Bone Diseases, Metabolic - blood; Bone Diseases, Metabolic - drug therapy; Bone Diseases, Metabolic - metabolism; Bones; Cancer; Chronic Disease Management; Clinical trials; Confidence intervals; Dietary Supplements; Double-Blind Method; Female; Fractures; Fractures, Bone - prevention & control; Humans; Medical research; Menopause (including hormone replacement therapy); Middle Aged; Nutrition and Metabolism; Osteocalcin - metabolism; Osteoporosis; Osteoporosis, Postmenopausal - prevention & control; Postmenopause; Proteins; Quality of life; 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; Women's Health; Womens health
• ISSN: 1549-1676; 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.0050196

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. 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. 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 cancer