Category Archives: Vitamin K1

Review: Vitamin K1 and MK-4 Reduce Bone Loss

Abstract

Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials.

Observational and some experimental data suggest that low intake of vitamin K may be associated with an increased risk of fracture.
To assess whether oral vitamin K (phytonadione and menaquinone) supplementation can reduce bone loss and prevent fractures.
The search included the following electronic databases: MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), the Cochrane Library (issue 2, 2005), the ISI Web of Science (1945 to June 2005), the National Research Register (inception to the present), Current Controlled Trials, and the Medical Research Council Research Register.
Randomized controlled trials that gave adult participants oral phytonadione and menaquinone supplements for longer than 6 months were included in this review.
Four authors extracted data on changes in bone density and type of fracture. All articles were double screened and double data extracted.
Thirteen trials were identified with data on bone loss, and 7 reported fracture data. All studies but 1 showed an advantage of phytonadione and menaquinone in reducing bone loss. All 7 trials that reported fracture effects were Japanese and used menaquinone. Pooling the 7 trials with fracture data in a meta-analysis, we found an odds ratio (OR) favoring menaquinone of 0.40 (95% confidence interval [CI], 0.25-0.65) for vertebral fractures, an OR of 0.23 (95% CI, 0.12-0.47) for hip fractures, and an OR of 0.19 (95% CI, 0.11-0.35) for all nonvertebral fractures.
This systematic review suggests that supplementation with phytonadione and menaquinone-4 reduces bone loss. In the case of the latter, there is a strong effect on incident fractures among Japanese patients.

Cockayne S, Adamson J, Lanham-New S, Shearer MJ…
Arch. Intern. Med. Jun 2006
PMID: 16801507

Review: Vitamin K and Bone Health

Abstract

Chemistry, nutritional sources, tissue distribution and metabolism of vitamin K with special reference to bone health.

Vitamin K occurs in nature as a series of compounds with a common 2-methyl- 1,4 naphthoquinone nucleus and differing isoprenoid side chains at the 3 position. They comprise a single major plant form, phylloquinone with a phytyl side chain and a family of bacterially synthesized menaquinones (MKs) with multiprenyl side chains. The major dietary source to humans is phylloquinone for which the chief food contributors are green, leafy vegetables followed by certain vegetable oils (soybean, rapeseed and olive oils). Recent analyses by high pressure liquid chromatography are now providing a wide-ranging database of phylloquinone in foods. Menaquinones are found in moderate concentrations in only a few foods such as cheeses (MK-8 and MK-9). A wider spectrum of MKs is synthesized by the gut microflora, and their intestinal absorption probably accounts for most of the hepatic stores, particularly those with very long side chains (MKs-10-13) synthesized by members of the genus Bacteroides. The site of absorption of floral MKs is not known, but reasonable concentrations are found in the terminal ileum where bile salt-mediated absorption is possible. Both phylloquinone and menaquinones are bioactive in hepatic gamma-carboxylation but long-chain MKs are less well absorbed. Liver stores of vitamin K are relatively small and predominantly MKs-7-13. The hepatic reserves of phylloquinone (approximately 10% of the total) are labile and turn over at a faster rate than menaquinones. Trabecular and cortical bone appear to contain substantial concentrations of both phylloquinone and menaquinones. A majority (approximately 60-70%) of the daily dietary intake of phylloquinone is lost to the body by excretion, which emphasizes the need for a continuous dietary supply to maintain tissue reserves.

Shearer MJ, Bach A, Kohlmeier M
J. Nutr. Apr 1996
PMID: 8642453 | Free Full Text


At the present time the human requirements for vitamin K are based solely on its classical function in coagulation being listed as a Recommended Dietary Allowance (RDA) in the United States (Suttie 1992) and a Safe and Adequate Intake in the United Kingdom (Department of Health Report 1991). In both cases these requirements were set at a value of 1 mcg/kg/d. If, as argued by Vermeer et al. and Kohlmeier et al. in this volume, vitamin K is important to bone health and its requirements for this bone function are greater than for its hepatic function, a great challenge to researchers and future committees alike is to determine whether these putative extra demands can be quantified more precisely. Finally, it should be noted that the concept of reexamining the optimal intake of a vitamin with respect to the extra health benefits, which may be conferred by giving amounts over and above those required to protect against the originally discovered deficiency disease, is not new. There is already a recognition of the newer and often unexpected roles played by several other vitamins including in some cases the beneficial effects of extra intakes (Sauberlich and Machlin 1992).

Vitamin K1 Not Associated with Bone Density or Fracture in Perimenopausal Women

Abstract

No effect of vitamin K1 intake on bone mineral density and fracture risk in perimenopausal women.

Vitamin K functions as a co-factor in the post-translational carboxylation of several bone proteins, including osteocalcin.
The aim of this study was to investigate the relationship between vitamin K(1) intake and bone mineral density (BMD) and fracture risk in a perimenopausal Danish population.
The study was performed within the Danish Osteoporosis Prevention Study (DOPS), including a population-based cohort of 2,016 perimenopausal women. During the study approximately 50% of the women received hormone replacement therapy (HRT). Associations between vitamin K(1) intake and BMD were assessed at baseline and after 5-years of follow-up (cross-sectional design). Moreover, associations between vitamin K(1) intake and 5-year and 10-year changes in BMD were studied (follow-up design). Finally, fracture risk was assessed in relation to vitamin K(1) intake (nested case-control design).
In our cohort, dietary vitamin K(1) intake (60 mug/day) was close to the daily intake recommended by the Food and Agriculture Organization (FAO). Cross-sectional and longitudinal analyses showed no associations between intake of vitamin K(1) and BMD of the femoral neck or lumbar spine. Neither did BMD differ between those 5% that had the highest vitamin K(1) intake and those 5% that had the lowest. During the 10-years of follow-up, 360 subjects sustained a fracture (cases). In a comparison between the cases and 1,440 controls, logistic regression analyses revealed no difference in vitamin K(1) intake between cases and controls.
In a group of perimenopausal and early postmenopausal women, vitamin K(1) intake was not associated with effects on BMD or fracture risk.

Rejnmark L, Vestergaard P, Charles P, Hermann AP…
Osteoporos Int 2006
PMID: 16683180

Vitamin K1 + D + Minerals Reduced Bone Loss in Postmenopausal Women

Abstract

Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age.

Although several observational studies have demonstrated an association between vitamin K status and bone mineral density (BMD) in postmenopausal women, no placebo-controlled intervention trials of the effect of vitamin K1 supplementation on bone loss have been reported thus far. In the trial presented here we have investigated the potential complementary effect of vitamin K1 (1 mg/day) and a mineral + vitamin D supplement (8 microg/day) on postmenopausal bone loss. The design of our study was a randomized, double-blind, placebo-controlled intervention study; 181 healthy postmenopausal women between 50 and 60 years old were recruited, 155 of whom completed the study. During the 3-year treatment period, participants received a daily supplement containing either placebo, or calcium, magnesium, zinc, and vitamin D (MD group), or the same formulation with additional vitamin K1 (MDK group). The main outcome was the change in BMD of the femoral neck and lumbar spine after 3 years, as measured by DXA. The group receiving the supplement containing additional vitamin K1 showed reduced bone loss of the femoral neck: after 3 years the difference between the MDK and the placebo group was 1.7% (95% Cl: 0.35-3.44) and that between the MDK and MD group was 1.3% (95% Cl: 0.10-3.41). No significant differences were observed among the three groups with respect to change of BMD at the site of the lumbar spine. If co-administered with minerals and vitamin D, vitamin K1 may substantially contribute to reducing postmenopausal bone loss at the site of the femoral neck.

Braam LA, Knapen MH, Geusens P, Brouns F…
Calcif. Tissue Int. Jul 2003
PMID: 14506950