Update on the role of vitamin K in skeletal health.
A protective role for vitamin K in bone health has been suggested based on its role as an enzymatic cofactor. In observational studies, vitamin K insufficiency is generally associated with lower bone mass and increased hip fracture risk. However, these findings are not supported in randomized controlled trials (RCT) of phylloquinone (vitamin K(1)) supplementation and bone loss at the hip in the elderly. This suggests that increased vegetable and legume intakes may simultaneously improve measures of vitamin K status and skeletal health, even though the mechanisms underlying these improvements may be independent of each other. Menaquinone-4 (vitamin K(2)), when given at pharmacological doses, appears to protect against fracture risk and bone loss at the spine. However, there are emerging data that suggest the efficacy of vitamin K supplementation on bone loss is inconclusive.
This is a great review of the different forms of Vitamin K and their benefits for bone. The full study includes a table listing many studies dated from 1998 to 2008 with their outcomes. I highly recommend reading the full text.
MK-4 in doses of 45 mg/d is used as a pharmacological treatment for osteoporosis in Japan, so there are numerous randomized control studies that have assessed the efficacy of MK-4 supplementation on skeletal health. Such doses cannot be attained from the diet, regardless of the form of vitamin K consumed. Phylloquinone from the diet is converted to MK-4 in certain tissues, including bone, but the proportion of phylloquinone that is converted is not known and no dose-dependent data are available for this conversion.
As reviewed in an earlier volume of this journal,60 studies indicate a therapeutic dose (45 mg/day) of MK-4 has a beneficial effect on spine or metacarpal BMD and fracture61–76 (Table 2). There is also improvement in bone turnover, as measured by circulating markers of bone formation and bone resorption, in response to MK-4 supplementation studies.71,72,76,77 In a separate systematic review and analysis of randomized clinical trials assessing the influence of vitamin K supplementation on hip fracture, Cockayne et al.78 concluded that supplementation with MK-4 for longer than 6 months reduces risk for hip and vertebral fracture. Included in that analysis were 12 studies that used daily doses of 45 mg/d of MK-4. As discussed by the authors, several of the studies used for the meta-analysis lacked sufficient sample size,64–66,70,73,79 were non-placebo-controlled intervention trials,70–74,76,77,80 and/or used concurrent treatment with calcium and/or vitamin D.62,69,75,76
It was subsequently disclosed that a large unpublished surveillance study conducted in Japan (n > 3000) did not find a protective effect of MK-4 supplementation (45 mg/day) on bone loss and fracture in the elderly, and that inclusion of this study may have altered the results of the meta-analysis.81 More recently, two placebo-controlled studies with large sample sizes reported no protective effect of 45 mg/d of MK-4 on hip BMD.59,67 Prior to these two publications, the majority of MK-4 supplementation studies did not report hip BMD as an outcome (Table 2). Given the heterogeneous quality of the studies used and considering the null findings of more recent, larger, placebo-controlled trials and unpublished surveillance data, prior systematic reviews and meta-analyses may need to be revisited.