A growing body of science linking vitamin K to bone health benefits, as well as increased marketing and advertising from supplement makers, is raising public awareness of a vitamin traditionally less well known than vitamins A to E.
But, despite the impressive results, the authors of the new meta-analysis concluded that routine supplementation was "not justified until these results are confirmed in large pragmatic randomised clinical trials."
There are two main forms of vitamin K: phylloquinone, also known as phytonadione, (vitamin K1) which is found in green leafy vegetables such as lettuce, broccoli and spinach, and makes up about 90 per cent of the vitamin K in a typical Western diet; and menaquinones (vitamins K2), which make up about 10 per cent of Western vitamin K consumption and can be synthesised in the gut by microflora.
Menaquinones (MK-n: with the n determined by the number of prenyl side chains) can also be found in the diet; MK-4 can be found in animal meat, MK-7, MK-8, and MK-9 are found in fermented food products like cheese, and natto is a rich source of MK-7.
Some sources have said that MK-4, also known as menatetrenone, is synthetic vitamin K2, which is not correct. However, MK-4 is distinct from other MKs because it not a major constituent of the spectrum of MKs produced by gut microflora, but can be derived from K1 in vivo.
A synthetic form of vitamin K, known as K3, does exist but is not recommended for human consumption.
The new meta-analysis, published in the American Medical Association's Archives of Internal Medicine (Vol. 166, pp. 1256-1261), pooled 13 randomised control trials of vitamin K supplementation (phytonadione or MK-4) for bone health. Six trials were subsequently excluded because they contained no information about fractures.
The seven remaining trials all focussed on MK-4, with six using 45-milligram daily doses, and one used 15-milligram daily doses. Five studies used elderly women as the study population, while two used male and females.
The researchers, led by David Torgerson from the University of York, England, calculated that the menaquinone-4 supplements were associated with a consistent reduction in all fracture types.
Supplementation of vitamin K (MK-4) resulted in reductions in hip fractures of 77 per cent, vertebral fracture of 60 per cent, and all non-vertebral fractures of 81 per cent.
The fracture rates were also reduced at all fracture sites, say the researchers, with hip fracture rates reduced by six per cent, vertebral fracture of 13 per cent, and all non-vertebral fractures of nine per cent.
"In this systematic review and meta-analysis, we have shown that supplementation with phytonadione and menaquinone, particularly MK-4, is associated with increased bone mineral density (BMD) and reduced fracture incidence," wrote lead author Sarah Cockayne.
"The reduction in fracture incidence is particularly striking, with an approximate 80 per cent reduction in hip fractures," she said.
No serious adverse effects were recorded in any of the studies, although some minor gastrointestinal problems were occasionally noted.
The mechanism behind the benefits is proposed to be due to vitamin K's influence on the secondary modification of osteocalcin, a protein needed to bind calcium to the bone matrix.
"From a clinical perspective, the results of this review suggest that patients at risk for fracture should be encouraged to consume a diet rich in vitamin K, which is chiefly obtained from green leafy vegetable and certain vegetable oil," concluded the researchers.
One major limitation with this study is that the researchers did not look into the effects of other types of menaquinone, most notably MK-7, which is found in products such as the fermented soy product, natto. Many studies, mostly from Japan, have reported that increased MK-7 intake can also have significant benefits on bone health.
Osteoporosis is estimated to affect about 75m people in Europe, the USA and Japan. According to the International Osteoporosis Foundation, the total direct cost of osteoporotic fractures is €31.7bn in Europe, and 17.5bn in the US (2002 figure). The total annual cost of osteoporosis in the UK alone is over £1.7bn (€2.5bn), equivalent to £5m (€7.3m) each day.