Vitamin K has been indicated for many applications in optimal bone health, including the maintenance of osteocalcin (in bone), and matrix Gla protein (in cartilage). However, as evidence begins to accumulate it is suggested that high intake is required to provide optimal effect. The synthetic short-chain vitamin K1 is commonly used in food supplements, but recently the natural long-chain menaquinone-7 (MK-7) has also become available as a supplement.
In a recent study from the University of Maastricht, the Netherlands, the absorption and efficacy of K1 and MK-7 was compared in healthy volunteers.1 Vitamin K1 and MK-7 were absorbed well, with peak serum concentrations at four hours after intake. A major difference between these vitamin-K species was the long half-life of MK-7, resulting in more stable serum levels, and accumulation of MK-7 to higher levels (seven- to eight-fold) during prolonged intake. The hypothesis that can be gleaned from this work is that MK-7 induced a more complete carboxylation of osteocalcin, which may translate to better bone health.
As lead researcher Leon Schurgers, PhD, told Functional Ingredients, "Although K2 vitamins comprise only some 10 per cent of our total dietary vitamin K intake, they may form half of the total vitamin K absorbed. This is because of the much better, nearly complete absorption and also signfiicantly longer biological half-life of the long-chain menaquinones. It seems, therefore, that these long-chain menaquinones (eg, MK-7) are the main contributors to the vitamin K status in humans. In conclusion, high intakes are required for K vitamins with short half-life in the circulation. This problem can be solved by supplementing with the K2 vitamin MK-7, which when given on a daily basis results in high steady-state vitamin K levels at a relative low intake." [For the complete Schurgers interview, including more on K2's mechanism of action, effects with oral anticoagulants, emerging health benefits besides bone health, and more, click here.]
However, as with any powerful dietary supplement, some cautions should be given, and in the case of MK-7, preparations supplying 50mcg/day may interfere with oral anticoagulant treatment in a clinically relevant way.
The importance of K2 (MK-4, menatetrenone) vitamins for optimal bone health has been suggested primarily by animal and population-based studies. However, intervention studies using Dual-energy X-ray absorptiometry (DXA, previously DEXA) as a clinical endpoint of bone mineral density (BMD) have shown contradicting results. Unlike bone mineral content (BMC), DXA does not take into account the size and thickness of bone, which has an independent contribution to bone strength and fracture risk. A recent study, again from the Netherlands, tested whether BMC and femoral neck width are affected by high vitamin K2 intake.2
In this three-year study, 325 postmenopausal women were randomly assigned 45mg/day vitamin K2 or placebo. BMC and hip geometry were assessed by DXA, and bone-strength indices were calculated from DXA-BMD, femoral neck width (FNW), and hip axis length (HAL). The data show that although K2 did not affect the DXA-BMD, measurements taken through BMC and the FNW significantly increased relative to placebo. Over the three years of the trial, hip-bone strength was well maintained in those taking vitamin K2 but a significant decline was evident in those supplemented with placebo. The take-home of this study was that vitamin K2 helps maintain bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW.
New applications for rheumatoid
The effects of vitamin K2 on the development of arthritis have not been examined in relation to the proliferation of rheumatoid synovial cells or the development of arthritis. In a study from Japan, researchers analysed the effect of vitamin K2 on the proliferation of synovial cells (cells that produce fluid around the joint to help lubricate).3
The results of this study indicated that vitamin K2 inhibited the proliferation of synoviocytes fibroblasts and the development of collagen-induced arthritis in a dose-dependent manner.3 The authors conclude that vitamin K2 may represent a new agent for the treatment of rheumatoid arthritis and, as such, this may be a novel breakthrough in vitamin-K2 research.
Vitamin D: the synergistic nutrient
Vitamin D has become a popular ingredient, and over the past few years has been highly researched in multiple areas of health and disease. From the focus on calcium as the primary ingredient for better bone health, the shift toward vitamin D as an essential factor in the prevention and treatment of disease has arrived. Although many studies have examined the action of vitamin D on bone and joint health, little work has highlighted its action when combined with additional natural products.
Researchers from the University of Tokushima, Japan, had previously carried out a clinical trial with osteoporotic subjects. Subjects who supplemented with 200 or 400IU/day vitamin D3 with 0.75mcg/day of a new active vitamin D analog 'ED-71' for 12 months increased lumbar and hip-bone mineral density (BMD) by 3.4 per cent and 1.5 per cent respectively, compared to the placebo group. These effects on BMD were stronger than any previous results using 1alpha(OH)D3 (alphacalcidiol) or 1,25(OH)2D3 (the biologically active form of vitamin D). However, there still was a concern that the effect of ED-71 could be observed because serum 25(OH)D (calcidiol: this is the main storage and circulating form of vitamin D) in many of these subjects were below optimal levels.
In order to address this issue, authors performed post hoc analysis to compare the effect of ED-71 on lumbar and hip BMD between subjects with upper (>29ng/mL) and lower tertiles (
These results demonstrate that the effect of ED-71 on bone is independent of vitamin-D insufficiency, and suggest that ED-71 may have stronger effects on bone compared to the natural 1,25(OH)2D3.
Vitamin K plus D
In a two-year study carried out at the Nutrition Research Group, University of Dundee, Scotland, investigators looked at the role of high dietary vitamin-D intake on BMD and the possibility of interactive benefits with vitamin K1 or calcium.5 Over a two-year period, nonosteoporotic women received either placebo, 200mcg/day vitamin K1, 10mcg/day (400 IU) vitamin D3 plus 1,000mg calcium/day, or combined vitamins K1 and D3 plus calcium.
Significant bone mineral loss was seen only at the wrist, but with no significant difference between groups. However, women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the wrist. Serum indicators of bone turnover responded significantly to supplementation with vitamins K and D.
Vitamin D delivery issues
Many types of supplements are on the market, but little is known about whether vitamin D3 (cholecalciferol) obtained from fat-containing capsules differs in bioavailability from that of solid tablets. One study tested whether four weeks of daily intake of 10mcg vitamin D3 as a fish-oil capsule produced a larger increase in serum 25-hydroxyvitamin D (s-25(OH)D) concentration compared with the same dose of vitamin D3 given as a multivitamin tablet.6
Fifty-five subjects completed a self-administered questionnaire about diet and sunshine exposure and, having a nonfasting venous blood sample drawn, participants were randomised to receive daily multivitamin tablets or fish-oil capsules, each containing equal doses of vitamin D3.
When controlling for baseline s-25(OH)D, mean four-week increase in s-25(OH)D was 35.8nmol/l in the multivitamin group and 32.3nmol/l in the fish-oil group; the mean difference was 3.5nmol/l. The conclusion reached in the study was that fish-oil capsules and multivitamin tablets containing 10mcg cholecalciferol administered over a four-week period produced a similar mean increase in s-25(OH)D concentration. Although the trend was toward higher increases in s-25(OH)D from fish-oil capsules, it may be that longer or higher-dose supplementation would lead to a significant difference.
As the drive for natural mediums of enhancing bone health grows year on year, it is no surprise that innovative studies have evolved. The latest of these highlight synergistic relationships between different ingredients and the most efficient ways to deliver them. As work progresses beyond osteoporosis population groups, approval by the wider medical fraternity will maintain a healthy marketplace in these efficacious ingredients.
Mark J Tallon, PhD, is chief science officer of NutriSciences, a London-based consultancy specialising in health-claim substantiation, product development and technical writing. www.NutriSciences.net. Respond: [email protected]
For more on vitamin K, see ' Science Review.'
1. Schurgers LJ, et al. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 2007;15;109(8):3279-83.
2. Knapen MH, et al. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int 2007;18(7):963-72.
3. Okamoto H, et al.Anti-arthritis effects of vitamin K(2) (menaquinone-4)--a new potential therapeutic strategy for rheumatoid arthritis. FEBS J 2007;274(17):4588-94.
4. Matsumoto T, Kubodera N. ED-71, a new active vitamin D3, increases bone mineral density regardless of serum 25(OH)D levels in osteoporotic subjects. J Steroid Biochem Mol Biol 2007;103(3-5):584-6.
5. Bolton-Smith C, et al. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J Bone Miner Res 2007;22(4):509-19.
6. Holvik K, et al.A randomised comparison of increase in serum 25-hydroxyvitamin D concentration after 4 weeks of daily oral intake of 10 microg cholecalciferol from multivitamin tablets or fish oil capsules in healthy young adults. Br J Nutr 2007;98(3):620-5.