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| Paper The Bone Health Benefits of Vitamin K |
The Bone Health Benefits of Vitamin K
Summary
• Vitamin K is a fat-solube vitamin that is a coenzyme in the ã-Carboxylation of several special proteins, including osteocalcin (OC).
• OC is the most avundant non-collegenous protein in bone. Carboxylated OC Binds strongly to the hydroxyapatite mineral crystal lattice of the bone.
• Inadequate vitamin K prevents the complete corboxylation of OC; meaning higher levels of undercarboxylated OC are present. This ‘inactive’from has a lower affinity for calcium and binds poorly to the hydroxyapatite mineral crystal lattice.
• The US Adequate Intake (AI) for adult men and women over the ae of 19 years is 120ìg and 90ìg respectively per day.
• Researh indicates that this AI maybe too low for optimal bone health.
Background
Vitamin K is a fat-soluble vitamin found predominantly in green leafy vegetables, dairy products and meat. There are two natural forms of vitamin K. K1 (phylloquinone), which is made in plants, and K2 (menaquinone), which is produced by intestinal bacteria and also found in animal foods such as meat and dairy. Vitamin K1 is the major source of vitamin K found in the diet.
Function
Vitamin K is a coenzyme in the ã-carboxylation of several proteins needed for bone metabolism and blood coagulation. In bone mineralisation, vitamin K is needed for the synthesis of two proteins, OC and matrix Gla-protein (MGP). OC is the most abundant non-collagenous protein in bone. It is produced by bone forming cells called osteoblasts and binds strongly to the mineral matrix of bone. If adequate vitamin K is present, OC can be “carboxylated” (through the synthesis of ã-carboxyglutamic acid). This allows the carboxylated OC to bind calcium causing a conformational change. This “activated” OC binds strongly to the hydroxyapatite mineral crystal lattice of the bone. In contrast, inadequate vitamin K prevents complete carboxylation, meaning that more undercarboxylated OC, which binds poorly to the hydroxypatite crystal lattice, will be formed. In addition to its presence in bone, a small amount of newly formed OC is released into the blood, which enables it to be measured easily. Serum OC is commonly used as a marker of bone turnover. A high level of undercarboxylated OC in the blood, as a percentage of total OC is indicative of low vitamin K status.
Adequate Intakes of Vtamin K
The latest US dietary recommendation for vitamin K is set as an Adequate Intake (AI) and is based on the average vitamin K intakes of healthy individuals. The AI for adult men and women over the age of 19 years is 120 ìg and 90 ìg per day respectively. However, several metabolic studies indecate that this recommendation is too low for optimal bone health. Intakes of vitamin K close to the recommended dietary intake levels are associated with high levels of circulating undercarboxylation of OC is not maximised.
Observational Studies on Vitamin K & Bone Health
This link between vitamin K and bone health is supported by studies that reported low dietary intakes of vitamin K were associated with a greater risk of hip fracture and low BMD. The Nurses Health Study was a large 10 year prospective cohort study of women aged 38-63 years. Over 72,000 women were recruited and their average baseline vitamin K1 intake was estimated at 192 ìg/day. During the follow up, Feskanich et al. (1999) it was found that hip fracure risk increased when vitamin K1 intakes dropped below 109 ìg/day. It is important to note that this intake cut off is higher than the current US recommendation of 90 ìg/day for adult women. The Framingham study looked at vitamin K1 intakes in older women. In this study the average baseline vtiamin K1 intake was estimated at 155 ìg/day. Booth et al. (2000) showed that low vtiamin K1 intakes in elderly men and women were associated with a higher risk of hip fracture. The authors concluded that vtiamin K1 has a more pronounced effect on fracture than on BMD. The risk of fracture was signifucantly lower (RR:0.35; 95% Cl: 0.13, 0.94) at vitamin K1 intakes of 254 ìg/day. Booth et al. (2003) also looked at other cohorts of younger men and women from the Framingham Study. These studies found that women in the lowest quartile of vitamin K1 intakes (70.2ìg/day) had significantly lower BMD at the hip and spine compared to those in the highest quartile (309 ìg/day); and there was a positive correlation between BMD and blood parameters of vitamin K status (serum K1 adn undercarboxylated OC) in young men. These associations suggest that poor vitamin K status has a negative impact on bone metabolism and that additional vitamin K would be advantageous.
Intervention Studies on Vitamin K & Bone Health
Several research groups haver published over 20 studies that have evaluated the effect of increasing vitamin K intake on different aspects of bone health. The trials published so far can be divuded into two groups: (1) studies looking at the effects of vitamin K on the bone marker undercarbocylated OC; and (2) studies looking at the effects of vitamin K on BMD and fracture risk.
Intervention Studies on Vitamin K & Bone Health cont.
Of note in the first group of studies are two separate trials on healthy adults by Binkley et al. (2000;2002). They showed that various doses of vitamin K1 supplementation (250-2000 ìg/day) for 2 weeks significantly increased serum phylloquinone levels in a dose responsive manner and increased the percentage of ã-carboxylated OC. In these two intervention trials vitamin K has been supplemented at levels 12-15 times higher than the current recommended intake for men and women respectively. This suggest usual deitary intakes in these groups do not provide adequate vitamin K for maximal carboxylation of OC. Another study by Schaafsma et al. (2000) randomised postmenopausal women with normal or low bone mineral densities (BMD) to receive either vitamin D3 and vitamin K1 or placebo for 1 year. Women with low BMD had a lower percentage of carboxylated OC before supplementation started compared to those with normal BMD. This difference disappeared after vitamin K1 supplementation. This study also showed that as little as 80 ìg of vitamin K1 daily, on topof usual detary intake, can bringundercarboxylated OC levels in postmenopausal women back down to levels seen before menopause.
In the second group of studies the intervention trials measured the direct effects of vitamin K supplementation on age-related bone loss, incidence of new and recurring osteoporotic fractures; BMD; and BMC. The best examples of which are the Maastricht Osteostudy and the DundeeBones and Vitamins Intervention Study (D-BAVIS). The Maastricht Osteostudy was a 3-year randomised, double-blinded placebo controlled suppplementation trial. Subjects were given either a placebo, or a supplement containing 8 ìg vitamin D3, 500 mg Calcium, 150 mg Magnesium and 10 mg Zinc, with or without vitamin K1 (1 mg). The group receiving the supplement containing vitamin K1 lost significantly less bone at the femoral neck (hip) than the groups not taking vitamin K1. In fact, the rate of bone loss decreased by 35-40% as compared to placebo. It has been concluded that if the observed effects of vitamin K continue over decades, life long supplementation could delay fractures by up to 10 years. The D-BAVIS was a 2-year placebo controlled trial where the impact of three different therapies on BMD and BMC at the hip and wrist were compared. Subjects were randomised to receive either a placebo; or 200 ìg vitamin K1; or 10 ìg vitamin D3 and 1 g calcium; or a combination of the two interventions. The main fingdings of the study included: baseline vitamin K status was sub optimal; supplementation with vitamin K significantly increased serum vitamin K; and there was a significantly increase in BMC and BMD at the ultra-distal radius (wrist) in the combination intervention grioup. The authors concluded that the results from the combined supplementation suggested a synergy between vitamin K and vitamin D.
In another study by Kruger et al. (2005) vitamin K1 fortified milk powder was used as the intervention in a 16 week randomised controlled bonemarker trial. Women beween 20 and 35 years with a body mass index (BMI) between 20 and 30 were recruited and were randomised into three goups (n = 26 per group). The first group received no supplementation; the second received two sachets (50g) of high calcium skim milk (HCM) powder; and the third group received two sachets (50 g) of HCM powder, plus vitamin K1 per day. The milk powder supplements were identical (1000 mg Calcium, 5 ìg Vitamin D3, 3 mg Zinc, 495 ìg Vitamin A and 105 mg Magnesium per day), except for the vitamin K1 content (80 ìg per day). Replicate blood samples (within three days from each other) were collected between 8 and 10 a.m (overnight fast) for the baseline measurements, as well as, at weeks 2, 12 and 16 of the intervention. A full range of biochemical, hormone and bonemarker assays were completed. There were no significant differences between the groups at baseline. However, over the week intervention erum vitamin K increased and serum undercarboxylated OC decreased significantly in the HCM plus vitamin K1 supplement group. It is reasonable to conclude that these biochemical changes would be indicative of significant changes in BMD in the long-term.
Reference
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17. Kruger MC, et al. The effect of high calcium fortified milk supplementation on biochemical markers of bone resorption and formation in premenopausal women. Pending publication at the International Osteoporosis Symposium. Xi’an, China. 23-27 May 2005 |
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