Clinical Study Vitamin K in Children

Developing and growing bones are characterized by high metabolic activity and osteocalcin production. This implies that requirement for a high fraction of activated osteocalcin is present, thus also for vitamin K to support the activation process. Knowing that dietary intake of vitamin K among children has gradually decreased rather than increased during recent years, it is interesting to check the vitamin K status in growing children.

1. Serum percentage undercarboxylated osteocalcin, a sensitive measure of vitamin k status, and its relationship to bone health indices in Danish girls. (OConnor, British Journal of Nutrition 2007) Objective : Investigate the relationship between bone status indices (BMC & biochemical marker bone turn over) and % ucOC n : 223 healthy + , 11 12 years old, Denmark area Cross-sectional data study (association study 1 year Vit. D trial on bone health. www.optiford.org) Result : 1. % ucOC was not associated with marker Bone resorption & total osteocalcin. 2. % ucOC was inversely correlated with serum 25 (OH)O. 3. % ucOC was negatively associated with BMC total body & lumbar spine. 4. Better vitamin K status was associated with increase BMC but not bone turn over.

2. The effect of Menaquinone-7 (Vit K2) Objective : study the effect of 45 g menaquinone-7 on the circulating levels of undercarboxylated osteocalcin (ucOC) and carboxylated osteocalcin (Coc) in healthy prepubertal children. n : 55 healthy children, 6 10 years, Netherland (Placebo : 27, treatment : 28) t : 8 weeks Daily dosage : 45 g MK7 in capsule Measurement : serum ucOC serum Coc serum MK7 Bone marker (Bone alkalin phosphatase formation) (N-telopeptide coX Coagulation parameter for Bone resorption) for Bone

endogenous thrombin potential & maximal peak

Result : Treatment group : concentration ucOC , Ratio ucOC/Coc (UCR) improved Compare to placebo group : concentration ucOC, COC, UCR & serum MK7 not significantly change in 8 weeks In healthy prepubertal children, Modest supplementation with MK increases circulating MK7 & COC.

3. Vitamin K status is associated with childhood bone mineral content. (Van Summeren, Van Coeverden, Schurgers, Braam, Noirt, British Journal of Nutrition (2008)). Objective : to determine biochemical indicator vitamin K status are related to Bone Mineral Content (BMC) & markers of Bone metabolism in prepubertal children. n : 307 healthy prepubertal children (8 14 years, 11.2 years) at the end : n : 281 healthy children t : 2 years, place in Amsterdam Measurement : 1. At baseline : - BMC Total Body - BMC Lumbar spine - BMC femoral neck - UCR - markers of Bone metabolism - sex steroid (Oestradiol & Testosteron) - Vitamin D status - Insulin like growth Hormone

2. At Follow Up (After 2 years) : BMC Total Body BMC Femoral Nect BMC Lumbar spine UCR Result : 1. Large variation on UCR were found at baseline and follow up stage, indicating a substantial interidividual difference in vitamin K status. 2. Improvement Vit. K status over 2 years (n : 281) was associated with increase in Total Body BMC (p<0.001) 3. A better Vit. K status (associated with UCR) was associated with more pronounced increase in bone mass healthy prepubertal children.

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Vitamin K, Bone turn over, and Bone mass in girl. (Kalkwarf, khoury, Bean, Elliot, The American journal of clinical nutrition (2004)) Objective : to determine whether Vit. K intake and biochemical indicators of vitamin K status are related Bone mineral content (BMC) and markers of Bone formation and Bone resorption in girls. n : 245 healthy girls (3 16 years) t : 4 years Measurement : plasma phylloquinone concentration % undercarboxylated osteocalcin Nix (crosslink n tetopeptide type 1 colagen) Osteocalcin Alkaline phosphate BMC Total Body BMC Lumbar spine BMC Hip Dietary phylloquinone intake Result : 1. Intake phylloquinone ( 45 g/day) was not consistently associated with bone turn over markers or BMC. 2. Better Vit. K status (plasma phylloquinone concentration & % ucOC) was associated with lower bone resorption & formation. 3. Plasma phylloquinone was inversely associated with NIx & osteocalcin (p<0.001). 4. % ucOC positively associated with NIx and alkaline phosphate. 5. Indicators of Vit. K status (plasma phylloquinone concentration % ucOC) were not consistently associated with current BMC or gain in BMC over 4 years. 6. Better vitamin K status was associated with decreased bone turn over in healthy girls consuming a typical us died.