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Vitamins and plant ingredients

Steady-state vitamin K2 (menaquinone-7) plasma concentrations after intake of dairy products and soft gel capsules

European Journal of Clinical Nutrition volume 70, pages 831–836 (2016)Cite this article

Subjects

Abstract

Background:

In a previous human intervention study, we observed an improved vitamin K status after 8 weeks of intake of a yogurt that was fortified with vitamin K2 (as menaquinone-7, MK-7) and enriched with vitamins C and D3, magnesium and polyunsaturated fatty acids. It was hypothesized that the added nutrients contributed to this improvement. Here we report on a study in which we compared the fasting plasma concentrations of MK-7 from (a) yogurt enriched with MK-7, vitamins D3 and C, magnesium, n-3 poly unsaturated fatty acids (n-3 PUFA) and fish oil (yogurt Kplus), (b) yogurt fortified with MK-7 only (yogurt K) and (c) soft gel capsules containing only MK-7.

Subjects/Methods:

For 42 days, healthy men and postmenopausal women between 45 and 65 years of age daily consumed either yogurt K, yogurt Kplus or capsules. Circulating MK-7, 25-hydroxy vitamin D (25(OH)D) and markers for vitamin K status (uncarboxylated osteocalcin (ucOC) and desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP)) were assessed. Plasma MK-7 was also measured during the washout period of 2 weeks. MK-7 and dp-ucMGP were measured in citrated plasma, and 25(OH)D3 and ucOC were measured in the serum.

Results:

The increase in plasma MK-7 with the yogurt Kplus product was more pronounced than the increase in MK-7 with the capsules. Circulating dp-ucMGP and ucOC were significantly lowered after consumption of the yogurt products and the MK-7 capsules, reflecting vitamin K status improvement. No significant differences in fasting plasma concentrations of various biomarkers between the yogurts were found.

Conclusions:

Dairy matrix and nutrient composition may affect MK-7 delivery and improvement of vitamin K status. Yogurt fortified with MK-7 is a suitable matrix to improve the nutritional status of the fat-soluble vitamins.

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References

  1. Booth SL, Sadowski JA, Weihrauch JL, Ferland G . Vitamin K1 (phylloquinone) content of foods: a provisional table. J Food Comp Anal 1993; 6: 109–120.

    Article  CAS  Google Scholar 

  2. Shearer MJ, Bolton-Smith C . The U.K. food data-base for vitamin K and why we need it. Food Chem 2000; 68: 213–218.

    Article  CAS  Google Scholar 

  3. Schurgers LJ, Vermeer C . Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis 2000; 30: 298–307.

    CAS  Google Scholar 

  4. Soedamah-Muthu SS, Verberne LD, Ding EL, Engberink MF, Geleijnse JM . Dairy consumption and incidence of hypertension: a dose–response meta-analysis of prospective cohort studies. Hypertension 2012; 60: 1131–1137.

    Article  CAS  Google Scholar 

  5. Crichton GE, Elias MF, Dore GA, Abhayaratna WP, Robbins MA . Relations between dairy food intake and arterial stiffness: pulse wave velocity and pulse pressure. Hypertension 2012; 59: 1044–1051.

    Article  CAS  Google Scholar 

  6. Livingstone KM, Lovegrove JA, Cockcroft JR, Elwood PC, Pickering JE, Givens DI . Does dairy food intake predict arterial stiffness and blood pressure in men? Evidence from the Caerphilly Prospective Study. Hypertension 2013; 61: 42–47.

    Article  CAS  Google Scholar 

  7. Theuwissen E, Smit E, Vermeer C . The role of vitamin K in soft-tissue calcification. Adv Nutr 2012; 3: 166–173.

    Article  CAS  Google Scholar 

  8. Price PA, Faus SA, Williamson MK . Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler Thromb Vasc Biol 1998; 18: 1400–1407.

    Article  CAS  Google Scholar 

  9. Price PA, Chan WS, Jolson DM, Williamson MK . The elastic lamellae of devitalized arteries calcify when incubated in serum: evidence for a serum calcification factor. Arterioscler Thromb Vasc Biol 2006; 26: 1079–1085.

    Article  CAS  Google Scholar 

  10. Rennenberg RJ, de Leeuw PW, Kessels AG, Schurgers LJ, Vermeer C, van Engelshoven JM et al. Calcium scores and matrix Gla protein levels: association with vitamin K status. Eur J Clin Invest 2010; 40: 344–349.

    Article  CAS  Google Scholar 

  11. Dalmeijer GW, van der Schouw YT, Magdeleyns EJ, Vermeer C, Elias SG, Velthuis BK et al. Circulating species of matrix Gla protein and the risk of vascular calcification in healthy women. Int J Cardiol 2013; 168: e168–e170.

    Article  Google Scholar 

  12. Cranenburg EC, Vermeer C, Koos R, Boumans ML, Hackeng TM, Bouwman FG et al. The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. J Vasc Res 2008; 45: 427–436.

    Article  CAS  Google Scholar 

  13. Van den Heuvel EG, van Schoor NM, Lips P, Magdeleyns EJ, Deeg DJ, Vermeer C et al. Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease. Maturitas 2014; 77: 137–141.

    Article  CAS  Google Scholar 

  14. Schurgers LJ, Barreto DV, Barreto FC, Liabeuf S, Renard C, Magdeleyns EJ et al. The circulating inactive form of matrix gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report. Clin J Am Soc Nephrol 2010; 5: 568–575.

    Article  CAS  Google Scholar 

  15. Ueland T, Dahl CP, Gullestad L, Aakhus S, Broch K, Skardal R et al. Circulating levels of non-phosphorylated undercarboxylated matrix Gla protein are associated with disease severity in patients with chronic heart failure. Clin Sci 2011; 121: 119–127.

    Article  CAS  Google Scholar 

  16. Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr 2004; 134: 3100–3105.

    Article  CAS  Google Scholar 

  17. Gast GC, de Roos NM, Sluijs I, Bots ML, Beulens JW, Geleijnse JM et al. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis 2009; 19: 504–510.

    Article  CAS  Google Scholar 

  18. Knapen MHJ, Braam LAJLM, Teunissen KJ, Zwijsen RML, Theuwissen E, Vermeer C . Yogurt drink fortified with menaquinone-7 improves vitamin K status in a healthy population. J Nutr Sci 2015; 4: e35.

    Article  Google Scholar 

  19. Kromhout D, Bosschieter EB, de Lezenne Coulander C . The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985; 312: 1205–1209.

    Article  CAS  Google Scholar 

  20. Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989; 2: 757–761.

    Article  CAS  Google Scholar 

  21. Kris-Etherton PM, Harris WS, Appel LJ . Nutrition C. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler Thromb Vasc Biol 2003; 23: e20–e30.

    CAS  PubMed  Google Scholar 

  22. Fraser JD, Price PA . Induction of matrix Gla protein synthesis during prolonged 1,25-dihydroxyvitamin D3 treatment of osteosarcoma cells. Calcif Tissue Int 1990; 46: 270–279.

    Article  CAS  Google Scholar 

  23. Staal A, van Wijnen AJ, Birkenhager JC, Pols HA, Prahl J, DeLuca H et al. Distinct conformations of vitamin D receptor/retinoid X receptor-alpha heterodimers are specified by dinucleotide differences in the vitamin D-responsive elements of the osteocalcin and osteopontin genes. Mol Endocrinol 1996; 10: 1444–1456.

    CAS  PubMed  Google Scholar 

  24. Reddy V, Sivakumar B . Magnesium-dependent vitamin-D-resistant rickets. Lancet 1974; 1: 963–965.

    Article  CAS  Google Scholar 

  25. Rude RK, Adams JS, Ryzen E, Endres DB, Niimi H, Horst RL et al. Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency. J Clin Endocrinol Metab 1985; 61: 933–940.

    Article  CAS  Google Scholar 

  26. Daly RM, Brown M, Bass S, Kukuljan S, Nowson C . Calcium- and vitamin D3-fortified milk reduces bone loss at clinically relevant skeletal sites in older men: a 2-year randomized controlled trial. J Bone Miner Res 2006; 21: 397–405.

    Article  CAS  Google Scholar 

  27. Theuwissen E, Cranenburg EC, Knapen MH, Magdeleyns EJ, Teunissen KJ, Schurgers LJ et al. Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. Br J Nutr 2012; 108: 1652–1657.

    Article  CAS  Google Scholar 

  28. Booth SL, O'Brien-Morse ME, Dallal GE, Davidson KW, Gundberg CM . Response of vitamin K status to different intakes and sources of phylloquinone-rich foods: comparison of younger and older adults. Am J Clin Nutr 1999; 70: 368–377.

    Article  CAS  Google Scholar 

  29. Booth SL, Lichtenstein AH, Dallal GE . Phylloquinone absorption from phylloquinone-fortified oil is greater than from a vegetable in younger and older men and women. J Nutr 2002; 132: 2609–2612.

    Article  CAS  Google Scholar 

  30. Sato T, Schurgers LJ, Uenishi K . Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutr J 2012; 11: 93.

    Article  CAS  Google Scholar 

  31. Bruge F, Bacchetti T, Principi F, Littarru GP, Tiano L . Olive oil supplemented with menaquinone-7 significantly affects osteocalcin carboxylation. Br J Nutr 2011; 106: 1058–1062.

    Article  CAS  Google Scholar 

  32. Garber AK, Binkley NC, Krueger DC, Suttie JW . Comparison of phylloquinone bioavailability from food sources or a supplement in human subjects. J Nutr 1999; 129: 1201–1203.

    Article  CAS  Google Scholar 

  33. Holick MF . Vitamin D deficiency. N Engl J Med 2007; 357: 266–281.

    Article  CAS  Google Scholar 

  34. Al Mheid I, Patel R, Murrow J, Morris A, Rahman A, Fike L et al. Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol 2011; 58: 186–192.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. R&D Group VitaK, Biopartner Center Maastricht, Maastricht University, Maastricht, The Netherlands

    M H J Knapen, L A J L M Braam, K J Teunissen, C M van't Hoofd & C Vermeer

  2. FrieslandCampina,, Amersfoort, The Netherlands

    R M L Zwijsen & E G H M van den Heuvel

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  1. M H J Knapen
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  2. L A J L M Braam
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  3. K J Teunissen
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  5. R M L Zwijsen
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  7. C Vermeer
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Correspondence to C Vermeer.

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This study has been sponsored by FrieslandCampina (Amersfoort, The Netherlands).

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Knapen, M., Braam, L., Teunissen, K. et al. Steady-state vitamin K2 (menaquinone-7) plasma concentrations after intake of dairy products and soft gel capsules. Eur J Clin Nutr 70, 831–836 (2016). https://doi.org/10.1038/ejcn.2016.3

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