Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


Reproducibility and relative validity of a food frequency questionnaire to estimate intake of dietary phylloquinone and menaquinones



This study aims to investigate the reproducibility and relative validity of the Dutch food frequency questionnaire (FFQ), to estimate intake of dietary phylloquinone and menaquinones compared with 24-h dietary recalls (24HDRs) and plasma markers of vitamin K status.


In a cross-sectional study among 63 men and 58 women, the FFQ was completed three times over a 1-year period and the reproducibility was calculated over these measurements. Twelve-monthly 24HDR were collected to estimate relative validity. In addition, the relative validity of the FFQ, compared with plasma phylloquinone and desphospho-uncarboxylated matrix Gla protein (dpucMGP), was assessed cross-sectionally among 507 postmenopausal women.


Intraclass correlations showed a good reproducibility, with correlations ranging from 0.65 to 0.83. The relative validity for phylloquinone intake compared with 24HDR was lower for women (rs=0.28) than men (rs=0.40). The relative validity, compared with 24HDR, for intake of short-chain menaquinones were ranging between 0.30 and 0.34. Long-chain menaquinones showed good relative validity (rs=0.60–0.69). Plasma phylloquinone concentrations were weakly correlated with phylloquinone intake (rs=0.16 (0.07-0.24). Plasma dpucMGP was negatively but weakly correlated with phylloquinone intake (rs=−0.09 (−0.18; −0.01)) and long-chain menaquinones (rs=−0.13 (−0.21; −0.04)), but not with short-chain menaquinones (rs=−0.04 (−0.13; 0.05)).


The FFQ is reproducible to rank subjects for phylloquinone and menaquinone intake.The relative validity of our FFQ, compared with 24HDR, to estimate intake of phylloquinone and short-chain menaquinones was low, but the relative validity for long-chain menaquinones was good. The relative validity of our FFQ, compared with plasma phylloquinone and dpucMGP, was relatively low for both phylloquinone and menaquinone intake.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Schurgers LJ, Vermeer C . Determination of phylloquinone and menaquinones in food. Haemostasis 2001; 30: 298–307.

    Google Scholar 

  2. 2

    Shearer MJ, Newman P . Metabolism and cell biology of vitamin K. Thromb Haemost 2008; 100: 530–547.

    CAS  Article  Google Scholar 

  3. 3

    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.

    CAS  Article  Google Scholar 

  4. 4

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

    CAS  Article  Google Scholar 

  5. 5

    Beulens JWJ, Bots ML, Atsma F, Bartelink M-LEL, Prokop M, Geleijnse JM et al. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis 2009; 203: 489–493.

    CAS  Article  Google Scholar 

  6. 6

    Beulens JWJ, Van Der ADL, Grobbee DE, Sluijs I, Spijkerman AMW, Van Der Schouw YT . Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes. Diabetes Care 2010; 33: 1699–1705.

    CAS  Article  Google Scholar 

  7. 7

    Nimptsch K, Rohrmann S, Linseisen J . Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am J Clin Nutr 2008; 87: 985–992.

    CAS  Article  Google Scholar 

  8. 8

    Juanola-Falgarona M, Salas-Salvadó J, Estruch R, Portillo MP, Casas R, Miranda J et al. Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk. Cardiovasc Diabetol 2013; 12: 7.

    CAS  Article  Google Scholar 

  9. 9

    Presse N, Shatenstein B, Kergoat MJ, Ferland G . Validation of a semi-quantitative food frequency questionnaire measuring dietary vitamin K intake in elderly people. J Am Diet Assoc 2009; 109: 1251–1255.

    CAS  Article  Google Scholar 

  10. 10

    Cantin J, Latour E, Ferland-Verry R, Morales Salgado S, Lambert J, Faraj M et al. Validity and reproducibility of a food frequency questionnaire focused on the Mediterranean diet for the Quebec population. Nutr Metab Cardiovasc Dis 2016; 26: 154–161.

    CAS  Article  Google Scholar 

  11. 11

    Erkkilä AT, Järvinen R, Karvonen H, Keronen L, Tuppurainen MT . Validation of a semi-quantitative FFQ using food records as a reference in older women in the Kuopio Fracture Prevention Study (OSTPRE-FPS). Public Health Nutr 2012; 15: 635–639.

    Article  Google Scholar 

  12. 12

    Perreault M, Xu VYY, Hamilton S, Wright D, Foster W, Atkinson SA . Validation of a food frequency questionnaire for bone nutrients in pregnant women. Can J Diet Pract Res 2016; 77: 133–139.

    Article  Google Scholar 

  13. 13

    Kim E, Kim M, Sohn C . Validity and reliability of a self-administered food frequency questionnaire to assess vitamin K intake in Korean adults. Clin Nutr Res 2016; 5: 153–160.

    Article  Google Scholar 

  14. 14

    Booth SL, Tucker KL, McKeown NM, Davidson KW, Dallal GE, Sadowski JA . Relationships between dietary intakes and fasting plasma concentrations of fat-soluble vitamins in humans. J Nutr 1997; 127: 587–592.

    CAS  Article  Google Scholar 

  15. 15

    Freisling H, Elmadfa I, Schuh W, Wagner KH . Development and validation of a food frequency index using nutritional biomarkers in a sample of middle-aged and older adults. J Hum Nutr Diet 2009; 22: 29–39.

    CAS  Article  Google Scholar 

  16. 16

    Presse N, Gaudreau P, Greenwood CE, Kergoat M-J, Morais JA, Payette H et al. A single measurement of serum phylloquinone is an adequate indicator of long-term phylloquinone exposure in healthy older adults. J Nutr 2012; 142: 1910–1916.

    CAS  Article  Google Scholar 

  17. 17

    Thane CW, Bates CJ, Shearer MJ, Unadkat N, Harrington DJ, Paul AA et al. Plasma phylloquinone (vitamin K1) concentration and its relationship to intake in a national sample of British elderly people. Br J Nutr 2002; 87: 615–622.

    CAS  Article  Google Scholar 

  18. 18

    Thane CW, Wang LY, Coward WA . Plasma phylloquinone (vitamin K1) concentration and its relationship to intake in British adults aged 19-64 years. Br J Nutr 2006; 96: 1116–1124.

    CAS  Article  Google Scholar 

  19. 19

    Shea MK, Dallal GE, Dawson-Hughes B, Ordovas JM, O’Donnell CJ, Gundberg CM et al. Vitamin K, circulating cytokines, and bone mineral density in older men and women. Am J Clin Nutr 2008; 88: 356–363.

    CAS  Article  Google Scholar 

  20. 20

    Kyla Shea M, Booth SL . Concepts and controversies in evaluating vitamin K status in population-based studies. Nutrients 2016; 8: 1–25.

    Google Scholar 

  21. 21

    Vissers LET, Dalmeijer GW, Boer JMA, Monique Verschuren WM, van der Schouw YT, Beulens JWJ . Intake of dietary phylloquinone and menaquinones and risk of stroke. J Am Heart Assoc 2013; 2: e000455.

    Article  Google Scholar 

  22. 22

    Atsma F, Bartelink M-LEL, Grobbee DE, Rutten A, Bots ML, Prokop M et al. Reproductive factors, metabolic factors, and coronary artery calcification in older women. Menopause 2008; 15: 899–904.

    Article  Google Scholar 

  23. 23

    Ocké MC, Bueno-de-Mesquita HB, Goddijn HE, Jansen A, Pols MA, van Staveren WA et al. The Dutch EPIC food frequency questionnaire. I. Description of the questionnaire, and relative validity and reproducibility for food groups. Int J Epidemiol 1997; 26 (Suppl 1), S37–S48.

    Article  Google Scholar 

  24. 24

    Ocké MC, Bueno-de-Mesquita HB, Pols MA, Smit HA, van Staveren WA, Kromhout D . The Dutch EPIC food frequency questionnaire. II. Relative validity and reproducibility for nutrients. Int J Epidemiol 1997; 26 (Suppl 1), S49–S58.

    Article  Google Scholar 

  25. 25

    Beulens JWJ, Monninkhof EM, Verschuren WMM, van der Schouw YT, Smit J, Ocke MC et al. Cohort profile: the EPIC-NL study. Int J Epidemiol 2010; 39: 1170–1178.

    Article  Google Scholar 

  26. 26

    Stichting NEVO. Nederlands Voedingsstoffen bestand.

  27. 27

    Rødbotten R, Gundersen T, Vermeer C, Kirkhus B . Vitamin K2 in different bovine muscles and breeds. Meat Sci 2014; 97: 49–53.

    Article  Google Scholar 

  28. 28

    US Department of Agriculture, Agricultural Research Service USDA National Nutrient Database for Standard Reference, Release 24 2011.

  29. 29

    US Department of Agriculture ARS USDA National Nutrient Database for Standard Reference, Release 26. Nutrient Data Laboratory Home Page. United States Dep. Agric 2013:

  30. 30

    Davidson KW, Sadowski JA . Determination of vitamin K compounds in plasma or serum by high-performance liquid chromatography using postcolumn chemical reduction and fluorimetric detection. Methods Enzymol 1997; 282: 408–421.

    CAS  Article  Google Scholar 

  31. 31

    Dalmeijer GW, van der Schouw YT, Magdeleyns E, Ahmed N, Vermeer C, Beulens JWJ . The effect of menaquinone-7 supplementation on circulating species of matrix Gla protein. Atherosclerosis 2012; 225: 397–402.

    CAS  Article  Google Scholar 

  32. 32

    Shea MK, O’Donnell CJ, Vermeer C, Magdeleyns EJP, Crosier MD, Gundberg CM et al. Circulating uncarboxylated matrix Gla protein is associated with vitamin K nutritional status, but not coronary artery calcium, in older adults. J Nutr 2011; 141: 1529–1534.

    CAS  Article  Google Scholar 

  33. 33

    Willett WC, Howe GR, Kushi LH . Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 1997; 65: 1220S–1228S. Discussion 1229S–1231S.

    CAS  Article  Google Scholar 

  34. 34

    McKeown NM, Jacques PF, Gundberg CM, Peterson JW, Tucker KL, Kiel DP et al. Dietary and nondietary determinants of vitamin K biochemical measures in men and women. J Nutr 2002; 132: 1329–1334.

    CAS  Article  Google Scholar 

  35. 35

    Goldbohm RA, van den Brandt PA, Brants HA, van’t Veer P, Al M, Sturmans F et al. Validation of a dietary questionnaire used in a large-scale prospective cohort study on diet and cancer. Eur J Clin Nutr 1994; 48: 253–265.

    CAS  PubMed  Google Scholar 

  36. 36

    Macedo-Ojeda G, Vizmanos-Lamotte B, Márquez-Sandoval YF, Rodríguez-Rocha NP, López-Uriarte PJ, Fernández-Ballart JD . Validation of a semi-quantitative food frequency questionnaire to assess food groups and nutrient intake. Nutr Hosp 28: 2212–2220.

  37. 37

    Kesse-Guyot E, Castetbon K, Touvier M, Hercberg S, Galan P . Relative validity and reproducibility of a food frequency questionnaire designed for French adults. Ann Nutr Metab 2010; 57: 153–162.

    CAS  Article  Google Scholar 

  38. 38

    Field AE, Peterson KE, Gortmaker SL, Cheung L, Rockett H, Fox MK et al. Reproducibility and validity of a food frequency questionnaire among fourth to seventh grade inner-city school children: implications of age and day-to-day variation in dietary intake. Public Health Nutr 1999; 2: 293–300.

    CAS  Article  Google Scholar 

  39. 39

    Caluwé R, Vandecasteele S, Van Vlem B, Vermeer C, De Vriese AS . Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding study. Nephrol Dial Transplant 2013; 29: 1385–1390.

    Article  Google Scholar 

  40. 40

    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. 1–6.

    CAS  Article  Google Scholar 

  41. 41

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

    CAS  Article  Google Scholar 

  42. 42

    Booth SL . Vitamin K: food composition and dietary intakes. Food Nutr Res 2012; 56.

  43. 43

    Lamon-Fava S, Sadowski JA, Davidson KW, O’Brien ME, McNamara JR, Schaefer EJ . Plasma lipoproteins as carriers of phylloquinone (vitamin K1) in humans. Am J Clin Nutr 1998; 67: 1226–1231.

    CAS  Article  Google Scholar 

Download references


The EPIC-NL study was funded by 'Europe against Cancer' program of the European Commission, the Dutch Ministry of Health, Welfare and Sport, the Dutch Cancer Society, ZonMW, the Netherlands Organization for Health Research and Development and the World Cancer Research Fund (WCRF). JWJB and SRZ are supported by the Senior Dr Dekker grant (2013T120) from the Dutch Heart Foundation. SLB was supported by the USDA, Agricultural Research Service under Cooperative Agreement No. 58-1950-7-707. Any opinions, findings, conclusions or recommendations expressed in this publication are those of the authors, and do not necessarily reflect the view of the USDA. AIPE and EJMF were supported by Top Institute Food and Nutrition (TIFN), a public-private partnership on pre-competitive research in food and nutrition. TIFN had no role in the study design, data acquisition and analysis or drafting of the manuscript, or decision to publish.

Author contributions

JWJB and MCO designed the study; SRZ, AIPE, GWD, SLB, CV, JJMMD, MCO, EJMF, YTS and JWJB acquired data; SRZ analyzed the data; SRZ and JWJB interpreted data; SRZ and JWJB wrote the manuscript; SRZ, AIPE, GWD, SLB, CV, JJMMD, MCO, EJMF, YTS and JWJB reviewed/edited the manuscript.

Author information



Corresponding author

Correspondence to S R Zwakenberg.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on European Journal of Clinical Nutrition website

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zwakenberg, S., Engelen, A., Dalmeijer, G. et al. Reproducibility and relative validity of a food frequency questionnaire to estimate intake of dietary phylloquinone and menaquinones. Eur J Clin Nutr 71, 1423–1428 (2017).

Download citation


Quick links