Skip to main content

Advertisement

SpringerLink
Log in

High dephospho-uncarboxylated matrix Gla protein concentrations, a plasma biomarker of vitamin K, in relation to frailty: the Longitudinal Aging Study Amsterdam

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

No previous study has evaluated the relationship between vitamin K and frailty. Thus, we assessed the relationship between vitamin K status and frailty over 13 years in the Longitudinal Aging Study Amsterdam (LASA).

Methods

Prospective cohort study with 644 community-dwelling adults ≥ 55 years from the LASA cohort. In 2002–2003, plasma desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) was measured as marker of vitamin K status through a sandwich ELISA. Frailty was measured at baseline and in four follow-up examinations with the LASA Frailty Index (LASA-FI), which was used as both a continuous and a dichotomous measure (FI ≥ 0.25), as indicator of the degree of frailty and frailty risk, respectively. Statistical analyses were performed with multivariable generalized estimating equations using the lowest dp-ucMGP tertile, reflecting a high vitamin K status, as reference.

Results

The mean (SD) age was 59.9 (2.9) years, and 54% were female. Compared with the lowest tertile, the medium and highest dp-ucMGP tertile were associated with a higher degree of frailty [1.40, 95% confidence interval (0.01–2.81) and 1.62, (0.18–3.06), respectively. P trend: 0.03]. Additionally, the medium and highest dp-ucMGP tertile had a higher odds ratio of frailty [1.75 (1.11–2.77) and 1.63 (1.04–2.57), respectively]. The degree of frailty increased over time, but the differences by dp-ucMGP tertiles existed since baseline and remained stable during follow-up.

Conclusions

Baseline plasma low vitamin K status was associated with a greater degree of frailty and frailty risk in this cohort of older adults, which highlights the importance of ensuring an optimal nutritional status of this vitamin to prevent frailty in later life.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. van Ballegooijen AJ, Beulens JW (2017) The role of vitamin K status in cardiovascular health: evidence from observational and clinical studies. Curr Nutr Rep 6:197–205

    PubMed  PubMed Central  Google Scholar 

  2. Schurgers LJ, Geleijnse JM, Grobbee DE, Pols HAP, Hofman A, Witteman JCM (1999) Vermeer C (1996) nutritional intake of vitamins K1 (phylloquinone) and k2 (menaquinone) in the Netherlands. J Nutr Environ Med 9(2):115–122

    CAS  Google Scholar 

  3. Gijsbers BL, Jie KS, Vermeer C (1996) Effect of food composition on vitamin K absorption in human volunteers. Br J Nutr 76:223–229

    CAS  PubMed  Google Scholar 

  4. Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G (1997) Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386:78–81

    CAS  PubMed  Google Scholar 

  5. Zoch ML, Clemens TL, Riddle RC (2016) New insights into the biology of osteocalcin. Bone 82:42–49

    CAS  PubMed  Google Scholar 

  6. Misra D, Booth SL, Tolstykh I, Felson DT, Nevitt MC, Lewis CE, Torner J, Neogi T (2013) Vitamin K deficiency is associated with incident knee osteoarthritis. Am J Med 126:243–248

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Ohsaki Y, Shirakawa H, Hiwatashi K, Furukawa Y, Mizutani T, Komai M (2006) Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat. Biosci Biotechnol Biochem 70:926–932

    CAS  PubMed  Google Scholar 

  8. van Ballegooijen AJ, van Putten SR, Visser M, Beulens JW, Hoogendijk EO (2018) Vitamin K status and physical decline in older adults—the longitudinal aging study Amsterdam. Maturitas 113:73–79

    PubMed  Google Scholar 

  9. Clegg A, Young J, Lliffe S, Rikkert MO, Rockwood K (2013) Frailty in elderly people. Lancet 381:752–762

    PubMed  Google Scholar 

  10. Yannakoulia M, Ntanasi E, Anastasiou CA, Scarmeas N (2017) Frailty and nutrition: from epidemiological and clinical evidence to potential mechanisms. Metabolism 68:64–76

    CAS  PubMed  Google Scholar 

  11. Leon-Muñoz LM, Guallar-Castillon P, Lopez-Garcia E, Rodriguez-Artalejo F (2014) Mediterranean diet and risk of frailty in community-dwelling older adults. J Am Med Dir Assoc 15:899–903

    PubMed  Google Scholar 

  12. Bollwein J, Diekmann R, Kaiser MJ (2013) Diet quality is related to frailty in community-dwelling older adults. J Gerontol A Biol Sci Med Sci 68:483–489

    PubMed  Google Scholar 

  13. Huisman M, Poppelaars J, van der Horst M, Beekman AT, Brug J, van Tilburg TG, Deeg DJ (2011) Cohort profile: the Longitudinal Aging Study Amsterdam. Int J Epidemiol 40:868–876

    PubMed  Google Scholar 

  14. Hoogendijk EO, Deeg DJ, Poppelaars J, van der Horst M, Broese van Groenou MI, Comijs HC, Pasman HR, van Schoor NM, Suanet B, Thomése F et al (2016) The Longitudinal Aging Study Amsterdam: cohort update 2016 and major findings. Eur J Epidemiol 31:927–945

    PubMed  PubMed Central  Google Scholar 

  15. Cranenburg EC, Koos R, Schurgers LJ, Magdeleyns EJ, Schoonbrood TH, Landewé RB, Brandenburg VM, Bekers O, Vermeer C (2010) Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species. Thromb Haemost 104:811–822

    CAS  PubMed  Google Scholar 

  16. Rockwood K, Mitnitski A (2007) Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci 62:722–727

    PubMed  Google Scholar 

  17. Dent E, Kowal P, Hoogendijk EO (2016) Frailty measurement in research and clinical practice: a review. Eur J Intern Med 31:3–10

    PubMed  Google Scholar 

  18. Hoogendijk EO, Theou O, Rockwood K, Onwuteaka-Philipsen BD, Deeg DJH, Huisman M (2017) Development and validation of a frailty index in the Longitudinal Aging Study Amsterdam. Aging Clin Exp Res 29:927–933

    PubMed  Google Scholar 

  19. Rockwood K, Andrew M, Mitnitski A (2007) A comparison of two approaches to measuring frailty in elderly people. J Gerontol A Biol Sci Med Sci 67:738–743

    Google Scholar 

  20. Aartsen MJ, Comijs HC (2012) Alcohol consumption and depressive symptoms among older adults: results of the Longitudinal Aging Study Amsterdam. Tijdschr Gerontol Geriatr 43:127–136

    CAS  PubMed  Google Scholar 

  21. Wang YG, Fu L (2017) Selection of working correlation structure in generalized estimating equations. Stat Med 36:2206–2219

    PubMed  Google Scholar 

  22. Shea MK, Kritchevsky SB, Hsu FC, Nevitt M, Booth SL, Kwoh CK, McAlindon TE, Vermeer C, Drummen N, Harris TB et al (2015) The association between vitamin K status and knee osteoarthritis features in older adults: the Health, Aging and Body Composition Study. Osteoarthritis Cartilage 23:370–378

    CAS  PubMed  Google Scholar 

  23. Riphagen IJ, Keyzer CA, Drummen NEA, de Borst MH, Beulens JWJ, Gansevoort RT, Geleijnse JM, Muskiet FAJ, Navis G, Visser ST et al (2017) Prevalence and effects of functional vitamin K insufficiency: the PREVEND Study. Nutrients 9:E1334

    PubMed  Google Scholar 

  24. Ueland T, Dahl CP, Gullestad L, Aakhus S, Broch K, Skardal R, Vermeer C, Aukrust P, Schurgers LJ (2011) Circulating levels of non-phosphorylated under carboxylated matrix Gla protein are associated with disease severity in patients with chronic heart failure. Clin Sci (Lond) 121:119–127

    CAS  Google Scholar 

  25. Liu YP, Gu YM, Thijs L, Knapen MH, Salvi E, Citterio L, Petit T, Carpoini SD, Zhang Z, Jacobs L et al (2015) Inactive matrix Gla protein is causally related to adverse health outcomes: a Mendelian randomization study in a Flemish population. Hypertension 65:463–470

    CAS  PubMed  Google Scholar 

  26. Idoate F, Cadore EL, Casas-Herrero A, Zambom-Ferraresi F, Martínez-Velilla N, Rodriguez-Mañas L, Azcárate PM, Bottaro M, Ramírez-Vélez R, Izquierdo M (2017) Noncoronary vascular calcification, bone mineral density, and muscle mass in institutionalized frail nonagenarians. Rejuvenation Res 20:298–308

    CAS  PubMed  Google Scholar 

  27. Kleipool EE, Hoogendijk EO, Trappenburg MC, Handoko ML, Huisman M, Peters MJ, Muller M (2018) Frailty in older adults with cardiovascular disease: cause, effect or both. Aging Dis 9:489–497

    PubMed  PubMed Central  Google Scholar 

  28. Iwamoto J, Takeda T, Sato Y (2004) Effects of vitamin K2 on osteoporosis. Curr Pharm Des 10:2557–2576

    CAS  PubMed  Google Scholar 

  29. Oka H, Akune T, Muraki S, En-yo Y, Yoshida M, Saika A, Sasaki S, Nakamura K, Kawaguchi H, Yoshimura N (2009) Association of low dietary vitamin K intake with radiographic knee osteoarthritis in the Japanese elderly population: dietary survey in a population-based cohort of the ROAD study. J Orthop Sci 14:687–692

    CAS  PubMed  Google Scholar 

  30. Castell MV, van der Pas S, Otero A, Siviero P, Dennison E, Denkinger M, Pedersen N, Sanchez-Martinez M, Queipo R, van Schoor N et al (2015) Osteoarthritis and frailty in elderly individuals across six European countries: results from the European Project on OSteoArthritis (EPOSA). BMC Musculoskelet Disord 16:359

    PubMed  PubMed Central  Google Scholar 

  31. Landi F, Onder G, Russo A, Liperoti R, Tosato M, Martone AM, Capoluongo E, Bernabei R (2014) Calf circumference, frailty and physical performance among older adults living in the community. Clin Nutr 33:539–544

    PubMed  Google Scholar 

  32. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G et al (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56:M146–M156

    CAS  PubMed  Google Scholar 

  33. Walston J, McBurnie MA, Newman A, Tracy RP, Kop WJ, Hirsch CH, Gottdiener J, Fried LP (2002) Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med 162:2333–2341

    PubMed  Google Scholar 

  34. Hubbard RE, O’Mahony MS, Savva GM, Calver BL, Woodhouse KW (2009) Inflammation and frailty measures in older people. J Cell Mol Med 13:3103–3109

    PubMed  PubMed Central  Google Scholar 

  35. Barzilay JI, Blaum C, Moore T, Xue QL, Hirsch CH, Walston JD, Fried LP (2007) Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study. Arch Intern Med 167:635–641

    PubMed  Google Scholar 

  36. Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, Newman AB, Nevitt M, Harris TB (2002) Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci 57:M326–M332

    PubMed  Google Scholar 

  37. Mk Shea, Cushman M, Booth SL, Burke GL, Chen H, Kritchevsky SB (2014) Associations between vitamin K status and haemostatic and inflammatory biomarkers in community-dwelling adults. The Multi-ethnic Study of Atherosclerosis. Thromb Haemost 112:438–444

    Google Scholar 

  38. Cocchetto DM, Miller DB, Miller LL, Bjornsson TD (1985) Behavioral perturbations in the vitamin k-deficient rat. Physiol Behav 34:727–734

    CAS  PubMed  Google Scholar 

  39. Chouet J, Ferland G, Féart C, Rolland Y, Presse N, Boucher K, Barberger-Gateau P, Beauchet O, Annweiler C (2015) Dietary vitamin K intake is associated with cognition and behaviour among geriatric patients: the CLIP Study. Nutrients 7:6739–6750

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Soutif-Veillon A, Ferland G, Rolland Y, Presse N, Boucher K, Féart C, Annweiler C (2016) Increased dietary vitamin K intake is associated with less severe subjective memory complaint among older adults. Maturitas 93:131–136

    CAS  PubMed  Google Scholar 

  41. Baugreet S, Hamill RM, Kerry JP, McCarthy SN (2017) Mitigating nutrition and health deficiencies in older adults: a role for food innovation? J Food Sci 82:848–855

    CAS  PubMed  Google Scholar 

  42. Lorenzo-López L, Maseda A, de Labra C, Regueiro-Folgueira L, Rodríguez-Villamil JL, Millán-Calenti JC (2017) Nutritional determinants of frailty in older adults: a systematic review. BMC Geriatr 17:108

    PubMed  PubMed Central  Google Scholar 

  43. Shea MK, Booth SL (2016) Concepts and controversies in evaluating vitamin K status in population-based studies. Nutrients 8:8

    PubMed Central  Google Scholar 

Download references

Funding

Emiel O. Hoogendijk is supported by an NWO/ZonMw Veni fellowship [Grant number 91618067]. van Ballegooijen is supported by a personal postdoctoral grant from the Kidney Foundation (16OKG02). This work was supported by FIS grants 13/0288, 16/609 and 16/1512 (Instituto de Salud Carlos III, State Secretary of R+D+I and FEDER/FSE) and CIBERESP. The Longitudinal Aging Study Amsterdam is largely supported by a grant from the Netherlands Ministry of Health Welfare and Sports, Directorate of Long-Term Care.

Author information

Authors and Affiliations

  1. Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid, IdiPaz (Instituto de Investigación Sanitaria Hospital Universitario La Paz), Madrid, Spain

    Marcos D. Machado-Fragua, Ellen A. Struijk, Fernando Rodriguez-Artalejo & Esther Lopez-Garcia

  2. CIBERESP (CIBER of Epidemiology and Public Health), Madrid, Spain

    Marcos D. Machado-Fragua, Ellen A. Struijk, Fernando Rodriguez-Artalejo & Esther Lopez-Garcia

  3. Department of Epidemiology and Biostatistics, and the Amsterdam Public Health Research Institute, Amsterdam UMC—Location VU University Medical Center, Amsterdam, The Netherlands

    Emiel O. Hoogendijk, Joline W. Beulens & Adriana J. van Ballegooijen

  4. Department of Nephrology, and Amsterdam Cardiovascular Science, Amsterdam UMC—Location VU University Medical Center, Amsterdam, The Netherlands

    Adriana J. van Ballegooijen

Authors
  1. Marcos D. Machado-Fragua
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emiel O. Hoogendijk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ellen A. Struijk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fernando Rodriguez-Artalejo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Esther Lopez-Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joline W. Beulens
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Adriana J. van Ballegooijen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MMF and AJB designed and conducted research, analyzed data and wrote the paper; MMF and AJB had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analyses. All authors reviewed the manuscript for important intellectual content and approved the final version.

Corresponding author

Correspondence to Marcos D. Machado-Fragua.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 13 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Machado-Fragua, M.D., Hoogendijk, E.O., Struijk, E.A. et al. High dephospho-uncarboxylated matrix Gla protein concentrations, a plasma biomarker of vitamin K, in relation to frailty: the Longitudinal Aging Study Amsterdam. Eur J Nutr 59, 1243–1251 (2020). https://doi.org/10.1007/s00394-019-01984-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-019-01984-9

Keywords

Search

Navigation