Abstract
Introduction
Vitamin K is a fat-soluble vitamin discovered as an essential factor for blood coagulation. It is suggested that vitamin K can benefit several aging-related diseases, including osteoporosis, osteoarthritis, and dementia. We previously reported the cross-sectional association of vitamin K insufficiency with frailty in community-dwelling older adults.
Materials and methods
In October 2020, a health examination of community-dwelling older adults (The Otassha Study) was performed, including frailty evaluation and blood tests. We used a ucOC and OC ratio (ucOC/OC) to indicate vitamin K insufficiency. One year later, we conducted a follow-up evaluation of frailty on 518 people who were not frail at baseline. The serum ucOC/OC at the baseline examination was divided into quartiles (Q1, Q2, Q3, and Q4). Odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariate binary logistic regression for each quartile of ucOC/OC to determine the risk of incident frailty in the follow-up study, with the lowest quartile (Q1) as the reference.
Results
Among the 518 older adults who were not frail at baseline, 66 people (12.7%) became frail in the follow-up study. In the multivariate binary logistic regression analysis, setting the lowest quartile of ucOC/OC (Q1) as a reference, the OR of the incident frailty in the highest quartile (Q4) was 2.53 (95% CI 1.07, 4.92) which was significantly different from Q1.
Conclusion
The findings of this longitudinal study suggest that vitamin K insufficiency has nutritional importance in predicting the future incidence of frailty in the Japanese older adult population.
This is a preview of subscription content, access via your institution.
References
Suttie JW, Booth SL (2011) Vitamin K. Adv Nutr 2:440–441. https://doi.org/10.3945/an.111.000786
Tarvainen M, Fabritius M, Yang B (2019) Determination of vitamin K composition of fermented food. Food Chem 275:515–522. https://doi.org/10.1016/j.foodchem.2018.09.136
Fu X, Harshman SG, Shen X, Haytowitz DB, Karl JP, Wolfe BE, Booth SL (2017) Multiple vitamin K forms exist in dairy foods. Curr Dev Nutr 1:e000638. https://doi.org/10.3945/cdn.117.000638
Azuma K, Inoue S (2019) Mu modes of vitamin K actions in aging-related musculoskeletal disorders. Int J Mol Sci 20:2844. https://doi.org/10.3390/ijms20112844
Tabb MM, Sun A, Zhou C, Grün F, Errandi J, Romero K, Pham H, Inoue S, Mallick S, Lin M, Forman BM, Blumberg B (2003) Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. J Biol Chem 278:43919–43927. https://doi.org/10.1074/jbc.M303136200
Nakagawa K, Hirota Y, Sawada N, Yuge N, Watanabe M, Uchino Y, Okuda N, Shimomura Y, Suhara Y, Okano T (2010) Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature 468:117–121. https://doi.org/10.1038/nature09464
Mishima E, Ito J, Wu Z, Nakamura T, Wahida A et al (2022) A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature 608:778–783. https://doi.org/10.1038/s41586-022-05022-3
Azuma K, Osuka Y, Kojima N, Sasai H, Kim H, Inoue S (2022) Association of vitamin K insufficiency with cognitive dysfunction in community-dwelling older adults. Front Nutr 8:811831. https://doi.org/10.3389/fnut.2021.811831
Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA, Cardiovascular Health Study Collaborative Research Group (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56:M146-156. https://doi.org/10.1093/gerona/56.3.m146
Azuma K, Osuka Y, Kojima N, Sasai H, Kim H, Inoue S (2022) Association of vitamin K insufficiency as evaluated by serum undercarboxylated osteocalcin with frailty in community-dwelling older adults. Front Aging 3:865178. https://doi.org/10.3389/fragi.2022.865178
Satake S, Arai H (2020) The revised Japanese version of the Cardiovascular Health Study criteria (revised J-CHS criteria). Geriatr Gerontol Int 20:992–993. https://doi.org/10.1111/ggi.14005
Tsugawa N, Shiraki M, Suhara Y, Kamao M, Tanaka K, Okano T (2006) Vitamin K status of healthy Japanese women: age-related vitamin K requirement for gamma-carboxylation of osteocalcin. Am J Clin Nutr 83:380–386. https://doi.org/10.1093/ajcn/83.2.380
Pilleron S, Weber D, Pérès K, Colpo M, Gomez-Cabrero D, Stuetz W, Dartigues JF, Ferrucci L, Bandinelli S, Garcia-Garcia FJ, Grune T, Féart C, FRAILOMIC initiative (2019) Patterns of circulating fat-soluble vitamins and carotenoids and risk of frailty in four European cohorts of older adults. Eur J Nutr 58:379–389. https://doi.org/10.1007/s00394-017-1602-0
Hernández Morante JJ, Gómez MartÃnez C, Morillas-Ruiz JM (2019) Dietary factors associated with frailty in old adults: a review of nutritional interventions to prevent frailty development. Nutrients 11:102. https://doi.org/10.3390/nu11010102
Machado-Fragua MD, Hoogendijk EO, Struijk EA, Rodriguez-Artalejo F, Lopez-Garcia E, Beulens JW, van Ballegooijen AJ (2020) 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. https://doi.org/10.1007/s00394-019-01984-9
Shea MK, Loeser RF, Hsu FC, Booth SL, Nevitt M, Simonsick EM, Strotmeyer ES, Vermeer C, Kritchevsky SB, Health ABC Study (2016) Vitamin K status and lower extremity function in older adults: the health aging and body composition study. J Gerontol A Biol Sci Med Sci 71:1348–1355. https://doi.org/10.1093/gerona/glv209
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. https://doi.org/10.1016/j.maturitas.2018.04.013
Su X, Wang W, Fang C, Ni C, Zhou J, Wang X, Zhang L, Xu X, Cao R, Lang H, Wang F (2021) Vitamin K2 alleviates insulin resistance in skeletal muscle by improving mitochondrial function via SIRT1 signaling. Antioxid Redox Signal 34:99–117. https://doi.org/10.1089/ars.2019.7908
Azuma K, Osuka Y, Kojima N, Sasai H, Kim H, Inoue S (2022) Association of Vitamin K insufficiency as evaluated by serum undercarboxylated osteocalcin with depressive symptoms in community-dwelling older adults. Am J Geriatr Psychiatry 30:1051–1052. https://doi.org/10.1016/j.jagp.2022.04.012
Okano T, Shimomura Y, Yamane M, Suhara Y, Kamao M, Sugiura M, Nakagawa K (2008) Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice. J Biol Chem 283:11270–11279. https://doi.org/10.1074/jbc.M702971200
Lev M, Milford AF (1972) Effect of vitamin K depletion and restoration on sphingolipid metabolism in Bacteroides melaninogenicus. J Lipid Res 13:364–370
Liu D, Guo H, Griffin JH, Fernández JA, Zlokovic BV (2003) Protein S confers neuronal protection during ischemic/hypoxic injury in mice. Circulation 107:1791–1796. https://doi.org/10.1161/01.CIR.0000058460.34453.5A
Binder MD, Cate HS, Prieto AL, Kemper D, Butzkueven H, Gresle MM, Cipriani T, Jokubaitis VG, Carmeliet P, Kilpatrick TJ (2008) Gas6 deficiency increases oligodendrocyte loss and microglial activation in response to cuprizone-induced demyelination. J Neurosci 28:5195–5206. https://doi.org/10.1523/JNEUROSCI.1180-08.2008
Acknowledgements
We thank all the participants for The Otassha Study.
Funding
This study was funded by TMIG institutional project funding (SASM).
Author information
Authors and Affiliations
Contributions
All the authors conceived and designed the study. KA, YO, NK, and HS acquired the data and KA conducted the data analyses. All the authors contributed to the interpretation of data, drafted the manuscript, and approved the final version for publication.
Corresponding author
Ethics declarations
Conflict of interest
All the authors have no conflicts of interest.
Ethical standards
This study complied with the current laws regarding ethical standards in Japan and the study protocol was approved by the institutional ethical committee of the Tokyo Metropolitan Institute for Geriatrics and Gerontology (approved number: H18-17, R1-20).
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Azuma, K., Osuka, Y., Kojima, N. et al. Vitamin K insufficiency predicts incidence of frailty in community-dwelling older adults: The Otassha Study. J Bone Miner Metab 41, 817–821 (2023). https://doi.org/10.1007/s00774-023-01457-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00774-023-01457-4