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. 2025 Mar 27;13(4):807.
doi: 10.3390/biomedicines13040807.

Low Vitamin K Status and Risk of Chronic Obstructive Pulmonary Disease

Daniel Alexander Ackermann  1 , Allan Linneberg  2   3 , Ema Rastoder  1 , Anna Kubel Vognsen  1 , Anne Ahrendt Bjerregaard  2 , Lennart Friis-Hansen  2   4 , Niklas Rye Jørgensen  3   5 , Caroline Emma Hedsund  1 , Niklas Dyrby Johansen  6   7 , Daniel Modin  6   7 , Maria Dons  6   7 , Mats C Højbjerg Lassen  6   7 , Kristoffer Grundtvig Skaarup  6   7 , Ditte Vesterlev  6   7 , Mia Moberg  8 , Julie Janner  8 , Josefin Eklöf  1 , Lars Pedersen  9 , Elisabeth Bendstrup  10   11 , Christian B Laursen  12   13 , Jørn Carlsen  3   14 , Tor Biering-Sørensen  6   7   14   15 , Jens-Ulrik Stæhr Jensen  1   3 , Pradeesh Sivapalan  1   3
Affiliations

Low Vitamin K Status and Risk of Chronic Obstructive Pulmonary Disease

Daniel Alexander Ackermann et al. Biomedicines. .

Abstract

Background: Vitamin K is a cofactor necessary for the biological activity of proteins like Matrix Gla Protein (MGP), which reduce calcification and help preserve lung function. This study aims to determine, first, whether low vitamin K status is associated with chronic obstructive pulmonary disease (COPD), and secondary, whether the level of vitamin K is associated with COPD severity, smoking exposure, or mortality. Methods: The plasma concentration of dephosphorylated uncarboxylated (dp-uc) MGP was used as an inverse biomarker for vitamin K in 98 COPD patients from the CODEX-P COPD study and 986 controls from the DanFunD study. Low vitamin K status was defined as the upper quartile of dp-ucMGP (>589 pmol/L). Using a logistic regression model, we examined whether low vs. high/moderate vitamin K status increased the odds ratio (OR) of having COPD. Secondary analyses, in the COPD cohort only, examined the association between low vitamin K status and COPD severity, smoking exposure in packyears and all-cause mortality, using a Welch's t-test and log-rank test, respectively. Results: Low vitamin K status was associated with increased odds of having COPD, OR 9.7 (95% CI [5.5 to 17.5], p < 0.001). We found no associations between low vitamin K and COPD severity (est. -0.03, p = 0.7; 95% CI [-0.2 to 0.1]), smoking exposure (p = 0.7), or all-cause mortality (p = 0.5). Conclusions: Low vitamin K status was associated with substantially higher odds of having COPD compared to high/moderate vitamin K status. No association was found between low vitamin K status and COPD severity, smoking exposure, or all-cause mortality. Further studies are needed to determine if vitamin K plays a role in the pathophysiology of COPD and whether supplement therapy is indicated.

Keywords: COPD; biomarker; dp-ucMGP; vitamin K.

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Conflict of interest statement

Tor Biering-Sørensen reports receiving research grants from Sanofi Pasteur and GE Healthcare, is a Steering Committee member of the Amgen financed GALACTIC-HF trial, on advisory boards for Sanofi Pasteur and Amgen, and speaker honorariums from Novartis and Sanofi Pasteur. Elisabeth Bendstrup reports fees and grants from Boehringer Ingelheim, Hoffman la Roche, Galapagos, and Bristol-Myers-Squibb. Jørn Carlsen is a member of an advisory board for Merck and has received institutional research grants and institutional speaker fees. Christian B. Laursen received payment for lectures at educational events hosted by AstraZeneca, Chiesi, and GSK outside the submitted work as well as royalties as the author of book chapters for the publisher Munksgaard. All other authors declare no conflicts of interest.

Figures

Figure A1
Figure A1
Distribution of pack-years in the COPD-only cohort (CODEX-P) stratified by Vitamin K groups. The dashed lines represent median in pack years for low vitamin K (41) and high/moderate vitamin K (42). One pack-year equals to smoking 20 cigarettes a day for a year. Low vitamin K status is defined as dp-ucMGP levels > 1065.5 pmol/L (upper quartile).
Figure 1
Figure 1
Flowchart—inclusion and exclusion of study participants. Abbreviations: dp-ucMGP, dephosphorylated-uncarboxylated Matrix Gla Protein; FEV1, forced expiratory volume in one second; VKA, Vitamin K antagonists; ASA, acetylsalicylic acid; DOAK, direct oral anti-coagulants; NB, Notabene.
Figure 2
Figure 2
Visualization—risk of COPD in relation to age. Analysis shows probability of COPD in both cohorts (CODEX-P and DanFunD), stratified by Vitamin K status, in relation to age in years. COPD, chronic obstructive pulmonary disease; dp-ucMGP, dephosphorylated-uncarboxylated Matrix Gla Protein. *** refers to p ≤ 0.001.
Figure 3
Figure 3
Distribution of FEV1 in the COPD only cohort (CODEX-P). FEV1; forced expiratory volume in one second. The dashed lines represent the median in FEV1 (L) for low vitamin K (0.79 L) and high/moderate vitamin K (0.8 L). Low vitamin K status is defined as dp-ucMGP levels > 1065.5 pmol/L (upper quartile).
Figure 4
Figure 4
Association between low vitamin K status and mortality in the COPD-only cohort (CODEX-P). Mean time to death is 607 days. Low vitamin K status is defined as dp-ucMGP levels > 1065.5 pmol/L (upper quartile in COPD cohort). Log rank test performed shows insignificant results.
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