Biological Systems of Vitamin K: A Plasma Nutriproteomics Study of Subclinical Vitamin K Deficiency in 500 Nepalese Children (Lee SE et al)

Vitamin K (VK) is a fat-soluble vitamin whose deficiency disrupts coagulation and may disturb bone and cardiovascular health. However, Lee SE et al noted that the scale and systems affected by VK deficiency in pediatric populations remains unclear. To that end, the research team conducted a study of the plasma proteome of 500 Nepalese children 6-8 years of age (male/female ratio = 0.99) to identify proteins associated with VK status.

The researchers measured the concentrations of plasma lipids and protein induced by VK absence-II (PIVKA-II) and correlated relative abundance of proteins quantified by mass spectrometry with PIVKA-II. VK deficiency (PIVKA-II >2 lg/L) was associated with a higher abundance of low-density lipoproteins, total cholesterol, and triglyceride concentrations ( p < 0.01).

Among 978 proteins observed in >10% of the children, five proteins were associated with PIVKA-II and seven proteins were differentially abundant between VK deficient versus sufficient children, including coagulation factor-II, hemoglobin, and vascular endothelial cadherin, passing a false discovery rate (FDR) threshold of 10% (q < 0.10). Among 27 proteins associated with PIVKA-II or VK deficiency at a less stringent FDR (q < 0.20), a network comprised of hemoglobin subunits and erythrocyte anti-oxidative enzymes were highly and positively correlated each other (all r > 0.7).

The researchers concluded that “this study revealed that plasma proteomics can identify proteins revealing known and novel biological variation to suboptimal vitamin K status in healthy children. Because vitamin K deficiency likely co-exists with lipid metabolic conditions and have public health consequence, there is an increased need to assess and monitor vitamin K status in populations. Identified protein biomarkers in this study may improve understanding of potential health risks of childhood vitamin K deficiency, especially in undernourished populations.”

Dr. Katarzyna Maresz, president of the International Science and Health Foundation, pointed out that the authors have previously shown that plasma proteomics reliably discerns proteins known to circulate in association with vitamin A, E, and D, selenium and copper, and may uncover nutrient-associated biological pathways that to date have not been appreciated.

“Of at least 15 vitamin K-dependent proteins identified, 7 proteins are connected with coagulation system. Some extrahepatic D-dependent proteins function as regulators of bone mineral maturation and inhibitors of calcification of smooth muscle or vascular endothelium, but the physiological functions of others remain elusive,” she said “The plasma proteome may provide a unique opportunity to explore biological roles of vitamin K in populations.”


Lee SE, Schulze KJ, Cole RN, Wu LSF, Yager, JD, Groopman J, Christian P, West, Jr., KP. Biological Systems of Vitamin K: A Plasma Nutriproteomics Study of SubclinicalVitamin K Deficiency in 500 Nepalese Children. OMICS A Journal of Integrative Biology, Volume 20, Number 0, 2016. DOI: 10.1089/omi.2015.0178

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