Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Apr;91(4):1761–1768. doi: 10.1172/JCI116386

Dietary induced subclinical vitamin K deficiency in normal human subjects.

G Ferland 1, J A Sadowski 1, M E O'Brien 1
PMCID: PMC288156  PMID: 8473516

Abstract

A subclinical vitamin K deficiency was induced in 32 healthy subjects (four groups of eight males and females) aged 20-40 and 60-80 yr residing in the Metabolic Research Unit of the Human Nutrition Research Center on Aging at Tufts University. Volunteers were initially fed (4 d) a baseline-period diet containing the recommended daily allowance for vitamin K which is equivalent to 80 micrograms/d of phylloquinone (vitamin K1). During the baseline period various parameters of vitamin K nutritional status were monitored. The baseline period was followed by a 13-d depletion period during which the subjects were fed a very low vitamin K1 diet (approximately 10 micrograms/d). After depletion, the subjects entered a 16-d repletion period (four stages lasting 4 d each) during which time they were repleted with 5, 15, 25, and 45 micrograms of vitamin K1 per day. Vitamin K1 depletion dramatically and significantly decreased plasma vitamin K1 levels (P < 0.0001) in both elderly and young groups to values 13-18% of day 1 (elderly 0.22 nM, young 0.14 nM). Repleting the subjects with up to 45 micrograms of vitamin K1 per day failed, in the case of the young subjects, to bring plasma vitamin K1 levels back into the normal range. Dietary vitamin K1 restriction induced different responses in the urinary excretion of gamma-carboxyglutamic acid between the young and the elderly subjects with values decreasing significantly (P < 0.03) in the young while remaining unchanged in the elderly. The vitamin K1 depletion period had no significant effect on either prothrombin and activated partial thromboplastin times, or Factor VII and protein C (as determined by antigenic and functional assays). By using a monoclonal antibody, decarboxy prothrombin was found to increase slightly but significantly in both groups (P < 0.05) as a consequence of the low vitamin K1 diet. This study clearly shows that a diet low in vitamin K1 can result in a functional subclinical deficiency of vitamin K (decreased urinary gamma-carboxyglutamic acid excretion) without affecting blood coagulation.

Full text

PDF
1761

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allison P. M., Mummah-Schendel L. L., Kindberg C. G., Harms C. S., Bang N. U., Suttie J. W. Effects of a vitamin K-deficient diet and antibiotics in normal human volunteers. J Lab Clin Med. 1987 Aug;110(2):180–188. [PubMed] [Google Scholar]
  2. Bieri J. G., Tolliver T. J., Catignani G. L. Simultaneous determination of alpha-tocopherol and retinol in plasma or red cells by high pressure liquid chromatography. Am J Clin Nutr. 1979 Oct;32(10):2143–2149. doi: 10.1093/ajcn/32.10.2143. [DOI] [PubMed] [Google Scholar]
  3. Cancela M. L., Price P. A. Retinoic acid induces matrix Gla protein gene expression in human cells. Endocrinology. 1992 Jan;130(1):102–108. doi: 10.1210/endo.130.1.1727694. [DOI] [PubMed] [Google Scholar]
  4. Church W. R., Bhushan F. H., Mann K. G., Bovill E. G. Discrimination of normal and abnormal prothrombin and protein C in plasma using a calcium ion-inhibited monoclonal antibody to a common epitope on several vitamin K-dependent proteins. Blood. 1989 Nov 15;74(7):2418–2425. [PubMed] [Google Scholar]
  5. Ferland G., MacDonald D. L., Sadowski J. A. Development of a diet low in vitamin K-1 (phylloquinone). J Am Diet Assoc. 1992 May;92(5):593–597. [PubMed] [Google Scholar]
  6. Fernlund P. gamma-Carboxyglutamic acid in human urine. Clin Chim Acta. 1976 Oct 1;72(1):147–155. doi: 10.1016/0009-8981(76)90046-2. [DOI] [PubMed] [Google Scholar]
  7. Fraser J. D., Otawara Y., Price P. A. 1,25-Dihydroxyvitamin D3 stimulates the synthesis of matrix gamma-carboxyglutamic acid protein by osteosarcoma cells. Mutually exclusive expression of vitamin K-dependent bone proteins by clonal osteoblastic cell lines. J Biol Chem. 1988 Jan 15;263(2):911–916. [PubMed] [Google Scholar]
  8. Fraser J. D., Price P. A. Lung, heart, and kidney express high levels of mRNA for the vitamin K-dependent matrix Gla protein. Implications for the possible functions of matrix Gla protein and for the tissue distribution of the gamma-carboxylase. J Biol Chem. 1988 Aug 15;263(23):11033–11036. [PubMed] [Google Scholar]
  9. Frick P. G., Riedler G., Brögli H. Dose response and minimal daily requirement for vitamin K in man. J Appl Physiol. 1967 Sep;23(3):387–389. doi: 10.1152/jappl.1967.23.3.387. [DOI] [PubMed] [Google Scholar]
  10. Haroon Y., Bacon D. S., Sadowski J. A. Liquid-chromatographic determination of vitamin K1 in plasma, with fluorometric detection. Clin Chem. 1986 Oct;32(10):1925–1929. [PubMed] [Google Scholar]
  11. Haroon Y. Rapid assay for gamma-carboxyglutamic acid in urine and bone by precolumn derivatization and reversed-phase liquid chromatography. Anal Biochem. 1984 Aug 1;140(2):343–348. doi: 10.1016/0003-2697(84)90175-1. [DOI] [PubMed] [Google Scholar]
  12. Jones D. Y., Koonsvitsky B. P., Ebert M. L., Jones M. B., Lin P. Y., Will B. H., Suttie J. W. Vitamin K status of free-living subjects consuming olestra. Am J Clin Nutr. 1991 Apr;53(4):943–946. doi: 10.1093/ajcn/53.4.943. [DOI] [PubMed] [Google Scholar]
  13. Knapen M. H., Hamulyák K., Vermeer C. The effect of vitamin K supplementation on circulating osteocalcin (bone Gla protein) and urinary calcium excretion. Ann Intern Med. 1989 Dec 15;111(12):1001–1005. doi: 10.7326/0003-4819-111-12-1001. [DOI] [PubMed] [Google Scholar]
  14. Levy R. J., Lian J. B. gamma-Carboxyglutamate excretion and warfarin therapy. Clin Pharmacol Ther. 1979 May;25(5 Pt 1):562–570. doi: 10.1002/cpt1979255part1562. [DOI] [PubMed] [Google Scholar]
  15. O'Reilly R. A. Vitamin K in hereditary resistance to oral anticoagulant drugs. Am J Physiol. 1971 Nov;221(5):1327–1330. doi: 10.1152/ajplegacy.1971.221.5.1327. [DOI] [PubMed] [Google Scholar]
  16. Owen T. A., Aronow M. S., Barone L. M., Bettencourt B., Stein G. S., Lian J. B. Pleiotropic effects of vitamin D on osteoblast gene expression are related to the proliferative and differentiated state of the bone cell phenotype: dependency upon basal levels of gene expression, duration of exposure, and bone matrix competency in normal rat osteoblast cultures. Endocrinology. 1991 Mar;128(3):1496–1504. doi: 10.1210/endo-128-3-1496. [DOI] [PubMed] [Google Scholar]
  17. Preece M. A., O'Riordan J. L., Lawson D. E., Kodicek E. A competitive protein-binding assay for 25-hydroxycholecalciferol and 25-hydroxyergocalciferol in serum. Clin Chim Acta. 1974 Jul 31;54(2):235–242. doi: 10.1016/0009-8981(74)90241-1. [DOI] [PubMed] [Google Scholar]
  18. Price P. A. Gla-containing proteins of bone. Connect Tissue Res. 1989;21(1-4):51–60. doi: 10.3109/03008208909049995. [DOI] [PubMed] [Google Scholar]
  19. Sadowski J. A., Hood S. J., Dallal G. E., Garry P. J. Phylloquinone in plasma from elderly and young adults: factors influencing its concentration. Am J Clin Nutr. 1989 Jul;50(1):100–108. doi: 10.1093/ajcn/50.1.100. [DOI] [PubMed] [Google Scholar]
  20. Shah D. V., Tews J. K., Harper A. E., Suttie J. W. Metabolism and transport of gamma-carboxyglutamic acid. Biochim Biophys Acta. 1978 Mar 1;539(2):209–217. doi: 10.1016/0304-4165(78)90007-7. [DOI] [PubMed] [Google Scholar]
  21. Shearer M. J. Vitamin K and vitamin K-dependent proteins. Br J Haematol. 1990 Jun;75(2):156–162. doi: 10.1111/j.1365-2141.1990.tb02642.x. [DOI] [PubMed] [Google Scholar]
  22. Shino M. Determination of endogenous vitamin K (phylloquinone and menaquinone-n) in plasma by high-performance liquid chromatography using platinum oxide catalyst reduction and fluorescence detection. Analyst. 1988 Mar;113(3):393–397. doi: 10.1039/an9881300393. [DOI] [PubMed] [Google Scholar]
  23. Suttie J. W., Mummah-Schendel L. L., Shah D. V., Lyle B. J., Greger J. L. Vitamin K deficiency from dietary vitamin K restriction in humans. Am J Clin Nutr. 1988 Mar;47(3):475–480. doi: 10.1093/ajcn/47.3.475. [DOI] [PubMed] [Google Scholar]
  24. Usui Y., Tanimura H., Nishimura N., Kobayashi N., Okanoue T., Ozawa K. Vitamin K concentrations in the plasma and liver of surgical patients. Am J Clin Nutr. 1990 May;51(5):846–852. doi: 10.1093/ajcn/51.5.846. [DOI] [PubMed] [Google Scholar]
  25. Vermeer C. Gamma-carboxyglutamate-containing proteins and the vitamin K-dependent carboxylase. Biochem J. 1990 Mar 15;266(3):625–636. doi: 10.1042/bj2660625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Werlen D., Robert D., Leclerq M., Guelpa G., Pfister C. E. Modifications de l'excrétion urinaire de GLA (acide gamma-carboxyglutamique) induite par la vitamine K. Schweiz Med Wochenschr. 1988 Feb 13;118(6):203–205. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES