Journal of Nutrition OpenSOurce Diets- www.ResearchDiets.com

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Online Supporting Material
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Booth, S. L.
Right arrow Articles by Crivello, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Booth, S. L.
Right arrow Articles by Crivello, N.
© 2008 American Society for Nutrition J. Nutr. 138:492-496, March 2008

Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Age and Dietary Form of Vitamin K Affect Menaquinone-4 Concentrations in Male Fischer 344 Rats1–3,

Sarah L. Booth*, James W. Peterson, Donald Smith, M. Kyla Shea, John Chamberland and Natalia Crivello

Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111

* To whom correspondence should be addressed. E-mail: sarah.booth{at}tufts.edu.


   ABSTRACT
TOP
 ABSTRACT
Introduction
 Materials and Methods
 Results
 Discussion
 LITERATURE CITED
 
Phylloquinone, the primary dietary form of vitamin K, is converted to menaquinone-4 (MK-4) in certain tissues. MK-4 may have tissue-specific roles independent of those traditionally identified with vitamin K. Fischer 344 male rats of different ages (2, 12, and 24 mo, n = 20 per age group) were used to compare the conversion of phylloquinone to MK-4 with an equivalent dose of another dietary form of vitamin K, 2',3'-dihydrophylloquinone. Rats were age- and diet-group pair-fed phylloquinone (198 ± 9.0 µg/kg diet) or dihydrophylloquinone (172 ± 13.0 µg/kg diet) for 28 d. MK-4 was the primary form of vitamin K in serum, spleen, kidney, testes, bone marrow, and brain myelin fractions, regardless of age group. MK-4 concentrations were significantly lower in kidney, heart, testes, cortex (myelin), and striatum (myelin) in the dihydrophylloquinone diet group compared with the phylloquinone diet group (P < 0.05). The MK-4 concentrations in 2-mo-old rats were lower in liver, spleen, kidney, heart, and cortex (myelin) but higher in testes compared with 24-mo-old rats (P < 0.05). However, there were no age-specific differences in MK-4 concentrations among the rats fed the 2 diets. These data suggest that dihydrophylloquinone, which differs from phylloquinone in its side phytyl chain, is absorbed but its intake results in less MK-4 in certain tissues. Dihydrophylloquinone may be used in models for the study of tissue-specific vitamin K deficiency.


   Introduction
TOP
 ABSTRACT
 Introduction
Materials and Methods
 Results
 Discussion
 LITERATURE CITED
 
Vitamin K is a fat-soluble vitamin that has been implicated in bone and vascular health, in addition to its classic role in coagulation (1). There are also data to suggest that vitamin K has a role in the regulation of sphingolipid metabolism (2). Multiple dietary forms of vitamin K exist, all of which can function, albeit with different affinities, as a cofactor for the vitamin K–dependent {gamma}-carboxylation reaction that converts specific glutamic acid residues to {gamma}-carboxyglutamic acid residues in certain proteins (3).

There is consistent evidence that phylloquinone, the primary dietary form of vitamin K, is converted to menaquinone-4 (MK-4),4 either directly within certain tissues (4) or through an interconversion to menadione, followed by a prenylation to MK-4 (5). In certain tissues that have high lipid content, such as the brain, MK-4 appears to be the preferred form of vitamin K (6). It is currently not known why this conversion to MK-4 occurs because both phylloquinone and MK-4 are cofactors for the vitamin K–dependent {gamma}-carboxylation reaction. Of interest is the observation that those tissues high in MK-4, including the brain and reproductive organs, are often low in {gamma}-carboxylase (7,8). In one in vitro study, MK-4, and to a lesser extent, phylloquinone, was shown to prevent oxidative injury in oligodendrocyte precursors and immature fetal cortical neurons, independent of the vitamin K–dependent {gamma}-carboxylation reaction (7). In male rats, MK-4 was shown to be involved in steroid production through the regulation of Cyp11a (8). These observations suggest that MK-4 has roles independent of being a cofactor for the {gamma}-carboxylation reaction.

Another dietary form of vitamin K, 2',3'-dihydrophylloquinone, is a product of commercial hydrogenation of phylloquinone-rich oils and does not occur in nature (9). In contrast to phylloquinone, it has been reported that high doses of 2',3'-dihydrophylloquinone do not convert to MK-4 in a rat model treated with the vitamin K antagonist, warfarin (10). Should these findings be demonstrated through the manipulation of diet in an animal model not treated with warfarin, 2',3'-dihydrophylloquinone may have utility in animal studies in the identification of mechanisms by which phylloquinone is converted to MK-4. There is also the potential application of 2',3'-dihydrophylloquinone in the manipulation of vitamin K status in those tissues that are rich in MK-4, while conserving vitamin K–dependent coagulation.

We compared the conversion of 2',3'-dihydrophylloquinone to MK-4 with that of an equivalent dose of phylloquinone in male Fischer 344 rats of different ages.


   Materials and Methods
TOP
 ABSTRACT
 Introduction
 Materials and Methods
Results
 Discussion
 LITERATURE CITED
 
    Rats and diets. A total of 60 male Fischer 344 rats (2-, 12-, and 24-mo-old, n = 20 per age group) were obtained from the National Institute of Aging (Harlan Sprague Dawley). The rats were maintained individually in stainless steel suspended wire cages to enable monitoring of food consumption (including spillage) and to minimize coprophagy. Rats consumed vitamin K–deficient (Harlan Teklad TD97053) powdered diet (Supplemental Table 1) and water ad libitum during a 2-wk acclimation period. Body weights were recorded at the end of the 2-wk acclimation period to determine approximate intakes for the pair-fed experimental phase (Table 1).


View this table:
[in this window]
[in a new window]

  		TABLE 1 Sample sizes and body weights of 2-, 12-, and 24-mo-old male Fischer 344 rats fed phylloquinone or dihydrophylloquinone for 28 wk

 
These rats were assigned to 1 of 2 experimental groups [phylloquinone diet group (P) and dihydrophylloquinone diet group (D)], and rats of the same age grouping were group pair-fed (11) with a vitamin K–deficient powdered diet (Harlan Teklad TD97053) supplemented with either dihydrophylloquinone (a gift of J. Pyrek, University of Kentucky, Mass Spectrophotometry Facility) or phylloquinone (Sigma, product V3501). The target dose of 200 µg/kg diet, which was lower than the current recommended intake of 1.0 mg/kg diet (12), was selected to create a mild deficiency state while conserving coagulation (6). It was anticipated that our ability to detect any differences between dihydrophylloquinone and phylloquinone in their conversion to MK-4 would be maximized under mild dietary vitamin K–deficiency conditions. The duration of the dietary supplementation for all groups was 28 d. The diets were stored at –20°C under a nitrogen gas blanket during the entire period of the study. At the end of 28 d, all rats were subsequently anesthetized and terminally exsanguinated. This protocol was approved by the Human Nutrition Research Center on Aging Institutional Animal Care and Use Committee.

    Laboratory analyses. The phylloquinone and dihydrophylloquinone concentrations of the diets were determined by reversed-phase HPLC (13).

Tissues were harvested and stored at –80°C until the time of analyses. Tissues were homogenized using a Powergen homogenizer (Fisher Scientific) in phosphate-buffered saline. The weight of tissue homogenized and the volume of buffer used were adjusted to give an approximate final tissue concentration of 0.3 kg/L.

The concentrations of phylloquinone, dihydrophylloquinone, and MK-4 in tissue (spleen, kidney, heart, testes, and bone marrow), serum, and myelin fractions were determined by reversed-phase HPLC and were expressed relative to wet weight (with the exception of serum), as previously described (13,14). Because brain samples were used for another study that included the analysis of sulfatides in myelin fractions isolated from 3 brain regions (striatum, cortex, and hippocampus) (to be reported elsewhere), we were unable to measure the MK-4 concentrations of the whole brain; instead, we analyzed the myelin fraction within each brain region. Myelin was isolated using the procedures described elsewhere (15).

During the initial analysis of the liver, a substance was found to elute with the same retention time as our internal standard, [vitamin K1(25)]. The analytical procedure for determination of vitamin K in liver was subsequently modified to separate the internal standard from the interfering substance. This was accomplished by changing the analytical column, the mobile phase composition, and elution procedure; all other conditions were identical to methods described elsewhere (13,14). Specifically, the analytical column used was a Pronto SIL C30 column (particle size 5 µm; dimensions 4.6 x 250 mm) (MAC-MOD Analytical). The gradient elution procedure was programmed as follows: a solution of 95% solvent A [methanol, to which 5.5 mL of aqueous solution (2 mol/L zinc chloride, 1 mol/L acetic acid, and 1 mol/L sodium acetate) per L was added] and 5% solvent B (methylene chloride) was pumped at 0.8 mL/min for the first 30 min. For the next 10.5 min, the flow rate was increased to 1.0 mL/min, and the mobile phase composition was changed to 70:30 (A:B; v:v) to remove the more lipophilic compounds from the column. The mobile phase composition was then changed to 95:5 (A:B; v:v). To reequilibrate the column, 8.0 min later the flow rate was changed back to 0.8 mL/min. Each cycle was 50 min in length. This modification also resulted in the separation of the cis from the trans form of vitamin K. The cis isomer is retained longer in the liver but has lower biological activity compared with the parent trans isomer (16,17). The substance in liver that interfered with the internal standard was not detected in any other tissues.

    Statistical analysis. Data are reported as mean ± SD. Because the SD increased with mean response, a natural log transformation was applied prior to formal analyses. The statistics presented in the tables are in the original scale. The main effects of age and diet, as well as the interaction between age and diet, on MK-4 concentrations in each tissue were analyzed by 2-way ANOVA and Tukey's HSD for multiple comparisons. Likewise, the main effects of age and diet, as well as the interaction between age and diet, on phylloquinone concentrations in each tissue in the P were compared with dihydrophylloquinone concentrations in each tissue in the D using a 2-way ANOVA and Tukey's HSD for multiple comparisons. There were no significant interactions between age and diet with respect to any of the tissue concentrations of phylloquinone or dihydrophylloquinone. Data were analyzed using SPSS for Windows, version 14.0. Significance was set at P ≤ 0.05.


   Results
TOP
 ABSTRACT
 Introduction
 Materials and Methods
 Results
Discussion
 LITERATURE CITED
 
The phylloquinone and dihydrophylloquinone concentrations of the 2 diets were 198 ± 9.0 and 172 ± 13.0 µg/kg, respectively. The daily food intakes were 16.8 ± 2.9, 18.0 ± 2.6, and 17.9 ± 2.9 g for the 2-, 12-, and 24-mo-old rats, respectively. For rats of each age, body weights and food intakes did not differ between the diet groups (Table 1). Among the 24-mo-old rats, 2 died in the P whereas 4 died in the D. Of these deaths, 2 occurred during the acclimation period and 2 occurred within the first week of consuming the test diets. There was also a 2-mo-old rat in the P that died before the completion of the 28-d treatment period. None of the rats had clinical signs associated with vitamin K–deficiency, even though the dietary intakes were below current recommendations for vitamin K (12).

To test the hypothesis that dihydrophylloquinone does not convert to MK-4, we compared MK-4 concentrations in response to equimolar amounts of dihydrophylloquinone with phylloquinone in 3 different age groups of rats (Table 2). The MK-4 concentrations in kidney, heart, testes, cortex (myelin), and striatum (myelin) were significantly lower in the D compared with the P. In contrast, MK-4 concentrations in serum, liver, spleen, bone marrow, and hippocampus (myelin) did not differ between the 2 diet groups. There were no diet x age interactions in any of the tissues examined.


View this table:
[in this window]
[in a new window]

  		TABLE 2 MK-4 concentrations in 2-, 12-, and 24-mo-old Fischer 344 male rats fed phylloquinone or dihydrophylloquinone for 28 wk1

 
To test the hypothesis that less dihydrophylloquinone is absorbed, transported, and/or stored in peripheral tissues, we compared dihydrophylloquinone concentrations with phylloquinone concentrations in response to their respective intakes in 3 age groups of male rats (Table 3). The 12- and 24-mo-old rats in the D had higher dihydrophylloquinone concentrations in the liver compared with the phylloquinone concentrations in the P (P < 0.005). In contrast, the D had consistently lower dihydrophylloquinone concentrations in the kidney, heart, and testes (P < 0.001) compared with the phylloquinone concentrations in the P. No other consistent significant differences were noted. There were no detectable concentrations of either phylloquinone or dihydrophylloquinone in the myelin fractions isolated from the brain regions.


View this table:
[in this window]
[in a new window]

  		TABLE 3 Effect of age and diet on phylloquinone and dihydrophylloquinone concentrations in 2-, 12-, and 24-mo-old male Fischer 344 rats fed phylloquinone or dihydrophylloquinone12

 
In addition to diet effects, there were also significant age effects on MK-4 concentrations, with the exception of serum, bone marrow, and hippocampus (myelin), in which no age effects were observed (Table 2). The 24-mo-old male rats had significantly higher MK-4 concentrations in the liver, heart, and cortex (myelin), but significantly lower concentrations in the testes compared with the 2- and 12-mo-old rats. In the spleen, kidney, and striatum (myelin), the 12- and 24-mo-old rats had comparable MK-4 concentrations, but these concentrations were significantly higher compared with the 2-mo-old rats. Significant age effects on phylloquinone concentrations were noted in the serum, liver, kidney, heart, spleen, and testes among the P (Table 3). There were also significant age effects in dihydrophylloquinone concentrations in the serum, liver, spleen, kidney, and testes, but not other tissues, among the D.

Analysis of the liver revealed both stereoisomers of phylloquinone among those in the P. Across the age groups, there was consistently more of the trans than the cis isomer of phylloquinone (2 mo, 24.3 ± 26.7 and 16.2 ± 13.9; 12 mo, 11.5 ± 4.4 and 8.0 ± 3.1; and 24 mo, 36.4 ± 12.7 and 16.3 ± 7.7 nmol/g liver for trans and cis isomers, respectively). Although we examined other tissues for the cis isomer in a subset of the rats, we did not find any other tissue with >10% of this stereoisomer contributing to total vitamin K (data not shown).


   Discussion
TOP
 ABSTRACT
 Introduction
 Materials and Methods
 Results
 Discussion
LITERATURE CITED
 
In this study of Fischer 344 male rats, 2',3'-dihydrophylloquinone intake did not have equivalent tissue-specific conversion to MK-4 when compared with equal intake of phylloquinone. Dihydrophylloquinone was absorbed from the diet and there was tissue-specific MK-4 conversion in certain tissues. However, the MK-4 concentrations were lower in the kidney, heart, testes, and brain myelin in the D when compared with the P. This difference in conversion to MK-4 between the 2 forms of vitamin K did not vary by age (i.e., there were no diet x age interactions).

Dihydrophylloquinone differs from phylloquinone in the saturation of the 2',3' double bond in the phytyl side chain. The active site for vitamin K's role as a cofactor in the {gamma}-carboxylation of vitamin K–dependent proteins is situated on the 2-methyl-1,4 naphthoquinone nucleus, which is common to both phylloquinone and dihydrophylloquinone. However, in humans, differences in bioavailability and/or turnover have been noted when comparing these 2 dietary forms of vitamin K (18,19). The comparison of vitamin K urinary metabolite excretion in response to the intake of both forms suggests that dihydrophylloquinone has a faster metabolic clearance rate compared with phylloquinone (19). Our data support these findings because the dihydrophylloquinone was absorbed from the diet but there appeared to be less dihydrophylloquinone in peripheral tissues, hence less substrate for the tissue-specific conversion to MK-4. Because dihydrophylloquinone is not an ingredient in animal nonpurified diets, the study diet supplemented with dihydrophylloquinone would have been the only source contributing to the high dihydrophylloquinone concentrations in the liver of all the age groups. In contrast, the P did not have any measurable concentrations of dihydrophylloquinone in any of the tissues measured.

In this study, the spleen, kidney, testes, and brain myelin contained higher concentrations of MK-4 compared with phylloquinone or dihydrophylloquinone, which is consistent with the findings of others (20–22). It was not an unexpected finding that the MK-4 concentrations reported for brain myelin fractions in our study were lower than those reported by others (6,10) because our analyses were limited to the myelin fractions within each brain region, whereas others analyzed the whole brain or entire regions. MK-4 concentrations were lower in the D compared with the P in all these tissues, with the exception of the spleen and hippocampus (myelin). There are biochemical roles for MK-4 in both the brain and the testes that are independent of its role as a cofactor for the {gamma}-carboxylation reaction (7,8). It is currently not known if long-term dihydrophylloquinone consumption will modulate these biochemical roles through a reduction in conversion to MK-4. In contrast, vitamin K forms in the liver, spleen, and myelin isolated from the hippocampus were primarily phylloquinone or dihydrophylloquinone, depending on the diet. The differences between MK-4 and phylloquinone concentrations in most tissues are generally more pronounced among phylloquinone-deficient rats compared with phylloquinone-supplemented rats (20). For this reason, we chose to use a low dietary intake dose to maximize the differences between phylloquinone and dihydrophylloquinone in their conversion to MK-4. It is plausible that this attenuated our ability to observe differences in MK-4 between the 2 diets.

In this study, there were no apparent coagulation disorders, as characterized by bleeding, nor were there any diet effects on the vitamin K content of the liver. Although there were 4 rats that died in the 24-mo D, there was no indication that these were diet-related. It is plausible that we were statistically underpowered to detect significant age or diet differences in MK-4 concentration in all the tissues because of unanticipated deaths in the older rats. Although the rats were group pair-fed, there was large intragroup variation in MK-4 concentrations for any given tissue, which is consistent with reports by others (10,21). We currently do not have an explanation for this observation, but these data indicate that larger sample sizes are required for future vitamin K rodent studies.

In summary, there were lower MK-4 concentrations in certain tissues among male Fischer 344 rats fed dihydrophylloquinone compared with an equivalent amount of phylloquinone. The mechanism by which dihydrophylloquinone has less tissue-specific conversion to MK-4 compared with phylloquinone is currently not known. The use of dietary dihydrophylloquinone may be useful in models of vitamin K deficiency in certain, but not all, tissues for which the preferred form is MK-4.


   ACKNOWLEDGMENTS
 
The authors thank Andrea Pinella and Nicole Salisbury for their technical assistance and Jerry Dallal, PhD, for his statistical advice.


   FOOTNOTES
 
1 Supported in part by USDA agreement 58-1950-7-707 and NIH NIA R03AG25781 (to N.C.). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the USDA. Back

2 Author disclosures: S. L. Booth, J. W. Peterson, D. Smith, M. K. Shea, J. Chamberland, and N. Crivello, no conflicts of interest. Back

3 Supplemental Table 1 is available with the online posting of this paper at jn.nutrition.org. Back

4 Abbreviations used: D, dihydrophylloquinone diet group; MK-4, menaquinone-4; P, phylloquinone diet group. Back

Manuscript received 13 September 2007. Initial review completed 16 October 2007. Revision accepted 20 December 2007.


   LITERATURE CITED
TOP
 ABSTRACT
 Introduction
 Materials and Methods
 Results
 Discussion
 LITERATURE CITED
 

1. Booth SL. Vitamin K status in the elderly. Curr Opin Clin Nutr Metab Care. 2007;10:20–3.[Medline]

2. Denisova NA, Booth SL. Vitamin K and sphingolipid metabolism: evidence to date. Nutr Rev. 2005;63:111–21.[Medline]

3. Jin DY, Tie JK, Stafford DW. The conversion of vitamin K epoxide to vitamin K quinone and vitamin K quinone to vitamin K hydroquinone uses the same active site cysteines. Biochemistry. 2007;46:7279–83.[Medline]

4. Davidson RT, Foley AL, Engelke JA, Suttie JW. Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria. J Nutr. 1998;128:220–3.[Abstract/Free Full Text]

5. Thijssen HH, Vervoort LM, Schurgers LJ, Shearer MJ. Menadione is a metabolite of oral vitamin K. Br J Nutr. 2006;95:260–6.[Medline]

6. Carrie I, Portoukalian J, Vicaretti R, Rochford J, Potvin S, Ferland G. Menaquinone-4 concentration is correlated with sphingolipid concentrations in rat brain. J Nutr. 2004;134:167–72.[Abstract/Free Full Text]

7. Li J, Lin JC, Wang H, Peterson JW, Furie BC, Furie B, Booth SL, Volpe JJ, Rosenberg PA. Novel role of vitamin K in preventing oxidative injury to developing oligodendrocytes and neurons. J Neurosci. 2003;23:5816–26.[Abstract/Free Full Text]

8. Shirakawa H, Ohsaki Y, Minegishi Y, Takumi N, Ohinata K, Furukawa Y, Mizutani T, Komai M. Vitamin K deficiency reduces testosterone production in the testis through down-regulation of the Cyp11a a cholesterol side chain cleavage enzyme in rats. Biochim Biophys Acta. 2006;1760:1482–8.[Medline]

9. Davidson K, Booth S, Dolnikowski G, Sadowski J. Conversion of vitamin K-1 to 2',3'-dihydrovitamin K1 during the hydrogenation of vegetable oils. J Agric Food Chem. 1996;44:980–3.

10. Sato T, Ozaki R, Kamo S, Hara Y, Konishi S, Inobe Y, Saitoh S, Harada H. The biological activity and tissue distribution of 2',3'-dihydrophylloquinone in rats. Biochim Biophys Acta. 2003;1622:145–50.[Medline]

11. Wu D, Pae M, Ren Z, Guo Z, Smith D, Meydani SN. Dietary supplementation with white button mushroom enhances natural killer cell activity in C57BL/6 mice. J Nutr. 2007;137:1472–7.[Abstract/Free Full Text]

12. National Research Council. Nutrient Requirements of Laboratory Animals. 4th rev. ed. Washington, DC: The National Academies Press; 1995.

13. Davidson KW, Sadowski JA. Determination of vitamin K compounds in plasma or serum by high-performance liquid chromatography using postcolumn chemical reduction and fluorimetric detection. Methods Enzymol. 1997;282:408–21.[Medline]

14. Tovar A, Ameho CK, Blumberg JB, Peterson JW, Smith D, Booth SL. Extrahepatic tissue concentrations of vitamin K are lower in rats fed a high vitamin E diet. Nutr Metab (Lond). 2006;3:29.[Medline]

15. Denisova NA, Gorbunov NV, Avrova NF. Fatty acid composition of phospholipids of myelin and synaptosomal proteolipid complexes from vertebrate brain. Int J Biochem. 1991;23:811–8.[Medline]

16. Knauer TE, Siegfried C, Willingham AK, Matschiner JT. Metabolism and biological activity of cis- and trans-phylloquinone in the rat. J Nutr. 1975;105:1519–24.[Abstract/Free Full Text]

17. Lowenthal J, Vergel Rivera GM. Comparison of the activity of the cis and trans isomer of vitamin K1 in vitamin K-deficient and coumarin anticoagulant-pretreated rats. J Pharmacol Exp Ther. 1979;209:330–3.[Abstract/Free Full Text]

18. Booth SL, Lichtenstein AH, O'Brien-Morse M, McKeown NM, Wood RJ, Saltzman E, Gundberg CM. Effects of a hydrogenated form of vitamin K on bone formation and resorption. Am J Clin Nutr. 2001;74:783–90.[Abstract/Free Full Text]

19. Harrington DJ, Booth SL, Card DJ, Shearer MJ. Excretion of the urinary 5C- and 7C-aglycone metabolites of vitamin K by young adults responds to changes in dietary phylloquinone and dihydrophylloquinone intakes. J Nutr. 2007;137:1763–8.[Abstract/Free Full Text]

20. Thijssen HH, Drittij-Reijnders MJ. Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4. Br J Nutr. 1994;72:415–25.[Medline]

21. Ronden JE, Thijssen HH, Vermeer C. Tissue distribution of K-vitamers under different nutritional regimens in the rat. Biochim Biophys Acta. 1998;1379:16–22.[Medline]

22. Huber AM, Davidson KW, O'Brien-Morse ME, Sadowski JA. Tissue phylloquinone and menaquinones in rats are affected by age and gender. J Nutr. 1999;129:1039–44.[Abstract/Free Full Text]




This article has been cited by other articles:


Home page
 J. Nutr.Home page
X. Fu, X.-D. Wang, H. Mernitz, R. Wallin, M. K. Shea, and S. L. Booth
9-Cis Retinoic Acid Reduces 1{alpha},25-Dihydroxycholecalciferol-Induced Renal Calcification by Altering Vitamin K-Dependent {gamma}-Carboxylation of Matrix {gamma}-Carboxyglutamic Acid Protein in A/J Male Mice
J. Nutr., December 1, 2008; 138(12): 2337 - 2341.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Online Supporting Material
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Booth, S. L.
Right arrow Articles by Crivello, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Booth, S. L.
Right arrow Articles by Crivello, N.

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2008 by American Society for Nutrition