![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
,2
Department of Nutritional Sciences,
*
Institute on Aging, and
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
2To whom correspondence should be addressed.
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
KEY WORDS: • bioavailability • phylloquinone • vitamin K • humans
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
-carboxyglutamyl (Gla) residues in a limited number of proteins
(Suttie 1993
). These proteins include plasma
procoagulants and anticoagulants, two proteins (osteocalcin and matrix
Gla protein) originally isolated from bone, a cellular growth factor
and proteins of undetermined function (Ferland 1998
).
The current recommended dietary allowance (RDA) for vitamin K is 1
µg/(kg · d) (National Research Council 1989
), which is in the range of intake estimated for
younger adults in the U.S. population (Booth and Suttie 1998
). The current RDA was set on the basis of limited data,
utilizing the maintenance of normal clotting function as the primary
criterion for adequacy; this intake of the vitamin may not result in
maximum -carboxylation of osteocalcin (Knapen et al. 1989
). Because of this, there has been increased interest in
the possible involvement of higher intakes of vitamin K in the
maintenance of bone health (Binkley and Suttie 1995
,
Shearer et al 1996
, Vermeer et al. 1996
).
The primary form of vitamin K in the diet is phylloquinone from green
leafy vegetables. Comprehensive data on the vitamin K content of foods
are now available and have been reviewed (Booth and Suttie 1998
). However, little information on the relative
bioavailability of phylloquinone from various foods is available.
Gijsbers et al. (1996)
compared the relative
bioavailability, measured as area under an absorption curve, of
phylloquinone from a synthetic preparation and from a food matrix.
Phylloquinone in the form of cooked spinach was reported to be 4% as
bioavailable as that from a commercial detergent suspension of
phylloquinone (Konakion, Roche, Basel, Switzerland). Three times as
much phylloquinone was absorbed when butter was consumed with the
spinach. The purpose of this study was to compare the bioavailability
of phylloquinone from an oral tablet supplement with phylloquinone in a
food matrix, and to obtain preliminary data on the effects of cooking,
meal fat content and food source on the bioavailability of
phylloquinone.
|
SUBJECTS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
The study design was approved by the Human Subjects Committee of the University of Wisconsin-Madison, and signed consent was obtained from all subjects. Eleven subjects, ages 22–30 y, with no history of malabsorption and normal prothrombin times, complete blood count and serum chemistry panel participated. Some subjects participated in more than one trial. Baseline serum samples were obtained after an overnight fast and 1, 2, 3, 4, 5, 6, 7 and 9 h after consumption of a vitamin K source and a standard test meal, which consisted of 1 Egg McMuffin (McDonald's, Oakbrook, Il) with 240 mL of orange juice [402 kcal (1682 kJ), 27% energy from fat]. To compare the bioavailability of phylloquinone contained in spinach to phylloquinone from a tablet, 8 subjects (4 women, 4 men) consumed a 500-µg phylloquinone tablet (Hoffmann-La Roche, Paramus, NJ); 7 d later, the same subjects consumed either 50 g (n = 4) or 150 g (n = 4) of fresh spinach. Subsequently, groups of subjects (n = 3) consumed either raw or cooked broccoli or romaine lettuce with either a low or high fat meal. Serum and food samples were stored at -20°C for subsequent analysis.
Food preparation and analytical methods.
Fresh vegetables obtained from a local market were washed and trimmed. Stems were removed from spinach leaves, trimmed to 3–5 cm on broccoli flowerettes and shortened by 3–5 cm on romaine lettuce leaves. Broccoli was cooked by steaming for 20 min. The fat content of the test meals containing broccoli was adjusted to 30% energy from fat by the addition of butter, and the test meals containing romaine lettuce were adjusted to 30 or 45% energy from fat by the addition of corn oil.
Serum phylloquinone was measured by HPLC separation and fluorescence
detection utilizing dihydro-vitamin K as an internal standard as
described by Bach et al. (1996)
, and the phylloquinone
content of the study foods was determined as described by Booth et al. (1994)
.
Data compilation and statistical analysis.
Serum phylloquinone concentrations were plotted against time. Area
under the curve (AUC) values were determined after subtracting baseline
concentrations from subsequent time points using the trapezoidal rule
(SigmaPlot, Jandel Scientific, Chicago, IL). Data from two subjects,
one consuming raw broccoli and one consuming 150 g of spinach were
not used because of high baseline serum phylloquinone concentrations
(4.29 and 1.98 nmol/L, respectively). The baseline serum phylloquinone
concentration for the remaining 26 baseline serum samples was 0.89
± 0.26 nmol/L (SD). Significance between mean group
AUC was determined by unpaired Student's t test at 
= 0.05 (InStat, GraphPad Software, San Diego, CA).
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
1. Absorption of 500 µg phylloquinone from a tablet was
rapid and resulted in peak concentrations that exceeded 9 nmol/L before
decreasing after 3 h. Absorption of phylloquinone from spinach was
slower, peak concentrations were lower (~3 nmol/L) and the subsequent
decline less rapid. The AUC was significantly greater (P
< 0.001) for subjects consuming the tablet than for those
consuming 150 g spinach [27.55 ± 10.08 vs. 4.79 ± 1.11 nmol/(L · h)]. There was no gender difference (data not shown)
in absorption of phylloquinone from a tablet.
|
. Absorption, as measured by AUC, was greater (P < .05) in subjects fed 150 rather than 50 g of spinach (495 vs. 165
µg of phylloquinone). No significant differences were
observed in the absorption of phylloquinone from fresh vs. cooked
broccoli or from fresh romaine lettuce at 30 or 45% energy from fat.
There was no significant difference in the absorption of phylloquinone
from the foods tested, i.e., fresh spinach, fresh broccoli or fresh
romaine lettuce containing 165–214 µg of phylloquinone.
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
), little
information exists on the bioavailability of this vitamin. This study
has demonstrated that absorption of 500 µg of
phylloquinone, as measured by the area under a serum phylloquinone
concentration curve, is about six times greater when phylloquinone was
ingested in the pure form as a tablet than when it was present in a
food matrix, fresh spinach. As might be expected, the absorption of
phylloquinone from a tablet was also faster than from a food source.
Peak serum concentrations were seen at 2 or 3 h for the tablet,
whereas this peak was delayed in those subjects consuming a food source
of phylloquinone. A large number of variables undoubtedly influence the bioavailability of phylloquinone from the diet, i.e., specific foods, consumption of cooked vs. raw vegetables and fat content of the diet. In this study, five groups of subjects were fed a meal containing a food source that furnished ~180 µg (165–214 µg) phylloquinone. There was no significant difference in phylloquinone absorption (AUC) when fresh spinach, broccoli and romaine were compared, suggesting that choice of specific foods will not have a major influence on vitamin K availability. However, the variability among individual subjects in these small groups was large, and studies with larger groups of subjects might determine if there are substantial differences in phylloquinone absorption from different foods.
Cooking has been shown to positively influence the absorption of
ß-carotene and lycopene, food components with physical properties
similar to those of phylloquinone (Gartner et al. 1997
,
Rock et al. 1998
), and increased fat content of a meal
has been shown to increase absorption of dietary vitamin D (Van den Berg 1997
) and vitamin E (Cohn 1997
) but not
retinyl palmitate (Borel et al. 1997
). The variability
of phylloquinone absorption observed in both groups of subjects, those
receiving a tablet or those consuming various foods, indicates that a
determination of the influence of cooking or fat intake on
phylloquinone absorption from foods will require a large number of
subjects. Absorption of greater amounts of phylloquinone (1 mg) from
food (Gijsbers et al. 1996
) and a pharmacologic dose (15
mg) of menaquinone-4 (Uematsu et al. 1996
) have been
shown to be positively influenced by increased dietary fat.
The limited data that are available currently (Gijsbers et al. 1996
) would indicate that supplemental phylloquinone is much
more available than phylloquinone in a food source and that efficient
phylloquinone absorption is promoted by increasing the fat content of a
meal; these data extend these observations. The current RDA for vitamin
K (1 µg/kg body weight) is in the same range as the
average intake from food sources in the North American population
(Booth and Suttie 1998
). There are indications
(Bach et al. 1996
, Sokoll et al. 1997
)
that normal intakes of vitamin K do not support all measures of vitamin
K sufficiency, and there are some indications that skeletal health may
be improved by vitamin K intakes higher than those normally consumed
(Binkley and Suttie 1995
, Shearer et al. 1996
, Vermeer et al. 1996
). If future studies
support increased intakes of vitamin K, it is likely that the amounts
desired will be difficult to obtain from diets and that supplementation
will be needed. The low availability of phylloquinone from food sources
compared with that of the pure vitamin will have to be considered
carefully if possible levels of supplementation are discussed.
|
FOOTNOTES |
|---|
Manuscript received November 16, 1998. Revision accepted February 23, 1999.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
1.
Bach A. U., Anderson S. A., Foley A. L., Williams E. C., Suttie J. W. Assessment of vitamin K status in human subjects administered "minidose" warfarin. Am. J. Clin. Nutr. 1996;64:894-902
2. Binkley N. C., Suttie J. W. Vitamin K nutrition and osteoporosis. J. Nutr. 1995;125:1812-1821
3. Booth S. L., Davidson K. W., Sadowski J. A. Evaluation of an HPLC method for the determination of phylloquinone (vitamin K) in various food matrices. J. Agric. Food Chem. 1994;42:295-300
4.
Booth S. L., Suttie J. W. Dietary intake and adequacy of vitamin K. J. Nutr. 1998;128:785-788
5. Borel P., Dubois C., Mekki N., Grolier P., Partier A., Alexandre-Gouabau M. C., Lairon D., Azais-Braesco V. Dietary triglycerides, up to 40 g/meal, do not affect preformed vitamin A bioavailability in humans. Eur. J. Clin. Nutr. 1997;51:717-722[Medline]
6. Cohn W. Bioavailabililty of vitamin E. Eur. J. Clin. Nutr. 1997;51:S80-S85
7. Ferland G. The vitamin K-dependent proteins: an update. Nutr. Rev. 1998;56:223-230[Medline]
8.
Gartner C., Stahl W., Sies H. Lycopene is more bioavailable from tomato paste than from fresh tomatoes. Am. J. Clin. Nutr. 1997;66:116-122
9. Gijsbers B.L.M., Jie K.-S.G., Vermeer C. Effect of food composition on vitamin K absorption in human volunteers. Br. J. Nutr. 1996;76:223-229[Medline]
10. Knapen M.H.J., Hamulyak K., Vermeer C. The effect of vitamin K supplementation on circulating osteocalcin (bone Gla protein) and urinary calcium excretion. Ann. Intern. Med. 1989;111:1001-1005
11. National Research Council Recommended Dietary Allowances 10th ed. 1989 National Academy Press Washington, DC.
12.
Rock C. L., Lovalo J. L., Emenhiser C., Ruffink M. T., Schwartz S. J. Bioavailability of ß-carotene is lower in raw than in processed carrots and spinach in women. J. Nutr. 1998;128:913-916
13. Shearer M. J., Bach A., Kohlmeier M. Chemistry, nutritional sources, tissue distribution and metabolism of vitamin K with special reference to bone health. J. Nutr. 1996;126:1181S-1186S[Medline]
14.
Sokoll L. J., Booth S. L., O'Brien M. E., Davidson K. W., Tsaioun K. I., Sadowski J. A. Changes in serum osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid in response to altered intakes of dietary phylloquinone in human subjects. Am. J. Clin. Nutr. 1997;65:779-784
15. Suttie J. W. Synthesis of vitamin K-dependent proteins. FASEB J 1993;7:445-452[Abstract]
16. Uematsu T., Nagashima S., Masayuki N., Kohno K., Sassa T., Ishi M., Tomono Y., Yamato C., Kanamaru M. Effect of dietary fat content on oral bioavailability of menatetranone in humans. J. Pharmacol. Sci. 1996;85:1012-1016[Medline]
17. Van den Berg H. Bioavailability of vitamin D. Eur. J. Clin. Nutr. 1997;51:S76-S79
18. Vermeer C., Gijsbers B.L.M.G., Craciun A. M., Groenen-van Dooren M.M.C.L., Knapen M.H.J. Effects of vitamin K on bone mass and bone metabolism. J. Nutr. 1996;126:11875-11915
This article has been cited by other articles:
|
|
 |
|
  D. A. Pearson Bone Health and Osteoporosis: The Role of Vitamin K and Potential Antagonism by Anticoagulants Nutr Clin Pract, October 1, 2007; 22(5): 517 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Schurgers, M. J. Shearer, K. Hamulyak, E. Stocklin, and C. Vermeer Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects Blood, November 1, 2004; 104(9): 2682 - 2689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C Binkley, D. C Krueger, T. N Kawahara, J. A Engelke, R. J Chappell, and J. W Suttie A high phylloquinone intake is required to achieve maximal osteocalcin {gamma}-carboxylation Am. J. Clinical Nutrition, November 1, 2002; 76(5): 1055 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Booth, A. H. Lichtenstein, and G. E. Dallal Phylloquinone Absorption from Phylloquinone-Fortified Oil Is Greater than from a Vegetable in Younger and Older Men and Women , J. Nutr., September 1, 2002; 132(9): 2609 - 2612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. McKeown, P. F. Jacques, C. M. Gundberg, J. W. Peterson, K. L. Tucker, D. P. Kiel, P. W. F. Wilson, and S. L. Booth Dietary and Nondietary Determinants of Vitamin K Biochemical Measures in Men and Women J. Nutr., June 1, 2002; 132(6): 1329 - 1334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C Binkley, D. C Krueger, J. A Engelke, A. L Foley, and J. W Suttie Vitamin K supplementation reduces serum concentrations of under-{gamma}-carboxylated osteocalcin in healthy young and elderly adults Am. J. Clinical Nutrition, December 1, 2000; 72(6): 1523 - 1528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L Booth, M. E O'Brien-Morse, G. E Dallal, K. W Davidson, and C. M Gundberg Response of vitamin K status to different intakes and sources of phylloquinone-rich foods: comparison of younger and older adults Am. J. Clinical Nutrition, September 1, 1999; 70(3): 368 - 377. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
