(Circulation. 2001;103:2788.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Low Circulating Vitamin B6 Is Associated With Elevation of the Inflammation Marker C-Reactive Protein Independently of Plasma Homocysteine Levels
From the Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Mass (S.F., P.F.J., I.H.R., J.S.); and Boston University School of Medicine and the National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Mass (P.W.F.W.).
Correspondence to Jacob Selhub, PhD, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111. E-mail jselhub{at}hnrc.tufts.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—Lower vitamin B6 concentrations are reported to confer an increased and independent risk for cardiovascular disease (CVD). The mechanism underlying this relationship, however, remains to be defined. Other diseases, such as rheumatoid arthritis, are associated with reduced vitamin B6 levels. Despite a clear distinction in pathophysiology, inflammatory reaction may be the major link between these diseases. We hypothesized a relationship between pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, and the marker of inflammation C-reactive protein (CRP). We also evaluated whether total plasma homocysteine (tHcy), a well-defined risk factor for CVD and a major determinant of plasma PLP levels, had a possible role as a mediator of this hypothesized relationship.
Methods and
Results—Data from 891 participants from the
population-based Framingham Heart Study cohort were analyzed.
Subjects were divided into 2 groups according to normal or elevated CRP
values: group 1, CRP <6 mg/L; group 2, CRP 
6 mg/L. Plasma PLP levels
were substantially lower in group 2 than in group 1 (mean values in
group 2, 36.5 nmol/L versus 55.8 nmol/L in group 1,
P<0.001). In a multiple
logistic regression model adjusted for tHcy, the association of PLP
with CRP remained highly significant
(P=0.003).
Conclusions—Low plasma PLP is associated with higher CRP levels independently of tHcy. This observation may reflect a vitamin B6 utilization in the presence of an underlying inflammatory process and represent a possible mechanism to explain the decreased vitamin B6 levels in CVD.
Key Words: atherosclerosis • risk factors • homocysteine • vitamins • inflammation
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, participates in a wide range of reactions, including metabolism of homocysteine, a sulfur-containing amino acid that is thought to be a risk factor for occlusive vascular disease.1 2 Recent studies have shown that plasma PLP levels are significantly reduced in certain pathological conditions. An association with low plasma PLP levels has been demonstrated in patients with rheumatoid arthritis (RA),3 and lower concentrations of this coenzyme have been reported to be an independent risk factor for cardiovascular disease (CVD).4 5 Because plasma PLP is an important determinant of plasma total homocysteine (tHcy), an interpretation for a role of this coenzyme has been addressed primarily through its link with homocysteine metabolism. Nevertheless, the relationship between low PLP and diseases cannot be fully explained on the basis of an abnormal tHcy metabolism.5 6 Since the first description by Rinehart and Greenberg of arteriosclerotic lesions in pyridoxine-deficient monkeys,7 other mechanisms, related or unrelated to the homocysteine pathway, have been proposed for a role of vitamin B6 in vascular tissue damage. Vitamin B6 deficiency has been associated with impairment of enzymes involved in determining the structural integrity of the arterial wall,8 in altering platelet function,9 and in interfering with cholesterol metabolism.10 Nonetheless, no conclusive mechanism has been identified thus far. An alternative explanation is that the low PLP levels observed in these diseases are linked to inflammatory processes.6 As for RA, its chronic inflammatory nature is clearly recognized. There is also growing evidence suggesting that inflammation plays a key part in the pathogenesis of atherosclerosis.11 Indeed, there is an increasing body of evidence supporting the hypothesis that atherosclerosis shares many similarities with RA, a typical chronic inflammatory disease.12 13 C-reactive protein (CRP), one of the major acute-phase reactants, as well as cytokines regulating its plasma levels (eg, interleukin-6), have been used to predict the risk of cardiovascular events.14 Furthermore, it was recently demonstrated that CRP induces adhesion molecule expression in human endothelial cells, supporting the hypothesis of a direct role for CRP in promoting an inflammatory component in the atherosclerotic process.15 In patients with RA, low plasma PLP levels have been found to be associated also with erythrocyte sedimentation rate and levels of the inflammatory cytokine tumor necrosis factor-
.3 More evidence
for an inverse correlation between PLP and indices of acute-phase
reaction, such as plasma 1-antichymotrypsin,
copper, and blood leukocyte count, was also recently described in a
sample of elderly
subjects.16 To evaluate the relationship between plasma PLP, the inflammation marker CRP, and tHcy, we analyzed data available from the 20th examination of the Framingham Heart Study, a well-characterized, population-based cohort.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Study Population
The study sample consisted of the survivors from the original Framingham Heart Study cohort, an epidemiological study established in Framingham, Mass, during the period 1948 through 1950.17 The original cohort consisted of 5209 subjects of both sexes 30 to 62 years old. The surviving members of this cohort have been examined every 2 years, and in 1988 and 1989, 1402 survivors participated in the 20th examination. Institutional review boards approved the study, and all patients gave informed consent. Characteristics of the study population have been described in detail elsewhere.18
Additional covariables assessed for the present analyses were age, sex, cigarette smoking, diabetes, history of coronary artery disease, history of CVD, history of stroke events, and history of hypertension. Detailed operational definitions for all these covariables are provided elsewhere.19 20
Laboratory Testing
Samples of venous blood were drawn from each subject
to determine the concentration of CRP, tHcy, folate, vitamin
B12, and PLP. tHcy was determined by
high-performance liquid chromatography with
fluorimetric detection.21
Plasma folate was measured by a microbial assay
(Lactobacillus casei) in a
96-well plate.22 Plasma PLP
was assayed by the tyrosine decarboxylase apoenzyme
method.23 Plasma vitamin
B12 was measured with a (Magic) radioimmunoassay
kit from Ciba-Corning. Serum CRP was determined
by an immunoturbidimetric assay (SPQ antibody
reagent set II, DiaSorin). Creatinine levels were measured
in nonfasting plasma by the Jaffe method, adapted for
autoanalyzers. Dietary vitamin B6 intake
was estimated from diet records by use of a semiquantitative
food-frequency
questionnaire.24
Statistical Analysis
The statistical analyses were confined to a
subset of 891 subjects for whom a complete set of CRP, vitamin, and
tHcy values was available. To evaluate the relationships among plasma
PLP, tHcy, and CRP, we divided the population into 2 groups according
to CRP values: group 1, CRP <6 mg/L, ie, within the range of normality
(n=834, 93.6%); group 2, CRP 6 mg/L, ie, increased levels (n=57,
6.4%). Distributions of continuous variables were expressed as
mean±SD. Logarithmic transformation was performed on all skewed
variables to normalize their distributions. Therefore, geometric
means (antilogarithms of the transformed means) are presented
for tHcy, folate, PLP, vitamin B12,
creatinine, albumin, and dietary vitamin
B6 intake. Ninety-five percent CIs for the
geometric means were calculated by use of the transformed values, and
these intervals are displayed as the antilogarithm of the transformed
data. Adjustment for confounding variables (sex, age, smoking,
albumin, and creatinine) was performed by general
linear model analysis (specifically, ANCOVA) for plasma folate,
plasma PLP, vitamin B12, plasma tHcy,
albumin, and dietary vitamin B6 intake.
Statistical significance refers to a value of
P<0.05. All the statistical
computations were performed with an SAS PROC GLM
program (SAS user’s guide, version 8.0, SAS Institute,
1999).
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The relevant characteristics of the study sample divided according to CRP values, ie, group 1, CRP <6 mg/L and group 2, CRP
6 mg/L, are shown in
Table 1
. As indicated, the 2 groups did not differ
with respect to age, sex, plasma folate, vitamin
B12, dietary vitamin B6
intake, and creatinine levels. Neither were they
significantly different in terms of clinical characteristics, such as
prevalence of hypertension (group 1, 58.6%; group 2, 67.4%,
P=0.191), diabetes (group 1,
14.3%; group 2, 13.7%,
P>0.2), CVD (group 1, 33.8%;
group 2, 36.8%, P>0.2), and
coronary heart disease (group 1, 20.4%; group 2, 17.5%,
P>0.2). There was a higher
prevalence of stroke occurrence in group 2 (12.3%) than in group 1
(6.2%); however, the difference was not statistically significant
(P=0.08). Nonsmokers were
88.9% of the population sample, and the cumulative percentage of
subjects smoking <10 cigarettes/d was 91.6% (data not shown). Plasma
PLP was significantly lower in the group with abnormal CRP values than
in the other group (P<0.001).
Serum albumin was significantly lower in group 2 than in group
1 (P<0.001). Nevertheless, the
difference in albumin concentration between the 2 groups ranged
within the reference intervals and did not match the greater difference
in PLP concentration. The 2 groups did also differ in tHcy levels, but
the difference did not reach statistical significance
(P=0.063). To evaluate a
possible role for tHcy in the relationship between PLP and CRP values,
we performed a general linear model analysis. As shown in
Table 2, the strong association of PLP with CRP remained
highly significant even after adjustment for tHcy
(P<0.001). Conversely, after
adjustment for PLP concentrations, the relationship between CRP and
tHcy became clearly not statistically significant
(P=0.571).
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
These data demonstrate a strong association between decreased plasma PLP and increased levels of CRP, a major systemic marker of inflammation. Moreover, the association of PLP with CRP remained highly significant even after adjustment for tHcy, which is known to be an important metabolic indicator of vitamin B6 status as well as a cardiovascular risk factor. Furthermore, the low vitamin B6 levels were not attributable to impaired dietary intake, because it was similar in the 2 groups.
In a recent study, we also found a negative correlation between PLP and erythrocyte sedimentation rate, disease activity status, disease-related pain, joint swelling, and stiffness in patients with RA (E.-P. Chiang, PhD, et al, unpublished data, 2000). These results were consistent with data from similar studies.3 Furthermore, we demonstrated that the low PLP levels were not due to diminished vitamin B6 intake, nor were they associated with increased urinary excretion of 4-pyridoxic acid, an end product of vitamin B6 catabolism.
Despite the lack of a pathophysiological explanation for an association between PLP and markers of acute-phase status, a plausible interpretation of our data is that PLP is acting as a coenzyme for the inflammation-related functions. Because vitamin B6 is integrally involved in the synthesis of nucleic acids and consequently in mRNA and protein synthesis, the production of cytokines and other polypeptide mediators during the inflammatory response might require an increased utilization of this coenzyme. This model is consistent with the observation that vitamin B6 deficiency is associated with impairment in differentiation and maturation of monocyte-derived macrophages and T lymphocytes, inflammatory cells whose activation leads to the release of several enzymes and cytokines.25 Vitamin B6 deficiency was also reported to alter the regulation of interleukin-2 production.26
The present study, moreover, confirms observations from others of a lack of association of increased CRP and tHcy levels,27 28 suggesting that the relationship between tHcy and atherosclerosis cannot be explained through a link with CRP per se, whereas both are independent risk factors for CVD.
Various conditions such as renal failure, smoking, and age are known to be associated with reduced levels of PLP. In addition, PLP, the predominant form of plasma vitamin B6, is primarily bound to albumin, whose diminished levels may result in lower values of circulating PLP. Adjustment for albumin, creatinine, age, sex, and smoking, however, did not affect the observed association.
Indeed, additional studies are necessary to clarify whether inflammation-associated decreases in circulating PLP play a role in the cascade of metabolic events related to certain diseases. PLP is one of the most important coenzymes in maintaining the balance between protein synthesis and degradation. Therefore, it is likely that low levels of PLP may reflect a higher utilization of the coenzyme in an underlying inflammatory process, rather than a defective intake or excessive vitamin B6 catabolism. The low circulating PLP seen as a possible indicator of an inflammatory status as well as a major determinant of tHcy levels may further our understanding of the mechanisms by which this metabolite acts as a risk factor for CVD.
|
Footnotes |
|---|
This material is based on work supported by the US Department of Agriculture under agreement No. 58-1950-9-001. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the US Department of Agriculture.
Received January 29, 2001; revision received March 20, 2001; accepted March 29, 2001.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. D’Angelo A, Selhub J. Homocysteine and thrombotic disease. Blood. 1997;90:1–11.
2.
Ueland PM, Refsum
H, Beresford SAA, et al. The controversy over homocysteine and
cardiovascular risk.
Am J Clin Nutr. 2000;72:324–332.
3. Roubenoff R, Roubenoff RA, Selhub J, et al. Abnormal vitamin B6 status in rheumatoid cachexia: association with spontaneous tumor necrosis factor alpha production and markers of inflammation. Arthritis Rheum. 1995;38:105–109.[Medline] [Order article via Infotrieve]
4.
Folsom AR, Nieto
JF, McGovern PG, et al. Prospective study of coronary heart
disease incidence in relation to fasting total homocysteine, related
genetic polymorphisms, and B vitamins: the
Atherosclerosis Risk in Communities (ARIC) study.
Circulation. 1998;98:204–210.
5.
Robinson K, Arheart
K, Refsum H, et al, from the European COMAC Group. Low circulating
folate and vitamin B6 concentrations: risk
factors for stroke, peripheral vascular disease, and
coronary artery disease.
Circulation. 1998;97:437–443.
6. Roubenoff R, Dellaripa P, Nadeau MR, et al. Abnormal homocysteine metabolism in rheumatoid arthritis. Arthritis Rheum. 1997;40:718–722.[Medline] [Order article via Infotrieve]
7. Rinehart JF, Greenberg LD. Arteriosclerotic lesions in pyridoxine-deficient monkeys. Am J Pathol. 1949;25:481–491.[Medline] [Order article via Infotrieve]
8. Levene CI, Murray JC. The aetiological role of maternal vitamin-B6 deficiency in the development of atherosclerosis. Lancet. 1977;1:628–629.[Medline] [Order article via Infotrieve]
9. Is vitamin B6 an antithrombotic agent? Lancet. 1981;1:1299–1300.[Medline] [Order article via Infotrieve]
10. Chi MS. Vitamin B6 in cholesterol metabolism. Nutr Res. 1984;4:359–362.
11.
Ross R,
Atherosclerosis: an inflammatory disease.
N Engl J Med. 1999;340:115–126.
12.
Pasceri V, Yeh
ETH. A tale of two diseases: atherosclerosis and
rheumatoid arthritis.
Circulation. 1999;100:2124–2126.
13.
Manzi S, Wasko
MCM, Manzi S. Inflammation-mediated rheumatic diseases and
atherosclerosis. Ann Rheum
Dis. 2000;59:321–325.
14.
Ridker PM,
Hennekens CH, Buring JE, et al. C-reactive protein and other markers of
inflammation in the prediction of cardiovascular
disease in women. N Engl J
Med. 2000;342:836–843.
15.
Pasceri V,
Willerson JT, Yeh ETH. Direct proinflammatory effect of C-reactive
protein on human endothelial cells.
Circulation. 2000;102:2165–2168.
16. Bates CJ, Pentieva KD, Prentice A, et al. Plasma pyridoxal phosphate and pyridoxic acid and their relationship to plasma homocysteine in a representative sample of British men and women aged 65 years and over. Br J Nutr. 1999;8:191–201.
17. Dawber TR, Moore FE, Mann GV. Coronary heart disease in the Framingham Study. Am J Public Health. 1957;47:4–24.
18.
Selhub J, Jacques
PF, Wilson PWF, et al. Vitamin status and intake as primary
determinants of homocysteinemia in an elderly population.
JAMA. 1993;270:2693–2698.
19. Kannel WB, Wolf PA, Garrison RJ. Section 34: Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: Framingham Heart Study 30-year follow-up. In: The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease. Springfield, Va: National Technical Information Service; 1987:1–459.
20.
Wolf PA, Abbott
RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in
the elderly: the Framingham Heart Study.
Arch Intern Med. 1987;147:1561–1564.
21. Araki A, Sako Y. Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr. 1987;422:43–52.[Medline] [Order article via Infotrieve]
22. Tamura T, Freeberg LE, Cornwell PE. Inhibition by EDTA of growth of Lactobacillus casei in the folate microbiological assay and its reversal by added manganese or iron. Clin Chem. 1990;36:1993.[Medline] [Order article via Infotrieve]
23.
Camp VM, Chipponi
J, Farj BA. Radioenzymatic assay for direct measurement of plasma
pyridoxal 5'-phosphate. Clin
Chem. 1983;29:642–644.
24.
Rimm ED,
Giovannucci EL, Stampfer MJ, et al. Reproducibility and validity of an
expanded self-administered semiquantitative food frequency
questionnaire among male health professionals.
Am J Epidemiol. 1992;135:1114–1126.
25. Rall LC, Meydani SN. Vitamin B6 and immune competence. Nutr Rev. 1993;51:217–225.[Medline] [Order article via Infotrieve]
26.
Meydani SN,
Ribaya-Mercado JD, Russell RM, et al. Vitamin B6
deficiency impairs interleukin-2 production and lymphocyte
proliferation in elderly adults. Am J
Clin Nutr. 1991;53:1275–1280.
27.
Anderson JL,
Muhlestein JB, Horne BD, et al. Plasma homocysteine predicts mortality
independently of traditional risk factors and C-reactive protein in
patients with angiographically defined coronary artery disease.
Circulation. 2000;102:1227–1232.
28. Becker A, Van Hinsberg VW, Kostense PJ, et al. Serum homocysteine is weakly associated with von Willebrand factor and soluble vascular cell adhesion molecule 1, but not with C-reactive protein in type 2 diabetic and non-diabetic subjects: the Hoorn Study. Eur J Clin Invest.
This article has been cited by other articles:
 |
|
 |
|
  I. Cetin, C. Berti, and S. Calabrese Role of micronutrients in the periconceptional period Hum. Reprod. Update, June 30, 2009; (2009) dmp025v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Lee, H. Li, E. Giovannucci, I-M. Lee, J. Selhub, M. Stampfer, and J. Ma Prospective Study of Plasma Vitamin B6 and Risk of Colorectal Cancer in Men Cancer Epidemiol. Biomarkers Prev., April 1, 2009; 18(4): 1197 - 1202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ebbing, O. Bleie, P. M. Ueland, J. E. Nordrehaug, D. W. Nilsen, S. E. Vollset, H. Refsum, E. K. Ringdal Pedersen, and O. Nygard Mortality and Cardiovascular Events in Patients Treated With Homocysteine-Lowering B Vitamins After Coronary Angiography: A Randomized Controlled Trial JAMA, August 20, 2008; 300(7): 795 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Merete, L. M. Falcon, and K. L. Tucker Vitamin B6 Is Associated with Depressive Symptomatology in Massachusetts Elders J. Am. Coll. Nutr., June 1, 2008; 27(3): 421 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Morris, M. F. Picciano, P. F Jacques, and J. Selhub Plasma pyridoxal 5'-phosphate in the US population: the National Health and Nutrition Examination Survey, 2003-2004 Am. J. Clinical Nutrition, May 1, 2008; 87(5): 1446 - 1454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T Aasheim, D. Hofso, J. Hjelmesaeth, K. I Birkeland, and T. Bohmer Vitamin status in morbidly obese patients: a cross-sectional study Am. J. Clinical Nutrition, February 1, 2008; 87(2): 362 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Detopoulou, D. B Panagiotakos, S. Antonopoulou, C. Pitsavos, and C. Stefanadis Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study Am. J. Clinical Nutrition, February 1, 2008; 87(2): 424 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Hron, R. Lombardi, S. Eichinger, A. Lecchi, P. A. Kyrle, and M. Cattaneo Low vitamin B6 levels and the risk of recurrent venous thromboembolism Haematologica, September 1, 2007; 92(9): 1250 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Ronnenberg, S. A. Venners, X. Xu, C. Chen, L. Wang, W. Guang, A. Huang, and X. Wang Preconception B-Vitamin and Homocysteine Status, Conception, and Early Pregnancy Loss Am. J. Epidemiol., August 1, 2007; 166(3): 304 - 312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dierkes, C. Weikert, K. Klipstein-Grobusch, S. Westphal, C. Luley, M. Mohlig, J. Spranger, and H. Boeing Plasma pyridoxal-5-phosphate and future risk of myocardial infarction in the European Prospective Investigation into Cancer and Nutrition Potsdam cohort Am. J. Clinical Nutrition, July 1, 2007; 86(1): 214 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. Lima, S. R. Davis, A. D. Mackey, J. B. Scheer, J. Williamson, and J. F. Gregory III Vitamin B-6 Deficiency Suppresses the Hepatic Transsulfuration Pathway but Increases Glutathione Concentration in Rats Fed AIN-76A or AIN-93G Diets J. Nutr., August 1, 2006; 136(8): 2141 - 2147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Gori, F. Sofi, A. M. Corsi, A. Gazzini, I. Sestini, F. Lauretani, S. Bandinelli, G. F. Gensini, L. Ferrucci, and R. Abbate Predictors of Vitamin B6 and Folate Concentrations in Older Persons: The InCHIANTI Study Clin. Chem., July 1, 2006; 52(7): 1318 - 1324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Basu, S. Devaraj, and I. Jialal Dietary Factors That Promote or Retard Inflammation Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 995 - 1001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ullegaddi, H. J. Powers, and S. E. Gariballa Antioxidant Supplementation With or Without B-Group Vitamins After Acute Ischemic Stroke: A Randomized Controlled Trial JPEN J Parenter Enteral Nutr, March 1, 2006; 30(2): 108 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Davis, E. P. Quinlivan, P. W. Stacpoole, and J. F. Gregory III Plasma Glutathione and Cystathionine Concentrations Are Elevated but Cysteine Flux Is Unchanged by Dietary Vitamin B-6 Restriction in Young Men and Women J. Nutr., February 1, 2006; 136(2): 373 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Gori, A. M. Corsi, S. Fedi, A. Gazzini, F. Sofi, B. Bartali, S. Bandinelli, G. F. Gensini, R. Abbate, and L. Ferrucci A proinflammatory state is associated with hyperhomocysteinemia in the elderly Am. J. Clinical Nutrition, August 1, 2005; 82(2): 335 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. T Fung, M. L McCullough, P. Newby, J. E Manson, J. B Meigs, N. Rifai, W. C Willett, and F. B Hu Diet-quality scores and plasma concentrations of markers of inflammation and endothelial dysfunction Am. J. Clinical Nutrition, July 1, 2005; 82(1): 163 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dierkes, K. Hoffmann, K. Klipstein-Grobusch, C. Weikert, H. Boeing, B.-C. Zyriax, E. Windler, and J. Kratzsch Low plasma pyridoxal-5'phosphate and cardiovascular disease risk in women: results from the Coronary Risk Factors for Atherosclerosis in Women Study Am. J. Clinical Nutrition, March 1, 2005; 81(3): 725 - 727. [Full Text] [PDF]
|
|
|
|
|
|
S. Friso, D. Girelli, N. Martinelli, O. Olivieri, and R. Corrocher Reply to J Dierkes et al Am. J. Clinical Nutrition, March 1, 2005; 81(3): 727 - 728. [Full Text] [PDF]
|
|
|
|
|
|
S. Friso, D. Girelli, and R. Corrocher Reply to RD Reynolds and JE Leklem Am. J. Clinical Nutrition, November 1, 2004; 80(5): 1449 - 1449. [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Knight, E. B. Rimm, J. K. Pai, K. M. Rexrode, C. C. Cannuscio, J. E. Manson, M. J. Stampfer, and G. C. Curhan Kidney Dysfunction, Inflammation, and Coronary Events: A Prospective Study J. Am. Soc. Nephrol., July 1, 2004; 15(7): 1897 - 1903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Friso, D. Girelli, N. Martinelli, O. Olivieri, V. Lotto, C. Bozzini, F. Pizzolo, G. Faccini, F. Beltrame, and R. Corrocher Low plasma vitamin B-6 concentrations and modulation of coronary artery disease risk Am. J. Clinical Nutrition, June 1, 2004; 79(6): 992 - 998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L Tucker, B. Olson, P. Bakun, G. E Dallal, J. Selhub, and I. H Rosenberg Breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial Am. J. Clinical Nutrition, May 1, 2004; 79(5): 805 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. A. Ajani, E. S. Ford, and A. H. Mokdad Dietary Fiber and C-Reactive Protein: Findings from National Health and Nutrition Examination Survey Data J. Nutr., May 1, 2004; 134(5): 1181 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Gao, O. I. Bermudez, and K. L. Tucker Plasma C-Reactive Protein and Homocysteine Concentrations Are Related to Frequent Fruit and Vegetable Intake in Hispanic and Non-Hispanic White Elders J. Nutr., April 1, 2004; 134(4): 913 - 918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.J. Kelly, J.P. Kistler, V.E. Shih, R. Mandell, N. Atassi, M. Barron, H. Lee, S. Silveira, and K.L. Furie Inflammation, Homocysteine, and Vitamin B6 Status After Ischemic Stroke Stroke, January 1, 2004; 35(1): 12 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Kelly, V. E. Shih, J. P. Kistler, M. Barron, H. Lee, R. Mandell, and K. L. Furie Low Vitamin B6 but Not Homocyst(e)ine Is Associated With Increased Risk of Stroke and Transient Ischemic Attack in the Era of Folic Acid Grain Fortification Stroke, June 1, 2003; 34 (6): e51 - e54. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Chandalia, N. Abate, A. V. Cabo-Chan Jr., S. Devaraj, I. Jialal, and S. M. Grundy Hyperhomocysteinemia in Asian Indians Living in the United States J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1089 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Bor, H. Refsum, M. R. Bisp, O. Bleie, J. Schneede, J. E. Nordrehaug, P. M. Ueland, O. K. Nygard, and E. Nexo Plasma Vitamin B6 Vitamers before and after Oral Vitamin B6 Treatment: A Randomized Placebo-controlled Study Clin. Chem., January 1, 2003; 49(1): 155 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Lim and P. A. Cassano Homocysteine and Blood Pressure in the Third National Health and Nutrition Examination Survey, 1988-1994 Am. J. Epidemiol., December 15, 2002; 156(12): 1105 - 1113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Han, M. Xu, L. Tang, X. Tan, X. Tan, Y. Tan, and R. M. Hoffman Homogeneous, Nonradioactive, Enzymatic Assay for Plasma Pyridoxal 5-Phosphate Clin. Chem., September 1, 2002; 48(9): 1560 - 1564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Auer, R. Berent, B. Eber, S. Friso, P. F. Jacques, I. H. Rosenberg, J. Selhub, and P. W.F. Wilson Lack of Association of Increased C-Reactive Protein and Total Plasma Homocysteine Response Circulation, December 18, 2001; 104 (25): e164 - e164. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||