![[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}
|
|
|
|
|
||
* Vitamin Metabolism and Aging Laboratory and
Nutrition and Exercise Physiology Laboratory Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, and General Clinical Research Center, New England Medical Center, Boston, MA 02111
4To whom correspondence should be addressed. E-mail: jacob.selhub{at}tufts.edu.
 |
ABSTRACT |
|---|
 TOP ABSTRACT SUBJECT AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
EAST), a measure of vitamin B-6 status in the erythrocytes, compared with healthy subjects. The goal of the present study was to examine the correlations of PLP levels in these two compartments (plasma and erythrocytes) with other established indices of vitamin B-6 status, and to determine which indicator better reflects functional status of vitamin B-6 in patients with RA. Multiple indices of vitamin B-6 status were measured in 33 patients with RA. Plasma PLP, urinary 4-pyridoxic acid (4-PA), net increase in plasma total homocysteine after a methionine load (
tHcy) and net increase in urinary xanthurenic acid after a tryptophan load (XA) were log-transformed to reach normality for statistical analyses. We found that log-plasma PLP levels were inversely correlated with both log-tHcy (r = -0.368, P = 0.035) and log-XA (r = -0.333, P = 0.05). Plasma PLP was not correlated with EAST or urinary 4-PA excretion. In contrast, erythrocyte PLP was inversely correlated with EAST (r = -0.431, P = 0.012) and positively correlated with log-4-PA (r = 0.475, P = 0.005), but erythrocyte PLP was not correlated with the outcomes of a methionine or tryptophan load test. Erythrocyte PLP and log-4-PA, but not plasma PLP, were correlated with dietary intake of vitamin B-6 after adjusting for protein intake (r = 0.420, P = 0.015 and r = 0.333, P = 0.05, respectively). We suggest that in patients with RA, plasma PLP levels are a better diagnostic indicator of functional vitamin B-6 status than erythrocyte PLP levels.
KEY WORDS: • rheumatoid arthritis • pyridoxal 5'-phosphate • methionine load • tryptophan load • xanthurenic acid
Rheumatoid arthritis (RA) is associated with suboptimal nutritional conditions such as abnormal metabolism of iron, copper, zinc and certain vitamins (1
). Low circulating levels of vitamin B-6 (2
,3
) as well as abnormal tryptophan metabolism (4
–6
) have been reported in some patients with RA, suggesting that these patients could be at risk for vitamin B-6 deficiency. We showed previously that patients with RA have reduced plasma pyridoxal 5'-phosphate (PLP) levels but a normal erythrocyte aspartate aminotransferase activity coefficient ( EAST) compared with healthy subjects (3
), suggesting distinct roles of plasma and erythrocytes in vitamin B-6 metabolism during inflammation. The present study was undertaken to further investigate which indicator (plasma or erythrocyte) more accurately reflects systemic availability of vitamin B-6 in these patients. Both plasma and erythrocytes are common targets for nutritional assessment in humans. Plasma PLP (albumin-bound), the major form of vitamin B-6 in circulation (7
), is suggested to reflect the body stores of vitamin B-6 in healthy humans (8
). Plasma is easily accessible; hence plasma PLP level is also commonly used in assessing vitamin B-6 status in population-based studies (9
). On the other hand, the role of erythrocytes in vitamin B-6 transport and deposition remains to be established. It has been proposed that erythrocyte PLP levels reflect long-term vitamin B-6 status due to the lifespan of RBC (10
). Huang et al. (11
) noted a significant relationship between plasma and erythrocyte PLP with a ratio of 
1.0 in healthy women and concluded that plasma and erythrocyte PLP are equivalent measures of vitamin B-6 status in healthy subjects. However, in the case of RA, plasma and erythrocyte PLP do not appear to be equivalent measures of vitamin B-6 status.
Vitamin B-6 is excreted mainly in urine in the form of 4-pyridoxic acid (4-PA), an end product of vitamin B-6 metabolism (12 ). Urinary 4-PA is usually thought to reflect short-term dietary intake rather than vitamin B-6 status (13 ). In subjects with a constant daily intake of vitamin B-6, urinary 4-PA can also be an indicator for vitamin B-6 status (14 ). Exploration of the relationships between 4-PA excretion and other functional indices of vitamin B-6 status may help clarify the regulation of vitamin B-6 utilization in these patients.
The goals of the present study were to examine whether the compromised plasma PLP concentration seen in RA is associated with altered functional status of vitamin B-6, and to compare the usefulness of plasma vs. erythrocyte measurements in determining functional vitamin B-6 status in patients with RA. Easy and valid determination of nutritional status is important in patient care. Accuracy in determination of vitamin B-6 status in patients with RA would help to develop therapies to maintain optimal nutritional status in these patients.
|
SUBJECT AND METHODS |
|---|
|
TOPABSTRACTSUBJECT AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Adults with RA (n = 36) were recruited through the New England Medical Center (NEMC) Rheumatology Clinic. Written informed consent was obtained from all subjects in accordance with the regulations of the NEMC/Tufts University Human Investigation Review Committee. Men and women >18 y old fulfilling the American Rheumatology College criteria (15
) for RA were eligible. Patients with pregnancy, anemia (hemoglobin 
100 mg/L), thrombocytopenia (platelet count 50,000/µL), abnormal liver transaminase (serum aspartate aminotransferase or alanine aminotransferase 
50 IU/L), renal insufficiency (serum creatinine 15 mg/L), diabetes or cancer were excluded. Patients taking vitamin B-6 or multivitamin supplements were asked to stop for 1 mo before their participation in the study. Coburn et al. (16
) suggested that it takes 10–20 d for the body to reach a new steady state after a change of vitamin B-6 intake.
Study protocol.
This cross-sectional study was conducted in the General Clinical Research Center (GCRC) at NEMC. Before enrollment, blood chemistry and hematology screening and urinalysis were performed to ensure eligibility of the subject. Each subject provided a 24-h urine collection for measurement of baseline xanthurenic acid excretion. During the study period, RA disease activity was controlled; no changes in medications had been made for 1 mo preceding the study period for any of the subjects. In the 23 female participants, 12 were postmenopause and 11 were premenopause. To minimize the effect of hormonal fluctuation on our experimental procedures, test procedures for the premenopausal women were always performed during the luteal phase of the menstrual cycle.
On the day for tryptophan load test, each subject arrived in the GCRC at 0800 h having eaten breakfast. Each subject was given a standard oral tryptophan load test (powdered, 5 g L-tryptophan dissolved in chocolate milk; Ajinomoto, Teaneck, NJ) and a 24-h urine collection was begun. For each subject, the methionine load test was done within a week of the tryptophan load, usually 24 h after the tryptophan load was completed. Subjects were asked to fast overnight for 12 h before the methionine load test. On the day of the test, blood was drawn from fasting subjects into a tube containing EDTA for determination of plasma PLP and baseline total homocysteine level. Each patient was then given a standard oral methionine load test (100 mg/kg body, powdered L-methionine dissolved in orange juice; Ajinomoto). Blood was drawn 4 h after the methionine load for determination of the postload total homocysteine level. For assessment of dietary intake, each subject was instructed to complete a 2-d food record before this visit. During the 4-h period, the subject met with a registered dietitian to validate the details of the 2-d food diary including food preparation and portion size. A two-dimensional food model was used to standardize portion size among subjects. Dietary data were analyzed using the Minnesota Nutrition Data System (NDS) software (Food Database version 11A; Nutrient Database version 26).
Laboratory analyses
Blood hematology and chemistry analyses and urinalysis were performed at the NEMC clinical laboratory.
Plasma and erythrocyte PLP. RBC were washed with 9 g/L saline and then 250 µL freshly packed RBC was extracted with 250 µL of 10% perchloric acid. The RBC supernatant and plasma were stored at -70°C before analyses. PLP levels were assayed by a modification of the tyrosine decarboxylase procedure of Camp et al. (17 ), in which a 20-µL aliquot (plasma or supernatant) was precipitated with 80 µL of 5% trichloroacetic acid for deproteinization. The intra-assay CV was 5% and the interassay CV was 13%.
Plasma total homocysteine.
Plasma total homocysteine, which includes both the unbound and bound fractions of homocysteine, was measured by HPLC with fluorometric detection (18
). The net increase in plasma total homocysteine (tHcy) after the methionine load was calculated by subtracting the fasting total homocysteine level from the 4-h postmethionine load total homocysteine level.
Erythrocyte aspartate aminotransferase (EAST) activity.
EAST enzyme activity was measured by Cobas Fara II Centrifugal Analyzer (Roche Diagnostics System Inc., Montclair, NJ). The test procedure was based on a coupled enzymatic reaction in which the oxidation of NADH to NAD was followed by decreasing absorbance at 340 nm. The decrease in absorbance was proportional to the formation of oxaloacetate by the vitamin B-6–dependent EAST in the RBC. The assay conducted without added PLP was referred to as the nonstimulated value. The assay conducted with added PLP (0.41 mmol/L, 40 µL) was the stimulated value. The ratio of stimulated value to nonstimulated value was referred to as the activity coefficient ( EAST) (19
).
Urinary excretion of xanthurenic acid (XA). XA was measured by the colorimetric method of Hoes et al. (20 ). For the 24-h urine collection, each subject collected and stored urine in a dark bottle without additives at 4°C. After the collection was completed, the contents of the bottle were stirred, the total weight was recorded and aliquots were stored at -20°C until analyses. Indomethecin and thymol were added as preservatives to the aliquot in which XA was measured. The specimen for measurement of 4-PA was kept at -20°C without any additives.
Urinary excretion of 4-PA. 4-PA was measured by an isocratic HPLC method with fluorescence detection using an ODS Hypersil column (Keystone Scientific Inc., Bellefonte, PA) (21 ).
Statistical analysis.
A Pearson correlation matrix was performed to examine correlations between indices of vitamin B-6 status. Plasma PLP, total homocysteine, urinary 4-PA and urinary XA data underwent logarithmic transformation to achieve normality. A significant correlation was defined as P 0.05. All statistical analyses were performed using Systat 9.0 for Windows (SPSS, Chicago, IL).
|
RESULTS |
|---|
|
TOPABSTRACTSUBJECT AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
|
tHcy and post-tryptophan load XA.
Although log-plasma PLP correlated with erythrocyte PLP level (r = 0.371, P = 0.034), this modest correlation was strongly influenced by a single individual with much higher plasma PLP (154 nmol/L) and erythrocyte PLP (37 nmol/L) than the rest of the participants. The correlation was not significant when this individual’s data were excluded (r = 0.222, P = 0.223, Table 2
). Log-plasma PLP was inversely associated with log tHcy as well as with log XA. Furthermore, there was a correlation between postmethionine load tHcy and post-tryptophan load XA (Table 2)
. No correlation was found between log-plasma PLP and log-24-h urinary 4-PA, or log-plasma PLP and EAST (Table 2) .
|
EAST.
Erythrocyte PLP concentration was inversely correlated with EAST and directly correlated with 24-h 4-PA excretion (with and without log-transformation). Erythrocyte PLP levels did not correlate with postmethionine load tHcy or post-tryptophan load XA excretion. No correlation was found between EAST and postmethionine load tHcy (Table 2)
.
Correlations between dietary vitamin B-6 with erythrocyte PLP and 4-PA.
Dietary protein intake was a significant determinant of vitamin B-6 indices including plasma PLP level, urinary 4-PA excretion, post-tryptophan load urinary XA excretion, and EAST activity coefficient (22
). To account for the influence of dietary protein on vitamin B-6 indices, we adjusted dietary protein intake and examined the relationships between the vitamin B-6:protein ratio (B-6/protein) and indices of vitamin B-6 status. 4-PA excretion and erythrocyte PLP correlated with vitamin B-6 intake after adjusting for protein intake. 4-PA (with and without log-transformation) and erythrocyte PLP both correlated with dietary B-6/protein. Plasma PLP did not correlate with the dietary intake of vitamin B-6. None of the functional measures of vitamin B-6 status were related to dietary intake of vitamin B-6 in these subjects (Table 2) .
|
DISCUSSION |
|---|
|
TOPABSTRACTSUBJECT AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
EAST. These results suggest that the plasma and erythrocyte pools of PLP are differentially compartmentalized in these subjects. In healthy subjects, other researchers have found indications of compartmentalization of vitamin B-6 metabolism. Anderson et al. (24
) suggested that vitamin B-6 metabolism in erythrocytes might be distinct from systemic status. Coburn and colleagues (25
) reported that PL kinase activity decreases in erythrocytes but increases in muscle during diet-induced vitamin B-6 deficiency in otherwise healthy young men, indicating that erythrocytes are different from muscle, the major storage site of vitamin B-6, in the regulation of intracellular vitamin B-6 content. In patients with RA, the low plasma PLP but normal EAST compared with healthy controls may suggest localized deficiency of vitamin B-6 in liver and possibly other tissues, but not in erythrocytes (3
). Further studies investigating the regulation of vitamin B-6 in different body compartments are warranted. On the other hand, erythrocyte, but not plasma PLP levels, correlated with urinary 4-PA excretion (with and without log-transformation), and both erythrocyte PLP levels and 4-PA excretion reflected the dietary vitamin B-6 intake when adjusted for protein intake. These data indicate that erythrocytes may reflect the regulation of dietary pyridoxine uptake and excretion. Our data also indicate that, consistent with healthy individuals, urinary excretion of 4-PA is related to dietary intake of vitamin B-6 in patients with RA (12 ), hence inflammation does not appear to influence the relationship between intake and 4-PA. In contrast, unlike healthy subjects whose plasma PLP levels also reflect dietary intake of vitamin B-6 (26 –28 ), plasma PLP levels did not reflect dietary intake in patients with RA; it is related to inflammation status rather than to their external intake of vitamin B-6 (23 ).
Individuals with known physiologic or pharmacologic factors that could affect the indices of vitamin B-6 status used in the present study were excluded from the study. These included renal insufficiency (29 ) and diabetes (30 ), which have been found to be associated with abnormal homocysteine metabolism. Estrogen-based oral contraceptives have been found to interfere with tryptophan load (31 ); thus, we excluded patients taking oral contraceptives from this study. We did not recruit any patients taking D-penicillamine, which influences vitamin B-6 metabolism (32 ). Although the patients recruited in the present study were taking different medications for treatment of RA, the observed relationships among B-6 indicators were not affected by age, menopausal status, disease duration or use of any medications (including nonsteroidal anti-inflammatory drugs, prednisone, methotrexate, and sulfasalazine) because we did not find any interaction in the regression analyses. We concluded that these factors had a limited (if any) effect on the B-6 measurements in our study. To minimize potential effects of switching between medications, all patients were taking medications for symptom relief at the time of enrollment and had been taking the same medications for at least 2 mo preceding enrollment in the study. This minimized the potential effects of switching between medications on any experimental procedure and measurement. This criterion also avoided acute inflammation when subjects underwent flaring, which may cause acute reduction in plasma B-6 levels. It is unclear how RA noticably affects plasma and erythrocyte PLP pools. The serum alkaline phosphatase levels in our patients were mildly elevated. Plasma PLP and alkaline phosphatase tended to be correlated (r = -0.26, P = 0.15, n = 33) in our study group. Alkaline phosphatase has been shown to regulate extracellular levels of PLP in humans (33 ). The elevated alkaline phosphatase might account at least in part for the adequate deposition of PLP in erythrocytes in these patients, and may assist in the mobilization and uptake of vitamin B-6 during inflammation because vitamin B-6 is taken up by tissues primarily in the form of PL. We therefore speculate that vitamin B-6 is being mobilized between different body compartments in these patients.
In conclusion, in comparison with erythrocyte PLP levels, plasma PLP concentrations better reflect functional vitamin B-6 status in patients with RA. It should be noted that these patients have normal vitamin B-6 status in erythrocytes and they may or may not have whole-body vitamin B-6 deficiency (because muscle B-6 content, not plasma PLP level, reflects whole-body stores). However, the correlations between log-plasma PLP and the outcomes of methionine load and tryptophan load suggest that plasma PLP reflects liver stores of vitamin B-6 in these patients, which may be more relevant metabolically during inflammation.
|
FOOTNOTES |
|---|
2 This material is based upon work supported in part by the U.S. Department of Agriculture, under agreement No. 58–1950-9–001. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
3 Supported in part by Grant RR-00054 from the National Center for Research Resources, for the General Clinical Research Center, New England Medical Center and Tufts University School of Medicine, and by a Arthritis Foundation Dissertation Award (E.-P.C.).
5 Abbreviations used: EAST, erythrocyte aspartate aminotransferase activity coefficient; tHcy, net increase in plasma total homocysteine after a methionine load; XA, net increase in urinary xanthurenic acid after a tryptophan load; 4-PA, 4-pyridoxic acid; PLP, pyridoxal 5'-phosphate; RA, rheumatoid arthritis.
Manuscript received 17 September 2002. Initial review completed 9 October 2002. Revision accepted 19 November 2002.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTSUBJECT AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
1. Bollet, A. J. (1988) Nutrition and diet in rheumatic diseases. Shils, M. E. Young, V. N. eds. Modern Nutrition in Health and Disease 1988:1362-1372 Lea and Febiger Philadelphia, PA. .
2. Sanderson, C. R., Davis, R. E. & Bayliss, C. E. (1976) Serum pyridoxal in patients with rheumatoid arthritis. Ann. Rheum. Dis. 35:177-180.
3. Roubenoff, R., Roubenoff, R. A., Selhub, J., Nadeau, M. R., Canonn, J. G., Freeman, L. M., Dinarello, C. A. & Rosenberg, I. H. (1995) Abnormal vitamin B-6 status in rheumatoid cachexia. Arthritis Rheum 38:105-109.[Medline]
4. Bett, I. (1962) Urinary tryptophan metabolism in rheumatoid arthritis and some other diseases. Ann. Rheum. Dis. 25:556-562.
5. Flinn, J. H., Price, J. M., Yess, N. & Brown, R. R. (1964) Excretion of tryptophan metabolites by patients with rheumatoid arthritis. Arthritis Rheum 7:201-210.[Medline]
6. Bucker, F. E., Smith, H. G., Lakatos, C. & Chamberlain, M. A. (1972) Tryptophan metabolism in rheumatoid neuropathies. Ann. Rheum. Dis. 31:311-315.
7. Coburn, S. P. & Mahuren, J. D. (1983) A versatile cation-exchange procedure of measuring the seven major forms of vitamin B-6 in biological samples. Anal. Biochem. 129:310-307.[Medline]
8. Lui, A., Lumeng, L., Aronoff, G. R. & Li, T. K. (1985) Relationship between body store of vitamin B-6 and plasma pyridoxal-P clearance: metabolic balance studies in humans. J. Lab. Clin. Med. 106:491-497.[Medline]
9. Ubbink, J. B., Serfontein, W. J. & de Villiers, L. S. (1985) Stability of pyridoxal-5-phosphate semicarbazone: applications in plasma vitamin B-6 analysis and population surveys of vitamin B-6 nutritional status. J. Chromatogr. 342:277-284.[Medline]
10. Leklem, J. E. (1990) Vitamin B-6: a status report. J. Nutr. 120(suppl. 11):1503-1507.
11. Huang, Y. C., Chen, W., Evans, M. A., Mitchell, M. E. & Shultz, T. D. (1998) Vitamin B-6 requirement and status assessment of young women fed a high-protein diet with various levels of vitamin B-6. Am. J. Clin. Nutr. 67:208-220.[Abstract]
12. Reddy, S. K., Reynolds, M. S. & Price, J. M. (1958) The determination of 4-pyridoxic acid in human urine. J. Biol. Chem. 233:691-696.
13. Leklem, J. E. (1988) Vitamin B-6 metabolism and function in human. Leklem, J. E. Reynolds, R. D. eds. Clinical and Physiological Applications of Vitamin B-6 1988:3-28 A. R. Liss New York, NY. .
14. Brown, R. R., Rose, D. P., Leklem, J. E., Linkswiler, H. & Anand, R. (1975) Urinary 4-pyridoxic acid, plasma pyridoxal phosphate, and erythrocyte aminotransferase levels in oral contraceptive users receiving controlled intakes of vitamin B-6. Am. J. Clin. Nutr. 28:10-19.
15. Arnett, F. C., Edworthy, S. M., Bloch, D. A., McShane, D. J., Fries, J. F., Cooper, N. S., Healey, L. A., Kaplan, S. R., Liang, M. H., Luthra, H. S., Medsger, T. A. Jr, Mitchell, D. M., Neustadt, D. H., Pinals, R. S., Schaller, J. G., Sharp, J. T., Wilder, R. L. & Hunder, G. G. (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315-324.[Medline]
16. Coburn, S. P. (1990) Location and turnover of vitamin B-6 pools and vitamin B-6 requirements in humans. Ann. N.Y. Acad. Sci. 585:76-85.[Medline]
17. Camp, V. M., Chipponi, J. & Faraj, B. A. (1983) Radioenzyme assay for direct measurement of plasma PLP. Clin. Chem. 29:642-644.
18. Araki, A. & Sako, Y. (1987) Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J. Chromatogr. 422:43-52.[Medline]
19. Williams, D. G. (1976) Methods for the estimation of three vitamin dependent red cell enzymes. Clin. Biochem. 9:252-255.[Medline]
20. Hoes, M. & Kreutzer, E.K.J.K. (1981) Xanthurenic acid excretion in urine after oral intake of 5 g L-tryptophan by healthy volunteers: standardization of reference values. J. Clin. Chem. Biochem. 19:259-264.
21. Gregory, J. F., 3rd & Kirk, J. R. (1979) Determination of urinary 4-pyridoxic acid using high performance liquid chromatography. Am. J. Clin. Nutr. 32:879-883.
22. Kretsch, M. J., Sauberlich, H. E., Skala, J. H. & Johnson, H. L. (1995) Vitamin B-6 requirement and status assessment: young women fed a depletion diet followed by a plant- or animal-protein diet with graded amounts of vitamin B-6. Am. J. Clin. Nutr. 61:1091-1101.
23. Chiang, E-P., Bagley, P. J., Selhub, J., Nadeau, M. & Roubenoff, R. (2003) Abnormal vitamin B-6 status is associated with severity of disease symptoms in patients with rheumatoid arthritis. Am. J. Med. (in press).
24. Anderson, B. B., Fulford-Jones, C. E., Child, J. A., Beard, M. E. & Bateman, C. J. (1971) Conversion of vitamin B 6 compounds to active forms in the red blood cell. J. Clin. Investig. 50:1901-1909.
25. Coburn, S. P., Ziegler, P. J., Costill, D. L., Mahuren, J. D., Fink, W. J., Schaltenbrand, W. E., Pauly, T. A., Pearson, D. R., Conn, P. S. & Guilarte, T. R. (1991) Response of vitamin B-6 content of muscle to changes in vitamin B-6 intake in men. Am. J. Clin. Nutr. 53:1436-1442.
26. Brussaard, J. H., Lowik, M. R., van den Berg, H., Brants, H. A. & Bemelmans, W. (1997) Dietary and other determinants of vitamin B-6 parameters. Eur. J. Clin. Nutr. 51(suppl. 3):S39-S45.
27. Leklem, J. E. & Renolds, R. D. (1988) Challenges and direction in the search for clinical applications of vitamin B-6 status. Leklem, J. E. Reynolds, R. D. eds. Clinical and Physiological Applications of Vitamin B-6 1988:437-454 Plenum Press New York, NY. .
28. Bender, D. A. (1989) Vitamin B-6 requirements and recommendations. Eur. J. Clin. Nutr. 43:289-309.[Medline]
29. Henning, B. F., Riezler, R., Tepel, M., Langer, K., Raidt, H. & Graefe, U., Zidek & W (1999) Evidence of altered homocysteine metabolism in chronic renal failure. Nephron 83:314-322.[Medline]
30. Socha, M. W., Polakowska, M. J., Socha-Urbanek, K. & Fiedor, P. (1999) Hyperhomocysteinemia as a risk factor for cardiovascular diseases. The association of hyperhomocysteinemia with diabetes mellitus and renal transplant recipients. Ann. Transplant. 4:11-19.
31. Bender, D. A. (1987) Oestrogens and vitamin B-6–actions and interactions. World Rev. Nutr. Diet. 51:140-188.[Medline]
32. Takahashi, Y. & Matsuda, M. (1976) Effects of penicillamine on the contents of B-6 vitamers of the mouse brain. J. Nutr. Sci. Vitaminol. 22:375-379.
33. Whyte, M. P., Mahuren, J. D., Fedde, K. N., Cole, F. S., McCabe, E. R. & Coburn, S. P. (1988) Perinatal hypophosphatasia: tissue levels of vitamin B-6 are unremarkable despite markedly increased circulating concentrations of pyridoxal-5'-phosphate. Evidence for an ectoenzyme role for tissue-nonspecific alkaline phosphatase. J. Clin. Investig. 81:1234-1239.
This article has been cited by other articles:
|
|
 |
|
  O. Midttun, S. Hustad, J. Schneede, S. E Vollset, and P. M Ueland Plasma vitamin B-6 forms and their relation to transsulfuration metabolites in a large, population-based study Am. J. Clinical Nutrition, July 1, 2007; 86(1): 131 - 138. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
