Indicators and methods for folate, vitamin B-12, and vitamin B-6 status assessment in humans

Current Opinion in Clinical Nutrition and Metabolic Care

Volumn 14, Issue 5, 2011, Pages 445-454

  Lamers, Yvonne ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

cut off values; dried blood spots; liquid chromatography mass spectrometry; multianalyte platform; vitamin inadequacy

Indexed keywords

CYANOCOBALAMIN; CYSTATHIONINE; FOLIC ACID; HOMOCYSTEINE; METHYLMALONIC ACID; PYRIDOXAL 5 PHOSPHATE; PYRIDOXINE; TRANSCOBALAMIN;

ANALYTIC METHOD; CLINICAL INDICATOR; CLINICAL LABORATORY; ENZYME BLOOD LEVEL; FOLIC ACID BLOOD LEVEL; HIGH THROUGHPUT SCREENING; HUMAN; LIQUID CHROMATOGRAPHY; MEASUREMENT; NUTRITIONAL ASSESSMENT; REVIEW; SENSITIVITY AND SPECIFICITY; TANDEM MASS SPECTROMETRY; VITAMIN BLOOD LEVEL;

AVITAMINOSIS; CHROMATOGRAPHY, LIQUID; FOLIC ACID; HUMANS; MASS SPECTROMETRY; NUTRITION ASSESSMENT; NUTRITIONAL STATUS; RADIOISOTOPE DILUTION TECHNIQUE; REPRODUCIBILITY OF RESULTS; VITAMIN B 12; VITAMIN B 6; VITAMIN B COMPLEX;

EID: 80051766090     PISSN: 13631950     EISSN: 14736519     Source Type: Journal    
DOI: 10.1097/MCO.0b013e328349f9a7     Document Type: Review

References (85)

1. Institute of Medicine - Food and Nutrition Board. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington, D. C.: National Academy Press; 1998.
2. Lin PT, Cheng CH, Liaw YP, et al. Lowpyridoxal5'-phosphateis- associatedwith increased risk of coronary artery disease. Nutrition 2006;22:1146-1151.
3. de Bree A, Verschuren WM, Blom HJ, et al. Coronary heart disease mortality, plasma homocysteine, and B-vitamins: a prospective study. Atherosclerosis 2003;166:369-377. (Pubitemid 36071696)
4. Kelly PJ, Shih VE, Kistler JP, et al. 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 2003;34:e51-e54.
5. Miller JW, Green R, Mungas DM, et al. Homocysteine, vitamin B6, and vascular disease in AD patients. Neurology 2002;58:1471-1475. (Pubitemid 34552951)
6. Hin H, Clarke R, Sherliker P, et al. Clinical relevance of low serum vitamin B12 concentrations in older people: the Banbury B12 study. Age Ageing 2006;35:416-422. (Pubitemid 43941812)
7. Lin J, Lee IM, Cook NR, et al. Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women. Am J Clin Nutr 2008;87:734-743. (Pubitemid 351364556)
8. Kim YI. Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res 2007;51:267-292.
9. Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr 2000;71(5 Suppl):1295S-1303S. (Pubitemid 30230532)
10. Molloy AM, Kirke PN, Troendle JF, et al. Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic acid fortification. Pediatrics 2009;123:917-923.
11. Quinlivan EP, Hanson AD, Gregory JF. The analysis of folate and its metabolic precursors in biological samples. Anal Biochem 2006;348:163-184. (Pubitemid 41832521)
12. Gregory JF 3rd, Swendseid ME, Jacob RA. Urinary excretion of folate catabolites responds to changes in folate intake more slowly than plasma folate and homocysteine concentrations and lymphocyte DNA methylation in postmenopausal women. J Nutr 2000;130:2949-2952. (Pubitemid 32005323)
13. Allen LH. How common is vitamin B-12 deficiency? Am J Clin Nutr 2009;89:693S-696S.
14. Daly LE, Kirke PN, Molloy A, et al. Folate levels and neural tube defects. implications for prevention. JAMA 1995;274:1698-1702.
15. de Benoist B. Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. Food Nutr Bull 2008;29(2 Suppl):S238-S244.
16. Herrmann W, Obeid R, Schorr H, Geisel J. Functional vitamin B12 deficiency and determination of holotranscobalamin in populations at risk. Clin Chem Lab Med 2003;41:1478-1488. (Pubitemid 37493564)
17. Loikas S, Lopponen M, Suominen P, et al. RIA for serum holo-transcobalamin: method evaluation in the clinical laboratory and reference interval. Clin Chem 2003;49:455-462. (Pubitemid 36250206)
18. Pfeiffer CM, Caudill SP, Gunter EW, et al. Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999-2000. Am J Clin Nutr 2005;82:442-450.
19. Selhub J, Jacques PF, Dallal G, et al. The use of blood concentrations of vitamins and their respective functional indicators to define folate and vitamin B12 status. Food Nutr Bull 2008;29(2 Suppl):S67-S73.
20. Lamers Y, Prinz-Langenohl R, Moser R, Pietrzik K. Supplementation with [6S]-5-methyltetrahydrofolate or folic acid equally reduces plasma total homocysteine concentrations in healthy women. Am J Clin Nutr 2004;79:473-478. (Pubitemid 41115593)
21. Lamers Y. [6S]-5-methyltetrahydrofolate compared to folic acid supplementation: effect on risk markers of neural tube defects. Goettingen: Cuvillier; 2006.
22. Owen WE, Roberts WL. Comparison of five automated serum and whole blood folate assays. Am J Clin Pathol 2003;120:121-126. (Pubitemid 37046379)
23. Pfeiffer CM, Johnson CL, Jain RB, et al. Trends in blood folate and vitamin B-12 concentrations in the United States, 1988-2004. Am J Clin Nutr 2007;86:718-727. (Pubitemid 47435840)
24. Pawlosky RJ, Flanagan VP. A quantitative stable-isotope LC-MS method for the determination of folic acid in fortified foods. J Agric Food Chem 2001;49:1282-1286. (Pubitemid 32884949)
25. Pfeiffer CM, Fazili Z, McCoy L, et al. Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay. Clin Chem 2004;50:423-432. (Pubitemid 38156385)
26. Fazili Z, Pfeiffer CM. Measurement of folates in serum and conventionally prepared whole blood lysates: application of an automated 96-well plate isotope-dilution tandem mass spectrometry method. Clin Chem 2004;50:2378-2381. (Pubitemid 39552176)
27. Nelson BC, Satterfield MB, Sniegoski LT, Welch MJ. Simultaneous quantification of homocysteine and folate in human serum or plasma using liquid chromatography/tandem mass spectrometry. Anal Chem 2005;77:3586-3593. (Pubitemid 40799849)
28. Huang Y, Khartulyari S, Morales ME, et al. Quantification of key red blood cell folates from subjects with defined MTHFR 677C
29. Monch S, Netzel M, Netzel G, Rychlik M. Quantitation of folates and their catabolites in blood plasma, erythrocytes, and urine by stable isotope dilution assays. Anal Biochem 2010;398:150-160. This method was the first to use lyophilization to lyse and homogenize erythrocytes for quantification of multiple folate forms in human erythrocyte samples.
30. Rychlik M, Netzel M, Pfannebecker I, et al. Application of stable isotope dilution assays based on liquid chromatography-tandem mass spectrometry for the assessment of folate bioavailability. J Chromatogr B Analyt Technol Biomed Life Sci 2003;792:167-176. (Pubitemid 36830867)
31. Hannisdal R, Ueland PM, Svardal A. Liquid chromatography-tandem mass spectrometry analysis of folate and folate catabolites in human serum. Clin Chem 2009;55:1147-1154.
32. Gomez EA, Ehresmann DD, Ledebuhr LK, et al. Development and validation of an automated chemiluminometric immunoassay for human intrinsic factor antibodies in serum. Clin Chem 2005;51:232-235. (Pubitemid 40024043)
33. Hubl W, Zogbaum M, Boyd JC, et al. Evaluation of analytical methods and workflow performance of the Architect ci8200 integrated serum/plasma analyzer system. Clin Chim Acta 2005;357:43-54. (Pubitemid 40814433)
34. Bor MV, Nexo E, Hvas AM. Holo-transcobalamin concentration and transcobalamin saturation reflect recent vitamin B12 absorption better than does serum vitamin B12. Clin Chem 2004;50:1043-1049. (Pubitemid 38725792)
35. Nexo E, Hvas AM, Bleie O, et al. Holo-transcobalamin is an early marker of changes in cobalamin homeostasis. A randomized placebo-controlled study. Clin Chem 2002;48:1768-1771.
36. Hvas AM, Nexo E. Holotranscobalamin: a first choice assay for diagnosing early vitamin B deficiency? J Intern Med 2005;257:289-298. (Pubitemid 40342132)
37. Valente E, Scott JM, Ueland PM, et al. Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B12 status in the elderly. Clin Chem 2011;57:856-863. This study shows the sensitivity of holo-transcobalamin as an indicator of vitamin B-12 deficiency in the elderly.
38. Morkbak AL, Hvas AM, Milman N, Nexo E. Holotranscobalamin remains unchanged during pregnancy: longitudinal changes of cobalamins and their binding proteins during pregnancy and postpartum. Haematologica 2007;92:1711-1712. (Pubitemid 350248256)
39. Ulleland M, Eilertsen I, Quadros EV, et al. Direct assay for cobalamin bound to transcobalamin (holo-transcobalamin) in serum. Clin Chem 2002;48:526-532. (Pubitemid 34174583)
40. Nexo E, Christensen AL, Hvas AM, et al. Quantification of holotranscobalamin, a marker of vitamin B12 deficiency. Clin Chem 2002;48:561-562. (Pubitemid 34174588)
41. Kushnir MM, Komaromy-Hiller G. Optimization and performance of a rapid gas chromatography-mass spectrometry analysis for methylmalonic acid determination in serum and plasma. J Chromatogr B Biomed Sci Appl 2000;741:231-241. (Pubitemid 30243214)
42. Ueland PM, Midttun O, Windelberg A, et al. Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry. Clin Chem Lab Med 2007;45:1737-1745. (Pubitemid 350232967)
43. Windelberg A, Arseth O, Kvalheim G, Ueland PM. Automated assay for the determination of methylmalonic acid, total homocysteine, and related amino acids in human serum or plasma by means of methylchloroformate derivatization and gas chromatography-mass spectrometry. Clin Chem 2005;51:2103-2109. (Pubitemid 41532626)
44. Pfeiffer CM, Smith SJ, Miller DT, Gunter EW. Comparison of serum and plasma methylmalonic acid measurements in 13 laboratories: an international study. Clin Chem 1999;45:2236-2242.
45. Kushnir MM, Komaromy-Hiller G, Shushan B, et al. Analysis of dicarboxylic acids by tandem mass spectrometry: high-throughput quantitative measurement of methylmalonic acid in serum, plasma, and urine. Clin Chem 2001;47:1993-2002. (Pubitemid 33010716)
46. Magera MJ, Helgeson JK, Matern D, Rinaldo P. Methylmalonic acid measured in plasma and urine by stable-isotope dilution and electrospray tandem mass spectrometry. Clin Chem 2000;46:1804-1810.
47. Schmedes A, Brandslund I. Analysis of methylmalonic acid in plasma by liquid chromatography-tandem mass spectrometry. Clin Chem 2006;52:754-757.
48. Pedersen TL, Keyes WR, Shahab-Ferdows S, et al. Methylmalonic acid quantification in low serum volumes by UPLC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2011;879:1502-1506. This method uses the lowest volume of plasma (25 μL) for determination of methylmalonic acid, the preferred functional biomarker of vitamin B-12.
49. Blom HJ, van Rooij A, Hogeveen M. A simple high-throughput method for the determination of plasma methylmalonic acid by liquid chromatographytandem mass spectrometry. Clin Chem Lab Med 2007;45:645-650. (Pubitemid 46709740)
50. Hempen C, Wanschers H, van der Sluijs Veer G. A fast liquid chromatographic tandem mass spectrometric method for the simultaneous determination of total homocysteine and methylmalonic acid. Anal Bioanal Chem 2008;391:263-270.
51. laMarca G, Malvagia S, Pasquini E, et al. Rapid 2nd-tier test for measurement of 3-OH-propionic and methylmalonic acids on dried blood spots: reducing the false-positive rate for propionylcarnitine during expanded newborn screening by liquid chromatography-tandem mass spectrometry. Clin Chem 2007;53:1364-1369. (Pubitemid 47020995)
52. Lakso HA, Appelblad P, Schneede J. Quantification of methylmalonic acid in human plasma with hydrophilic interaction liquid chromatography separation and mass spectrometric detection. Clin Chem 2008;54:2028-2035. (Pubitemid 352774036)
53. La'ulu SL, Rawlins ML, Pfeiffer CM, et al. Performance characteristics of six homocysteine assays. Am J Clin Pathol 2008;130:969-975.
54. Persichilli S, Gervasoni J, De Martino D, et al. Reliability and correlation study of a new homocysteine assay. Clin Chem Lab Med 2008;46:1786-1788.
55. Friedman M. Applications of the ninhydrin reaction for analysis of amino acids, peptides, and proteins to agricultural and biomedical sciences. J Agric Food Chem 2004;52:385-406.
56. Magera MJ, Lacey JM, Casetta B, Rinaldo P. Method for the determination of total homocysteine in plasma and urine by stable isotope dilution and electrospray tandem mass spectrometry. Clin Chem 1999;45:1517-1522. (Pubitemid 29419005)
57. Rafii M, Elango R, Courtney-Martin G, et al. High-throughput and simultaneous measurement of homocysteine and cysteine in human plasma and urine by liquid chromatography-electrospray tandem mass spectrometry. Anal Biochem 2007;371:71-81. (Pubitemid 47538484)
58. Rafii M, Elango R, House JD, et al. Measurement of homocysteine and related metabolites in human plasma and urine by liquid chromatography electrospray tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2009;877:3282-3291.
59. Weaving G, Rocks BF, Iversen SA, Titheradge MA. Simultaneous quantitation of homocysteine, cysteine and methionine in plasma and urine by liquid chromatography-tandem mass spectrometry. Ann Clin Biochem 2006;43(Pt 6):474-480. (Pubitemid 44808272)
60. Husek P, Matucha P, Vrankova A, Simek P. Simple plasma work-up for a fast chromatographic analysis of homocysteine, cysteine, methionine and aromatic amino acids. J Chromatogr B Analyt Technol Biomed Life Sci 2003;789:311-322. (Pubitemid 36549200)
61. O'Broin SD, Gunter EW. Screening of folate status with use of dried blood spots on filter paper. Am J Clin Nutr 1999;70:359-367. (Pubitemid 29407156)
62. O'Broin S, Gunter E. Dried-serum spot assay for folate. Clin Chem 2002;48:1128-1130. (Pubitemid 34680920)
63. O'Broin SD, Kelleher BP. A dried serum spot assay for vitamin B (12). Clin Chem Lab Med 2008;46:354-358. (Pubitemid 351317776)
64. Turgeon CT, Magera MJ, Cuthbert CD, et al. Determination of total homocysteine, methylmalonic acid, and 2-methylcitric acid in dried blood spots by tandem mass spectrometry. Clin Chem 2010;56:1686-1695. This is the first method that simultaneously measures the two functional biomarkers of vitamin B-12, homocysteine and methylmalonic acid, in dried blood spots.
65. Accinni R, Campolo J, Parolini M, et al. Newborn screening of homocystinuria: quantitative analysis of total homocyst (e) ine on dried blood spot by liquid chromatography with fluorimetric detection. J Chromatogr B Analyt Technol Biomed Life Sci 2003;785:219-226. (Pubitemid 36126161)
66. McCann SJ, Gillingwater S, Keevil BG, et al. Measurement of total homocysteine in plasma and blood spots using liquid chromatography-tandem mass spectrometry: comparison with the plasma Abbott IMx method. Ann Clin Biochem 2003;40(Pt 2):161-165. (Pubitemid 36359868)
67. Rybak ME, Pfeiffer CM. Clinical analysis of vitamin B (6): determination of pyridoxal 5'-phosphate and 4-pyridoxic acid in human serum by reversed-phase high-performance liquid chromatography with chlorite postcolumn derivatization. Anal Biochem 2004;333:336-344. (Pubitemid 39278057)
68. Talwar D, Quasim T, McMillan DC, et al. Optimisation and validation of a sensitive high-performance liquid chromatography assay for routine measurement of pyridoxal 5-phosphate in human plasma and red cells using precolumn semicarbazide derivatisation. J Chromatogr B Analyt Technol Biomed Life Sci 2003;792:333-343. (Pubitemid 36830883)
69. Hansen CM, Shultz TD, Kwak HK, et al. Assessment of vitamin B-6 status in young women consuming a controlled diet containing four levels of vitamin B-6 provides an estimated average requirement and recommended dietary allowance. J Nutr 2001;131:1777-1786. (Pubitemid 32520446)
70. Lamers Y, O'Rourke B, Gilbert LR, et al. Vitamin B-6 restriction tends to reduce the red blood cell glutathione synthesis rate without affecting red blood cell or plasma glutathione concentrations in healthy men and women. Am J Clin Nutr 2009;90:336-343.
71. Midttun O, Hustad S, Schneede J, et al. Plasma vitamin B-6 forms and their relation to transsulfuration metabolites in a large, population-based study. Am J Clin Nutr 2007;86:131-138. (Pubitemid 47041602)
72. Davis SR, Stacpoole PW, Williamson J, et al. Tracer-derived total and folate-dependent homocysteine remethylation and synthesis rates in humans indicate that serine is the main one-carbon donor. Am J Physiol Endocrinol Metab 2004;286:E272-E279. (Pubitemid 38140319)
73. (Erratum 2004;286:E674).
74. Lamers Y, Coats B, Ralat M, et al. Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women. J Nutr 2011;141:835-842.
75. Lamers Y, Williamson J, Ralat M, et al. Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women. J Nutr 2009;139:452-460.
76. Adams JB, George F, Audhya T. Abnormally high plasma levels of vitamin B6 in children with autism not taking supplements compared to controls not taking supplements. J Altern Complement Med 2006;12:59-63. (Pubitemid 43346324)
77. Han Q, Xu M, Tang L, et al. Homogeneous, nonradioactive, enzymatic assay for plasma pyridoxal 5-phosphate. Clin Chem 2002;48:1560-1564. (Pubitemid 34925792)
78. Ericson KL, Mahuren JD, Zubovic YM, Coburn SP. Use of chlorite to improve HPLC detection of pyridoxal 5'-phosphate. J Chromatogr B Analyt Technol Biomed Life Sci 2005;823:218-220. (Pubitemid 41116768)
79. Midttun O, Hustad S, Solheim E, et al. Multianalyte quantification of vitamin B6 and B2 species in the nanomolar range in human plasma by liquid chromatography-tandem mass spectrometry. Clin Chem 2005;51:1206-1216. (Pubitemid 43079399)
80. Midttun O, Hustad S, Ueland PM. Quantitative profiling of biomarkers related to B-vitamin status, tryptophan metabolism and inflammation inhuman plasma by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 2009;23:1371-1379.
81. Han Q, Hoffman RM. Nonradioactive enzymatic assay for plasma and serum vitamin B (6). Nat Protoc 2008;3:1815-1819.
82. Rybak ME, Jain RB, Pfeiffer CM. Clinical vitamin B6 analysis: an interlaboratory comparison of pyridoxal 5'-phosphate measurements in serum. Clin Chem 2005;51:1223-1231. (Pubitemid 43079401)
83. Eussen SJ, Vollset SE, Hustad S, et al. Plasma vitamins B2, B6, and B12, and related genetic variants as predictors of colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2010;19:2549-2561.
84. Eussen SJ, Vollset SE, Hustad S, et al. Vitamins B2 and B6 and genetic polymorphisms related to one-carbon metabolism as risk factors for gastric adenocarcinoma in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 2010;19:28-38.
85. Holm PI, Ueland PM, Kvalheim G, Lien EA. Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry. Clin Chem 2003;49:286-294. (Pubitemid 36143452)