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1 Vol. 35, No 4 (2012).. Folate Up-to-date Kazuko Nishimura and Kazuo Mori Summary Folate is one of essential vitamin, and vital to normal cell growth and DNA synthesis. Folate deficiencies lead to megaloblastic anemia and ultimately to severe neurological problems. Folate concentration can be different depending on methods used for assessments. Therefore, there are needs for international reference materials as well as universal cutoffs of the deficiencies so that population prevalences of the deficiency can be properly determined and compared.

2 Recently, World Health Organization (WHO) International Standard (IS) 03/178 and Standard Reference Material (SRM) 1955. were launched as reference materials for serum folate. These materials were determined using isotope dilution liquid chromatography-tandem mass spectrometry (LC/MS/MS). As a conse- quence, the restandardized Access folate assay, with WHO IS 03/178, is upcoming. In addition, WHO. Technical Consultation defined the cutoffs for folate deficiencies. Key words: Folate, Access, Standardization, WHO IS 03/178, SRM 1955.

3 B 1941 . [Herschel K. Mitchell 1913-2000 ] . 1) .. folium acid Folic acid 2), 3) . Diagnostics Scientific Affairs & Product Marketing & Beckman Coulter 135-0053 3-5-7, TOC TOC Ariake West Tower, 3-5-7 Ariake, Koto-ku, Tokyo 135-0063, Japan 24 7 20 . 24 8 3 . 299 .. 2) 6) .. 1) . B12 . 5- DNA . 4) . 1) . 50% 1) .. 5) .. 10 .. 1), 6) .. 7) .. 300 . Vol. 35, No 4 (2012).. 35 . 75 8), 9), 10), 11), 12) . 60 . 13), 14), 15), 16), 17) . 2002 .. 1.. 2008 10 .. 18), 19) .. 13 . 13 .. 2.. B12 . 301 .. 1986 Dr. David Barker.

4 2,500g . 1975 DNA . 3,000g H3 . 20) .. 302 . Vol. 35, No 4 (2012). CH3 . S- . S- .. DNA .. 20) Coulter LH . DxC 800&AU . DxI 800 . DNA 21) .. Lactobacillus Casei .. 20) .. 5- . 3.. IFCC The WHO Technical Consultation on folate and C-PP vitamin B12 deficiencies B12 . C-RIDL . (APFCB) . B12 . 2009 2010 . (1) . B12 .. (2) 2008 . 22) . ng/mL . " " . HDL-C IgG C3 C4 CRP . CA15-3 PTH adiponectin . 18 23) .. 303 .. WHO IS 03/178 SRM1955.. WHO 2005-2006 . WHO. International Standard 03/178 WHO IS 03/178 . 24 24) . 10.

5 Reference Measurement procedure Access2. LC/MS/MS .. 5- . 5- . WHO IS 03/178 LC/MS/MS . ng/mL .. CV ~ . CV . 24) . WHO IS 03/178 . 5- . nmol/L 5- . nmol/L nmol/L . nmol/L ng/mL DxI 800.. 304 . Vol. 35, No 4 (2012).. ng/mL . 24) . WHO IS 03/178 mL . 3,750 . NIBSC .. WHO IS 03/178.. SRM1955 . 25), 26) . SRM1955 WHO . NIST . WHO IS 03/178 LC/MS/MS .. WHO IS 03/178 .. WHO IS 03/178 .. 2) . FOL2 DxI800 10. WHO IS 03/178 ng/mL. FOLW CV ng/mL CV . FOLW ng/mL CV . 10 20. ng/mL CV ng/mL 1) ng/mL . FOLW Access . 3) . Access 2 S0 S0 10.

6 100 / DxI600 2SD Limit of 200 / DxI800 Blank LoB, Analytical Sensitivity . 400 / ng/mL S0 . S0 . 2SD 2SD RLU . Limit of Detection LoD ng/mL .. 4) . S0 .. 305 .. 5) . 151 x y . y= - . r= .. WHO . NHANES 27) .. 6) . 22) . 4 ng/mL 10 nmol/L . 151 ng/mL 340 nmol/L . FOLW . 90 Jacques . ng/mL28) . ng/mL .. 306 . Vol. 35, No 4 (2012). WHO 46(2): 157-61, 1992. 10) Milunsky A, Jick H: Multivitamin/folic acid supple- ng/mL 10 nmol/L 22), 27) mentation in early pregnancy reduces the prevalence of neural tube defects. JAMA, 262(20): 2847-52, 1989.

7 Ng/mL 10. 11) Werler MM, Shapiro S: Periconceptional folic acid nmol/L . exposure and risk of occurrent neural tube defects. JAMA, 269(10): 1257-61, 1993.. 12) Shaw GM, Schaffer D: Periconceptional vitamin use, dietary folate, and the occurrence of neural tube defects. B12 WHO Epidemiology, 6(3): 219-26, 1995. 13) Laurence KM, James N: Double-blind randomised controlled trial of folate treatment before conception to prevent recurrence of neural-tube defects. Br Med J. LC/MS/MS . (Clin Res Ed), 282(6275): 1509-11, 1981.

8 14) Wald NJ: Folic acid and neural tube defects: the current evidence and implications for prevention. Ciba Found Symp, 181: 192-208 discussion 208-11, 1994. 15) Smithells RW, Nevin NC: Further experience of vitamin supplementation for prevention of neural tube defect recurrences. Lancet, 1(8332): 1027-31, 1983. 16) Vergel RG, Sanchez LR: Primary prevention of neural tube defects with folic acid supplementation: Cuban . experience. Prenat Diagn, 10(3): 149-52, 1990.. 17) Czeizel AE, Dud I: Prevention of the first occur- rence of neural-tube defects by periconceptional vitamin supplementation.

9 N Engl J Med, 327(26): 1832-5, 1992. 18) . ( ). ) : , , 19) . , (1996) ( ) ). : 2010 , 20) : . , , (2010) . , 118(8): 501-514, 2009. ) : , 21) : : . , , (2002) Ver. 37 : 15-54, ) : 2012. , , , (2002) 22) de Benoist B: Conclusion of a WHO technical consul- ) : , tation on folate and vitamin B12 deficiencies. Food Nutr , , (1999) Bull, 29: S238- S244, 2008. ) : 10 , 23) Ihara H, Hashizume N, Totani M, Inage H, Kimura S, , , (2004) Nagamura Y, Sudo K, Aoki Y, Saeki H, Sagawa N, ) : 18 , Kamioka K, Shimizu K, Watanabe R, Watanabe M, BP , , (2006) Hirayama K, Nakamori M, Takenami K, Yoshida M, ) Mulinare J, Cordero JF: Periconceptional use of multi- Kawasaki Y, Ogiwara T, Kawai T, Watanabe T: vitamins and the occurrence of neural tube defects.

10 Traditional reference values for serum vitamin B12 and JAMA, 260(21): 3141-5, 1988. folate are not applicable to automated serum vitamin B12. ) Bower C, Stanley FJ: Periconceptional vitamin supple- and folate assays: comparison of value from three mentation and neural tube defects; evidence from a automated serum vitamin B12 and folate assays. J Anal case-control study in Western Australia and a review of Bio-Sci, 31: 291-298, 2008. recent publications. J Epidemiol Community Health, 24) Thorpe SJ, Heath A, Blackmore S, Lee A, Hamilton M, 307.