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European Journal of Nutrition

, Volume 52, Issue 2, pp 497–504 | Cite as

Factors affecting the distribution of folate forms in the serum of elderly German adults

  • Susanne H. Kirsch
  • Wolfgang Herrmann
  • Rudolf Eckert
  • Jürgen Geisel
  • Rima ObeidEmail author
Original Contribution

Abstract

Purpose

We investigated the roles of age, vitamin B12 markers, and the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism as determinants of folate forms in serum.

Methods

We measured the serum concentrations of (6S)-5-CH3–H4folate, (6S)-H4folate, (6S)-5-HCO–H4folate, (6R)-5,10-CH+–H4folate, and folic acid in 146 non-supplemented older participants (median age 74 years). The concentrations of total vitamin B12, holotranscobalamin (holoTC), methylmalonic acid (MMA), and total homocysteine (tHcy) were also measured.

Results

Elevated metabolites (MMA > 271 nmol/L and tHcy > 12.0 μmol/L) were found in 24.0 and 63.0 % of the participants, respectively. We found a significant age-dependent decrease (participants with a median age of 87 years compared with participants with a median age of 60 years) in the sum of serum folate levels, the (6S)-5-CH3–H4folate concentration, and the (6S)-5-CH3–H4folate proportion. In addition, participants with elevated metabolite levels were older, had lower concentrations of the sum of folates and (6S)-5-CH3–H4folate, and had higher concentrations of (6S)-5-CHO–H4folate and creatinine but had a comparable holoTC/total vitamin B12 ratio. No association was found between the MTHFR C677T genotype and serum folate forms.

Conclusion

Low serum (6S)-5-CH3–H4folate concentrations and the proportion of (6S)-5-CH3–H4folate (percentage of the sum of folate forms) are related to older age and elevated MMA and tHcy levels.

Keywords

Folate Folic acid Age Elderly Vitamin B12 

Abbreviations

holoTC

Holotranscobalamin

MMA

Methylmalonic acid

MTHFR

5,10-Methylenetetrahydrofolate reductase

tHcy

Total homocysteine

UPLC–MS/MS

Ultra-performance liquid chromatography/tandem mass spectrometry

Notes

Acknowledgments

We thank Mrs. Marion Bodis and Mrs. Vera Kruse for their excellent assistance in the course of this study.

Conflict of interest

None.

References

  1. 1.
    Pfeiffer CM, Fazili Z, McCoy L, Zhang M, Gunter EW (2004) Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay. Clin Chem 50:423–432CrossRefGoogle Scholar
  2. 2.
    Kirsch SH, Knapp JP, Herrmann W, Obeid R (2010) Quantification of key folate forms in serum using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 878:68–75CrossRefGoogle Scholar
  3. 3.
    Smulders YM, Smith DE, Kok RM, Teerlink T, Gellekink H, Vaes WH, Stehouwer CD, Jakobs C (2007) Red blood cell folate vitamer distribution in healthy subjects is determined by the methylenetetrahydrofolate reductase C677T polymorphism and by the total folate status. J Nutr Biochem 18:693–699CrossRefGoogle Scholar
  4. 4.
    Blencowe H, Cousens S, Modell B, Lawn J (2010) Folic acid to reduce neonatal mortality from neural tube disorders. Int J Epidemiol 39(Suppl 1):i110–i121CrossRefGoogle Scholar
  5. 5.
    Herrmann W, Herrmann M, Obeid R (2007) Hyperhomocysteinaemia: a critical review of old and new aspects. Curr Drug Metab 8:17–31CrossRefGoogle Scholar
  6. 6.
    Wang X, Qin X, Demirtas H, Li J, Mao G, Huo Y, Sun N, Liu L, Xu X (2007) Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 369:1876–1882CrossRefGoogle Scholar
  7. 7.
    Cui R, Iso H, Date C, Kikuchi S, Tamakoshi A (2010) Dietary folate and vitamin b6 and B12 intake in relation to mortality from cardiovascular diseases: Japan collaborative cohort study. Stroke 41:1285–1289CrossRefGoogle Scholar
  8. 8.
    Ulrich CM (2007) Folate and cancer prevention: a closer look at a complex picture. Am J Clin Nutr 86:271–273Google Scholar
  9. 9.
    Kennedy DA, Stern SJ, Moretti M, Matok I, Sarkar M, Nickel C, Koren G (2011) Folate intake and the risk of colorectal cancer: a systematic review and meta-analysis. Cancer Epidemiol 35:2–10CrossRefGoogle Scholar
  10. 10.
    Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM (1998) Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 55:1449–1455CrossRefGoogle Scholar
  11. 11.
    Yang Q, Botto LD, Erickson JD, Berry RJ, Sambell C, Johansen H, Friedman JM (2006) Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation 113:1335–1343CrossRefGoogle Scholar
  12. 12.
    Obeid R, Schadt A, Dillmann U, Kostopoulos P, Fassbender K, Herrmann W (2009) Methylation status and neurodegenerative markers in Parkinson disease. Clin Chem 55:1852–1860CrossRefGoogle Scholar
  13. 13.
    Herrmann W, Quast S, Ullrich M, Schultze H, Bodis M, Geisel J (1999) Hyperhomocysteinemia in high-aged subjects: relation of B-vitamins, folic acid, renal function and the methylenetetrahydrofolate reductase mutation. Atherosclerosis 144:91–101CrossRefGoogle Scholar
  14. 14.
    Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH (1993) Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 270:2693–2698CrossRefGoogle Scholar
  15. 15.
    Flynn A, Hirvonen T, Mensink GB, Ocke MC, Serra-Majem L, Stos K, Szponar L, Tetens I, Turrini A, Fletcher R, Wildemann T (2009) Intake of selected nutrients from foods, from fortification and from supplements in various European countries. Food Nutr Res 53. doi: 10.3402/fnr.v53i0.2038
  16. 16.
    Drogan D, Klipstein-Grobusch K, Dierkes J, Weikert C, Boeing H (2006) Dietary intake of folate equivalents and risk of myocardial infarction in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam study. Public Health Nutr 9:465–471CrossRefGoogle Scholar
  17. 17.
    Obeid R, Schorr H, Eckert R, Herrmann W (2004) Vitamin B12 status in the elderly as judged by available biochemical markers. Clin Chem 50:238–241CrossRefGoogle Scholar
  18. 18.
    Clarke R, Grimley EJ, Schneede J, Nexo E, Bates C, Fletcher A, Prentice A, Johnston C, Ueland PM, Refsum H, Sherliker P, Birks J, Whitlock G, Breeze E, Scott JM (2004) Vitamin B12 and folate deficiency in later life. Age Ageing 33:34–41CrossRefGoogle Scholar
  19. 19.
    Baik HW, Russell RM (1999) Vitamin B12 deficiency in the elderly. Annu Rev Nutr 19:357–377CrossRefGoogle Scholar
  20. 20.
    Homocysteine Lowering Trialists’ Collaboration (2005) Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr 82:806–812Google Scholar
  21. 21.
    Fried LF, Shlipak MG, Crump C, Bleyer AJ, Gottdiener JS, Kronmal RA, Kuller LH, Newman AB (2003) Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals. J Am Coll Cardiol 41:1364–1372CrossRefGoogle Scholar
  22. 22.
    Stabler SP, Lindenbaum J, Savage DG, Allen RH (1993) Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency. Blood 81:3404–3413Google Scholar
  23. 23.
    Orning L, Rian A, Campbell A, Brady J, Fedosov SN, Bramlage B, Thompson K, Quadros EV (2006) Characterization of a monoclonal antibody with specificity for holo-transcobalamin. Nutr Metab (Lond) 3:3. doi: 10.1186/1743-7075-3-3 CrossRefGoogle Scholar
  24. 24.
    Ronaghi M, Uhlen M, Nyren P (1998) A sequencing method based on real-time pyrophosphate. Science 281:363–365CrossRefGoogle Scholar
  25. 25.
    Verri A, Focher F, Tettamanti G, Grazioli V (2005) Two-step genetic screening of thrombophilia by pyrosequencing. Clin Chem 51:1282–1284CrossRefGoogle Scholar
  26. 26.
    Herrmann W, Obeid R, Schorr H, Geisel J (2003) Functional vitamin B12 deficiency and determination of holotranscobalamin in populations at risk. Clin Chem Lab Med 41:1478–1488Google Scholar
  27. 27.
    Obeid R, Kirsch SH, Kasoha M, Eckert R, Herrmann W (2011) Concentrations of unmetabolized folic acid and primary folate forms in plasma after folic acid treatment in older adults. Metabolism 60:673–680Google Scholar
  28. 28.
    Fazili Z, Pfeiffer CM, Zhang M (2007) Comparison of serum folate species analyzed by LC–MS/MS with total folate measured by microbiologic assay and Bio-Rad radioassay. Clin Chem 53:781–784CrossRefGoogle Scholar
  29. 29.
    Shane B, Stokstad EL (1985) Vitamin B12-folate interrelationships. Annu Rev Nutr 5:115–141CrossRefGoogle Scholar
  30. 30.
    Bailey RL, Mills JL, Yetley EA, Gahche JJ, Pfeiffer CM, Dwyer JT, Dodd KW, Sempos CT, Betz JM, Picciano MF (2010) Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged ≥60 y in the United States. Am J Clin Nutr 92:383–389CrossRefGoogle Scholar
  31. 31.
    Reed LS, Archer MC (1980) Oxidation of tetrahydrofolic acid by air. J Agric Food Chem 28:801–805CrossRefGoogle Scholar
  32. 32.
    De Meer K, Smulders YM, Dainty JR, Smith DE, Kok RM, Stehouwer CD, Finglas PM, Jakobs C (2005) [6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults. Eur J Clin Nutr 59:1409–1416CrossRefGoogle Scholar
  33. 33.
    Tisman G, Herbert V (1973) B 12 dependence of cell uptake of serum folate: an explanation for high serum folate and cell folate depletion in B 12 deficiency. Blood 41:465–469Google Scholar
  34. 34.
    Nixon PF, Bertino JR (1972) Impaired utilization of serum folate in pernicious anemia. A study with radiolabeled 5-methyltetrahydrofolate. J Clin Invest 51:1431–1439CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Susanne H. Kirsch
    • 1
  • Wolfgang Herrmann
    • 1
  • Rudolf Eckert
    • 2
  • Jürgen Geisel
    • 1
  • Rima Obeid
    • 1
    Email author
  1. 1.Department of Clinical Chemistry and Laboratory MedicineSaarland University HospitalHomburgGermany
  2. 2.Geriatric Health CenterSt. IngbertGermany

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