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Making Sense of Laboratory Tests of Folate Status: Folate Requirements to Sustain Normality

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Folates and Cobalamins

Abstract

The first event in the sequence leading to nutrient deficiency is development of negative nutrient balance, i.e., nutrient utilization, requirement, catabolism, and excretion exceeds nutrient ingestion, absorption, and anabolism. Persistent negative nutrient balance produces a sequence of stages or degrees along a continuum of nutrient depletion which are not always clearly demarcated one from the next but show an increasing deficiency, usually marked by sequential appearance of various biochemical and clinical deficits. In the case of folate, the continuum from normality to folate-deficiency megaloblastic anemia begins with negative folate balance and proceeds through three sequential stages, or degrees, of folate depletion, each defined by the appearance of specific biochemical and/or hematologic markers (Table 1, Fig. 1).

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References

  1. Herbert V (1962) Experimental nutritional folate deficiency in man. Trans Assoc Am Physicians 75:307–320

    PubMed  CAS  Google Scholar 

  2. Herbert V (1962) Minimal daily adult folate requirement. Arch Intern Med 110:649–652

    Article  PubMed  CAS  Google Scholar 

  3. Herbert V (1985) Biology of disease: megaloblastic anemia. Lab Invest 52:3–19

    PubMed  CAS  Google Scholar 

  4. Chanarin I (1979) The megaloblastic anemias, 2nd ed. Blackwell, Oxford

    Google Scholar 

  5. Herbert V, Colman N, Drivas G (1985) A proposed model of sequential stages in the development of folate deficiency anemia. Blood 66 (Suppl 1):30A

    Google Scholar 

  6. bis. Herbert V (1986) Folate deficiency, Book of abstracts. XXI congress, International Society of Hematology Sydney, Australia, 11–16 May 1986, p 216

    Google Scholar 

  7. Herbert V (1964) Studies of folate deficiency in man. Proc R Soc Med (Lond) 57:377–384

    CAS  Google Scholar 

  8. Weir DG, Ming PG, Scott JM (1985) Commentary: folate metabolism, the enterohepatic circulation and alcohol. Biochem Pharmacol 34:1–7

    Article  PubMed  CAS  Google Scholar 

  9. Herbert V, Das KC (1976) The role of vitamin B12 and folic acid in hemato- and other cell-poesis. Vitam Horm 34:1–30

    Article  PubMed  CAS  Google Scholar 

  10. Herbert V, Zalusky R (1962) Interrelations of vitamin B12 and folic acide metabolism: folic acid clearance studies. J Clin Invest 1263–1276

    Google Scholar 

  11. Noronha JM, Silverman M (1962) On folic acid, vitamin B12, methionine, and formiminu-noglutamate metabolism. In: Heinrich HC (ed) Vitamin B12 and intrinsic factor, 2nd European symposium Enke, Stuttgart, pp 728–736

    Google Scholar 

  12. Shane B, Stokstad ELR (1985) Vitamin B12-folate interrelationships, vol. 5. Ann Rev Nutr 5:115–141

    Google Scholar 

  13. Perry J, Chanarin I (1977) Abnormal folate polyglumate ratios in untreated pernicious anemia corrected by therapy. Br J Haematol 35:397–402

    Article  PubMed  CAS  Google Scholar 

  14. Herbert V (1977) Folic acid requirement in adults (including pregnant and lactating females) Summary of the workshop. In: Folic acid. Biochemistry and physiology in relation to the human nutrition requirement. National Research Council. Food and Nutrition Board, Washington DC. National Academy of Sciences Ed., pp 247–55, 277–293

    Google Scholar 

  15. Lindenbaum J. (1977) Folic acid requirement in situations of increased need. In: Folic acid. Biochemistry and physiology in relation to the human nutrition requirement. National Research Council. Food and Nutrition Board, National Academy of (Ed) Sciences, pp 256–276

    Google Scholar 

  16. Scott JM, Weir DG (1981) The methyl trap hypothesis. A physiological response in man to prevent methyl group deficiency in kwashiorkor (methionine deficiency) and an explanation for folic acid-induced exacerbation of subacute combined degeneration in pernicious anemia. Lancet 2:337–340

    Article  PubMed  CAS  Google Scholar 

  17. Carmel R, Karnaze DS (1985) The deoxyuridine suppression test identifies subtle cobal-amin deficiency in patients without typical megaloblastic anemia. JAMA 253:1284–1287

    Article  PubMed  CAS  Google Scholar 

  18. Metz J, Kelly A, Swett VC et al. (1968) Deranged DNA synthesis by bone marrow from vitamin B12 deficient humans. Br J Haematol 14:575

    Article  PubMed  CAS  Google Scholar 

  19. Das KC, Herbert V (1978) The lymphocyte as a marker of past nutritional status: Persistence of abnormal lymphocyte deoxyuridine () suppression test and chromosomes in patients with past deficiency of folate and vitamin B12. Br J Haematol 38:219–233

    Article  PubMed  CAS  Google Scholar 

  20. Das KC, Manusselis C, Herbert V (1980) Simplifying lymphocyte culture and the deoxyuridine suppression test by using whole blood (0.1 ml) instead of separated lymphocytes. Clin Chem 26:72

    PubMed  CAS  Google Scholar 

  21. Das KC, Herbert V, Colman N, Longo D (1978) Unmasking covert folate deficiency in iron-deficient subjects with neutrophil hypersegmentation: suppression tests on lymphocytes and bone marrow. Br J Haematol 39:357–375

    Article  PubMed  CAS  Google Scholar 

  22. Colman H, Herbert V (1980) Abnormal lymphocyte deoxyuridine suppression test: a reliable indicator of decreased lymphocyte folate levels. Am J Hematol 8:169–174

    Article  Google Scholar 

  23. Steinberg SE, Fonda S, Campbell CL, Hillman RS (1983) Cellular abnormalities of folate deficiency. Br J Haematol 54:605–612

    Article  PubMed  CAS  Google Scholar 

  24. Bothwell TH, Charlton RW, Cook JD, Finch CA (1979) Iron metabolism in man. Blackwell, St-Louis

    Google Scholar 

  25. English E, Finch CA (1984) Iron deficiency: A systematic approach. Drug Ther Bull 14(4): 45–46, 51–53

    Google Scholar 

  26. Green R, Kuhl W, Jacobson R et al. (1982) Masking of macrocytosis ba a-thalassemia in blacks with pernicious anemia. N Engl J Med 307:1322

    Article  PubMed  CAS  Google Scholar 

  27. Herbert V (1963) Current concepts in therapy: megaloblastic anemia. N Engl J Med 268:201–203, 368–371

    Article  PubMed  CAS  Google Scholar 

  28. Herbert V, Colman N, Jacob E (1980) Folic acid and vitamin B12. In: Goddhart RS, Shils ME (eds) Modern nutrition in health and disease. Lea and Febiger, Philadelphia, pp 229–259

    Google Scholar 

  29. Zalusky R, Herbert V (1961) Megaloblastic anemia in scurvy with response to 50 µg folic acid daily. N Engl J Med 265:1033–1038

    Article  PubMed  CAS  Google Scholar 

  30. Herbert V (1968) Nutritional requirements for vitamin B12 and folic acid. Am J Clin Nutr 21:743–752

    CAS  Google Scholar 

  31. Hoogstraten B, Cutner J, Natovitz B (1984) Sequence of recovery from multiple manifestations of folic acid deficiency. Mt Sinai J Med 31:10–16

    Google Scholar 

  32. Marshall RA, Jandl JH (1960) Response to “physiologic” doses of folic acid on megaloblastic anemia. Arch Intern Med 105:352

    Article  PubMed  CAS  Google Scholar 

  33. Amos RJ, Amess JAL, Hind CJ, Mollin DL (1982) Incidence and pathogenesis of acute megaloblastic bone marrow change in patients reveicing intensive care. Lancet 2:835–839

    Article  PubMed  CAS  Google Scholar 

  34. Amos RJ, Amess JAL, Nancekievill DG, Rees GM (1984) Prevention of nitrous oxide-induced megaloblastic changes in bone marrow using folinic acid. Br J Anaesth 56:103–107

    Article  PubMed  CAS  Google Scholar 

  35. Gailani SD, Carey RW, Holland JF, O’Malley JA (1970) Studies of folate deficiency in patients with neoplastic diseases. Cancer Res 30:327–333

    PubMed  CAS  Google Scholar 

  36. Canada Bureau of Nutritional Sciences Dept. of Health and Welfare Nutrition Canada. Ottawa (1977) Food consumtpion report, 1977.

    Google Scholar 

  37. Hoppner K, Lampi B (1980) Folate levels in human liver from autopsies in Canada. Am J Clin Nutr 33:862–864

    PubMed  CAS  Google Scholar 

  38. Bates CJ, Fleming M, Paul AA et al. (1980) Folate status and its relation to vitamin C in healthy elderly men and women. Age Ageing 9:241–248

    Article  PubMed  CAS  Google Scholar 

  39. Wu AI, Chanarin I, Slavin G, Levi AJ (1975) Folate deficiency in the alcoholic - its relationship to clinical and hematological abnormalities, liver disease, and folate stores. Br J Haematol 29:469–478

    Article  PubMed  CAS  Google Scholar 

  40. 40.National Research Council. Folic acid: biochemistry and physiology in relation to the human nutrition requirement. DC: Food and Nutrition Board, National Academy of Sciences, Washington

    Google Scholar 

  41. Spring JA, Robertson J, Buss DH (1979) Trace nutrients. 3. Magnesium, copper, zinc, vitamin B6, vitamin B12, and folic acid in the British national household food supply. Br J Nutr 41:487–493

    Article  PubMed  CAS  Google Scholar 

  42. Chanarin I, Rothman D, Ward A, Perry J (1968) Folate status and requirement in pregnancy. Br Med J 2:390–394

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  43. Colman N, Green R, Metz J (1975) Prevention of folate deficiency by food fortification. II. Absorption of folic acid from fortified staple foods. Am J Clin Nutr 28:459–464

    PubMed  CAS  Google Scholar 

  44. World Health Organization (WHO) (1968) Nutritional anemias: Report of a WHO scientific group. WHO technical report series 405. WHO, Geneva, p 37

    Google Scholar 

  45. Ek J (1983) Plasma, red cell, and breast milk folacin concentrations in lactating women. Am J Clin Nutr 38:929

    PubMed  CAS  Google Scholar 

  46. Herbert V (1981) Nutritional anemias of childhood - folate, B12: The megaloblastic anemias. In: Suskind RM (ed) Textbook of pediatric nutrition. Raven, New York, pp dl33–144

    Google Scholar 

  47. Asfour R, Wahbea N, Waslien C et al. (1977) Folacin requirements of children. III. Normal infants. Am J Clin Nutr 30:1098–1105

    PubMed  CAS  Google Scholar 

  48. Dallman P (1974) Iron deficiency and related nutritional anemias. In: Nathan DG, Oski F (eds) Hematology of infancy and childhood. Saunders, Philadelphia, pp 126–134

    Google Scholar 

  49. FAO/WHO (Food and Agriculture Organization/World Health Organization) (1970) Expert Group: requirements of ascorbic acid, vitamin D, vitamin B12, folate and iron. WHO technical report series 452. WHO, Geneva, p 75

    Google Scholar 

  50. Colman N, Hettiarachchy N, Herbert V (1980) Detection of a milk factor that facilitates folate uptake by intestinal cells. Science 211:1427–1429

    Article  Google Scholar 

  51. Colman N, Chen J-F, Gavin W, Herbert V (1981) Factors affecting enhancement by milk of folate uptake into intestinal cells. Blood 58(Suppl 1):26A

    Google Scholar 

  52. Rosenberg IH, Bowman BB, Cooper BA et al. (1982) Folate nutrition in the elderly. In: Symposium on the evidence relating selected vitamins and minerals to health and disease in the elderly population in the United States. Am J Clin Nutr 36 (Suppl): 1060–1066

    PubMed  CAS  Google Scholar 

  53. Russell RM, Krasinski SD, Samloff IM (1984) Correction of impaired folic acid (Ptlu) absorption by orally administered HCI in subjects with gastric atrophy. Clin Res 32:633A

    Google Scholar 

  54. Drasar BS, Hill MJ (1974) Human intestinal flora. Academic, New York

    Google Scholar 

  55. Herbert V, Drivas G, Manusselis C et al. (1984) Are colon bacteria a major source of cobal-amin analogues in human tissues? 24-hour human stool contains only about 5 µg cobalamin but about 100 µg apparent analogue (and 200 jig folate). Trans Assoc Am Physicians 97:161–171

    PubMed  CAS  Google Scholar 

  56. Ettinger S, Colman N (1985) Altered relationship between red cell and serum folate in the aged, suggesting impaired erythrocyte folate transport. Fed Proc 44(4): 1283

    Google Scholar 

  57. Blair JA (1983) Chemistry and biology of pteridines: pteridines and folic acid derivatives, de Gruyter, New York

    Google Scholar 

  58. Goldman ID, Chabner BA, Bertino JR (1983) Folyl and antifolyl polyglutamates. Plenum, New York

    Book  Google Scholar 

  59. Blakley RL, Benkovic SJ (1984) Folates and pterins: chemistry and biochemistry of folates, vol I. Wiley, New York

    Google Scholar 

  60. Hillman RS, Finch C (1985) The red cell manual, edn 5. Davis, Philadelphia

    Google Scholar 

  61. Herbert V (1987) The Herman Award Lecture. Nutrition science as a continually unfolding story: the folate and vitamin B12 paradigm. Am J Clin Nutr 46:387–402

    PubMed  CAS  Google Scholar 

  62. Lindenbaum J, Nath B (1980) Megaloblastic anemia and neutrophil hypersegmentation. Br J Haematol 44:551

    Article  Google Scholar 

  63. Lindenbaum J (1983) Status of laboratory testing in the diagnosis of megaloblstic anemia. Blood 61:624–627

    PubMed  CAS  Google Scholar 

  64. Herbert V, Memoli D, McAleer E, Colman N (1986) What is normal? Variation from the individuals norm for granulocyte “lobe average” and holo-transcobalamin II (holo-TC II) diagnoses vitamin B12 deficiency before variation from the laboratory norm. Clin Res 34:718A.

    Google Scholar 

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Herbert, V. (1989). Making Sense of Laboratory Tests of Folate Status: Folate Requirements to Sustain Normality. In: Cooper, B.A., Zittoun, J.A. (eds) Folates and Cobalamins. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74364-1_8

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  • DOI: https://doi.org/10.1007/978-3-642-74364-1_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-50653-9

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