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. 1985 Aug;31:1523–1526.

Effects of Oral Contraceptive Usage on B12 and Folate Levels

J A Mountifield
PMCID: PMC2327375  PMID: 21274038

Abstract

Evidence shows a fall in folate and vitamin B12 levels in women taking oral contraceptives. These levels do not return to normal until about three months after usage has stopped, but many women become pregnant during this time. This paper examines the evidence for an effect on such pregnancies of lowered folate and B12 levels, and concludes that nutritional counselling should begin in schools, should continue in the medical care of women in their childbearing years, and folic acid supplementation should begin as soon as pregnancy is confirmed. This supplementation should be periconceptional in women at higher risk of bearing a child with neural tube defects, and greater in multiple pregnancy, malabsorption, hemolytic anemia and concomitant use of drugs known to be folate antogonists.

Keywords: Oral contraceptives, vitamin B12, serum folate

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Selected References

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  1. Blot I., Papiernik E., Kaltwasser J. P., Werner E., Tchernia G. Influence of routine administration of folic acid and iron during pregnancy. Gynecol Obstet Invest. 1981;12(6):294–304. doi: 10.1159/000299659. [DOI] [PubMed] [Google Scholar]
  2. Blot I., Rey A., Kaltwasser J. P., Francoual J., Papiernik E., Tchernia G. Folate and iron deficiencies in mothers and their newborn children. Blut. 1982 May;44(5):297–303. doi: 10.1007/BF00320704. [DOI] [PubMed] [Google Scholar]
  3. Botez M. I. Folate deficiency and neurological disorders in adults. Med Hypotheses. 1976 Jul-Aug;2(4):135–140. doi: 10.1016/0306-9877(76)90068-2. [DOI] [PubMed] [Google Scholar]
  4. Briggs M., Briggs M. Endocrine effects on serum-vitamin-B 12 . Lancet. 1972 Nov 11;2(7785):1037–1037. doi: 10.1016/s0140-6736(72)92457-9. [DOI] [PubMed] [Google Scholar]
  5. Butterworth C. E., Jr, Hatch K. D., Gore H., Mueller H., Krumdieck C. L. Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am J Clin Nutr. 1982 Jan;35(1):73–82. doi: 10.1093/ajcn/35.1.73. [DOI] [PubMed] [Google Scholar]
  6. Castrén O. M., Rossi R. R. Effect of oral contraceptives on serum folic acid content. J Obstet Gynaecol Br Commonw. 1970 Jun;77(6):548–550. doi: 10.1111/j.1471-0528.1970.tb03565.x. [DOI] [PubMed] [Google Scholar]
  7. Daniel W. A., Jr, Mounger J. R., Perkins J. C. Obstetric and fetal complications in folate-deficient adolescent girls. Am J Obstet Gynecol. 1971 Sep 15;111(2):233–238. doi: 10.1016/0002-9378(71)90895-7. [DOI] [PubMed] [Google Scholar]
  8. Davis R. E., Smith B. K. Pyridoxal, vitamin B12 and folate metabolism in women taking oral contraceptive agents. S Afr Med J. 1974 Sep 21;48(46):1937–1940. [PubMed] [Google Scholar]
  9. FRASER J. L., WATT H. J. MEGALOBLASTIC ANEMIA IN PREGNANCY AND THE PUERPERIUM. Am J Obstet Gynecol. 1964 Jun 15;89:532–534. doi: 10.1016/0002-9378(64)90559-9. [DOI] [PubMed] [Google Scholar]
  10. Flury R., Angehrn W. Folsäuremangelanämie infolge Einnahme oraler Kontrazeptiva. Schweiz Med Wochenschr. 1972 Nov 4;102(44):1628–1629. [PubMed] [Google Scholar]
  11. HERBERT V. Experimental nutritional folate deficiency in man. Trans Assoc Am Physicians. 1962;75:307–320. [PubMed] [Google Scholar]
  12. HIBBARD B. M., HIBBARD E. D. AETIOLOGICAL FACTORS IN ABRUPTIO PLACENTAE. Br Med J. 1963 Dec 7;2(5370):1430–1436. doi: 10.1136/bmj.2.5370.1430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hibbard B. M. Folates and the fetus. S Afr Med J. 1975 Jul 16;49(30):1223–1226. [PubMed] [Google Scholar]
  14. Hibbard B. M., Hibbard E. D., Jeffcoate T. N. Folic acid and reproduction. Acta Obstet Gynecol Scand. 1965;44(3):375–400. doi: 10.3109/00016346509155874. [DOI] [PubMed] [Google Scholar]
  15. Hibbard B. M., Jeffcoate T. N. Abruptio placentae. Obstet Gynecol. 1966 Feb;27(2):155–167. [PubMed] [Google Scholar]
  16. Laurence K. M., James N., Campbell H. Quality of diet and blood folate concentrations. Br Med J (Clin Res Ed) 1982 Jul 17;285(6336):216–216. doi: 10.1136/bmj.285.6336.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Laurence K. M., James N., Miller M., Campbell H. Increased risk of recurrence of pregnancies complicated by fetal neural tube defects in mothers receiving poor diets, and possible benefit of dietary counselling. Br Med J. 1980 Dec 13;281(6255):1592–1594. doi: 10.1136/bmj.281.6255.1592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lewis F. B. Folate deficiency due to oral contraceptives. Minn Med. 1974 Dec;57(12):945–946. [PubMed] [Google Scholar]
  19. Liu F. T., Lin H. S. Effect of the contraceptive steroids norethynodrel and mestranol on dental caries activity in young adult female rats. J Dent Res. 1973 Jul-Aug;52(4):753–757. doi: 10.1177/00220345730520041901. [DOI] [PubMed] [Google Scholar]
  20. Martinez O., Roe D. A. Effect of oral contraceptives on blood folate levels in pregnancy. Am J Obstet Gynecol. 1977 Jun 1;128(3):255–261. doi: 10.1016/0002-9378(77)90618-4. [DOI] [PubMed] [Google Scholar]
  21. McLean F. W., Heine M. W., Held B., Streiff R. R. Relationship between the oral contraceptive and folic acid metabolism. Serum folate concentrations. Am J Obstet Gynecol. 1969 Jul 1;104(5):745–747. doi: 10.1016/0002-9378(69)90619-x. [DOI] [PubMed] [Google Scholar]
  22. Paine C. J., Grafton W. D., Dickson V. L., Eichner E. R. Oral contraceptives, serum folate, and hematologic status. JAMA. 1975 Feb 17;231(7):731–733. [PubMed] [Google Scholar]
  23. Paton A. Oral contraceptives and folate deficiency. Lancet. 1969 Feb 22;1(7591):418–418. doi: 10.1016/s0140-6736(69)91386-5. [DOI] [PubMed] [Google Scholar]
  24. Prasad A. S., Oberleas D., Moghissi K. S., Stryker J. C., Lei K. Y. Effect of oral contraceptive agents on nutrients: II. Vitamins. Am J Clin Nutr. 1975 Apr;28(4):385–391. doi: 10.1093/ajcn/28.4.385. [DOI] [PubMed] [Google Scholar]
  25. Prasad A. S., Oberleas D., Moghissi K. S., Stryker J. C., Lei K. Y. Effect of oral contraceptive agents on nutrients: II. Vitamins. Am J Clin Nutr. 1975 Apr;28(4):385–391. doi: 10.1093/ajcn/28.4.385. [DOI] [PubMed] [Google Scholar]
  26. Pritchard J. A., Scott D. E., Whalley P. J., Haling R. F., Jr Infants of mothers with megaloblastic anemia due to folate deficiency. JAMA. 1970 Mar 23;211(12):1982–1984. [PubMed] [Google Scholar]
  27. Pritchard J. A., Scott D. E., Whalley P. J. Maternal folate deficiency and pregnancy wastage. IV. Effects of folic acid supplements, anticonvulsants, and oral contraceptives. Am J Obstet Gynecol. 1971 Feb 1;109(3):341–346. doi: 10.1016/0002-9378(71)90326-7. [DOI] [PubMed] [Google Scholar]
  28. Reynolds S. R. Hydatidiform mole: a vascular congenital anomaly. Obstet Gynecol. 1976 Feb;47(2):244–250. [PubMed] [Google Scholar]
  29. Roberts P. D., James H., Petrie A., Morgan J. O., Hoffbrand A. V. Vitamin B 12 status in pregnancy among immigrants to Britain. Br Med J. 1973 Jul 14;3(5871):67–72. doi: 10.1136/bmj.3.5871.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ryser J. E., Farquet J. J., Petite J. Megaloblastic anemia due to folic acid deficiency in a young woman on oral contraceptives. Acta Haematol. 1971;45(5):319–324. doi: 10.1159/000208642. [DOI] [PubMed] [Google Scholar]
  31. SOLOMONS E., LEE S. L., WASSERMAN M., MALKIN J. Association of anaemia in pregnancy and folic acid deficiency. J Obstet Gynaecol Br Emp. 1962 Oct;69:724–728. doi: 10.1111/j.1471-0528.1962.tb01270.x. [DOI] [PubMed] [Google Scholar]
  32. Scott D. E., Whalley P. J., Pritchard J. A. Maternal folate deficiency and pregnancy wastage. II. Fetal malformation. Obstet Gynecol. 1970 Jul;36(1):26–28. [PubMed] [Google Scholar]
  33. Shojania A. M., Hornady G. J., Barnes P. H. The effect of oral contraceptives on folate metabolism. Am J Obstet Gynecol. 1971 Nov;111(6):782–791. doi: 10.1016/0002-9378(71)90489-3. [DOI] [PubMed] [Google Scholar]
  34. Shojania A. M., Hornady G., Barnes P. H. Oral contraceptives and serum-folate level. Lancet. 1968 Jun 22;1(7556):1376–1377. doi: 10.1016/s0140-6736(68)92081-3. [DOI] [PubMed] [Google Scholar]
  35. Shojania A. M. Oral contraceptives: effect of folate and vitamin B12 metabolism. Can Med Assoc J. 1982 Feb 1;126(3):244–247. [PMC free article] [PubMed] [Google Scholar]
  36. Smithells R. W. Environmental teratogens of man. Br Med Bull. 1976 Jan;32(1):27–33. doi: 10.1093/oxfordjournals.bmb.a071319. [DOI] [PubMed] [Google Scholar]
  37. Smithells R. W., Sheppard S., Schorah C. J., Seller M. J., Nevin N. C., Harris R., Read A. P., Fielding D. W. Possible prevention of neural-tube defects by periconceptional vitamin supplementation. Lancet. 1980 Feb 16;1(8164):339–340. doi: 10.1016/s0140-6736(80)90886-7. [DOI] [PubMed] [Google Scholar]
  38. Smithells R. W., Sheppard S., Schorah C. J. Vitamin deficiencies and neural tube defects. Arch Dis Child. 1976 Dec;51(12):944–950. doi: 10.1136/adc.51.12.944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stebbins R., Scott J., Herbert V. Drug-induced megaloblastic anemias. Semin Hematol. 1973 Jul;10(3):235–251. [PubMed] [Google Scholar]
  40. Stephens M. E., Craft J., Peters T. J., Hoffbrand A. V. Oral contraceptives and folate metabolism. Clin Sci. 1972 Apr;42(4):405–414. doi: 10.1042/cs0420405. [DOI] [PubMed] [Google Scholar]
  41. Stone M. L., Luhby A. L., Feldman R., Gordon M., Cooperman J. M. Folic acid metabolism in pregnancy. Am J Obstet Gynecol. 1967 Nov 1;99(5):638–648. doi: 10.1016/0002-9378(67)90412-7. [DOI] [PubMed] [Google Scholar]
  42. Streiff R. R. Folate deficiency and oral contraceptives. JAMA. 1970 Oct 5;214(1):105–108. [PubMed] [Google Scholar]
  43. Streiff R. R., Little A. B. Folic acid deficiency in pregnancy. N Engl J Med. 1967 Apr 6;276(14):776–779. doi: 10.1056/NEJM196704062761403. [DOI] [PubMed] [Google Scholar]
  44. The pacing industry. Br Med J (Clin Res Ed) 1981 Jan 3;282(6257):2–3. [PMC free article] [PubMed] [Google Scholar]
  45. Thornton W. E. Folate deficiency in puerperal psychosis. Am J Obstet Gynecol. 1977 Sep 15;129(2):222–223. doi: 10.1016/0002-9378(77)90752-9. [DOI] [PubMed] [Google Scholar]
  46. Thornton W. E., Thornton B. P. Folic acid, mental function, and dietary habits. J Clin Psychiatry. 1978 Apr;39(4):315-9, 322. [PubMed] [Google Scholar]
  47. Wertalik L. F., Metz E. N., LoBuglio A. F., Balcerzak S. P. Decreased serum B 12 levels with oral contraceptive use. JAMA. 1972 Sep 18;221(12):1371–1374. [PubMed] [Google Scholar]
  48. Whalley P. J., Scott D. E., Pritchard J. A. Maternal folate deficiency and pregnancy wastage. I. Placental abruption. Am J Obstet Gynecol. 1969 Nov 1;105(5):670–678. doi: 10.1016/0002-9378(69)90003-9. [DOI] [PubMed] [Google Scholar]
  49. Whitehead N., Reyner F., Lindenbaum J. Megaloblastic changes in the cervical epithelium. Association with oral contraceptive therapy and reversal with folic acid. JAMA. 1973 Dec 17;226(12):1421–1424. [PubMed] [Google Scholar]

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