View / Download pdf
version of this article
Dave and other members of the bpacnz team answer your clinical questions
Is there an association between the use of the combined oral contraceptive and Vitamin B12 deficiency?
Contributed by Linda Bryant MClinPharm FPSNZ Clinical Advisory Pharmacists Association (CAPA)
An association between use of the combined oral contraceptive and reduced Vitamin B12 serum concentrations
has been noted since 19691, but the clinical significance of this is debated.
Mean serum B12 concentrations may be 33-40% lower in women using the combined oral contraceptive compared
to non-users2,3. One study of 71 women using low dose (20 micrograms ethinyl estradiol) oral contraception
vs. 170 control non-users found that 13% of combined oral contraceptive users had Vitamin B12 concentrations
less than 130 pmol/L compared to none in the control group; 15% had subnormal Vitamin B12 concentrations (130-170
pmol/L) compared to 4% in the non-users; and 72% had normal Vitamin B12 concentrations compared to 92% of the
non-users.4 Another study found 50% of combined oral contraceptive users have serum B12 concentrations
less than normal (< 170 pmol/L) and 15% were clearly deficient (< 70 pmol/L).
Despite apparent low serum B12 concentrations in some users of the combined oral contraceptive, clinical
symptoms and macrocytosis are rare and tend only to be reported as case studies.5 An early study of 201 cases
of megaloblastic anaemia found only one case to be associated with oral contraceptive use.6
The reduction in serum Vitamin B12 in women using the combined oral contraceptive is not usually clinically
significant as vitamin metabolism and stores are normal. Further investigations are warranted if there are signs and
symptoms suggestive of deficiency or other factors such as diet.
It is now accepted that the reduced serum B12 concentrations observed in OC users do not usually represent
a true deficiency as absorption, excretion and stores of Vitamin B12 are usually normal. In addition, metabolic
markers for deficiency (methylmalonic acid and homocysteine) remain unchanged and clinical symptoms are rare.6
It is postulated that the low serum B12 is due to a reduction in Vitamin B12 binding proteins
in serum. In particular it may be due to reduced haptocorrin, the major binding protein for Vitamin B12, although
the mechanism is still unknown and under investigation.6
The reduction in serum B12 in women using the combined oral contraceptive is not usually clinically significant
as vitamin metabolism and stores are normal. Further investigations are warranted if there are signs and symptoms suggestive
of deficiency or other factors such as diet.
- Hjelt K, Brynskov J, Hippe E, Lundstrom P, Munck O. Oral contraceptives and cobalamin (Vitamin B12) metabolism.
Acta Obstet et Gynecol Scand. 1985;64:59-63
- Green T, Houghton L, Donovan U, Gibson R, O'Connor D. Oral contraceptives did not affect biochemical folate indexes
and homocysteine concentrations in adolescent females. J Am Diet Assoc. 1998;98:49-55
- Wynn V. Vitamins and oral contraceptive use. Lancet. 1975; 1(7906):561-4
- Sutterlin M, Bussen S, Rieger L, Dietl J, Steck T. Serum folate and Vitamin B12 levels in women using
modern oral contraceptives (OC) containing 20 micrograms ethinyl estradiol. Eur J Obstet Gynecol Reprod Biol. 2003;107:57-61
- Kornberg A, Segal R, Theitler J et al. Folic acid deficiency, megaloblastic anaemia and peripheral polyneuropathy
due to oral contraceptives. Isr J Med Sci. 1989;23:142-5
- Bor M. Do we have any good reason to suggest restricting the use of oral contraceptives in women with pre-existing
Vitamin B12 deficiency? Eur J Obstet Gynecol Reprod Biol. 2004;115:240-1