Phytotherapy Review & Commentary: Blue Cohosh; Not for Labor?

FNIMH = Fellow, National Institute of Medical herbalists (UK)

FNHAA = Fellow, National Herbalists Association of Australia

Several adverse events have been associated with maternal ingestion of blue cohosh (Caulophyllum thalictroides) or products containing blue cohosh. A midwife attempted induction of labor using a combination of blue and black cohosh given orally at around 42 weeks gestation.[ 1] After normal labor, the female baby was not able to breathe spontaneously and was administered cardiac massage and oxygen. The child sustained CNS hypoxic-ischemic damage, which may have been related to myocardial toxicity.[ 2] In their discussion of possible mechanisms behind this adverse reaction the authors offered extrapolations and generalizations from animal studies.[ 1] The relevance of these extrapolations was appropriately challenged, particularly those pertaining to black cohosh (Cimicifuga racemosa).[ 3]

Profound neonatal congestive heart failure was linked to maternal consumption of blue cohosh tablets.[ 4] Beginning about one month before delivery the mother took three tablets a day, even though she was advised to take only one per day. The infant exhibited signs of severe cardiac injury and was hospitalized for a total of 31 days. On follow-up at 2 years of age the child was doing well, but remained on digoxin therapy. Cardiomegaly and mildly reduced left ventricular function were evident.

The FDA's Special Nutritionals Adverse Event Monitoring System database (which lists adverse events but is not subject to preconditions, analysis or peer review) also contains two cases possibly associated with blue cohosh, including stroke in an infant.[ 5]

Attempts have been made to understand these adverse events in terms of the phytochemical content of blue cohosh.[ 6] Four known alkaloids were newly identified in blue cohosh and a novel alkaloid thalictroidine, was discovered. The alkaloids in blue cohosh belong to several phytochemical classes, but are predominantly from the quinolizidine class. These alkaloids were tested in an in vitro rat embryo culture. Taspine showed high embryotoxicity and N-methylcytisine was found to be teratogenic. The authors caution that more experiments are needed to substantiate their outcomes and examine possible consequences for the human fetus.

Commentary

Blue cohosh was traditionally used to alleviate dysmenorrhea and pain of childbirth and to promote delivery.[ 7] It was also used for amenorrhea, rheumatic pain and epilepsy. More recently it has been included in a clinically-researched proprietary formula (Mastodynon) for the alleviation of premenstrual syndrome and mastalgia.[ 8]

A recent survey reported that herbal therapy was recommended by 75% of US midwives for pregnant and post partum patients). A pertinent finding was that blue cohosh was among the herbs commonly prescribed for women past their due dates. The question which must be asked, given this widespread usage, is why more adverse events have not been reported.

It is generally acknowledged that blue cohosh is contraindicated in pregnancy, although this restriction is not always promoted or observed. However, toxicity from short-term use of blue cohosh to induce labor (as in the first case history) is unlikely to explain the serious adverse effects observed. Perhaps the blue cohosh was used for longer periods than stated, or maybe the adverse effects were idiosyncratic rather than toxic.

Given these recent findings concerning the blue cohosh alkaloids, and the possible association with serious adverse reactions, caution should prevail with its use to promote delivery. Alternative herbal treatments are recommended until more information becomes available.

The presence of quinolizidine alkaloids including sparteine in blue cohosh could explain both its oxytocic activity and its occasional toxicity. Sparteine was once widely used as an oxytocic drug, but it fell out of favor because of the uterine spasm which occurred in women who were unable to metabolize it effectively. About 5% of male and female subjects studied were unable to metabolize sparteine by N-oxidation[ 10] and this defect appears to have a genetic basis.[ 11]

N-methylcytisine, the proposed teratogenic compound in blue cohosh, is a quinolizidine alkaloid with a structure closely related to sparteine. Perhaps, like sparteine, a percentage of women are unable to efficiently metabolize this alkaloid (and others in blue cohosh?) resulting in the observed adverse effects.
References

1. Gunn TR, Wright IM. The use of black and blue cohosh in labour. N Z Med J 1996; 109(1032):410-411

2. Wright IMR. Neonatal effects of maternal consumption of blue cohosh. J Pediatr 1999; 134(3):384-385

3. Baillie N, Rasmussen P. Black and blue cohosh in labour. NZ Med J 1997; 110(1036):20-21

4. Jones TK, Lawson BM. Profound neonatal congestive heart failure caused by maternal consumption of blue cohosh herbal medication. J Pediatr 1998; 132:550-552

5. http://vm.cfsan.fda.gov/~dms/aems.html#searchbox

6. Kennelly EJ, Flynn TJ, Mazzola EP et al. Detecting potential teratogenic alkaloids from blue cohosh rhizomes using an in vitro rat embryo culture. J Nat Prod 1999; 62(10):1385-1389

7. Felter HW, Lloyd JU. King's American Dispensatory, 18th Edn, 3rd revision, Vol 1, 1905; reprinted Portland: Eclectic Medical Publications, 1983: pp 468-472

8. Kubista E, Muller G, Spona J. [Treatment of mastepathies with cyclic mastodynia. Clinical results and hormonal profiles]. Rev Fr Gynecol Obstet 1987; 82(4):221-227

9. Allaire AD, Moos MK, Wells SR. Complementary and alternative medicine in pregnancy: a survey of North Carolina certified nurse-midwives. Obstet Gynecol2000; 95(1):19-23

10. Eichelbaum M, Spannbrucker N, Steincke Bet al. Defective N-oxidation of sparteine in man: A new pharmacogenetic defect. Eur J Clin Pharmacol 1979; 16:183-187

11. Vinks A, Inaba T, Otton SV et al. Sparteine metabolism in Canadian Caucasians. Clin Pharmacol Ther 1982; 31(1):23-29

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By Kerry Bone

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