Drugs in Pregnancy and Lactation: Tenth Edition

GOLDENSEAL

Herb

PREGNANCY RECOMMENDATION: Contraindicated

BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity (High or Frequent Doses)

PREGNANCY SUMMARY

Goldenseal and its active isoquinoline alkaloids, hydrastine and berberine, should be avoided in pregnancy because they can stimulate uterine contractions and induce labor. Although dosage information and clinical reports are lacking, goldenseal has been used traditionally as an abortifacient. Nevertheless, goldenseal preparations have been available for centuries, and the absence of reports describing human pregnancy toxicity suggests low risk, at least from usual doses. However, the safest course is to avoid this herb in pregnancy, especially high doses and/or frequent use.

FETAL RISK SUMMARY

The perennial herb, goldenseal is found in the woods of the Ohio River valley and other locations in the northeastern United States. It also is grown commercially in Washington State, New York, North Carolina, and Canada (1). Goldenseal has been used for hundreds of years and is one of the five top-selling herbal products in the United States (2). The principal active components, found in the roots, include the isoquinoline alkaloids (range of concentrations) hydrastine (1.5%–4%) and berberine (0.5%–6%). Other alkaloids with apparently less activity include canadine (tetrahydroberberine), palmatine, and berberastine. For goldenseal, the typical daily doses for tablets and capsules is 0.75–3.4 g/day, 0.9–3 mL of fluid extract, 6–12 mL of tincture, and 1.5–3 g of dried root as a decoction (1,2).

Goldenseal is a component of many over-the-counter products, such as dietary supplements, digestive aids, eardrops, cold/flu and allergy remedies, and laxatives. The herb or individual alkaloids have been used for their antimicrobial, antidiarrheal, anti-inflammatory, antiproliferative, cardiovascular, ophthalmic, immunostimulant, and other effects, but controlled trials are lacking. Moreover, the alkaloids are poorly absorbed when taken orally (1,2).

Reproduction studies have been conducted in rats and mice (38). In pregnant rats, a daily oral dose that was 65 times the human dose based on body weight was given on gestation days 1–8 or 8–15 (3). Compared with controls, there was no increase in pre- or postimplantation losses, no change in fetal weight, and no difference in the incidence of external or internal malformations. In a separate study, rat embryos were explanted on gestation day 10.5 and cultured with increasing concentrations (0.5–6 µL/mL) of goldenseal extract for 26 hours in rat serum. Compared with nonexposed embryos, growth restriction and embryotoxicity were observed in a dose-dependent manner beginning at 1 µL/mL. The different results observed were thought to be due to the poor oral absorption of goldenseal. Because goldenseal is unlikely to be absorbed to the same extent as the concentrations used in the in vitro study, the authors thought that the herb, at the prescribed human dose, would not cause human embryo toxicity (3).

In a series of studies conducted by the National Toxicology Program, no developmental toxicity was observed in pregnant rats and mice at doses that were less than the maternal toxic dose (49).

It is not known if the active isoquinoline alkaloids of goldenseal cross the human placenta. The molecular weights of two alkaloids, berberine (about 353) and canadine (about 339), are low enough to cross. However, the poor systemic bioavailability after recommended oral doses suggests that little will reach the maternal circulation and be available to expose the embryo–fetus. Higher doses, however, may result in greater bioavailability and, consequently, greater embryo–fetal exposure.

Hydrastine and berberine are known to be uterine stimulants (1,2). Although published clinical trials are lacking, herbs containing these constituents have been used traditionally as abortifacients (2). The dose required for this effect has not been published.

BREASTFEEDING SUMMARY

No reports describing the use of goldenseal or its active constituents during lactation have been located. Systemic absorption is poor after ingestion of recommended doses, so the amount of alkaloids in milk is most likely very low. High or frequent doses, however, might result in systemic concentrations and excretion into breast milk. Berberine, one of the active isoquinoline alkaloids of goldenseal, is known to displace bilirubin from albumin in animal studies, resulting in increased serum total and direct bilirubin concentrations (2). The risk of this for a nursing infant is unknown but probably low if the mother is ingesting low, infrequent doses of goldenseal. However, high doses or frequent use of goldenseal, or use of the specific alkaloids, could place the infant at risk of icterus or jaundice. Until human data are available, the safest course is to avoid goldenseal or its active alkaloids while breastfeeding (10).

References

1.Goldenseal. The Review of Natural Products. St. Louis, MO: Facts and Comparisons, 2008.

2.Goldenseal (Hydrastis canadensis). Natural Standard Monograph. Available at www.naturalstandard.com. Accessed March 3, 2009.

3.Yao M, Ritchie HE, Brown-Woodman D. A reproductive screening test for goldenseal. Birth Defects Res B Dev Reprod Toxicol 2005;74:399–404.

4.NTP Study TER98007. Developmental Toxicity Evaluation for Goldenseal Root Powder (Hydrastis canadensis) Administered in the Feed to Sprague-Dawley (CD®) Rats on Gestational Days 6 to 20. National Toxicology Program. Springfield, VA: National Technical Information Services, 2002.

5.NTP Study TER98008. Developmental Toxicity Evaluation for Berberine Chloride Dihydrate (CAS no. 5956-60-5) Administered in the Feed to Sprague-Dawley (CD®) Rats on Gestational Days 6 to 20. National Toxicology Program. Springfield, VA: National Technical Information Services, 2003.

6.NTP Study TER99002. Developmental Toxicity Evaluation for Berberine Chloride Dihydrate (CAS no. 5956-60-5) Administered in the Feed to Swiss (CD-1®) Mice on Gestational Days 6 to 17. National Toxicology Program. Springfield, VA: National Technical Information Services, 2003.

7.NTP Study TER99004. Developmental Toxicity Evaluation for Goldenseal (Hydrastis canadensis) Root Powder Administered in the Feed to Swiss (CD-1®) Mice on Gestational Days 6-17. National Toxicology Program. Springfield, VA: National Technical Information Services, 2002.

8.NTP Study TER20102. Developmental Toxicity Research Evaluation for Berberine Chloride Dihydrate (CAS no. 5956-60-5) Administered by Gavage to Sprague-Dawley (CD®) Rats on Gestational Days 6 Through 19. National Toxicology Program. Springfield, VA: National Technical Information Services, 2002.

9.NTP Study TER20103. Developmental Toxicity Research Evaluation for Berberine Chloride Dihydrate (CAS no. 5956-60-5) Administered by Gavage to Swiss (CD-1®) Mice on Gestational Days 6 Through 16. National Toxicology Program. Springfield, VA: National Technical Information Services, 2003.

10.National Center for Complementary and Alternative Medicine. Goldenseal. Herbs at A Glance. National Institutes of Health, U.S. Department of Health and Human Services, 2008. Available at http://nccam.nih.gov/health/goldenseal. Accessed August 3, 2009.