Herb
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
Ginseng is an ancient popular herb that is used extensively throughout the world. The reproductive effects of the herb in pregnant animals, except in one case, have not been studied. Similarly, only one small study has investigated its effect in human pregnancy, but the study did not mention if birth defects were observed. As with most herbal preparations, there appears to be little or no quality control in the production of commercial products, and mislabeling of these products is probably common. Ginseng is known to act on multiple organ systems. Depending on the product ingested and the dose and duration of use, the herb can produce clinically significant adverse reactions in nonpregnant patients. Hypertension and hypoglycemia have been reported with ginseng (1). These effects could complicate pregnancies with hypertensive disorders or diabetes. However, because ginseng has been used in medicine for more than 2000 years and its current use is widespread, it is doubtful if it causes major birth defects or other clinically significant developmental toxicity. More subtle or low-incidence effects, however, including structural and behavioral teratogenicity, the induction of abortions, and infertility, may have escaped detection. Further study using products identified by chemical analysis is required before human reproductive risk or safety can be assessed.
FETAL RISK SUMMARY
Ginseng is a plant that is found throughout the world. The root is considered the most important part of the plant because it contains the pharmacologically active ginsenosides. Ginseng has been used in medicine for >2000 years. The herb is promoted as having multiple pharmacologic effects, including adaptogenic, CNS, cardiovascular, endocrine, ergogenic, antineoplastic, and immunomodulatory effects. It is available as fresh or dried roots, extracts, solutions, tablets, sodas, teas, chewing gum, cigarettes, and candy (1–3).
Although the name ginseng (common names, if given, shown in parentheses) commonly refers to Panax quinquefollus L. (American or Canadian ginseng) or P. ginseng C.A. Meyer (Asian, Chinese, Korean, or Oriental ginseng; red ginseng [steamed]), one source listed seven other recognized medicinal ginsengs (1). They are P. japonicus var bipinnatifidus, P. japonicus C.A. Meyer (Japanese, Chikusetsu, or zhu je ginseng), P. japonicus var major, P. notoginseng (Western or Five-fingers ginseng; Sang; San-chi; Tien-chan or tienqi ginseng), P. pseudoginsengsubsp. himalaicus (Himalayan ginseng), P. pseudoginseng var major (Zhuzishen), and P. vietnamensis Ha et Grushv. (Vietnamese ginseng) (1).
A 1994 letter stated that there were eight species and three varieties of genus Panax in the Northern Hemisphere (4). The eight species were ginseng, quinquefolium, notoginseng, pseudoginseng, zingigerensis, trifolus, stipuleanatus, and japonicus. The varieties of P. japonicus were identified as var major, var angustifolius, and var bipinnatifidus.
Ginseng products are commercially available as food flavorings and herbal medicines. Although the minor constituents of ginseng listed below might have some role, the principal pharmacologically active ingredients of ginseng appear to be a group of steroid-like compounds linked to sugars, called saponins (ginsenosides) (1). At least 13 major saponins, as well as numerous minor glycosides, have been identified. Minor constituents include volatile oils, β-elemine, sterols, acetylenes, polysaccharides, starch, flavonoids, peptides, various B-complex vitamins, minerals, enzymes, and choline (1). Xanthines (e.g., caffeine, theophylline, and theobromine), produced by the plant, may also be present in various concentrations and may contribute to the pharmacologic action of the product (1).
The actual amount of ginsenosides in commercial preparations varies widely. This variance partially reflects poor quality control, but may also depend on the species, age of the root, location, season of harvest, and preservation or curing method (1). In addition, products sold as ginseng may actually contain no ginsenosides (2,5). For example, other herbal species that do not contain ginsenosides are also called “ginseng,” such as Siberian ginseng (Eleutherococcus senticosus; active constituents are eleutherosides) and Brazilian ginseng (Pfaffia paniculata) (6). In addition, Chinese silk vine (Periploca sepium), an herb that contains cardiac glycosides but no ginsenosides, is a common substitute for Siberian ginseng (7).
A reproduction study with rats was conducted with an extract (G115) of Oriental ginseng (P. ginseng) (8). Two generations of rats, male and female, were fed a diet supplemented with ginseng extract at doses of 1.5, 5, or 15 mg/kg/day or a control diet. No differences in treatment-related effects were observed between the groups in terms of body weights, food consumption, hematologic and clinical chemical data. In addition, no differences were noted in ophthalmic, gross and histopathologic examinations, or in autopsies (8).
Ginseng (P. ginseng) was used as a fetal protectant in a study involving rats given hexavalent chromium throughout gestation (9). Hexavalent chromium, the most toxic form of chromium for the embryo and fetus, was fed to two groups of female rats in their drinking water. In one of the groups, ginseng (20 mg/kg/day) was also given. A third group received ginseng only, whereas a control group received neither agent. The rats receiving chromium plus ginseng had significantly better pregnancy outcomes than those receiving only chromium in terms of increased maternal weight gain, fewer pre- and postimplantation losses, resorptions, and stillbirths, and lower rates of visceral and skeletal anomalies (9).
The effects of American ginseng (P. quinquefolium) on male copulatory behavior have been studied in rats (10). Doses of 10–100 mg/kg/day given for 28 days significantly stimulated copulatory behavior. In comparison with controls, no effects were noted on plasma luteinizing hormone or testosterone levels, or on sex organs, but plasma prolactin concentrations were significantly decreased in ginseng-treated animals (10).
Three brief reports have described an estrogen-like effect (11) and vaginal bleeding (12,13) in three postmenopausal women taking ginseng (P. ginseng in two; unknown source in one).
A 30-year-old woman took an herbal preparation alleged to be pure Siberian ginseng (1300 mg/day—twice the manufacturer’s recommended dose) throughout pregnancy and during the first 2 weeks of breastfeeding (14). In late pregnancy, she had repeated occurrences of premature uterine contractions. She also thought that the hair growth on her head, face, and pubic region had increased and was thicker. The term, 3.3-kg male infant had thick black hair in the pubic region and over the entire forehead, and swollen, red nipples (14). The mother stopped breastfeeding 2 weeks postpartum on medical advice because she did not want to stop taking the herb. At 7.5 weeks of age, the infant’s weight (5.8 kg) and length (60.6 cm) were above the 97th percentile, but the pubic and forehead hair, which had begun to fallout at 2 weeks, was scant. A physical examination revealed testes that were enlarged (volume = 3 mL) but were otherwise normal. In addition, there was no evidence of adrenogenital syndrome because the serum concentrations of 17-hydroxyprogesterone, testosterone, and cortisol were within normal ranges. The investigators noted that ginseng increases testosterone levels in male rats and testes growth in rabbits, and could significantly increase corticotropin and corticosteroid levels. Therefore, they concluded that the product she was taking might have caused the hirsutism in the mother and infant and the infant’s excessive weight gain (14).
In response to the above case, a representative for a government agency argued that the cited animal studies involving ginseng had no relevance because the active constituents of Siberian ginseng were eleutherosides that are completely different from ginsenosides (15). In reply, one of the investigators stated that they had recently given the woman doses either of her Siberian ginseng or placebo in a double-blind manner. Her testosterone levels were undetectable when she was taking the herb and normal when she received placebo. The investigator hypothesized that the product she was taking contained a compound that suppressed, but acted like, endogenous testosterone (16). In the last correspondence on this case, three bulk lots of powder supposedly containing Siberian ginseng were obtained from the manufacturer of the product taken by the woman. The lot dates overlapped the period of her pregnancy. Chemical analysis revealed that the powder was actually Chinese silk vine (P. sepium), the bark of which contains cardioactive glycosides (17). Inadvertent substitution of Chinese silk vine for Siberian ginseng had occurred previously and may have resulted because of confusion surrounding the Chinese names of the herbs (17).
A brief 1991 correspondence compared the outcomes of 88 Asian women who had taken ginseng during pregnancy with 88 matched controls who had not taken the herb (18). No statistically significant differences were found in the mode of delivery, birth weight, low birth weight (<2500 g), preterm delivery (<37 weeks), low Apgar scores (<7), and stillbirths or neonatal deaths. Regarding pregnancy complications, there were no differences in the incidence of gestational diabetes, or antepartum or postpartum hemorrhage, but significantly more controls than subjects had preeclampsia (1 vs. 8; p <0.02). No mention was made of congenital malformations in either group (18).
BREASTFEEDING SUMMARY
No studies describing the use of ginseng during human lactation have been located. Confusion has arisen over the actual identity of commercial products (see above) and without chemical analysis, the actual herb ingested is uncertain. Ginseng can affect multiple organ systems in users and, potentially, could adversely affect a nursing infant if the ginsenosides (active constituents) were excreted into breast milk. However, it is doubtful if ginseng has caused clinically significant effects in nursing infants because of its ancient and widespread use. Although more subtle effects on a nursing infant could have been missed, the proven benefits of breastfeeding may outweigh the unknown risk from exposure to the active and inactive constituents of ginseng. Women taking this herb and nursing should be informed of this uncertainty.
References
1.Ginseng, Panax. The Review of Natural Products. St. Louis, MO: Facts and Comparisons, 2001.
2.Robbers JE, Tyler VE. Tyler’s Herbs of Choice. Binghamton, NY: Haworth Herbal Press, 1999:238.
3.Attele AS, Wu JA, Yuan CS. Ginseng pharmacology. Multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685–93.
4.Vigano C, Ceppi E. What is in ginseng? Lancet 1994;344:619.
5.Cui J, Garle M, Eneroth P, Bjorkem I. What do commercial ginseng preparations contain? Lancet 1994;344:134.
6.Walker AF. What is in ginseng? Lancet 1994;344:619.
7.Wong HCG. Probable false authentication of herbal plants: ginseng. Arch Intern Med 1999;159:1142.
8.Hess FG Jr, Parent RA, Cox GE, Stevens KR, Becci PJ. Reproduction study in rats of ginseng extract G115. Food Chem Toxicol 1982;20:189–92.
9.Elsaleed EM, Nada SA. Teratogenicity of hexavalent chromium in rats and the beneficial role of ginseng. Bull Environ Contam Toxicol 2002;68:361–8.
10.Murphy LL, Cadena RS, Chavez D, Ferraro JS. Effect of American ginseng (Panax quinquefolium) on male copulatory behavior in the rat. Physiol Behav 1998;64:445–50.
11.Punnonen R, Lukola A. Oestrogen-like effect of ginseng. Br Med J 1980; 281:1110.
12.Greenspan EM. Ginseng and vaginal bleeding. JAMA 1983;249:2018.
13.Palop-Larrea V, Gonzálvez-Perales JL, Catalán-Oliver C, Belenguer-Varea A, Martínez-Mir I. Metrorrhagia and ginseng. Ann Pharmacother 2000;34:1347–8.
14.Koren G, Randor S, Martin S, Danneman D. Maternal ginseng use associated with neonatal androgenization. JAMA 1990;264:2866.
15.Awang DVC. Maternal use of ginseng and neonatal androgenization. JAMA 1991;265:1828.
16.Koren G. Maternal use of ginseng and neonatal androgenization. JAMA 1991;265:1828.
17.Awang DVC. Maternal use of ginseng and neonatal androgenization. JAMA 1991;266:363.
18.Chin RKH. Ginseng and common pregnancy disorders. Asia Oceania J Obstet Gynaecol 1991;17:379–80.