Microsoft word - cjcp07034reviewf_e87-e94

SAFETY AND EFFICACY OF PANAX GINSENG DURING PREGNANCY
AND LACTATION
Dugald Seely1,2, Jean-Jacques Dugoua1,3,4, Daniel Perri5, Edward Mills1,6, Gideon Koren 4,5 1Department of Research and Clinical Epidemiology, The Canadian College of Naturopathic Medicine,2Institute of Medical Science, University of Toronto, 3Graduate Department of Pharmaceutical Sciences,Leslie Dan Faculty of Pharmacy, University of Toronto, 4Motherisk Program, The Hospital for SickChildren, Toronto, 5Division of Clinical Pharmacology and Toxicology, University of Toronto, 6ClinicalEpidemiology & Biostatistics, McMaster University, Hamilton, Canada Corresponding Author: _____________________________________________________________________________________ ABSTRACT
Background
There is a lack of basic knowledge on the part of both clinicians and patients as to the indications for use
and the safety of herbs used by women during pregnancy and lactation. This is one article in a series that
systematically reviews the evidence for herbs commonly used during pregnancy and lactation.
Objectives
To systematically review the literature for evidence on the use, safety and pharmacology of Panax
ginseng, focusing on issues pertaining to pregnancy and lactation.
Methods
We searched 7 electronic databases and compiled data according to the grade of evidence that was found.
Results
Based on strong scientific evidence from a cohort study, Panax ginseng was not associated with adverse
effects when used during pregnancy. Panax ginseng was misreported in the literature as causing
androgenization, when, in fact, the case reported was due to an adulterant. There is in vitro evidence of
teratogenicity with exposure to ginsenosides; however, this evidence is derived from animal embryos and
is based on exposure to isolated ginsenosides at much higher levels than achievable through normal
consumption in humans. There is also conflicting evidence as to whether or not Panax ginseng has
estrogenic properties. In lactation, there are no human studies on the safety of Panax ginseng, only in
vitro evidence based on three animal studies reporting minimal risk.
Conclusions
Panax ginseng should be consumed with caution during pregnancy, especially during the first trimester,
and during lactation.
Key words: Panax ginseng, asian ginseng, ginseng, pregnancy, lactation, breastfeeding, systematic review
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Korean or Asian ginseng. Preparations of P. TAmerican, Chinese, Korean, Japanese and ginsengincludethesteam-driedrootthatiscalled Siberian (or Russian) and it is important to be able ‘red ginseng’, and the air-dried root that is called to distinguish between them. The commercially ‘white ginseng’.1 Fresh ginseng extract is also available product ‘ginseng’ usually refers to the consumed, but is not generally the preparation dried root of Panax ginseng, commonly known as available commercially.2 Panax ginseng is a Can J Clin Pharmcol Vol 15 (1) Winter 2008:e87-e94; January 18, 2008 2008 Canadian Society for Clinical Pharmacology. All rights reserved.
Safety and efficacy for panax ginseng during pregnancy and lactation popular herbal remedy that has been in use for lactation. Our search included the following thousands of years. It has been an important part databases from inception to June 2006: AMED, of the pharmacopoeia of Traditional Chinese Medicine and is classified as an adaptogen that is Library, MedLine, Natural Database and Natural thought to increase the body’s overall resistance Standard. The common and the Latin names of the to stress and infection.3 This herb has a wide base herb were used as the key words along with of application and is considered the most popular “pregnancy”, “lactation” and “breastfeeding”. In herbal medicine worldwide.4 It has been used to addition, we searched the Complete German treat a variety of disorders including: anaemia, confusion, decreased libido, chronic fatigue, Each relevant journal article was collected angina, diabetes mellitus and herpes simplex type- and referenced in our database. The nature of the findings and the grade of evidence were then P. ginseng is not considered an herb specific abstracted and compiled in the final report. The to women’s health issues. However, its broad base grade of evidence for indications was evaluated as of popularity will invariably involve its usage by displayed in Table 1. Evidence of harm was rated women of reproductive age and women who may systematic review of the literature to assess issues of efficacy, and potential safety for women whoare pregnant, planning to become pregnant or Indications for Use
Evidence
Synonyms/Common Names/Related Substances
Asian ginseng, Asiatic ginseng, Chinese ginseng, ginseng root, guigai, hong shen, Japanese ginseng, jen-shen, jinsao, jintsam, insam, Korean ginseng, Korean panax ginseng, Korean red ginseng, ninjin, Oriental ginseng, Panax ginseng, Radix ginseng rubra, red ginseng, ren shen, renshen, renxian, sang, seng, sheng shai shen, white Constituents
Triterpenoid Saponins: ginsenosides (Rg1, Rb1)
Use and Safety during Pregnancy
Level of evidence
for potential harm
Part Used
androgenization31,32Protection of neonatal brain In keeping with the principles of evidence-based against ethanol damage33Teratogenicity34-37 practice, we endeavoured to identify and analyse all the relevant scientific medical literature that provided information as to the safety, efficacy and pharmacology of Panax ginseng in pregnancy and Can J Clin Pharmacol Vol 15 (1) Winter 2008:e87-e94; January 18, 2008 2008 Canadian Society for Clinical Pharmacology. All rights reserved.
Safety and efficacy for panax ginseng during pregnancy and lactation A randomized controlled trial of 384 women Researchers conducted a review of the herbs used receiving either ginseng extract or placebo for 16 during pregnancy in Singapore.39 Panax ginseng weeks, showed that the beneficial effects in the was used in various combinations and in various treatment of menopause are most likely not mediated by hormone replacement-like effects, as pregnancy.39 The researchers could not confirm that the claims made by Chinese herbalists on the estradiol levels, endometrial thickness, maturity efficacy of Panax ginseng in pregnancy were real index and vaginal pH were not affected by the or not.39 They concluded that there is no specific effect on pregnant women, but that it does not On the other hand, there are case reports and animal studies indicating potential estrogenic psychosomatic effect.39 The researchers also noted that the active principles can cross the placenta and reach the fetus.39 The authors did not discuss if Panax ginseng was safe or contraindicated phytoestrogenic actions of ginsenoside Rb1.40-46 A review article on the potential value of plants assources of anti-fertility agents also reported that Use and Safety during Lactation
Korean ginseng has estrogenic activity.30 Zhang et al. (1994) conducted a comparison Level of evidence for
study on pregnant women with intrauterine potential harm
women received ginseng, while the other groupwas nutritionally treated as controls.29 The height of fundus, fetal diparietal diameter, urinary Staphylococcus aureus were given subcutaneous injections of an extract of the Panax ginseng lactogen and neonatal weights approached normal root.47 Based on blood leukocyte measurements, pregnancy values.29 The authors did not report any ginseng treatment was found to activate the innate immunity of cows and contribute to the cow's recovery from mastitis.47 The authors did not A case was reported of a 30-year-old woman report any adverse effects associated with the use who gave birth to a full-term baby boy with signs of Panax ginseng during lactation.47 Two other studies by the same authors, conducted in “ginseng” during her pregnancy.32 After further lactating cows, found similar results where Panax investigation, the herbal preparation used by the ginseng increased leukocyte activity and no mother appeared to be adultered by the herb silk Okamura et al. (1994) reported that ginseng Toxicity and Adverse Effects
extract prevented an ethanol-induced reduction of Very low incidence of toxicity has been observed neonatal brain weight in rats.33 The ginseng in ginseng clinical trials using well-characterized saponins, including ginsenosides Rg1, Rb2, Rd, preparations.50 When used inappropriately, Panax Rf and Re, were shown to stimulate a potent ginseng has been noted to cause hypertension, diarrhea, sleeplessness, mastalgia, eruptions and vaginal bleeding.1 Siegel has coined a condition called “ginseng abuse syndrome”, in reference to teratogenic effects on rat embryos.34,37 A separate the long-term effects of ginseng use. This group of investigators also found embryotoxicity ‘syndrome’ is characterized by hypertension, when rat and mice whole embryos cultures were nervousness, sleeplessness, skin rash, diarrhea, exposed to high concentrations of the two confusion, depression or depersonalization.51 from Panax ginseng were found to activate DNApolymerase Can J Clin Pharmacol Vol 15 (1) Winter 2008:e87-e94; January 18, 2008 2008 Canadian Society for Clinical Pharmacology. All rights reserved.
Safety and efficacy for panax ginseng during pregnancy and lactation Pharmacology
aware of the possible risks attendant to such usage It is clear that Panax ginseng is pharmacologically and to be able to plan and advise accordingly.
active. While it is uncertain to what extent isolated constituents are biologically active, the demonstrating that P. ginseng is unsafe during ginseng saponins (or ginsenosides) are considered pregnancy and lactation. Observations during a to be responsible for a majority of this species’ cohort, and from traditional use, have not biological activity.52 Ginsenosides are unique to uncovered any adverse events from ginseng with Panax ginseng and over 30 of these compounds respect to pregnancy and lactation. A single case report was found in the literature that reported on pharmacological effects are detailed in Table 3, a potential link between P. ginseng use by a and attest to the wide range of potential pregnant woman and the death and androgenization therapeutic applicability of this incredibly popular and seemingly potent herbal medicine.
containing-product was adulterated, however, andas such, we cannot infer that ginseng was the Drug Interactions
causative agent. In addition, this is an isolated There is some evidence of potential interactions case and the anecdotal nature of the evidence does between ginseng and prescription drugs; however, not provide anything beyond speculation. Of most of the evidence is derived from preclinical somewhat greater concern, however, are the repeated findings of teratogenicity in mice and studies should be conducted to establish true rats when exposed to ginsenosides. Again, this interactions. Current evidence requires that Panax evidence must be interpreted with caution, as it is ginseng be used with caution in conjunction with derived from animal embryos and is based on exposure to isolated ginsenosides at much higher consumption in humans. Evidence regarding conflicting; some concern may be justified regarding this possibility, especially with respect to exposure during early fetal development.
Our study is limited primarily by the lack of evidence available. Given the vulnerabilities of a developing fetus and newborn child, and the fact that their metabolism can vary substantially from the adult, extreme caution is required in makingrecommendations for women of child bearing age.
The totality of the evidence that we analysed in DISCUSSION
ginseng may well be safe for consumption during Panax ginseng is frequently used as a general pregnancy; however, to ensure safety to the tonic or "adaptogen" to fight stress, and possibly developing fetus, consumption of this herb is best to enhance physical and mental performance. This avoided, especially during the first trimester.
herb is not specifically used during pregnancy and No human evidence could be found regarding lactation in the same way that ginger might be the safety of consuming Panax ginseng while used to treat nausea and vomiting, or how horse breastfeeding. Nonetheless, there is in vitro chestnut seed extract might be used to treat evidence based on three animal studies that Panax varicose veins.63,64 However, the fact that it is one ginseng was of minimal risk when consumed by of the most commonly used herbs worldwide, lactating cows. Research is necessary to determine inevitably women will end up taking the herb if ginsenosides and other potentially active during pregnancy or while breastfeeding. As such, compounds are carried in the human breast milk, it is critical that both women and clinicians be and also how this might affect a newborn child.
Can J Clin Pharmacol Vol 15 (1) Winter 2008:e87-e94; January 18, 2008 2008 Canadian Society for Clinical Pharmacology. All rights reserved.
Safety and efficacy for panax ginseng during pregnancy and lactation There is evidence to support the use of Panax and to enhance cognitive and physical function; however, more research is necessary to establish dysfunction; care of type II diabetics; amelioration its use in these areas as well as to establish safety of symptoms from influenza and the common cold LEVEL OF EVIDENCE
VERY STRONG SCIENTIFIC EVIDENCE
Statistically significant evidence of benefit from one or more systematic reviews/
meta-analysis.
STRONG SCIENTIFIC EVIDENCE
Statistically significant evidence of benefit from one or more properly conducted
random control trials (RCTs).
GOOD SCIENTIFIC EVIDENCE
Statistically significant evidence of benefit from one or more RCTs. The RCTs,
however, are either of small sample size OR have discrepancies in their
methodologies.
WEAK SCIENTIFIC EVIDENCE
Statistically significant evidence of benefit from one or more cohort studies OR
case control studies.
VERY WEAK SCIENTIFIC EVIDENCE
Evidence from case series OR case reports.
INDIRECT EVIDENCE
Expert opinion OR laboratory studies.
HISTORICAL OR TRADITIONAL EVIDENCE
Historical or traditional use by medical professionals, herbalists, scientists or
aboriginal groups.
EVIDENCE
STRONG SCIENTIFIC EVIDENCE
Statistically significant evidence from one or more systematic reviews or RCTs.
ACCEPTABLE SCIENTIFIC EVIDENCE
Statistically significant evidence from one or more well designed cohort studies
OR case control studies.
WEAK SCIENTIFIC EVIDENCE
Evidence from one or more case series.
VERY WEAK SCIENTIFIC EVIDENCE
Evidence based on case reports.
INDIRECT SCIENTIFIC EVIDENCE
Evidence based on scientific studies conducted on animals, insects or
microorganisms OR laboratory studies on human cells.
THEORETICAL EVIDENCE
Evidence based on scientific theory OR expert opinion.
UNKNOWN
No available information.
Can J Clin Pharmacol Vol 15 (1) Winter 2008:e87-e94; January 18, 2008 2008 Canadian Society for Clinical Pharmacology. All rights reserved.
Safety and efficacy for panax ginseng during pregnancy and lactation Pharmacological Actions Attributable to Panax Ginseng PHARMACOLOGICAL ACTION
Ginsenosides increase serum cortisol levels, stimulate adrenal function and in women, increase dehydroepiandrosterone sulfate (DHEA-S) Ginsenoside Rb1 may lowers blood pressure and acts as a CNS Ginsenosides interfere with platelet aggregation and coagulation47Panax ginseng may lower cholesterol and triglycerides18 Ginsenosides have analgesic and anti-inflammatory effects18 Panax ginseng has shown inhibitory activity on Helicobacter pylori69Panax ginseng promotes the growth of normal intestinal flora while The protein isolate panaxagin may have antiviral and antifungal activity where it appears to inhibit HIV reverse transcriptase and ribosomalactivity of some fungi9 Ginsenosides potentiate nerve growth factor and may have a neuroprotective effect through nicotinic activity11,71 Panax ginseng increases penile vibratory threshold and reduces the amplitude of penile somatosensory evoked potentials13 Ginsenosides have anti-asthmatic effects through the relaxation of human bronchial smooth muscle by stimulating the release of nitrous oxide fromairway epithelium72 Panax ginseng may prevent insulin resistance and change gene expression Some studies report that P. ginseng has phytoestrogenic properties40-46 REFERENCES
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