Ginseng
 
Clinical Overview
Uses
Ginseng is popularly used for its adaptogenic, antineoplastic, immunomodulatory, cardiovascular, CNS, endocrine, and ergogenic effects, but these uses have not been confirmed by clinical trials.

Dosing
Ginseng root is standardized on content of ginsenosides, which should be greater than 1.5%. Extracts typically contain from 4% to 7% ginsenosides. Note that the profile of particular ginsenosides differs between American and Asian ginseng; however, total ginsenoside content is similar. In numerous clinical trials, the dosage of crude root has ranged from 0.5 to 3 g/day and dosage of extracts has generally ranged from 100 to 400 mg. Each CVT-E002 capsule contains American ginseng root 200 mg standardized to 80% poly-furanosyl-pyranosyl-saccharides. Typical dosage regimens used in clinical trials have ranged from 400 mg once a day for 4 months to 200 mg twice a day for 2 to 3 months.

Contraindications
Hypersensitivity to any of the components of ginseng. Ginseng is contraindicated in patients who take warfarin, loop diuretics, or phenelzine. Patients with high blood pressure should not take ginseng and patients who must control their blood glucose level should use ginseng with caution. One postmarketing report documents an anaphylactic-like reaction (mouth and tongue swelling) with the use of CVT-E002. CVT-E002 should be avoided in autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. Patients with allergic rhinitis, asthma, or eczema should avoid using ginseng products.

Pregnancy/Lactation
Avoid use during pregnancy and lactation because of documented hormonal activity.

Interactions
A case of refractoriness to furosemide has been reported in a patient receiving ginseng. Ginseng may elevate plasma concentrations of nifedipine, increasing therapeutic and adverse reactions. Manic-like symptoms, headache, and tremulousness were reported during concurrent use of phenelzine and ginseng. Ginseng has been reported to decrease the anticoagulant effect of warfarin. Caution patients taking these drugs to avoid use of ginseng. Advise all patients to consult their health care provider before taking herbal products.

Adverse Reactions
The most common adverse reactions with ginseng are nervousness and excitation. However, there have been reports of diffuse mammary nodularity and vaginal bleeding. A hypoglycemic effect has also been documented. Postmarketing surveillance of CVT-E002 in Canada from 1996 to 2006 led to 100 documented adverse reaction reports, for the over 200 million doses of CVT-E002 sold. Reactions included abdominal pain, confusion, diuresis, dizziness, drowsiness, headache, insomnia, joint pain, lowered blood pressure, nausea, and vomiting.

Toxicology
Research reveals little or no toxicology information.

 
Botany

 Ginseng
 Scientific name Synonyms Common name Distribution
  Panax ginseng
C.A. Meyer
    Panax pseudoginseng Wallich;
Panax schinseng Nees
 Asian, Chinese, Korean,
or Oriental ginseng 1 , 2 ;
red ginseng (steamed)
 Northeast China, Korea,
Eastern Siberia
  Panax japonicus
var bipinnatifidus 2
   China
  Panax japonicus
C.A. Meyer 2
  P. pseudoginseng
(Will.) subsp. japonicus
 Japanese ginseng 1 , 2
Chikusetsu ginseng, 3
or zhu je ginseng 4
 India, Southern China, Japan
  P. japonicus
var. major 2
   China
  P. notoginseng
(Burkhill) Hoo & Tseng 2 ;
([Buck] F.H. Chen)
  P. pseudoginseng
Wallich var. notoginseng
 Western ginseng;
Five-fingers; Sang 2 ; San-chi 1 , 5 ;
Tien-chan 1 or tienqi 4
ginseng
 Asia
  P. pseudoginseng
subsp. himalaicus
  Himalayan ginseng Nepal
  P. pseudoginseng
var. major
  Zhuzishen China
  Panax quinquefolius L.  American or
Canadian ginseng 1 , 6
 Eastern and central
United States and Canada
  Panax vietnamensis
Ha et Grushv.
  Vietnamese ginseng 1 , 5  Vietnam

Ginseng commonly refers to P. quinquefolius L. or P. ginseng C.A. Meyer, two members of the family Araliaceae. The ginsengs were classified as members of the genus Aralia in older texts. In the eastern and central United States and Canada, 3 ginseng is found in rich, cool woods; a large crop is grown commercially in Wisconsin. Asian ginseng is cultivated in Korea and China. The short plant grows 3 to 7 compound leaves that drop in the fall and bears a cluster of red or yellowish colored fruits from June to July. The shape of the root can vary depending on the species and has been used to distinguish types of ginseng. Medicinally, the root is considered most valuable in providing the pharmacologically active ginsenosides. Ginsenoside content varies with the age of the root, season of harvest, and method of preservation. While at least 4 ginsenosides are detectable in most young roots, this number more than doubles after 6 years of growth. High-quality ginseng is generally collected in the fall after 5 to 6 years of growth. 3
 
History
Ginseng is perhaps the most widely recognized plant used in traditional medicine and now plays a major role in the herbal health care market. For more than 2,000 years, various forms have been used medicinally. The name Panax derives from the Greek word for “all healing,” and its properties have been so touted. Ginseng root's man-shaped figure (shen-seng means “man-root”) led proponents of the doctrine of signatures, an ancient European philosophy, to believe that the root could strengthen any part of the body. Through the ages, the root has been used in the treatment of asthenia, atherosclerosis, blood and bleeding disorders, and colitis, as well as to relieve the effects of aging, cancer, and senility.
Evidence of the root's general strengthening effect is its ability to raise mental and physical capacity, as well as its protectant effect against experimental diabetes, neurosis, radiation sickness, and some cancers has been reported. Today, its popularity is widely due to the proposed adaptogenic effect (stress-protective) of the saponin content. CVT-E002 (ie,   Cold-fX ), an herbal preparation made from the roots of North American ginseng, is marketed as a natural health product in Canada. The following claim has been approved by a branch of Health Canada: “CVT-E002 helps reduce the frequency, severity, and duration of cold and flu symptoms by boosting the immune system.” 7
 
Chemistry
The first study of the plant was reported in 1854 when a saponin called panaquilon was isolated from P. quinquefolium . 8 Subsequent analysis of ginseng has focused on this group of compounds, which has several naming conventions and may be referred to as ginsenosides, panaxosides, chikusetsu-saponins, or dammarane derivatives. 2 , 3 Saponins, or triterpenoid glycosides, are steroid-like compounds linked to sugars. 3 , 5 , 9 , 10 About 13 major ginsenosides have been isolated. 3 , 11 Several dozen minor glycosides also have been identified.
The saponin content varies among Panax species based on the species, age of the root, location, season, and curing method. 12 Of the 13 major saponins (ginsenosides) isolated from P. ginseng , only 2 (Rg2 and Ro ) are common to Japanese, Chinese, Korean, and American ginseng species. 3 Because saponins are difficult to purify on a large scale, the whole root is typically used in herbal preparations.
Many other minor components have been isolated and may contribute to the pharmacologic effects. These include volatile oils; beta-elemine; sterols; acetylenes; polysaccharides; starch; flavonoids; peptides; vitamins B1 , B2 , B12 ; pantothenic acid; biotin; minerals; enzymes; and choline. 2 , 13
Most traditional ginseng herbal preparations contain saponin (ginsenosides) glycosides. However, a commercially available product, known as CVT-E002 and marketed as   Cold-fX , does not contain ginsenosides. Instead, its biological activity is solely based on a patented aqueous extract of approximately 80% to 90% poly-furanosyl-pyranosyl-saccharides from the roots of North American ginseng ( P. quinquefolius L., Araliaceae). Based on information from the manufacturer, CVT-E002 is composed of 80% poly-furanosyl-pyranosyl-saccharides (including rhamnose, glucose, galacturonic acid, galactose, and arabinose), 10% protein, and the remaining 10% includes amino acids, vitamins, minerals, and small organic molecules. 7
A wide range of ginseng products are available over the counter both as food flavorings and herbal medicines, including fresh and dried roots, extracts, solutions, capsules, tablets, sodas, and teas. 1 , 14 , 15 Many individuals find the taste of ginseng to be disagreeable.
A study analyzing various commercial ginseng products from 11 countries revealed that among the 14 purest preparations, ginsenoside content varied between 1.9% to 8.1% (wt/wt). Among 20 extract preparations, the concentration varied from 4.9% to 13.3%. 3 Of 17 different products analyzed from Sweden, total ginsenoside content per capsule or tablet was 2.1 to 13.3 mg. 3 These variations, as do other comparative studies, emphasize the need for quality control. 3 , 16 , 17 The Complete German Commission E Monographs defines ginseng root ( ginseng radix ) as containing at least 1.5% ginsenosides, calculated as ginsenoside Rg1 . 14 , 15
In addition to ginsenoside content variation, methylxanthines are produced by the ginseng plant and can also be contained within commercial ginseng preparations. The type and concentration of xanthines (eg, caffeine, theophylline, theobromine) also varies with the variety of ginseng and may contribute to some reported physiological effects. Levels of xanthines have ranged from 0.1 mg/dose in American ginseng products to 200 mg/dose in Asian ginseng products. 3
Physical and chemical analyses have shown that while some commercial products closely resemble the whole root in composition, many contain little or no detectable ginsenoside concentrations. 12 , 18 Some preparations have been adulterated with phenylbutazone, aminopyrine, or mandrake root, while others have been contaminated with pesticides and fungicides. 3 , 19 , 20 Other preparations labeled “Native American ginseng” did not to contain any species of Panax . The root of Siberian ginseng ( Acanthopanax senticosus Harms. or Eleutherococcus senticosus Maxim) is sometimes used in herbal medicine for the same purposes as traditional ginseng, but it is an entirely different plant from the Asme family (see the Eleutherococcus monograph).
Variances in cultivation and processing methods, as well as the individual genetics of each plant source, result in varying chemical compositions among commercial products. This may contribute to the lack of consensus among studies on the pharmacology and efficacy of ginseng and should be considered when interpreting and conducting research. A second factor that may have produced the erratic results is the recent discovery that ginsenosides are metabolized extensively by the human gut microflora, and that some of the metabolites are pharmacologically active. Colonic bacteria remove the 3 sugars from ginsenoside Rb1 in stepwise fashion, and the deglycosylated compounds are then esterified in the liver with the fatty acids (stearic, palmitic, and oleic acid). These esters persist in the liver for as long as 24 hours. 21
 
Uses and Pharmacology
Over the past 40 years, in vitro and animal studies have identified a diverse array of pharmacologic effects of ginseng. These effects vary with dose, duration of treatment, and animal species, and include CNS depression or stimulation, variable effects on systemic blood pressure, a papaverine-like action on smooth muscle, and analgesic and anti-inflammatory activity. 22 Most studies have used whole-root preparations, with considerable variations (eg, uncertain species identification, age of the roots, curing process used). Variations in saponins among the various species also may contribute to the lack of consensus among researchers on ginseng's pharmacology.
Adaptogenic effects   From the earliest times, there have been claims that ginseng exerts a strengthening effect and raises physical and mental capacity for work. These properties have been defined as an “adaptogenic effect” or a nonspecific increase in resistance to the noxious effects of physical, chemical, or biological stress. 9
Animal and in vitro data   Animal studies have shown that ginseng extracts can prolong swimming time, prevent stress-induced ulcers, stimulate the proliferation of hepatic ribosomes, increase natural killer-cell activity, and possibly enhance the production of interferons. 23 A saponin in Vietnamese ginseng (MR2) has been described as having antistress effects in rats from a study suggesting that modulation of opioid, gamma-aminobutyric acid (GABA), corticotropin-releasing factor, or resulting interactions were responsible for the effects of MR2. 5 However, a study in mice found no adaptogenic effects of the saponin. 24
The antinociceptive effects of CVT-E002 were investigated in a mouse model. The experimental group consisted of 23 mice treated with a standardized CVT-E002 0.3 mL solution for 4 consecutive days, and the placebo group consisted of 20 mice treated with water. A pain response was elicited by injecting a formalin solution into the paws of all mice in both groups. Results documented that the CVT-E002-treated group spent significantly less time licking or biting the injured paw at 25 to 30 minutes after injection compared with the control group ( P < 0.05). 25
CVT-E002 extract may have immunomodulating activity. CVT-E002 extract increased spleen B lymphocyte proliferation and serum immunoglobulin production in an animal model. Results also documented increased peritoneal exudate macrophage production of the cytokines IL-1, TNF-a, and IL-6 and the production of nitric oxide. 26 , 27 Another study by the same investigators examined the effects of CVT-E002 on concanavalin A (ie, a lymphocyte mitogen) activated cultured mouse spleen cells. When compared with controls, immune cells exposed to CVT-E002 led to a dose-dependent increase of IL-2 and interferon gamma IFN-y (both of these cytokines help protect against respiratory pathogens). 28 , 29 The immunomodulating activity of CVT-E002 on natural killer cells may be associated with monocyte activation when the influenza virus is present. 7
Clinical data   Two randomized, double-blind, placebo-controlled trials conducted during the 2000 (8 weeks) and 2000 to 2001 (12 weeks) influenza seasons examined the efficacy of CVT-E002 in preventing acute respiratory illness (ARI) in an institutional setting. The average age of each subject was 81 years of age; 78 subjects completed the first study and 103 subjects completed the second study. Nearly 90% of the subjects had received an influenza vaccine. Each subject received either CVT-E002 extract 200 mg or placebo orally twice a day. Primary outcome measures included incidence of clinically confirmed ARI. Secondary end points included severity and duration of respiratory illness, laboratory-confirmed respiratory illness, and severity and duration of influenza illness. Overall, the incidence of laboratory-confirmed influenza illness was lower in the CVT-E002–treated group compared with the placebo group. 30
The efficacy of CVT-E002 in preventing colds was examined in a randomized, double-blind, placebo-controlled study of 323 subjects 18 to 65 years of age who had contracted at least 2 colds in the past year. Each subject was administered CVT-E002 400 mg or placebo every day for 4 months. A total of 130 subjects in the CVT-E002 group and 149 in the placebo group completed the study. The primary outcome measure was the number of colds reported and Jackson-verified per subject (the Jackson criteria are a common and well-established measures in these trials).
Secondary measures included symptom severity, total number of days for symptoms, and duration of all colds during the 4-month treatment period. Results were clinically and statistically significant for nearly all outcome measures in the CVT-E002–treated group. A lower total symptom score and fewer total days of symptoms were reported in the ginseng group than in the placebo group. 31 , 32 A proposed mechanism of action involves CVT-E002 increasing the activity of T-helper and natural killer cells and decreasing immunoglobulin A levels in plasma when compared with placebo. 33
Another randomized, double-blind, placebo-controlled trial with 43 adults 65 years of age and older examined the efficacy of CVT-E002 in preventing ARI. Subjects received either CVT-E002 400 mg or placebo orally every morning for 4 months. During week 4, patients received a standard dose of influenza vaccine. The primary outcome measure was the incidence and symptom duration of ARI. The duration of ARI symptoms during the final 2 months of the study was shorter in the CVT-E002–treated group when compared with the placebo group (5.6 days vs 12.6 days, P = 0.04). The following mild adverse reactions (primarily GI complaints) were reported during the trial: diarrhea, dry mouth, heartburn, joint and muscle pain, and nausea. 34
Antineoplastic/Immunomodulatory effects
Animal data   Ginsenosides have exerted anticancer effects in vitro, including direct cytotoxic and growth inhibitory effects, induced differentiation, and inhibited metastasis. High concentrations of M1, an active metabolite of Rb1 , Rb2 , and Rc , induced cell death of mouse melanoma cells by regulating proteins involved in apoptosis. Rh2 - and Rh3 -induced differentiation of promyelocytic leukemia cells into granulocytes; Rg3 inhibited adhesion and invasion of melanoma cells and decreased pulmonary metastasis. 35 Animal studies have supported these immunomodulatory effects. Rg1 has increased cell-mediated and humoral immune responses; ginsenosides and polysaccharides found in ginseng root have stimulated antibody production and phagocytosis of the reticuloendothelial system. 35 , 36
Clinical data   Two studies in healthy volunteers measuring T-lymphocyte immunomodulation yielded equivocal results. 1 , 35
Cardiovascular effects   Ginseng saponins have been reported to act as selective calcium antagonists and enhance the release of nitric oxide from endothelial and neuronal cells. In vitro studies have shown that total ginseng saponins extracted from P. notoginseng and P. quinquefolius inhibited calcium entry through receptor-operated calcium channels without affecting calcium entry through voltage channels or intracellular calcium release. 37
Animal data   In studies involving rabbits and dogs, ginsenosides Ro and Rb from P. ginseng offered a protective effect in myocardial ischemia and reperfusion injuries. 38 This effect may be partly mediated by increased release of prostacyclin and by activation of nitric oxide synthase and subsequent release of nitric oxide. Evidence from studies in the corpus cavernosum in which ginsenosides not only induced relaxation but also enhanced both acetylcholine- and transmural nerve stimulation-induced relaxation of the corpus cavernosum, actions mediated by nitric oxide, supports this theory. 38 These effects may also contribute to the historical use of ginseng in China for cardiovascular diseases and as an aphrodisiac.
Clinical data   There are no clinical data supporting the use of ginseng for cardiovascular effects.
CNS effects   Rb1 and Rg1 appear to play a major role in CNS stimulatory and inhibitory effects and may modulate neurotransmitters. Cholinergic activity, implicated in mediating learning and memory processes, is affected by certain ginsenosides.
Animal data   Animal studies show that Rb1 , Rg1 , and Re prevent scopolamine-induced memory deficits, and that Rb1 and Rg1 appear to increase central choline uptake and facilitate the release of acetylcholine from hippocampal tissues. Results from a study in aged rats suggest that daily oral administration of P. ginseng extract 8 g/kg/day for 12 days improved learning performance. 3 In animal tissues, ginseng extract inhibited GABA, glutamine, dopamine, noradrenalin, and serotonin uptake in a concentration-dependent manner. An in vivo study suggested possible CNS depressant effects of ginsenosides when a mixture of Rb1 , Rb2 , and Rc prolonged hexobarbital sleeping time in mice. Ginseng saponins also prevented dopamine receptor supersensitivity and physical dependence induced by chronic morphine, methamphetamine, and cocaine administration, while the total extract and Rf were reported to inhibit sensory neuron calcium channels in a manner equal to that of opioids. 34 , 35 However, while ginseng exhibits anti-opioidergic actions, it is not affected by the opioid receptor antagonist naloxone. 34 It was observed in mice that administration of opioids and psychostimulants (eg, cocaine) can suppress certain immune responses (eg, macrophage activity, tumor necrosis factor levels), and that administration of ginsenosides and ginseng polysaccharides that block opioid behavioral dependence also markedly stimulated these and other immune responses. 34 , 35 Some researchers believe that these processes may be related and that ginseng's immune-activating effects may play a role in inhibiting opioid and psychostimulant behavioral dependence. 34
Clinical data   In humans, 2 randomized double-blind, placebo-controlled studies (n = 32, n = 127) using P. ginseng (200 to 400 mg/day for 8 to 12 weeks) reported improvements in cognitive functioning, specifically mental arithmetic and abstraction. 1 However, another evaluation of one of these same studies claimed that the improvements were not statistically significant. 3 A third study of 50 elderly patients 65 to 80 years of age comparing P. ginseng (dose not reported) with a neurotrophic amino acid/vitamin B12 combination reported improvements for the ginseng group over baseline; however, these results were inferior compared with those of the neurotrophic combination group. 3
Endocrine effects
Animal data   There are no animal data regarding the use of ginseng for endocrine effects.
Clinical data   Randomized, placebo-controlled human trials have examined the hypoglycemic effects of ginseng reported in earlier animal studies. 39 , 40 , 41 One study reported statistically significant ( P < 0.01) improvement in fasting blood glucose and reduction in glycosylated hemoglobin in subjects with type 2 diabetes mellitus treated for 8 weeks with ginseng 100 and 200 mg, respectively (manufacturer listed but species not noted). Also, all patients lost weight, which may be considered a beneficial overall result. Two studies have shown that 3 g ground root of P. quinquefolius exerts a glucose-lowering effect only postprandially or when stimulated by glucose ingestion. 40 , 41 Evidence appears to support the modulation of insulin sensitization and secretion based on the fact that cholinergic, dopaminergic, adrenergic, and nitric oxide actions found with ginsenosides also have been noted to affect glucose metabolism in animal studies. 40 , 41
Ergogenic effects   Evidence supporting the efficacy of ginseng in improving physical performance is conflicting. Physical performance in young, active volunteers did not improve in 4 studies; however, other studies reported a decrease in heart rate and an increase in maximal oxygen uptake. 1 One comprehensive literature search evaluated data from human studies on P. ginseng preparations. Properly controlled studies using higher doses (standardized to 2 g/day of dried root) administered for at least 8 weeks and in larger subject numbers more often exhibited statistically significant improvement in physical or psychomotor performance. Benefit was most likely seen in untrained subjects or in those older than 40 years of age. 4
 
Administration & Dosage
Ginseng root is standardized on content of ginsenosides, which should be greater than 1.5%. Extracts typically contain from 4% to 7% ginsenosides. Note that the profile of particular ginsenosides differs between American and Asian ginseng; however, total ginsenoside content is similar. In numerous clinical trials, the dosage of crude root has ranged from 0.5 to 3 g/day and dosage of extracts has generally ranged from 100 to 400 mg. 1 , 39 , 42 , 43
Each CVT-E002 capsule contains American ginseng root 200 mg standardized to 80% poly-furanosyl-pyranosyl-saccharides. Typical dosage regimens used in clinical trials have ranged from 400 mg once a day for 4 months to 200 mg twice a day for 2 to 3 months. 7
 
Pregnancy/Lactation
Avoid use during pregnancy and lactation because of documented hormonal activity. 2
 
Interactions
Pathology evidence from an animal study reported that a poly-furanosyl-pyranosyl-saccharide-rich CVT-E002 product had no statistically significant effect on CYP-450 metabolism. 44 , 45 However, commercially available ginseng products containing ginsenosides may interact with CYP-450 metabolism and some of these interactions are listed below.
Furosemide   Refractoriness to furosemide was reported in a man 63 years of age approximately 10 days after he started taking nutritional products, including ginseng. 46 He was hospitalized for edema and hypertension, where he did not receive nutritional products and responded to intravenous furosemide. After discharge, nutritional supplements were resumed and he developed worsening edema and hypertension. It is not known why the diuretic effect of furosemide was decreased.
Nifedipine   Ginseng inhibits the metabolism of nifedipine, elevating nifedipine plasma levels and increasing therapeutic and adverse reactions. Twenty-one subjects received nifedipine 10 mg before and after 18 days of pretreatment with ginseng 200 mg/day. 47 Compared with giving nifedipine alone, ginseng administration resulted in a 53% increase in nifedipine plasma concentrations when measured 0.5 hours after giving nifedipine.
Phenelzine   A woman 64 years of age experienced headache, insomnia, and tremulousness on two occasions while taking phenelzine and ginseng. 48 The symptoms did not occur when she took phenelzine or ingested ginseng alone. Manic-like symptoms occurred in a woman 42 years of age during concomitant use of phenelzine, ginseng, and bee pollen. 49 The mechanism for this interaction is unknown.
Warfarin   Reports are conflicting. A man 47 years of age stabilized on warfarin 5 mg daily, with the exception of 7.5 mg on one day, experienced a decrease in his international normalized ratio (INR) from 3.1 to 1.5 two weeks after starting ginseng. 50 Ginseng was discontinued and the INR value increased to 3.3 within 2 weeks. The mechanism for this interaction is unknown. A man 58 years of age, maintained on warfarin, experienced thrombosis on a mechanical bileaflet aortic valve prosthesis after starting ginseng. 51 The thrombosis was attributed to an inability to maintain therapeutic INR levels after taking ginseng. In a randomized, open-label, crossover study in 12 men, 7 days of pretreatment with ginseng extract ( P. ginseng root 0.5 g plus ginsenosides 8.93 mg) did not affect the pharmacokinetics or pharmacodynamics of warfarin. 52
 
Adverse Reactions
It is estimated that more than 6 million people ingest ginseng regularly in the United States. There have been few reports of severe reactions.
Patients hypersensitive to any of the components of ginseng should avoid its use. One postmarketing report documents an anaphylactic-like reaction (mouth and tongue swelling) with the use of CVT-E002. CVT-E002 should be avoided in autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. Patients with allergic rhinitis, asthma, or eczema should also avoid using ginseng products. 7
Postmarketing surveillance of CVT-E002 in Canada from 1996 to 2006 led to 100 documented adverse reaction reports for the over 200 million doses of CVT-E002 sold. Reactions included headache, insomnia, dizziness, drowsiness, confusion, nausea, vomiting, abdominal pain, diuresis, lowered blood pressure, and joint pain. 7
Several reports have implicated ginseng as having an estrogen-like effect in women. 53 One case of diffuse mammary nodularity has been reported 54 as well as a case of vaginal bleeding in a woman 72 years of age. 55
Neonatal death has been reported; avoid use during pregnancy and lactation.
The most common adverse reactions with ginseng are nervousness and excitation, which usually diminish after the first few days of use or with dosage reduction. It has been suggested that methylxanthine constituents of ginseng root (eg, caffeine, theophylline) may contribute to these physiological effects. 3 Inability to concentrate has also been reported following long-term use. 56
The hypoglycemic effect of the whole root and individual panaxosides has been reported by many investigators. Although no cases of serious reactions in diabetic patients have been reported, people who must control their blood glucose levels should take ginseng with caution.
People with high blood pressure should not use ginseng.
 
Toxicology
Research reveals little evidence of toxicity with the use of ginseng. A doping-control urinalysis was conducted under International Olympic Committee (IOC) doping control guidelines in 39 Canadian athletes taking CVT-E002 200 mg by mouth twice a day for 28 days. The results demonstrated that a total daily dose of CVT-E002 400 mg did not contain or generate IOC-banned substances that might induce a positive doping-control urinalysis. 57
 
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