Essentials of Complementary and Alternative Medicine (June 1999)

A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z
Alfalfa (Medicago sativa)
Prolonged ingestion of seeds or commercial tablets has been associated with a lupus-like syndrome (
78
, 
79
). Dermatitis has also been recorded (
80
).
Ammi fruit
Prolonged use or overdosing of the greater ammi (Ammi majus) may produce nausea, dizziness, obstipation, loss of appetite, headache, pruritus, and sleeping 
disorders. The psoralens in toothpick ammi (Ammi visnaga) can produce phototoxic reactions (
81
).
Amygdalin
The raw pits or kernels of certain  Prunus species (e.g., apricot, bitter almond, choke cherry, peach) have been promoted as health foods. When ingested in sufficient 
quantity, they are poisonous because of the cyanogenic glycoside amygdalin, which yields hydrogen cyanide after ingestion. Teratogenicity has been observed in 
animals.
Anise fruit (Pimpinella anisum)
Occasionally allergic reactions.
Anthranoid derivatives
Anthranoid derivatives occur in various laxative herbs, such as aloe ( Aloe spp.), buckthorn and cascara sagrada ( Rhamnus spp.), medicinal rhubarb (Rheum 
palmatum), and senna (Cassia spp.). They are present in the form of free anthraquinones, anthrones, dianthrones and/or O- and C-glycosides derived from these 
substances. In the case of Rhamnus, the fresh drug contains anthrones and is strongly emetic; for this reason it must be stored for at least one year or be submitted 
to an artificial aging process. Anthranoid derivatives produce harmless discoloration of the urine. Depending on intrinsic activity and dose, they can also produce 
abdominal discomfort and cramps, nausea, violent purgation, and dehydration. They can be distributed into breast milk, but not always in sufficient amounts to affect 
the suckling infant. Long-term use may result in electrolyte disturbances and atony and dilation of the colon. Several anthranoid derivatives (notably the aglycones 
aloe-emodin, chrysophanol, emodin, and physcion) show genotoxic potential in bacterial and/or mammalian test systems (
82
), and two anthranoid compounds (the 
synthetic laxative danthrone and the naturally occurring 1-hydroxyanthraquinone) have shown carcinogenic activity in rodents (
83
). In one epidemiologic study, 
chronic abusers of anthranoid laxatives (identified by the detection of  pseudomelanosis coli) showed an increased relative risk for colorectal cancer (
84
). More 
studies are needed to clarify this issue, if only to exclude the possibility that chronic constipation per se might increase the risk for colorectal cancer and would thus 
act as a confounding factor.
Pending the results of such studies, the German health authorities have restricted the indication of herbal anthranoid laxatives to constipation that is unresponsive to 
bulk-forming therapy (which rules out their inclusion in weight-reduction products). In addition, the German authorities have imposed restrictions to the laxative use 
of anthranoid-containing herbs (e.g., not to be used for more than 1 to 2 weeks without medical advice, not to be used in children under 12 years of age, and not to 
be used during pregnancy and lactation) (
85
, 
86
 and 
87
).
Aristolochic acids
Plants belonging to the genus  Aristolochia are rich in aristolochic acids and aristolactams. For example, the roots of birthwort ( Aristolochia clematitis) yield a 
substance called aristolochic acid, which is mainly a mixture of aristolochic acids I and II. Aristolochic acid passes into human breast milk. It is mutagenic and proved 
so highly carcinogenic in rats that the German health authorities have even banned homoeopathic  Aristolochia dilutions up to D10 from the market. The closely 
related aristolactams are mutagenic as well (
88
).
It has been known for a long time that aristolochic acid is nephrotoxic in animals and humans (
88
). In 1993, the nephrotoxic effects of aristolochic acid in the rat were 
described in detail; histologically, there was evidence of necrosis of the epithelium of the renal tubules (
89
). In the same year, a human outbreak of renal toxicity of 
Aristolochia was reported from Belgium, where nephropathy was observed in more than 70 users of a slimming preparation, which had been substituted or 
contaminated with a Chinese Aristolochia species (see below for a detailed discussion). Subsequently, rapidly progressive interstitial renal fibrosis has also been 
associated with chronic intake of the European species  Aristolochia pistolochia (
90
).
Arnica flower (Arnica spp.)
Skin-sensitizing sesquiterpene lactones are present. Ingestion of arnica tea can cause gastroenteritis, and large oral doses of undiluted tincture are said to produce 
various serious symptoms.
Asafetida (Ferula assa-foetida)
A case of methemoglobinemia in a 5-week-old infant treated with a gum asafetida preparation has been recorded (
91
).
Atractylis gummifera
Renal and hepatic toxicity have been reported (
92
, 
93
).
Basil (Ocimum basilicum)
Contains up to 0.5% of essential oil, which contains up to 85% of estragole. Estragole is mutagenic after metabolic activation and there is animal evidence to 
suggest carcinogenicity. The herb and essential oil should not be used during pregnancy and lactation or for prolonged periods. The German health authorities have 
no objection to the use of the herb as an admixture to herbal teas in levels up to 5%.
Bearberry leaf (Arctostaphylos uva-ursi)
Gastrointestinal disturbances. Reports of carcinogenicity of hydroquinone after prolonged administration of high doses to rats or mice raise a question about the 
long-term safety of bearberry and other medicinal herbs containing substantial amounts of arbutin. Arbutin is the monoglucoside of hydroquinone, and when it is 
administered orally to humans, it is hydrolyzed to hydroquinone and finally excreted in the urine as hydroquinone glucuronide and sulphate. These conjugates are 
also the major urinary metabolites, when rats are treated orally with hydroquinone (
83
). Bearberry should not be used for prolonged periods without consulting a 
physician.
Boldo leaf (Peumus boldus)

administered orally to humans, it is hydrolyzed to hydroquinone and finally excreted in the urine as hydroquinone glucuronide and sulphate. These conjugates are 
also the major urinary metabolites, when rats are treated orally with hydroquinone (
83
). Bearberry should not be used for prolonged periods without consulting a 
physician.
Boldo leaf (Peumus boldus)
The essential oil and other preparations rich in ascaridole should not be used because of the toxicity of this constituent.
Broom, Scotch (Sarothamnus scoparius = Cytisus scoparius)
The herb contains sparteine and related quinolizidine alkaloids. Sparteine can reduce cardiac conductivity and stimulate uterine motility (
38
). Pharmacokinetic 
studies have shown that its metabolic oxidation exhibits genetic polymorphism and that about 6 to 9% of the Caucasian population are poor metabolizers (
37
). 
Inexpert self-medication with a broom tea has resulted in fatal poisoning with clinical symptoms of ileus, heart failure, and circulatory weakness (
94
). It is prudent to 
avoid broom preparations during pregnancy, not only because sparteine has abortifacient potential, but also because of preliminary information that the plant 
produces malformed lambs in feeding trials. According to the German health authorities, hydroalcoholic preparations of the herb should contain no more than 1 
mg/mL of sparteine.
Broom flower contains only a low level of alkaloids but hypertension is a contraindication, and concurrent use with MAO-inhibitors should be avoided as over 2% of 
tyramine may be present. The German authorities have no objection to the addition of broom flower to herbal teas in levels up to 1%.
Bryony root (Bryonia spp.)
Drastic laxative and emetic properties due to the presence of cucurbitacins.
Burdock root (Arctium spp.)
Contact dermatitis (
95
).
Butcher's broan (Ruscus aculeatus)
Rarely gastric complaints, nausea. A case of enterocolitis caused by a preparation containing an extract of the rhizome of Butcher's broan has been reported (
96
). 
Topical use may lead to allergic contact dermatitis (
97
).
Caffeine
Occurs not only in coffee, tea, and cacao, but also in cola seeds ( Cola spp.), mate leaves (Ilex paraguariensis), guayusa leaves (Ilex guayusa), yaupon leaves (Ilex 
vomitoria), guarana seeds (Paullinia cupana), and yoco bark (Paullinia yoco) (
58
). High doses of these herbs may therefore produce hyperexcitability, nervousness, 
and sleeping disturbances.
Canthaxanthin
This orange carotenoid has been promoted as a skin-tanning agent. It entails a risk of adverse effects when used in amounts exceeding the levels in which it is 
normally consumed as a food additive. Retinopathy with gold-yellow deposits around the macula has been reported, and there has also been a case of aplastic 
anaemia (
98
).
Caper plant (Capparis spinosa)
Allergic contact dermatitis following application of this plant in the form of wet compresses has been reported (
99
).
California poppy (Eschscholtzia californica)
It would be prudent to avoid use during pregnancy because the major alkaloid cryptopin has shown a stimulating effect on guinea pig uterus in vitro.
Camphor tree (Cinnamomum camphora)
Contact eczema is possible. Camphor preparations should not be applied near the nose of infants.
Cardiac glycosides
Occur in Adonis vernalis (pheasant's eye), Asclepias tuberosa (pleurisy root), Convallaria majalis (lily of the valley),  Digitalis spp. (foxglove), Nerium oleander 
(oleander), Strophanthus spp., and Urginea maritima = Scilla maritima (squill). Although the cardiotoxic risks are well known, case reports continue to appear 
because plants rich in cardiac glycosides still serve as a folk remedy (
100
) or because they are erroneously mistaken for an innocuous herb (
101
, 
102
).
Cassia bark (Cinnamomum aromaticum)
Often allergic skin and mucosal reactions.
Castor oil (Ricinus communis)
When taken by mouth, especially in large doses, castor oil may produce violent purgation with nausea, vomiting, colic, and a risk of miscarriage.
Cayenne pepper (Capsicum frutescens)
Irritant properties and, rarely, allergic reactions.
Celandine (Chelidonium majus)
Warnings that use in children should be discouraged because fatal poisonings have been observed in children appear to go back to an unconvincing German case 
of fatal colitis in a 3-year-old boy. The original report does not provide conclusive evidence that celandine had been taken (
103
). A case of hemolytic anaemia 
following oral use has been reported (
104
).
Chamomile flower
Chamomile is an ambiguous vernacular name, as it can refer to Chamomilla recutita = Matricaria chamomilla (wild chamomile) and to Anthemis nobilis = 
Chamaemelum nobile (Roman chamomile). The latter herb is a more potent skin sensitizer than the former, presumably because it contains a higher level of the 
sesquiterpene lactone anthecotulid. This allergenic compound is present, at low levels, in only one of four chemotypes of wild chamomile.
Chamomile tea has been rarely associated with anaphylactic reactions (
105
) and its application as an eye wash can cause allergic conjunctivitis (
106
). When 
inhalation of steam from chamomile tea is used in children as a home remedy for inflammation of the upper respiratory tract, appropriate caution is needed to avoid 
serious burns (
107
).
Chaparral (Larrea tridentata)
At least nine cases of hepatotoxicity have been published (
108
, 
109
, 
110
, 
111
, 
112
 and 
113
), and in one of these cases inadvertent rechallenge led to recurrence 
within four weeks (
109
). Nordihydroguaiaretic acid (which is the major phenolic component) is able to produce lymphatic and renal lesions when given chronically in 

serious burns (
107
).
Chaparral (Larrea tridentata)
At least nine cases of hepatotoxicity have been published (
108
, 
109
, 
110
, 
111
, 
112
 and 
113
), and in one of these cases inadvertent rechallenge led to recurrence 
within four weeks (
109
). Nordihydroguaiaretic acid (which is the major phenolic component) is able to produce lymphatic and renal lesions when given chronically in 
high doses to rodents (
114
, 
115
 and 
116
). A possible human case of cystic renal cell carcinoma and acquired renal cystic disease associated with consumption of 
chaparral tea has been reported (
117
).
Chaste tree fruit (Vitex agnus-castus)
Skin reactions may occur. The herb has been associated with multiple follicular development in a female user (
118
).
Chenopodium oil (Chenopodium ambrosioides)
Formerly used as an anthelminthic but, because of the toxicity of its principle ascaridole, now superseded by less toxic alternatives.
Cinchona bark (Cinchona spp.)
Allergic skin reactions, fever; rarely thrombocytopaenia.
Cinnamon bark (Cinnamomum verum = Cinnamomum zeylanicum)
Often allergic skin reactions and mucosal reactions.
Coffee enemas
Two fatal cases related to therapy with voluminous coffee enemas have been described. These were assumed to be caused by electrolyte disturbances, because 
toxicological results in both cases indicated that not enough caffeine had been absorbed to cause a substantial toxic effect (
119
). The delivery of coffee enemas has 
also been associated with Campylobacter sepsis and amoebiasis (
120
).
Colocynth fruit (Citrullus colocynthis)
The dried pulp of the fruit is a drastic laxative because of the presence of toxic cucurbitacins. Colitis has been reported (
121
, 
122
).
Coumarin
This plant lactone is found in tonka beans (the seeds of  Dipteryx odorata and Dipteryx oppositofolia), dried sweet clover (Melilotus officinalis), sweet vernal grass 
(Anthoxanthum odoratum), and woodruff (Asperula odorata). It has hepatotoxic potential in humans when taken in daily doses of 25 to 100 mg (
123
). Coumarin is 
not to be confused with coumarin anticoagulants because it is devoid of anticoagulant activity. However, the molding of sweet clover can increase the hemorrhagic 
potential of this herb by transforming coumarin to the anticoagulant dicoumarol. This transformation may explain a case of abnormal clotting function and mild 
bleeding after the drinking of an herbal tea prepared from tonka beans, sweet clover, and several other ingredients (
124
).
Croton oil (Croton tiglium)
The seeds, seed oil, and resin of  Croton tiglium were formerly valued for purgative, abortifacient, and counterirritant properties. Their medicinal use has declined, 
however, after the isolation of skin irritant and tumor-promoting phorbol esters (diterpene esters of the tigliane type). Chronic exposure of humans to croton oil or 
croton tincture should be discouraged (
125
).
Dandelion root (Taraxacum officinale)
Gastric complaints are possible.
Dionaea muscipula
Reddening of the face, headache, dyspnea, nausea and vomiting; shivers, fever, and anaphylactic shock after intramuscular administration (
126
, 
127
 and 
128
).
Diterpene esters
Several medicinal plants belonging to the Euphorbiaceae and Thymelaeaceae (such as  Croton tiglium, Euphorbia spp., and Daphne spp.) contain diterpene esters 
of the tigliane, ingenane, or daphnane type. These substances cause irritation, inflammation, and blistering of the skin, and they are also tumor-promoting (i.e., 
capable of promoting the growth of a tumor initiated by another trigger). Animal experiments have shown that a threshold dose is needed for the tumor-promoting 
activity (
129
).
Dyer's broom (Genista tinctoria)
Contains toxic quinolizidine alkaloids, such as anagyrin, cytisine, and N-methylcytisine. The latter two constituents have similar peripheral effects as nicotine, 
whereas their central activity may be different. Anagyrine is a suspected animal teratogen and cytisine has been shown to have teratogenic activity in rabbits.
Echinacea (Echinacea spp.)
Intravenous administration has been associated with anaphylactic reactions. It has been suggested that oral ingestion may also lead to allergic symptoms, such as 
skin reactions and respiratory reactions (
130
, 
131
).
Elfdock root (Inula helenium)
Allergic contact dermatitis is possible, and higher doses produce vomiting, diarrhea, cramps, and paralytic symptoms.
Ergot (Claviceps purpurea)
The sclerotium of this fungus (secale cornutum) is rich in toxic alkaloids.
Essential oils
Essential oils are capable of producing systemic toxicity, particularly when they are ingested in undiluted form. Among the reported effects are central depression, 
nephrotoxicity, hepatotoxicity, and abortion. Allergic contact dermatitis and phototoxic reactions are also possible (
132
, 
133
). Inhalation by infants and small children 
should be avoided.
A common way of using essential oils in complementary medicine is through aromatherapy, which involves the topical application (massage oils, oil baths, facial 
dressings), oral use (drops), or inhalation (aroma lamps) of fragrances. Allergic airborne contact dermatitis has been described (
134
), as has occupational eczema 
in an aromatherapist (
135
).
Euphorbia cyparissias
This plant is one of the Euphorbia spp. containing skin irritant and tumor-promoting diterpene esters of the ingenane type (
129
). Chronic exposure of humans to the 

dressings), oral use (drops), or inhalation (aroma lamps) of fragrances. Allergic airborne contact dermatitis has been described (
134
), as has occupational eczema 
in an aromatherapist (
135
).
Euphorbia cyparissias
This plant is one of the Euphorbia spp. containing skin irritant and tumor-promoting diterpene esters of the ingenane type (
129
). Chronic exposure of humans to the 
tincture should be discouraged (
136
).
Evening primrose oil (Oenothera biennis)
The seeds yield evening primrose oil, which is used in various disorders, such as atopic eczema, premenstrual syndrome, and benign breast pain. When used as 
directed, it seems to produce no or only minor side effects, such as nausea, diarrhea, and headache. Allegations that evening primrose oil may make manifest 
undiagnosed temporal lobe epilepsy in patients receiving known epileptogenic drugs (e.g., phenothiazines) still need to be substantiated.
Fenugreek seed (Trigonella foenum-graecum)
Skin reactions to repeated external use.
Feverfew (Tanacetum parthenium)
Contact dermatitis is possible and is caused by allergenic sesquiterpene lactones, such as parthenolide. Mouth ulceration, inflammation of the oral mucosa and 
tongue, swelling of the lips, and loss of taste have also been reported.
Forking larkspur (Delphinium consolida)
The herb contains toxic diterpenoid alkaloids, but there are no reliable data on the alkaloid level in the flowers. The German health authorities have no objection to 
the use of the flowers as admixture to herbal teas in levels up to 1%.
Furocoumarins
Photosensitizing compounds, which are found in various medicinal plants, such as European angelica ( Angelica archangelica) and rue (Ruta graveolens).
Garlic bulb (Allium sativum)
Gastrointestinal disturbances (rarely). Nondietary intake or excessive dietary intake may increase the risk of bleeding and postoperative hemorrhagic complications 
in patients undergoing surgery (
137
, 
138
). One case of spinal hematoma causing paraplegia in association with excessive ingestion was reported (
139
). Topical 
exposure can lead to contact dermatitis or burnlike skin lesions, and occupational inhalation may produce asthma (
140
, 
141
 and 
142
).
Gentian root (Gentiana spp.)
Occasionally headache.
Ginkgo leaf (Ginkgo biloba)
Gastrointestinal complaints, headache, and allergic skin reactions. Recent case reports have associated the chronic ingestion of ginkgo with spontaneous bilateral 
subdural hematomas and increased bleeding time (
143
) and the combined use of ginkgo plus aspirin with spontaneous bleeding from the iris into the anterior 
chamber of the eye (
144
).
Ginseng
Ginseng is an ambiguous vernacular term; it may refer to  Panax species, such as P.ginseng (Asian ginseng) and P.quinquefolius (American ginseng), 
Eleutherococcus senticosus (Siberian ginseng),  Pfaffia paniculata (Brazilian ginseng), or unidentified material (e.g., Rumanian ginseng). Of all these sources, only 
the Panax species contain ginsenosides. Among the variety of adverse effects, which have been attributed in the literature to ginseng preparations, are 
hypertension, pressure headaches, dizziness, estrogenlike effects, vaginal bleeding, and mastalgia. Prolonged use has been associated with a “ginseng abuse 
syndrome,” including symptoms of hypertension, edema, morning diarrhea, skin eruptions, insomnia, depression, and amenorrhea. Most reports are difficult to 
interpret, however, because of the absence of a control group, the simultaneous use of other agents, insufficient information about dosage, and, last but not least, 
the lack of botanical authentication. For example, when a case of neonatal androgenization was associated with maternal use of Siberian ginseng tablets during 
pregnancy (
145
), botanical analysis showed that the incriminated material almost certainly came from  Periploca sepium (Chinese silk vine) (
146
).