Essentials of Complementary and Alternative Medicine (June 1999)

Guar gum (Cyamopsis tetragonolobus)
Esophageal obstruction (
58
) and interference with the absorption of other drugs (
50
).
Haronga bark with leaf (Harungana madagascariensis)
Photosensitivity.
Hellebore (Veratrum spp.)
The rhizome and root of Veratrum album (white hellebore) and the rhizome of Veratrum viride (green hellebore) contain many alkaloidal constituents, including 
hypotensive ester alkaloids. Among the major toxic symptoms are hypotension and bradycardia (
147
). The related species  Veratrum californicum has 
well-established teratogenic activity in livestock, due to the presence of the alkaloids cyclopamine, cycloposine, and jervine. The latter alkaloid is also found in white 
and green hellebore.
Horse chestnut seed (Aesculus hippocastanum)
Gastrointestinal disturbances (rarely).
Horseradish root (Armoracia rusticana)
Gastrointestinal disturbances. Convulsive syncope and abdominal discomfort have been observed following the ingestion of raw horseradish that had not been 
properly aired before use (
148
).
Ipecacuanha (Cephaelis spp.)
Ipecac syrup contains the toxic alkaloids cephaeline and emetine. When it is used as an emetic in accidental poisoning, serious adverse effects are usually absent, 
but misuse by anorectic and bulimic patients has resulted in severe myopathy, lethargy, erythema, dysphagia, cardiotoxicity, and even death (
149
).
Ispaghula seed and seed-shell (Plantago ovata)
Allergic reactions are possible. Fatal bronchospasm after oral ingestion has been reported (
150
).
Jalap resin (Exogonium purga)
Drastic cathartic with irritant action, which has been superseded by less toxic laxatives.

Allergic reactions are possible. Fatal bronchospasm after oral ingestion has been reported (
150
).
Jalap resin (Exogonium purga)
Drastic cathartic with irritant action, which has been superseded by less toxic laxatives.
Jessamine rhizome, yellow (Gelsemium sempervirens)
Narrow therapeutic window has resulted in many cases of poisoning, including fatal ones. Characteristic symptoms are dizziness, loss of speech, dysphagia, dry 
mouth, visual disturbances, trembling of extremities, muscular rigidity or weakness, and falling of the jaw.
Juniper berry (Juniperus communis)
The volatile oil distilled from the berries can act as a gastrointestinal irritant. It is said that excessive doses may result in renal damage, and use during pregnancy is 
discouraged because of a fear that this might stimulate not only the intestine, but also the uterus.
Kelp
General name for seaweed preparations obtained from different botanical species ( Fucus vesiculosus, Fucus serratus, Ascophyllum nodosum, Macrocystis pyrifera). 
Because kelp contains iodine, it occasionally produces hyperthyroidism, hypothyroidism, or extrathyroidal reactions, such as skin eruptions. The ingestion of kelp 
has been associated with a case of severe dyserythropoiesis and autoimmune thrombocytopenia (
151
).
Kombucha
The Kombucha “mushroom” is a symbiotic colony of several species of yeast and bacteria that are bound together by a surrounding thin membrane. Kombucha tea 
has been associated with hepatotoxicity (
152
, 
153
) and severe metabolic acidosis (
154
).
Levant wormseed (Artemisia cina)
Contains the toxic lactone santonin, which was formerly used as an anthelminthic, but has now been superseded by other less toxic anthelmintics. It should not be 
confused with American wormseed (Chenopodium ambrosioides). The latter yields chenopodium oil, which has caused numerous poisonings due to the presence of 
ascaridole.
Licorice root (Glycyrrhiza glabra)
Prolonged use and/or high doses may produce mineralocorticoid adverse effects and drug interactions due to the saponin glycoside glycyrrhizin, which is naturally 
present in liquorice root in the form of calcium and potassium salts of glycyrrhizinic acid. Most persons can consume 400 mg of glycyrrhizin daily without adverse 
effects, but some individuals will develop adverse effects following regular daily intake of as little as 100 mg of glycyrrhizin (
155
, 
156
).
Madder root (Rubia tinctorum)
The use of herbal medicines prepared from madder root is no longer permitted in Germany (
157
). Root extracts have shown genotoxic effects in several test 
systems, which are attributed to the presence of the anthraquinone derivative lucidin. One of the other main components, alizarin primeveroside, is transformed into 
1-hydroxyanthraquinone, when given orally to the rat, and this metabolite shows carcinogenic activity in rats (
158
).
Male fern (Dryopteris filix-mas)
The rhizome was formerly used as an anthelmintic, but it is highly toxic and has been superseded by other less dangerous agents. Despite poor absorption, serious 
poisoning may occur (e.g., when absorption is increased by the presence of fatty foods).
Mandrake, American (Podophyllum peltatum)
The resin from the dried rhizome and roots contains podophyllotoxin, a-peltatin, and b-peltatin. When applied topically, it is a strong irritant to the skin and mucous 
membranes and may lead to poisoning because of systemic absorption. When taken orally, it has a drastic laxative action and produces violent peristalsis. Ingestion 
of large doses can result in severe neuropathic toxicity (
159
, 
160
). The oral and local use of the resin should be avoided during pregnancy because this has been 
associated with teratogenicity and fetal death. American mandrake should not be confused with the European mandrake ( Mandragora officinarum), which contains 
belladonna alkaloids.
Marsh herb (Ledum palustre)
The essential oil is a potent gastrointestinal, renal, and urinary irritant. Other toxic effects include abortion.
Meadow windflower (Pulsatilla vulgaris)
Higher doses may irritate the kidneys and urinary tract, and pregnancy is considered a contraindication.
Meadow saffron (Colchicum autumnale)
Contains the toxic alkaloid colchicine.
Methylsalicylate
Constitutes more than 95% of the volatile oil of wintergreen leaves ( Gaultheria procumbens). It has been associated with rare cases of allergic skin reactions, and 
accidental ingestion in young children has resulted in fatal salicylate poisoning. Methylsalicylate is also an important constituent of the red flower oil, which is used 
in Southeast Asia as a topical herbal analgesic. Some Southeast Asian users also take small amounts of the oil orally to enhance the analgesic effect. A suicide 
attempt by deliberate ingestion of a large dose ended in severe poisoning (
161
).
Mistletoe
This vernacular term is ambiguous; it may refer to  Phoradendron species, such as Phoradendrom flavescens (American mistletoe) or to Viscum album (European 
Mistletoe). The stems and leaves of the latter plant have been reported to contain alkaloids, viscotoxins, and lectins. The viscotoxins and lectins have been found to 
be poisonous in animals when given parenterally, but the consulted literature has not provided experimental data on their oral toxicology profile. Parenteral 
preparations of Viscum album can give serious allergic reactions (
162
), and they should not be administered to patients with hypersensitivity to proteins or with a 
chronic progressive infection (e.g., tuberculosis).  Phoradendron species contain phoratoxins (related to the viscotoxins). Teas prepared from unspecified plant parts 
or berries of Phoradendron have been associated with fatal intoxications.
Statements in the literature that mistletoe has hepatotoxic potential can be traced back to a single case report of hepatitis due to a herbal combination product 
claimed to have had mistletoe as one of its ingredients (
163
). However, because the incriminated product also contained skullcap, which has been repeatedly 
associated with hepatotoxic reactions, the attribution of this case to mistletoe is not acceptable.
Mugwort (Artemisia vulgaris)
This herb contains an essential oil with variable composition; depending on origin, 1,8-cineole, camphor, linalool, and thujone may all be major components. Allergic 
skin reactions (
164
) and abortive activity have been described.

p
p
Mugwort (Artemisia vulgaris)
This herb contains an essential oil with variable composition; depending on origin, 1,8-cineole, camphor, linalool, and thujone may all be major components. Allergic 
skin reactions (
164
) and abortive activity have been described.
Mustard (Brassica spp.)
White mustard seed (Brassica alba = Sinapis alba) should not be used externally for more than two weeks because skin and nervous damage can result from 
prolonged use. External application of black mustard ( Brassica nigra) is also associated with prominent local reactions.
Myrrh gum-resin (Commiphora spp.)
The undiluted tincture may produce burning and local irritation.
Nettle (Urtica dioica).
The blister-raising properties of locally applied nettle extracts are well-known. They are said to subside by drying or heat-treatment. Oral use of root preparations 
occasionally gives rise to mild gastrointestinal complaints.
Nutmeg seed (Myristica fragrans)
Psychic disturbances by 5 g or more taken orally, atropinelike action by 9 teaspoons of seed powder, and abortion by higher doses. The essential oil contains the 
mutagenic and animal carcinogenic compound safrole. However, the use to correct smell or taste is considered acceptable.
Nux vomica seed (Strychnos nux-vomica)
Contains the toxic alkaloid strychnine.
Papain
Proteolytic enzyme or mixture of enzymes from the juice of the unripe fruit of Carica papaya. Allergic reactions may occur after oral ingestion (
165
) and topical 
application (
166
). Cross-allergenicity with chymopapain has been documented (
167
).
Parsley (Petroselinum crispum = Apium petroselinum)
Phototoxicity and allergic reactions of skin and mucosae (rarely). The pure essential oil and its constituent apiole are toxic.
Pennyroyal oil (Hedeoma pulegioides and Mentha pulegium)
This volatile oil has a long history as a folk medicine for the induction of menses and abortion. Ingestion of large doses has resulted in serious symptoms including 
vomiting, abortion, seizures, hallucinations, renal damage, hepatotoxicity, shock, and death (
168
). The hepatotoxic potential of pulegone, the major constituent of the 
oil, has been confirmed in animal experiments. A case report describes serious pennyroyal toxicity in two Hispanic infants (one of whom died) who had been treated 
with teas brewed from home-grown mint plants. Both infants were positive for mentofuran, a toxic metabolite of pulegone, and one of them was also positive for 
pulegone (
169
).
Peru balsam (Myroxylon balsamum var. pereira)
Allergic skin reactions.
Poison oak (Rhus toxicodendron)
Allergic contact dermatitis (
170
).
Pokeweed (Phytolacca americana)
Severe emesis, diarrhea, and tachycardia may occur after ingestion of the raw leaves or after drinking tea prepared from the powdered root. A case of type I Mobitz 
heart block following the intake of uncooked pokeweed leaves has been reported (
171
).
Pollen
Gastrointestinal complaints (rarely). Anaphylactic reactions to oral ingestion have also been reported (
172
, 
173
 and 
174
).
Poplar bud, black (Populus nigra)
External use is occasionally associated with allergic skin reactions.
Primrose flower and root (Primula veris)
Gastrointestinal disturbances (occasionally). Rarely contact allergy.
Psyllium seed (Plantago afra and Plantago indica)
Ingestion has been rarely associated with generalized urticarial rash and anaphylactic shock (
175
, 
176
).
Pyrrolizidine alkaloids
Pyrrolizidine alkaloids with a saturated necine base are nontoxic, but most of the pyrrolizidine alkaloids with an unsaturated necine base are hepatotoxic, mutagenic, 
and hepatocarcinogenic. Among the numerous plants, which contain the latter type, are  Adenostyles alliariae (
1
), Alkanna tinctoria, Anchusa officinalis, Borago 
officinalis, Crotalaria spp., Cynoglossum spp., Echium spp., Erechtites hieracifolia, Eupatorium spp., Heliotropium spp., Lithospermum officinale, Packera 
candidissima (
177
), Petasites spp., Pulmonaria spp., Senecio spp., Symphytum spp., and Tussilago farfara (
178
, 
179
 and 
180
). A venoocclusive disease of the liver 
can be produced with clinical features, such as abdominal pain with ascites, hepatomegaly and splenomegaly, anorexia with nausea, vomiting, and diarrhea. 
Sometimes damage to the pulmonary region occurs as well (
178
, 
179
, 
180
, 
181
, 
182
 and 
183
). Animal studies have shown transplacental passage and transfer to 
breast milk, and a human case of fatal neonatal liver injury has been associated with maternal use of a herbal cough tea containing pyrrolizidine alkaloids 
throughout the pregnancy (
184
, 
185
).
The German health authorities no longer permit herbal medicines providing more than 1 µg of unsaturated pyrrolizidine alkaloids internally or more than 100 µg 
externally per day; herbal medicines providing 0.1–1 µg internally or 10–100 µg externally per day, when used as directed, may be applied only for a maximum of 6 
weeks per year and they should not be used during pregnancy or lactation (
186
, 
187
).
Radish, black (Raphanus sativus var. niger)
Urticarial manifestations from oral therapy have been reported (
188
). Consumption of several roots is said to have produced miosis, pain, vomiting, slowed 
respiration, stupor, and albuminuria. It is also claimed that poisoning secondary to the use of black radish sap for bile stones has occurred.

p
y
y
g p g
y
(
,
)
Radish, black (Raphanus sativus var. niger)
Urticarial manifestations from oral therapy have been reported (
188
). Consumption of several roots is said to have produced miosis, pain, vomiting, slowed 
respiration, stupor, and albuminuria. It is also claimed that poisoning secondary to the use of black radish sap for bile stones has occurred.
Rauwolfia root (Rauvolfia serpentina)
Contains numerous alkaloids, of which reserpine and rescinnamine are said to be the most active as hypotensive agents. Among the reported adverse effects of 
0.25 to 0.50 mg/day of reserpine are lethargy, depression, nightmares, sexual dysfunction, anxiety, and gastrointestinal symptoms (
189
). Although depression has 
already been observed at a dose level of 0.25 mg/day (
189
, 
190
), this adverse effect mostly occurs at doses greater than 0.5 mg per day (
191
).
Rhatany root (Krameria triandra)
Rarely allergic mucosal reactions (local use in mouth). Undiluted tincture may produce burning and local irritation.
Rhododendron ferrugineum
Adverse effects have not been reported for herbal tea from the leaves, but toxic diterpenes may be present and chronic use might lead to hydroquinone poisoning 
(due to the presence of arbutin).
Rue (Ruta graveolens)
The essential oil not only can produce contact dermatitis and phototoxic reactions (due to the presence of furocoumarins), but can also induce severe hepatic and 
renal toxicity. Use as an abortive agent has resulted in fatal intoxications. Therapeutic doses can lead to melancholia, sleeping disorders, fatigue, dizziness, and 
cramps. The sap of the fresh leaf can give painful gastrointestinal irritation, fainting, sleepiness, weak pulse, abortion, swollen tongue, and cool skin.
Saffron stigma (Crocus sativus)
No risks have been documented for daily doses up to 1.5 g, but 5 g is toxic, 10 g is abortive, and 20 g may be lethal.
Sage leaf (Salvia officinalis)
The leaf contains 1 to 2.5% of essential oil consisting of 35 to 60% of thujone. This compound may produce toxicity, when the herb is taken in overdoses (more than 
15 g per dose) or for a prolonged period. Pregnancy is listed as a contraindication for the use of the essential oil or alcoholic extracts.
Santalum album wood
Nausea, skin itching.
Saponins
Saponins with irritant properties occur, for example, in the rhizome of the German sarsaparilla ( Carex arenaria), Senega snakeroot (Polygala senega), primrose 
flower and root (Primula veris), and soapwort (Saponaria officinalis).
Sassafras wood (Sassafras albidum)
Sassafras wood contains 1 to 2% of essential oil, which consists of about 80% of safrole. Some of the known or possible metabolites of this compound show 
mutagenic activity in bacterial testing, and it has been proven to have weak hepatocarcinogenic effects in rodents. Experiments in mice suggest the possibility of 
transplacental and lactational carcinogenesis. All in all, prolonged internal use is to be discouraged. Of particular concern seems to be the uncontrolled availability 
of sassafras oil for so-called aromatherapy, which may result in a daily intake up to 0.2 g of safrole, when ingested as recommended (
192
). The German health 
authorities have proposed a withdrawal of sassafras-containing medicines from the market, including that of homoeopathic products up to D3 (
193
).
Saw palmetto fruit (Serenoa repens = Sabal serrulata)
Gastric complaints (rarely).
Scammony, Mexican (Convolvulus scammonia)
The resin is a drastic purgative with irritant properties, which has been superseded by less toxic alternatives.
Senna (Cassia spp.)
Mutagenicity testing of sennosides has produced negative results in several bacterial and mammalian systems, except for a weak effect in  Salmonella typhimurium 
strain TA102 (
194
, 
195
). A well-defined purified senna extract was not carcinogenic when administered orally to rats in daily doses up to 25 mg/kg for two years 
(
196
). No evidence of reproductive toxicity of sennosides has been found in rats and rabbits (
197
). When a standardized preparation containing senna pods 
(providing 15 mg/day of sennosides) was given to breast-feeding mothers, the suckling infants were only exposed to a nonlaxative amount of rhein, which remained 
a factor 10
–3
 below the maternal intake of this active metabolite (
198
). Considering these findings, the German health authorities do not forbid the use of senna fruit 
during pregnancy and lactation (
163
, 
164
 and 
165
). Exceptional complications of senna abuse include hepatitis (
199
), finger clubbing, and hypertrophic osteopathy 
(
200
, 
201
).
Sesquiterpene lactones
Can produce allergic contact dermatitis. Among the medicinal herbs with moderate or strong sensitizing capacity due to the presence of sesquiterpene lactones are 
alant (Inula helenium), arnica (Arnica spp.), artichoke (Cynara scolymus), blessed thistle (Cnicus benedictus), costus root (Saussurea lappa), feverfew (Tanacetum 
parthenium), laurel (Laurus nobilis), pyrethrum (Tanacetum cinerariifolium), and sunflower (Helianthus annuus) (
202
). Sensitizing sesquiterpene lactones are also 
found in camomile (Chamomilla recutita), chicory (Cichorium intybus), dandelion (Taraxacum officinale), lettuce (Lactuca spp.), and yarrow (Achillea millefolium) 
(
202
, 
203
). Cross-sensitivity with other plants containing related allergenic sesquiterpene lactones is possible.
Silverweed (Potentilla anserina)
Gastrointestinal disturbances.
Skullcap
Herbal therapies comprising skullcap as one of their ingredients have been repeatedly associated with hepatotoxic reactions. One of these cases was originally 
attributed to mistletoe, although there were insufficient grounds for this allusion (
163
). Although Western skullcap preparations are supposed to come from 
Scutellaria lateriflora, it remains unclear whether this plant is responsible. In the United Kingdom, the American germander ( Teucrium canadense) has been widely 
used to replace S. lateriflora in commercial skullcap materials and products. In one United Kingdom case of skullcap-associated hepatotoxicity, the material was 
found to come from Teucrium canadense, raising the possibility that other cases of skullcap toxicity may also have involved  Teucrium rather than Scutellaria (
83
).
Snakeroot, black (Cimicifuga racemosa)
Occasionally gastric complaints.

found to come from Teucrium canadense, raising the possibility that other cases of skullcap toxicity may also have involved  Teucrium rather than Scutellaria (
83
).
Snakeroot, black (Cimicifuga racemosa)
Occasionally gastric complaints.
Snakeroot, white (Eupatorium rugosum)
Can produce livestock poisoning as well as milk sickness. This latter syndrome can occur when humans ingest the milk from animals with abundant access to the 
plant. Symptoms include trembles, weakness, nausea and vomiting, prostration, delirium, and even death. Tremetol has long been considered to be the poisonous 
principle in white snakeroot, but chemically this substance is a mixture of many different compounds, including the ketones tremetone, hydroxytremetone, and 
dehydrotremetone. Tremetone seems to be the major toxic component but it is only toxic after microsomal activation. It readily decomposes to dehydrotremetone, 
which is not toxic, not even after microsomal activation (
204
).