Toxicoses in Animals From Human Dietary and Herbal Supplements

5-Hydroxytryptophan (5-HTP) is both a drug and a natural component of some dietary supplements. It comes in a variety of forms and may also be labeled as oxitriptan or Griffonia seed extract. It is used in humans to promote relaxation and to alleviate symptoms related to depression, insomnia, headaches, and various other ailments. 

5-HTP is a precursor to serotonin and can cause serotonin syndrome.

In animals, clinical signs associated with toxicosis due to 5-HTP ingestion include CNS depression, tremors, hyperesthesia, ataxia, seizures, hyperthermia, mydriasis, transient blindness, tachycardia, tachypnea, vocalization, vomiting, and diarrhea. Clinical signs develop within 1–4 hours of ingestion and last 12–36 hours.

Decontamination after recent 5-HTP ingestion is indicated if the patient is not exhibiting neurological signs, to avoid the risk of aspiration. GI decontamination consists of inducing emesis or performing gastric lavage and then administering activated charcoal with sorbitol. The patient is then placed on IV fluid therapy, cardiac function and thermoregulation are monitored, and CNS signs are managed with methocarbamol and anticonvulsants.

Vocalization and dysphoria are common clinical signs of 5-HTP toxicosis and can be managed with cyproheptadine, a serotonin antagonist (in dogs: 1.1 mg/kg, PO, every 1–6 hours as needed until resolution of clinical signs; in cats: 2–4 mg/cat, PO, every 4 hours, as needed).

Benzodiazepines should be administered with caution to patients with 5-HTP toxicosis because these drugs can exacerbate CNS signs; however, they can be used if no other options are available. 5-HTP is not lipophilic, so IV lipid therapy is not typically useful in these patients. 

Loss of vision is expected to resolve; however, full recovery can take several days to weeks after hospitalization is complete.

Common hops (Humulus lupulus) are used as an herbal supplement in humans to alleviate insomnia, pain, anxiety, menopausal symptoms, digestive problems, and other ailments. 

There are no reports of hops poisoning in species other than dogs. The exact mechanism that causes hops toxicosis is not known; however, phenolic compounds in the plant material are suspected to trigger the uncoupling of oxidative phosphorylation, leading to clinical signs.

Clinical signs of hops toxicosis include severe malignant hyperthermia, tachycardia, tachypnea, vomiting, diarrhea, and agitation or lethargy. Clinical signs develop within 8–24 hours of ingestion and last 24–48 hours.

Treatment of hops toxicosis is to decontaminate by inducing emesis or by performing gastric lavage and then administering activated charcoal with a cathartic. If the patient has severe hyperthermia, a CBC, a serum biochemical profile, electrolyte concentrations, and a baseline coagulation panel should be obtained. Dantrolene (2–3 mg/kg, IV, or 3.5 mg/kg, PO, which may be repeated at up to 10 mg/kg, IV or PO, as needed) can be used as an antidote for severe malignant hyperthermia. NSAIDs and dipyrone should not be used to control hyperthermia.

Active cooling is important for successful treatment of hops toxicosis. IV fluid therapy, cool-water enemas, fans, and alcohol applied to footpads can decrease the patient's body temperature; however, active cooling should be stopped at 39.7°C (103.5°F) to avoid overcooling. In addition, cool towels should not be placed on the patient, because they can trap heat and prevent evaporation. Patients should also not be bathed in ice water, which can lead to shock and DIC.

Ma huang comes from the Ephedra plant. Other names include Chinese ephedra, epitonin, and Sida cordifolia. The plant contains both ephedrine and pseudoephedrine. Ma huang can be sold alone or as a combination product. 

Guarana (Paullinia cupana), also known as kola nuts or Brazilian cocoa, is a natural source of caffeine that can have a more prolonged effect than do more common forms of caffeine. It is frequently used as a combination product with Griffonia seed (5-HTP), chromium, and grape seed. In humans, guarana is used as a dietary aid and energy stimulant.

Combining guarana with ma huang has a synergistic effect that increases the risk of toxicosis when the supplement is ingested in large amounts.

Clinical signs of ma huang and guarana toxicosis in animals include vomiting, agitation, mydriasis, tachycardia, hypertension, arrhythmias, ataxia, tremors, seizures, and, potentially, serotonin syndrome. Clinical signs develop within 30 minutes to 8 hours of ingestion and last 24–72 hours, depending on how much is ingested and whether ma huang and guarana are consumed together.

Within 4 hours of ingestion, treatment for ma huang/guarana toxicosis is to decontaminate by inducing emesis and then administering activated charcoal with a cathartic. IV fluid therapy should be initiated while cardiac function is monitored and neurological support is provided.

Beta-adrenergic receptor antagonists can be used to manage tachycardia and hypertension. Benzodiazepines should be avoided because they can have a paradoxical effect and exacerbate clinical signs.

Serotonin syndrome, if it develops, can be managed with cyproheptadine (in dogs: 1.1 mg/kg, PO, every 4 hours as needed; in cats: 2–4 mg/cat, PO, every 4 hours as needed).

Ginseng (genus Panax) is a common herbal supplement used in humans to decrease inflammation, lower blood sugar, boost immune system function, and increase energy, as well as for other beneficial effects. Common products are sold as Panax ginseng, Asian ginseng, red ginseng, and ginseng complex.

Some animals that ingest very large amounts of ginseng develop agitation, restlessness, tachycardia, hypertension, and GI signs. 

Recent ingestions of ginseng can be treated with early decontamination, starting with induction of vomiting; however, activated charcoal is typically not warranted with this exposure because the signs are generally self-limiting. If tachycardia and hypertension develop, they can be managed with sedation and supportive care.

Kratom, which is derived from Mitragyna speciosa, a tree in the coffee family, is a controversial herbal supplement that can be abused. It is used as an energy booster, mood enhancer, pain reliever, and remedy for opioid withdrawal. The leaves contain mitragynine, which has psychoactive properties that have opioid-like effects. The product can be sold as tablets, capsules, or a tea.

Clinical signs associated with kratom toxicosis in animals include agitation, restlessness, and tachycardia at low doses; large doses can have opioid effects that include vomiting, sedation, and stupor.

In most cases of only a small exposure, decontamination is not indicated. For large ingestions of kratom, treatment is to decontaminate by inducing emesis or performing gastric lavage. Activated charcoal can be administered in a large dose, but only if the patient can swallow safely. 

Information on naloxone use to treat kratom toxicosis in human medicine is limited, and it is not considered an antidote at this time. Further evaluation is needed to determine whether naloxone would be effective in animals.

In severe cases of kratom toxicosis, patients can be treated with IV fluid therapy and management of neurological signs. If seizures develop, levetiracetam (30–60 mg/kg, IV slowly, diluted to a final concentration of not more than 15 mg/mL in saline solution [0.9% NaCl] or 5% dextrose solution, up to every 8 hours as needed) can be administered. To avoid additional sedative effects, phenobarbital should not be used. If respiratory depression occurs, intubation and oxygen therapy can be indicated.

Arnica extract (from Arnica montana) is an herbal supplement used in humans to help with pain relief, as an anti-inflammatory, to prevent hair loss, and for skin conditions such as acne and psoriasis. Products can be formulated in various strengths—ie, in milligrams or as a homeopathic formulation. 

Homeopathic products have historically been highly diluted (eg, a homeopathic formulation labeled as 60X or 30C HPUS has been diluted in a 1:10 ratio 30 times; it is a 1:10⁶⁰ dilution) and are likely not a concern for poisoning. However, some products labeled as homeopathic may contain low dilutions, or the ingredients and concentrations may not be standardized or may not be listed.

Clinical signs associated with arnica toxicosis in animals include vomiting, diarrhea, CNS depression, muscle weakness, hypertension, and cardiotoxicity.

In general, arnica toxicosis is well tolerated, having only mild GI effects. For very large ingestions, early treatment is to decontaminate by inducing emesis or performing gastric lavage. Activated charcoal with a cathartic can be administered once, if no CNS signs are present.

In arnica toxicosis cases that require hospitalization, the patient should be placed on IV fluid and monitored for cardiovascular signs. If hypertension develops, it can be managed with sedation. If severe cardiovascular signs are observed, they should be monitored with ECG. Neurological signs of CNS depression and muscle weakness can be managed with supportive care.

St. John’s wort is an herbal supplement used in humans for depression and anxiety. In human medicine, the product is a potential concern for the development of serotonin syndrome in humans (vocalization, dysphoria, tachycardia, tremors, seizures, hyperthermia). However, serotonin syndrome brought on by St. John's wort in humans typically results only when the supplement is ingested at high doses along with other drugs, such as selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase (MAO) inhibitors. 

In most cases of St. John's wort toxicosis in animals, only mild CNS depression occurs. However, animals that ingest very large amounts of St. John’s wort can develop serotonin syndrome.

Very large ingestions of St. John's wort should be treated with decontamination by inducing emesis or performing gastric lavage. When serotonin syndrome develops, its clinical signs usually become evident within hours after the ingestion. 

Cases of serotonin syndrome should be treated with IV fluid therapy, as well as with cyproheptadine (in dogs: 1.1 mg/kg, PO, every 4 hours as needed; in cats: 2–4 mg/cat, PO, every 4 hours as needed) to help manage dysphoria and vocalization, and cardiac parameters should be monitored. If CNS signs are present, benzodiazepines should be avoided, to prevent exacerbation of those signs. 

Seizures should be managed with phenobarbital (4–8 mg/kg, IV slowly, every 1–4 hours as needed) or levetiracetam (30–60 mg/kg, IV slowly, diluted to a final concentration of not more than 15 mg/mL in saline solution [0.9% NaCl] or 5% dextrose solution, up to every 8 hours as needed).

Ginkgo (Ginkgo biloba) is an herbal supplement frequently used in humans for its antioxidant and anti-inflammatory properties, as a cough suppressant, to decrease anxiety, to improve brain function, and for other properties. It is sold alone or in combination with other herbal supplements.

In animals, clinical signs resulting from large ingestions of ginkgo can include vomiting, diarrhea, agitation, and, with very large ingestions, seizures. Clinical signs develop within 1–12 hours after ingestion. GI signs generally resolve within hours. 

Early treatment for a large exposure to ginkgo is to decontaminate by inducing emesis or performing gastric lavage and then administering activated charcoal with a cathartic.

GI signs should be treated with an antiemetic, SC or IV fluid therapy, and supportive care. For neurological signs, vitamin B₆ (pyridoxine) can be administered as an antidote. Seizures can be managed with anticonvulsants, including benzodiazepines.

Ashwagandha (Withania) is an herbal supplement used in humans to help with anxiety, depression, fatigue, and memory problems. Sometimes called winter cherry or Indian ginseng, this supplement is typically well tolerated by animals; however, it can lead to mild GI signs. Treatment is supportive care.

Rauwolfia (genus Rauwolfia) is an herbal supplement used in humans as an antihypertensive and to improve brain function. 

Clinical signs of rauwolfia toxicosis in animals include hypotension, bradycardia, diarrhea, melena, and GI ulceration. Clinical signs develop within hours after ingestion and can last several days.

Early treatment of rauwolfia toxicosis is to decontaminate by inducing emesis and performing gastric lavage, and then administering activated charcoal with a cathartic. IV fluid therapy should be initiated, and the patient monitored for hypotension and bradycardia. GI protectants such as sucralfate (250–1,000 mg/animal, PO, every 8 hours as needed) are indicated, along with supportive care. 

IV lipid therapy (using 20% lipid emulsion at 1.5 mL/kg, IV over 5–15 minutes, followed by 0.25 mL/kg/minute, IV CRI, over 1–2 hours, which can be repeated up to twice if there is no clinical improvement and if plasma or serum is no longer lipemic) has been used in dogs with some success.

Saw palmetto (Serenoa repens) is an herbal supplement used in humans to improve prostate health and relieve urinary tract symptoms. It is well tolerated in animals, and notable clinical signs are not anticipated in cases of ingestion. With large ingestions, mild GI signs can develop. Decontamination is typically not indicated.

Mugwort (Artemisia vulgaris), also known as wormwood, is an herbal supplement used in humans to alleviate anxiety, boost energy, improve digestion, relieve pain, and address a variety of other ailments. 

The primary result of mugwort ingestion is GI irritation. With large ingestions, clinical signs can include tremors, seizures, coma, and respiratory failure. Elevations in liver enzyme activity and renal marker concentrations have also been reported.

Early treatment for a large ingestion of mugwort is to decontaminate by inducing emesis or performing gastric lavage and then administering activated charcoal with a cathartic if the patient is able to swallow safely and no neurological signs are present.

IV fluid therapy should be initiated for mugwort toxicosis, and the patient's hepatic and renal values should be monitored for several days. Hepatic protectants can be started if liver values elevate. For neurological signs, tremors can be treated with methocarbamol starting at 30 mg/kg and titrated to effect. For seizure activity, benzodiazepines and levetiracetam can be administered; however, phenobarbital should not be used as an anticonvulsant, because it can worsen respiratory depression.

Alpha-lipoic acid (ALA) is a dietary supplement that has a variety of health benefits in humans, including regenerating antioxidants, scavenging reactive oxidant species, and providing antidiabetic effects such as decreasing glucose concentrations and helping with weight loss. 

In animals, ALA toxicosis can result in clinical signs that include vomiting, hypoglycemia, ataxia, tremors, seizures, and hepatic and renal damage. Cats are more susceptible to developing clinical signs at lower doses than dogs. Hypoglycemia is one of the main concerns.

If the patient remains clinically healthy, early treatment of ALA ingestion is to decontaminate by inducing emesis or performing gastric lavage and then administering a single dose of activated charcoal with sorbitol. The patient's blood glucose concentration should be monitored every 2–4 hours for the first 12–24 hours; hepatic and renal function should be monitored for 72 hours.

Elevations in hepatic enzyme activities should be treated with either N-acetylcysteine (5% concentration, 140–180 mg/kg, IV slowly over at least 15–20 minutes; or 280 mg/kg, PO via gastric tube once, followed by 70 mg/kg, PO or IV, every 6 hours for a minimum of seven treatments) or other hepatoprotectants. The patient should be monitored for hypoglycemia and hypokalemia for the first several hours, and dextrose and potassium should be administered as needed.

Large ingestions of ALA can result in neurological signs, including tremors and seizures. If these signs develop, blood glucose concentration should be measured. If hypoglycemia is present, dextrose should be administered. Otherwise, seizures can be managed with anticonvulsants such as phenobarbital (4–8 mg/kg, IV slowly, every 1–4 hours as needed), levetiracetam (30–60 mg/kg, IV slowly, diluted to a final concentration of not more than 15 mg/mL in saline solution [0.9% NaCl] or 5% dextrose solution, up to every 8 hours as needed), or benzodiazepines.

Severe tremors can be managed with methocarbamol (55–220 mg/kg, IV slowly, to effect). The dose can be repeated as needed; however, cumulative doses > 330 mg/kg every 24 hours should be avoided to avoid CNS and respiratory depression.