Toxicoses in Animals From Human Multivitamins and Supplements

Calcium is a very common constituent of multivitamins and is commonly found as a supplement, often in combination with vitamin D. High calcium intake by animals can result in GI upset, constipation, and chalky, white stools.

Hypercalcemia can result from excessive calcium or vitamin D intake. However, although a single high dose of calcium could lead to hypercalcemia, it would be too transient to cause systemic toxicosis. Concurrent ingestion of a high dose of vitamin D is generally toxic and requires treatment.

Dietary calcium intake for dogs is recommended at 0.27 g/kg/day (1). Calcium intake in animals at higher levels can result in GI upset, constipation, and chalky, white stools.

Copper is often present in small amounts in multivitamins. Copper salts (such as those found in cattle footbaths and algicides) can cause corrosive injury; however, a single high ingestion of copper-containing multivitamins would be expected to result in only mild GI upset, even in dogs or cats with underlying copper storage disorders.

Multivitamin preparations contain varying amounts of iron. Iron is generally listed in multivitamin preparations as "iron" or "elemental iron."

Iron can directly irritate the GI mucosa and, in severe cases, can be caustic. It can also be a specific mitochondrial toxin. Once the iron-carrying capacity of serum has been exceeded, free iron is deposited in the liver, where it damages mitochondria and leads to necrosis of periportal hepatocytes.

Clinical signs of iron toxicosis usually develop within 6 hours after exposure. Initial signs typically include vomiting and diarrhea, with or without blood, which can be followed by hypovolemic shock, depression, fever, acidosis, and liver failure 12–24 hours later, often with a period of apparent recovery in between. Oliguria and anuria secondary to shock-induced renal failure can also occur.

Ingestion of elemental iron at > 50 mg/kg generally warrants decontamination (emesis) and administration of GI protectants. Activated charcoal does not bind iron well. Magnesium hydroxide and calcium carbonate, which can complex with iron to decrease its absorption from the GI tract, are commonly used for decontamination.

Additional treatment and monitoring are necessary for patients that have ingested > 80 mg/kg of elemental iron. Serum iron concentrations can be checked at 4–6 hours after exposure to iron. If serum iron is > 500 mcg/dL, or it is < 500 mcg/dL but noteworthy clinical signs are evident, chelation therapy might be needed.

Deferoxamine is a specific iron chelator and is most effective within 24 hours after ingestion, before iron has been distributed from blood to tissues. Chelation with deferoxamine should continue until urine color returns to normal (12–72 hours). Other clinical signs should be treated with supportive care.

Magnesium is a common constituent of multivitamins; it can also be found as a single-ingredient supplement. Excessive intake of magnesium impairs neuromuscular transmission by decreasing acetylcholine concentrations, and it slows sinoatrial-node impulse formation and myocardial conduction.

Magnesium toxicosis is uncommon but can occur with large oral ingestions. Clinical signs typically begin within 2–3 hours after exposure and include GI upset, bradycardia, and weakness. Hypocalcemia and hypokalemia also commonly occur. Clinical signs typically last 12–48 hours; however, underlying renal disease can prolong excretion and the duration of toxicosis.

Treatment of magnesium toxicosis consists of fluid support to promote cardiac output. Furosemide also can be administered to increase excretion of magnesium by the kidneys and thereby decrease blood levels of magnesium. IV calcium gluconate can be administered to antagonize the effects of excess magnesium at neuromuscular junctions and to help reestablish normal blood calcium levels.

Vitamin A toxicosis after consumption of large amounts of cod liver oil, polar bear liver, or seal liver has been well documented; however, ingestion of vitamin A in supplements rarely leads to toxicosis. There are no known cases of intoxication with beta carotene, a provitamin A carotenoid.

The amount of vitamin A needed to produce toxic effects is 10–1,000 times the dietary requirements for most species. The vitamin A requirement for cats is 10,000 IU/kg of diet fed, and amounts up to 100,000 IU/kg of diet are considered safe. For dogs, the requirement is 3,333 IU/kg of diet fed, and up to 333,300 IU/kg of diet is considered safe.

Clinical signs associated with acute vitamin A toxicosis include general malaise, anorexia, nausea, peeling skin, weakness, tremors, seizures, paralysis, and death. Clinical signs generally resolve when vitamin A exposure is discontinued.

Supplements can contain a single B vitamin or multiple B vitamins. These often include thiamine (vitamin B₁), riboflavin (vitamin B₂), niacin (vitamin B₃), pantothenic acid (vitamin B₅), pyridoxine (vitamin B₆), biotin (vitamin B₇), folate (vitamin B₉), and cyanocobalamin or methylcobalamin (vitamin B₁₂).

Ingestion of B vitamins can result in GI upset, and high doses can discolor the urine. Rarely, however, does vitamin B ingestion result in more substantial clinical signs in animals.

Vitamin C has a wide margin of safety. It can cause GI upset and mild GI irritation when ingested orally; however, systemic clinical signs requiring treatment are not expected.

Vitamin D is included in many calcium supplements to aid the absorption of calcium. Most multivitamins contain cholecalciferol (vitamin D₃). After consumption, cholecalciferol is converted in the liver into 25-hydroxycholecalciferol (calcifediol), which is subsequently converted in the kidneys to the active metabolite 1,25-dihydroxycholecalciferol (calcitriol). One IU of vitamin D₃ is equivalent to 0.025 mcg of cholecalciferol.

Even though the oral LD₅₀ of cholecalciferol in dogs has been reported as 88 mg/kg, clinical signs of toxicosis have been reported at doses as low as 0.5 mg/kg. Vomiting, depression, and polyuria/polydipsia can develop within 12–48 hours of a substantial vitamin D exposure, followed by hypercalcemia and azotemia in 24–48 hours. Acute kidney injury can occur in later stages of the toxicosis. The kidneys, heart, and GI tract might become necrotic and mineralized.

Initial treatment of vitamin D toxicosis should include decontamination; low-calcium diet; and assessment of baseline calcium, phosphorus, BUN, and creatinine. Cholestyramine binds to intestinal bile acids and interferes with the absorption of fat-soluble vitamin D, thereby increasing its excretion.

If clinical signs of toxicosis and marked hypercalcemia or hyperphosphatemia develop, treatment consists of saline diuresis and the administration of furosemide, corticosteroids, and phosphate binders.

Specific agents such as pamidronate (a bisphosphonate that decreases serum calcium levels by preventing bone resorption and may also decrease intestinal absorption of calcium) might be required if hypercalcemia persists despite supportive care. Stabilization of serum calcium might require days of treatment because of the long half-life of calcifediol (16–30 days).

Vitamin E is well tolerated by animals, and toxicosis is rare. Ingestion can lead to mild GI upset or flatulence; however, more severe clinical signs from single high doses are not typical.

Excessive intake of vitamin E can interfere with vitamin K–dependent carboxylase, which might lead to decreased vitamin K–dependent clotting factors and occult bleeding in patients on warfarin.

Zinc is a common ingredient in multivitamins and can be found in lozenges that are designed to treat the common cold.

The development of zinc toxicosis resulting from ingestion of US pennies minted after 1982 has been well documented in small animals; rarely, though, does toxicosis occur upon ingestion of zinc in supplements.

Although no effects are expected with onetime exposures to pharmaceutical formulations of zinc, prolonged high blood concentrations of zinc result in hemolysis, icterus, pancreatitis, and acute kidney injury secondary to hemoglobinuria.

Treatment of zinc toxicosis is aimed at removing the source of zinc, providing IV fluids to prevent renal injury, and administering blood transfusions if severe anemia is appreciated.

• DeClementi C, Sobczak BR. Common rodenticide toxicoses in small animals. Vet Clin North Am Small Anim Pract. 2018;48(6):1027-1038.

• National Research Council. Mineral Tolerance of Animals. 2nd rev. ed. National Academies Press; 2005.

• Puls R, ed. Mineral Levels in Animal Health: Diagnostic Data. 2nd ed. Sherpa International; 1994.

• Also see pet owner content regarding multivitamin and supplement poisoning.

1. Puls R, ed. Mineral Levels in Animal Health: Diagnostic Data. 2nd ed. Sherpa International; 1994.