Multivitamins and Iron (Toxicity)
The common ingredients in multivitamins include ascorbic acid (vitamin C), cyanocobalamin (vitamin B12), folic acid, thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), biotin, pantothenic acid, pyridoxine (vitamin B6), calcium, phosphorus, iodine, iron, magnesium, copper, zinc, and vitamins A, D, and E. Among these ingredients, iron and vitamins A and D may cause significant systemic signs. Acute ingestion of other listed ingredients in companion animals can result in self-limiting GI upset (eg, vomiting, diarrhea, anorexia, lethargy). However, toxicity is typically rare in pets.
Multivitamin preparations contain varying amounts of iron. Unless otherwise listed, iron should be assumed to be elemental iron. Various iron salts may contain 12%–48% elemental iron. Iron has direct caustic or irritant effects on the GI mucosa. It can also be a direct mitochondrial poison. 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. Signs of iron toxicosis usually develop within 6 hr. Initial vomiting and diarrhea, with or without blood, may be followed by hypovolemic shock, depression, fever, acidosis, and liver failure 12–24 hr later, often with a period of apparent recovery in between. Oliguria and anuria secondary to shock-induced renal failure may also occur. Ingestion of elemental iron at >20 mg/kg generally warrants decontamination (emesis) and administration of GI protectants. Activated charcoal does not bind iron well. Additional treatment and monitoring is necessary for patients that have ingested elemental iron at >60 mg/kg. Milk of magnesia (magnesium hydroxide; 5–30 mL once or twice daily, per dog) can complex with iron to decrease its absorption from the GI tract. Serum iron levels and the total serum iron binding capacity should be checked at 3 hr and again at 8–10 hr after exposure. If serum iron is >300 mcg/dL along with clinical signs such as repeated vomiting and shock, or greater than the total iron binding capacity, chelation therapy may be needed. Deferoxamine (40 mg/kg, IM, every 4–8 hr) is a specific iron chelator and is most effective within 24 hr of ingestion, before iron has been distributed from blood to tissues. Other signs should be treated symptomatically.
Vitamin A toxicity after consumption of large amounts of fish oil or bear’s liver has been well documented, but it is less likely to occur after acute ingestion of multivitamins. The amount of vitamin A needed to cause 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, with levels up to 100,000 IU/kg of diet considered to be safe. For dogs, the requirement is 3,333 IU/kg of diet fed, with up to 333,300 IU/kg of diet considered to be safe. Signs associated with acute vitamin A toxicity include general malaise, anorexia, nausea, peeling skin, weakness, tremors, convulsions, paralysis, and death.
Vitamin D is included in many calcium supplements to aid the absorption of the calcium. Most vitamins contain cholecalciferol (vitamin D3). After consumption, cholecalciferol is converted into 25-hydroxycholecalciferol (calcifediol) in the liver, which is subsequently converted to the active metabolite 1,25-dihydroxycholecalciferol (calcitriol) in the kidneys. 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, signs have been seen at dosages as low as 0.5 mg/kg. Vomiting, depression, polyuria and polydipsia, and hyperphosphatemia may be seen within 12 hr of a significant vitamin D exposure, followed by hypercalcemia and acute renal failure in 24–48 hr. In addition to renal failure, the kidneys, heart, and GI tract may show signs of necrosis and mineralization. Initial treatment should include decontamination and assessment of baseline calcium, phosphorus, BUN, and creatinine. Multiple doses of activated charcoal with a cathartic should be administered. If clinical signs of toxicosis and significant hypercalcemia/hyperphosphatemia develop, treatment consists of saline diuresis and the use of furosemide, corticosteroids, and phosphate binders. Specific agents such as (salmon) calcitonin or pamidronate may be needed for animals that remain hypercalcemic despite symptomatic treatment. Stabilization of serum calcium may require days of treatment because of the long half-life of calcifediol (16–30 days).