Vitamin Toxicity Clinical Presentation

Be wary of large or chronic ingestions of all vitamins in children, especially the fat-soluble vitamins A and D.

Nonspecific symptoms, such as nausea, vomiting, diarrhea, and rash, are common with any acute or chronic vitamin overdose. Vitamin-related symptoms may be secondary to those associated with additives (eg, mannitol), colorings, or binders; these symptoms usually are not severe.

Vitamin A

In acute vitamin A toxicity, a history of some or all of the following may be present:

• Nausea
• Vomiting
• Anorexia
• Irritability
• Drowsiness
• Altered mental status
• Abdominal pain
• Blurred vision
• Headache
• Muscle pain with weakness
• Seizures

In chronic vitamin A toxicity, a history of some or all of the following may be present:

• Anorexia
• Hair loss
• Dryness of mucus membranes
• Fissures of the lips
• Pruritus
• Fever
• Headache
• Insomnia
• Fatigue
• Irritability
• Weight loss
• Bone fracture ^[41]
• Hyperlipidemia
• Hypercalcemia ^[42]
• Anemia
• Bone and joint pains
• Diarrhea
• Menstrual abnormalities
• Epistaxis

Carotenemia, the ingestion of excessive amounts of vitamin A precursors in food, mainly carrots, is manifested by a yellow-orange coloring of the skin, primarily the palms of the hands and the soles of the feet. It differs from jaundice in that the sclerae remain white.

Do not forget to evaluate for ingestion of other potentially toxic substances, such as other vitamins, aspirin, and acetaminophen. Inquire about the intake of other supplements and evaluate for possible overdose accordingly.

Isotretinoin, a drug used for the treatment of severe forms of acne, is closely related to the chemical structure of vitamin A and therefore has similar pharmacologic and toxic attributes (see Pathophysiology and Etiology). A careful drug history to uncover possible isotretinoin use is important in patients presenting with manifestations suggestive of vitamin A intoxication.

Vitamin C

The effects of vitamin C toxicity can include the following:

• Renal colic (ie, nephrolithiasis)
• Diarrhea
• Nausea
• Rebound scurvy - In infants born to women taking high doses
• Hemolysis - If glucose-6-phosphate dehydrogenase (G6PD) deficiency is present
• Dental decalcification
• Increased estrogen levels
• Occult rectal bleeding

Vitamin D

The effects of acute vitamin D toxicity are characteristic of hypercalcemia and may include the following:

• Muscle weakness
• Apathy
• Headache
• Anorexia
• Irritability
• Nausea
• Vomiting
• Bone pain

Chronic toxicity effects include the above symptoms, as well as the following:

• Constipation
• Abdominal cramps
• Polydipsia
• Polyuria
• Backache

Findings may also include calcinosis, followed by hypertension and cardiac arrhythmias (due to a shortened refractory period). Hypercalciuria, kidney stones, ectopic calcification of soft tissues, and acute pancreatitis have also been reported. ^[43]

Khan et al published a case series of 19 elderly patients (mean age of 72.3 years) seen in the emergency department with vitamin D toxicity. The presenting complaint in 85% of patients was altered mental status, which was found to be due to hypercalcemia. ^[44]

In case reports of two young breast-fed infants who developed vitamin D toxicity from inadvertent overdose of highly concentrated vitamin D formulations, the infants presented with decreased feeding, lethargy, and inconsolable crying. Toddlers with vitamin D overdose have presented with irritability, vomiting, constipation, and hypertension. ^[45]

Vitamin E

Patients with vitamin E toxicity are likely to have been using vitamin E supplements; obtain the dose and duration of vitamin E usage. Assess concurrent use of anticoagulants or aspirin. Since vitamin E may block absorption of vitamin K, a nutritional assessment for vitamin K deficiency is useful in patients who present with bleeding and a prolonged prothrombin time (PT).

The effects of acute vitamin E toxicity include the following:

• Nausea
• Gastric distress
• Abdominal cramps
• Diarrhea
• Headache
• Fatigue
• Easy bruising and bleeding - Prolonged PT and activated partial thromboplastin time (aPTT)
• Inhibition of platelet aggregation
• Diplopia - At dosages as low as 300 IU
• Muscle weakness
• Creatinuria

Chronic toxicity effects include all of the above, as well as suppression of other antioxidants and increased risk of hemorrhagic stroke.

Vitamin K

Vitamin K toxicity is typically seen in formula-fed infants or those receiving synthetic vitamin K3 (menadione) injections. Because of its toxicity, menadione is no longer used for treatment of vitamin K deficiency.

The effects of vitamin K toxicity can include jaundice in newborns, hemolytic anemia, and hyperbilirubinemia. Toxicity also blocks the effects of oral anticoagulants.

Vitamin A

Acute toxicity

Acute vitamin A toxicity can result in the following:

• Headache
• Photophobia
• Abdominal pain
• Drowsiness
• Irritability
• Desquamation

Manifestations of acute toxicity also include muscle and bone tenderness, especially over the long bones of the upper and lower extremities, as well as neurologic manifestations with signs of increased intracranial pressure (eg, children may have bulging fontanelles).

Chronic toxicity

Chronic vitamin A toxicity affects the skin, the mucous membranes, and the musculoskeletal and neurologic systems. Skin and mucous membrane effects include erythema, eczema, pruritus, dry and cracked skin, angular cheilitis, conjunctivitis, palmar and plantar peeling, and alopecia.

Musculoskeletal effects include pain and tenderness, particularly in the long bones of the upper and lower extremities, which may be exacerbated by exercise. Neurologic effects include blurred vision and frontal headache, which is often the first sign of toxicity.

In addition, studies suggest that elevated levels of vitamin A may cause increased bone resorption and promote the development of osteoporosis. ^{[3, 46]}

Manifestations of chronic vitamin A toxicity also include the following:

• Alopecia
• Erythematous dermatitis
• Skin desquamation
• Brittle nails
• Exanthema
• Cheilitis
• Conjunctivitis
• Petechiae
• Liver cirrhosis
• Hepatosplenomegaly
• Peripheral neuritis
• Benign intracranial hypertension
• Ataxia
• Papilledema
• Diplopia
• Hyperostosis
• Edema
• Hepatic hydrothorax ^[47]
• Hepatomegaly
• Ascites
• Migratory arthritis
• Craniotabes (in children)
• Bulging fontanelle (in infants)
• Epiphyseal capping and premature epiphyseal closure

Vitamins B1, B2, B3, and B6

The effects of toxicity may be minimal and nonspecific for these vitamins.

Vitamin B1

Vitamin B1 (ie, thiamine) toxicity effects may include the following (single acute toxicity is rare):

• Tachycardia
• Hypotension
• Cardiac dysrhythmias
• Headache
• Anaphylaxis
• Vasodilation
• Weakness
• Convulsions

Vitamin B2

Vitamin B2 (ie, riboflavin) toxicity turns the patient’s urine yellow-orange.

Vitamin B3

Acute toxicity effects related to vitamin B3 (ie, niacin, nicotinic acid) are prostaglandin-mediated and include the following:

• Flushing
• Pruritus
• Wheezing
• Vasodilation
• Headache
• Increased intracranial blood flow
• Headache
• Diarrhea
• Vomiting

Chronic toxicity effects include the following:

• Jaundice
• Abnormal liver function test (LFT) results
• Signs and symptoms of liver toxicity - Most common with sustained-release preparations
• Acanthosis nigricans (rare)

Vitamin B6

Effects of vitamin B6 (ie, pyridoxine) toxicity include tachypnea and sensory neuropathies, such as the following:

Burning pains

• Paresthesias
• Ataxia
• Clumsiness
• Paralysis
• Perioral numbness

Findings range from normal central nervous system (CNS) function to progressive sensory ataxias, profound impairment of position and vibration sense, and diminished tendon reflexes.

Vitamin E

Physical examination findings are likely to be normal in patients with vitamin E toxicity; however, evidence of easy bleeding may be present if the PT is elevated.

Patients with intracranial hemorrhage may show signs of focal neurologic deficits on a detailed neurologic examination or may have a decreased level of consciousness.