Hypervitaminosis

Vitamins are good for you. Therefore even more vitamins are even better. This appears to be the erroneous philosophy expounded by some, especially the "health foods" industry. It is as fundamentally flawed as the concept that anything "natural" is entirely beneficial and devoid of adverse effects.

There is still a public perception that megadosage vitamin C is beneficial for the common cold despite the overwhelming evidence to the contrary. The fact that many expensive proprietary preparations of paracetamol, which does help the symptoms of viral infection, also contain vitamin C, bolsters this myth.

By and large, excessive dosage of water soluble vitamins is only a waste of money as excesses of water soluble vitamins such as vitamin C are just excreted in the urine. Most fat soluble vitamins are toxic in excess. Overdose may result from strange diets or from the belief that the more the better is applicable.

Vitamin A is present as fatty-acid esters in food sources such as liver, kidney, and milk, and as provitamin A carotenoids in plants usually as β-Carotene. High intake of β-Carotene (hypercarotenaemia) can colour the skin yellow, sparing the eyes, in contrast to jaundice where the sclera is also yellow.

Vitamin A toxicity can be acute or chronic. It is well absorbed and there is no effective mechanism for removing or metabolising large amounts. Adults require 500 μg retinol equivalents/day, children 250-350μg /day. Pregnant women should not exceed their recommended intake of 600μg /day. High doses of vitamin A can be teratogenic.¹

Acute hypervitaminosis A

This is usually from a large overdose such as in eating polar bear's liver that is known to be exceptionally high in the vitamin. Symptoms include:

• Headache
• Abdominal pain
• Nausea or vomiting
• Lethargy
• Visual changes
• Impaired consciousness

There are features suggestive of raised intracranial pressure such as bulging fontanelle in an infant, papilloedema and diplopia. Anaemia and thrombocytopenia have also been described.²

Chronic hypervitaminosis A

This requires in excess of 50,000 units/day for more than 3 months. Symptoms often include bone pain and bony swelling due to increased bone resorption and periosteal bone formation, often associated with hypercalcaemia. Other symptoms can be quite non-specific:

• Scaly seborrhoic eczema
• Patchy hair loss
• Stomatitis
• Loss of appetite
• Nausea
• Vomiting
• Malaise
• Hepatosplenomegaly
• Raised intracranial pressure

Children can present with craniotabes, irritability, failure to thrive, decreased appetite and pruritis. Craniotabes is abnormally soft bones of the skull and is unrelated to tabes dorsalis. Complications include:

• Hypercalcaemia
• Hypercalciuria and renal stones
• Benign intracranial hypertension
• Increased bone fragility with increased risk of fractures

It may be unwise to give Vitamin A supplements to older patients with good diets, particularly if at risk of osteoporosis.³

Investigation

• FBC
• U&E especially if there is vomiting
• LFTs
• Ca⁺⁺
• In chronic intoxication get a DEXA scan for bone density

Management

Stop supplements. If there are changes in mental state, admission to hospital is required.

Prognosis

Mortality is rare. Once identified, the prognosis is good. The yellow coloration of skin will reverse with time.

Usually this is caused by excessive ingestion⁴ or over prescription of prescribed medications such as calcium with vitamin D. Occasionally there is increased calcitriol production as in hyperparathyroidism or malignancy including some renal adenomas, sarcomas and lymphomas. In sarcoidosis there is a hypersensitivity to vitamin D. Excessive levels of vitamin D are unlikely to result from excessive exposure to sunlight.

Presentation

Most symptoms occur because of secondary hypercalcaemia with increased bone resorption and hypercalciuria. They include:

• Polyuria
• Polydypsia
• Vomiting
• Anorexia
• Lethargy
• Dehydration
• Constipation
• Hypertension
• Tetany
• Seizures can be fatal

The traditional description of hypercalcaemia is stones, bones and groans. Hypervitaminosis D is also recognised as a cause of depression,⁵ and in childhood can result in dental enamel hypoplasia and focal pulp calcification.⁶

Investigations

Serum calcium and phosphate and 25 hydroxy-vitamin D and 1,25 dihydroxy-vitamin D levels.

Management

Stop supplements and treat the cause. Bisphosphonates such as pamidronate may be used to treat hypercalcaemia. Glucocorticoids are occasionally used for a short while in severe cases of vitamin D intoxication.⁷

Complications

These may include:

• Nephrolithiasis
• Nephrocalcinosis (calcium oxalate and calcium phosphate are radio-opaque stones)
• Calcinosis of joints and periarticular tissues
• Ultimately chronic renal failure

Prognosis

Renal disease is usually reversible if recognised early.

Vitamin E is present in a great many foods and 3 or 4 decades ago it appeared to be a vitamin in search of a deficiency. Its importance had been demonstrated only for reproductive efficacy in rats. Vitamin E (alpha-tocopherol) is a fat soluble vitamin which acts as an anti-oxidant and disposes of free radicals. Problems only usually occur after very large overdose.⁸ The recommended daily dose is 30mg per day, and side-effects are usually experienced at doses above 1g/kg.

Symptoms

Bruising and bleeding with increased prothrombin time is mediated by the inhibition of vitamin K dependent carboxylase, and reversed by administering vitamin K. Platelet thromboxane production is also reduced. Some studies have also reported fatigue, weakness, headache and GI upset. Impaired immunity with secondary necrotizing enterocolitis has been observed in premature infants given vitamin E to prevent retrolental fibroplasia.

Investigations

• Clotting screen
• Alpha-tocopherol serum levels

Management

Stop supplements. Consider vitamin K if prothrombin time is prolonged.

Toxicity from excess of vitamins A and D and, exceptionally vitamin E, can occur but it is important not to exaggerate the risk for fear of resultant deficiency. However, the ethos of vitamins are good, therefore lots of vitamins are even better is to be opposed. As in all things, moderation is the key.

The 1597, Gerrit de Veer wrote in his diary about taking refuge in the winter in Nova Zembla during an attempt to reach Indonesia by the northern passage. He and his men became gravely ill after eating polar-bear liver. They feared for their lives but ultimately recovered. De Veer's diary also notes widespread and striking desquamation during recovery.