Hypervitaminosis

Vitamins are readily available and sold in many different formulations and a wide variety of retail outlets. The food industry occasionally supplement foods with vitamins. It is perhaps understandable that there is a widely held perception that vitamin deficiency is the only concern. In fact vitamins can be taken in excess and we should be aware of the problems from hypervitaminosis which, although uncommon, do occur.

The belief that megadosage vitamin C is beneficial for the common cold was given credence by the American scientist Linus Pauling (1901- 1994). This view is not supported by medical evidence. However this belief is still propagated and given tacit support by, for example, the inclusion of vitamin C in cold remedies. The use of vitamin supplements in 'sweet-like' formulations is not without hazards.¹

Generally speaking any excess of water soluble vitamins is excreted in the urine. However fat soluble vitamins can be toxic in excess. Hypervitaminosis can result from unusual dietary factors or from excessive supplementation.

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 are 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 quantities. 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.² Toxicity has been reported in children from vitamin supplements.¹

Acute hypervitaminosis A

This occurs after large overdosage of the vitamin. This can occur with unusual dietary intake such as, for example, ingestion of polar bear liver which has a very high vitamin A content. Symptoms include:

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

Other features suggestive of raised intracranial pressure such as bulging fontanelle (in an infant), papilloedema and diplopia may also occur. Anaemia and thrombocytopenia have also been described.³

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 seborrhoeic eczema
• Patchy hair loss
• Stomatitis
• Loss of appetite
• Nausea
• Vomiting
• Malaise
• Hepatosplenomegaly
• Liver failure⁴
• Raised intracranial pressure

Children can present with craniotabes, irritability, failure to thrive, decreased appetite and pruritus. 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.⁵

Investigation

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

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 ingestion⁶ 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.⁷ In children it can result in dental enamel hypoplasia and focal pulp calcification.⁸

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.⁹

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.¹⁰ The recommended daily dose is 30 mg per day, and side-effects are usually experienced at doses above 1 g/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 gastrointestinal 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 . However, the belief that vitamins are good, therefore lots of vitamins are even better is inaccurate and simplistic. There has been an explosion of interest in vitamin supplementation and a great deal of interest in nutritional medicine. This may help inform better diets and better dietary supplementation. It is important for doctors to be informed and to be able to identify misinformation, harmful diets and potentially harmful misuse of vitamin supplements.

The 1597, Gerrit de Veer wrote in his diary about taking refuge through 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. They were the first Westerners to observe the effects of hypervitaminosis A.