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Effects of vitamin D overdose

By Razak Hj. Lajis
The Sun, December 14, 1996

THERAPEUTICALLY, VITAMIN preparations should be used where prompt relief of vitamin deficiency (hypovitaminosis) is indicated. In such situations, the demand for vitamins may be increased or some dietary restriction may be enforced. Vitamin supplements are also indicated in conditions of severe stress, injury or illnesses.

Ingestion of vitamins in quantities larger than the recommended for the maintenance of good health has been promoted as therapy for a wide variety of medical conditions.

The quantity of vitamins and the duration of ingestion of such preparations required to cause toxicity varies with the individual. The symptoms of vitamin toxicity also vary considerably between the vitamins. Toxicity due to massive ingestion of vitamin D has to be taken into serious consideration. That is an essential nutrient does not mean it is devoid of potential toxicity.

Vitamin D and its analogues are a group of sterol compounds that occur naturally, chiefly in animals. It can also be found in plants and yeasts. The D vitamins are generated from the provitamins ergosterol and 7-dehydrocholesterol, which are found in plants and animals.

Ultraviolet irridiation of a variety of this animal and plant sterols results in the conversion of provitamins to compounds with vitamin D activity. Ergosterol, which is derived from plants, can be converted into ergocalciferol (vitamin D2) with the aid of ultraviolet irridiation. For instance, vitamin D was once made available in commercial quantities when vitamin D2 was manufactured by irridiation of ergosterol derived from yeast.

In animal tissues, 7-dehydrocholesterol, which occurs naturally in the epidermal layers of the skin, can be converted by ultraviolet irridiation to cholesterol (vitamin D3). Vitamin D3 is also present in fish oil. Both ergocalciferol and cholecalciferol are of equal biologic potency as D vitamins.

Basically, humans have two main sources of vitamin D. It can be obtained through ingestion of appropriate foods in the diet and photolysis of 7-dehydrocholesterol in the skin. Once absorbed and bound to a specific globulin. It is transported in the blood to the liver. The major storage form of vitamin D in the body is 25-hydroxy vitamin D3. However, this is not the active form of the vitamin. Instead, vitamin D3 undergoes several chemical modifications before it is transported in its modified form to the target tissue. The active compound is known as 125-dihydroxycholecalciferol. It is a potent stimulator of calcium absorption in physiologic dosages. At above physiologic levels, it stimulates reabsorption of bones.

Vitamin D has two important physiological functions. It is a fat-soluble vitamin that promotes utilisation of calcium and phosphorus in the body by enhancing absorption of these two mineral from the intestine. It is required for normal mineralisation of bone and it plays an essential role in the homeostatic regulation of plasma calcium concentration.

A deficiency of vitamin D results in inadequate absorption of calcium and phosphate. A child with inadequate vitamin D may develop rickets due to poor calcification of the bones. In adults, vitamin D deficiency results in osteomalacia or adult rickets, which is likely to occur during times of increased calcium need, such as pregnancy and lactation. The disease is characterised by a generalised decrease in bone density. Demineralisation of bone may result in multiple fractures.

Vitamin D deficiency is not simply due to malnutrition. More importantly, it can be due to lack of exposure to the sun. This vitamin can be formed in the skin when the skin is exposed to sunlight. For children living in climates where frequent exposure to the sun is not possible, a dietary source is necessary.

Vitamin D is present in substantial amounts in many vitamin formulations, some calcium supplements and most milk products. It is also found in fish oils and fortified foods such as margarine.

It is generally accepted that an intake of 400IU of vitamin D is the standard recommended daily allowance for infants. An equal amount is also recommended for children up to 18 years of age. In a few studies, it has been noted that as little as 100IU of vitamin D may prevent rickets. It has also been noted that an area of skin of just 20 cm square exposed to the sun for three hours daily will prevent rickets.

In adults, vitamin D deficiency is noted most frequently in pregnant women. It appears as painful malformations of pelvis and femur. The average curative dose of vitamin D in rickets is about 5,000IU daily. The administration of the vitamin should be always accompanied by adequate calcium and phosphorus intakes in the daily diet. Exposure to sunlight is also helpful.

The prescription of high doses of vitamin D in the absence of a deficiency can result in hypercalcaemia - excessive calcium in blood. If this condition is prolonged, it may lead to heart and kidney damage. Symptoms of vitamin D toxicity include nausea, vomiting, anorexia, headache, weakness, apathy, polyuria and bone pain. As vitamin plays an important role in mineralisation and calcification of bones, the symptoms of excessive ingestion of vitamin D are the result of abnormalities in calcium metabolism. These are largely due to hypercalcaemia which cause calcification of soft tissue and produce renal impairment.

Clinically, most cases of hypervitaminosis D seen in adults are the result of large doses of the vitamin used for the treatment of conditions that are not associated with vitamin D deficiency. Daily ingestion in excess of 2,000IU in children or 75,000IU in adults may produce toxic symptoms related to hypervitaminosis D. For example, most cases of vitamin D toxicity have been reported to occur after the ingestion of greater than 50,000IU daily for several years.

There is wide individual variation in the amount of vitamin D that causes hypervitaminosis. The continued ingestion of 50,000IU or more daily by a person with normal vitamin D sensitivity may result in poisoning. Doses of 60,000IU per day can cause hypercalcaemia, with muscle weakness, Proteinuria, hypertension and irregular heartbeat. Symptoms and signs generally appear two to eight days after acute intoxication with massive doses of vitamin D.

Chronic hypercalcaemia can lead to generalised vascular calcification with high concentration of calcium salts in soft tissues, especially in the kidney. This will exacerbate rapid deterioration of kidney functions. Other sites of calcification may include blood vessels, heart, lungs and skin. The stored vitamin in the body will be released slowly as it has a long plasma half-life of three months. Therefore after discontinuation.

Another potentially toxic action of vitamin D is the effect on fat metabolism. There is some evidence that 700IU to 2,500IU daily in adults may raise the plasma cholesterol level.

Maternal ingestion of large doses of vitamin D may cause hypercalcaemia in nursing infants. Vitamin D toxicity may also manifest in the foetus. It may also result in suppression of parathyroid function in the newborn which will lead to hypocalcaemia, tetany and seizures. Excess maternal; vitamin D intake or extreme sensitivity to the vitamin has been shown to cause some congenital birth defects.

Massive doses of vitamin D up to a concentration of 10,000IU/kg during pregnancy are teratogenic. Vitamin D intake of 1,000IU to 4,000IU per day may be toxic to infants. The toxic dose for children ranges from 10,000IU/day for four months to 200,000IU/day for two weeks. Twenty per cent of normal adults receiving 100,000IU/day for several weeks or months develop hypercalcaemia.

Serious toxicity may result from excessive ingestion of the vitamin. The supplemental requirements vary not only with age, pregnancy and lactation, but also with the quality of the diet. It is clear therefore that any recommendation for vitamin D supplementation must be made only after careful scrutiny of the diet. The indiscriminate use of over-the-counter vitamin D preparations for irritional purposes can be dangerous. People must be made aware of the potential hazards of overdosage.

The writer is a pharmacist at the National Poison Centre, Universiti Sains Malaysia, Penang.

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