Vitamin A toxicity

By Razak Hj. Lajis
The Sun, December 7, 1996

THAT VITAMINS ARE ESSENTIAL TO the normal functioning of our body is undisputable. An adequate intake of vitamins is necessary for good health as well as proper growth and development of children.

In a broader scope, vitamins are substances required for the maintenance of normal metabolic functions. With few exceptions, the body cannot manufacture or synthesis vitamins. Since they are not synthesised in the body, most of the supply must come from external sources, especially foods.

Vitamins are chemical compounds essential to life and are required in our diet in very minute quantities. The act as precursors of essential cofactors participating in metabolic reactions. They are available in the foods supply is a varied and appropriately selected diet is consumed.

A healthy individual will normally face few problems with his or her daily dietary vitamin requirement if he or she maintains a well-balanced diet. Vitamin deficiency is rare in individuals who maintain a balanced diet.

Increased interest in nutrition and general well-being, in addition to the persistent requests of consumers for more information on nutrition, are factors that lead to the development of many vitamin research on the roles of vitamins yield more indications for the use of nutritional supplements, leading to more new products being developed.

With many supplements and preparations and preparations available over the counter, the question of people inadvertently overdosing themselves has stirred much anxiety among the public. In many cases, massive doses of vitamins are normally employed for the treatment of disorders that are not etiologically related to vitamin deficiency.

One school of thought often relates large intakes of vitamins both for prophylactic (preventive) purposes and for the treatment of a variety of illnesses. Although many such claims have been made, many of them are not carefully supported by properly controlled objective studies.

Vitamins are categorised as either water-soluble or fat-soluble. Excessive consumption of certain vitamins, notably lipid-soluble vitamins, can cause toxic manifestations.

Compared to water-soluble vitamins, they are stored in much larger amounts in the body. Little is lost through urination.

On the other hand, water-soluble vitamins seem to do much less harm to the body because of the low toxicity of this class of compounds. This is probably attributable to the fact that excess quantities of the compounds are rapidly excreted through urination.

With respect to this, toxicity involving excessive intake of fat-soluble vitamin A is no exception. Also known as an antioxidant, vitamin A us necessary for growth and repair of body tissue. The three main general functions of vitamin A are in maintaining the integrity of the epithelium, promoting synthesis of sterols and preventing night blindness and weak eyesight.

The common rationale of using vitamin A is for treating vitamin A deficiency and prophylactic administration during infancy, pregnancy and lactation, generally, the recommended daily allowances are between 1,500IU and 4,500IU for infants and children up to 12 years of age and a maximum of 8,000IU in pregnant and lactating mothers. Normal adults would require approximately 5,000IU daily.

Vitamin A can be ingested in the forms of retinol and carotenoids (provitamins A or beta-carotene). Retinol is mainly found in foods of animals origin. Mammal and fish livers, for example, contain high amounts of retinol. Foods such as chicken liver, seal liver, fish, swordfish and halibut contain vitamin A. It is also found in animal fats, whole milk and butter.

The other form of vitamin A, the carotenoids, are found in foods of vegetable origin. The main sources are carrots, green leafly vegetables, corn, bananas, tomatoes, papayas, mangoes and unrefined red palm oil. People who regularly eat meat and fish are never deficient in vitamin A.

A number of factors influence the absorption of vitamin A. Bile secretion is essential for absorption. Normal functioning of the gastrointestinal tract is also required to ensure proper absorption of vitamin A. Other factors that influence vitamin A toxic reactions include age, state of nutrition, type of vitamin A preparation and route of administration.

Excessive vitamin A intake results in a toxic syndrome known as hypervitaminosis A. Vitamin A toxicities in humans may be generally categorised as either acute or chronic. Acute toxicity occurs following ingestion of high doses of vitamin A. It may occur within hours or at most a day or two after a very large intake.

Chronic toxicity occurs after consuming smaller amounts of vitamin A for a long period of time. - several weeks, months or years. Vitamin A has a long biological half-life and it tends to accumulate in the body. The tendency of vitamin A to bio-accumulate suggests that chronic exposure to excessive amounts would be unsafe.

Since vitamin A is stored in the liver, chronic ingestion of megadoses may result in hepatic toxicities. The range of vitamin A doses leading to liver damage vary from 15,000IU per day to 1.4 million IU per day, with an average daily toxic dose of 120,000IU per day.

In patients with renal failure, as little as 4,000IU per day has been known to cause substantial liver damage. Long-term alcohol consumption also enhances liver toxic reactions of vitamin A.

Vitamin A toxicity can occur if diets extremely high in the pre-formed vitamin A, retinol, are indiscriminately consumed. Pre-formed vitamin A is found in animal products primarily liver. High intake of this form of vitamin of vitamin A among children results from overzealous prophylactic vitamin therapy initiated by parents.

Fish oil supplements may also contain high concentrations of vitamin A and can produce hypervitaminosis A following chronic excessive use in children. Preformed vitamin A also be added to fortified foods such as breakfast cereals and dietary supplements.

Vitamin A in fruits and vegetables occur naturally in the form of beta-carotene. It is considered less toxic than pre-formed vitamin A. Beta-carotene is converted to retinol in the wall of small intestine and is further oxidised to retinoic acid and retinol.

Doses of commercial vitamin A preparations in the range of two million IU in adults and 75,000IU in infants can cause acute intoxication. Some individuals are very tolerant and require larger amounts to develop toxicity.

In the United States for example, approximately 10 to 15 cases of vitamin A toxic reactions reported annually involve doses greater than 100,000IU per day. Chronic toxicity has been reported following ingestion of 50,000IU daily for three months. Similarly, continuous consumption of 25,000IU to 50,000IU per day for periods of several months or more can produce multiple adverse effects.

Children may develop hypervitaminosis A with chronic doses of only 10 times of the recommended dietary allowances for vitamin A. An example of such a case occurred in a one-year-old boy who received 6,000IU vitamin A daily for three months.

Daily use in pregnant women and those who wish to become pregnant should not exceed 8,000IU per day. Larger amounts taken during pregnancy have been associated with an increased incidence of birth defects. It was found that those who took more than 10,000IU of vitamin A has a higher risk of delivering babies with birth defects compared with women taking 5,000IU.

On the question of the minimum amount of vitamin A that would trigger perceptible adverse effects, scientific information available on vitamin A toxicity is not sufficient to provide a more definitive answer.

However, an intake of 25,000IU per days is considered nutritionally high and conveys some risk of toxicity. Similarly, currently available data are not sufficient to determine the limit that can be considered safe. Although an intake of 10,000IU per day is considered low enough to avoid toxicity in most people, it cannot be guaranteed to be safe for all individuals in a large population. In general, chronic intake of 3,000IU per kg per day can produce clinical signs of toxicity.

The spectacular effects of vitamins have subjected vitamins to much manipulation and exploitation by commercial sources. With so many products to choose from, the rationale of getting the correct ingredient and concentration may be downplayed by certain quarters as long as commercial targets are met.

While some people may take vitamin supplements as a preventive measure against deficiency, others may attempt to obtain therapeutic effects out of it.

Some of the popularly promoted benefits of vitamin use range from treating cancer and arthritis to improving interpersonal relationship. In attempting to achieve their targets, many people may keep supplementing their diet with vitamins in quantities large enough to result in toxic manifestations. once individuals start taking large quantities of vitamins as a form of therapy on their own, the potential dangers are myriad.

VITAMIN A AND BIRTH DEFECTS
ADRAC RECENTLY REVIEWED A report of a child born with microcephaly and dystonia whose mother has inadvertently ingested large quantities of vitamin A during the first four or five weeks of pregnancy. The child subsequently died.

While it was not possible to implicate the ingestion of vitamin A as a definite cause of the birth defects in this case, excess amounts of vitamin A are suspected causes of birth defects and its therapeutically used congeners are established causes of birth defects. This report highlights a possible problem.

It is important for prescribers to realise that the recommended adult daily allowance of vitamin A from all sources is 2,500IU. One of the products implicated in the above case was freeze dried liver extract. One tablet was derived from 10g of liver. Depending on the source of the liver and the method of preparation, each of these tablets may contain from 6,500IU to 48,000IU vitamin A, which is far in excess of the recommended daily allowance. There us no warning label on such products.

Vitamin A preparations which are labelled for a daily amount of 5,000IU or less of vitamin A are freely available provided there is a statement of the recommended daily amount.

Furthermore, there should be a warning statement to the following effect: "Warning - Taking more than 2,500IU a day during pregnancy may cause birth defects." Other vitamin A preparations are available only on prescription. There is no need for additional vitamin A during pregnancy.

ADRAC urges prescribers to advise their patients who are pregnant or are likely to become pregnant not to exceed the recommended daily allowance of vitamin A from all sources, and if possible, not to take any vitamin A-containing products.


Source: Australian Adverse Drug Reactions Bulletin, Vol.15, No.4, November 1996.

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


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