Vitamin A Overdose, Toxic effects of excess intake

As vitamin A is fat soluble and can be stored in the liver for long periods of time, it has a high potential for toxicity. The first sign of vitamin A overdose is usually headache, followed by chapped lips, dry skin, fatigue, emotional instability and bone and joint pain. There may also be hair loss, vertigo, vision problems, poor appetite, loss of weight, vomiting, liver damage and amenorrhea (cessation of menstrual periods). Individual tolerance to vitamin A varies widely and these effects can occur at doses over 7500 mcg RE (25,000 IU) although in most adults signs of toxicity occur with single doses over 75,000 mcg RE (250,000 IU) or smaller doses of 15 000 mcg RE (50,000 IU) taken for long periods. It is recommended that regular daily intake of vitamin A does not exceed 7500 mcg RE (25,000 IU) for adults and 3000 mcg RE (10,000 IU) in children.

Pregnant women who take above 3000 mcg RE (10,000 IU) per day have a greater chance of giving birth to malformed babies. Vitamin A acne cream has been known to cause birth deformities and is now available only on prescription.

Vitamin A OverdoseIn a study published in 1995, researchers at Boston University School of Medicine assessed the links between vitamin A from food and supplements in 22,748 women who were pregnant between October 1984 and June 1987. Women who consumed more than 4500 mcg RE (15,000 IU) of pre-formed vitamin A per day from food and supplements were over three times more likely to have a baby with a birth defect than women who consumed 1500 mcg RE (5000 IU) or less per day. For vitamin A from supplements alone, women who consumed more than 3000 mcg RE (10,000 IU) per day had almost five times the risk of birth defects than women who consumed less than 1500 mcg RE (5000 IU) per day. The increased frequency of defects was concentrated

among the babies born to women who had consumed high levels of vitamin A before the seventh week of pregnancy. The researchers estimated that among the babies born to women who took more than 3 000 mcg RE (10,000 IU) of pre-formed vitamin A per day in the form of supplements, about one infant in 57 had a malformation attributable to the supplement.

However, a 1997 study conducted by researchers at the National Institute of Child Health and Human Development did not find a link between vitamin A consumption and birth defects. Their results showed that the proportion of women consuming doses of vitamin A between 2400 mcg RE (8000 IU) and 7500 mcg RE (25,000 IU) was no higher in those with birth defects than in the normal control group.

Overdose is reasonably common with as many as 5 per cent of people taking vitamin A suffering from the toxicity symptoms. Stopping the large doses usually reverses the symptoms with no lasting damage, although in children damage can be permanent.

Therapeutic uses of supplements

The main use of vitamin A supplements the prevention and treatment of deficiency. They are often used in developing countries to protect against or treat measles and other viral infections.

Immunity

Adequate vitamin A intake, either from diet or supplements, is very important in boosting immunity and preventing sickness and death in children. Many studies have found that vitamin A supplementation reduces the risk of infectious diseases in areas where vitamin A deficiency is widespread. A recent research review analyzing the results of several studies found that adequate vitamin A intake in children resulted in a 30 per cent decrease in deaths from all causes. Children in developing countries are often at high risk of vitamin A deficiency. In developed countries, ensuring adequate vitamin A intake is particularly important in those with life threatening infections such as measles and in those at risk of relative deficiency, such as premature infants.

In a 1995 double-blind, randomized trial done in South Africa, vitamin A supplements were shown to reduce sickness rates in children born to HIV- infected women. The patients in this study were not in a population at high risk for vitamin A deficiency and the effect was particularly noticeable in those children who were HIV-positive.

Cancer

Many studies suggest that high blood levels of vitamin A can help prevent certain forms of cancer, particularly cancers of epithelial tissue. This may be due to the importance of vitamin A in maintaining healthy epithelial cells, strengthening the immune system and stimulating the response to abnormal cells.

A1993 Italian study tested the effects of vitamin A on cancer recurrence in smokers who had undergone surgery for lung cancer. The 307 patients took daily doses of 90,000 mcg RE (300,000 IU) for one year. After a follow-up period of 46 months, the number of patients with either recurrence or new tumors was 56 (37 per cent) in the vitamin A group and 75 (48 per cent) in the control group. Eighteen patients in the treated group developed a second primary tumor, and 29 patients in the control group developed 33 second primary tumors.

Results from the recent large scale Beta Carotene and Retinol Efficacy Trial (CARET) involving a total of 18 314 smokers, former smokers, and workers exposed to asbestos failed to show any benefit of vitamin A supplementation on lung cancer. This may be due to the adverse effects of cigarette smoke on beta carotene.

In a 1998 study done in Western Australia, 1024 blue asbestos workers known to be at high risk of diseases such as mesothelioma and lung cancer, were enrolled in a cancer prevention program using vitamin A. Half the subjects were given 30 mg per day of beta carotene and the other half 7500 mcg (25,000 IU) of retinol. The workers were followed up from the start of the study in June 1990 until May 1995. Four cases of lung cancer and three cases of mesothelioma were observed in those in the vitamin A group, and six cases of lung cancer and 12 cases of mesothelioma in the beta carotene group. In the retinol group, there was also a significantly lower rate of death from all causes.9 When the researchers compared these results with those workers who had not taken part in the study they found that those taking part in the study had significantly lower death rates than non-participants.

Vitamin A has also been shown to exert protective effects against leukoplakia, a pre-cancerous change in mucous membranes. It often occurs in the mouth and throat and is related to smoking. In a study done in 1997 researchers tested the effects of the retinyl palmitate form of vitamin A on leukoplakia of the larynx. The treatment period was five weeks and the doses used ranged from 90,000 mcg RE per day (300,000 IU) to 270,000 mcg (1.5 mil- lionlU) per day. Complete remission was observed in 15 out of 20 patients and partial response was seen in the remaining five patients.

Results of a US study reported in the Journal of the National Cancer Institute in 1997 suggest that the development of lung cancer may be due to a decreased ability of cells to respond to vitamin A-related compounds known as retinoids. When researchers at the University of Texas looked at the lung tissue from 79 patients with lung cancer and 17 without lung cancer they found that all the healthy cells carried receptors that bound retinoids. However, only 42 to 76 per cent of the cancerous cells had this ability. Of the six different types of retinoid receptors, three were found at lower levels in cancer cells.12 Retinoids play an important role in the growth and differentiation of cells. This study raises the possibility that increasing dietary intake of vitamin A or taking supplements can be used to reduce the risk of lung cancer.

Lung function

Vitamin A supplements may be useful in treating chronic obstructive pulmonary disease. Researchers involved in a Brazilian study published in 1996 examined vitamin A levels in healthy non-smokers, healthy smokers, those with mild chronic obstructive pulmonary disease, and those with more severe symptoms. Patients in the last group had low vitamin A levels. Supplements of 1000 mcg RE (3330 IU) per day improved lung function.

In a study reported in Nature Medicine in 1997, researchers at Georgetown University in Washington investigating the treatment of emphysema in rats found that the retinoic acid form of vitamin A reversed the lung abnormalities seen in the disease. The researchers induced emphysema in the rats and then gave them injections of retinoic acid for 12 days. The condition of the lungs improved almost to pre-disease levels.

Skin disorders

Because of its important role in the formation of healthy skin, vitamin A is used to treat skin disorders including rashes, ulcers and wounds.

Acne

Vitamin A may have some benefit in the treatment of acne although most of the studies that support the effectiveness of vitamin A have involved the use of very large doses. Synthetic vitamin A derivative drugs known as retinoids are used to treat cases of severe acne which have not responded to other treatment or which have only shown partial response to antibiotic therapy. These drugs, including tretinoin, isotretinoin and etretinate are prescription medications which are used under the supervision of a doctor. Side effects are relatively common and are similar to the symptoms of vitamin A toxicity. These drugs can cause

birth defects if taken during pregnancy and should also be avoided by breastfeeding women. A 1995 study by National Cancer Institute researchers suggests that long-term therapy with etretinate may increase the risk of osteoporosis.

Psoriasis

Vitamin A derivative drugs are also used to treat psoriasis, particularly pustular psoriasis. These drugs help to normalize skin development by reducing the increased growth, turnover and keratinization of skin which occurs in the disorder. Similar cautions apply to the use of these drugs in the treatment of psoriasis.

Skin aging

According to a 1997 report in the New England Journal of Medicine, creams that contain the vitamin A derivative tretinoin, may help to combat premature skin aging. Researchers studied the activity of enzymes known as metalloproteinases which break down collagen and found that exposure to ultraviolet light increased the activity of these enzymes. Even a small amount of ultraviolet light, although not sufficient to cause redness, was enough to increase enzyme activity. This suggests that exposure to a few minutes of sunlight periodically over several years may lead to premature skin aging.

This increase in enzyme activity was blocked by treatment with tretinoin before radiation. The researchers conclude that tretinoin may be useful in treating patients with signs of premature skin aging but note that careful monitoring of tretinoin use is essential as over-treatment can cause irritation and reddening of skin. The results of this study may lead to the development of new sunscreens and anti-aging creams containing vitamin A derivatives.

Other uses

Vitamin A eye drops have been used to treat eye problems including blurred vision, cataracts, glaucoma, conjunctivitis and dry eyes. Other disorders for which vitamin A has been tried include asthma, sebaceous cysts, fibrocystic breast disease and premenstrual syndrome.

Vitamin A may also be useful in the prevention of ulcers. In a study involving almost 48,000 men reported in 1997 in the American Journal of Epidemiology researchers found a lower risk of ulcer in those with high intakes of vitamin A, either from food or supplements.

 
 
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