Vitamin A

What is Vitamin A?

Vitamin A is one of a group of fat soluble vitamins that are essential for life and health. Vitamin A plays a critical role in:

• Vision
• Epithelial differentiation
• Growth
• Reproduction
• Pattern formation during embryogenesis
• Bone development
• Hematopoiesis
• Brain development
• Immune system function

Certain carotenoids, such as beta-carotene alpha-carotene and beta-cryptoxanthin, are dietary precursors of vitamin A. Collectively, these substances are called provitamin A.

All of the fat soluble vitamins, including A,D,E,K and F are stored in the body tissues and can accumulate toxic quantities if taken in excess. Deficiencies of these vitamins are also responsible for a variety of health and disease problems. It is, therefore, important to maintain the intake of fat soluble vitamins between the deficiency and toxicity levels.

Preformed vitamin A is derived from animal sources while provitamin A, or the carotenes, are obtained from plant sources. Preformed vitamin A is present in food in the form of retinyl esters. The principal nutritional supplement forms of preformed vitamin A are retinyl palmitate and retinyl acetate. Preformed vitamin A is efficiently absorbed from the small intestine with an efficiency of from 60%-90%. Vitamin A absorption requires bile salts, pancreatic enzymes and dietary fat.

The carotenes, provitamin A, are water soluble and readily absorbed. Excess consumption of carotenes can cause the skin and whites of the eyes to turn yellow. This is not harmful and goes away when carotene consumption is reduced.

Vitamin A Deficiency

Despite vitamin A's reputation for potential toxicity, vitamin A deficiency is far more common than cases of toxicity. There are an estimated 200 cases of hypervitaminosis A annually versus one million persons developing vitamin A deficiency each year. In underdeveloped countries vitamin A deficiency is the second most common health problem and leads to progressive blindness. In the US, the NHANES II study showed 20% or more of the population was receiving less than 70% of the RDA of vitamin A. A shortage is particularly critical during pregnancy when a vitamin A deficiency can result in birth defects. The World Health Organization estimates that there are 250 million preschool-age children worldwide whose health may be compromised by vitamin A deficiency.

Danger to the fetus from high doses of preformed vitamin A ( as well as from a vitamin A deficiency) is a risk in the first few weeks of pregnancy. The intake of vitamin A and vitamin A analogues must be adequate, and not excessive in the month prior to pregnancy and during pregnancy. The most commonly reported source of excess vitamin A-caused birth defects is the dermatological use of vitamin A analogues such as Accutane, Roaccutane, and Tigasan. These, then, must be used under a physician's supervision and discontinued a month or more prior to any pregnancy.

Vitamin A deficiency can be caused by:

• Inadequate dietary intake of vitamin A or provitamin A
• Malabsorption syndromes (cystic fibrosis, Whipple's disease, Crohn's disease, ulcerative colitis, short bowel syndrome)
• Pancreatic disease
• Chronic liver disease
• Weight Loss Surgery

Forms of Vitamin A

The parent compound of the vitamin A family is all-trans-retinol. It is also the most abundant dietary form of vitamin A. All-trans-retinol occurs naturally in the form of fatty acid esters, such as vitamin A palmitate (retinyl palmitate). Vitamin A palmitate and vitamin A acetate (retinyl acetate) are the principal forms used as nutritional supplements. Natural sources, such as fish liver oils are also used as sorces of vitamin A.

The carotenes especially beta carotene are frequently confused with vitamin A. Carotenes are not vitamin A. Rather, they are compounds that can be converted by the liver into vitamin A. Carotenes by themselves do not have vitamin A activity or toxicity. They are, therefore not as efficient as a vitamin A supplement nor as toxic as vitamin A when used in excess amounts.

Vitamin A for Vision Health

Vitamin A deficiency can result in night blindness and blindness due to the destruction of the cornea (xerophthalmia). The ability of vitamin A to prevent these two visual problems and its mechanism of action in doing so is well known. Recent reports reports suggest that vitamin A may affect some visual problems in those who are not vitamin A-deficient. Sorsby's fundus dystrophy (SFD) is a retinal degeneration disorder which can result in night blindness and shares similarities with age-related macular degeneration. Macular degeneration is the most common cause of loss of vision in the elderly.

In an SFD family, it was found that vitamin A at 50,000 IU daily resolved night blindness within a week in those members of the family who were at early stages of the disease. The mechanism of this effect is not clear. Some other visual disorders have also shown improvement from the use of vitamin A analogues.

Vitamin A for Cancer Treatment and Prevention

Vitamin A and retinoids have been found to inhibit tumor development, especially those of epithelial origin, in a variety of in vitro (in a lab dish) studies. All-trans-retinol has been demonstrated to suppress the malignant behavior of cultured cells transformed by radiation, chemicals or viruses, to delay the development of transplanted tumors and to prevent malignancy in animals exposed to various potent carcinogens. All-trans-retinoic acid is an approved drug for the treatment of acute promyelocytic leukemia.

While the use of retinoids has demonstrated anti-cancer activity for some types of cancers, it has not proven to be a universal cancer treatment. A recent two-year study (EUROSCAN) of high-dose retinyl palmitate showed no benefit-in terms of survival, event-free survival, or secondary primary tumors-for patients with head and neck cancer or with lung cancer, most of whom were previous or current smokers.

The use of vitamin A and vitamin A analogues for cancer treatment is a juggling act between the therapeutic benefits and potential toxicity.

Vitamin A Antioxidant Properties

Vitamin A deficiency has been found to cause oxidative damage to liver mitochondria in rats. Vitamin A has also been found to protect against chemical induced lipid peroxidation in the heart, brain and liver.

Vitamin A for Immune System Support

Vitamin A deficiency results in a decreased resistance to infection affecting both cell mediated and antibody mediated immune responses. Nonspecific immune responses involving neutrophils, macrophages and natural killer cells, are also affected by vitamin A deficiency.

Retinol may also stimulate the immune response in animals and humans who are not vitamin A deficient. In animal studies, high doses of retinyl palmitate have been found to stimulate the nonspecific immune system and enhance the antibody response to specific antigens.

In one study, surgical patients developed lymphocyte proliferation after seven days of treatment with high doses of vitamin A. The effects were only apparent toward the end of the seven day period.

Vitamin A's effects on immunity appear to be broad. It was demonstrated some years ago that high-dose vitamin A can significantly protect against some of the immune-depressing effects of radiation and cancer chemotherapy. Animal studies, in vitro studies, and some human studies, have shown that vitamin A can protect immune function by helping to maintain the integrity of epithelial barriers to infection and by activating phagocytes and cytotoxic T-cells. An in vitro experiment showed that a form of vitamin A found in breast milk inhibits herpes simplex virus-1.

Vitamin A for Skin Disorders

Vitamin A in large doses has been used in the management of several skin disorders, including acne, Darier's disease (keratosis follicularis), pityriasis rubra pilaris, Kyrle's disease. None of these treatments are FDA approved. FDA-approved retinoids, Vitamin A analogues that are available by prescription only, include tretinoin, which is used topically for acne vulgaris; isotretinoin, for cystic acne; etretinate, for psoriasis; and acitretin, also for psoriasis.

Vitamin A and Birth Defects

Recent research has suggested that vitamin A might be helpful in preventing some birth defects. High doses of vitamin A is itself associated with increased risk of birth defects. Current research shows that retinoic acid signaling is crucial for proper development of the early embryonic mesoderm. It is possible that vitamin A deficiency could have adverse affects on neurologic and behavioral development and function later in life. Some researchers even believe that schizophrenia may result from vitamin A deficiency.

Vitamin A and Skin Cancer

Vitamin A may be one of the better-documented vitamins to protect against several types of human cancers. One of its mechanisms is to induce healthy differentiation and apoptosis of aged cells. The value of vitamin A in protecting the skin is to help facilitate cell renewal and possibly prevent skin cancers.

Studies show that the upper layer of the skin (epidermis) can be easily loaded with natural vitamin A by topical application. Besides being a precursor for retinoic acid, vitamin A also has a free radical scavenging potential. Vitamin A absorbs ultraviolet light to help protect the most delicate areas of the skin against damaging free radical attack. Natural vitamin A thus functions via several pathways to guard against normal and sun-induced skin aging.

Vitamin A Drug and Food Interactions

Vitamin A absorption may be reduced by the following drugs, health conditions and foods:

• Cholestyramine
• Colestipol
• Mineral Oil
• Orlistat
• Intestinal Malabsorption Syndromes
• Liver, Gallbladder and Pancreatic Conditions
• Weight Loss Surgery
• Olestra (the fat substitute) inhibits the absorption of all fat soluble vitamins including A,D,E,K,F

Vitamin A and retinoid drugs may act synergistically in several ways including increasing the toxicity of each. Retinoid Drugs include acitretin, all-trans-retinoic acid, bexarotene, etretinate and isotretinoin. Oral contraceptives may also increase serum retinol.

Large doses of vitamin A may decrease the absorption of vitamin K. Vitamin A and Vitamin D may act synnergistically to cause excess calcium absorption and deposition in tissues. This would only be an issue when one or both vitamins are taken in excess. Young and developing childen are the most vulnerable to this type of toxicity.

Vitamin A Toxicity and Overdosage

Acute toxicity in infants or children may occur with a single dose of 25,000 IU per kilogram of body weight (the conversion is 2.2 pounds per kilogram). For example, a child weighing 22 pounds (10 Kg.) would have to take a single dose of 250,000 units to manifest an acute toxic reaction. A dose of 2,000,000 IU or greater in adults may cause acute toxic symptoms. Most of the reported cases of vitamin A toxicity and overdosage has been from arctic explorers who consumed livers of polar animals, polar bears and seals in particular. There have been very few reports of fatalities from high doses of vitamin A.

Supplemental doses of 10,000 IU of vitamin A daily or greater have been reported to increase the risk of birth defects when used by pregnant women.

Subjects in the EUROSCAN study were given 300,000 IU/day of vitamin A for one year followed by 150,000 IU/day for the second year. Typical side effects were mucocutaneous ones including dryness, desquamation, itching, bleeding and hair loss. Hepatotoxicity has been reported in one patient who took 25,000 IU/day of vitamin A over a six-year period.

Symptoms of Vitamin A Toxicity

Signs and Symptoms of Vitamin A Toxicity include:

• Blurred vision
• Bone pain
• Diarrhea
• Dryness of the skin and mucous membranes
• Fatigue
• Headache
• Liver damage and liver enlargement
• Loss of hair
• Nausea
• Skin rashes
• Small cracks and scales on the lips and at the corners of the mouth
• Vomiting
• Irritability
• Pseudotumor cerebri (benign intracranial hypertension)
• Elevated serum liver enzymes
• Reversible noncirrhotic portal hypertension
• Hepatic fibrosis and cirrhosis

Treatment for Vitamin A Toxicity

The treatment for vitamin A toxicity is to discontinue taking any vitamin A supplements and avoid foods rich in vitamin A. As the stored vitamin A is used by the body, the symptoms should diminish. If you suspect that you may be experiencing vitamin A toxicity, see your phsician. Your physician will be able to perform tests to properly diagnose your condition and recommend proper treatment if needed.

Vitamin A Dosage

By law, the use of vitamin A or any retinoid for the treatment of any medical condition must be prescribed and supervised by a physician.

Vitamin supplements may contain one or more of retinyl acetate and retinyl palmitate and beta carotene. Rarely are doses higher than 5,000 IU of vitamin A exceeded in these formulas. The beta carotene content does not count toward the vitamin A dosage from a toxicological standpoint. Many take beta-carotene for vitamin A supplements for this reason. Vitamin A is also available in the form of cod liver oil.

The current recommended dietary allowances (RDA) for vitamin A by the Food and Nutrition Board of the U.S. National Academy of Sciences are:

• Infants up to 1 year old - 1,250 IU per day
• Children 1 through 3 years old - 1,333 IU per day
• Children 4 through 6 years old - 1,667 IU per day
• Children 7 through 10 years old - 2,333 IU per day
• Males 11 years and older - 3,333 IU per day
• Females 11 years and older - 3,333 IU per day
• Pregnant/Lactating 1st 6 months - 4,333 IU per day
• Pregnant/Lactating 2nd 6 months - 4,000 IU per day

One IU or one USP unit equals 0.30 micrograms of all-trans retinol, 0.344 micrograms of retinyl acetate or 0.55 micrograms of retinyl palmitate.

Remember that the RDA is the dose that is believed to prevent the symptoms of deficiency disease. The dosage that provides optimum health and disease resistance is likely higher than the RDA. Unfortunately, there is no research data showing what optimum levels are. The optimum level for different individuals is likely to vary because of different genetics and metabolic needs. The fact that vitamin A can be toxic means that one must be cautious about overdosing.

I once met a doctor who claimed to have taken 50,000 IU per day for 25 years without apparent adverse effects. He was a large bodied man. His opinion was that vitamin A is a very important nutrient for health and disease resistance and that the RDA is ridiculously low. I also found one study of a small bodied female who developed symptoms of vitamin A toxicity after taking 25,000 IU per day for two years.

The potential for greatest harm from vitamin A toxicity is first to the unborn and second to young children. Research has shown that both excess and deficiency can be very harmful. More research is needed to clarify what the boundaries in dosage are. For now, it is wise to stick to the RDA numbers if pregnant, nursing or very young.

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