Vitamin A is a nutritional term that describes a family of essential compounds that are structurally related. A family includes retinol, retinal or retinaldehyde, retinyl esters, retinoic acid, and provitamin carotenoids such as -carotene.
Vitamin A is a fat-soluble vitamin.
Vitamin A is essential for growth and life, taking part not only in vision but also in developmental processes that begin early in embryogenesis. Vitamin A continues to be necessary to maintain normal cellular differentiation throughout life.
Preformed vitamin A comes from animal origin, such as liver and egg yolk, while the provitamin -carotene is found only in foods of plant origin, particularly carrots and dark leafy vegetables.
Vitamin A requires some fat present in the digestive system for absorption and is better absorbed than the carotenoids. Protein enhances the conversion of carotenoids to retinol.
The human body stores only limited amounts of vitamin A, mostly in the liver, making dietary intake essential. The liver stores 50 - 80% of body vitamin A. Small amounts are also found in lungs, body fat and kidneys. Unlike most vitamins, vitamin A concentrations tend to increase with age.
Excess and deficiency of vitamin A in the mother's diet during pregnancy has been shown to cause malformations of fetal brain and hydrocephalus.
Beta-Carotene Facts
Beta-carotene is one of almost 600 carotenoids. Fifty of these compounds have vitamin A activity. Beta-carotene may provide as much as two-thirds of the vitamin A in the human diet. Carotenoids are deposited more widely throughout the body than retinoids and are found in adipose tissues, adrenals and liver.
Six carotenoids found in the highest concentrations in human serum are beta-carotene, alpha-carotene, beta-cryptoxanthin, lycopene, lutein, and zeaxanthin.
Certain carotenoids, such as beta-carotene, alpha-carotene and beta-cryptoxanthin, are dietary precursors of vitamin A, called provitamin A.
Provitamin beta-carotene is found only in foods of plant origin, particularly carrots and dark leafy vegetables.
Beta-carotene becomes an essential nutrient when dietary intake of retinol is inadequate.
Night vision, due to its involvement in photochemical reactions in the retina.
Growth and maintenance of epithelial tissue including the cornea, all mucous membranes of gastrointestinal tract, lungs, vagina, urinary tract, bladder and skin.
Reproductive function in humans.
Nerve formation and function.
Epithelial cell proliferation and epidermal differentiation. Natural and synthetic retinoids have been used increasingly as systemic or topical agents in the treatment of hyperkeratotic disorders, acne, and certain skin cancers.
Antioxidants may play a preventive role in heart disease and epithelial cancers.
Both cell-mediated and antibody-mediated immune response.
Signal transduction, via retinoic acid's hormonal action.
Beta-carotene functions
Beta-carotene functions as an antioxidant, regulator of cell communication and growth, and has shown immunomodulatory activities thought to be independent of its role as a pro-vitamin A compound.
As an antioxidant, beta-carotene may quench certain free radicals and inhibit lipid peroxidation.
Beta-carotene may exert anti-carcinogenic activity.
Vitamin A dietary reference intakes (DRIs) are expressed in IU (international units), RAE (retinol activity equivalents) or mcg (micrograms). One RAE is equivalent to 1 mcg of retinol, and one RAE is also equivalent to 3.33 IU of vitamin A activity from retinol.
A generally recognized safe upper limit of intake for vitamin A is 8000 to 10,000 IU/day (2400 mcg and 3000 mcg respectively). There is no established recommended daily allowance (RDA) for beta-carotene.
Studies of beta-carotene indicate that 6 mg/day (10,000 IU) should be adequate. One mg of beta-carotene is equivalent to 1,667 IU of beta-carotene.
Symptoms of vitamin A deficiency are due to its participation in skin, bone, dental health and immune function. The earliest symptom of vitamin A deficiency is inability to see in dim light, called night blindness or nyctalopia. Other symptoms soon appear including rough, scaly skin (called follicular hyperkeratosis), sinus infection, chronic sore throat and abscesses in mouth and ears.
In children, deficiency results in growth retardation, impaired bone and tooth formation.
Both deficiency and excess vitamin A cause fetal malformations.
Vitamin A deficiency causes spermatogenesis cessation and interrupts estrus cycle.
Symptoms of vitamin A toxicity include loss of appetite, headache, blurred vision, irritability, hair loss, drying and flaking of the skin, swelling in the extremities, drowsiness, diarrhea, nausea, and enlargement of the spleen and liver.
Since vitamin A stores increase with age, the elderly are at particular risk for toxicity.
Vitamin A excess during the first trimester of pregnancy can result in severe craniofacial and oral clefts and limb defects of the fetus.
High doses of vitamin A (retinol and retinyl esters) during pregnancy have been associated with birth defects. It is recommended that women who are pregnant or may become pregnant do not exceed the tolerable Upper Limits.
Beta-Carotene toxicity
Chronic doses of 30 mg/day or higher of beta-carotene may cause carotenodermia. Carotenodermia is characterized by yellowish discolorization of the skin and is considered harmless and reversible with the discontinuation of beta-carotene supplementation.
Supplementation of 20 mg/day or greater of beta-carotene has been linked to increased lung cancer incidence in smokers. Smokers should avoid >15 mg/day beta-carotene supplementation pending further research.
Rich sources of vitamin A are liver and cod liver oil. The major source of vitamin A in the diet is from beta-carotene; provitamin A. Sources of beta-carotene include yellow and green leafy vegetables such as carrots, spinach, sweet potatoes, squash, and yellow fruits such as peaches and cantaloupe.
Synthetic derivative of vitamin A, Accutane®, has
been proven to be teratogenic in animals and humans. Therefore, it is
recommended that women who want to become pregnant not take it.
Vitamin A absorption is impaired by intestinal disorders that alter absorption of fats. Retinyl palmitate is a form of vitamin A that is absorbed even without dietary fat and is useful in management of long-term intestinal diseases, such as sprue, cystic fibrosis, or celiac disease.
Vegetarians, people who do not consume enough calories and those with disorders that cause fat malabsorption, are also at risk for vitamin A deficiency.
Obese patients treated with Orlistat should take vitmain A at least 2 hours before or after Orlistat administration.
Warfarin [Coumadin®], an anticoagulant, increases the
risk of abnormal bleeding when taken with high-dose supplements of fat-soluble
vitamins, including vitamin A. It is recommended to avoid combining
vitamin A with warfarin unless supervised by a physician or pharmacist.
Bile acid sequestrants such as cholestyramine
[Questran®] and colestipol [Colestid®] are used to lower cholesterol
concentrations by preventing reabsorption of bile acids from the digestive
system and by preventing micelle formation in gastrointestinal (GI)
lumen. Since fat-soluble vitamin A requires the presence of bile for
absorption, deficiency may occur if these drugs are used for a long period of
time. During long-term administration of these medications, it is
recommended to take a daily supplement that is a water-miscible preparation of
vitamin A.
Oral antibiotics such as neomycin [Mycifradin®]
decrease absorption of many nutrients including vitamin A. People
taking antibiotics greater than 10 days should take multivitamin supplements.
Chronic use of laxatives that contain mineral oil can
lead to malabsorption of fat-soluble vitamins, including vitamin A. It is
recommended to take the vitamin two hours before or after mineral oil is used.
Retinoid drugs, such as tretinoin [Retin-A®],
isotretinoin [Accutane®], and 13-cis as well as all-trans-retinoic acids, are
structurally similar to vitamin A. They are used topically and
systemically for the reduction of acne and the appearance of wrinkles.
People using these compounds should avoid vitamin A-containing supplements due
to a possible toxicity.
Orlistat [Xenical®], a weight loss GI agent, may decrease GI absorption of fat-soluble vitamins. In clinical studies, vitamin concentrations during drug therapy remained within normal range for most patients. Vitamin supplementation was only occasionally needed. Orlistat and vitamin A supplementation should be at least 2 hours from each other; fat-soluble vitamins may be taken conveniently at bedtime.
Information on the relationship between substances and disease is provided for general information, in order to convey a balanced review of the scientific literature. In many cases the relationship between a substance and a disease is tentative and additional research is needed to confirm such a relationship.567
Breast cancer: By use of multivariate analysis, researchers at the Harvard School of Public Health, examined associations between intakes of specific carotenoids, vitamin A, C, and E, consumption of fruits and vegetables, and breast cancer risk in prospective cohort study of 83,234 women (aged 33-60 years in 1980) who were participating in the Nurses Health Study. Results showed that intake of beta-carotene from food and supplements, lutein/zeaxanthin, and vitamin A from foods was weakly inversely associated with breast cancer risk in premenopausal women. Sixty percent reduction in breast cancer risk was found by increasing intake of alpha-carotene, beta-carotene, lutein/zeaxanthin, total vitamin C from foods, and total vitamin A among premenopausal women with positive family history of breast cancer.
89 Lung cancer:
A study conducted by Holick and colleagues found that high fruit and vegetable intake, particularly a diet rich in carotenoids, tomatoes, and tomato-based products, may reduce risk of lung cancer. It was noted from multivariate models that participants who consumed high quantities verses low of lycopene, lutein/zeaxanthin, beta-cryptoxanthin, and total carotenoids had a significant 15-28% lower lung cancer risk (p < 0.05).15
Results from several observational studies have shown a consistent association of increased lung cancer risk with low dietary beta-carotene or low serum beta-carotene concentrations. However, three large intervention trials failed to confirm this relation.15
The Alpha-Tocopherol, Beta-Carotene Prevention Study (ATBC), a randomized, double-blind, placebo-controlled trial, tested beta-carotene alone or with alpha-tocopherol in Finnish smokers for 5-8 years. The study found no protective effect in lung cancer and noted a significant increase in lung cancer incidence in the beta-carotene, cigarette smoking group. In a follow up analysis of the study, the authors concluded: “Beta-carotene at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake."16
The Beta-Carotene, Retinol Efficacy Trial’s (CARET) preliminary results also showed no protective effects for smokers supplementing with beta-carotene (30 mg/day). The increase in lung cancer was noted but non-significant. An analysis of subgroups showed a greater risk of lung cancer in those in the highest quartile of alcohol intake.17
The Physicians’ Health Study (PHS) revealed neither an increase nor decrease in overall cancer risk for those supplementing with beta-carotene (50 mg QOD) for 12 years.18
It is important to note that these studies do not erase hundreds of studies showing the need for a diet rich in carotenoids and antioxidants for reducing cancer risk and cardiovascular disease. Some possible mechanisms for the increased risk of lung cancer in smokers given beta-carotene include:
Pro-oxidant effect of beta-carotene under 100% oxygen pressure in a biological membrane model.
Increased squamous metaplasia and the level of cell proliferation in beta-carotene supplemented animals, and this increase was found to be further enhanced by tobacco smoke.
Free radical-rich milieu in the lungs of cigarette smokers, which might enhance beta-carotene oxidation and formation of oxidative metabolites.19
Head and Neck Cancer:Mayne and colleagues evaluated the anticarcinogenic effects of beta-carotene in the prevention of head/neck cancer. This was a randomized, placebo-controlled, double-blinded clinical trial evaluating 264 patients who had been curatively treated for a recent early-stage squamous cell carcinoma of the oral cavity, pharynx, or larynx. The patients were given 50 mg of beta-carotene or placebo daily and were followed for up to 90 months for development of second primary tumors and local recurrences. The point estimates suggested a non-significant decrease in second head/neck cancer risk, but a possible increase in lung cancer risk. The authors state if these results were replicated, it suggests a critical need for mechanistic studies addressing differential responses of beta-carotene in one epithelial site (head/neck) verses another (lung). Considering the totality of evidence, including their own, the authors do not recommend supplemental beta-carotene for the prevention of second head and neck cancers at this time.20 Children in developing countries: In children, vitamin A supplementation during illness is beneficial in a) reducing mortality in measles, b) reducing persistent diarrhea episodes in children with acute diarrhea, but no benefit has been seen in pneumonia.21
The WHO recommends a single large dose of vitamin A in the treatment of clinically severe measles and the use of vitamin A as a component of a micronutrient mixture daily to treat persistent diarrhea and severe malnutrition.21
Immunity and Seniors: Researchers at Tufts University and Harvard University in Boston followed 59 middle-aged men (51-64 years old) and 21 seniors (65-86 years-old) who took 50 mg of beta-carotene daily for 10 to 12 years, as part of the ongoing Physicians Health Study. Beta-carotene supplementation brought immune function concentrations in seniors up to that of the younger men, while seniors not taking supplements showed continued low immune activity. It was concluded that long-term beta-carotene supplementation augments natural killer cell activity in elderly people, which may be helpful for viral and tumoral surveillance.10
Vitamin A can stimulate or inhibit various aspects of the cellular or humoral immune response.
Vitamin A supplementation studies showed decreased respiratory infections and neutrophil counts and increased reticuloendothelial system function, lymphocyte proliferation, tumor resistance, graft rejection, and cytotoxic T-cell activities.
Vitamin A deficiency is often associated with depressed immune system and higher morbidity and mortality due to infectious diseases such as diarrhea, measles, and respiratory infections.
Supplemental beta-carotene helps prevent UV-induced suppression of immune responses in older men, thus preserving immune function.
AIDS: Studies of the micronutrient status in people with HIV have revealed that as much as 70% of infected people also have vitamin A deficiency. Since this vitamin plays an integral role in immunity, deficiency can disturb response to infection. This disturbance may lead to illness due to infections or to an increase in HIV viral load.1112
Heart Disease: The epidemiologic evidence suggests that vitamin A and carotenoids are important dietary factors for reducing the incidence of heart diseases.
Researchers at Erasmus University Medical School in Rotterdam, The Netherlands, have examined the association between dietary intake of beta-carotene and vitamins E and C and myocardial infarction (MI) among 4,802 men and women, aged 55 to 95 years old. Results demonstrated that risk of MI was 45% lower among persons with the highest intakes of beta-carotene compared to those with the lowest intakes. The protective effect of beta-carotene was even more pronounced among current and former smokers, with the risk of MI reduced by 55 to 65%, respectively.13
In another cross-cultural study of nineteen European and five western developed countries, dietary supply of beta-carotene, based on national food supply data, was associated with a significantly lower risk of premature death (< 65 years old) due to coronary heart disease.14
Lee and colleagues tested the hypothesis that beta-carotene supplementation may be beneficial in cardiovascular disease (and cancer) in those with low plasma concentrations. Using data from the Women’s Health Study (treatment duration 2.1 years, median f/up 4.1 years), the authors conclude that these data do not suggest that beta-carotene supplementation is beneficial to those with the lowest plasma levels of beta-carotene. This population was adequately nourished and could not be compared to a malnourished population.22
Bone Mineral Density:
In a Swedish study, women aged 28 to 74 years were asked their retinol intake and measured bone density. For intake greater than 1.5 mg/day compared with intake of less than 0.5 mg/day, bone mineral density was significantly reduced by 10% at the femoral neck, 14% at the lumbar spine and 6% for the total body. Risk for hip fracture was doubled. The results suggest that high intake of retinol may be associated with osteoporosis.23
The Nurses Health Study showed that women in the highest quintile of total vitamin A intake (>/= 3000 mcg/day of retinol equivalents) had a significantly elevated relative risk of hip fracture compared with women in the lowest quintile of intake (< 1250 mcg/day of retinol equivalents). Â-carotene did not contribute significantly to fracture risk. The authors concluded: “long term intake of a diet high in retinol may promote the development of osteoporotic hip fractures in women.”24
The dietary supplement information contained on this site has been compiled from published sources thought to be reliable, but it cannot be guaranteed. Efforts have been made to assure this information is accurate and current. However, some of this information may be purported or outdated due to ongoing research or discoveries. The authors, editors and publishers cannot accept responsibility for errors or omissions or for any consequences from applications of the information in this site and make no warranty, expressed or implied, with respect to the contents herein.
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