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Vitamin A (Retinol)

Nutrient Names: Vitamin A, retinol.
Synonym: Preformed vitamin A.
Related Substances: Retinal (retinaldehyde); retinoic acid; retinyl esters, such as retinyl acetate, retinyl palmitate, and retinyl propionate; all-trans dehydroretinol, vitamin A2; beta-carotene (provitamin A) and other provitamin A carotenoids: alpha-carotene, cryptoxanthin, lutein, lycopene, zeaxanthin.

Summary Table
nutrient description

This monograph reviews interactions issues relating to and deriving from intake of retinol and other forms of preformed vitamin A and the metabolic processes of these substances within physiological/healthy, dysfunctional, and pathological processes and states. The monograph for beta-carotene focuses on interactions issues involving intake, assimilation, and metabolic processes that constitute provitamin A activity and affect retinol and its metabolic activity. Interactions with some pharmaceutical agents inherently involve both substances and their respective class of related substances.

Chemistry and Forms

Vitamin A is a generic term used to describe the class of compounds that exhibit the biological activity of retinol. The two main sources of vitamin A in foods are retinol and the provitamin A carotenoids. Retinol (an alcohol), retinal (an aldehyde), and retinoic acid are collectively known as “retinoids”; they naturally occur only in animal products and can be classified as “preformed vitamin A.” Some structurally related synthetic analogs (e.g., tretinoin) are also considered retinoids and may exhibit significant, partial, or no retinol-like activity.

Carotenoids are a class of related compounds found exclusively in plants (fruits, vegetables, algae, phytoplankton) and animals that feed directly on high-carotenoid plant sources, such as krill, small saltwater and freshwater crustaceans that accumulate astaxanthin from phytoplankton. Approximately 600 carotenoids have been identified thus far. Beta-carotene, alpha-carotene, lutein, lycopene, cryptoxanthin, and zeaxanthin are principal among those specifically classified as “provitamin A carotenoids”; they are so named because humans can metabolically convert them into retinol. Bonds within beta-carotene are cleaved to form all- trans retinol (and possibly retinal); divergent theories exist regarding the site of this cleavage, the products, and their proportion, although molecular structures suggest that one molecule of beta-carotene would result in two molecules of retinol. It is unreasonable, however, to equate the predicted retinol yields of the various provitamin A carotenoids, then add these to provide units of “vitamin A equivalents,” because in non–vitamin A–deficient humans, only a small proportion of provitamin A carotenoids are actually converted to retinol or retinal.

The dietary supplement labeling convention of stating provitamin A carotenoid content in units of “retinol equivalents” (REs) or international units (IUs) of vitamin A activity has led to a widespread misperception among the lay public and many medical professionals alike, that such supplements contain potentially toxic levels of vitamin A. Potential toxicity of carotenoids such as synthetic beta-carotene in smokers is another issue, unique to beta-carotene, and unrelated to issues of vitamin A toxicity (see section on beta-carotene and other provitamin A carotenoids).

Physiology and Function

In 1913, vitamin A was the first vitamin to be isolated, thus the nomenclature “A”. Researchers initially focused on its key role in vision, particularly in preventing night blindness and xerophthalmia. In 1929, Moore demonstrated that beta-carotene was converted to vitamin A, and 2 years later the chemical structures of both vitamin A and beta-carotene were determined.

Vitamin A is readily absorbed in the duodenum and jejunum in the presence of gastric secretions, bile salts, pancreatic and intestinal lipase, protein, and dietary fat. More than 90% of all dietary retinol is in the form of esters, usually retinyl palmitate. These esters must be hydrolyzed in the intestinal lumen by pancreatic enzymes and within the brush border of the intestinal epithelial cells before absorption. Retinol can be absorbed from a micelle in the presence of bile salts or a nonionic detergent. Retinol is absorbed by diffusion when present in high doses, but at low doses its transport across intestinal epithelial cells is mediated by cellular retinol-binding protein (RBP). In average doses, retinol is almost entirely absorbed, with peak concentrations in 4 hours. Retinol is absorbed two to five times more efficiently than beta-carotene, the bioavailability and absorption of which are also influenced by multiple factors, including the amount of carotenoid in the diet, interactions with other carotenoids, dietary fat and fiber, nutritional deficiencies of zinc and protein, and other disease states.

Excess retinol is converted to retinyl esters again and stored in the liver. Retinol binds to RBP, which serves as the carrier associated with vitamin A transport in the blood. When the amount of vitamin A exceeds the capacity of RBP to bind to it, the excess retinol binds to lipoproteins, and in this form it has toxic effects. The liver holds 90% (or more) of the body's vitamin A stores, which typically approximate 2 years’ requirement for an adult; consequently, it generally does not need to be consumed daily. The lungs and kidneys also store retinol in small amounts. Retinol in storage has a half-life of 50 to 100 days. Vitamin A is present in breast milk. Vitamin A metabolites are eliminated in the bile and urine. When large amounts of retinol are ingested, a portion can be excreted in the feces, independent of biliary absorption and excretion.

Vitamin A is a key micronutrient needed to combat infection and maintain immunity and epithelial cell differentiation and turnover. Retinol and retinoic acid are necessary for maintenance of the structural and functional integrity of epithelial tissue and the immune system, cellular differentiation and proliferation, bone growth, gonadal (testicular and ovarian) function, and embryonic development. Vitamin A also acts as a cofactor in numerous biochemical reactions. A single effect or mechanism cannot account for the diverse vitamin A actions on the immune system.

Retinal is essential for the normal function of the retina, particularly visual adaptation to darkness. Both retinyl esters and beta-carotene from the diet are converted to retinal (11- cis isomer). Retinal is combined with the protein opsin to form rhodopsin in the rods of the retina and iodopsin in the cones. Light hitting the retina causes visual excitation and changes the cis configuration into the all- trans form of retinaldehyde. The rods are particularly sensitive to vitamin A deficiency. When in low supply, the all- trans form generated during the light reaction cannot be converted back to the active rhodopsin. Retinal can be also converted to retinoic acid, the form of vitamin A most directly involved in gene transcription. Approximately 20% to 35% of the retinol in food sources (e.g., cod and other fish liver oils) is in the cis configuration, whereas virtually all the vitamin A in supplements and vitamin A–fortified foods (e.g., dairy products) is in the all- trans configuration. Some evidence suggests that the cis configuration may be essential to certain visual and brain functions, at least in certain individuals.

A small amount of beta-carotene is converted into vitamin A in the body, but beta-carotene and the other carotenoids act independently from vitamin A as antioxidants. Only 30% to 50% of the more than 600 known carotenoids are thought to be converted into vitamin A by the body, with alpha-carotene, beta-carotene, and cryptoxanthin the most widely distributed of the provitamin A carotenoids.

nutrient in clinical practice

Known or Potential Therapeutic Uses

In conventional practice, supplemental vitamin A is generally thought to have no established therapeutic uses other than correcting frank deficiencies. The evidence for efficacy from administration of exogenous vitamin A (as retinol) is often considered “mixed” and “preliminary.” However, both natural and synthetic retinoids have been used as pharmacological agents to treat dermatological disorders, with their action most likely deriving from their effect on the transcription of skin growth factors and their receptors. Acitretin (and previously etretinate) has been employed in the treatment of psoriasis, and tretinoin (Retin-A) and isotretinoin (Accutane) are typically used to treat severe cases of acne vulgaris; tretinoin is also used cosmetically to reduce signs of skin aging. Most oncology uses of retinoids involve retinoic acid, including 13- cis , 9- cis , and all- trans forms.

Historical/Ethnomedicine Precedent

Vitamin A (retinol) is not used historically as an isolated nutrient.

Possible Uses

Acne vulgaris, acute promyelocytic leukemia, alcohol withdrawal support, Alzheimer's disease, anemia (associated with deficiency), autism ( cis-containing fish liver–derived form only), blepharitis, breast cancer, bronchitis, burns, cataracts, celiac disease, cervical dysplasia, childhood diseases, colorectal cancer, conjunctivitis, Crohn's disease (associated with deficiency), cystic fibrosis, diabetes mellitus, diabetic retinopathy (in combination with selenium, vitamins C and E), diarrhea, diverticulitis, eczema, fibrocystic breast disease, food poisoning, gastritis, glaucoma, goiter, hemorrhoids, human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) support, hypothyroidism, ichthyosis (noninflammatory skin peeling), immune function, intestinal parasites, iron deficiency anemia (with iron), keratosis follicularis (Darier's disease), leukoplakia, lichen planus pigmentosus, lung cancer, menorrhagia, mucopolysaccharidosis (Hurler syndrome), myocardial infarction, myeloproliferative disorders, night blindness (nyctalopia), osteoarthritis, osteoporosis, peptic ulcer, peritonitis, pityriasis rubra pilaris, premenstrual syndrome, psoriasis, respiratory syncytial virus (RSV), retinitis pigmentosa, retinopathy (in combination with selenium, vitamins C and E), rosacea, roundworms, rubeola (measles, severe cases, with deficiency, especially to reduce measles mortality in developing countries), seborrhea, sickle cell anemia, skin cancer, sprains and strains (associated with deficiency), surgery (preparation and recovery), tuberculosis, ulcerative colitis, urinary tract infection, varicella (chickenpox), vaginitis, warts, wound healing, xerophthalmia (classic manifestation of vitamin A deficiency).

Vitamin A deficiency is widespread, in association with general malnutrition, in developing countries, particularly among young children. Frank deficiencies are generally considered uncommon in developed countries, especially in adults, but marginal intake and deficiency status are known to occur with inadequate and poor-quality diet, especially in children and elderly persons. Furthermore, individuals who restrict their dietary intake of liver, dairy products, and vegetables rich in beta-carotene increase their risk of developing vitamin A deficiency. Chronic consumption of alcohol can deplete liver stores of vitamin A, which can be further complicated by alcohol-induced liver damage. Chronic consumption of alcohol and acetaminophen can greatly increase the hepatotoxicity of vitamin A supplements (but not of provitamin A carotenoid supplements).

Special Populations

Extremely low-birth-weight infants (≤1 kg [2.2 lb]) are at high risk of a deficiency at birth. Individuals with vitamin A deficiency caused by abnormal storage and transport conditions, including abetalipoproteinemia, diabetes mellitus, fever, hyperthyroidism, cystic fibrosis (with liver involvement), liver disease, and protein deficiency.

Deficiency Symptoms

Blindness, defective tooth and bone formation, diarrhea, diminished immune function, dry skin, increased susceptibility to respiratory and urinary tract infections, loss of appetite, metaplasia and keratinization of respiratory tract cells and other systems/organs, night blindness (nyctalopia), papular eruptions, reduced synthesis of steroid hormones, visual impairment, xerophthalmia.

Dietary Sources

Free retinol is not generally found in foods.

The richest readily available dietary source of vitamin A is fish liver oil, especially cod liver oil. In particular, all- trans dehydroretinol, previously known as vitamin A2, is a vitamin A–related compound found in freshwater fish flesh and liver and, to a lesser extent, in some marine fish; it is estimated to have 40% to 50% of the vitamin A activity of all- trans retinol. Likewise, cis isomers of retinol, exhibiting up to 75% relative activity of all- trans retinol, can account for up to 35% of preformed vitamin A measured in fish liver oils. Oily fish such as herring, pilchards, tuna, and sardines are considered rich sources. Retinyl palmitate , a precursor and storage form of retinol, is found in foods from animal sources and is, along with the acetate ester, the most common form in dietary supplements. Good food sources of vitamin A include liver, kidney, butter, egg yolk, whole milk and cream, whole-milk yogurt, and fortified skim milk. Cod liver oil and halibut fish oil contain high levels of vitamin A and have been used therapeutically.

Carotenoid sources are reviewed in the Beta-carotene monograph.

Nutrient Preparations Available

Many supplements provide a combination of retinol and beta-carotene. Some individuals appear to be able to absorb water-soluble forms of vitamin A supplements better than fat-soluble vitamin A, particularly those with compromised biliary function.

Dosage Forms Available

Capsule, liquid, tablet.

Source Materials for Nutrient Preparations

The primary forms of preformed vitamin A (retinol) in supplements are the vitamin A esters retinyl palmitate and retinyl acetate. Vitamin A can be produced by extraction from fish liver oil, although the more common process is synthesis from beta-ionone.

Dosage Range

One international unit (1 IU) of beta-carotene is equivalent to 1 IU of vitamin A; 1 mg (1000 micrograms [µg]) of beta-carotene is equivalent to 500 µg of vitamin A.

Nutrient values of preformed vitamin A and provitamin A carotenoids are often combined into a single numerical value designating functional vitamin A activity. Originally, the internationally accepted values were international units, with 1 IU being defined as 0.30 µg of all- trans retinol, or 0.60 µg of all- trans beta-carotene. Although the system of retinol equivalents has become the accepted standard, these earlier are still found in many food composition tables and scientific publications.

Strong evidence for lower bioavailability of beta-carotene than previous estimates led to revision of the values for the biological activity of various forms of vitamin A and carotenoids. On the basis of rodent studies, the other provitamin A carotenoids have an estimated 50% of the growth-promoting activity of beta-carotene. Although further research has revealed greater diversity in bioavailability, absorption, and differential biological activity, the initial proportional estimates resulted in units of expression for vitamin A activity called retinol equivalents (REs). Retinol equivalents are now used as the internationally accepted units for vitamin A activity and can be summarized as follows: 1000 REs =1 mg all-trans retinol =6 mg all-trans beta-carotene =12 mg other provitamin A carotenoids =3330 IU vitamin A (retinol) =10,000 IU carotene

However, differences in equivalency when converting beta-carotene to retinol has produced persistent confusion between IU and RE. Calculating total vitamin A activity using the RE system reduces the contribution of provitamin A compared with the IU system. The resultant formula for interconversion follows: RE=IU retionol/3 .33 + IU beta-carotene/10 .0 =µg retinol =µg beta-carotene/6 + µg other provitamin A carotenoids/12

Continued uncertainty about the meaning of bioavailability of carotenoids, shortcomings in methods for determining bioavailability and absorption, and emerging knowledge of numerous factors in individual variability reveal fundamental inadequacies and inaccuracy in current systems for evaluating and comparing various forms of vitamin A, particularly those from dietary intake of carotenoid-containing foods. Given the wide range of reported conversion ratios of beta-carotene to vitamin A in humans, including the ratio of 6:1 for beta-carotene and 12:1 for alpha-carotene and cryptoxanthin devised by the World Health Organization (WHO), it appears prudent to consider all such approaches as, at best, providing only an average estimate that is not applicable to all diets or individuals. Furthermore, isomerization remains a largely unaddressed issue in quantifying provitamin A activity in processed forms of plant products.

Adult

Dietary: 2333 IU/day for women and 3000 IU/day for men, from dietary sources of both vitamin A and beta-carotene, will generally be adequate to support normal gene expression, immune function, and vision. Breast-feeding women: 4000 to 4333 IU (1200-1300 µg) daily.

Supplemental/Maintenance: 2500 IU of vitamin A as retinol, or 5000 IU of vitamin A, total, with at least 50% in the form of beta-carotene.

Pharmacological/Therapeutic: 25,000 IU (7500 µg) of vitamin A daily is typically used. Doses of 100,000 to 400,000 IU/day have been used for limited periods in the treatment of certain conditions with professional supervision. A maximum of 15,000 IU/day may be more appropriate for individuals over age 65 and those with liver disease outside the context of professional supervision.

Toxic: Doses greater than 50,000 IU/day have resulted in toxicity. Adverse effects may occur in adults at intake levels above 25,000 IU (7500 µg) daily, with higher levels, at or above 100,000 IU/day, more likely to result in cumulative toxicity. Pregnant women (or those who could become pregnant during or shortly after extended supplementation) should not exceed 10,000 IU (3000 µg) daily because of the risk of birth defects, less if foods fortified with vitamin A are consumed to a significant degree with any regularity.

Pediatric (<18 years)

  • Dietary and   Supplemental (combined):
  • Infants, birth to 6 months: 1333 IU (400 µg), or retinol equivalent (RE) (AI, adequate intake).
  • Infants 7 to 12 months: 1667 IU (500 µg), or retinol equivalent (RE) (AI)
  • Children, 1 to 3 years: 1000 IU (300 µg)/day (AI)
  • Children, 4 to 8 years: 1333 IU (400 µg)/day (RDA)
  • Children, 9 to 13 years: 2000 IU (600 µg)/day (RDA)
  • Adolescents, females, 14 to 18 years: 2333 IU (700 µg)/day
  • Adolescents, male, 14 to 18 years: 3000 IU (900 µg)/day (RDA)
  • Note:   Supplementation often advised for children 6 months to 5 years of age (unless diet known to provide adequate intake)
  • Pharmacological/Therapeutic:   10,000 IU or greater daily for a child is considered high-dose therapy
  • Toxic:   10,000 IU (3000 µg) daily

Laboratory Values

  • Plasma retinol:   levels less than 1.05 mmol/L indicate deficiency.
  • Note:   Plasma retinol levels are maintained at the expense of liver stores of vitamin A. Thus, a decline in plasma retinol levels appears only when vitamin A deficiency is progressed to a severe degree.
  • Liver vitamin A content (biopsy):   Levels less than 0.07 mmol/g indicate deficiency.
  • Note:   Liver biopsy provides an accurate assessment of body stores of vitamin A.

safety profile

Overview

Vitamin A toxicity is relatively rare. Hypervitaminosis A is caused by excessive intake of preformed vitamin A and has never been attributed to consumption of carotenoids. Preformed vitamin A is rapidly absorbed and slowly cleared from the body. The risk of developing hypervitaminosis A is derived from total cumulative vitamin A intake rather than a specific daily dosage level, and dosage levels necessary to induce hypervitaminosis A vary significantly among individuals. Thus, vitamin A toxicity can occur in two forms: acute and chronic; that is, toxicity may result acutely from high-dose exposure over a short time, or chronically from lower intake.

Acute hypervitaminosis A results from ingestion of a very high dose of vitamin A over a brief period. Typical symptoms include bulging fontanels in infants and headache in adults, nausea, vomiting, fever, vertigo, and visual disorientation. Peeling of the skin may also occur. Chronic hypervitaminosis A is more common than the acute form and results from continued ingestion of high doses for months or even years. Symptoms include anorexia, dry itchy skin, alopecia, increased intracranial pressure, fatigue, irritability, somnolence, pronounced craniotabes (congenital cranial osteoporosis) and occipital edema, skin desquamation, fissuring of the lips, pain in the legs and forearms, neurological disturbances, and lethargy. Elevated blood lipids are also common. Furthermore, because vitamin A is fat soluble, excesses tend to accumulate in fatty tissues.

Doses up to 25,000 units (U) per day of vitamin A are generally regarded as safe, although toxicity has been associated with doses as low as 20,000 IU/day. Alleged toxicity at this lower dose has occurred in persons with liver dysfunction caused by drugs, chronic alcohol intake, viral hepatitis, aging, or protein-calorie malnutrition. Most cases of toxicity in nonpregnant females result from more than 200,000 IU/day supplementation for at least 6 to 8 months. Although widely discussed, the teratogenic risks of vitamin A intake appear to occur rarely; however, the teratogenic risk associated with ingestion of the synthetic retinoids (e.g., all- trans and 13- cis retinoic acid) during pregnancy appears to be much higher.

Reports of adverse effects are associated with doses and durations as low as 20,000 IU/day supplementation for 4 to 6 months. However, doses as high as 500,000 to 1 million IU/day over several years have not caused adverse effects in many people.

Nutrient Adverse Effects

General Adverse Effects

Typical symptoms, especially in children, include drowsiness, fatigue, irritability, vomiting, and bulging of the fontanel. In adults, headaches, dry itchy or scaly skin, brittle nails, alopecia, fatigue, anorexia, diarrhea, gingivitis, cheilosis, bone pain, hepatosplenomegaly, abnormal liver function, and visual disturbances have been reported. Severe cases of hypervitaminosis A may result in hemorrhage, liver damage, and coma. 1

Generally, discontinuation of vitamin A intake causes symptoms to disappear within a few days with no permanent repercussions, although permanent liver injury has been reported.

Findings from several recent prospective studies suggest that long-term intake of preformed vitamin A in excess of 1500 µg (5000 IU) per day are associated with decreased bone mineral density (BMD) and increased risk of osteoporotic fracture in older men and women, particularly a greater risk of hip fractures in women. 2-6However, because vitamin D deficiency (defined as a serum 25-hydroxyvitamin D level <20 mg/mL) appears to be relatively common in the general population (particularly older age groups), because vitamin A may antagonize the effects of vitamin D, 7 and because vitamin D status was not investigated in any of these reports, the role (if any) of vitamin D status in the higher fracture risk associated with higher intakes of vitamin A is unclear.

Adverse Effects Among Specific Populations

Lower dosage levels are generally recommended in elderly individuals because of increased risk of compromised liver function and attendant increased risk of toxicity, as well as potentially elevated risk of osteoporosis. Individuals with liver disease or diabetes may also have diminished ability to release vitamin A stored in the liver and therefore an elevated risk of toxic accumulation. Individuals with a genetic predisposition to hypercholesterolemia may also be more susceptible to toxicity at lower doses.

Pregnancy and Nursing

The greatest concerns about toxicity are the embryotoxic effects that may occur during early pregnancy. Large doses of vitamin A and most of the retinoids can interfere with normal fetal cell development and cause birth defects, although this is usually observed with other retinoids (compounds related to vitamin A, such as retinoic acid), rather than for vitamin A itself. Thus, excessive dietary intake of vitamin A has been associated with birth defects in humans in fewer than 20 reported cases over the past 30 years. 8,9Other studies combining human and animal data suggest that up to 30,000 U/day is safe in pregnancy. 10 Nevertheless, until more conclusive, large-scale data are available, most experts suggest limiting vitamin A intake from food and supplements combined to 10,000 U during pregnancy. This standard recommendation of a 10,000 IU safe limit became institutionalized after the 1995 New England Journal of Medicine report on vitamin A–related teratogenicity. 11

However, a subsequent report by Mastroiacovo et al. 12 observed only three major malformations among several hundred women exposed to 10,000 to 300,000 IU (median exposure of 50,000 IU) per day, a typical rate of occurrence regardless of vitamin A intake. Furthermore, congenital malformations were lacking in any of the 120 infants exposed to maternal intakes of vitamin A greater than 50,000 IU/day, and this high-exposure group actually demonstrated a 50% decreased risk for malformations, compared with infants not exposed to vitamin A, and a risk level lower than those exposed to midlevel doses (10,000-40,000 IU/day). 12 Other research has found a beneficial effect of vitamin A supplements in reducing free-radical–induced lipid peroxidation associated with third-trimester pregnancy–induced hypertension, 13 thus demonstrating this vitamin's antioxidant activity in an important clinical situation.

In a randomized clinical trial, Fawzi et al. 14 found that a multivitamin supplement reduced death and prolonged HIV-free survival significantly among children born to women with low maternal immunological or nutritional status. Vitamin A alone, however, was associated with increased risk of HIV transmission from mother to child while nursing. Further research is inappropriate, but prudence advises limited use of vitamin A by HIV-infected women who are nursing or susceptible to pregnancy.

Contraindications

Retinol is contraindicated in patients with compromised liver, hepatitis, or any liver disease. High alcohol intake can induce vitamin A deficiency, but ethanol and retinol may interact to increase oxidative stress and the risk of hepatotoxicity. 15

Precautions and Warnings

High doses (>10,000 IU/day) of supplemental retinol are contraindicated in women who are or might become pregnant. This upper level may be reduced to 1500 µg (5000 IU) of vitamin A per day if foods fortified with preformed vitamin A constitute a significant component of their diet.

High doses should not be administered to older men and women, especially those with decreased BMD and corresponding increased risk of osteoporotic fractures.

At high dosage levels, especially outside the context of broad-based antioxidant nutrient networks, both vitamin A and synthetic beta-carotene have the potential to elevate triglycerides and increase oxidative stress and thereby increase risk of death from heart disease, particularly in smokers. Supplementation with synthetic all- trans beta-carotene has also been associated with an increased risk of lung cancer in smokers. Notably, however, retinoid therapy in former smokers, using 9- cis-retinoic acid, reverses loss of retinoic acid receptor-beta expression in the bronchial epithelium and may help prevent lung cancer. 16

interactions review

Strategic Considerations

Vitamin A is generally used in supporting healthy function and treating disorders of the tissues for which it has the greatest affinity: eyes and vision, skin and mucous membranes, cell regeneration and immune function. Both animal and plant foods can serve as dietary sources of vitamin A, but only the preformed vitamin A (primarily retinyl esters and retinol) can contribute to toxicity from excessive dietary intake.

As a nutritional supplement or as a pharmaceutical agent, retinol is primarily administered for its pharmacological activity and not as an antioxidant, as might be a primary intended function of beta-carotene and other carotenoids. In general, retinoids, whether synthetic or natural in origin, should be considered as prescription drugs because their typical use in high doses will usually override normal physiological regulatory mechanisms, thus introducing the risk of accumulation, toxicity, and adverse effects. Apart from application in supporting development and immune function in infants and children, vitamin A has largely been displaced by synthetic retinoids in conventional practice.

Vitamin A continues to play a limited role in oncology therapeutics. In some cases, particularly involving squamous tumors, up to 1 million units/day emulsified vitamin A (the preferred form because of lower hepatic accumulation) is administered daily until significant cheilosis develops, then lowered to 100,000 IU/day and gradually increased again. With such use, experienced physicians follow the blood retinol level, pushing it to the upper limit of normal, and take care to monitor hepatic enzymes, symptoms, and skeletal metabolism and adjust as needed to prevent bone loss. It is important to remain aware that liver damage may result from long-term use of 25,000 IU nonemulsified A, especially in conjunction with chemotherapeutic agents such as tamoxifen. Within conventional oncology practice, all- trans retinoic acid (ATRA), combined with chemotherapy, has become standard treatment for promyelocytic leukemia over the past 10 years. In contrast to such uses within conventional pharmacology, retinol and its esters are really the only “nutrient” forms of vitamin A.

nutrient-drug interactions
Antacids
Anthelmintic Drugs
Chemotherapy (Cytotoxic Agents)
Cholestyramine, Colestipol, and Related Bile Acid Sequestrants
Colchicine
Corticosteroids, Oral
HMG-CoA Reductase Inhibitors (Statins)
Medroxyprogesterone
Methyltestosterone
Mineral Oil
Neomycin
Oral Contraceptives: Monophasic, Biphasic, and Triphasic Estrogen Preparations (Synthetic Estrogen and Progesterone Analogs)
Orlistat (Xenical)
Retinoids
Tetracycline Antibiotics
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Antibiotics
Anticonvulsant Medications, Including Phenobarbital, Phenytoin, and Valproic Acid

Evidence: Carbamazepine (Carbatrol, Tegretol), divalproex semisodium, divalproex sodium (Depakote), ethosuximide (Zarontin), phenobarbital (phenobarbitone; Luminal, Solfoton), phenytoin (diphenylhydantoin; Dilantin, Phenytek), sodium valproate (Depacon), valproic acid (Depakene, Depakene Syrup), valproate semisodium.

Extrapolated, based on similar properties: Clonazepam (Klonopin), clorazepate (Tranxene), ethotoin (Peganone), felbamate (Felbatol), fosphenytoin (Cerebyx, Mesantoin), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), mephobarbital (Mebaral), methsuximide (Celontin), oxcarbazepine (Trileptal), pentobarbital (Nembutal), piracetam (Nootropyl), primidone (Mysoline), topiramate (Topamax), trimethadione (Tridione), vigabatrin (Sabril), zonisamide (Zonegran).

Conventional practice regards both vitamin A and anticonvulsant drugs as carrying significant risks of teratogenic adverse effects, especially when taken in high doses during pregnancy, although the mechanism involved has thus far eluded researchers. Preliminary evidence suggests that anticonvulsant medications can significantly alter endogenous retinoid metabolism in several ways. In particular, numerous studies have found that antiepileptic drugs (AEDs) alter endogenous retinoid concentrations, and that this effect could provide a possible mechanism for the pattern of teratogenesis observed with anticonvulsant therapy.

Although birth defects have been presented as a significant risk of high levels of vitamin A intake, other research indicates that supplemental vitamin A might prevent birth defects in children born to women receiving multiple-anticonvulsant therapy. All- transretinoic acid (ATRA) and other vitamin A metabolites significantly influence embryonic development (e.g., growth, differentiation, morphogenesis), and imbalances in vitamin A status, both excess and deficiency, have been associated with teratogenic effects. Thus, medications such as AEDs that disrupt healthy levels of plasma retinoids could result in adverse effects, which could vary depending on the pathophysiology of the patient's underlying disorder(s), the medications and dosage levels being used, as well as the clinical response, nutritional status, general state of health, and other characteristics of the mother.

Evidence indicates that the toxicity of anticonvulsant drugs, and most likely some of their teratogenic effect, may be related to low blood levels of vitamin A. Nau et al. 97 measured plasma levels of retinol and its oxidative metabolites all- trans, 13- cis, and 13- cis-4-oxo retinoic acid in 75 infants and children treated with various AEDs for seizures and in 29 untreated controls of comparable age. Retinol levels increased with age, whereas the concentrations of retinoic acid compounds did not exhibit age dependency. Valproic acid monotherapy increased retinol levels in the young age group, and a trend toward increased retinol concentrations was seen in all other patient groups. The authors also noted significant declines in plasma levels of 13- cisand 13- cis-4-oxo retinoic acid in all patient groups treated with phenytoin, phenobarbital, carbamazepine, and ethosuximide, in combination with valproic acid, to levels below one third and one tenth of corresponding control values, respectively. Only minor changes were observed with ATRA, except in one patient group treated with valproic acid plus ethosuximide who demonstrated increased levels of this retinoid.

The available research does not conclusively answer whether coadministration of anticonvulsants and vitamin A inherently results in adverse effects or increases the risk of birth defects when taken during pregnancy. Because both retinoids and AEDs are highly associated with teratogenicity, clinical trials adding retinoid to AEDs in pregnant epileptic women are unlikely and inadvisable. Ultimately, characterization of these interactions remains important for understanding pharmacology and physiology, but it does little to change the recommendations of clinicians for their female patients of childbearing age; that is, neither anticonvulsants nor moderate to high doses of vitamin A should be considered as safe during pregnancy; and alternative therapeutic strategies of lesser toxicity are required.

Furthermore, these cautions need to be extended because of “off-label” prescribing of medications broadly classified as “anticonvulsants.” These medications may be more often prescribed for pain, insomnia, anxiety, migraines, postherpetic neuralgia, and conditions other than seizure disorders. For example, up to 90% of gabapentin (Neurontin) is prescribed for off-label purposes, which are aggressively promoted by drug manufacturers and marketers. Such off-label use, however, is generally for conditions with less serious consequences than uncontrolled seizure disorders, and thus continued medication use during pregnancy is less likely to occur for such conditions.

Arachidonic Acid Cascade Inhibitors
Methotrexate
Tamoxifen
Thioridazine
Warfarin and Related Oral Vitamin K Antagonist Anticoagulants
nutrient-nutrient interactions
Calcium
Iron
Vitamin D
Vitamin E
Zinc
Citations and Reference Literature
  • 1.Russell RM. The vitamin A spectrum: from deficiency to toxicity. Am J Clin Nutr 2000;71:878-884.View Abstract
  • 2.Melhus H, Michaelsson K, Kindmark A et al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med 1998;129:770-778.View Abstract
  • 3.Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA 2002;287:47-54.
  • 4.Binkley N, Krueger D. Hypervitaminosis A and bone. Nutr Rev 2000;58:138-144.View Abstract
  • 5.Promislow JH, Goodman-Gruen D, Slymen DJ, Barrett-Connor E. Retinol intake and bone mineral density in the elderly: the Rancho Bernardo Study. J Bone Miner Res 2002;17:1349-1358.View Abstract
  • 6.Michaelsson K, Lithell H, Vessby B, Melhus H. Serum retinol levels and the risk of fracture. N Engl J Med 2003;348:287-294.View Abstract
  • 7.Johansson S, Melhus H. Vitamin A antagonizes calcium response to vitamin D in man. J Bone Miner Res 2001;16:1899-1905.View Abstract
  • 8.Biesalski HK. Comparative assessment of the toxicology of vitamin A and retinoids in man. Toxicology 1989;57:117-161.View Abstract
  • 9.Azais-Braesco V, Pascal G. Vitamin A in pregnancy: requirements and safety limits. Am J Clin Nutr 2000;71:1325S-1333S.View Abstract
  • 10.Wiegand UW, Hartmann S, Hummler H. Safety of vitamin A: recent results. Int J Vitam Nutr Res 1998;68:411-416.View Abstract
  • 11.Rothman KJ, Moore LL, Singer MR et al. Teratogenicity of high vitamin A intake. N Engl J Med 1995;333:1369-1373.View Abstract
  • 12.Mastroiacovo P, Mazzone T, Addis A et al. High vitamin A intake in early pregnancy and major malformations: a multicenter prospective controlled study. Teratology 1999;59:7-11.View Abstract
  • 13.Pandey S, Srivastava R, Mukerjee D et al. Effect of vitamin “A” on free radical cascade in pregnancy induced hypertension. Boll Chim Farm 2000;139:98-102.View Abstract
  • 14.Fawzi WW, Msamanga GI, Hunter D et al. Randomized trial of vitamin supplements in relation to transmission of HIV-1 through breastfeeding and early child mortality. AIDS 2002;16:1935-1944.View Abstract
  • 15.Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr 1999;69:1071-1085.View Abstract
  • 16.Kurie JM, Lotan R, Lee JJ et al. Treatment of former smokers with 9-cis-retinoic acid reverses loss of retinoic acid receptor-beta expression in the bronchial epithelium: results from a randomized placebo-controlled trial. J Natl Cancer Inst 2003;95:206-214.View Abstract
  • 17.Patty I, Benedek S, Deak G et al. Cytoprotective effect of vitamin A and its clinical importance in the treatment of patients with chronic gastric ulcer. Int J Tissue React 1983;5:301-307.View Abstract
  • 18.Persson V, Ahmed F, Gebre-Medhin M, Greiner T. Relationships between vitamin A, iron status and helminthiasis in Bangladeshi school children. Public Health Nutr 2000;3:83-89.
  • 19.Rai SK, Nakanishi M, Upadhyay, MP et al. Effect of intestinal helminth infection on retinol and beta-carotene status among rural Nepalese. Nutr Res 2000;20:15-23.
  • 20.Jalal F, Nesheim MC, Agus Z et al. Serum retinol concentrations in children are affected by food sources of beta-carotene, fat intake, and anthelmintic drug treatment. Am J Clin Nutr 1998;68:623-629.View Abstract
  • 21.Mwaniki D, Omondi B, Muniu E et al. Effects on serum retinol of multi-micronutrient supplementation and multi-helminth chemotherapy: a randomised, controlled trial in Kenyan school children. Eur J Clin Nutr 2002;56:666-673.View Abstract
  • 22.Sacks PG, Oke V, Calkins DP et al. Effects of beta-all-trans retinoic acid on growth, proliferation, and cell death in a multicellular tumor spheroid model for squamous carcinomas. J Cell Physiol 1990;144:237-243.View Abstract
  • 23.Sacks PG, Harris D, Chou TC. Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: a rationale for combination therapy with chemotherapeutic agents. Int J Cancer 1995;61:409-415.View Abstract
  • 24.Israel L, Hajji O, Grefft-Alami A et al. [Vitamin A augmentation of the effects of chemotherapy in metastatic breast cancers after menopause: randomized trial in 100 patients]. Ann Med Interne (Paris) 1985;136:551-554.View Abstract
  • 25.Nakagawa M, Yamaguchi T, Ueda H et al. Potentiation by vitamin A of the action of anticancer agents against murine tumors. Jpn J Cancer Res 1985;76:887-894.View Abstract
  • 26.Ghosh J, Das S. Role of vitamin A in prevention and treatment of sarcoma 180 in mice. Chemotherapy 1987;33:211-218.View Abstract
  • 27.Jaakkola K, Lahteenmaki P, Laakso J et al. Treatment with antioxidant and other nutrients in combination with chemotherapy and irradiation in patients with small-cell lung cancer. Anticancer Res 1992;12:599-606.View Abstract
  • 28.Vinitha R, Thangaraju M, Sachdanandam P. Effect of administering cyclophosphamide and vitamin E on the levels of tumor-marker enzymes in rats with experimentally induced fibrosarcoma. Jpn J Med Sci Biol 1995;48:145-156.View Abstract
  • 29.Venugopal M, Jamison JM, Gilloteaux J et al. Synergistic antitumor activity of vitamins C and K3 on human urologic tumor cell lines. Life Sci 1996;59:1389-1400.View Abstract
  • 30.Venugopal M, Jamison JM, Gilloteaux J et al. Synergistic antitumour activity of vitamins C and K3 against human prostate carcinoma cell lines. Cell Biol Int 1996;20:787-797.View Abstract
  • 31.Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology (Huntingt) 1999;13:1003-1008; discussion 1008, 1011-1012.
  • 32.Taper HS, de Gerlache J, Lans M, Roberfroid M. Non-toxic potentiation of cancer chemotherapy by combined C and K3 vitamin pre-treatment. Int J Cancer 1987;40:575-579.View Abstract
  • 33.Prasad KN, Hernandez C, Edwards-Prasad J et al. Modification of the effect of tamoxifen, cisplatin, DTIC, and interferon-alpha 2b on human melanoma cells in culture by a mixture of vitamins. Nutr Cancer 1994;22:233-245.
  • 34.Albini A, D’Agostini F, Giunciuglio D et al. Inhibition of invasion, gelatinase activity, tumor take and metastasis of malignant cells by N-acetylcysteine. Int J Cancer 1995;61:121-129.
  • 35.Kurbacher CM, Wagner U, Kolster B et al. Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro. Cancer Lett 1996;103:183-189.View Abstract
  • 36.Wagdi P, Fluri M, Aeschbacher B et al. Cardioprotection in patients undergoing chemo- and/or radiotherapy for neoplastic disease: a pilot study. Jpn Heart J 1996;37:353-359.View Abstract
  • 37.Fujiwaki R, Iida K, Ohnishi Y et al. Intra-arterial neoadjuvant chemotherapy followed by radical surgery and radiotherapy for stage IIb cervical carcinoma. Anticancer Res 1997;17:3751-3755.View Abstract
  • 38.Weijl NI, Cleton FJ, Osanto S. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treat Rev 1997;23:209-240.View Abstract
  • 39.Gillissen A, Nowak D. Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy. Respir Med 1998;92:609-623.View Abstract
  • 40.Weijl NI, Hopman GD, Wipkink-Bakker A et al. Cisplatin combination chemotherapy induces a fall in plasma antioxidants of cancer patients. Ann Oncol 1998;9:1331-1337.View Abstract
  • 41.Kong Q, Lillehei KO. Antioxidant inhibitors for cancer therapy. Med Hypotheses 1998;51:405-409.View Abstract
  • 42.Domenighetti G, Quattropani C, Schaller MD. [Therapeutic use of N-acetylcysteine in acute lung diseases]. Rev Mal Respir 1999;16:29-37.View Abstract
  • 43.Kodama J, Ikuhashi H, Hongo A et al. [Neoadjuvant chemotherapy for advanced cervical cancer]. Gan To Kagaku Ryoho 1999;26:89-92.View Abstract
  • 44.Prasad KN, Kumar A, Kochupillai V, Cole WC. High doses of multiple antioxidant vitamins: essential ingredients in improving the efficacy of standard cancer therapy. J Am Coll Nutr 1999;18(1):13-25. ReviewView Abstract
  • 45.Simone CB, Simone NL, Simone CB 2nd. Nutrients and cancer treatment. Int J Integr Med 1999;1:20-24.
  • 45a.Simone CB 2nd, Simone NL, Simone V, Simone CB. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, Part 1. Altern Ther Health Med 2007;13(1):22-28. (Review)
  • 45b.Simone CB 2nd, Simone NL, Simone V, Simone CB: Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, Part 2. Altern Ther Health Med 2007;13(2):40-47. (Review)
  • 45c.Prasad KN, Cole WC, Prasad JE. Multiple antioxidant vitamins as an adjunct to standard and experimental cancer therapies. Z Onkol/J Oncol 1999;31:1201-1078.
  • 46.Salignik R et al. Avoiding vitamins A and E may improve cancer therapy. 39th Annual Meeting of the American Society for Cell Biology; 1999.
  • 46a.Block KI, Koch AC, Mead MN, et al. Impact of antioxidant supplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomized controlled trials. Cancer Treat Rev 2007;33(5):407-418. Epub 2007 March 23.
  • 47.Roe DA. Risk factors in drug-induced nutritional deficiencies. In: Roe DA, Campbell T, eds. Drugs and Nutrients: the Interactive Effects. New York: Marcel Dekker; 1984:505-523.
  • 48.Roe DA. Drug-Induced Nutritional Deficiencies. 2nd ed. Westport, Conn: Avi Publishing; 1985.
  • 49.Hathcock JN. Metabolic mechanisms of drug-nutrient interactions. Fed Proc 1985;44:124-129.View Abstract
  • 50.Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2:10-32.View Abstract
  • 51.Diuretics and cardiovasculars, antihyperlipidemic agents, bile acid sequestrants. In: Threlkeld DS, ed. Facts and Comparisons Drug Information. St Louis: Facts and Comparisons; February 1997:171i.
  • 52.West RJ, Lloyd JK. The effect of cholestyramine on intestinal absorption. Gut 1975;16:93-98.View Abstract
  • 53.Probstfield JL, Lin TL, Peters J, Hunninghake DB. Carotenoids and vitamin A: the effect of hypocholesterolemic agents on serum levels. Metabolism 1985;34:88-91.View Abstract
  • 54.Tonstad S, Sivertsen M, Aksnes L, Ose L. Low dose colestipol in adolescents with familial hypercholesterolaemia. Arch Dis Child 1996;74:157-160.View Abstract
  • 55.Race TF, Paes IC, Faloon WW. Intestinal malabsorption induced by oral colchicine: comparison with neomycin and cathartic agents. Am J Med Sci 1970;259:32-41.View Abstract
  • 56.Robinson C, Weigly E. Basic Nutrition and Diet Therapy. New York: Macmillan; 1984.
  • 57.Hunt TK, Ehrlich HP, Garcia JA, Dunphy JE. Effect of vitamin A on reversing the inhibitory effect of cortisone on healing of open wounds in animals and man. Ann Surg 1969;170:633-641.View Abstract
  • 58.Hormones, adrenal cortical steroids, glucocorticoids. In: Threlkeld DS, ed. Facts and Comparisons Drug Information. St Louis: Facts and Comparisons; April 1991:128b.
  • 59.Atukorala TM, Basu TK, Dickerson JW. Effect of corticosterone on the plasma and tissue concentrations of vitamin A in rats. Ann Nutr Metab 1981;25:234-238.View Abstract
  • 60.Georgieff MK, Radmer WJ, Sowell AL et al. The effect of glucocorticosteroids on serum, liver, and lung vitamin A and retinyl ester concentrations. J Pediatr Gastroenterol Nutr 1991;13:376-382.View Abstract
  • 61.Shenai JP, Mellen BG, Chytil F. Vitamin A status and postnatal dexamethasone treatment in bronchopulmonary dysplasia. Pediatrics 2000;106:547-553.View Abstract
  • 62.Muggeo M, Zenti MG, Travia D et al. Serum retinol levels throughout 2 years of cholesterol-lowering therapy. Metabolism 1995;44:398-403.View Abstract
  • 63.Amatayakul K, Sivasomboon B, Thanangkul O. Vitamin and trace mineral metabolism in medroxyprogesterone acetate users. Contraception 1978;18:253-269.View Abstract
  • 64.Joshi UM, Virkar KD, Amatayakul K et al. Impact of hormonal contraceptives vis-a-vis non-hormonal factors on the vitamin status of malnourished women in India and Thailand. World Health Organization: Special Programme of Research, Development and Research Training in Human Reproduction; Task Force on Oral Contraceptives. Hum Nutr Clin Nutr 1986;40:205-220.View Abstract
  • 65.Amatayakul K, Underwood BA, Ruckphaopunt S et al. Oral contraceptives: effect of long-term use on liver vitamin A storage assessed by the relative dose response test. Am J Clin Nutr 1989;49:845-848.View Abstract
  • 66.Downer S, Joel S, Allbright A et al. A double blind placebo controlled trial of medroxyprogesterone acetate (MPA) in cancer cachexia. Br J Cancer 1993;67:1102-1105.View Abstract
  • 67.Meram I, Balat O, Tamer L, Ugur MG. Trace elements and vitamin levels in menopausal women receiving hormone replacement therapy. Clin Exp Obstet Gynecol 2003;30:32-34.View Abstract
  • 68.Wien EM, Ojo OA. Serum vitamin A, carotene and cholesterol levels in Nigerian women using various types of contraceptives. Nutr Rep Int 1982;25:687-696.
  • 69.Nisbett SB, Parker JA, Habal F. Methyltestosterone-induced night blindness. Can J Ophthalmol 1985;20:254-256.View Abstract
  • 70.Clark JH, Russell GJ, Fitzgerald JF, Nagamori KE. Serum beta-carotene, retinol, and alpha-tocopherol levels during mineral oil therapy for constipation. Am J Dis Child 1987;141:1210-1212.
  • 71.Favaro RM, Silva HC, Vannucchi H. Bioavailability of vitamin A in the rat following ingestion of neomycin sulfate or aluminum hydroxide. Int J Vitam Nutr Res 1994;64:98-103.
  • 72.Jacobson ED, Faloon WW. Malabsorptive effects of neomycin in commonly used doses. JAMA 1961;175:187-190.
  • 73.Wynn V. Vitamins and oral contraceptive use. Lancet 1975:561-564.View Abstract
  • 74.Werbach MR. Foundations of Nutritional Medicine. Tarzana, Calif: Third Line Press; 1997.
  • 75.Tyrer LB. Nutrition and the pill. J Reprod Med 1984;29:547-550.View Abstract
  • 76.Cumming FJ, Briggs MH. Changes in plasma vitamin A in lactating and non-lactating oral contraceptive users. Br J Obstet Gynaecol 1983;90:73-77.View Abstract
  • 77.Mooij PN, Thomas CM, Doesburg WH, Eskes TK. Multivitamin supplementation in oral contraceptive users. Contraception 1991;44:277-288.View Abstract
  • 78.Horwitt MK, Harvey CC, Dahm CH Jr. Relationship between levels of blood lipids, vitamins C, A, and E, serum copper compounds, and urinary excretions of tryptophan metabolites in women taking oral contraceptive therapy. Am J Clin Nutr 1975;28:403-412.
  • 79.Melia AT, Koss-Twardy SG, Zhi J. The effect of orlistat, an inhibitor of dietary fat absorption, on the absorption of vitamins A and E in healthy volunteers. J Clin Pharmacol 1996;36:647-653.View Abstract
  • 79a.Van Gaal LF, Broom JI, Enzi G, Toplak H. Efficacy and tolerability of orlistat in the treatment of obesity: a 6-month dose-ranging study. Orlistat Dose-Ranging Study Group. Eur J Clin Pharmacol 1998;54(2):125-132.
  • 80.Finer N, James WP, Kopelman PG et al. One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor. Int J Obes Relat Metab Disord 2000;24:306-313.View Abstract
  • 81.McDuffie JR, Calis KA, Booth SL et al. Effects of orlistat on fat-soluble vitamins in obese adolescents. Pharmacotherapy 2002;22:814-822.View Abstract
  • 82.Rollman O, Vahlquist A. Oral isotretinoin (13-cis-retinoic acid) therapy in severe acne: drug and vitamin A concentrations in serum and skin. J Invest Dermatol 1986;86:384-389.View Abstract
  • 83.Vahlquist A, Rollman O, Holland DB, Cunliffe WJ. Isotretinoin treatment of severe acne affects the endogenous concentration of vitamin A in sebaceous glands. J Invest Dermatol 1990;94:496-498.View Abstract
  • 84.Walters BN, Gubbay SS. Tetracycline and benign intracranial hypertension: report of five cases. Br Med J (Clin Res Ed) 1981;282:19-20.View Abstract
  • 85.Lee AG. Pseudotumor cerebri after treatment with tetracycline and isotretinoin for acne. Cutis 1995;55:165-168.View Abstract
  • 86.Gerber A, Raab AP, Sobel AE. Vitamin A poisoning in adults; with description of a case. Am J Med 1954;16:729-745.View Abstract
  • 87.Siegel NJ, Spackman TJ. Chronic hypervitaminosis A with intracranial hypertension and low cerebrospinal fluid concentration of protein: two illustrative cases. Clin Pediatr (Phila) 1972;11:580-584.View Abstract
  • 88.Lombaert A, Carton H. Benign intracranial hypertension due to A-hypervitaminosis in adults and adolescents. Eur Neurol 1976;14:340-350.View Abstract
  • 89.Bonnetblanc JM, Hugon J, Dumas M, Rupin D. Intracranial hypertension with etretinate. Lancet 1983;2:974.View Abstract
  • 90.Selhorst JB, Waybright EA, Jennings S, Corbett JJ. Liver lover’s headache: pseudotumor cerebri and vitamin A intoxication. JAMA1984;252:3365.
  • 91.Roytman M, Frumkin A, Bohn TG. Pseudotumor cerebri caused by isotretinoin. Cutis 1988;42:399-400.View Abstract
  • 92.Spector RH, Carlisle J. Pseudotumor cerebri caused by a synthetic vitamin A preparation. Neurology 1984;34:1509-1511.View Abstract
  • 93.Marcus R, Coulston AM. Fat-soluble vitamins, vitamin A, K, and E. Goodman & Gillman’s the Pharmacological Basis of Therapeutics. 9th ed; New York: McGraw-Hill; 1996.
  • 94.Moskowitz Y, Leibowitz E, Ronen M, Aviel E. Pseudotumor cerebri induced by vitamin A combined with minocycline. Ann Ophthalmol 1993;25:306-308.View Abstract
  • 95.Hossain S, Biswas R, Kabir I et al. Single dose vitamin A treatment in acute shigellosis in Bangladesh children: randomised double blind controlled trial. BMJ 1998;316:422-426.View Abstract
  • 96.Salam MA, Khan WA, Dhar U et al. Vitamin A for treating shigellosis: study did not prove benefit. BMJ 1999;318:939-940.View Abstract
  • 97.Nau H, Tzimas G, Mondry M et al. Antiepileptic drugs alter endogenous retinoid concentrations: a possible mechanism of teratogenesis of anticonvulsant therapy. Life Sci 1995;57:53-60.View Abstract
  • 98.Spingarn A, Sacks PG, Kelley D et al. Synergistic effects of 13-cis retinoic acid and arachidonic acid cascade inhibitors on growth of head and neck squamous cell carcinoma in vitro. Otolaryngol Head Neck Surg 1998;118:159-164.View Abstract
  • 99.McKee DL. Personal communication; 2004.
  • 100.Curtis JL, Swicord W. Effects of medication of plasma vitamin A concentrations [letter]. Clin Chem 1976;22:695.View Abstract
  • 101.Harris JE. Interaction of dietary factors with oral anticoagulants: review and applications. J Am Diet Assoc 1995;95:580-584.View Abstract
  • 102.Mejia LA, Chew F. Hematological effect of supplementing anemic children with vitamin A alone and in combination with iron. Am J Clin Nutr 1988;48:595-600.View Abstract
  • 103.Suharno D, West CE, Muhilal et al. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Lancet 1993;342:1325-1328.View Abstract
  • 104.Muñoz EC, Rosado JL, Lopez P et al. Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers. Am J Clin Nutr 2000;71:789-794.
  • 105.Christian P, West KP Jr. Interactions between zinc and vitamin A: an update. Am J Clin Nutr 1998;68:435S-441S.
  • .[No authors listed.] MRC/BHF Heart Protection Study of cholesterol-lowering therapy and of antioxidant vitamin supplementation in a wide range of patients at increased risk of coronary heart disease death: early safety and efficacy experience. Eur Heart J 1999;20(10):725-741.
  • .[No authors listed.] Leads from the MMWR: use of supplements containing high-dose vitamin A: New York State, 1983-1984. JAMA 1987;257(10):1292, 1297.
  • .[No authors listed.] The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers: the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med 1994;330(15):1029-1035.
  • .[No authors listed.] Use of supplements containing high-dose vitamin A: New York State, 1983-1984. MMWR Morb Mortal Wkly Rep 1987;36(6):80-82.
  • .Abahusain MA, Wright J, Dickerson JWT, et al. Retinol, alpha-tocopherol and carotenoids in diabetes. Eur J Clin Nutr 1999;53:630-635.
  • .Aboulafia DM, Norris D, Henry D, et al. 9-cis-Retinoic acid capsules in the treatment of AIDS-related Kaposi sarcoma: results of a phase 2 multicenter clinical trial. Arch Dermatol 2003;139(2):178-186.
  • .Ahmed F, Bamji MS. Vitamin supplements to women using oral contraceptives (studies of vitamins B1, B2, B6 and A). Contraception 1976;14(3):309-318.
  • .Aktuna D, Buchinger W, Langsteger W, et al. [Beta-carotene, vitamin A and carrier proteins in thyroid diseases.] Acta Med Austriaca 1993;20:17-20. [German]
  • .Alberts D, Ranger-Moore J, Einspahr J, et al. Safety and efficacy of dose-intensive oral vitamin A in subjects with sun-damaged skin. Clin Cancer Res 2004;10(6):1875-1880.
  • .Albright CD, Salganik RI, Van Dyke T. Dietary depletion of vitamin E and vitamin A inhibits mammary tumor growth and metastasis in transgenic mice. J Nutr 2004;134(5):1139-1144.
  • .Amatruda TTD, Sidell N, Ranyard J, et al. Retinoic acid treatment of human neuroblastoma cells is associated with decreased N-myc expression. Biochem Biophys Res Community 1985;126:1189-1195.
  • .Ames BN. An enthusiasm for metabolism. J Biol Chem 2003;278(7):4369-4380. (Review)
  • .Ames BN. Delaying the mitochondrial decay of aging. Ann N Y Acad Sci 2004;1019:406-411. (Review)
  • .Ames BN. DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res 2001;475(1-2):7-20. (Review)
  • .Ames BN. Increasing longevity by tuning up metabolism: to maximize human health and lifespan, scientists must abandon outdated models of micronutrients. EMBO Rep 2005;6(Suppl 1):S20-24.
  • .Ames BN. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc Natl Acad Sci U S A 2006;103:17589-17594.
  • .Ames BN. The metabolic tune-up: metabolic harmony and disease prevention. J Nutr 2003;133(5):1544S-1548S.
  • .Ames BN, Atamna H, Killilea DW. Mineral and vitamin deficiencies can accelerate the mitochondrial decay of aging. Mol Aspects Med 2005;26(4-5):363-378. (Review)
  • .Amichai B, Shemer A, Grunwald MH. Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol 2006;54(4):644-646.
  • .Andersson SO, Wolk A, Bergstrom R, et al. Energy, nutrient intake and prostate cancer risk: a population-based case-control study in Sweden. Int J Cancer 1996;68(6):716-722.
  • .Anstead GM. Steroids, retinoids, and wound healing. Adv Wound Care 1998;11(6):277-285. (Review)
  • .Antoon AY, Donovan DK. Burn injuries. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson textbook of pediatrics. Philadelphia: Saunders; 2000:287-294.
  • .Arnhold T, Elmazar MM, Nau H. Prevention of vitamin A teratogenesis by phytol or phytanic acid results from reduced metabolism of retinol to the teratogenic metabolite, all-trans-retinoic acid. Toxicol Sci 2002;66(2):274-282.
  • .Ayello EA, Thomas DR, Litchford MA. Nutritional aspects of wound healing. Home Healthc Nurse 1999;17(11):719-729.
  • .Ayres S Jr, Mihan R. Acne vulgaris and lipid peroxidation: new concepts in pathogenesis and treatment. Int J Dermatol 1978;17:305.
  • .Azais-Braesco V, Pascal G. Vitamin A in pregnancy: requirements and safety limits. Am J Clin Nutr 2000;71(5 Suppl):1325S–133S. (Review)
  • .Barrowman J, Broomhall J, Cannon A, et al. Impairment of vitamin A absorption by neomycin. Clin Sci 1972;42:17P.
  • .Basu TK. Vitamins: cytotoxic drug interaction. Int J Vitam Nutr Res Suppl 1983;24:225-233.
  • .Basualdo CG, Wein EE, Basu TK. Vitamin A (retinol) status of First Nation adults with non-insulin-dependent diabetes mellitus. J Am Coll Nutr 1997;16(1):39-45.
  • .Baum MK, Shor-Posner G, Lu Y, et al. Micronutrients and HIV-1 disease progression. AIDS 1995;9(9):1051-1056.
  • .Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Safety 1998;19(5):355-371. (Review)
  • .Ben-Amotz A, Levy Y. Bioavailability of a natural isomer mixture compared with synthetic all-trans beta-carotene in human serum. Am J Clin Nutr 1996;63:729-734.
  • .Ben-Amotz A, Mokady S, Edelstein S, et al. Bioavailability of a natural isomer mixture as compared with synthetic all-trans-beta-carotene in rats and chicks. J Nutr 1989;119(7):1013-1019.
  • .Bendich A, Langseth L. Safety of vitamin A. Am J Clin Nutr 1989;49:358-371.
  • .Benn CS, Martins C, Rodrigues A, et al. Randomised study of effect of different doses of vitamin A on childhood morbidity and mortality. BMJ 2005;331:1428-1432.
  • .Berger M, Spertini F, Shenkin A, et al. Trace element supplementation modulates pulmonary infection rates after major burns: a double-blind, placebo-controlled trial. Am J Clin Nutr 1998;68:365-371.
  • .Bernhardt I, Dorsey D. Hypervitaminosis A and congenital renal anomalies in a human infant. Obstetr Gynecol 1974;43:750-755.
  • .Bershad SV. The modern age of acne therapy: a review of current treatment options. Mt Sinai J Med 2001;68(4-5):279-286. (Review)
  • .Berson EL, Rosner B, Sandberg MA, et al. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol 1993;111(6):761-772.
  • .Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment. Arch Ophthalmol 2004;122(9):1297-1305.
  • .Biesalski HK. Comparative assessment of the toxicology of vitamin A and retinoids in man. Toxicology 1989;57:117-161.
  • .Binkley N, Krueger D. Hypervitaminosis A and bone. Nutr Rev 2000;58:138-144. (Review)
  • .Bland J. Circadian rhythms in antioxidant dosing following chemotherapy. Funct Med Update 1999.
  • .Block E. The use of vitamin A in premenstrual tension. Acta Obstet Gynecol Scand 1960;39:586-592.
  • .Blumenthal RD, Lew W, Reising A, et al. Anti-oxidant vitamins reduce normal tissue toxicity induced by radio-immunotherapy. Int J Cancer 2000;86:276-280.
  • .Bohlke K, Spiegelman D, Trichopoulou A, et al. Vitamins A, C and E and the risk of breast cancer: results from a case control study in Greece. Br J Cancer 1999;79:23-29.
  • .Boik J. Natural compounds in cancer therapy. Princeton, MN: Oregon Medical Press; 2001.
  • .Booth SL, Tucker KL, McKeown NM, et al. Relationships between dietary intakes and fasting plasma concentrations of fat-soluble vitamins in humans. J Nutr 1997;127(4):587-592.
  • .Bousvaros A, Zurakowski D, Duggan C. Vitamins A and E serum levels in children and young adults with inflammatory bowel disease: effect of disease activity. J Pediatr Gastroenterol Nutr 1998;26:129-135.
  • .Bray GP. Liver failure induced by paracetamol. BMJ 1993;306(6871):157-158.
  • .Bray BJ, Goodin MG, Inder RE, et al. The effect of retinol on hepatic and renal drug-metabolising enzymes. Food Chem Toxicol 2001;39(1):1-9.
  • .Bray BJ, Rosengren RJ. Retinol potentiates acetaminophen-induced hepatotoxicity in the mouse: mechanistic studies. Toxicol Appl Pharmacol 2001;173(3):129-136.
  • .Brenner S, Horwitz C. Possible nutrient mediators in psoriasis and seborrheic dermatitis: I: prevalence, etiology, symptomatology, histological and biochemical features. World Rev Nutr Diet 1988;55:153-164. (Review)
  • .Brenner S, Horwitz C. Possible nutrient mediators in psoriasis and seborrheic dermatitis: II: nutrient mediators: essential fatty acids; vitamins A, E and D; vitamins B1, B2, B6, niacin and biotin; vitamin C selenium; zinc; iron. World Rev Nutr Diet 1988;55:165-182. (Review)
  • .Bresee JS, Fischer M, Dowell SF, et al. Vitamin A therapy for children with respiratory syncytial virus infection: a multicenter trial in the United States. Pediatr Infect Dis J 1996;15:777-782.
  • .Brooks AD, Tong W, Benedetti F, et al. Inhaled aerosolization of all-trans-retinoic acid for targeted pulmonary delivery. Cancer Chemother Pharmacol 2000;46(4):313-318.
  • .Carman JA, Pond L, Nashold F, et al. Immunity to Trichinella spiralis infection in vitamin A-deficient mice. J Exp Med 1992;175(1):111-120.
  • .Carter CA, Pogribny M, Davidson A, et al. Effects of retinoic acid on cell differentiation and reversion toward normal in human endometrial adenocarcinoma (RL95-2) cells. Anticancer Res 1996;16(1):17-24.
  • .Cartmel B, Moon TE, Levine N. Effects of long-term intake of retinol on selected clinical and laboratory indexes. Am J Clin Nutr 1999;69:937-943.
  • .Chasan-Taber L, Willett WC, Seddon JM, et al. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. Am J Clin Nutr 1999;70:509-516.
  • .Chen C, Mistry G, Jensen B, et al. Pharmacokinetics of retinoids in women after meal consumption or vitamin A supplementation. J Clin Pharmacol 1996;36(9):799-808.
  • .Chiang MY, Misner D, Kempermann G, et al. An essential role for retinoid receptors RARbeta and RXRgamma in long-term potentiation and depression. Neuron 1998;21(6):1353-1361.
  • .Chinery R, Brockman JA, Peeler MO, et al. Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer: a p53-independent induction of p21WAFI/CIPI via C/EBPb. Nature Med 1997;3:1233-1241.
  • .Ching S, Ingram D, Hahnel R, et al. Serum levels of micronutrients, antioxidants and total antioxidant status predict risk of breast cancer in a case control study. J Nutr 2002;132(2):303-306.
  • .Choquet-Kastylevsky G, Dumas V, Vial T, et al. [Recurrent subcutaneous edema induced by isotretinoin.] Therapie 1999;54(2):263-264. [French]
  • .Ciaccio M, Tesoriere L, Pintaudi AM, et al. Vitamin A preserves the cytotoxic activity of adriamycin while counteracting its peroxidative effects in human leukemic cells in vitro. Biochem Mol Biol Int 1994;34(2):329-335.
  • .Cole WC, Prasad KN. Contrasting effects of vitamins as modulators of apoptosis in cancer cells and normal cells: a review. Nutr Cancer 1997;29:97-103. (Review)
  • .Conley BA, Egorin MJ, Sridhara R, et al. Phase I clinical trial of all-trans-retinoic acid with correlation of its pharmacokinetics and pharmacodynamics. Cancer Chemother Pharmacol 1997;39(4):291-299.
  • .Comstock GW, Helzlsouer KJ. Preventive nutrition and lung cancer. In: Bendich A, Decklebaum RJ, eds. Preventive nutrition: the comprehensive guide for health professionals. 2nd ed. Totowa, NJ: Humana Press, Inc; 2001:97-129.
  • .Congdon NG, West KP. Nutrition and the eye. Curr Opin Opthamol 1999;10:484-473. (Review)
  • .Corball M, O’Dwyer P, Brady MP. The interaction of vitamin A and corticosteroids on wound healing. Ir J Med Sci 1985;154(8):306-310.
  • .Corrales F, Ochoa P, Rivas C, et al. Inhibition of glutathione synthesis in the liver leads to S-adenosyl-L-methionine synthetase reduction. Hepatology 1991;14(3):528-533.
  • .Coutsoudis A, Broughton M, Coovadia HM. Vitamin A supplementation reduces measles morbidity in young African children: a randomized, placebo-controlled, double-blind trial. Am J Clin Nutr 1991;54(5):890-895.
  • .Coutsoudis A, Kiepiela P, Coovadia HM, et al. Vitamin A supplementation enhances specific IgG antibody levels and total lymphocyte numbers while improving morbidity in measles. Pediatr Infect Dis J 1992;11(3):203-209.
  • .Cramer DW, Kuper H, Harlow BL, et al. Carotenoids, antioxidants and ovarian cancer risk in pre- and postmenopausal women. Int J Cancer 2001;94(1):128-134.
  • .Cumming RG, Mitchell P, Smith W. Diet and cataract: the Blue Mountains Eye Study. Ophthalmology 2000;107(3):450-456.
  • .Curtis JL, Swicord W. Effects of medication of plasma vitamin A concentrations. Clin Chem 1976;22(5):695. (Letter)
  • .Dai G, Chou N, He L, et al. Retinoid X receptor alpha regulates the expression of glutathione s-transferase genes and modulates acetaminophen-glutathione conjugation in mouse liver. Mol Pharmacol 2005;68(6):1590-1596.
  • .Dalmiya N, Palmer A, Darnton-Hill I. Sustaining vitamin A supplementation requires a new vision. Lancet 2006;368(9541):1052-1054. (Letter)
  • .de Botton S, Coiteux V, Chevret S, et al. Outcome of childhood acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy. J Clin Oncol 2004;22(8):1404-1412.
  • .DeLaney TF, Afridi N, Taghian AG, et al. 13-cis-Retinoic acid with alpha-2a-interferon enhances radiation cytotoxicity in head and neck squamous cell carcinoma in vitro. Cancer Res 1996;56:2277-2280.
  • .de Menezes AC, Costa IM, El-Guindy MM. Clinical manifestations of hypervitaminosis A in human gingiva: a case report. J Periodontol 1984;55(8):474-476.
  • .De-Souza DA, Greene LJ. Pharmacological nutrition after burn injury. J Nutr 1998;128:797-803.
  • .Dorgan JF, Sowell A, Swanson CA, et al. Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States). Cancer Causes Control 1998;9(1):89-97.
  • .Drott PW, Meurling S, Kulander L, et al. Effects of vitamin A on endotoxaemia in rats. Eur J Surg 1991;157(10):565-569.
  • .Dvorak AM. Vitamin A in Crohn’s disease. Lancet 1980;1(8181):1303-1304.
  • .Eckhoff C, Nau H. Vitamin A supplementation increases levels of retinoic acid compounds in human plasma: possible implications for teratogenesis. Arch Toxicol 1990;64(6):502-503.
  • .Elinder LS, Hadell K, Johansson J, et al. Probucol treatment decreases serum concentrations of diet-derived antioxidants. Arterioscler Thromb Vasc Biol 1995;15(8):1057-1063.
  • .Ehrlich HP, Hunt TK. Effects of cortisone and vitamin A on wound healing. Ann Surg 1968;167(3):324-328.
  • .Facchini F, Coulston AM, Reaven GM. Relation between dietary vitamin intake and resistance to insulin-mediated glucose disposal in healthy volunteers. Am J Clin Nutr 1996;63:946-949.
  • .Faloon WW. Metabolic effects of nonabsorbable antibacterial agents. Am J Clin Nutr 1970;23(5):645-651.
  • .Faloon WW, Paes IC, Woolfolk D, et al. Effect of neomycin and kanamycin upon intestinal absorption. Ann N Y Acad Sci 1966;132(2):879-887.
  • .Farmer JA, Gotto AM Jr. Antihyperlipidaemic agents: drug interactions of clinical significance. Drug Safety 1994;11(5):301-309.
  • .Farmer JA, Gotto AM Jr. Choosing the right lipid-regulating agent: a guide to selection. Drugs 1996;52(5):649-661.
  • .Fawzi WW. Vitamin A supplementation and child mortality. JAMA 1993;269:898-903.
  • .Fawzi WW, Mbise R, Spiegelman D, et al. Vitamin A supplements and diarrheal and respiratory tract infections among children in Dar es Salaam, Tanzania. J Pediatr 2000;137:660-667.
  • .Fawzi WW, Msamanga G, Hunter D, et al. Randomized trial of vitamin supplements in relation to vertical transmission of HIV-1 in Tanzania. J Acquired Immune Defic Syndrome 2000;23(3):246-254.
  • .Fawzi W, Msamanga G, Spiegelman D, et al. Transmission of HIV-1 through breastfeeding among women in Dar es Salaam, Tanzania. J Acquired Immune Defic Syndrome 2002;31(3):331-338.
  • .Fenech M. Recommended dietary allowances (RDAs) for genomic stability. Mutat Res 2001;480-481:51-54.
  • .Fenech M, Baghurst P, Luderer W, et al. Low intake of calcium, folate, nicotinic acid, vitamin E, retinol, beta-carotene and high intake of pantothenic acid, biotin and riboflavin are significantly associated with increased genome instability: results from a dietary intake and micronucleus index survey in South Australia. Carcinogenesis 2005;26(5):991-999.
  • .Feskanich D, Singh V, Willett WC, et al. Vitamin A intake and hip fractures among postmenopausal women. JAMA 2002;287(1):47-54.
  • .Field CJ, Johnson IR, Schley PD. Nutrients and their role in host resistance to infection. J Leukoc Biol 2002;71(1):16-32.
  • .Food and Nutrition Board, Institute of Medicine. Vitamin A: dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press; 2001:65-126.
  • .Fortes C, Forastiere F, Agabiti N, et al. The effect of zinc and vitamin A supplementation on immune response in an older population. J Am Geriatr Soc 1998;46:19-26.
  • .Frame B, Jackson CE, Reynolds WA, et al. Hypercalcemia and skeletal effects in chronic hypervitaminosis A. Ann Intern Med 1974;80(1):44-48.
  • .Franceschi S. Micronutrients and breast cancer. Eur J Cancer Prev 1997;6(6):535-539.
  • .French AL, Kirstein LM, Massad LS, et al. Association of vitamin A deficiency with cervical squamous intraepithelial lesions in human immunodeficiency virus-infected women. J Infect Dis 2000;182(4):1084-1089.
  • .Futoryan T, Gilchrest BA. Retinoids and the skin. Nutr Rev 1994;52:299-310.
  • .Gabriel EP, Lindquist BL, Abud RL, et al. Effect of vitamin A deficiency on the adherence of fimbriated and nonfimbriated Salmonella typhimurium to isolated small intestinal enterocytes. J Pediatr Gastroenterol Nutr 1990;10:530-535.
  • .Gaby SK, Bendich A, Singh VN, et al, eds. Vitamin intake and health: a scientific review. New York: Marcel Dekker; 1991:36-39.
  • .Gardner EM, Bernstein ED, Popoff KA, et al. Immune response to influenza vaccine in healthy elderly: lack of association with plasma beta-carotene, retinol, alpha-tocopherol, or zinc. Mech Ageing Dev 2000;117(1-3):29-45.
  • .Genser D, Kang M-H, Vogelsang H, et al. Status of lipidsoluble antioxidants and TRAP in patients with Crohn’s disease and healthy controls. Eur J Clin Nutr 1999;53:675-679.
  • .Gerster H. Anticarcinogenic effect of common carotenoids. Int J Vitam Nutr Res 1993;63:93-121.
  • .Gilchrest BA. Treatment of photodamage with topical tretinoin: an overview. J Am Acad Dermatol 1997;36(3 Pt 2):S27-S36. (Review)
  • .Glasziou PP, Mackerras DEM. Vitamin A supplementation in infectious diseases: a meta-analysis. BMJ 1993;306:366-370.
  • .Gollnick HP, Krautheim A. Topical treatment in acne: current status and future aspects. Dermatology 2003;206(1):29-36. (Review)
  • .Greenberg ER, Baron JA, Tosteson TD, et al. A clinical trial of antioxidant vitamins to prevent colorectal adenoma: Polyp Prevention Study Group. N Engl J Med 1994;331(3):141-147.
  • .Granot E, Kohen R. Oxidative stress in abetalipoproteinemia patients receiving long-term vitamin E and vitamin A supplementation. Am J Clin Nutr 2004;79(2):226-230.
  • .Gueguen S, Leroy P, Gueguen R, et al. Genetic and environmental contributions to serum retinol and [alpha]-tocopherol concentrations: the Stanislas Family Study. Am J Clin Nutr 2005;81(5):1034-1044.
  • .Gueguen S, Pirollet P, Leroy P, et al. Changes in serum retinol, alpha-tocopherol, vitamin C, carotenoids, zinc and selenium after micronutrient supplementation during alcohol rehabilitation. J Am Coll Nutr 2003;22(4):303-310.
  • .Guénégou A, Leynaert B, Pin I, et al. Serum carotenoids, vitamins A and E, and 8 year lung function decline in a general population. Thorax 2006;61:320-326.
  • .Hak AE, Ma J, Powell CB, et al. Prospective study of plasma carotenoids and tocopherols in relation to risk of ischemic stroke. Stroke 2004;35(7):1584-1588.
  • .Hammond BR Jr, Wooten BR, Curran-Celentano J. Carotenoids in the retina and lens: possible acute and chronic effects on human visual performance. Arch Biochem Biophys 2001;385(1):41-46.
  • .Hanekom WA, Potgieter S, Hughes EJ, et al. Vitamin A status and therapy in childhood pulmonary tuberculosis. J Pediatr 1997;131(6):925-927.
  • .Harrell CC, Kline SS. Vitamin K-supplemented snacks containing olestra: implication for patients taking warfarin. JAMA 1999;282(12):1133-1134. (Letter)
  • .Hatchigian EA, Santon JE, Broitman SA, et al. Vitamin A supplementation improves macrophage function and bacterial clearance during experimental Salmonella infection. PSEBM 1989;191:47-54.
  • .Hathcock JN, Hattan DG, Jenkins MY, et al. Evaluation of vitamin A toxicity. Am J Clin Nutr 1990;52(2):183-202.
  • .Hathcock JN. Metabolic mechanisms of drug-nutrient interactions. Fed Proc 1985;44(1 Pt 1):124-129. (Review)
  • .Hardison WG, Rosenberg IH. The effect of neomycin on bile salt metabolism and fat digestion in man. J Lab Clin Med 1969;74(4):564-573.
  • .Heber D, Bowerman S. Applying science to changing dietary patterns. J Nutr 2001;131(11 Suppl):3078S-3081S. (Review)
  • .Hemila H, Virtamo J, Albanes D, et al. Vitamin E and beta-carotene supplementation and hospital-treated pneumonia incidence in male smokers. Chest 2004;125:557-565.
  • .Hendler SS, Rorvik DR, eds. PDR for nutritional supplements. Montvale, NJ: Medical Economics Company, Inc; 2001.
  • .Henquin N, Havivi E, Reshef A, et al. Nutritional monitoring and counselling for cancer patients during chemotherapy. Oncology 1989;46(3):173-177.
  • .Hercberg S, Preziosi P, Galan P, et al. “The SU.VI.MAX Study”: a primary prevention trial using nutritional doses of antioxidant vitamins and minerals in cardiovascular diseases and cancers: SUpplementation on VItamines et Mineraux AntioXydants. Food Chem Toxicol 1999;37(9-10):925-930.
  • .Hill FW. An investigation of the effects of oral neomycin on intestinal absorption and serum cholesterol levels in the dog. Br Vet J 1973;129(4):337-344.
  • .Hodis HN, Mack WJ, LaBree L, et al. Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis. JAMA 1995;273(23):1849-1854.
  • .Hoffer A. High doses of antioxidants including vitamin C do not decrease the efficacy of chemotherapy. Townsend Letter for Doctors and Patients 2000;204:120-121. (Letter)
  • .Hoffer A. Orthomolecular oncology. In: Quillin P, Williams RM, eds. Adjuvant nutrition in cancer treatment (1992 Symposium proceedings sponsored by the Cancer Treatment Research Foundation and the American College of Nutrition). Arlington Heights, Ill: Cancer Treatment Research Foundation; 1994:331-362.
  • .Holt GA. Food and drug interactions. Chicago: Precept Press, 1998.
  • .Hozumi M, Murata T, Morinobu T, et al. Plasma beta-carotene, retinol, and alpha-tocopherol levels in relation to glycemic control of children with insulin-dependent diabetes mellitus. J Nutr Sci Vitaminol (Tokyo) 1998;44(1):1-9.
  • .Hulten K, Van Kappel AL, Winkvist A, et al. Carotenoids, alpha-tocopherols, and retinol in plasma and breast cancer risk in northern Sweden. Cancer Causes Control 2001;12(6):529-537.
  • .Hunter DJ, Manson JE, Colditz GA, et al. A prospective study of the intakes of vitamins C, E, and A and the risk of breast cancer. N Engl J Med 1993;329:234-240.
  • .Hussey GD, Klein M. A randomized, controlled trial of vitamin A in children with severe measles. N Engl J Med 1990;323(3):160-164.
  • .Jacques PF. The potential preventive effects of vitamins for cataract and age-related macular degeneration. Int J Vitam Nutr Res 1999;69(3):198-205.
  • .Janne PA, Mayer RJ. Chemoprevention of colorectal cancer. N Engl J Med 2000;342(26):1960-1968. (Review)
  • .Kang S, Fisher GJ. Voorhees JJ. Photoaging: pathogenesis, prevention, and treatment. Clin Geriatr Med 2001;17(4):643-659.
  • .Kapil U. Evaluation of vitamin A status during pregnancy. J Indian Med Assoc 2003;101(3):206.
  • .Karyadi E, West CE, Schultink W, et al. A double-blind, placebo-controlled study of vitamin A and zinc supplementation in persons with tuberculosis in Indonesia: effects on clinical response and nutritional status. Am J Clin Nutr 2002;75(4):720-727.
  • .Kaul S, Olson JA. Effect of vitamin A deficiency on the hydrolysis of retinoyl beta-glucuronide to retinoic acid by rat tissue organelles in vitro. Int J Vitam Nutr Res 1998;68(4):232-236.
  • .Kawahara TN, Krueger DC, Engelke JA, et al. Short-term vitamin A supplementation does not affect bone turnover in men. J Nutr 2002;132(6):1169-1172.
  • .Kennedy DD, Tucker KL, Ladas ED, et al. Low antioxidant vitamin intakes are associated with increases in adverse effects of chemotherapy in children with acute lymphoblastic leukemia. Am J Clin Nutr 2004;79(6):1029-1036.
  • .Kindmark A, Rollman O, Mallmin H, et al. Oral isotretinoin therapy in severe acne induces transient suppression of biochemical markers of bone turnover and calcium homeostasis. Acta Derma Venereol 1998;78:266-269.
  • .Kligman AM, Mills OH Jr, Leyden JJ, et al. Oral vitamin A in acne vulgaris: preliminary report. Int J Dermatol 1981;20(4):278-285.
  • .Krausz MM, Feinsod M, Beller AJ. Bilateral transverse sinus obstruction in benign intracranial hypertension due to hypervitaminosis A. Isr J Med Sci 1978;14(8):858-861.
  • .Kummet T, Moon TE, Meyskens FL Jr. Vitamin A: evidence for its preventive role in human cancer. Nutr Cancer 1983;5(2):96-106. (Review)
  • .Kune GA, Bannerman S, Field B, et al. Diet, alcohol, smoking, serum beta-carotene, and vitamin A in male nonmelanocytic skin cancer patients and controls. Nutr Cancer 1992;18:237-244.
  • .Kurie JM, Lotan R, Lee JJ, et al. Treatment of former smokers with 9-cis-retinoic acid reverses loss of retinoic acid receptor-beta expression in the bronchial epithelium: results from a randomized placebo-controlled trial. J Natl Cancer Inst 2003;95(3):206-214.
  • .Kuroki F, Iida M, Tominaga M, et al. Multiple vitamin status in Crohn’s disease. Dig Dis Sci 1993;38(9):1614-1618.
  • .Kuznetsova LM, Kovaleva VM. [Effect of cortisone on the content and conversion of vitamin A forms in rats.] Ukr Biokhim Zh 1965;37(3):397-404. [Ukrainian]
  • .Lachili B, Faure H, Smail A, et al. Plasma vitamin A, E, and beta-carotene levels in adult post-partum Algerian women. Int J Vitam Nutr Res 1999;69(4):239-242.
  • .Landrum JT, Bone RA, Kilburn MD. The macular pigment: a possible role in protection from age-related macular degeneration. Adv Pharmacol 1997;38:537-556.
  • .Lee IH, Lee JH, Lee MJ, et al. Involvement of CCAAT/enhancer-binding protein alpha in haptoglobin gene expression by all-trans-retinoic acid. Biochem Biophys Res Commun 2002;294(5):956-961.
  • .Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr 1999;69(6):1071-1085.
  • .Leonard JP, Desager JP, Beckers C, et al. In vitro binding of various biological substances by two hypocholesterolaemic resins: cholestyramine and colestipol. Arzneimittelforschung 1979;29(7):979-981.
  • .Levy AP, Friedenberg P, Lotan R, et al. The effect of vitamin therapy on the progression of coronary artery atherosclerosis varies by haptoglobin type in postmenopausal women. Diabetes Care 2004;27(4):925-930.
  • .Lindeboom GA. Historical milestones in the treatment of night blindness. Clio Med 1984;19(1-2):40-49.
  • .Lippman SM, Kavanagh JJ, Parades M, et al. 13-cis-Retinoic acid (13-cRA), interferon 2a and radiotherapy for locally advanced cancer of cervix. Proc Am Soc Clin Oncol 1993;12:257.
  • .Lips P. Hypervitaminosis A and fractures. N Engl J Med 2003;348(4):347-349.
  • .Lithgow DM, Politzer WM. Vitamin A in the treatment of menorrhagia. Afr Med J 1977;51(7):191-193.
  • .Liu T, Soong SJ, Wilson NP, et al. A case control study of nutritional factors and cervical dysplasia. Cancer Epidemiol Biomarkers Prev 1993;2(6):525-530.
  • .Longnecker JB, Basu SG. Effects of cholestyramine on absorption of amino acids and vitamin A in man. Fed Proc 1965;24:375.
  • .Longnecker MP, Newcomb PA, Mittendorf R, et al. Intake of carrots, spinach, and supplements containing vitamin A in relation to risk of breast cancer. Cancer Epidemiol Biomarkers Prev 1997;6(11):887-892.
  • .Lyle BJ, Mares-Perlman JA, Klein BE, et al. Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study. Am J Epidemiol 1999;149:801-809.
  • .Lynch SR. Interaction of iron with other nutrients. Nutr Rev 1997;55(4):102-110. (Review)
  • .Macsai MS, Agarwal S, Gamponia E. Bilateral corneal ulcers in primary vitamin A deficiency. Cornea 1998;17(2):227-229.
  • .Mahmood T, Tenenbaum S, Niu XT, et al. Prevention of duodenal ulcer formation in the rat by dietary vitamin A supplementation. JPEN J Parenter Enteral Nutr 1986;10(1):74-77.
  • .Malvy DJ, Favier A, Faure H, et al. Effect of two years’ supplementation with natural antioxidants on vitamin and trace element status biomarkers: preliminary data of the SU.VI.MAX study. Cancer Detect Prev 2001;25(5):479-485.
  • .March of Dimes. Accutane and other retinoids. 2002. Available at: http://www.marchofdimes.com/professionals/681_1168.asp. Accessed January 19, 2003.
  • .Mares-Perlman JA, Brady WE, Kleain R, et al. Serum antioxidants and age-related macular degeneration in a population-based case-control study. Arch Ophthalmol 1995;113:1518-1523.
  • .Marrakchi S, Kim I, Delaporte E, et al. Vitamin A and E blood levels in erythrodermic and pustular psoriasis associated with chronic alcoholism. Acta Derm Venereol 1994;74:298-230.
  • .Martinoli L, Di Felice M, Seghieri G, et al. Plasma retinol and alpha-tocopherol concentrations in insulin-dependent diabetes mellitus: their relationship to microvascular complications. Int J Vitam Nutr Res 1993;63(2):87-92.
  • .Marz R. Medical nutrition from Marz. 2nd ed. Portland, OR: Omni Press; 1997.
  • .Mastroiacovo P, Mazzone T, Addis A, et al. High vitamin A intake in early pregnancy and major malformations: a multicenter prospective controlled study. Teratology 1999;59:7-11.
  • .Mathews-Roth MM, Pathak MA , Fitzpatrick TB, et al. Beta carotene therapy for erythropoietic protoporphyria and other photosensitivity diseases. Arch Dermatol 1977;113(9):1229-1232.
  • .McCullough FS, Northrop-Clewes CA, Thurnham DI. The effect of vitamin A on epithelial integrity. Proc Nutr Soc 1999;58(2):289-293. (Review)
  • .McKee DL. A scientific review of natural products that support healthy antioxidant function. Batesville, AR: GP Publications; 2001.
  • .McLaren DS. Vitamin A deficiency disorders. J Indian Med Assoc 1999;97(8):320-323.
  • .Megson MN. Is autism a G-alpha protein defect reversible with natural vitamin A? Med Hypotheses 2000;54(6):979-983.
  • .Meigel WN. How safe is oral isotretinoin? Dermatology 1997;195(Suppl 1):22-28, 38-40. (Review)
  • .Meyer NA, Muller MJ, Herndon DN. Nutrient support of the healing wound. N Horiz 1994;2(2):202-214.
  • .Meyskens FL Jr. Role of vitamin A and its derivatives in the treatment of human cancer. In: Prasad KN, Santamaria L, Williams RM, eds. Nutrients in cancer prevention and treatment. Totowa, NJ: Humana Press; 349-362;1995.
  • .Meyskens FL Jr, Kopecky KJ, Appelbaum FR, et al. Effects of vitamin A on survival in patients with chronic myelogenous leukemia: a SWOG randomized trial. Leuk Res 1995;19(9):605-612.
  • .Meyskens FL Jr, Surwit E, Moon TE, et al. Enhancement of regression of cervical intraepithelial neoplasia II (moderate dysplasia) with topically applied all-trans-retinoic acid: a randomized trial. J Natl Cancer Inst 1994;86(7):539-543.
  • .Michaelsson K, Lithell H, Vessby B, et al. Serum retinol levels and the risk of fracture. N Engl J Med 2003;348(4):287-294.
  • .Michaud DS, Feskanich D, Rimm EB, et al. Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts. Am J Clin Nutr 2000;72(4):990-997.
  • .Michels KB, Holmberg L, Bergkvist L, et al. Dietary antioxidant vitamins, retinol, and breast cancer incidence in a cohort of Swedish women. Int J Cancer 2001;91(4):563-567.
  • .Mitchell AA. Oral retinoids: what should the prescriber known about their teratogenic hazards among women of child-bearing potential? Drug Safety 1992;7(2):79-85. (Review)
  • .Mooij PN, Thomas CM, Doesburg WH, et al. The effects of oral contraceptives and multivitamin supplementation on serum ferritin and hematological parameters. Int J Clin Pharmacol Ther Toxicol 1992;30(2):57-62.
  • .Moon TE, Levine N, Cartmel B, et al. Effect of retinol in preventing squamous cell skin cancer in moderate-risk subjects: a randomized, double-blind, controlled trial. Cancer Epidemiol Biomarkers Prev 1997;6(11):949-956.
  • .Moss RW. Antioxidants against cancer. Brooklyn, NY: Equinox Press, Inc; 2000:33.
  • .Nagao A, Olson JA. Enzymatic formation of 9-cis, 13-cis, and all-trans retinals from isomers of beta-carotene. FASEB J 1994;8(12):968-973. Erratum in FASEB J 1995;9(8):691.
  • .Nagata C, Shimizu H, Higashiiwai H, et al. Serum retinal level and risk of subsequent cervical cancer in cases with cervical dysplasia. Cancer Invest 1999;17(4):253-258.
  • .Nau H, Tzimas G, Mondry M, et al. Antiepileptic drugs alter endogenous retinoid concentrations: a possible mechanism of teratogensis of anticonvulsant therapy. Life Sci 1995;57:53-60.
  • .Neuzil KM, Gruber WC, Chytil F, et al. Safety and pharmacokinetics of vitamin A therapy for infants with respiratory syncytial virus infections. Antimicrob Agents Chemother 1995;39(5):1191-1193.
  • .Neuzil KM, Gruber WC, Chytil F, et al. Serum vitamin A levels in respiratory syncytial virus infection. J Pediatr 1994;124(3):433-436.
  • .Neuzil KM, Gruber WC, Graham BS. Vitamin A therapy for respiratory syncytial virus infection. Pediatr Infect Dis J 1997;16(1):84-85.
  • .NRC (National Research Council). Diet and health: implications for reducing chronic disease risk. Washington, DC: The National Academy Press; 1989:516.
  • .Olson JA. Bioavailability of carotenoids. Arch Latinoam Nutr 1999;49(3 Suppl 1):21S-25S.
  • .Olson JA. Carotenoids and human health. Arch Latinoam Nutr 1999;49(3 Suppl 1):7S-11S. (Review)
  • .Olson JA. Provitamin A function of carotenoids: the conversion of beta-carotene into vitamin A. J Nutr 1989;119(1):105-108. (Review)
  • .Olson JA. The conversion of carotene to vitamin A (Thomas Moore, 1930). J Nutr 1997;127(5 Suppl):1036S-1038S.
  • .Olson JA. Vitamin A. In: Ziegler EE, Filer LJ, eds. Present knowledge in nutrition. 7th ed. Washington, DC: ILSI Press; 1996:109-118.
  • .Olson JA. Vitamin A and carotenoids as antioxidants in a physiological context. J Nutr Sci Vitaminol (Tokyo) 1993;39(Suppl):S57-S65. (Review)
  • .Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996;334(18):1150-1155.
  • .Omenn GS, Goodman GE, Thornquist MD, et al. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst 1996;88(21):1550-1559. (Abstract)
  • .Omenn GS, Goodman G, Thornquist M, et al. The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos exposed workers. Cancer Res 1994;54:2038S-2043S.
  • .Ozpolat B, Lopez-Berestein G, Adamson P, et al. Pharmacokinetics of intravenously administered liposomal all-trans-retinoic acid (ATRA) and orally administered ATRA in healthy volunteers. J Pharm Pharm Sci 2003;6(2):292-301.
  • .Patel P, Hanning RM, Atkinson SA, et al. Intoxication from vitamin A in an asthmatic child. CMAJ 1988;139:755-756.
  • .Patrick L. Nutrients and HIV: part 2: vitamins A and E, zinc, B-vitamins, and magnesium. Altern Med Rev 2000;5(1):39-51.
  • .Penniston KL, Tanumihardjo SA. The acute and chronic toxic effects of vitamin A. Am J Clin Nutr 2006;83:191-201. (Review)
  • .Perrotta S, Nobili B, Rossi F, et al. Vitamin A and infancy: biochemical, functional, and clinical aspects. Vitam Horm 2003;66:457-591. (Review)
  • .Polidori MC, Mecocci P, Stahl W, et al. Plasma levels of lipophilic antioxidants in very old patients with type 2 diabetes. Diabetes Metab Res Rev 2000;16:15-19.
  • .Prakash P, Krinsky NI, Russell RM. Retinoids, carotenoids, and human breast cancer cell cultures: a review of differential effects. Nutr Rev 2000;58(6):170-176. (Review)
  • .Prasad AS, Oberleas D, Moghissi KS, et al. Effect of oral contraceptive agents on nutrients: II: vitamins. Am J Clin Nutr 1975;28(4):385-391.
  • .Prasad KN, Cole WC, Hovland P. Cancer prevention studies: past, present and future. Nutrition 1998;14:197-210.
  • .Prasad KN, Cole WC, Kumar B, et al. Scientific rationale for using high-dose multiple micronutrients as an adjunct to standard and experimental cancer therapies. J Am Coll Nutr 2001; 20(5 Suppl):450S-463S, 473S-475S.
  • .Prasad KN, Edwards-Prasad J. Expressions of some molecular cancer risk factors and their modification by vitamins. J Am Coll Nutr 1990;9:28-34.
  • .Prasad KN, Kumar R. Effect of individual antioxidant vitamins alone and in combination on growth and differentiation of human non-tumorigenic and tumorigenic parotid acinar cells in culture. Nutr Cancer 1996;26:11-19.
  • .Prasad KN, Kumar A, Kochupillai MD, et al. High doses of multiple antioxidant vitamins: essential ingredients in improving the efficacy of standard cancer therapy. J Am Coll Nutr 1999b;18:13-25.
  • .Pratt S. Dietary prevention of age-related macular degeneration. J Am Optom Assoc 1999;70:39-47.
  • .Promislow JH, Goodman-Gruen D, Slymen DJ, et al. Retinol intake and bone mineral density in the elderly: the Rancho Bernardo Study. J Bone Miner Res 2002;17(8):1349-1358.
  • .Quadro L, Gamble MV, Vogel S, et al. Retinol and retinol-binding protein: gut integrity and circulating immunoglobulins. J Infect Dis 2000;182(Suppl 1):S97-S102.
  • .Race TF, Paes IC, Faloon WW. Intestinal malabsorption induced by oral colchicine: comparison with neomycin and cathartic agents. Am J Med Sci 1970;259(1):32-41.
  • .Ramakrishna BS, Varghese R, Jayakumar S, et al. Circulating antioxidants in ulcerative colitis and their relationship to disease severity and activity. J Gastroenterol Hepatol 1997;12:490-494.
  • .Rasmussen BM, Vessby B, Uusitupa M, et al. Effects of dietary saturated, monounsaturated, and n3 fatty acids on blood pressure in healthy subjects. Am J Clin Nutr 2006;83(2):221-226.
  • .Redlich CA, Chung JS, Cullen MR, et al. Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol EfficacyTrial (CARET). Atherosclerosis 1999;143:427-434.
  • .Rees D, Miles EA, Banerjee T, et al. Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. Am J Clin Nutr 2006;83(2):331-342.
  • .Regoly-Merei A, Ferencz A, Frenkl R, et al. Effect of fat and retinol loading on serum triglyceride and retinol levels in patients with ulcerative colitis. Nahrung 1991;35(1):21-26.
  • .Renner S, Rath R, Rust P, et al. Effects of beta-carotene supplementation for six months on clinical and laboratory parameters in patients with cystic fibrosis. Thorax 2001;56(1):48-52.
  • .Robinson C, Weigly E. Basic nutrition and diet therapy. New York: MacMillan; 1984.
  • .Rock CL, Dechert RE, Khilnani R, et al. Carotenoids and antioxidant vitamins in patients after burn injury. J Burn Care Rehabil 1997;18(3):269-278.
  • .Rock CL, Michael CW, Reynolds RK, et al. Prevention of cervix cancer. Crit Rev Oncol Hematol 2000;33(3):169-185.
  • .Roe DA. Diet and drug interactions. New York: Van Nostrand Reinhold; 1989.
  • .Roe DA. Drug-induced nutritional deficiencies. 2nd ed. Westport, CT: Avi Publishing; 1985.
  • .Roe DA. Risk factors in drug-induced nutritional deficiencies. In: Roe DA, Campbell T, eds. Drugs and nutrients: the interactive effects. New York: Marcel Decker; 1984:505-523.
  • .Rohde CM, DeLuca H. Bone resorption activity of all-trans retinoic acid is independent of vitamin D in rats. J Nutr 2003;133(3):777-783.
  • .Rojas AI, Phillips TJ. Patients with chronic leg ulcers show diminished levels of vitamins A and E, carotenes, and zinc. Dermatol Surg 1999;25(8):601-604.
  • .Roncucci L, Di Donato P, Carati L, et al. Antioxidant vitamins or lactulose for the prevention of the recurrence of colorectal adenomas. Dis Colon Rectum 1993;36(3):227-234.
  • .Ross AC. Vitamin A and retinoids. In: Shils M, ed. Nutrition in health and disease. 9th ed. Baltimore: Williams & Wilkins; 1999:305-327.
  • .Rothman KJ, Moore LL, Singer MR, et al. Teratogenicity of high vitamin A intake. N Engl J Med 1995;333:1369-1373.
  • .Russell RM. The vitamin A spectrum: from deficiency to toxicity. Am J Clin Nutr 2000;71(4):878-884.
  • .Salganik RI. The benefits and hazard of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J Am Coll Nutr 2001;20(5 Suppl):464S-475S.
  • .Salganik R, Albright C, Rodgers J, et al. Enhancement of apoptosis and inhibition of brain tumor growth in transgenic mice by depletion of antioxidants: American Society for Cell Biology Annual Meeting, Washington, DC. Am Soc Cell Biol 1999;444a.
  • .Salganik RI, Albright CD, Rodgers J, et al. Dietary antioxidant depletion: enhancement of tumor apoptosis and inhibition of brain tumor growth in transgenic mice. Carcinogenesis 2000;21(5):909-914.
  • .Sato R, Helzlsouer KJ, Alberg AJ, et al. Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2002;11(5):451-457. (Review)
  • .Saurat JH. Retinoids and psoriasis: novel issues in retinoid pharmacology and implications for psoriasis treatment. J Am Acad Dermatol 1999;41(3 Pt 2):S2-S6.
  • .Schlagheck TG, Riccardi KA, Zorich NL, et al. Olestra dose response on fat-soluble and water-soluble nutrients in humans. J Nutr 1997;127(8 Suppl):1646S-1665S.
  • .Schuurman AG, Goldbohm RA, Brants HA, et al. A prospective cohort study on intake of retinol, vitamins C and E, and carotenoids and prostate cancer risk (Netherlands). Cancer Causes Control 2002;13(6):573-582.
  • .Seddon JM, Ajani UA, Sperduto RD, et al. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. JAMA 1994;272:1413-1420.
  • .Segasothy M, Phillips PA. Vegetarian diet: panacea for modern lifestyle diseases? QJM 1999;92(9):531-544.
  • .Seifter E, Rettura A, Padawar J, et al. Vitamin A and beta-carotene as adjunctive therapy to tumor excision, radiation therapy and chemotherapy. In: Prasad KN, ed. Vitamins, nutrition and cancer. Basel, Switzerland: Karger; 1984:1-19.
  • .Semba RD. Impact of vitamin A on immunity and infection in developing countries. In: Bendich A, Decklebaum RJ, eds. Preventive nutrition: the comprehensive guide for health professionals. 2nd ed. Totowa, NJ: Humana Press, Inc; 2001:329-346.
  • .Semba RD. The role of vitamin A and related retinoids in immune function. Nutr Rev 1998;56(1 Pt 2):S38-S48.
  • .Semba RD. Vitamin A and human immunodeficiency virus infection. Proc Nutr Soc 1997;56(1B):459-469.
  • .Semba RD. Vitamin A, immunity and infection. Clin Infect Dis 1994;19:489-499.
  • .Semba RD, Graham NM, Caiaffa WT, et al. Increased mortality associated with vitamin A deficiency during human immunodeficiency virus type 1 infection. Arch Intern Med 1993;153(18):2149-2154.
  • .Semba RD, Miotti PG, Chiphangwi JD, et al. Maternal vitamin A deficiency and mother-to-child transmission of HIV-1. Lancet 1994;343(8913):1593-1597.
  • .Shekelle RB, Lepper M, Liu S, et al. Dietary vitamin A and risk of cancer in the Western Electric Study. Lancet 1981;2(8257):1185-1190.
  • .Shepherd AA. Nutrition for optimum wound healing. Nurs Stand 2003;18(6):55-58. (Review)
  • .Sherman SI, Gopal J, Haugen BR. Central hypothyroidism associated with Retinoid X receptor-selective ligands. N Engl J Med 1999;340:1075-1079.
  • .Shi HL, Olson JA. Site of conversion of endogenous all-trans-retinoids to 11-cis-retinoids in the bovine eye. Biochim Biophys Acta 1990;1035(1):1-5.
  • .Sibulesky L, Hayes KC, Pronczuk A, et al. Safety of <7500 RE (<25000 IU) vitamin A daily in adults with retinitis pigmentosa. Am J Clin Nutr 1999;69:656-663.
  • .Silvagno F, Guarnieri V, Capizzi A, et al. Synergistic effect of retinoic acid and dehydroepiandrosterone on differentiation of human neuroblastoma cells. FEBS Lett 2002;532(1-2):153-158.
  • .Simone CB, Simone NL, Simone CB. Nutrients and cancer treatment. Int J Integrative Med 1999;1:20-24.
  • .Simsek M, Naziroglu M, Simsek H, et al. Blood plasma levels of lipoperoxides, glutathione peroxidase, beta carotene, vitamin A and E in women with habitual abortion. Cell Biochem Funct 1998;16(4):227-231.
  • .Smith MA, Parkinson DR, Cheson BD, et al. Retinoids in cancer therapy. J Clin Oncol 1992;10(5):839-864.
  • .Smith W, Mitchell P, Webb K, et al. Dietary antioxidants and age-related maculopathy: the Blue Mountains Eye Study. Ophthalmology 1999;106(4):761-767.
  • .Smolle J, Wawschinek O, Hayn H, et al. [Vitamin A and carotene in thyroid disease.] Acta Med Austriaca 1983;10:71-73. [German]
  • .Sowers MF, Lachance L. Vitamins and arthritis: the roles of vitamins A, C, D, and E. Rheum Dis Clin North Am 1999;25(2):315-331.
  • .Sporn MB, Roberts AB. Role of retinoids in differentiation and carcinogenesis. Cancer Res 1983;43:3034-3040.
  • .Sporn M, Roberts A, Goodman D. The retinoids: biology, chemistry and medicine. New York: Raven Press; 1994.
  • .Steineck G, Hagman U, Gerhardsson M, et al. Vitamin A supplements, fried foods, fat and urothelial cancer: a case-referent study in Stockholm in 1985-87. Int J Cancer 1990;45(6):1006-1011.
  • .Stich HF, Mathew B, Sankaranarayanan R, et al. Remission of precancerous lesions in the oral cavity of tobacco chewers and maintenance of the protective effect of beta-carotene or vitamin A. Am J Clin Nutr1991;53(1 Suppl):298S-304S. (Review)
  • .Stratton SP, Dorr RT, Alberts DS. The state-of-the art in chemoprevention of skin cancer. Eur J Cancer 2000;36(10):1292-1297.
  • .Straub RH, Rokitzki L, Schumacher T, et al. No evidence of deficiency of vitamins A, E, beta-carotene, B1, B2, B6, B12 and folate in neuropathic non-insulin-dependent diabetic women. Int J Vitam Nutr Res 1993;63(3):239-240.
  • .Strosser AV, Nelson LS. Synthetic vitamin A in the treatment of eczema in children. Ann Allergy 1952;10:703-704.
  • .Sturniolo GC, Mestriner C, Lecis PE, et al. Altered plasma and mucosal concentrations of trace elements and antioxidants in active ulcerative colitis. Scand J Gastroenterol 1998;33(6):644-649.
  • .Suan EP, Bedrossian EH Jr, Eagle RC Jr, et al. Corneal perforation in patients with vitamin A deficiency in the United States. Arch Ophthalmol 1990;108(3):350-353.
  • .Thompson HJ, Meeker LD, Becci PJ. Effect of combined selenium and retinyl acetate treatment on mammary carcinogenesis. Cancer Res 1981;41(4):1413-1416.
  • .Thornquist MD, Kristal AR, Patterson RE, et al. Olestra consumption does not predict serum concentrations of carotenoids and fat-soluble vitamins in free-living humans: early results from the sentinel site of the olestra post-marketing surveillance study. J Nutr 2000;130(7):1711-1718.
  • .Threlkeld DS, ed. Diuretics and Cardiovasculars, antihyperlipidemic agents, bile acid sequestrants. In: Facts and Comparisons drug information. St Louis: Facts and Comparisons; 1997:171i–171l.
  • .Thurnham DI, Northrop-Clewes CA. Optimal nutrition: vitamin A and the carotenoids. Proc Nutr Soc 1999;58(2):449-457.
  • .Tomita Y. Immunological role of vitamin A and its related substances in prevention of cancer. Nutr Cancer 1983;5(3-4):187-194.
  • .Trovato A, Nuhlicek DN, Midtling JE. Drug-nutrient interactions. Am Fam Physician 1991;44(5):1651-1658.(Review)
  • .Tyson JE, Wright LL, Oh W, et al. Vitamin A supplementation for extremely-low-birth-weight infants. N Engl J Med 1999;340:1962-1968.
  • .Underwood BA, Arthur P. The contribution of vitamin A to public health. FASEB J 1996;10(9):1040-1048.
  • .USDA: Composition of foods. USDA handbook #8. Washington, DC: ARS, USDA; 1976-1986.
  • .van Dam RM, Huang Z, Giovannucci E, et al. Diet and basal cell carcinoma of the skin in a prospective cohort of men. Am J Clin Nutr 2000;71(1):135-141.
  • .van Soest S, Westerveld A, de Jong PT, et al. Retinitis pigmentosa: defined from a molecular point of view. Surv Ophthalmol 1999;43(4):321-334.
  • .van Zandwijk N, Dalesio O, Pastorino U, et al. EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer: for the European Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups. J Natl Cancer Inst 2000;92(12):959-960.
  • .Villamor E, Fawzi WW. Vitamin A supplementation: implications for morbidity and mortality in children. J Infect Dis 2000;182(Suppl 1):S122-S133.
  • .Villamor E, Mbise R, Spiegelman D, et al. Vitamin A supplements ameliorate the adverse effect of HIV-1, malaria, and diarrheal infections on child growth. Pediatrics 2002;109(1):E6.
  • .Von Lennep E, El Khazen N, De Pierreux G, et al. A case of partial sirenomelia and possible vitamin A teratogenesis. Prenat Diagn 1985;5(1):35-40.
  • .Vourlekis JS, Szabo E. Predicting success in cancer prevention trials. J Natl Cancer Inst 2003;95(3):178-179.
  • .Wang XD. Chronic alcohol intake interferes with retinoid metabolism and signaling. Nutr Rev 1999;57(2):51-59.
  • .Watkins DW, Khalafi R, Cassidy MM, et al. Alterations in calcium, magnesium, iron, and zinc metabolism by dietary cholestyramine. Dig Dis Sci 1985;30(5):477-482.
  • .Werbach MR. Foundations of nutritional medicine. Tarzana, CA: Third Line Press; 1997:221-222. (Review)
  • .West CE. Vitamin A and measles. Nutr Rev 2000;58(2 Pt 2):S46-S54.
  • .Wiegand UW, Hartmann S, Hummler H. Safety of vitamin A: recent results. Int J Vitam Nutr Res 1998;68(6):411-416. (Review)
  • .Wolff KM, Scott AL. Brugia malayi: retinoic acid uptake and localization. Exp Parasitol 1995;80(2):282-290.
  • .Wright JP, Mee AS, Parfitt A, et al. Vitamin A therapy in patients with Crohn’s disease. Gastroenterology 1985;88(2):512-514.
  • .Wylie-Rosett JA, Romney SL, Slagle NS, et al. Influence of vitamin A on cervical dysplasia and carcinoma in situ. Nutr Cancer 1984;6(1):49-57.
  • .Wysowski DK, Swann J, Vega A. Use of isotretinoin (Accutane) in the United States: rapid increase from 1992 through 2000. J Am Acad Dermatol 2002;46(4):505-509.
  • .Yamaguchi T. [Effect of various drugs on the abnormality induced by excessive intake of vitamin A: 1: effect of cortisone.] Shikwa Gakuho 1967;67(11):1329-1339. [Japanese]
  • .Yeum K-J, Taylor A, Tang G, et al. Measurement of carotenoids, retinoids, and tocopherols in human lenses. Ophthalmol Vis Sci 1995;36:2756-2761.
  • .Yeum KJ, Ferland G, Patry J, et al. Relationship of plasma carotenoids, retinol and tocopherols in mothers and newborn infants. J Am Coll Nutr 1998;17(5):442-447.
  • .Zambou NF, Mbiapo TF, Lando G, et al. [Effect of Onchocerca volvulus infestation on plasma vitamin A concentration in school children in a rural region of Cameroon.] Cahiers Sant 1999;9:151-155. [French]
  • .Zhan HC, Gudas LJ, Bok D, et al. Differential expression of the enzyme that esterifies retinol, lecithin:retinol acyltransferase, in subtypes of human renal cancer and normal kidney. Clin Cancer Res 2003;9(13):4897-4905.
  • .Zhang S, Hunter DJ, Forman MR, et al. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J Natl Cancer Inst 1999;91(6):547-556.
  • .Zouboulis CC. Retinoids: which dermatological indications will benefit in the near future? Skin Pharmacol Appl Skin Physiol 2001;14(5):303-315.