Vitamin
A (Retinol)
Natural
StandardŽ Patient Monograph, Copyright Š 2007
(www.naturalstandard.com). Commercial distribution prohibited. This
monograph is intended for informational purposes only, and should not
be interpreted as specific medical advice. You should consult with a
qualified healthcare provider before making decisions about therapies
and/or health conditions.
ARTICLE SECTIONS
Background
Synonymss
Evidence
Dosing
Safety
Methodology
Selected references
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Background
Vitamin
A is a fat-soluble vitamin which is derived from two sources: preformed
retinoids and provitamin carotenoids. Retinoids such as retinal,
retinal, and retinoic acid are found in animal sources like liver,
kidney, eggs, and dairy produce. Carotenoids like beta-carotene (which
has the highest vitamin A activity) are found in plants such as dark or
yellow vegetables and carrots.
Natural
retinoids are present in all living organisms, either as preformed
vitamin A or as carotenoids, and are required for a vast number of
biological processes like vision and cellular growth. A major biologic
function of vitamin A (as the metabolite retinal) is in the visual
cycle. Research also suggests that vitamin A may reduce the mortality
rate from measles, prevent some types of cancer, aid in growth and
development, and improve immune function.
Recommended
daily allowance (RDA) levels for vitamin A oral intake have been
established by the U.S. Institute for Medicine of the National Academy
of Sciences to prevent deficiencies in vitamin A. At recommended doses,
vitamin A is generally considered non-toxic. Excess dosing may lead to
acute or chronic toxicity.
Vitamin
A deficiency is rare in industrialized nations but remains a concern in
developing countries, particularly in areas where malnutrition is
common. Prolonged deficiency can lead to xerophthalmia (dry eye) and
ultimately to night blindness or total blindness, as well as to skin
disorders, infections (such as measles), diarrhea, and respiratory
disorders.
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Synonyms
Synonyms
: 3,7-dimethyl-9-(2,6,6,
trimethyl-1-cyclohexen-1-yl)-2,4,6,8-natetraen-1-ol, 3-dehydroretinol,
antixerophthalmic vitamin, axerophtholum, beta-carotene oleovitamin A,
retinaldehyde (RAL), retinyl acetate, retinyl palmitate, vitamin A,
vitamin A1, vitamin A USP, vitaminum A.
Brands : Aquasol AŽ,
Palmitate-AŽ, SolateneŽ.
Combination
products : Vitamin A is included in most multivitamin preparations as
well as in combination with vitamin D in topical products.
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Evidence
These
uses have been tested in humans or animals. Safety and effectiveness
have not always been proven. Some of these conditions are potentially
serious, and should be evaluated by a qualified healthcare provider.
Uses based on scientific
evidence Grade*
Acne
Derivatives
of vitamin A, retinoids, are used to treat skin disorders such as acne.
Topical and oral prescription medications, such as tretinoin (AvitaŽ,
RenovaŽ, Retina-AŽ, Retin-A MicroŽ) and isotretinoin (AccutaneŽ), are
available for treatment. Isotretinoin may cause severe side effects and
should be used only for severe resistant acne. Isotretinoin must not be
used in women who are pregnant, plan to become pregnant, or have a
chance of being pregnant due to a risk of severe birth defects. These
medications should be prescribed and coordinated by a qualified
licensed healthcare professional. Vitamin A supplements should not be
used simultaneously due to a risk of increased
toxicity.
A
Acute promyelocytic
leukemia (treatment, All-trans retinoic acid)
The
prescription drug All- Trans -Retinoic Acid (ATRA, VesanoidŽ) is a
vitamin A derivative which is an established treatment for acute
promyelocytic leukemia and improves median survival in this disease.
Treatment should be under strict medical supervision. Vitamin A
supplements should not be used simultaneously with ATRA due to a risk
of increased toxicity. A
Measles (supportive
agent)
Vitamin
A should be administered to children diagnosed with measles in areas
where vitamin A deficiency may be present. Measles is a viral disease
that can lead to serious complications such as diarrhea, pneumonia, and
encephalitis. Supplementation with vitamin A in children with measles
has been shown to be beneficial, by decreasing the length and impact of
the disease. Side effects such as diarrhea, pneumonia, and death have
been reduced with the use of vitamin A. Management of measles should be
under strict medical supervision. A
Vitamin A deficiency
Vitamin
A deficiency may occur after chronic lack of adequate amounts of
vitamin A or beta-carotene. Vitamin A is necessary for vision, and an
early sign of vitamin A deficiency is keratomalacia (night blindness).
Prolonged deficiency may lead to xerophthalmia (dry eye). Eventually,
blindness can occur due to damage to the retina and cornea. Vitamin A
is necessary for healthy growth and development, and recommended daily
amounts (RDA) should be assured, particularly in
children.
A
Xerophthalmia (dry eye)
Oral
vitamin A is the treatment of choice for xerophthalmia due to prolonged
vitamin A deficiency, and should be given immediately once the disorder
is established. A
Malaria (supportive
agent)
Limited
research suggests that vitamin A may reduce fever, morbidity, and
parasite blood levels in patients with malaria ( Plasmodium falciparum
infection). However, there is no evidence that vitamin A is equivalent
or superior to well-established drug therapies used for prevention or
treatment of malaria. Patients with malaria or living/traveling in
endemic areas should speak with a physician about appropriate
measures. B
Retinitis pigmentosa
Retinitis
pigmentosa is a genetic disorder that affects night vision. Early
symptoms include night blindness and progressive loss of vision over
time. Based on recent findings, 15,000 IU daily of vitamin A in the
palmitate form has been recommended in patients with retinitis
pigmentosa. B
Antioxidant
The benefits to humans
of potential antioxidant activity are not clear.
C
Breast cancer
Research
results are not clear as to whether vitamin A is beneficial in the
treatment or prevention of breast cancer. Patients receiving
chemotherapy or radiation therapy for cancer should speak with their
doctor(s) before taking antioxidants such as vitamin A during
treatment, due to possible interference. C
Cataract prevention
Vitamin
A has been suggested to prevent cataract formation. Carotenoids such as
beta-carotene, lutein, and zeaxanthin may decrease the risk of severe
cataracts. There is not sufficient evidence to form a clear conclusion
at this time. C
Diarrhea
Vitamin
A may reduce the severity and duration of diarrheal episodes in
malnourished children but not in well-nourished children. Since
diarrhea is a major cause of morbidity and mortality in developing
countries, vitamin A supplementation may be considered in
undernourished children with diarrhea. C
HIV Infection
The
role of vitamin A in the prevention, transmission, or treatment of HIV
is controversial and not well established. A clear conclusion cannot be
formed based on the available scientific research.
C
Immune function
Vitamin
A deficiency may compromise immunity, but there is no clear evidence
that additional vitamin A supplementation is beneficial for immune
function in patients who are not vitamin A
deficient.
C
Infant mortality
There
is a limited amount of research in this area, with mixed results. Some
evidence suggests possible decreases in infant mortality with vitamin A
supplementation, while other research reports no benefits. A clear
conclusion cannot be formed based on the available scientific
research. C
Iron deficiency anemia
Vitamin
A supplementation in combination with iron may have beneficial effects
in patients with iron deficiency anemia, including children and
pregnant women. It is not clear that there are benefits in individuals
who are not vitamin A deficient. This area remains controversial, and
further evidence is necessary before a clear conclusion can be
drawn. C
Photoreactive keratectomy
Photoreactive
keratectomy is a type of laser eye surgery used to correct
nearsightedness. High-dose vitamin A supplementation (50,000 to 75,000
units) in addition to vitamin E (230mg) has been suggested to help
improve ocular healing after surgery and to improve visual acuity,
although additional evidence is necessary before a definitive
conclusion can be reached. C
Pneumonia (children)
One
study found no effect of a moderate dose of vitamin A supplementation
on the duration of uncomplicated pneumonia in underweight or
normal-weight children aged <5 years. However, a beneficial
effect
was seen in children with high basal serum retinol
concentrations. C
Polyp prevention
Alpha-carotene
and vitamin A may protect against recurrence of polyps and adenoma in
nonsmokers and nondrinkers or be indicative of compliance or another
healthy lifestyle factor that reduces risk. Further research is needed
before a conclusion can be drawn C
Pregnancy-related
complications
Maternal
vitamin A deficiency is common in developing countries. Beta-carotene
may reduce pregnancy-related complications and mortality in such
individuals. However, excess intake of vitamin A has been reported to
increase the risks of some birth defects. Vitamin A supplementation
above the RDA is therefore not recommended in
pregnancy.
C
Skin cancer prevention
It
is not clear if vitamin A or beta-carotene, taken by mouth or used on
the skin with sunscreen, is beneficial in the prevention or treatment
of skin cancers. C
Weight loss
Daily
vitamin A with calcium has been suggested for weight loss, and in one
study an average loss of 2 pounds was reported after two years of
supplementation in young women. C
Wound healing
In
preliminary study, retinol palmitate significantly reduced rectal
symptoms of radiation proctopathy, perhaps because of wound-healing
effects. Further research is needed to confirm these
results. C
Lung cancer
Vitamin
A has been studied as a possible treatment for lung cancer, without
evidence of benefits. Available evidence suggests that high-dose
Vitamin A and beta-carotene may actually increase the risk of adverse
effects, especially among alcohol users and
smokers. D
Chemotherapy adverse
effects
Vitamin
A supplementation does not appear to improve chemotherapy-related side
effects including nausea, vomiting, diarrhea, or mouth
sores. D
Key to grades
A Strong scientific
evidence for this use
B Good scientific
evidence for this use
C Unclear scientific
evidence for this use
D Fair scientific
evidence against this use (it may not work)
F Strong scientific
evidence against this use (it likely does not work)
Grading
rationale
Uses based on tradition
or theory
The
below uses are based on tradition or scientific theories. They often
have not been thoroughly tested in humans, and safety and effectiveness
have not always been proven. Some of these conditions are potentially
serious, and should be evaluated by a qualified healthcare provider.
Aging,
allergic rhinitis, asthma, atrophic rhinitis, atrophic vaginitis,
blurred vision, bronchopulmonary dysplasia in premature infants, burns,
candidiasis, cellulite (topical retinal), cold sores, conjunctivitis,
Crohn's disease, cystic fibrosis, deafness, diabetes, eczema, enhancing
tissue integrity, fibrocystic breast disease, gastrointestinal
disorders, glaucoma, heart disease, Hurler syndrome, hyperthyroidism,
ichthyosis, infections , keratosis follicularis (Darier's disease),
kidney stones, leukoplakia, lichen planus pigmentosus, liver disease,
menorrhagia, myopia (nearsightedness), neurodegenerative diseases,
periodontal disease, persistent headache, pityriasis rubra pilaris,
plantar warts, pollutant protection, premenstrual syndrome , protein
deficiency, psoriasis, reduced sperm count, sebaceous cysts, sinusitis,
stress ulcers in severely ill hospitalized patients, sunburn, tinnitus,
ulcers, urinary tract infections, wounds, wrinkles.
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Dosing
The
below doses are based on scientific research, publications, traditional
use, or expert opinion. Many herbs and supplements have not been
thoroughly tested, and safety and effectiveness may not be proven.
Brands may be made differently, with variable ingredients, even within
the same brand. The below doses may not apply to all products. You
should read product labels, and discuss doses with a qualified
healthcare provider before starting therapy.
Standardization:
As
retinol activity equivalents (RAEs), 1 RAE = 1 mcg retinal, 12 mcg
beta-carotene, 24 mcg alpha-carotene, or 24 mcg beta cryptoxanthin in
foods. To calculate RAEs from REs of provitamin A carotenoids in foods,
divide the REs by 2. For preformed vitamin A in foods or supplements
and for provitamin A carotenoids in supplements, 1 RE=1 RAE.
Sources
of vitamin A : Vitamin A is found in dairy products, fish, darkly
colored fruits and vegetables. Consumption of 5 servings of fruits and
vegetables per day supplies 5 to 6 mg per day of provitamin A
carotenoids, which provides about 50-65% of the adult RDA for vitamin A.
Adults (18 years and
older):
U.S.
Recommended Daily Allowance (RDA) for adults : RDAs have been
established by the U.S. Institute of Medicine of the National Academy
of Sciences. Recommendations are: 900mcg/day (3000 IU) for men; 700
mcg/day (2300 IU) for women. For pregnant women between 14-18
years-old, 750mcg/day (2500 IU) is recommended; for pregnant women 19
years and older, 770mcg/day (2600 IU) is recommended. For lactating
women between 14-18 years-old, 1200mcg/day (4000 IU) is recommended;
for lactating women 19 years and older, 1300mcg/day (4300 IU) is
recommended.
Multivitamins : Vitamin
A is included in most multivitamins, often in 5000 IU doses as
softgels, capsules, tablets, or liquid.
Vitamin
A deficiency : For vitamin A deficiency not involving xerophthalmia,
100,000 IU orally or intramuscularly administered daily for 3 days,
followed by 50,000 IU per day for 2 weeks has been used. A maintenance
dose of 10,000 to 20,000 IU per day for 2 months has been recommended.
Xerophthalmia
: Oral vitamin A is the treatment of choice for xerophthalmia and
should be given immediately once the disorder is established. Patients
should obtain 200,000 IU immediately of vitamin A in an oil-based
preparation. The same dose should be repeated the following day and 2
weeks later.
Children (younger than
18 years):
Recommended
Dietary Allowance (RDA) : RDAs have been established by the U.S.
Institute of Medicine of the National Academy of Sciences.
Recommendations are: For children 1-3 years-old, 300mcg/day (1000 IU);
for children 4-8 years-old, 400mcg/day (1300 IU); for children 9-13
years-old, 600mcg/day (2000 IU). For pregnant women between 14-18
years-old, 750mcg/day (2500 IU) is recommended; for lactating women
between 14-18 years-old, 1200mcg/day (4000 IU) is recommended.
Vitamin
A deficiency/prevention : The World Health Organization (WHO) has
established dosage guidelines for children between 6-11 months-old to
receive 100,000 IU of vitamin A. This increases to 200,000 IU every six
months from 12 to 59 months of age.
Xerophthalmia
: Children 6 months-old to 1 year-old: 100,000 IU by mouth as a single
dose, repeated the next day and again at 4 weeks. Children 1 year-old
or older: 200,000 IU as a single dose, repeated the next day and again
at 4 weeks.
Measles
: Vitamin A should be administered to children diagnosed with measles
in areas where vitamin A deficiency may be present. The recommended
dose is 100,000 IU for children 6 months-old to 1 year-old, and 200,000
IU for children older than 12 months-old. The dose should be repeated
the next day and again after at least 2 weeks. Vitamin A deficiency is
not recognized as a problem in the United States, and supplementation
above the RDA should only be given in special situations under strict
medical supervision.
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Safety
The
U.S. Food and Drug Administration does not strictly regulate herbs and
supplements. There is no guarantee of strength, purity or safety of
products, and effects may vary. You should always read product labels.
If you have a medical condition, or are taking other drugs, herbs, or
supplements, you should speak with a qualified healthcare provider
before starting a new therapy. Consult a healthcare provider
immediately if you experience side effects.
Allergies
Known
hypersensitivity/allergy to vitamin A.
Side Effects and Warnings
Toxicity
(hypervitaminosis A) : Vitamin A toxicity, or hypervitaminosis A, is
rare in the general population. Vitamin A toxicity can occur with
excessive amounts of vitamin A taken over short or long periods of
time. Consequently, toxicity can be acute or chronic. An infant with
acute toxicity can develop a bulging fontalle (the soft spot on the
head) and symptoms similar to a brain tumor. Adults experience less
specific symptoms such as headache, dizziness, fatigue, malaise, blurry
vision, bone pain and swelling, nausea, and/or vomiting. Severe
toxicity can lead to eye damage, high levels of calcium, and liver
damage. Persons with liver disease and high alcohol intake may be at
risk for hepatotoxicity from vitamin A supplementation. Smokers who
consume alcohol and beta-carotene may be at an increased risk for lung
cancer or cardiovascular disease.
Pregnancy and
Breastfeeding
U.S.
Recommended Daily Allowance (RDA) for adults : RDAs have been
established by the U.S. Institute of Medicine of the National Academy
of Sciences. For pregnant women between 14-18 years-old, 750mcg/day
(2500 IU) is recommended; for pregnant women 19 years and older,
770mcg/day (2600 IU) is recommended. For lactating women between 14-18
years-old, 1200mcg/day (4000 IU) is recommended; for lactating women 19
years and older, 1300mcg/day (4300 IU) is recommended.
Pregnancy
: Vitamin A should only be used within the recommended dietary
allowance, because Vitamin A excess as well as deficiency have been
associated with birth defects. Excessive doses of vitamin A have been
associated with central nervous system malformations.
Lactation : Vitamin A is
excreted in human breast milk. Benefits or dangers to nursing infants
are not clearly established.
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Methodology
This
patient information is based on a professional level monograph edited
and peer-reviewed by contributors to the Natural Standard Research
Collaboration (www.naturalstandard.com).
Monograph methodology
Search strategy
To
prepare each Natural Standard monograph, electronic searches are
conducted in nine databases, including AMED, CANCERLIT, CINAHL, CISCOM,
the Cochrane Library, EMBASE, HerbMed, International Pharmaceutical
Abstracts, Medline, and NAPRALERT. Search terms include the common
name(s), scientific name(s), and all listed synonyms for each topic.
Hand searches are conducted of 20 additional journals (not indexed in
common databases), and of bibliographies from 50 selected secondary
references. No restrictions are placed on language or quality of
publications. Researchers in the field of complementary and alternative
medicine (CAM) are consulted for access to additional references or
ongoing research.
Selection criteria
All
literature is collected pertaining to efficacy in humans (regardless of
study design, quality, or language), dosing, precautions, adverse
effects, use in pregnancy/lactation, interactions, alteration of
laboratory assays, and mechanism of action (in vitro, animal research,
human data). Standardized inclusion/exclusion criteria are utilized for
selection.
Data analysis
Data
extraction and analysis are performed by health care professionals
conducting clinical work and/or research at academic centers, using
standardized instruments that pertain to each monograph section
(defining inclusion/exclusion criteria and analytic techniques,
including validated measures of study quality). Data are verified by a
second reviewer.
Review process
Blinded
review of monographs is conducted by multidisciplinary
research-clinical faculty at major academic centers with expertise in
epidemiology and biostatistics, pharmacology, toxicology, complementary
and alternative medicine (CAM) research, and clinical practice. In
cases of editorial disagreement, a three-member panel of the Editorial
Board addresses conflicts, and consults experts when applicable.
Authors of studies are contacted when clarification is required.
Update process
Natural
Standard regularly monitors scientific literature and industry
warnings. When clinically relevant new data emerge, best efforts are
made to update content immediately. In addition, regular updates with
renewed searches occur every 3-18 months, variable by topic.
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