Vitamin A

What is Vitamin A?

Vitamin A is a vitamin which is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal. This molecule is absolutely necessary for both scotopic and color vision. Vitamin A also functions in a very different role, as an irreversibly oxidized form retinoic acid, which is an important hormone-like growth factor for epithelial and other cells.

In foods of animal origin, the major form of vitamin A is an ester, primarily retinyl palmitate, which is converted to an alcohol (retinol) in the small intestine. The retinol form functions as a storage form of the vitamin, and can be converted to and from its visually active aldehyde form, retinal. The associated acid (retinoic acid), a metabolite which can be irreversibly synthesized from vitamin A, has only partial vitamin A activity, and does not function in the retina or some essential parts of the reproductive system.

All forms of vitamin A have a beta-ionone ring to which an isoprenoid chain is attached, called a ''retinyl group''. This structure is essential for vitamin activity. The orange pigment of carrots - beta-carotene - can be represented as two connected retinyl groups, which are used in the body to contribute to vitamin A levels. Alpha-carotene and gamma-carotene also have a single retinyl group which give them some vitamin activity. None of the other carotenes have vitamin activity. The carotenoid beta-cryptoxanthin possesses an ionone group and has vitamin activity in humans.

Vitamin A can be found in two principal forms in foods:

  • retinol, the form of vitamin A absorbed when eating animal food sources, is a yellow, fat-soluble substance. Since the pure alcohol form is unstable, the vitamin is found in tissues in a form of retinyl ester. It is also commercially produced and administered as esters such as retinyl acetate or palmitate.
  • The carotenes alpha-carotene, beta-carotene, gamma-carotene; and the xanthophyll beta-cryptoxanthin (all of which contain beta-ionone rings), but no other carotenoids, function as vitamin A in herbivores and omnivore animals, which possess the enzyme required to convert these compounds to retinal. Carnivores in general are poor converters of ionine-containg carotenoids, and pure carnivores such as cats and ferets lack beta-carotene 15 and cannot convert any carotenoids to retinal (resulting in ''none'' of the carotenoids being forms of vitamin A for these species).

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Vitamin A History

The discovery of vitamin A may have stemmed from research dating back to 1906, indicating that factors other than carbohydrates, proteins, and fats were necessary to keep cattle healthy. By 1917 one of these substances was independently discovered by Elmer McCollum at the University of Wisconsin–Madison, and Lafayette Mendel and Thomas Burr Osborne at Yale University. Since "water-soluble factor B" (Vitamin B) had recently been discovered, the researchers chose the name "fat-soluble factor A" (vitamin A). Later, a unit called retinol equivalent (RE) was introduced. 1 RE corresponded to 1 μg retinol, 2 μg β-carotene dissolved in oil (it is only partly dissolved in most supplement pills, due to very poor solubility in any medium), 6 μg β-carotene in normal food (because it is not absorbed as well as when in oils), and 12 μg of either α-carotene, γ-carotene, or β-cryptoxanthin in food (these molecules only provide 50% of the retinol as β-carotene, due to only half the molecule being convertible to usable vitamin).

Newer research has shown that the absorption of provitamin-A carotenoids is only half as much as previously thought, so in 2001 the US Institute of Medicine recommended a new unit, the retinol activity equivalent (RAE). 1 μg RAE corresponds to 1 μg retinol, 2 μg of β-carotene in oil, 12 μg of "dietary" beta-carotene, or 24 μg of the three other dietary provitamin-A carotenoids.

Substance and its chemical environmentMicrograms of retinol equivalent per microgram of the substance
retinol1
beta-carotene, dissolved in oil1/2
beta-carotene, common dietary1/12
alpha-carotene, common dietary1/24
gamma-carotene, common dietary1/24
beta-cryptoxanthin, common dietary1/24

Because the production of retinol from provitamins by the human body is regulated by the amount of retinol available to the body, the conversions apply strictly only for vitamin A deficient humans. The absorption of provitamins also depends greatly on the amount of lipids ingested with the provitamin; lipids increase the uptake of the provitamin.

The conclusion that can be drawn from the newer research is that fruits and vegetables are not as useful for obtaining vitamin A as was thought; in other words, the IU's that these foods were reported to contain were worth much less than the same number of IU's of fat-dissolved oils and (to some extent) supplements. This is important for vegetarians. (Night blindness is prevalent in countries where little meat or vitamin A-fortified foods are available.)

A sample vegan diet for one day that provides sufficient vitamin A has been published by the Food and Nutrition Board (page 120:

Life Stage GroupRecommended Dietary Allowances (RDA)
Adequate Intakes (AI*)

μg/day

Upper Limit
μg/day
Infants0–6 months
7–12 months

400*
500*

600
600
Children1–3 years
4–8 years

300
400

600
900
Males9–13 years
14–18 years
19 - >70 years

600
900
900

1700
2800
3000
Females9–13 years
14–18 years
19 - >70 years

600
700
700

1700
2800
3000
Pregnancy<19 years
19 - >50 years

750
770

2800
3000
Lactation<19 years
19 - >50 years

1200
1300

2800
3000

(Note that the limit refers to synthetic and natural retinoid forms of vitamin A. Carotene forms from dietary sources are not toxic.)

According to the Institute of Medicine of the National Academies, "RDAs are set to meet the needs of almost all (97 to 98 percent) individuals in a group. For healthy breastfed infants, the AI is the mean intake. The AI for other life stage and gender groups is believed to cover the needs of all individuals in the group, but lack of data prevent being able to specify with confidence the percentage of individuals covered by this intake."

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Vitamin A Food Sources

Vitamin A is found naturally in many foods:

  • liver (beef, pork, chicken, turkey, fish) (6500 μg 722%)
  • carrot (835 μg 93%)
  • broccoli leaf (800 μg 89%) - According to USDA database broccoli florets have much less.
  • sweet potato (709 μg 79%)
  • butter (684 μg 76%)
  • kale (681 μg 76%)
  • spinach (469 μg 52%)
  • pumpkin (400 μg 41%)
  • collard greens (333 μg 37%)
  • Cheddar cheese (265 μg 29%)
  • cantaloupe melon (169 μg 19%)
  • egg (140 μg 16%)
  • apricot (96 μg 11%)
  • papaya (55 μg 6%)
  • mango (38 μg 4%)
  • pea (38 μg 4%)
  • broccoli (31 μg 3%)
  • milk (28 μg 3%)

Note: data taken from USDA database bracketed values are retinol activity equivalences (RAEs) and percentage of the adult male RDA per 100g.

Conversion of carotene to retinol varies from person to person and bioavailability of carotene in food varies.

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Vitamin A Deficiency

Vitamin A deficiency is estimated to affect millions of children around the world. Approximately 250,000-500,000 children in developing countries become blind each year owing to vitamin A deficiency, with the highest prevalence in Southeast Asia and Africa. According to the World Health Organization (WHO), vitamin A deficiency is under control in the United States, but in developing countries vitamin A deficiency is a significant concern. With the high prevalence of vitamin A deficiency, the WHO has implemented several initiatives for supplementation of vitamin A in developing countries. Some of these strategies include intake of vitamin A through a combination of breast feeding, dietary intake, food fortification, and supplementation. Through the efforts of WHO and its partners, an estimated 1.25 million deaths since 1998 in 40 countries due to vitamin A deficiency have been averted.

Vitamin A deficiency can occur as either a primary or secondary deficiency. A primary vitamin A deficiency occurs among children and adults who do not consume an adequate intake of yellow and green vegetables, fruits and liver. Early weaning can also increase the risk of vitamin A deficiency. Secondary vitamin A deficiency is associated with chronic malabsorption of lipids, impaired bile production and release, low fat diets, and chronic exposure to oxidants, such as cigarette smoke. Vitamin A is a fat soluble vitamin and depends on micellar solubilization for dispersion into the small intestine, which results in poor utilization of vitamin A from low-fat diets. Zinc deficiency can also impair absorption, transport, and metabolism of vitamin A because it is essential for the synthesis of the vitamin A transport proteins and the oxidation of retinol to retinal. In malnourished populations, common low intakes of vitamin A and zinc increase the risk of vitamin A deficiency and lead to several physiological events.

Since the unique function of retinyl group is the light absorption in retinylidene protein, one of the earliest and specific manifestations of vitamin A deficiency is impaired vision, particularly in reduced light - night blindness. Persistent deficiency gives rise to a series of changes, the most devastating of which occur in the eyes. Some other ocular changes are referred to as xerophthalmia. First there is dryness of the conjunctiva (xerosis) as the normal lacrimal and mucus secreting epithelium is replaced by a keratinized epithelium. This is followed by the build-up of keratin debris in small opaque plaques (Bitot's spots) and, eventually, erosion of the roughened corneal surface with softening and destruction of the cornea (keratomalacia) and total blindness. Other changes include impaired immunity, hypokeratosis (white lumps at hair follicles), keratosis pilaris and squamous metaplasia of the epithelium lining the upper respiratory passages and urinary bladder to a keratinized epithelium. With relations to dentistry, a deficiency in Vitamin A leads to enamel hypoplasia.

Adequate supply of Vitamin A is especially important for pregnant and breastfeeding women, since deficiencies cannot be compensated by postnatal supplementation.. However, excess Vitamin A, especially through vitamin supplementation, can cause birth defects and should not exceed recommended daily values.

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Vitamin A Toxicity

Since vitamin A is fat-soluble, disposing of any excesses taken in through diet is much harder than with water-soluble vitamins B and C, thus vitamin A toxicity may result. This can lead to nausea, jaundice, irritability, anorexia (not to be confused with anorexia nervosa, the eating disorder), vomiting, blurry vision, headaches, hairloss, muscle and abdominal pain and weakness, drowsiness and altered mental status.

Acute toxicity generally occurs at doses of 25,000 IU/kg of body weight, with chronic toxicity occurring at 4,000 IU/kg of body weight daily for 6–15 months. However, liver toxicities can occur at levels as low as 15,000 IU per day to 1.4 million IU per day, with an average daily toxic dose of 120,000 IU per day. In people with renal failure 4000 IU can cause substantial damage. Additionally, excessive alcohol intake can increase toxicity. Children can reach toxic levels at 1,500 IU/kg of body weight.

It has been estimated that 75% of people may be ingesting more than the RDA for vitamin A on a regular basis in developed nations. Intake of twice the RDA of preformed vitamin A chronically may be associated with osteoporosis and hip fractures. This may be due to the fact that an excess of vitamin A can block the expression of certain proteins that are dependent on vitamin K. This could hypothetically reduce the efficacy of vitamin D, which has a proven role in the prevention of osteoporosis and also depends on vitamin K for proper utilization.

High vitamin A intake has been associated with spontaneous bone fractures in animals. Cell culture studies have linked increased bone resorption and decreased bone formation with high vitamin A intakes. This interaction may occur because vitamins A and D may compete for the same receptor and then interact with parathyroid hormone which regulates calcium. Indeed, a study by Forsmo ''et al.'' shows a correlation between low bone mineral density and too high intake of vitamin A.

Toxic effects of vitamin A have been shown to significantly affect developing fetuses. Therapeutic doses used for acne treatment have been shown to disrupt cephalic neural cell activity. The fetus is particularly sensitive to vitamin A toxicity during the period of organogenesis.

These toxicities only occur with preformed (retinoid) vitamin A (such as from liver). The carotenoid forms (such as beta-carotene as found in carrots), give no such symptoms, but excessive dietary intake of beta-carotene can lead to carotenodermia, which causes orange-yellow discoloration of the skin.

Researchers have succeeded in creating water-soluble forms of vitamin A, which they believed could reduce the potential for toxicity. However, a 2003 study found that water-soluble vitamin A was approximately 10 times as toxic as fat-soluble vitamin.

A 2006 study found that children given water-soluble vitamin A and D, which are typically fat-soluble, suffer from asthma twice as much as a control group supplemented with the fat-soluble vitamins.

Chronically high doses of Vitamin A can produce the syndrome of "pseudotumor cerebri". This syndrome includes headache, blurring of vision and confusion. It is associated with increased intracerebral pressure.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Vitamin A" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.