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 Wisconsinadison, 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). Vitamin A was first synthesized in 1947 by two Dutch chemists, David Adriaan van Dorp and Jozef Ferdinand Arens.
Equivalencies of retinoids and carotenoids (IU)
As some carotenoids can be converted into vitamin A, attempts have been made to determine how much of them in the diet is equivalent to a particular amount of retinol, so that comparisons can be made of the benefit of different foods. Unfortunately the situation is confusing because the accepted equivalences have changed. For many years, a system of equivalencies was used in which an international unit (IU) was equal to 0.3 g of retinol, 0.6 g of -carotene, or 1.2 g of other provitamin-A carotenoids. Later, a unit called retinol equivalent (RE) was introduced. 1 RE corresponded to 1 g retinol, 2 g -carotene dissolved in oil (it is only partly dissolved in most supplement pills, due to very poor solubility in any medium), 6 g -carotene in normal food (because it is not absorbed as well as when in oils), and 12 g of either -carotene, -carotene, or -cryptoxanthin in food (these molecules only provide 50% of the retinol as -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 g RAE corresponds to 1 g retinol, 2 g of -carotene in oil, 12 g of “dietary” beta-carotene, or 24 g of the three other dietary provitamin-A carotenoids.
Substance and its chemical environment
Micrograms of retinol equivalent per microgram of the substance
retinol
1
beta-carotene, dissolved in oil
1/2
beta-carotene, common dietary
1/12
alpha-carotene, common dietary
1/24
gamma-carotene, common dietary
1/24
beta-cryptoxanthin, common dietary
1/24
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). On the other hand, reference values for retinol or its equivalents, provided by the National Academy of Sciences, have decreased. The RDA (for men) of 1968 was 5000 IU (1500 g retinol). In 1974, the RDA was set to 1000 RE (1000 g retinol), whereas now the Dietary Reference Intake is 900 RAE (900 g or 3000 IU retinol). This is equivalent to 1800 g of -carotene supplement (3000 IU) or 10800 g of -carotene in food (18000 IU).
Recommended daily intake
Vitamin A
Dietary Reference Intake:
Life Stage Group
Recommended Dietary Allowances (RDA)
Adequate Intakes (AI*)
g/day
Upper Limit
g/day
Infants
06 months
712 months
400*
500*
600
600
Children
13 years
48 years
300
400
600
900
Males
913 years
1418 years
19 – >70 years
600
900
900
1700
2800
3000
Females
913 years
1418 years
19 – >70 years
600
700
700
1700
2800
3000
Pregnancy
19 – >50 years
750
770
2800
3000
Lactation
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.”
Sources
Egg.
Vitamin A is found naturally in many foods:
liver (beef, pork, chicken, turkey, fish) (6500 g 722%)
carrot (835 g 93%)
broccoli leaf (800 g 89%) – According to USDA database broccoli florets have much less.
sweet potato (709 g 79%)
butter (684 g 76%)
kale (681 g 76%)
spinach (469 g 52%)
pumpkin (400 g 41%)
collard greens (333 g 37%)
Cheddar cheese (265 g 29%)
cantaloupe melon (169 g 19%)
egg (140 g 16%)
apricot (96 g 11%)
papaya (55 g 6%)
mango (38 g 4%)
pea (38 g 4%)
broccoli (31 g 3%)
milk (28 g 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.
Metabolic functions
Vitamin A plays a role in a variety of functions throughout the body, such as:
Vision
Gene transcription
Immune function
Embryonic development and reproduction
Bone metabolism
Haematopoiesis
Skin health
Antioxidant Activity
Vision
The role of vitamin A in the vision cycle is specifically related to the retinal form. Within the eye, 11-cis-retinal is bound to rhodopsin (rods) and iodopsin (cones) at conserved lysine residues. As light enters the eye the 11-cis-retinal is isomerized to the all-”trans” form. The all-”trans” retinal dissociates from the opsin in a series of steps called bleaching. This isomerization induces a nervous signal along the optic nerve to the visual center of the brain. Upon completion of this cycle, the all-”trans”-retinal can be recycled and converted back to the 11-”cis”-retinal form via a series of enzymatic reactions. Additionally, some of the all-”trans” retinal may be converted to all-”trans” retinol form and then transported with an interphotoreceptor retinol-binding protein (IRBP) to the pigment epithelial cells. Further esterification into all-”trans” retinyl esters allow this final form to be stored within the pigment epithelial cells to be reused when needed. The final conversion of 11-cis-retinal will rebind to opsin to reform rhodopsin in the retina. Rhodopsin is needed to see black and white as well as see at night. It is for this reason that a deficiency in vitamin A will inhibit the reformation of rhodopsin and lead to night blindness.
Gene transcription
Vitamin A, in the retinoic acid form, plays an important role in gene transcription. Once retinol has been taken up by a cell, it can be oxidized to retinal (by retinol dehydrogenases) and then retinal can be oxidized to retinoic acid (by retinal oxidase). The conversion of retinal to retinoic acid is an irreversible step, meaning that the production of retinoic acid is tightly regulated, due to its activity as a ligand for nuclear receptors. Retinoic acid can bind to two different nuclear receptors to initiate (or inhibit) gene transcription: the retinoic acid receptors (RARs) or the retinoid “X” receptors (RXRs). RAR and RXR must dimerize before they can bind to the DNA. RAR will form a heterodimer with RXR (RAR-RXR), but it does not readily form a homodimer (RAR-RAR). RXR, on the other hand, readily forms a homodimer (RXR-RXR) and will form heterodimers with many other nuclear receptors as well, including the thyroid hormone receptor (RXR-TR), the Vitamin D3 receptor (RXR-VDR), the peroxisome proliferator-activated receptor (RXR-PPAR) and the liver “X” receptor (RXR-LXR). The RAR-RXR heterodimer recognizes retinoid acid response elements (RAREs) on the DNA whereas the RXR-RXR homodimer recognizes retinoid “X” response elements (RXREs) on the DNA. The other RXR heterodimers will bind to various other response elements on the DNA. Once the retinoic acid binds to the receptors and dimerization has occurred, the receptors undergo a conformational change that causes co-repressors
