Vitamin A (Retinol)

Differential diagnosis of hypervitaminosis A. A combination of a low serum carotene level and a low vitamin A suggests inadequate vitamin A nutrition.

This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration (FDA).

Vitamin A is the name given to a group of biologically active, fat-soluble molecules that includes retinol, retinal and retinoic acid.1,2 These retinoid compounds are derived from the plant precursor molecule, β-carotene. β-carotene (also referred to as provitamin A) has a structure that consists of two molecules of retinal linked at their aldehyde ends.1 β-carotene is converted to vitamin A by intestinal absorptive cells and hepatocytes.1,2 Vitamin A is stored in the liver and transported to extrahepatic tissues bound to retinol binding protein and albumin.1 Both retinol and β-carotene levels are measured in plasma for assessing vitamin A inadequacy and/or toxicity.

Vitamin A exists in humans in several forms and is tightly controlled. Naturally occuring forms of vitamin A include retinol, retinol esters, retinal and retinoic acid. The alcohol form, retinol, predominates in the circulation, but it is too toxic for storage. Instead, the liver stores as retinyl esters - principally palmitate. The active form of vitamin A in the visual cycle is the aldehyde form, retinal. Retinoic acid is the form in tissues responsible for the biological actions of vitamin A in cellular division and differentiation.11

The most important measurand for the estimation of vitamin A status is circulating vitamin A as retinol. Serum retinol levels do not accurately reflect liver retinyl ester levels. Despite this limitation, serum retinol is still useful because the levels will diminish once the supply from the liver is diminished. The serum retinol level at which vitamin A deficiency occurs will coincide with the manifestation of night blindness, due to the interruption of the visual cycle by lack of retinal. Other more serious symptoms will occur later when retinoic acid is depleted by even less available hepatic retinyl esters.12

The body must acquire vitamin A from the diet in order to sustain a number of essential physiological processes.3 These include vision, organogenesis, tissue differentiation, immune function, reproduction, embryonic development and maintenance of healthy skin and barrier functions.3-7 More than five hundred genes are thought to be regulated by vitamin A.3

Vitamin A deficiency only manifests when liver stores are depleted by prolonged reduction of dietary intake.1,10 In healthy individuals, serum retinol concentrations are homeostatically controlled and do not begin to decline until liver reserves of vitamin A are dangerously low.2,4,10 The initial symptom of vitamin A deficiency is an inability to adapt vision to darkness (ie, night blindness).1 Vitamin A is an essential component of rhodopsin, a protein that absorbs light in the retinal receptors.2 Vitamin A also supports the normal differentiation and functioning of the conjunctival membranes and cornea.2 Protracted vitamin A deficiency causes degenerative changes in the retina due to progressive keratinization of the cornea, a condition referred to as xerophthalmia.2 In developing countries, vitamin A deficiency is the most common cause of preventable blindness.

Additional symptoms of vitamin A deficiency include follicular hyperkeratinosis, increased susceptibility to infection and an anemia similar to iron deficient anemia.1 β-carotene is an important, but insufficient, source of vitamin A among poor populations due to the inefficiency of the conversion to retinol.5 Vitamin A deficiency in poor countries is also a significant cause of infection and death, particularly from diarrhea and measles.6

Excessive levels of vitamin A can lead to toxicity. Vitamin A intoxication is a concern in normal adults who ingest more than 15 mg per day and children who ingest more than 6 mg per day of vitamin A for a period of several months. The symptoms of acute vitamin A toxicity include dizziness, nausea, vomiting, headaches, blurred vision, vertigo, reduced muscle coordination, skin exfoliaton.13,14 More chronic vitamin A toxicity symptoms include weight loss, fatigue cheilosis, glossitis, alopecia, bone demineralization, hypercalcemia, lymph node enlargement, hyperlipidemia and amenorrhea. Excess accumulation of vitamin A in the liver can also lead to hepatosplenomegaly, liver fibrosis with portal hypertension.1,13 Congenital malformations, including craniofacial abnormalities and valvular heart disease as well as spontaneous abortions have been reported in children born to pregnant women taking vitamin A in excess. A number of studies have reported an increased risk of lung cancer among high-risk individuals (smokers and asbestos workers) who were given high doses of β-carotene alone or in combination with other antioxidants.5

Toxicity generally results from excessive ingestion of vitamin A supplements but regular intake of large amounts of liver, although usually not a problem in vitamin A-deficient areas, may also result in toxicity due to its high content of vitamin A.15

The World Health Organization recommendations supplementation when vitamin A levels fall below 20.0 ug/dL.16 Severe deficiency is indicated at levels <10.0 ug/dL. 2,9,10

1. The Medical Biochemistry Page. Vitamin A. Accessed at http://themedicalbiochemistrypage.org/vitamins.php#a on January 26, 2014.

2. Office of Dietary Supplements, National Institutes of Health. Dietary Supplement Fact Sheet: Vitamin A. Accessed at http://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/ on January 26, 2014.

3. D'Ambrosio DN, Clugston RD, Blaner WS. Vitamin A metabolism: an update. Nutrients. 2011 Jan;3(1):63-103. PubMed 21350678

4. Tanumihardjo SA. Vitamin A: biomarkers of nutrition for development. Am J Clin Nutr. 2011 Aug;94(2):658S-665S. PubMed 21715511

5. Sommer A, Vyas KS. A global clinical view on vitamin A and carotenoids. Am J Clin Nutr. 2012 Nov;96(5):1204S-1206S. PubMed 23053551

6. Semba RD. The role of vitamin A and related retinoids in immune function. Nutr Rev. 1998 Jan;56(1 Pt 2):S38-S48. PubMed 9481123

7. Clagett-Dame M, Knutson D. Vitamin A in reproduction and development. Nutrients. 2011 Apr;3(4):385-428. PubMed 22254103

8. West Jr, KP. Vitamin A: deficiency and interventions. In: Caballero B, Allen L, Prentice A, editors. Encyclopedia of human nutrition. 2nd ed. Amsterdam: Elsevier Ltd.; 2006. pp. 348-359.

9. U.S. Centers for Disease Control and Prevention. Second national report on biochemical indicators of diet and nutrition in the U.S. population 2012. Atlanta (GA): National Center for Environmental Health; April 2012. Available from: http://www.cdc.gov/nutritionreport.

10. Greaves RF, Woollard GA, Hoad KE, et al. Laboratory medicine best practice guideline: vitamins a, e and the carotenoids in blood. Clin Biochem Rev. 2014 May;35(2):81-113. PubMed 25210208

11. Kurlandsky SB, Xiao JH, Duell EA, Voorhees JJ, Fisher GJ. Biological activity of all-trans retinol requires metabolic conversion to all-trans retinoic