Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Elsevier Science full text link Elsevier Science Free PMC article
Full text links

Actions

Share

Review
.2016 Sep;146(9):1816S-48S.
doi: 10.3945/jn.115.229708. Epub 2016 Aug 10.

Biomarkers of Nutrition for Development (BOND)-Vitamin A Review

Affiliations
Review

Biomarkers of Nutrition for Development (BOND)-Vitamin A Review

Sherry A Tanumihardjo et al. J Nutr.2016 Sep.

Abstract

The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-informed advice to anyone with an interest in the role of nutrition in health. The BOND program provides information with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect, which will be especially useful for readers who want to assess nutrient status. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutritional status at the individual and population levels. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, folate, zinc, iron, vitamin A, and vitamin B-12. This review of vitamin A is the current article in this series. Although the vitamin was discovered >100 y ago, vitamin A status assessment is not trivial. Serum retinol concentrations are under homeostatic control due in part to vitamin A's use in the body for growth and cellular differentiation and because of its toxic properties at high concentrations. Furthermore, serum retinol concentrations are depressed during infection and inflammation because retinol-binding protein (RBP) is a negative acute-phase reactant, which makes status assessment challenging. Thus, this review describes the clinical and functional indicators related to eye health and biochemical biomarkers of vitamin A status (i.e., serum retinol, RBP, breast-milk retinol, dose-response tests, isotope dilution methodology, and serum retinyl esters). These biomarkers are then related to liver vitamin A concentrations, which are usually considered the gold standard for vitamin A status. With regard to biomarkers, future research questions and gaps in our current understanding as well as limitations of the methods are described.

Keywords: BOND; breast milk; dose response tests; dried blood spot; isotope dilution; retinol-binding protein; serum retinol; vitamin A biomarkers; vitamin A review; xerophthalmia.

© 2016 American Society for Nutrition.

PubMed Disclaimer

Conflict of interest statement

3 Author disclosures: SA Tanumihardjo, RM Russell, CB Stephensen, BM Gannon, NE Craft, MJ Haskell, G Lietz, K Schulze, and DJ Raiten, no conflicts of interest. The original Expert Panel consisted of SAT, RMR (chair), CBS, GL, and Keith West Jr. The BOND project thanks the European Recommendations Aligned (EURRECA) program, the Micronutrient Genomics Project, the WHO, and the CDC for their partnership.

Figures

FIGURE 1
FIGURE 1
The structures of the major dietary forms of vitamin A. Preformed retinol is primarily found as retinyl palmitate in most animal livers, fortificants, and supplements. From ∼50 provitamin A carotenoids in plants, the common ones include α-carotene, β-carotene, and β-cryptoxanthin. These forms of provitamin A carotenoids are often quantified in human serum.
FIGURE 2
FIGURE 2
Vitamin A and provitamin A carotenoids are fat-soluble. Therefore, lipid is needed for the best absorption. After consumption, retinyl esters are hydrolyzed by nonspecific hydrolases and mixed with lipid and bile salts to form micelles along with the provitamin A carotenoids. After the micelles are absorbed into the enterocyte, provitamin A carotenoids can be cleaved to retinol by β-carotene 15,15′-dioxygenase. Retinol is then esterifed to FAs and incorporated into chylomicra along with carotenoids that were not cleaved. The chylomicra travel through the lymph into the bloodstream and lose some of the retinyl esters and carotenoids to tissues while in circulation. Ultimately, the remaining retinyl esters and carotenoids are taken up by the liver as chylomicron remnants.
FIGURE 3
FIGURE 3
Schematic diagram showing the metabolic pathways of vitamin A metabolism. CRBP, cellular retinol-binding protein; CYP26, cytochrome P450 26; LRAT, lecithin:retinol acyltransferase; RALDH, retinaldehyde dehydrogenase; RDH, retinol dehydrogenase; retSDR1, short-chain retinol dehydrogenase/reductase; RPE65, retinal pigment epithelium-specific protein 65kDa; SDR, short-chain dehydrogenase/reductases. Adapted from reference with permission.
FIGURE 4
FIGURE 4
After absorption, retinyl esters and carotenoids can be released from chylomicra into tissues. Malformed chylomicra can be scavenged by the spleen. However, the bulk of retinyl esters and carotenoids make their way to the liver in chylomicron remnants. In the liver, the retinyl esters can be hydrolyzed by retinyl ester hydrolase. Retinol can then be either complexed with RBP and released into the plasma or re-esterifed by LRAT for long-term storage. The carotenoids can be cleaved to retinol (although not a major pathway in the liver), stored, or packaged into VLDLs and released into the circulation. Retinol uptake from RBP by cells can be facilitated by STRA6. BCO2, β-carotene 9,10-oxygenase; LPL, lipoprotein lipase; LRAT, lecithin:retinol acyltransferase; RBP, retinol-binding protein; RE, retinyl esters; REH, retinyl ester hydrolase; ROH, retinol; ROOH, retinoic acid; STRA6, stimulated by retinoic acid 6 receptor; αC, α-carotene; βC, β-carotene.
FIGURE 5
FIGURE 5
Dietary intake of vitamin A is in 2 major forms: preformed vitamin A from animal-source foods, supplements, and fortificants and provitamin A carotenoids from plant foods and some supplements. The body can regulate how much vitamin A is formed from provitamin A carotenoids, but preformed vitamin A is highly bioavailable. Thus, as dietary intake increases beyond requirements so do liver retinol reserves. The manifestations of vitamin A deficiency are severe, from blindness to death. The manifestations of vitamin A excess are not entirely known, but when severe, can also lead to ill health and death. RBP, retinol-binding protein.
FIGURE 6
FIGURE 6
The definition of vitamin A status related to liver vitamin A concentrations and the range of liver reserves in which the vitamin A biomarker has utility in predicting vitamin A status. In the past, 0.7–1 μmol/g was considered excessive, but until more biologically meaningful data are generated this range is considered high. Updated in 2015. VA, vitamin A. Reproduced from reference with permission.
FIGURE 7
FIGURE 7
The rod-cone break period measured in luminance (log micro-microlamberts) occurs in<10 min in normal individuals when placed in a dark room. Vitamin A–deficient subjects have a higher luminance need to see in the dark as depicted by patients (n = 13) with chronic small intestinal disease compared with the range of 7 controls. Reproduced from reference with permission.
FIGURE 8
FIGURE 8
The electroretinogram response in the μvolts is generated by light stimulation of the retina and occurs in milliseconds. The electroretinogram is characterized by a negative “a” wave originating from the photoreceptor inner segments followed by a positive “b” wave, which originates from the retinal bipolar cell layer. The electroretinogram amplitude is proportional to the intensity of light, the degree of dark adaptation, the number of photoreceptors, and the rhodopsin visual pigment concentration. Reproduced from reference with permission.
FIGURE 9
FIGURE 9
Kernel density estimation visually depicts smoothed distribution trends in serum retinol concentration shifts (μmol/L) by infection stage. The acute-phase response lowers circulating concentrations of retinol. Adapted from reference with permission.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. WHO. Global prevalence of vitamin A deficiency in populations at risk: 1995–2005. WHO Global Database on Vitamin A Deficiency. Geneva (Switzerland): WHO; 2009.
    1. Wolf G. A history of vitamin A and retinoids. FASEB J 1996;10:1102–7. - PubMed
    1. Guggenheim KY. Nutrition and nutritional diseases. Lexington (MA): Collamore Press; 1981.
    1. McCollum EV, Davis M. The necessity of certain lipins in the diet during growth. J Biol Chem 1913;15:167–75. - PubMed
    1. Osborne TB, Mendel LB. The influence of butter-fat on growth. J Biol Chem 1913;16:423–37.

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full text links
Elsevier Science full text link Elsevier Science Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp