Scientific Opinion on Dietary Reference Values for vitamin A

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Article
Panel on Dietetic Products, Nutrition and Allergies
EFSA Journal
EFSA Journal 2015;13(3):4028 [84 pp.].
doi
10.2903/j.efsa.2015.4028
Panel members at the time of adoption
Carlo Agostoni, Roberto Berni Canani, Susan Fairweather-Tait, Marina Heinonen, Hannu Korhonen, Sébastien La Vieille, Rosangela Marchelli, Ambroise Martin, Androniki Naska, Monika Neuhäuser-Berthold, Grażyna Nowicka, Yolanda Sanz, Alfonso Siani, Anders Sjödin, Martin Stern, Sean (J.J.) Strain, Inge Tetens, Daniel Tomé, Dominique Turck and Hans Verhagen
Acknowledgements

The Panel wishes to thank the members of the Working Group on Dietary Reference Values for vitamins: Christel Lamberg-Allardt, Monika Neuhäuser-Berthold, Grażyna Nowicka, Kristina Pentieva, Hildegard Przyrembel, Sean (J.J.) Strain, Inge Tetens, Daniel Tomé and Dominique Turck for the preparatory work on this scientific opinion and EFSA staff: Anja Brönstrup, Agnès de Sesmaisons-Lecarré, Liisa Valsta, Fanny Héraud and Sofia Ioannidou for the support provided to this scientific opinion.

Contact
Type
Opinion of the Scientific Committee/Scientific Panel
On request from
European Commission
Question Number
EFSA-Q-2011-01226
Adopted
5 February 2015
Published
5 March 2015
Affiliation
European Food Safety Authority (EFSA), Parma, Italy
Note
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Abstract

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies derived Dietary Reference Values for vitamin A. The Panel considered that a concentration of 20 µg retinol/g liver can be used as a target for establishing the Average Requirement (AR) for vitamin A. In the absence of a better characterisation of the relationship between vitamin A intake and liver stores, a factorial approach was applied. This approach considered a total body/liver retinol store ratio of 1.25, a liver/body weight ratio of 2.4 %, a fractional catabolic rate of body retinol of 0.7 % per day, an efficiency of storage in the whole body for ingested retinol of 50 % and reference weights for women and men in the EU of 58.5 and 68.1 kg, respectively. ARs of 570 µg retinol equivalent (RE)/day for men and 490 µg RE/day for women were derived. Assuming a coefficient of variation (CV) of 15 %, Population Reference Intakes (PRIs) of 750 µg RE/day for men and 650 µg RE/day for women were set. For infants aged 7–11 months and children, the same equation as for adults was applied by using specific values for reference weight and liver/body weight ratio. For catabolic rate, the adult value corrected on the basis of a growth factor was used. ARs range from 190 µg RE/day in infants aged 7–11 months to 580 µg RE/day in boys aged 15–17 years. PRIs for infants and children were estimated using a CV of 15 % and range from 250 to 750 µg RE/day. For pregnancy and lactation, additional vitamin A requirements related to the accumulation of retinol in fetal and maternal tissues and transfer of retinol into breast milk were considered and PRIs of 700 and 1 300 µg RE/day, respectively, were set.

Summary

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on Dietary Reference Values (DRVs) for the European population, including vitamin A.

Vitamin A is a fat-soluble vitamin obtained from the diet either as preformed vitamin A (mainly retinol and retinyl esters) in foods of animal origin or as provitamin A carotenoids in plant-derived foods. The term vitamin A comprises all-trans-retinol (also called retinol) and the family of naturally occurring molecules associated with the biological activity of retinol (such as retinal, retinoic acid, retinyl esters), as well as provitamin A carotenoids that are dietary precursors of retinol. The biological value of substances with vitamin A activity is expressed as retinol equivalent (RE). Specific carotenoids/retinol equivalency ratios are defined for provitamin A carotenoids, which account for the less efficient absorption of carotenoids and their bioconversion to retinol. On the basis of available evidence, the Panel decided to maintain the conversion factors proposed by the Scientific Committee for Food (SCF) for the European populations, namely 1 μg RE equals 1 μg of retinol, 6 μg of β-carotene and 12 μg of other provitamin A carotenoids. Vitamin A requirement can be met with any mixture of preformed vitamin A and provitamin A carotenoids that provides an amount of vitamin A equivalent to the reference value in terms of µg RE/day.

Vitamin A is involved in vision as retinal, which plays a central role in the mechanisms of photo-transduction, and in the systemic maintenance of the growth and integrity of cells in body tissues through the action of retinoic acid, which acts as regulator of genomic expression. The most specific clinical consequence of vitamin A deficiency is xerophthalmia, which encompasses a clinical spectrum of ocular manifestations. In low-income countries, vitamin A deficiency in young infants and children has been associated with increased infectious morbidity and mortality, including respiratory infection and diarrhoea. 

Preformed vitamin A is efficiently absorbed (70–90 %). The absorption of β-carotene appears to be highly variable (5–65 %), depending on food- and diet-related factors, genetic characteristics and the health status of the subject. The intestine is the primary tissue where dietary provitamin A carotenoids are converted to retinol. Retinol, in the form of retinyl esters, and provitamin A carotenoids enter the body as a component of nascent chylomicrons secreted into the lymphatic system. Most dietary retinol (in chylomicrons and chylomicron remnants) is taken up by the liver, which is the major site of retinol metabolism and storage. Hepatic retinyl esters are hydrolysed to free retinol, and delivered to tissues by retinol-binding protein. The efficiency of storage and catabolism of retinol depends on vitamin A status. Low retinol stores are associated with a reduced efficiency of storage and decreased absolute catabolic rate. The majority of retinol metabolites are excreted in urine, in faeces via bile and to a lesser extent in breath.

Vitamin A status is best expressed in terms of total body store of retinol (i.e. as free retinol and retinyl esters) or, alternatively, as liver concentration of the vitamin. A concentration of 20 µg retinol/g liver (0.07 µmol/g) in adults represents a level assumed to maintain adequate plasma retinol concentration, to prevent clinical signs of deficiency and to provide adequate stores. The Panel considered that this can be used as a target value for establishing the Average Requirement (AR) for vitamin A for all age groups. The relationship between dietary intake of vitamin A and retinol liver stores has been explored with stable isotope dilution methods but available data are considered insufficient to derive an AR. A factorial approach was applied. This approach considered a total body/liver retinol store ratio of 1.25 (i.e. 80 % of retinol body stores are in the liver), a liver/body weight ratio of 2.4 %, a fractional catabolic rate of retinol of 0.7 % per day of total body stores, an efficiency of storage in the whole body of ingested retinol of 50 % and the reference body weights for women and men in the EU of 58.5 and 68.1 kg, respectively. On the basis of this approach, ARs of 570 µg RE/day for men and 490 µg RE/day for women were derived after rounding. Assuming a coefficient of variation (CV) of 15 % because of the variability in requirement and the large uncertainties in the dataset, Population Reference Intakes (PRIs) of 750 µg RE/day for men and 650 µg RE/day for women were set after rounding.

For infants aged 7–11 months and children, the same target concentration of retinol in the liver and the same equation as for adults was used to calculate ARs. Specific values for reference body weight and for liver/body weight ratio were used. There are some indications that retinol catabolic rate may be higher in children than in adults, but data are limited. The Panel decided to apply the value for catabolic rate in adults and correct it on the basis of a growth factor. Estimated ARs range from 190 µg RE/day in infants aged 7–11 months to 580 µg RE/day in boys aged 15–17 years. PRIs for infants and children were estimated based on a CV of 15 % and range from 250 to 750 µg RE/day.

For pregnant women, the Panel assumed that a total amount of 3 600 µg retinol is accumulated in the fetus over the course of pregnancy. Considering that the accretion mostly occurs in the last months of pregnancy, and assuming an efficiency of storage of 50 % for the fetus, an additional daily requirement of 51 µg RE was calculated for the second half of pregnancy. In order to allow for the extra need related to the growth of maternal tissues, the Panel applied this additional requirement to the whole period of pregnancy. Consequently, an AR of 540 µg RE/day was estimated for pregnant women. Considering a CV of 15 % and rounding, a PRI of 700 µg RE/day was derived for pregnant women.

For lactating women, an increase in the AR was based on the vitamin A intake required to compensate for the loss of retinol in breast milk. Based on an average amount of retinol secreted in breast milk of 424 μg/day and an absorption efficiency of retinol of 80 %, an additional vitamin A intake of 530 µg RE/day was considered sufficient to replace these losses. An AR of 1 020 μg RE/day was estimated and, considering a CV of 15 % and rounding down, a PRI of 1 300 μg RE/day was proposed for lactating women.

Foods rich in retinol include offal and meat, butter, retinol-enriched margarine, dairy products and eggs, while foods rich in β-carotene include vegetables and fruits, such as sweet potatoes, carrots, pumpkins, dark green leafy vegetables, sweet red peppers, mangoes and melons. On the basis of data from 12 dietary surveys in nine EU countries, vitamin A intake was assessed using food consumption data from the EFSA Comprehensive Food Consumption Database and vitamin A composition data from the EFSA nutrient composition database. Average vitamin A intake ranged between 409 and 651 μg RE/day in children aged 1 to < 3 years, between 607 and 889 μg RE/day in children aged 3 to < 10 years, between 597 and 1 078 μg RE/day in children aged 10 to < 18 years and between 816 and 1 498 μg RE/day in adults.

Keywords
vitamin A, retinol, carotenoids, Average Requirement, Population Reference Intake, Dietary Reference Value
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Number of Pages
84