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Implementing food-based dietary guidelines for - United Nations ...

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Establishing nutrient intake values<br />

Annex<br />

Example of deriving an average nutrient<br />

requirement (ANR): vitamin A<br />

Vitamin A functions in many biological systems:<br />

11-cis-retinal, the active aldehyde <strong>for</strong>m of vitamin A,<br />

is part of rhodopsin, required <strong>for</strong> vision in the brain,<br />

<strong>for</strong> normal growth and maintenance of the cornea<br />

and conjunctival membranes of the eye (to prevent<br />

xerophthalmia), and as a regulator of genes that <strong>for</strong>m<br />

structural proteins, enzymes, and retinol-binding proteins<br />

in the blood, including those involved in normal<br />

embryonic development and immune function related<br />

to cytokines and T and B lymphocyte production [7].<br />

It is not surprising that some of these functions continue<br />

normally at comparatively low levels of intake,<br />

while others are depressed or inactive, resulting in<br />

detectable changes in indicators that denote vitamin<br />

A inadequacy.<br />

In selecting the indicators or functional outcomes<br />

to use to establish an ANR and an NIV x <strong>for</strong> vitamin A,<br />

a number of choices are available (see Annex table 1).<br />

In reviewing research and studies available in the year<br />

2000, the DRI process selected as the main criterion<br />

to establish adequacy <strong>for</strong> vitamin A in Canada and<br />

the <strong>United</strong> States adequate liver stores, with adequacy<br />

defined as at least 20 µg retinol/g liver tissue. This<br />

resulted in an EAR (estimated average requirement,<br />

TABLE 1. Possible indicators <strong>for</strong> evaluating vitamin A adequacy<br />

S49<br />

equivalent to an ANR) of 625 µg/day <strong>for</strong> men and 500<br />

µg/day <strong>for</strong> women 19 years of age and older [7].<br />

However, it is recognized that significant liver retinol<br />

stores are not required <strong>for</strong> normal function. Thus, dark<br />

adaptation was identified as the most sensitive criterion<br />

<strong>for</strong> which adequate data were available to establish an<br />

average requirement. There were data supporting the<br />

ability of dark adaptation to identify individuals with<br />

inadequate intakes of vitamin A, and there were data<br />

from individuals inadequate in vitamin A whose dark<br />

adaptation was measured and who then were given various<br />

levels of vitamin A and underwent additional dark<br />

adaptation tests to ascertain at what level of intake the<br />

function returned to normal. The level at which dark<br />

adaptation returned to normal (defined as at least –4.6<br />

± 0.3 log candela/m 2 ) in half of those studied (while<br />

dark adaptation in the other half remained abnormal)<br />

was 300 µg/day. This could be considered the ANR<br />

<strong>for</strong> vitamin A <strong>based</strong> on dark adaptation. One of the<br />

primary limitations of selecting this criterion was that<br />

there were only 13 individuals studied in this way.<br />

According to this example, when the selected criterion<br />

or indicator of adequacy is dark adaptation, the<br />

ANR is 300 µg; this is less than half the amount identified<br />

if liver stores at the level of 20 µg/g are chosen (650<br />

µg) [7]. This demonstrates that the important question<br />

that must be asked in establishing nutrient requirements,<br />

and a potential barrier to harmonizing such<br />

Function Test Definition of adequacy<br />

Dark adaptation Dark adaptometry: final dark-adapted<br />

threshold after 35–40 min<br />

Circulating levels of vitamin<br />

A<br />

≥ – 4.6 ± 0.3 log candela/m 2<br />

Pupillary response test A high threshold in response to incremental<br />

pulses of light = low retinal sensitivity due to<br />

vitamin A deficiency<br />

Serum or plasma retinol concentration; retinol-binding<br />

protein concentration<br />

Total liver reserves (TLR) Isotope dilution using TLR = F × dose × [(H:<br />

D) – 1]; F = efficiency of storage of early<br />

administered dose; dose = dose of labeled<br />

retinol; H:D = ratio of H to 2 H-retinol in<br />

plasma after equilibration<br />

Relative dose–response<br />

(RDR)<br />

Modified relative dose–<br />

response (MRDR)<br />

Conjunctival impression<br />

cytology (CIC)<br />

Change in plasma retinol concentration in<br />

response to a test dose after 5 h<br />

Amount of test dose vitamin A 2 (dehydroretinol)<br />

appearing in plasma after 5 h<br />

Microscopic examination of periodic acid<br />

Schiff–hematoxylin-stained epithelial cells<br />

Immune function Humoral antibody responses and cell-mediated<br />

immunity<br />

Source: Institute of Medicine [7].<br />

Considered insensitive indicators and thus<br />

not used<br />

TLR ≥ 20 µg/g retinol<br />

RDR < 20%<br />

MRDR < 20%<br />

Lack of abnormal cells<br />

Normal number of natural killer cells and<br />

normal cytotoxic activity

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