De Pee and West (1996) proposed that control of VADD depends to a large extent on an adequate supply of vitamin A and the vitamin A supply is determined by:
Food intake x (pro)-vitamin A content x bioavailability/bioefficacy, where Bioavailability = fraction of ingested nutrient available for normal physiological functions and storage (Jackson, 1997) Bioefficacy = efficiency of absorption and conversion of ingested nutrient to the active form e.g. b-carotene to retinol (van Lieshout et al, 2001).
3.4.1 Relationship between bioefficacy and vitamin A requirements
The RNI for children up to 5 years of age is 400 mg retinol equivalents (RE)/day, which can easily be met from the diet if animal foods are available e.g. 1 egg (50g) contains about 100 mg RE, 25g chicken liver contains 3000 mg RE. Plants also contribute to vitamin A intake e.g. 1 raw carrot (20g) contains 400 mg b-carotene, a 70 g portion of spinach contains 600 mg b-carotene and with a bioefficacy of 100% would supply 400 and 600 mg RE respectively. But the pro-vitamin A carotenoids are absorbed less efficiently than retinol, that is, their bioefficacy is less than 100%. Therefore the effective supply of vitamin A from fruits and vegetables is much lower than that from retinol in animal foods (van Lieshout et al, 2001). If 1 mole b-carotene (Fig. 3.1) yields 2 moles retinol then, using 100% bioefficacy, 1 mmol (0.537 mg) b-carotene would be absorbed and converted totally to 2 mmol (0.572 mg) retinol, i.e. 0.537/0.572 = 0.94 mg b-carotene is equivalent to 1 mg retinol. The results of the 'Sheffield' studies carried out by the Medical Research Council (MRC) during the Second World War provided important information to establish the relative equivalency of carotenoids and retinol (Hume and Krebs, 1949). These and other studies suggested that 6 mg b-carotene or 12 mg of other pro-vitamin A carotenoids in a mixed diet had the same activity as 1 mg retinol (FAO/WHO 1967). Therefore, according to FAO/WHO the bioefficacy of b-carotene in food is (100%*0.94)/6 = 16%. But in the 1990s evidence was accumulating that the bioefficacy of provitamin A carotenoids in fruit and vegetables was only 20-30% of the FAO/WHO estimates of 16%. The efficiency with which b-carotene in dark green leafy vegetables (DGLV) is metabolised to vitamin A was re-examined and various bioconversion factors have been put forward:
Fig. 3.1 Structures of all-trans-retinol and ß-carotene.
Assuming that 100g DGLV contains 3000 mg b-carotene and a child of 4 years needs an RNI of 400 mg RE/day then using bioconversion factors of 12:1, 21:1 or 26:1, the child would need 160g, 280g or 360g of DGLV each day to meet requirements.
In January 2001, the US National Academy of Sciences/Institute of Medicine (IOM) announced a new equivalence factor (12:1) for the conversion of b-carotene to retinol. The basis for formulating the equivalency factor was to relate the absorption of b-carotene in a principally mixed vegetable diet to that from oil in healthy and nutritionally-adequate individuals. The recommendations were based on a product of relative absorption of b-carotene in mixed vegetable diet (1:6) (van het Hof et al, 1999) to the amount of retinol formed (1 mg) when 2 mg b-carotene was fed in oil (Sauberlich et al, 1974). In the van het Hof study, the increase in serum b-carotene concentration after consumption of b-carotene-rich vegetables was 1/7 or 14% of the increase after consumption of b-carotene in oil. The Institute of Medicine (IOM) (2001) adjusted the value to 1/6 or 17%, because of the low fruit content in the diet used. From these two studies, the IOM concluded that the bioefficacy of b-carotene in oil was (100% *0.94)/2 = 47% (Sauberlich et al, 1974) and 17% from mixed vegetables (van het Hof et al, 1999). Thus bioefficacy from vegetables in a mixed diet was 17%* 0.47 = 8%, that is 12 mg b-carotene in food has the same vitamin A activity as 1 mg retinol. The
12: 1 ratio is referred to as the retinol activity equivalence (RAE) (Northrop-Clewes, 2001a).
In the calculation, the IOM used the mean ratio from only one 'oil study'. There were in fact 5 'oil' studies (Booher et al, 1939; Wagner, 1940; Hume and Krebs, 1949; Sauberlich et al, 1974; Tang et al, 2000) and if the data from all the studies had been used a bioconversion value of 3.5 mg b-carotene to 1 mg retinol would have been calculated giving an RAE of 21 instead of 12 as quoted. The IOM are at present reconsidering the published data (van Lieshout, 2001). How we interpret the bioconversion factors for b-carotene proposed by IOM or by others still needs much more thought before any of them can be put to practical use. However, even if the RAE is only 12:1, there are probably not sufficient vegetables in developing countries to meet that required, therefore, there must be other, as yet undiscovered factors, that influence bioefficacy. Despite this, intake of fruit and vegetable-sources of provitamin A should be encouraged, for although the bioefficacy of b-carotene is apparently so poor, it has to be remembered that the majority of the world's children are not VAD.
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