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Program in International Nutrition, Department of Nutrition, University of California, Davis, CA 95616
2To whom correspondence should be addressed. E-mail: lhallen{at}ucdavis.edu.
| ABSTRACT |
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KEY WORDS: human milk infants complementary foods B vitamins fortification
This article recommends levels at which complementary foods might be fortified with B vitamins to improve the nutritional status of infants and young children in Latin America and the Caribbean. Risk factors for deficiency, prevalence of deficiency, adverse effects of deficiency and how recommended intakes for infants and young children are derived are considered for each of the B vitamins. Estimates of the required amount and density (amount per 100 kcal) needed in complementary foods are then calculated based on the difference between recommended intakes and the amounts obtained from human milk by young children in developing countries. The period considered is from 6 mo through 2 y of age; infants should be exclusively breast-fed for the first 6 mo. After age 2 y children are assumed to be less dependent on complementary feeding and more likely to consume usual household foods.
| The contribution of human milk to meeting requirements for B vitamins |
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For predicting risk of micronutrient deficiencies in breast-fed children and their mothers and for planning appropriate interventions including fortification of complementary foods, it is useful to classify micronutrients into two groups during lactation (1). The B vitamins in group I include thiamin, riboflavin, niacin, vitamin B-6, vitamin B-12, pantothenic acid, biotin and choline. Group I micronutrients are of greatest concern during lactation because low maternal intake or stores of these nutrients results in lower concentrations in human milk, which could adversely affect infant status and development. In addition, infants stores of these nutrients are readily depleted, increasing the childs dependence on adequate amounts in complementary foods. Maternal supplementation with these nutrients is likely to increase their concentrations in human milk rapidly. Folate is the only B vitamin in group II. For nutrients in this group, maternal intake from diet or supplements has relatively little effect on their concentration in human milk, which is relatively independent of maternal intake and status. Consequently, the child is relatively well protected from maternal deficiency and the mother runs the greatest risk of depletion during lactation if her intake does not meet requirements.
The concentrations of B vitamins in the human milk of well-nourished women are shown in Tables 1, , . These values were taken from the report on Dietary Reference Intakes (DRI)2 for the B vitamins issued by the Institute of Medicine (2). They were estimated on the basis of all available information about normal milk concentrations. The sources of the data used to make these estimates are referenced in the Institute of Medicine report.
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| Derivation of recommended intakes for infants and young children |
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For ages 1224 mo, all EAR recommendations were extrapolations down from the adult EAR + 2 SD to derive the Recommended Dietary Allowance (RDA). The RDA is expected to meet the needs of practically all children in that age group. For two of the B vitamins (pantothenic acid and biotin) and choline, the recommended intakes between ages 1 and 2 y are set as AIs because the adult recommendations are also set as AIs (data were not sufficient for estimating EAR).
The above explanation of how the recommended intakes were derived shows why the recommended intakes for infants are probably generous and that there is a substantial lack of supporting quantitative data with which to set more precise recommendations.
| Comparison with Dietary Reference Values of the United Kingdom |
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50 µg/L) rather than the 85 µg/L used in the DRI calculations. The discrepancy may be due to the analytical difficulty of completely extracting milk folate so that the lower value is an underestimate of the true concentration. | B vitamin and choline deficiencies in infants and young children |
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The average concentration of thiamin in human milk is estimated to be 0.21 mg/L. The concentration falls rapidly and substantially during maternal depletion of the vitamin, which can result in infantile beriberi within a few weeks after birth (2,6). Symptoms of thiamin deficiency in infants include peripheral neuropathy, encephalopathy and cardiac failure (6). Low human milk thiamin values have been reported in undernourished lactating women in India [0.11 mg/L, increasing to 0.22 mg/L after maternal supplementation (7)] and The Gambia [0.16 mg/L, increasing to 0.22 mg/L after maternal supplementation (8)]. Clinical manifestations of thiamin deficiency are now isolated to locations such as refugee camps (16), although they used to be quite common in populations consuming polished rice as their dietary staple. Grain products are the most important dietary source of thiamin but most of the vitamin is lost during the production of polished rice and white flour. The main dietary sources in industrialized countries are enriched or fortified cereal products, whole-grain cereals, pork and pork products. It seems probable that subclinical thiamin deficiency could be a common problem where complementary foods consist of polished or refined cereals but this has been inadequately investigated.
Riboflavin.
Similar to the situation with thiamin, human milk riboflavin concentrations are very sensitive to maternal intake and status and respond to maternal supplementation with the vitamin. Reported low human milk values, compared with the 0.35 mg/L in well-nourished women, include 0.20 mg/L in undernourished Indian women consuming only 0.18 mg/d [compared with the RDA of 1.6 mg/d for lactating women (17)], 0.22 mg/L in poor East Indian women (18) and 0.16 mg/L in Gambian women consuming 0.5 mg/d (9). Only 36% of the East Indian infants had a normal erythrocyte glutathione reductase activity coefficient (EGRAC) at ages 06 mo as did 9% of their mothers. A supplement of 2 mg/d for 12 wk increased the milk riboflavin in the Gambian women to 0.23 mg/L.
Riboflavin deficiency is more common where the intake of animal products is low. The global prevalence is uncertain but very high prevalences were reported in China (19), lactating women (20) and the elderly in Guatemala (21) and rural children in Mexico (22). Reports of the prevalence of riboflavin deficiency in infants and children are limited. Based on usually accepted EGRAC values, infants in The Gambia were born riboflavin deficient and if not supplemented remained so during their 1st 2 y (23). A weaning food supplement, providing 0.150.20 mg of riboflavin/d in addition to their normal intake from human milk and local complementary foods (0.130.21 mg/d), normalized riboflavin status during the supplementation period but it rapidly became abnormal again once the fortified food was withdrawn (23). In a study of Ghanaian infants, 208 were assigned to various dietary treatments from ages 6 to 12 mo: Weanimix, a local cereal-legume blend; Weanimix fortified with vitamins and minerals including either 19.5 or 9.8 mg riboflavin/kg; Weanimix plus dried fish powder; or a fermented maize porridge plus fish powder (24). At age 12 mo the fortified Weanimix contributed 0.87 mg of riboflavin/d compared with an intake of
0.1 mg/d from the other three complementary foods. The erythrocyte riboflavin content did not change during the 612 mo and surprisingly no significant difference occurred among the dietary groups at 12 mo. Foods high in riboflavin include meats, milk and dairy products, eggs and fish. In developing countries most of the riboflavin usually comes from green vegetables whereas cereals have a relatively low content.
Niacin.
Because niacin can be synthesized from tryptophan, this amino acid makes a substantial contribution to niacin status; 1 mg niacin can be synthesized from 60 mg tryptophan (1 mg niacin equivalents), although there is believed to be substantial interindividual variability in the efficiency of this conversion and it is positively related to tryptophan intake. The tryptophan in human milk (which contains only 2.1 mg of tryptophan/L) is assumed to make a relatively small contribution to the niacin status of infants aged 06 mo because of the high demand for tryptophan for protein synthesis and the low amounts consumed. Thus the recommended intake for infants of this age is for preformed niacin rather than niacin equivalents (3). For older age groups the requirement is expressed on the basis of niacin equivalents and is obtained by extrapolating down from adult requirements on the basis of body weight.
Pellagra is the classical clinical syndrome caused by niacin deficiency. It is characterized by a pigmented rash upon exposure to sunlight, a red tongue, gastrointestinal disturbances and neurological abnormalities, including apathy. Once a common condition in populations consuming maize, which is low in both available niacin and in tryptophan unless alkali treated to improve niacin bioavailability, clinical symptoms of deficiency are rarely reported today. Exceptions include occasional cases in India, China, Africa and in refugee populations (25). Apart from the obvious contribution of niacin fortification in cereals in some parts of the world, it is not clear why the global prevalence of clinical deficiency has become much less common. Marginal deficiency may occur in infants and young children fed predominantly untreated maize or low protein starchy foods. No studies have addressed this question. Deficiencies of riboflavin (26), vitamin B-6 (27) and iron (required for the conversion of tryptophan to niacin) may contribute to the risk of niacin deficiency.
Good dietary sources of bioavailable niacin include meat (especially liver), fish, poultry and legumes. Other sources include cereals, seeds, milk and green leafy vegetables. Enriched and whole-grain cereals and fortified ready-to-eat cereals are major sources of niacin in industrialized countries. There is a lack of information on the bioavailable niacin in various foods.
Vitamin B-6 [pyridoxine (PN)].
Normal human milk vitamin B-6 concentrations are
0.13 mg/L. Deficiency symptoms (convulsions) occurred in infants consuming an inadequate formula that provided
0.06 mg/L but not in those fed a formula containing
0.1 mg/L (0.075 mg/d) (11). Little information exists on the prevalence of vitamin B-6 deficiency in developing countries but deficiency may be more common than is generally recognized. In a peri-urban community near Cairo in Egypt, one-third of a group of lactating women had low concentrations (<0.068 mg/L) of vitamin B-6 in their milk (10); the mean milk vitamin B-6 concentration was 0.084 mg/L. Those women with lower milk concentrations showed changes in behavior as did their infants. Milk vitamin B-6 concentrations in poor Indian women averaged 0.08 mg/L, which increased to 0.16 mg/L when maternal intake was increased from 0.35 mg/d by a 40-mg/d supplement (7). Surprisingly, the average milk vitamin B-6 concentration was 0.12 mg/L in Gambian women and was not increased by supplementation (8).
A group in Finland reported vitamin B-6 deficiency in breast-fed infants and its association with poor growth. Vitamin B-6 status was assessed in infants who were exclusively breast-fed for 6 mo, given additional solids from 6 to 9 mo and given formula after 9 mo if needed (12). Of the 44 infants, 7 had at least one abnormal vitamin B-6 status measurement between ages 4 and 6 mo. These 7 infants grew more slowly in length between 6 and 9 mo, even after sex, size at birth, parental height and previous rate of length and weight increase were controlled for. These associations between vitamin B-6 status and growth are surprising but consistent with the fetal growthpromoting effects of 2 mg/d of PN hydrochloride provided to pregnant women in Japan (28). In a subsequent report by the Finnish group, infant and maternal vitamin B-6 status was followed longitudinally between 2 and 12 mo postpartum (29). The number of mother-infant pairs fell from 119 at 2 mo to 7 at 12 mo but >100 were studied at 6 mo. Half of the mothers took vitamin B-6 supplements during pregnancy and all took 1 mg/d of PN hydrochloride during lactation. Infant vitamin B-6 status was adequate during the 1st 4 mo of life and independent of maternal status. However, some infants had low values at 4 mo, and these were born to mothers who did not take vitamin B-6 supplements during pregnancy. By 6 mo more infants were vitamin B-6 deficient even if their mothers status was adequate. The authors suggested that maternal vitamin B-6 intake during pregnancy was the most important determinant of infant vitamin B-6 status and that for some infants (especially those whose mothers did not take supplements in pregnancy) human milk alone was not an adequate source of the vitamin. Good dietary sources of vitamin B-6 include enriched and fortified cereals (in industrialized countries), meats, potatoes, bananas, legumes, nuts and seeds. The milling of cereals removes a high proportion of this vitamin.
Folate.
Human milk contains a relatively high concentration of folate in the monoglutamate form. The folate concentration falls little as a result of maternal folate depletion, so that the mother rather than the infant tends to become more depleted and human milk folate is maintained at the expense of maternal stores (13). There are no reports of folate deficiency anemia occurring in an exclusively breast-fed infant even if the mother is deficient in the vitamin. Low erythrocyte folate occurred in
35% of Gambian children ages 3 mo to 4 y and was corrected by a 5-mg (relatively high dose) folic acid supplement (30). We have found a low (usually zero) prevalence of low serum folate concentrations in adults, preschoolers and schoolchildren in Mexico (22,31,32) and in schoolchildren in Guatemala (33) and Kenya (34).
In rats mild and severe iron deficiency imposed during pregnancy and lactation significantly reduces the secretion of folate into human milk (35). This is not corrected by folic acid supplementation (36). Whether this association occurs in humans is not clear.
Vitamin B-12.
Data are accumulating to show that vitamin B-12 deficiency is highly prevalent in young children in developing regions of the world including countries in Latin America. In a sample of 128 Guatemalan infants aged 712 mo, we found that 25% had vitamin B-12 deficiency (serum vitamin B-12 < 150 pmol/L) and an additional 36% had low serum vitamin B-12 (150220 pmol/L) (unpublished data). These infants had been predominantly breast-fed. Low maternal milk concentrations are probably the cause of this high prevalence of deficiency. In a peri-urban Guatemalan community, concentrations of vitamin B-12 in milk were low in 31% of women at 3 mo of lactation (15). Deficient or low serum vitamin B-12 occurred in 32% of the women and elevated urinary methylmalonic acid occurred in 12% of their infants; milk vitamin B-12 concentration was inversely correlated with infant urinary methylmalonic acid (which increases in vitamin B-12 deficiency). In rural Mexico, milk vitamin B-12 was low in 62% of women at 68 mo of lactation and was strongly correlated with maternal plasma vitamin B-12 (31). Plasma vitamin B-12 was deficient in 30% of these women and low in an additional 25%. A strong association between maternal intake of vitamin B-12 and the concentration of the vitamin in human milk was observed in several studies, including a study of strict vegetarian women in Boston (14). In the Boston study, maternal avoidance of animal products for 45 y was associated with lower milk levels of vitamin B-12.
The early onset of deficiency in these infants would be exacerbated by a low intake of animal products and subsequently of vitamin B-12 in complementary foods. For children aged 1.52.5 y in three separate studies in rural Mexico, mean prevalences of deficient and low plasma vitamin B-12 concentrations ranged from 10 to 40% and 1633%, respectively (22,32). As is the situation for most nutrients in children in this age range, the prevalence of deficiency tended to fall spontaneously as the children grow older. Nonetheless, vitamin B-12 deficiency is of concern because it has been associated with slow growth and developmental delays in infants and children.
Pantothenic acid, biotin and choline.
Dietary pantothenic acid deficiency can be created only by feeding individuals diets completely devoid of the vitamin (3,37). In mice a certain amount is synthesized by intestinal bacteria, but the contribution of bacterial synthesis to human pantothenic acid status is not known. No studies of pantothenic acid status in children have been done. Pantothenic acid is widely distributed in both plant and animal foods, but relatively little good quantitative information exists because of a lack of interest in the vitamin and slow development of analytical methods. Chicken, beef, potatoes, oat cereals, tomatoes, eggs, broccoli and whole grains are major sources; refined grains have a lower content. For example, processing and refining grains produced a 3774% loss of pantothenic acid (38). Usual maternal intakes of pantothenic acid were correlated with the milk concentration of the vitamin in poor Indian women (17) and in a group of 17 women in Utah (39). Maternal supplementation increased the amount in milk fivefold (39).
Thus the possibility exists that pantothenic acid deficiency may occur in infants consuming milk produced by mothers deficient in the vitamin who consume predominantly refined cereals. However, because of the widespread distribution of the vitamin in foods and the fact that the diets of adults have to be devoid of the vitamin to induce deficiency, fortification of complementary foods with pantothenic acid does not appear to be a priority.
Clinical symptoms of biotin deficiency (including neurological symptoms, loss of hair, and a red scaly facial rash) occur only in individuals who consume raw egg white, which binds biotin, and in patients with malabsorption who are given total parenteral nutrition solutions devoid of the vitamin. Biotin status is somewhat lower in pregnant women, based on biochemical indices. Symptoms of deficiency occurred within 36 mo of infants being supported on total parenteral nutrition solutions lacking biotin (40). No cases of deficiency in infants fed normal foods have been reported and justification is not sufficient to support a recommendation to add biotin to complementary foods.
The recent DRI for B vitamins also included, for the first time, recommended intakes for choline (3). The adult AI for choline is based on the observation that liver damage occurred when low choline diets were fed. Choline is widely distributed in foods; rich sources include peanuts, milk, liver and eggs. Choline in human milk is correlated with maternal choline intake (41). At this time, evidence is not sufficient to support the need for choline as a complementary food fortificant.
| Upper safe levels of intake |
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| Estimated amounts for fortification of complementary foods |
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The amount of each vitamin consumed in human milk was calculated from the concentration of each B vitamin in human milk (3) and the estimated average milk volume consumed by infants in each age group in developing countries (42). For ages 68, 911 and 1224 mo, respectively, average milk intakes were taken to be 0.607, 0.557 and 0.509 L/d, equivalent to 413, 379 and 346 kcal/d. The amount of the vitamins needed in complementary foods was calculated as the percentage of the AI or RDA, the actual amount (weight) and the amount per 100 kcal (density; energy from complementary foods estimated as the difference between energy requirements and the energy consumed in human milk, which is 202, 307 and 548 kcal/d for ages 68, 911 and 1224 mo, respectively). Based on this nutrient density, the amount of each vitamin that should be added to 40 g (for ages 612 mo) or 60 g (for ages 1224 mo) of complementary food is presented. These typical intakes of dry complementary food are estimated on the basis of observations from Mexico, Ghana and Peru, with the energy content assumed to be 440 kcal/100 g dry food (4).
The final recommendations for the amounts of vitamins to be added are summarized in Table 6. In addition to the values from the last columns of Tables 13, Table 6 provides values for the amounts to be added to a generic product in the event that the same product was to be consumed across the age span from 6 to 24 mo, with a usual intake of 50 g/d of dry food. These values are simply the highest estimates across the three age groups of the amount that should be added per 50 g food. Because of the negligible toxicity of these vitamins, this is a safe approach. Note that these estimates assume that human milk contains the amounts of B vitamins present in the milk of well-nourished women. Where local data indicate that the concentration of one or more B vitamins in maternal milk is low, these recommendations should be adjusted upward accordingly.
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20% during storage of white wheat flour for 2 mo and breakfast cereals for 3 mo. Cooking breakfast rolls causes a 2025% loss of fortificant folic acid (43). Light in the presence of moisture will destroy riboflavin, vitamins B-6, B-12, and folic acid, making the use of opaque packaging important. No storage losses are assumed in the estimates provided in Table 5 because these can be minimized by good packaging and are relatively small. Of greater concern is the loss of B vitamins during heating. The additional amounts suggested in the final column of Table 6 are based on losses during cooking of unfortified foods. They are probably not valid for synthetic vitamins, which depending on their form, may be more or less stable than those that occur naturally. Most commercial fortified foods are produced in an "instant" form so that prolonged heating is not required. The possible cooking losses are included in Table 6 as a reminder that the final content at the point of consumption must be measured to estimate the appropriate overage and that appropriate recommendations for preparation should be clearly stated on the packaging. Losses during storage and preparation must also be assessed under field conditions as one step in product development. Losses during food preparation may be so large that adjusting recommended fortification levels for age, geographic location and usual human milk consumption could be relatively unimportant in practice. The adequacy and safety of these recommended fortification levels must be evaluated by assessments of the nutritional status of the children consuming the fortified products.
| FOOTNOTES |
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3 Abbreviations used: AI, Adequate Intake; DRI, Dietary Reference Intake; EAR, Estimated Average Requirement; EGRAC, erythrocyte glutathione reductase activity coefficient; PN, pyroxidine; RDA, Recommended Dietary Allowance; UL, Tolerable Upper Intake Level. ![]()
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S. Taneja, N. Bhandari, T. A Strand, H. Sommerfelt, H. Refsum, P. M Ueland, J. Schneede, R. Bahl, and M. K. Bhan Cobalamin and folate status in infants and young children in a low-to-middle income community in India Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1302 - 1309. [Abstract] [Full Text] [PDF] |
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T. A Strand, S. Taneja, N. Bhandari, H. Refsum, P. M Ueland, H. K Gjessing, R. Bahl, J. Schneede, M. K Bhan, and H. Sommerfelt Folate, but not vitamin B-12 status, predicts respiratory morbidity in north Indian children Am. J. Clinical Nutrition, July 1, 2007; 86(1): 139 - 144. [Abstract] [Full Text] [PDF] |
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G. Papastoyiannidis, A. Polychroniadou, A.-M. Michaelidou, and E. Alichanidis Fermented Milks Fortified with B-group Vitamins: Vitamin Stability and Effect on Resulting Products Food Science and Technology International, December 1, 2006; 12(6): 521 - 529. [Abstract] [PDF] |
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C. K. Lutter and K. G. Dewey Proposed Nutrient Composition for Fortified Complementary Foods J. Nutr., September 1, 2003; 133(9): 3011S - 3020. [Abstract] [Full Text] [PDF] |
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