Growth and micronutrient needs of adolescents

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1 (2000) 54, Suppl 1, S11±S15 ß 2000 Macmillan Publishers Ltd All rights reserved 0954±3007/00 $ B Olmedilla* and F Granado Servicio de NutricioÂn, Unidad de Vitaminas, ClõÂnica Puerta de Hierro, Madrid, Spain Objective: This paper focuses on micronutrients in relation to needs throughout adolescence, a period which involved growth and development that occur through a complex interaction of genetic instructions, hormones and environmental in uences, many of them of dietary origin. In the context of micronutrient `needs' it is of special importance to differentiate between the `nutritional needs' and `metabolic needs'. Two main questions arise in relation to the micronutrient needs: (1) why are micronutrients necessary? and (2) how are their needs assessed? Results: The `necessary' amount will differ according to the objectives pursued: (a) to achieve a satisfactory rate of growth and development; and (b) to maintain `optimal health'. The assesment of micronutrient needs and status has proved to be dif cult, but when elucidating and establishing them, it is imperative to arrive at the estimates in the light of their interdependent role in metabolism and functions. The knowledge of micronutrient metabolic needs can be approached through epidemiological observations, bioavailability studies and clinical trials. However, there is a nearly total absence of reports on the particular metabolic and dietary needs of adolescents. Conclusion: Thus more studies are required in relation to the effect of features associated with adolescence on `needs', evaluating their impact on bioavailablility and turnover (storage and losses), and the interactions among micronutrients in the assessment of metabolic and nutritional needs. Another aim should be to establish static and functional indexes, reference values and cut-off points in adolescence, to be used in clinical and epidemiological studies. Future studies should focus on needs to determine those required to maintain `optimal functions' and regarding the potential prevention of chronic adult diseases. Descriptors: micronutrient needs; adolescence; metabolic needs; nutritional needs; growth (2000) 54, Suppl 1, S11±S15 Introduction The micronutrients are a group of dietary constituents characterized by the low amounts in which they are found in the diet, but which nevertheless are the key to optimal macronutrient metabolism, and by the interdependent role of many of them in metabolism and functions. Micronutrients are essential for growth and development, utilization of macronutrients, maintenance of adequate defences against infectious diseases and for many other metabolic and physiological functions (WHO, 1996). The micronutrients classically considered as essential comprise just 13 vitamins and around 16 minerals, although our diet includes a multitude of other compounds, some of which most likely, but not de nitely, are responsible for actions that are bene cial to the human body. In this paper we will focus on the micronutrients in relation to the needs throughout adolescence, a period which involves growth and development that occur through a complex interaction of genetic instructions, hormones and environmental in uences, most of them of dietary origin (Lachance, 1998a). This `dietary origin' is also linked to the third key word of this communication: nutrient needs. In the context of micronutrients, it is of special importance to keep in mind the difference between the two words *Correspondence: B. Olmedilla, Clinica de Puerta de Hierro, Servicio de NutricioÂn, c/san Martin de Porres 4, E Madrid, Spain. bego.olmedilla@nutr.cph.es Guarantor: B. Olmedilla. Contributors: BO: responsibility for the planning and writing of the manuscript. FG: advice and bibliography search for the manuscript. `needs' and `requirements', which are often used indistinctly. We have a great deal more information on the micronutrient `requirements' in terms of `nutritional needs', that is, the amount of a nutrient that must be supplied in the diet in order to satisfy the `metabolic need'. The concept that is crucial between the two is bioavailability, meaning the fraction of the ingested nutrient that is utilized or stored for normal physiological functions. In general, the amounts of micronutrients considered as `needs' are lower than those estimated as requirements which, in turn, are lower than the recommendations, especially when we refer to cationic minerals and fat-soluble vitamins. Needs: why are micronutrients necessary? This is the rst point that must be addressed before any evaluation of the needs for a given nutrient, since the `necessary' amount will differ according to the objectives pursued, which will depend on what it is known about micronutrient functions and metabolism in the human body (Figure 1). Therefore, two general aims can be expressed as follows: (a) to achieve a satisfactory rate of growth and development (the basic aim); and (b) to maintain `optimal health'. The rst aim is related to metabolic needs and efforts to avoid de ciency. However, on compiling information from the literature, it is surprising how scanty the data upon which the recommendations (`nutritional needs') for adolescent nutrient `needs' are based and the fact that they are

2 S12 Figure 1 pursued. Micronutrient needs are different according to the objectives usually obtained by interpolating or extrapolating data collected in adults and children, rather than basing them on actual experimental evidence (Dwyer, 1981, 1996; RDA, 1989). First, the assumption is accepted that, after infancy, micronutrients are needed in increasing amounts in proportion to energy requirements for metabolic demands of growth, until the levels recommended for adults are reached. Second, nutritional needs or `requirements' are established by evaluating dietary micronutrient intakes and comparing them with the `recommendations' made by different scienti c organisms to determine whether or not these recommendations are met. Finally, when we actually nd information on the needs (metabolic needs), these are investigated generally in relation to special situations such as pregnancy, the practice of sports, certain diseases, etc., but not in apparently healthy adolescents who need, for tissue growth, an amount equal to the rate of accretion plus the content of newly formed tissue. The second objective, to maintain `optimal health', is pursued by growing numbers of researchers whose aim is to achieve the maximum development of physical and psychological aptitudes. From this perspective, not only the `classical' functions but also the newer roles ascribed to several micronutrients, as well as the saturation of body stores, should probably be considered. In the context of adolescence, this aim would involve the creation and veri cation of dietary regimens that include `proper attitudes' to carry on into adulthood, rather than sporadic supplementation of the diet with certain micronutrients, given that `inappropriate micronutrient intakes' over long periods of time are considered to contribute to the development of chronic and degenerative diseases, the etiology of which is associated with micronutrient imbalance. The micronutrients with potential health bene ts for disease prevention during adulthood include Ca and others involved in reaching maximum peak bone mass Figure 2 In uencing factors and approaches to the assessment of micronutrient needs. and osteoporosis prevention, certain micronutrients or non-nutrients (carotenoids, vitamins E and C, etc.) with roles in preventing some chronic and degenerative diseases (certain cancers, cardiovascular disease, macular disease) by means of mechanisms such as antioxidant activity, regulation of expression of key genes, etc., and those involved in enhancing the immune system (to reach `optimum' performance) (Weaver, 1992; Berdanier, 1996; WCRF=AICR, 1997). Other examples of micronutrients linked to health and diseases in a nontraditional fashion are those related to anemia (Fe, folic acid, vitamins B-12, B-6 and A, Cu, Co, Mg and Zn), birth defects (vitamin A, folate), cancer (vitamins E and C, folate, carotenoids, Fe), central nervous system function (Fe, I, Se, Zn), cognitive function (Fe, Zn, vitamins B-1 and B-12), gene interactions (Fe, Zn, vitamins B-6, C and K), heart disease (vitamins E, C, B-6 and B-12, carotenoids, folic acid and Fe), immune system development and host defence (Zn and vitamin E) and osteoporosis (Ca, vitamins D and K). Needs: how are they assessed? Assessment of micronutrient needs and status has proved dif cult. These estimates must be elucidated and established in the light of their interdependent role in metabolism and functions. Metabolic steps require the concomitant involvement of one or more vitamins and minerals and, as a general consequence, the interactions among the micronutrients as well as other food components (nutrient and nonnutrient) are of great importance and may occur at different levels (Figure 2). Especially during the second decade of life, nutrient requirements (nutritional needs) and metabolic needs are more closely associated with physiological than chronological age; thus, it is useful to consider this decade as consisting of two periods, pubescence and adolescence, since these needs are affected by growth and the resulting changes from sex hormone secretion. The knowledge of micronutrient metabolic needs, which in general are considered to be met if normal functions, health and body weight are maintained and depletion prevented, can be approached through epidemiological observations, bioavailability studies and clinical trials involving supplementation. Epidemiological observations Epidemiological observations are based on surveys of dietary intake or biochemical analysis of blood. In general, micronutrient recommendations in adolescence are established by interpolating from those obtained by measuring the intake of apparently healthy breastfed infants, children or adults. However, they may differ greatly in adolescents given that pubertal growth requires a higher nutrient-toenergy ratio for many micronutrients if they are to sustain the needs for the growth and accretion of lean tissues and their maintenance (Dwyer, 1996). Epidemiological studies of micronutrients based on diet and=or blood levels present a number of problems. On the one hand, there is little information on dietary and biochemical related factors and interactions. In addition, Food Composition Tables present widely varying micronutrient contents due to the characteristic variations in concentrations and=or to the use of differing analytical procedures or conceptual approaches. The latter results from the lack of

3 uniformity in the terminology utilized. Moreover, a large number of micronutrients are used as food additives or to fortify and enrich foods, and the amounts ingested in this manner are not usually included in the estimates of intake. Finally, the correlation between their content in food and in blood is usually poor. Bioavailability studies Bioavailability is the response of the individual to the diet and re ects an integration of the various components of the processes whereby an ingested nutrient becomes absorbed and utilized for a metabolic function. Absorption is usually the major component of bioavailability, but assimilation Ð comprising transport, cellular uptake, and incorporation into a molecularly active form Ð is signi cant in the case of some nutrients. The determinants of bioavailability can be classi ed as intrinsic factors (i.e. physiological status, body stores, homeostatic control, sex) and extrinsic or dietary factors (i.e. amount ingested, the chemical form of the compound in the intestine and, the interactions of inhibitors or enhancers in the diet). The methods for assessing micronutrient bioavailability include metabolic studies involving foods labelled with stable or radioactive isotopes, intestinal lavage, balance studies, tolerance tests and growth measurements (Fairweather-Tait, 1998). The studies of micronutrient bioavailability are complicated by endogenous levels of the nutrient, the extensive (and possibly ill-de ned) metabolism of the nutrient potentially to numerous bioactive metabolites and the lack of knowledge of the kinetics of turnover and excretion of some nutrients. Clinical trials The fact that low protein intake is usually accompanied not only by low energy intake but by inadequate amounts of important micronutrients (Fe, Zn, Cu, Ca and vitamin A), and that improvement in the linear growth of stunted children after supplementation with energy-rich or protein-rich foods (alone or in combination with other foods or nutrients) has been observed in some supplementation trials but not in others, has raised the question of the extent to which micronutrient de ciencies impair linear growth of human populations. To check the implication of a certain micronutrient in the achievement of adequate growth, any clinical or biochemical manifestation of its inadequate supply prior to supplementation would be desirable, but this is rarely the case. The clinical manifestations of micronutrient de ciency result when the change in metabolism is such that homeostatic controls can not supply the various pools necessary for maintaining biochemical functions. The administration of a micronutrient may produce a positive response when the de ciency is due to a micronutrient that acts as a limiter (e.g. it is quite possible that linear growth only responds to iron supplementation if the child was initially anemic), on the other hand, except in the case of iodine de ciency, where status is less dependent on the general adequacy of the food supply, a lack of response in an individual may indicate the existence of multiple rather than a single, growth-limiting nutrient de ciency. Studies of intervention with single micronutrients have focused on children up to the onset of puberty (as knowledge of needs during adolescence is apparently of lower priority) and have produced con icting results concerning the ability of this approach to reverse stunted growth. There are several possible explanations for the lack of consistency among studies, the most important being poorly de ned groups (no selection criteria or inclusion of short or underweight children; inclusion of patients with recent diarrhea or protein-energy malnutrition; exclusion of severely anemic individuals; age of children unde ned, etc.) and differences in the amounts and chemical forms of the micronutrients used. Moreover, identical results may have several interpretations, leading to different conclusions. Concerns on the assessment of micronutrient needs There are still no ideal clinical or biochemical criteria to assess micronutrient de ciency (or toxicity) for many of these substances. And, in those cases in which they exist, there is usually a period during which a compensatory mechanism (i.e. catabolism, functions) can mask a latent de ciency. In addition, there is wide variability among analytical techniques with respect to sensitivity, precision, and analytical quality control of data. Finally, there are still only a few studies on micronutrient bioavailability that focus on other compounds in addition to that which is the object of evaluation. Some comments on micronutrient needs of special relevance during adolescence There is less data on vitamin requirements for adolescents than on minerals. Of the latter, we have the greatest amount of direct information on needs in adolescents for iron, calcium, zinc, copper and uorine. Classical studies have shown calcium, iron and zinc to be essential micronutrients for growth and sexual maturity, and their retention by the body increases signi cantly during the growth spurt. One example of how adolescence may in uence absorption and metabolism that will lead to speci c needs and requirements is the case of calcium, the body stores of which are contained mainly in the skeleton. Approximately 45% of the total adult skeletal mass is laid down during adolescence, and most of the skeletal growth takes place during pubescence. For many of the variables used to calculate the calcium requirement (dietary and physiological factors), too few data points are available or there are none whatsoever for certain age groups (Moro et al, 1996). In a recent review, calcium requirements at various stages of growth were estimated by summing up the needs for skeletal accretion plus endogenous losses and adjusting for intestinal absorption (Weaver, 1994). Regarding absorption of ingested calcium (for calcium intake <1200 mg=day), it has been observed that adolescents are no more ef cient at absorbing calcium than adults, the rate (35% for children and adolescents) being one-third lower than that assumed for adults (50%) (Andon et al, 1994). Whether this absorption increases during the adolescent growth spurt is controversial (Weaver, 1994). With respect to obligatory losses of calcium, in adolescence they are assumed to be no greater than average. However, although there are few studies on this aspect, obligatory losses are most likely greater during the adolescence growth spurt, as compared with preadolescents, at a time of greater need, although they are still much lower than those observed in adults (Weaver, 1994). Calcium intake in the healthy individual allows the body to maintain a balance, but short-term studies fail to predict S13

4 S14 adaptation to speci c levels of calcium intake, and adolescents should maintain a suf ciently positive balance to meet skeletal demands, presumably to maximize bone mass. According to the current recommendations for calcium, the goal during youth is to maintain a calcium intake that allows individuals to reach their full genetic potential for acquiring skeletal mass, which helps to prevent osteoporosis in adulthood. The various estimates of peak daily calcium retention vary widely. The same circumstance is observed with the timing of the peak retention rates, which vary according to the approach. Nevertheless, all methods show that peak daily increments are greater, last longer, and occur later in males than in females, and that total body calcium content differs depending on sex and on size. With respect to iron, concerns during adolescence are related to the need to increase the body stores during growth and to maintain the hemoglobin concentration (25% increase in red blood cell mass in total body iron during the year of peak growth). Boys increase their muscle mass and blood volume more rapidly than girls, who require less iron for growth but have increased iron needs due to menstrual losses. Iron-de ciency can lead to anemia, which involves impaired physical growth, mental and motor development and learning capacity in children and adolescents and may impair body temperature regulation, lower resistance to infection and possibly affect attention. Iron-de ciency anemia is not eradicated by iron supplementation, perhaps because iron is not always the limiting nutrient and others required in the formation of blood are more limiting (i.e. vitamin B-6, folate, magnesium and zinc) (Lachance, 1998b). Zinc needs are higher at times of maximal rates of protein synthesis, so adolescents may be susceptible to Zn de ciency. The signs of this de ciency are the result of the diminution of one or more of its biological functions (catalytic, structural, regulatory and immune), leading to metabolic disturbances of a wide range of hormones, cytokines and enzymes involved in growth and bone development (e.g. IGF-1, growth hormone, thyroid hormone, etc.), as well as of the immune system, the structure of the skin and dark adaptation. That reduced function of the immune system may be related to impaired protein synthesis, dependent, in turn, on an intact IGF-1 system (Clausen & Dùrup, 1998). In Zn-depleted children, growth is impaired and Zn repletion promotes growth and increases serum IGF-1. There are a number of observations that suggest that a moderate-to-severe Zn de ciency in children depresses growth (without an apparent reduction in tissue concentrations), appetite, skeletal maturation and gonad development, which can be reversed with Zn treatment. However, measurements of endogenous losses using Zn stable isotopes con rm that there is a reduction in the losses coinciding with reduced dietary Zn (resulting from an adaptation to low Zn intake). Studies in adolescents have dealt with Zn de ciency in association with de ciencies of other nutrients. Interdependent role of micronutrients and its potential impact on their biological activities In the metabolism and functions of the micronutrients, there are numerous interactions at different levels (absorption, transport and functions), a circumstance which explains why the underlying cause of a de cit is not always an inadequate supply of the major micronutrient involved. Some of the interactions in which the aforementioned minerals are involved at different levels are mentioned below. Interactions between calcium and other dietary components The effects of calcium and phosphorus de ciencies may arise from an imbalance between the two bone-forming minerals in the diet. Another mineral implicated in bone composition is magnesium, and there is evidence in animals that its de ciency can provoke growth retardation and disturbance of calcium metabolism. Metabolic synergism involving calcium, magnesium and potassium in uences the physiological and functional effectiveness of all three elements in the maintenance of healthy nervous tissue and of skeletal integrity. Elevated calcium, either due to dietary intake or to supplementation, has been reported to reduce absorption of iron, zinc, magnesium and other essential minerals, especially those from diets rich in vegetables (rich in phytic acid), and to increase fecal zinc loss. Calcium absorption is potentiated by vitamin D, and diminished by oxalates in the diet. An excessive intake of protein or dietary acidosis leads to greater calcium losses. Interactions between iron and other micronutrients It should be pointed out that vitamin A de ciency increases the liver storage of iron and that this sequestered iron is not available for incorporation into hemoglobin. The precise mechanisms of this relationship between vitamin A and iron metabolism remain to be elucidated; they are in uenced by many factors, one of the most important of which is the presence or absence of infection. One explanation that has been suggested is that the administration of vitamin A reduces the level of infection and that this switches off the acute-phase response, allowing increased plasma concentrations of transferrin and improved iron status (Northrop-Clewes et al, 1996). Other interactions involving iron are those occurring with vitamin C that increase non-heme iron absorption which, in turn, is decreased by tannins and by excess of calcium. High intakes of non-heme iron depress zinc absorption. Copper, as a component of proteins and enzymes, is essential for the proper utilization of iron. Interactions between zinc and other micronutrients Zinc intervenes in absorption, transport and utilization of vitamin A. In addition, an interaction between zinc and copper is suggested by the fact that supplementation with 50 mg Zn=day over a relatively short period of time results in decreased activity of the Cu-containing enzyme, superoxide dismutase, and in decreased serum ferritin concentrations. Larger doses of zinc have led to the development of anemia not responsive to iron supplementation, probably mediated through an impaired Cu status. Why it is of interest to study the micronutrient needs of adolescents As mentioned above, there is nearly a total absence of reports on the particular metabolic and dietary needs of adolescents. Thus more studies on this population are required to address the lack of knowledge on relevant

5 aspects such as the effect of features associated with adolescence (i.e. sex hormones) on `needs', evaluating their impact on bioavailability and turnover (storage and losses), and the interactions among micronutrients in the assessment of `needs' and `requirements' (synergistic, antagonist, compensatory metabolisms and bodily functions). These interactions may be important since many of them are interrelated and few studies have considered all (or at least as many as possible) of the potential determinants. Another aim should be to establish static and functional indexes (biomarkers), reference values and cut-off points in adolescence, to be used in clinical and epidemiological (long-term follow-up) studies. Future studies should focus on `needs' to determine those required to maintain `optimal functions', especially those involved in immunity and in resistance to infections. Finally, the attempt should be made to approach micronutrient status and needs during adolescence with regard to the potential prevention of chronic adult diseases that may begin in youth. References Andon MB, Lloyd T, Matkovic V (1994): Supplementation trials with calcium citrate malate: evidence in favor of increasing the calcium RDA during childhood and adolescence. J. Nutr. 124, S1412 ± S1417. Berdanier CD (1996): Nutrient-gene interactions. In: Present Knowledge in Nutrition, 7th edn, ed. EE Ziegler & LJ Filer Jr, pp 574 ± 580. Washington DC: ILSI Press. Clausen T, Dùrup I (1998): Micronutrients, minerals and growth control. In: Role of Trace Elements for Health Promotion and Disease Prevention. ed. B SandstroÈm & P Walter. Bibl. Nutr. Dieta. 54, pp 84 ± 92. Basel: Karger. Dwyer J (1981): Nutritional requirements of adolescence. Nutr. Rev. 39, 56 ± 72. Dwyer JT (1996): Adolescence. In: Present Knowledge in Nutrition, 7th edn, ed. EE Ziegler & LJ Filer Jr, pp 404 ± 413. Washington, DC: ILSI Press. Fairweather-Tait SJ (1998): Trace element bioavailability. In: Role of Trace Elements for Health Promotion and Disease Prevention, ed. B SandstroÈm & P Walter. Bibl. Nutr. Dieta 54, pp 29 ± 39. Basel: Karger. Lachance PA (1998a): Overview of key nutrients: micronutrient aspects. Nutr. Rev. 56, S34 ± S39. Lachance PA (1998b): International perspective: basis, need, and application of recommended dietary allowances. Nutr. Rev. 56, S2 ± S4. Moro M, van der Meulen MCH, Kiratli BJ, Marcus R, Bachrach LK, Carter DR (1996): Body mass is the primary determinant of midfemoral bone acquisition during adolescent growth. Bone 19, 519 ± 526. Northrop-Clewes CA, Paracha PI, McLoone UJ, Thurnham DI (1996): Effect of improved vitamin A status on response to iron supplementation in Pakistani infants. Am. J. Clin. Nutr. 64, 694 ± 699. RDA (1991): Recommended Dietary Allowances. National Research Council, 10th ed, Spanish version. Ed Consulta. WCRF=AICR (1997): World Cancer Research Fund=American Institute for Cancer Research, Food, Nutrition and the Prevention of Cancer: a global perspective. Washington DC: AICR. Weaver CM (1992): Calcium bioavailability and its relation to osteoporosis. Proc. Soc. Exp. Biol. Med. 200, 157 ± 160. Weaver CM (1994): Age related Ca requirements due to changes in absorption and utilization. J. Nutr. 124, S1418 ± S1435. WHO (1996): Preparations and Use of Food-based Dietary Guidelines, NUT=96.6. Geneva: WHO. S15

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