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European Journal of Clinical (2000) 54, Suppl 1, S11±S15 ß 2000 Macmillan Publishers Ltd All rights reserved 0954±3007/00 $15.00 www.nature.com/ejcn

Growth and micronutrient needs of adolescents

B Olmedilla* and F Granado

Servicio de NutricioÂn, Unidad de Vitaminas, ClõÂnica Puerta de Hierro, 28035-Madrid, Spain

Objective: This paper focuses on micronutrients in relation to needs throughout adolescence, a 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 European Journal of Clinical Nutrition (2000) 54, Suppl 1, S11±S15

Introduction `needs' and `requirements', which are often used indis- tinctly. We have a great deal more information on the The micronutrients are a group of dietary constituents micronutrient `requirements' in terms of `nutritional characterized by the low amounts in which they are needs', that is, the amount of a that must be found in the diet, but which nevertheless are the key to supplied in the diet in order to satisfy the `metabolic optimal macronutrient metabolism, and by the interdepen- need'. The concept that is crucial between the two is dent role of many of them in metabolism and functions. bioavailability, meaning the fraction of the ingested nutri- Micronutrients are essential for growth and development, ent that is utilized or stored for normal physiological utilization of macronutrients, maintenance of adequate functions. defences against infectious diseases and for many other In general, the amounts of micronutrients considered as metabolic and physiological functions (WHO, 1996). `needs' are lower than those estimated as requirements The micronutrients classically considered as essential which, in turn, are lower than the recommendations, espe- comprise just 13 and around 16 minerals, although cially when we refer to cationic minerals and fat-soluble our diet includes a multitude of other compounds, some of vitamins. 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 Needs: why are micronutrients necessary? relation to the needs throughout adolescence, a period which involves growth and development that occur through This is the ®rst point that must be addressed before any a complex interaction of genetic instructions, hormones and evaluation of the needs for a given nutrient, since the environmental in¯uences, most of them of dietary origin `necessary' amount will differ according to the objectives (Lachance, 1998a). This `dietary origin' is also linked to pursued, which will depend on what it is known about the third key word of this communication: nutrient needs. micronutrient functions and metabolism in the human body In the context of micronutrients, it is of special importance (Figure 1). Therefore, two general aims can be expressed as to keep in mind the difference between the two words follows: (a) to achieve a satisfactory rate of growth and development (the basic aim); and (b) to maintain `optimal health'. *Correspondence: B. Olmedilla, Clinica de Puerta de Hierro, Servicio de The ®rst aim is related to metabolic needs and efforts to NutricioÂn, c/San Martin de Porres 4, E-28035 Madrid, Spain. avoid de®ciency. However, on compiling information from E-mail: [email protected] Guarantor: B. Olmedilla. the literature, it is surprising how scanty the data upon Contributors: BO: responsibility for the planning and writing of the which the recommendations (`nutritional needs') for ado- manuscript. FG: advice and bibliography search for the manuscript. lescent nutrient `needs' are based and the fact that they are Growth and micronutrient needs of adolescents B Olmedilla and F Granado S12 and osteoporosis prevention, certain micronutrients or non- (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 `opti- mum' 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, Figure 1 Micronutrient needs are different according to the objectives Mg and Zn), birth defects ( A, ), cancer pursued. (vitamins E and C, folate, carotenoids, Fe), central nervous system function (Fe, I, Se, Zn), cognitive function (Fe, Zn, usually obtained by interpolating or extrapolating data vitamins B-1 and B-12), gene interactions (Fe, Zn, vitamins collected in adults and children, rather than basing them B-6, C and K), heart disease (vitamins E, C, B-6 and B-12, on actual experimental evidence (Dwyer, 1981, 1996; carotenoids, folic acid and Fe), immune system develop- RDA, 1989). First, the assumption is accepted that, after ment and host defence (Zn and vitamin E) and osteoporosis infancy, micronutrients are needed in increasing amounts in (Ca, vitamins D and K). proportion to energy requirements for metabolic demands of growth, until the levels recommended for adults are Needs: how are they assessed? reached. Second, nutritional needs or `requirements' are established by evaluating dietary micronutrient intakes and Assessment of micronutrient needs and status has proved comparing them with the `recommendations' made by dif®cult. These estimates must be elucidated and estab- different scienti®c organisms to determine whether or not lished in the light of their interdependent role in metabo- these recommendations are met. Finally, when we actually lism and functions. Metabolic steps require the concomitant ®nd information on the needs (metabolic needs), these are involvement of one or more vitamins and minerals and, as a investigated generally in relation to special situations such general consequence, the interactions among the micronu- as , the practice of sports, certain diseases, etc., trients as well as other components (nutrient and non- but not in apparently healthy adolescents who need, for nutrient) are of great importance and may occur at different tissue growth, an amount equal to the rate of accretion plus levels (Figure 2). the content of newly formed tissue. Especially during the second decade of life, nutrient The second objective, to maintain `optimal health', is requirements (nutritional needs) and metabolic needs are pursued by growing numbers of researchers whose aim is to more closely associated with physiological than chrono- achieve the maximum development of physical and psy- logical age; thus, it is useful to consider this decade as chological aptitudes. From this perspective, not only the consisting of two periods, pubescence and adolescence, `classical' functions but also the newer roles ascribed to since these needs are affected by growth and the resulting several micronutrients, as well as the saturation of body changes from sex hormone secretion. stores, should probably be considered. In the context of The knowledge of micronutrient metabolic needs, which adolescence, this aim would involve the creation and in general are considered to be met if normal functions, veri®cation of dietary regimens that include `proper atti- health and body weight are maintained and depletion tudes' to carry on into adulthood, rather than sporadic prevented, can be approached through epidemiological supplementation of the diet with certain micronutrients, observations, bioavailability studies and clinical trials given that `inappropriate micronutrient intakes' over long involving supplementation. periods of time are considered to contribute to the devel- opment of chronic and degenerative diseases, the etiology Epidemiological observations of which is associated with micronutrient imbalance. Epidemiological observations are based on surveys of The micronutrients with potential health bene®ts for dietary intake or biochemical analysis of blood. In general, disease prevention during adulthood include Ca and micronutrient recommendations in adolescence are estab- others involved in reaching maximum peak bone mass lished 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-to- energy 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 bio- chemical related factors and interactions. In addition, Food Composition Tables present widely varying micronutrient contents due to the characteristic variations in concentra- Figure 2 In¯uencing factors and approaches to the assessment of tions and=or to the use of differing analytical procedures or micronutrient needs. conceptual approaches. The latter results from the lack of

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

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

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