Les éléments-traces dans la nutrition humaine
Los oligoelementos en la nutrición humana
Salient issues from the Joint FAO/WHO/IAEA Expert Consultation
Robert C. Weisell, Ph.D., is a Nutrition Officer in the Nutrition Planning, Assessment and Evaluation Service of the Food Policy and Nutrition Division, FAO. He is responsible for activities in nutrient and energy requirements, nutrition assessment and food composition.
In June 1990, the Joint FAO/WHO/IAEA Expert Consultation on Trace Elements in Human Nutrition was held in Geneva.1 This article draws attention to some of the important and unique aspects of the meeting. Perhaps the most notable feature was the large number (19) of nutrients discussed: iodine, zinc, selenium, copper, molybdenum, chromium, manganese, silicon, nickel, boron, vanadium, fluoride, arsenic, aluminium, lithium, tin and toxic heavy metals - lead, cadmium and mercury. Also significant was the increased attention given to the interaction between some of these nutrients. The meeting addressed the continuum of trace elements issues, from deficiencies to toxicities. Trace elements recently found to be essential were discussed,2 as were new ways of conceptualizing the application of nutrient requirements.
1 The report of this consultation will be published by the World Health Organization in 1992.
2 I the context of this consultation, an element was considered essential to an organism when reduction of exposure to it below a certain limit would result consistently in a reduction of a physiologically important function or when the element is an integral part of an organic structure with a vital function in that organism. Proof of essentiality of an element in one animal species does not prove essentiality in another, but the probability that a function is essential in any species (including the human) increases with the number of other species in which essentiality has been proved. The definitions presented are not absolute; they depend on the judgement of what constitutes a "physiologically important function" or "consistent" functional impairment, etc.
In addition, the following general subjects were discussed:
· concepts and definitions;
· trace element bioavailability;
· analytical methodology;
· trace elements in diets;
· detection and anticipation of trace element- related disorders;
· recommendations for consideration and research.
Nutrient interactions, toxicity and deficiencies
The trace elements were not examined in isolation as in the past. Instead, consideration was given to the interaction of nutrients and other components in the diet. Among the recent investigations focusing on the interaction among trace elements is the research on the essential elements selenium and iodine. There is evidence that selenium acts as a component of the enzyme responsible for converting thyroxine to triiodothyronine (T3); thus it is possible that the systemic utilization of iodine is impaired in subjects who are deficient in selenium (Arthur and Beckett, 1989; Arthur, Nicol and Beckett, 1990).
Consideration was given both to the essential trace elements and to those potentially toxic elements whose public health effects are modified by other elements. An example of this latter phenomenon is the reduced absorption of lead by a high fibre (phytate) diet. Because toxicity is covered by other units within FAO and WHO, an exploration of all aspects of toxicity was not attempted; however, reference was made to the issue.
Unlike investigations of the macronutrients (energy, protein and fat) and micronutrients (e.g. vitamin A, riboflavin), trace elements research draws on a relatively close link between the studies conducted on humans and the studies of other animals. This is because, as a general rule, trace element deficiencies elicit non-specific symptoms such as reduced growth and development; therefore when deficiencies occur they are not easily recognized. In the laboratory it is difficult to create a deficiency and, in the case of studies involving human participants, unethical. Thus research on trace elements has relied heavily upon animal studies, with attempts to relate the findings to human conditions. One example of this practice is in research on linkages between iron, copper and lead. For some time it has been recognized that iron deficiency affects the learning ability of rats and that copper deficiency and/or excessive lead intakes exacerbate the situation. Now there is increasing evidence that the same may be true in children.
Public health implications
The Expert Consultation addressed topics that are particularly relevant to an understanding of the factors governing responses to trace element deficiency or excess. The discussion extended beyond the mere levels indicating deficiency and toxicity. Subjects such as the physiological variables modifying requirements and tolerance levels were addressed, as well as topics such as bioavailability phenomena and analytical procedures. By inclusion of these issues, it was hoped that those risks related to trace element-related diseases could be identified.
Iodine, fluorine, zinc and selenium are generally thought to be essential in humans and to present substantial public health problems if deficient. Fluorine was considered essential because of its role in resistance against dental caries - was considered a physiologically important function. Even though uncomplicated selenium deficiency has not yet been demonstrated in humans, the enzyme glutathione peroxidase was considered to be a structure with a vital function and, therefore, its constituent selenium was also considered essential. Deficiencies of copper, molybdenum and chromium in humans have been described, but their importance for public health is poorly understood at present. The essential elements cobalt (in the form of vitamin B12) and iron were excluded from the consultation because they have been discussed in an FAO/WHO publication (FAO/WHO, 1988).
Cadmium, lead and mercury are of primary concern as contaminants; the danger of overexposure and excessive concentrations of these elements occurs in food chains in many parts of the world. They have been studied intensively, and the results of these studies and recommendations of safe intakes are documented in several WHO publications (WHO 1989a, 1989b, 1989c, 1990). For this reason they were treated only briefly.
New trace elements
Boron, chromium, manganese, nickel, tin, vanadium, molybdenum, arsenic, lithium, aluminium, strontium, cesium and silicon are regarded as new trace elements in the sense that they have only recently been considered essential in human diets. These elements are the subject of exciting research in animals, particularly ruminants, where they have been shown to be essential in one or more species. For example, ruminants feeding on grass grown in soil where molybdenum levels are abnormally high have demonstrated an increased tendency to exhibit copper deficiency. However, for many of these new trace elements, such as manganese, there is no evidence at the present time that abnormally low or high dietary intakes cause substantial nutritional problems in human populations.
PREPARING FOR THE CONSULTATION
The process of preparing for the consultation was itself unique. In earlier expert-consultations, 12 to 20 experts in various aspects of the subject were invited to prepare background papers and to attend the expert committee or consultation1 in their individual capacity. Normally there was no meeting prior to the committee meeting or consultation itself. In contrast, the preparation for the 1990 consultation entailed a series of preliminary gatherings at which the specific problems could be dealt with by those expert in that field and a solution sought.
1 One of the earliest and continuing activities of FAO has been determining the requirement level for energy and selected macro-and micronutrients. Normally, the review process was accomplished through a standing Expert Committee, a body established by the FAO Conference on a periodic basis, but later reliance rested with the less formal Expert Consultation. The first Committee on Calorie Requirements was sponsored solely by FAO but, very soon, FAO and WHO undertook the review process jointly, initiating what has become a successful and cordial partnership. The decision to conduct an expert committee or expert consultation on a particular nutrient or group of nutrients is usually based on the perceived need, both in terms of the new scientific information available for consideration and in terms of the public health problems associated with the nutrient or nutrients. Normally one consultation is held in a biennium.
Regarding this particular expert consultation, in August 1988 the three organizations convened an expert advisory group with the charge of considering the content and format of the report and recommending an action plan for its implementation. That group included five scientists from both developing and developed countries and a representative of the secretariat. The group agreed on the contents and the organization of the consultation and its report and proposed coordinators who would be responsible for individual chapters while drawing upon inputs from solicited contributors. It was recognized that the value of the final document would depend on the applicability of its recommendations to a large variety of nutritional situations and cultures; thus contributions from scientists of many different backgrounds were needed.
For most of the chapters communication between contributors and coordinators was by correspondence, but for the chapters on copper, zinc and selenium personal contact was considered necessary. For these elements small workshops were convened in Washington, D.C., consisting of four to six experts who not only Contributed important original data, but also represented different philosophies in their interpretation.
A subsequent informal gathering of the Expert Advisory Group and most of the coordinators was held in August 1989 in Tokyo, taking advantage of the meeting of the International Society on Trace Element Research in Humans. The consensus reached at this informal meeting, findings of the workshops and contributions by correspondence were incorporated into the draft chapters, which were examined and discussed at a meeting of the Expert Advisory Group and coordinators of most the chapters in Geneva in October 1989. The participants agreed on content, style and format and on a timetable for submission of the revised drafts, and recommended an editor to consolidate the chapters.
The Expert Consultation itself consisted of 18 participants and six representatives of the WHO, FAO and IAEA secretariats who met in Geneva in June 1990 to discuss and approve the form and content of the chapters.
Varying knowledge for particular elements
Because of the vast differences in knowledge of dietary intakes, metabolism and requirements, the quality of the data bases upon which the final decisions regarding requirements must be made varies substantially among the individual elements. For example, there is an impressive amount of data relating different levels of intake to deficiency, adequacy and toxicity of selenium. In contrast, there is only indirect and often fragmentary evidence for other trace elements. Homeostasis of different elements is maintained by different means, and the mechanisms regulating absorption of excretion in response to changes in nutritional status are poorly quantified. Yet these mechanisms, together with hundreds of dietary interactions affecting biological availability, have a profound effect on dietary requirements. Whenever the experts lacked exact data to make a strict statistical derivation of requirements, common sense and consensus after extensive discussion produced a final recommendation.
Concepts and definitions
Considerable attention was devoted to definitions (e.g. essentiality) and the conceptual framework of requirements. Although the definitions and concepts were not identical to those used in previous expert consultations (FAO/WHO, 1973, 1988; FAO/WHO/UNU, 1985), there was a logical extension of the thinking and rationale underlying the earlier reports. It was difficult to develop and assimilate some concepts; this occurred most often with the "minor" trace elements for which there was a lack of data. In addition, information for applying the concepts was not always available for some nutrients.
Recommendations for populations
In the report, the recommendations are presented in the form of safe ranges of intake for population groups, wherever the available data permit. These ranges do not represent individual requirements but describe the limits of adequacy and safety of the mean intake of whole populations. If the population mean intake falls within these limits, practically all members of that population are considered to have an adequate intake. An understanding of the conceptual framework of the recommendations is imperative to the application of the recommendations.
The practical applications and limitations of the information on dietary content and availability of the trace elements were considered. When possible, recommendations were made for acceptable lower and upper limits of mean population intakes. There were some surprising conclusions; for example, the recommended range for chromium was reduced by a factor of several hundred, primarily because of extreme measurement errors in the older laboratory techniques.
The final part of the report presents the recommendations of the experts for future activities. A few recommendations relate to research approaches needed to fill important gaps in our knowledge and in our ability to diagnose marginal states of trace element nutrition. The intention of the remaining recommendations is to increase awareness of the great potential health benefits of intervention programmes for whole populations in which trace element deficiencies, environmental or dietary, have been diagnosed. The conquest of iodine deficiency disorders in many countries (Hetzel, 1988) and of Keshan disease in China (Keshan Disease Research Group, 1979) are cited as examples of what can be achieved.
Arthur, J.R. & Beckett, G.J. 1989. Selenium deficiency and thyroid hormone metabolism. In A. Wendel, ed. Selenium in biology and medicine, p. 90-95. Berlin, Springer.
Arthur, J.R., Nicol, F. & Beckett, G.J. 1990. Hepatic iodothyronine 5' deiodinase: the role of selenium. Biochem. J., 272 (2): 537-540.
FAO/WHO. 1973. Energy and protein requirements, Report of a Joint FAO/WHO Ad Hoc Expert Committee. FAO Nutr. Meet, Rep. Ser. No. 52; WHO Tech. Rep. Ser. No. 522, Rome, FAO/Geneva, WHO.
FAO/WHO. 1988. Requirements of vitamin A, iron, folate and vitamin B12. Report of a Joint FAO/WHO Expert Consultation. FAO Food Nutr. Ser. No. 23, Rome, FAO.
FAO/WHO/UNU. 1985. Energy and protein requirements. Report of a Joint FAO/WHO/UNU Expert Consultation. WHO Tech. Rep. Ser. No. 724. Geneva, WHO.
Hetzel, B.S. 1988, Iodine deficiency disorders, Lancet, 1988 (1): 1386-1387.
Keshan Disease Research Group. 1979. Observations on effect of sodium selenite in prevention of Keshan disease. Chin. Med. J., 92: 471-476.
WHO. 1989a. Environmental health criteria 85: lead. Geneva, WHO.
WHO. 1989b. Environmental health criteria 86: mercury-environmental aspects. Geneva, WHO.
WHO. 1989c. Toxicological evaluation of certain food additives and contaminants. WHO Food Additives Ser. No. 24. Geneva, WHO.
WHO. 1990. Environmental health criteria 101: methylmercury. Geneva, WHO.
Cet article passe en revue les principaux points mis en relief par la Consultation d'experts FAO/OMS/AIEA sur les éléments-traces dans la nutrition humaine, la plus récente d'une série de consultations sur les besoins énergétiques et nutritifs dont la première eut lieu juste après la fondation de la FAO. Il contient également une description des préparatifs et des travaux eux-mêmes, qui ont culminé avec la tenue de la Consultation à Genève du 18 au 22 juin 1990.
Cette consultation a revêtu une importance exceptionnelle compte tenu du grand nombre d'éléments nutritifs examinés (19) et de leur grande diversité du point de vue de leur importance, de leur caractère essentiel sur le plan nutritionnel, de leur fonction et de leur importance pour la santé publique. Pour chaque élément nutritif, la Consultation a examiné, selon le cas, le spectre complet carence-toxicité, présenté dans un cadre conceptuel qui a évolué au cours des 15 dernières années et que l'article du professeur Beaton décrit plus en détail (voir pages 3 à 15 de ce numéro). La tendance, Jadis, consistait à examiner les éléments nutritifs isolément mais, dans le cas des éléments-traces, une attention spéciale était réservée aux interactions entre éléments nutritifs d'une part et les autres éléments constitutifs du régime alimentaire d'autre part.
Etant donné les différences d'importance et d'essentialité, les niveaux recommandés n'étaient pas toujours pertinents. Toutefois, lorsqu'on disposait de données sur leur teneur dans le régime alimentaire et que leur rôle biologique précis avait été défini, des limites supérieures et inférieures ont été recommandées concernant les doses moyennes d'absorption d'une population.
Un autre aspect particulier de la Consultation a été la succession de faits qui a conduit à la réunion elle-même. Normalement, un certain nombre de documents de travail sont rédigés par des experts qui sont censés assister à la Consultation. Il n'y a cependant pas de réunions préparatoires. Dans le cas présent, des groupes d'experts ont travaillé en collaboration sur chaque élément nutritif, groupe d'éléments nutritifs ou aspects importants des éléments-traces. Ces groupes ont rédigé les chapitres les concernant respectivement; ces chapitres ont ensuite été examinés par un Groupe consultatif d'experts à plusieurs reprises pendant la période de préparation et, pour finir, ont été soumis à l'examen de la Consultation elle-même.
En este artículo se examinan los principales aspectos abordados por la Consulta FAO/OMS/OIEA de Expertos sobre los Oligoelementos en la Nutrición Humana, la más reciente de una serie de consultas sobre las necesidades de energía y nutrientes iniciada inmediatamente después del establecimiento de la FAO. También se hace una breve descripción de los preparativos y el proceso que culminaron en la celebración de la Consulta en Ginebra del 18 al 22 de junio de 1990.
La Consulta fue extraordinaria por el gran número de nutrientes examinados (19) y por su amplia diversidad en cuanto a importancia, carácter nutricional esencial, función y significación desde el punto de vista de la salud pública. Se estudió todo el espectro de deficiencia-toxicidad de cada nutriente, cuando procedía, y las conclusiones se presentaron en un marco conceptual elaborado durante los últimos 15 años, examinado en forma más detallada en el artículo del Prof. Beatón. Tradicionalmente se ha registrado una tendencia a abordar los nutrientes por separado, pero en el caso de los oligoelementos se prestó especial atención a la interacción de los nutrientes y los demás componentes de la dieta.
A causa de la diversidad en cuanto a importancia y esencialidad, los niveles recomendados no siempre fueron relevantes. Sin embargo, cuando se disponía de información sobre el contenido dietético y se había definido una función biológica precisa, se formularon recomendaciones en relación con los límites inferior y superior de las ingestas medias de la población.
Otro aspecto de la Consulta único en su género fue la serie de acontecimientos que dieron lugar a la reunión propiamente dicha. Normalmente los distintos expertos cuya asistencia se prevé preparan varios documentos de trabajo; sin embargo, no se celebran reuniones preliminares. En el caso presente, varios grupos de expertos trabajaron en colaboración con respecto a cada nutriente, grupo de nutrientes o algún aspecto importante de los oligoelementos. Esos grupos redactaron los capítulos respectivos que después fueron examinados varias veces por un grupo asesor de expertos durante el periodo preparatorio y, por último, se presentaron a la Consulta para su debate.