Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on Dietary Reference Values (DRVs) for the European population, including zinc.
Zinc has a wide array of vital physiological functions. It has a catalytic role in each of the six classes of enzymes. The human transcriptome has 2 500 zinc finger proteins, which have a broad intracellular distribution and the activities of which include binding of RNA molecules and involvement in protein–protein interactions. Thus, their biological roles include transcriptional and translational control/modulation and signal transduction.
The majority of dietary zinc is absorbed in the upper small intestine. The luminal contents of the duodenum and jejunum, notably phytate, can have a major impact on the percentage of zinc that is available for absorption. Absorption of zinc by the enterocyte is regulated in response to the quantity of bioavailable zinc ingested. Albumin is the major transporter of zinc in both portal and systemic circulation. Virtually no zinc circulates in a free ionised form, and the majority of total body zinc is in muscle and bone; zinc does not have an identified major storage site. The quantity of zinc secreted into and excreted from the intestinal tract depends on body zinc concentrations, and the quantities of endogenous zinc in the faeces and exogenous zinc absorbed in normal adults are related. The kidneys and integument are minor routes of loss of endogenous zinc.
Plasma/serum zinc concentration and other putative biomarkers of zinc adequacy, deficiency and excess are not useful for estimating DRVs for zinc. Zinc requirements have been estimated by the factorial approach involving two stages. The first is the estimation of physiological requirements, defined as the minimum quantity of absorbed zinc needed to match losses of endogenous zinc and to meet any additional requirements for absorbed zinc that may be necessary for growth in healthy well-nourished infants and children, and in pregnancy and lactation. The second stage is the determination of the quantity of dietary zinc available for absorption that is needed to meet these physiological requirements. From the published literature, 15 studies were identified that included data on endogenous faecal zinc and total absorbed zinc that enabled an estimation to be made of the physiological zinc requirements of adults. Individual’s data from these studies were supplied by the authors. Data were assessed for physiological plausibility and, after careful evaluation, some data were excluded from further calculations. The final numbers of subjects contributing data to the estimate of physiological zinc requirements were 31 males and 54 females, from a total of 10 studies. Dietary phytate intakes were available for some of the included studies, either as mean study values or as individual’s data. The range of dietary phytate intakes in the available data was 0–2 080 mg/day. Multiple regression analysis was used to evaluate the possible relationships between physiological requirements and sex, zinc balance (difference between absorbed zinc and total losses of endogenous zinc) and body size. The coefficient of determination (R2) values for the models with body weight, height, body mass index and body surface area variables were 0.46, 0.42, 0.37 and 0.47, respectively. It was decided to use the equation relating physiological requirement to body weight in further analyses, for reasons of convenience and accuracy of measurement. The equation for physiological requirement was calculated on the basis that physiological requirement is equivalent to total absorbed zinc when absorbed zinc minus total endogenous zinc losses equals zero at a given body weight. For deriving the dietary zinc requirement, a trivariate saturation response model of the relationship between zinc absorption, and dietary zinc and phytate was established using 72 mean datasets (reflecting 650 individual measurements) reported in 18 publications. The R2 of the fit of this model was 0.81. From this model, the Average Requirement (AR) was determined as the intercept of the total absorbed zinc needed to meet physiological requirements. Estimated ARs and Population Reference Intakes (PRIs) for zinc are provided for phytate intake levels of 300, 600, 900 and 1 200 mg/day, which cover the range of mean/median phytate intakes observed in European populations. ARs range from 6.2 to 10.2 mg/day for women with a reference body weight of 58.5 kg and from 7.5 to 12.7 mg/day for men with a reference body weight of 68.1 kg. PRIs for adults were estimated as the zinc requirement of individuals with a body weight at the 97.5th percentile for reference body weights for men and women, respectively, and range from 7.5 to 12.7 mg/day for women and from 9.4 to 16.3 mg/day for men.
For infants from seven months of age and children, DRVs for zinc were derived using the factorial approach, taking into account endogenous zinc losses via urine, sweat and integument, faeces and, in adolescent boys and girls, semen and menses, respectively, as well as zinc required for synthesis of new tissue for growth. Urinary and integumental losses were extrapolated based on estimates of adult losses, whereas endogenous faecal zinc losses were estimated by linear regression analysis of endogenous faecal zinc losses versus body weight for the subjects contributing data to the adult estimates, and for infants and young children from two studies from China and the USA. Zinc requirements for growth were taken into account based on the zinc content of new tissue, and by estimating daily weight gains for each age group. Absorption efficiency of zinc from mixed diets was assumed to be 30 %. Estimated ARs range from 2.4 mg/day in infants aged 7–11 months to 11.8 mg/day in adolescent boys. Owing to the absence of reference body weights for infants and children at the 97.5th percentile, and in the absence of knowledge about the variation in requirements, PRIs for infants and children were estimated based on a coefficient of variation (CV) of 10 %, and range from 2.9 to 14.2 mg/day.
The physiological requirements for pregnancy and lactation can be calculated by adding the increases in physiological requirements that are predicted to meet the demands for new tissue primarily of the conceptus, and the replacement of zinc that is secreted in breast milk. For pregnancy, an additional requirement for zinc for the four quarters of pregnancy of about 0.4 mg/day was assumed because of zinc accumulation in the fetus; placental, uterine and mammary tissue; amniotic fluid and maternal blood. The Panel decided not to use the trivariate model to estimate the dietary zinc intake required to meet the additional physiological requirement. Instead, the Panel applied a mean fractional absorption of zinc of 0.3 that has been observed in healthy adults to the physiological requirement of 0.4 mg/day. The additional requirement for pregnant women was calculated to be 1.3 mg/day and the additional PRI for pregnancy was estimated based on a CV of 10 % and was 1.6 mg/day.
For lactation, taking into account breast milk zinc concentration, the breast milk volume transferred and the postnatal redistribution of zinc owing to involution of the uterus and reduction of maternal blood volume, the additional physiological requirement calculated over six months of lactation was estimated to be 1.1 mg/day. Assuming that fractional absorption of zinc is increased 1.5-fold in lactation, and applying a fractional absorption of zinc of 0.45 to the additional physiological requirement of 1.1 mg/day, resulted in an additional dietary requirement for lactating women of 2.4 mg/day. The additional PRI for lactation, based on a CV of 10 %, was 2.9 mg/day.
Meat, legumes, eggs, fish, and grains and grain-based products are rich dietary zinc sources. On the basis of data from 12 dietary surveys in nine European Union (EU) countries, zinc intake was assessed using food consumption data from the EFSA Comprehensive Food Consumption Database and zinc composition data from the EFSA nutrient composition database. Average zinc intake ranged from 4.6 to 6.2 mg/day in children aged one to less than three years, from 5.5 to 9.3 mg/day in children aged 3 to < 10 years, from 6.8 to 14.5 mg/day in adolescents (10 to < 18 years) and from 8.0 and 14.0 mg/day in adults. The main food groups contributing to zinc intake were meat and meat products, grains and grain-based products, and milk and dairy products. Published data on phytate intake in the EU are limited and indicate a wide range of dietary phytate intakes.