Estimation of micronutrient intake distributions: development of methods to support food and nutrition policy making

Introduction Adequate and safe micronutrient intake is important. Both insufficient and excessive intakes should be prevented as these can be associated with negative health effects. Therefore, the population intake distribution will ideally lay between insufficient and excessive intakes. For the development and evaluation of nutrition and food policy a good estimation of dietary micronutrient intake is of great importance. Aim Three challenges were addressed to improve the estimation of population micronutrient intake distributions: 1) how to estimate current habitual micronutrient intake when (detailed) data are lacking or data from different sources should be combined, 2) how to predict future intakes in order to support policy making, and 3) how to estimate a maximum safe fortification level per food item. The aim of this PhD-thesis is to further develop and apply statistical models which can cope with these challenges. Methods & Results Data from the Dutch National Food Consumption Surveys (DNFCSs) were used to develop and apply statistical models which can cope with the defined challenges. In addition, data from the Dutch food composition database (NEVO) and the Dutch dietary supplement database (NES) were used. Three main methodological improvements have been made. First, the combination of a deterministic approach with probabilistic approaches to be able to take into account uncertainty and variability were needed. This method was applied to estimate habitual iodine and salt intake distributions. From DNFCSs no detailed information was available on the discretionary use of (iodized) salt and no up to date information was available on the use of iodized salt in industrially processed foods. Estimates of the proportion of the population discretionarily using (iodized) salt and the proportion of industrially processed foods applying iodized salt were obtained from other data sources. The model accurately estimates habitual iodine and salt intake distributions when compared with studies measuring urinary iodine and sodium excretion. Additionally a framework was developed to simulate the habitual intake distribution for potential scenarios of future fortification strategies. Within this framework, deterministic and probabilistic approaches were combined when uncertainty or variability had to be taken into account. This framework was illustrated by the estimation of habitual folate-equivalent intake for different scenarios of mandatory or voluntary fortification with folic acid. Further this framework was applied to estimate the habitual iodine intake for several potential changes in the Dutch iodine policy and also for several scenarios of salt reduction strategies. A second methodological improvement was the development of a new statistical model to estimate habitual total micronutrient intake aggregated from food and dietary supplements. Within this 3-part model, habitual intake is estimated separately for a) intake from food for non-users of dietary supplements, b) intake from food for users of dietary supplements, and c) intake from dietary supplements for users only. Habitual total intake for the whole population was obtained by combination of the three separate habitual intake distributions (‘first shrink then add’). This 3-part model was illustrated by vitamin D intake for young children. With a more simple ‘first add then shrink’ approach the estimation of habitual total vitamin D intake distribution may give inconsistent results for the distribution of intake from foods and dietary supplements combined as compared to the intake from food only. In addition, this more simple approach may not be able to cope with multi modal distributions. With the newly developed model this inconsistency problem was solved and the multi-modal shape of the distribution as observed in the ‘raw’ data was preserved. Third, a model calculating the maximum safe fortification level per 100 kcal of a food was developed for the Dutch situation. By considering the tolerable upper intake level and reasonable high micronutrient intakes from food and dietary supplements, the ‘free space’ for voluntary fortification was calculated. This amount was divided over the amount of energy intake that can and may be fortified. The model was applied to derive safe maximum fortification levels for vitamin A, D, and folic acid. Based on these results the risk manager decided to legally allow voluntary fortification with vitamin D and folic acid up to a maximum level of 4.5 and 100 μg/100 kcal respectively. Conclusion The methodological improvements have resulted in higher accuracy for estimations of habitual intake distributions, which are essential for nutritional and food policy making. Furthermore, scenario analyses provide (under specific conditions) quantitative insight into proposed changes or areas such as maximum safe fortification levels. Several results and methods described are currently being used in research to assist Dutch and European food and nutrition policy making, which shows these methodologies are of immediate value to the practice of policy development and support. </p

Reduction of salt: will iodine intake remain adequate in The Netherlands?

Salt is the main vehicle for iodine fortification in The Netherlands. A reduction in salt intake may reduce the supply of iodine. Our aim was to quantify the effect of salt reduction on the habitual iodine intake of the Dutch population and the risk of inadequate iodine intake. We used data of the Dutch National Food Consumption Survey (1997–8) and an update of the food composition database to estimate habitual salt and iodine intake. To take into account uncertainty about the use of iodised salt (industrial and discretionary) and food supplements, a simulation model was used. Habitual iodine and salt intakes were simulated for scenarios of salt reduction and compared with no salt reduction. With 12, 25 and 50 % salt reduction in industrially processed foods, the iodine intake remained adequate for a large part of the Dutch population. For the extreme scenario of a 50 % reduction in both industrially and discretionary added salt, iodine intake might become inadequate for part of the Dutch population (up to 10 %). An increment of the proportion of industrially processed foods using iodised salt or a small increase in iodine salt content will solve this. Nevertheless, 8–35 % of 1- to 3-year-old children might have iodine intakes below the corresponding estimated average requirement (EAR), depending on the salt intake scenario. This points out the need to review the EAR value for this age group or to suggest the addition of iodine to industrially manufactured complementary food

Evaluation of the Dutch general exemption level for voluntary fortification with folic acid

Introduction: Fortification with folic acid was prohibited in the Netherlands. Since 2007, a general exemption is given to fortify with folic acid up until a maximum level of 100 &#x00B5;g/100 kcal. This maximum level was based on a calculation model and data of adults only. The model requires parameters on intake (diet, supplements, energy) and on the proportion of energy that may be fortified. This study aimed to evaluate the model parameters considering the changing fortification market. In addition, the risk of young children exceeding the UL for folic acid was studied. Methods: Folic acid fortified foods present on the Dutch market were identified in product databases and by a supermarket inventory. Together with data of the Dutch National Consumption Survey-Young Children (2005/2006) these inventory results were used to re-estimate the model parameters. Habitual folic acid intake of young children was estimated and compared to the UL for several realistic fortification scenarios. Results: Folic acid fortified foods were identified in seven different food groups. In up to 10% of the population, the proportion of energy intake of folic acid fortified foods exceeded 10% &#x2013; the original model parameter. The folic acid intake from food supplements was about 100 &#x00B5;g/day, which is lower than the intake assumed as the original model parameter (300 &#x00B5;g). In the scenarios representing the current market situation, a small proportion (&#60;5%) of the children exceeded the UL. Conclusion: The maximum fortification level of 100 &#x00B5;g/100 kcal is sufficiently protective for children in the current market situation. In the precautionary model to estimate the maximum fortification levels, subjects with high intakes of folic acid from food and supplements, and high energy intakes are protected from too high folic acid intakes. Combinations of high intakes are low in this population. The maximum levels should be monitored and revised with increasing fortification and supplementation practices

The Associations of Maternal and Neonatal Vitamin D with Dental Development in Childhood

Background: Vitamin D influences the formation and mineralization of teeth. Objective: To investigate the association of maternal and neonatal vitamin D concentrations with the dental development of 10-y-old children, in a population-based prospective cohort study among 3,770 mothers and children in the Netherlands. Methods: Maternal venous blood samples were collected in the second trimester (median 20.4 weeks of gestation; range: 18.5-23.2 wk) whereas umbilical cord blood samples were collected immediately after delivery (median 40.1 weeks of gestation; range 35.9-42.3 wk). Dental development was defined using the Demirjian method. Multivariate regression models were built to analyze the studied associations. Results: High concentrations of 25-hydroxyvitamin D [25(OH)D] during midpregnancy (beta: -0.04; 95% CI: -0.08, -0.01) and at birth (beta: -0.06; 95% CI: -0.10, -0.02) were associated with a lower dental age in children. The children of mothers with severe vitamin D deficiency [25(OH)D /=75.0 nmol/L). Children with vitamin D deficiency [25(OH)D 25.0-49.9 nmol/L] at birth exhibited a higher dental age (beta: 0.11; 95% CI: 0.01, 0.20), higher developmental stages of the mandibular second premolar (beta: 0.27; 95% CI: 0.02, 0.51), and higher developmental stages of the mandibular second molar (beta: 0.24; 95% CI: 0.00, 0.48) compared with children with sufficient-to-optimal values of 25(OH)D (>/=50.0 nmol/L) at birth. Conclusion: Higher maternal and neonatal 25(OH)D concentrations are associated with decelerated dental development in childhood. The lower the vitamin D level during midpregnancy or at birth, the higher the dental age of children, and the higher the developmental stages of the mandibular teeth

Vitamins and minerals: issues associated with too low and too high population intakes

There is an ongoing increase in the availability of foods fortified with micronutrients and dietary supplements. This may result in differing intakes of micronutrients within the population and perhaps larger differences in intakes. Insight into population micronutrient intakes and evaluation of too low or too high intakes is required to see whether there are potential problems regarding inadequacy or excessive intakes. Too low population intakes are evaluated against an estimated average requirement; potential too high population intakes are evaluated against a tolerable upper intake level (UL). Additional health effects, seriousness, and incidence of these health effects are not considered but these can be taken into account in a benefit-risk assessment. Furthermore, authorities would like to regulate food fortification and supplementation in such a way that most of the population is not at risk of potentially high intakes. Several models are available for estimating maximum levels of micronutrients for food fortification and dietary supplements. Policy makers and risk managers need to decide how to divide the ‘free space’ between food fortification and/or dietary supplements, while protecting populations from adverse health effects

Update of the tolerable upper intake level for vitamin D for infants

Following a request from the European Commission, the Panel&nbsp;on Dietetic Products, Nutrition and Allergies (NDA) was asked to revise the tolerable upper intake level (UL) for vitamin D for infants ( 64&nbsp;1&nbsp;year) set in 2012. From its literature review, the Panel&nbsp;concluded that the available evidence on daily vitamin D intake and the risk of adverse health outcomes (hypercalciuria, hypercalcaemia, nephrocalcinosis and abnormal growth patterns) cannot be used alone for deriving the UL for infants. The Panel&nbsp;conducted a meta-regression analysis of collected data, to derive a dose\u2013response relationship between daily supplemental intake of vitamin D and mean achieved serum 25(OH)D concentrations. Considering that a serum 25(OH)D concentration of 200&nbsp;nmol/L or below is unlikely to pose a risk of adverse health outcomes in infants, the Panel&nbsp;estimated the percentage of infants reaching a concentration above this value at different intakes of vitamin D. Based on the overall evidence, the Panel&nbsp;kept the UL of 25&nbsp;\u3bcg/day for infants aged up to 6 months and set a UL of 35&nbsp;\u3bcg/day for infants 6\u201312&nbsp;months. The Panel&nbsp;was also asked to advise on the safety of the consumption of infant formulae with an increased maximum vitamin D content of 3&nbsp;\u3bcg/100&nbsp;kcal (Commission Delegated Regulation (EU) 2016/127 repealing Directive 2006/141/EC in 2020). For infants aged up to 4&nbsp;months, the intake assessment showed that the use of infant formulae containing vitamin D at 3&nbsp;\u3bcg/100&nbsp;kcal may lead some infants to receive an intake above the UL of 25&nbsp;\u3bcg/day from formulae alone without considering vitamin D supplemental intake. For infants aged 4\u201312&nbsp;months, the 95th percentile of vitamin D intake (high consumers) estimated from formulae and foods fortified or not with vitamin&nbsp;D does not exceed the ULs, without considering vitamin D supplemental intake

Safe maximum daily dosage retinol in dietary supplements

Alleen digitaal verschenenMensen die te veel retinol (de actieve vorm van vitamine A) binnenkrijgen, kunnen problemen krijgen aan hun lever. Zwangere vrouwen lopen het risico dat er problemen ontstaan bij de ontwikkeling van hun ongeboren kind. Daarom is voor verschillende leeftijdsgroepen een maximum bepaald voor de hoeveelheid retinol die ze mogen binnenkrijgen, de zogeheten aanvaardbare bovengrens. Retinol zit in bepaalde voedingsmiddelen, zoals producten die lever bevatten, maar kan ook via supplementen worden ingenomen. Het RIVM heeft voor de verschillende leeftijdsgroepen berekend hoeveel retinol zij via voeding binnenkrijgen. Op basis hiervan is vervolgens geschat hoeveel retinol deze leeftijdsgroepen maximaal via supplementen kunnen innemen totdat de aanvaardbare bovengrens wordt bereikt. Afhankelijk van de leeftijd ligt bij 5 tot 33 procent van de kinderen tot en met 3 jaar de retinolinname boven de aanvaardbare bovengrens; zij eten vaak producten die veel retinol bevatten, zoals smeerleverworst. Bij meer dan 95 procent van de kinderen van 4 tot en met 14 jaar blijft de retinolinname uit de voeding onder de bovengrens. Zij zouden, afhankelijk van de leeftijd, naast de voeding nog circa 100 tot 950 microgram retinol per dag kunnen binnenkrijgen uit supplementen totdat de bovengrens wordt bereikt. Voor jongens en mannen vanaf 15 jaar is deze 'ruimte' circa 1450 microgram per dag. Voor vrouwen die de overgang hebben doorgemaakt, is een lagere maximale inname vastgesteld vanwege het risico op botontkalking. Hun veilige maximale 'ruimte' uit supplementen komt op circa 400 microgram per dag. Voor vrouwen in de vruchtbare leeftijd is er 'ruimte' voor maximaal 1200 microgram per dag. Voor zwangere vrouwen en vrouwen die borstvoeding geven zijn te weinig voedselconsumptiegegevens bekend om deze 'ruimte' vast te stellen. Aanbevolen wordt om deze gegevens ook voor deze groepen regelmatig te verzamelen. Hetzelfde geldt voor kinderen onder de twee jaar, waarvoor geen recente voedselconsumptiegegevens beschikbaar zijn.Too high intake of vitamin A (retinol) may result in toxicity of liver and during pregnancy, in problems in the development of an unborn child. Therefore a tolerable upper intake limit has been set. Vitamin A is present in foods, but also in some dietary supplements. The RIVM calculated the vitamin A intake from food sources in the Dutch population. Based on this information the maximum amount that can be consumed from dietary supplements was estimated. About 5-33% of the children aged 0-3 years old had retinol intakes above the tolerable upper intake level. They often consume foods with a relatively high retinol level, like liver sausage. For children aged 4-14 years old more than 95% had retinol intakes below the upper intake limit. Depending on age, their maximum daily dosage is circa 100 to 950 microgram retinol, besides the intake from food. For boys and men aged 15 years and older the safe maximum is circa 1450-1500 microgram retinol per day. For postmenopausal women there is a lower advised maximum intake due to the risk of osteoporosis. Their safe maximum daily dosage retinol from supplements is circa 400 microgram. For women of childbearing age the safe maximum is circa 1200 microgram per day. Too little food consumption data are available for pregnant and breastfeeding women to calculate a specific safe maximum daily dosage. It is recommended to collect these data regularly for these groups. Similar is recommended for young children aged 2 years or younger, as no recent food consumption data is available in the Netherlands.Ministerie van VW

Advice general dispensation fortification of food with zinc

Het is in Nederland niet toegestaan om zink aan levensmiddelen toe te voegen. Dat is verboden omdat de hoeveelheid zink die mensen nodig hebben dicht bij de hoeveelheid ligt die als veilig maximum wordt gezien. De Europese Food and Safety Authority (EFSA) heeft bepaald hoeveel zink mensen maximaal via voeding mogen binnenkrijgen. Onder deze hoeveelheid zijn er zeker geen schadelijke effecten voor de gezondheid. Daarboven zou dat misschien kunnen. Dat hangt onder andere af van de hoeveelheid die mensen binnenkrijgen en of dat korte of langere tijd duurt. Het RIVM heeft in 2018 onderzocht of een algemene ontheffing op het verbod mogelijk was. Anders gezegd: of het mogelijk is om toe te staan dat producenten zink mogen toevoegen aan voedingsmiddelen die door de hele Nederlandse bevolking kunnen worden gegeten. Dit blijkt niet het geval te zijn. Een deel van de Nederlandse bevolking, zowel kinderen als volwassenen, krijgen meer zink binnen via voeding en eventuele supplementen dan het maximum dat EFSA hieraan stelt. Dit komt het vaakst voor bij kinderen. Het is daarom gerechtvaardigd om het verbod te laten bestaan. Het onderzoek is in opdracht van het ministerie van VWS uitgevoerd. Het ministerie neemt het besluit of zij verrijking van voedingsmiddelen met zink in het algemeen zal toestaan, of eventueel onder bepaalde voorwaarden. Zink zit van nature in heel veel voedingsmiddelen. Doordat zink en koper op een zelfde manier worden opgenomen in het lichaam, zijn ze elkaars ‘concurrent’. Daarom kan door een te veel aan zink in het lichaam een tekort aan koper ontstaan. Dit zou de werking van bijvoorbeeld het immuunsysteem kunnen verminderen. Bijschrift In 2018 is het advies van het RIVM over de algemene ontheffing van het verbod op verrijking van voedingsmiddelen met zink gedeeld met het ministerie van VWS. Tegelijkertijd is er een specifiek advies gegeven over een ontheffingsverzoek dat een fabrikant had aangevraagd. Dit specifieke advies bevat bedrijfsgevoelige informatie. Er is toen voor gekozen om zowel het algemene advies als het specifieke advies over het ontheffingsverzoek van een fabrikant niet op de website te plaatsen. Achteraf gezien was dat niet nodig geweest voor het advies over de mogelijkheden voor een algemene ontheffing. Daarom wordt deze publicatie alsnog openbaar gemaakt.Adding zinc to food is not permitted in the Netherlands. It is prohibited on the grounds that the quantity of zinc that people require is close to the quantity regarded as the tolerable upper limit. The European Food Safety Authority (EFSA) has calculated the maximum amount of zinc that people should be consuming through food. There will definitely not be any adverse effects on health if consumption is kept below this level. Adverse effects are possible if exceeding the maximum, however this will depend on factors such as the quantity consumed and whether this is over the short term or the long term. In 2018, the National Institute for Public Health and the Environment (RIVM) studied whether a general dispensation on the ban might be possible. In other words, whether it might be possible to allow food producers to add zinc to foods eaten by the general Dutch population. It turns out that this will not be possible. A proportion of the Dutch population, both children and adults, are consuming higher quantities of zinc through food and any supplements they may be taking, than the maximum set by the EFSA. This is most common among children. As a result, keeping the ban in place is justified. The study was commissioned by the Ministry of Health, Welfare and Sport. The Ministry is deciding whether or not to allow fortification of foods with zinc in general or subject to certain conditions. Zinc is naturally found in a wide array of foods. Because zinc and copper are absorbed by the body in a similar way, they are ‘competitors’. As a result, excessive consumption of zinc can lead to a copper deficiency. This could dampen the immune system’s functioning. Caption The RIVM shared its advice on general dispensations to the ban on fortification foods with zinc with the Ministry of Health, Welfare and Sport in 2018. It simultaneously issued a specific advice on a dispensation request submitted by a producer. This specific advice contains sensitive commercial information. At that juncture, a decision was made not to publish both the general advice and the specific advice on the producer’s dispensation request on the website. With hindsight, there was no need to refrain from publishing the advice on the possibility of a general dispensation. Hence, the advice is now being published

Neonatal heel prick screening TSH concentration in the Netherlands as indicator of iodine status.

BACKGROUND: Neonatal Thyroid Stimulating Hormone (nTSH) is proposed as indicator of iodine deficiency in a population. Population’s iodine sufficiency is indicated by a proportion of the newborns less than 3% having nTSH above 5 mIU/L. The aim of this study was to explore the Dutch neonatal heel prick screening TSH data to assess iodine status in the Netherlands and identify determinants and potential confounders of this assessment. METHODS: All newborns born in the Netherlands between 2007 and 2015 with a heel prick collection at day 3-7 were included (n = 1,435,600), except preterm neonates and baby’s with a low birth weight. Total T4 was measured for all children, nTSH was measured in the ~ 20% children with lowest total T4. RESULTS: The proportion with nTSH > 5mIU/L fluctuated between 0.6-1.3% in 2007-2015. nTSH was significantly associated with laboratory performing the nTSH assay and age of heel prick sampling. The overall increasing trend in proportion nTSH >1mIU/L was confounded by the laboratories with different and changed assays. CONCLUSIONS: The low proportion neonates with high nTSH suggests a sufficient iodine status in the Netherlands. Whether the increased proportion nTSH>1mIU/L over the years is an early indicator of deterioration of the iodine status remains unclear, due to differences and changes in analytical assays. nTSH might be a valuable and inexpensive way to get crude insight in the (trend in) iodine status, but more research is needed on the validity and potential conditions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12937-021-00722-4