Regulatory and Policy-Related Aspects of Calcium Fortification of Foods. Implications for Implementing National Strategies of Calcium Fortification.

Daily calcium intake is well below current recommendations in most low- and middle-income countries (LMICs). Calcium intake is usually related to bone health, however an adequate calcium intake has also been shown to reduce hypertensive disorders of pregnancy, lower blood pressure and cholesterol values, and to prevent recurrent colorectal adenomas. Food fortification of foods has been identified as a cost-effective strategy to overcome micronutrient gaps in public health. This review summarizes regulatory aspects of fortification of commonly consumed foods with micronutrients, with an emphasis on calcium. We selected a convenient sample of 15 countries from different WHO regions and described the regulatory framework related to calcium fortification of staple foods. We assessed the relevant policies in electronic databases including the WHO Global database on the Implementation of Nutrition Action (GINA) for fortification policies and the Global Fortification Data Exchange Database, a fortification database developed and maintained by Food Fortification Initiative (FFI), Global Alliance for Improved Nutrition (GAIN), Iodine Global Network (IGN), and Micronutrient Forum. Food fortification with micronutrients is widely used in many of the selected countries. Most countries had national legislation for the addition of micronutrients to staple foods, especially wheat flour. These national legislations, that includes regulations and standards, can provide the framework to consider the implementation of adding calcium to the fortification strategies, including the selection of the adequate food vehicle to reach the targeted population at risk safely. The strategy to include calcium in the fortification mix in fortified staple foods seems promising in these countries. However, potential undesired changes on the organoleptic characteristics of fortified foods and products thereof, and operational feasibility at the manufacturing site should be evaluated by the stakeholders during the planning stage. Codex Alimentarius standards should be considered by regulators in order to assure adherence to international standards. While the selected countries already have established national regulations and/or standards for fortification of key staple food vehicles, and there are experiences in the implementation of fortification of some staple foods, national food intake surveys can help plan, design, and modify existing fortification programs as well as monitor food and nutrient consumption to assess risk and benefits.

Situation analysis of procurement and production of multiple micronutrient supplements in 12 lower and upper middle-income countries.

Globally, there are few vitamin and mineral ingredient manufacturers. To support local, in-country or regional procurement and production of multiple micronutrient supplements (MMS), the following production scenarios are possible: (a) straight ingredients of vitamins and minerals forms imported or locally produced that are mixed, tableted, or encapsulated and packaged by a local manufacturer; (b) import or local production of a vitamin and minerals premix that is tableted or encapsulated and packaged locally; (c) import of a bulk, finished product (tablets or capsules) that is packaged and branded; and (d) or import of a branded packaged product. This paper is a situation analysis of the market, manufacturing, and policy factors that are driving the production of MMS in 12 lower and upper middle-income countries. Key informants completed a self-administered structured questionnaire, which examined the local context of products available in the market and their cost, regulations and policies, in Brazil, Colombia, Guatemala, Mexico, Peru, Bangladesh, India, Vietnam, Ghana, Kenya, Nigeria, and South Africa. Our study found that although most countries have the capacity to produce locally MMS, the major barriers observed for sustainable and affordable production include (a) poor technical capacity and policies for ensuring quality along the value chain and (b) lack of policy coherence to incentivize local production and lower the manufacture and retail price of MMS. Also, better guidelines and government oversight will be required because not one country had an MMS formulation that matched the globally recommended formulation of the United Nations Multiple Micronutrient Preparation (UNIMMAP).

Quantifiable risk-benefit assessment of micronutrients: From theory to practice.

The EU Food Supplements Directive (2002/46/EC) mandates the determination of both maximum and minimum permitted levels (MPLs) for micronutrients. In order to determine MPLs which are feasible for particular population groups, a scientific approach should be used in which risk of high intake, risk of inadequacy and benefits are assessed in an integrated way taking all available data and severity and incidence of effect into account. In 2004, Renwick et al. (ILSI Europe) published a scientifically valid, flexible and pragmatic basis for a risk-benefit approach, which has been further developed here to make it a practical and quantifiable approach to be used by risk managers. The applicability of the approach is demonstrated using demo cases on iron and folate. The proposed approach has the capacity to utilize all relevant data available, including data from human studies, bioavailability data showing variability between specific forms of micronutrients and, in the case of animal studies, data on species comparability. The approach is therefore both practical and flexible, making it well suited to risk managers tasked with determining safe intake levels for micronutrients in different forms and for particular population groups.

Micronutrient intake and food sources in the very old: analysis of the Newcastle 85+ Study.

A number of socio-economic, biological and lifestyle characteristics change with advancing age and place very old adults at increased risk of micronutrient deficiencies. The aim of this study was to assess vitamin and mineral intakes and respective food sources in 793 75-year-olds (302 men and 491 women) in the North-East of England, participating in the Newcastle 85+ Study. Micronutrient intakes were estimated using a multiple-pass recall tool (2×24 h recalls). Determinants of micronutrient intake were assessed with multinomial logistic regression. Median vitamin D, Ca and Mg intakes were 2·0 (interquartile range (IQR) 1·2-6·5) µg/d, 731 (IQR 554-916) mg/d and 215 (IQR 166-266) mg/d, respectively. Fe intake was 8·7 (IQR 6·7-11·6) mg/d, and Se intake was 39·0 (IQR 27·3-55·5) µg/d. Cereals and cereal products were the top contributors to intakes of folate (31·5 %), Fe (49·2 %) and Se (46·7 %) and the second highest contributors to intakes of vitamin D (23·8 %), Ca (27·5 %) and K (15·8 %). More than 95 % (n 756) of the participants had vitamin D intakes below the UK's Reference Nutrient Intake (10 µg/d). In all, >20 % of the participants were below the Lower Reference Nutrient Intake for Mg (n 175), K (n 238) and Se (n 418) (comparisons with dietary reference values (DRV) do not include supplements). As most DRV are not age specific and have been extrapolated from younger populations, results should be interpreted with caution. Participants with higher education, from higher social class and who were more physically active had more nutrient-dense diets. More studies are needed to inform the development of age-specific DRV for micronutrients for the very old.

Stability of Vitamin A, Iron and Zinc in Fortified Rice during Storage and Its Impact on Future National Standards and Programs--Case Study in Cambodia.

Fortified rice holds great potential for bringing essential micronutrients to a large part of the world population. The present study quantified the losses of three different micronutrients (vitamin A, iron, zinc) in fortified rice that were produced using three different techniques (hot extrusion, cold extrusion, and coating) and stored at two different environments (25 ± 5 °C at a humidity of 60% and 40 ± 5 °C at a humidity of 75%) for up to one year. Fortified rice premix from the different techniques was mixed with normal rice in a 1:100 ratio. Each sample was analyzed in triplicate. The study confirmed the high stability of iron and zinc during storage while the retention of vitamin A was significantly affected by storage and the type of techniques used to make rice premix. Losses for iron and zinc were typically <10% for any type of rice premix. After 12 months at mild conditions (25 °C and humidity of 60%), losses for vitamin A ranged from 20% for cold extrusion, 30% for hot extruded rice 77% for coated rice premix. At higher temperatures and humidity, losses of vitamin A were 40%-50% for extruded premix and 93% for coated premix after 6 months. We conclude that storage does lead to a major loss of vitamin A and question whether rice is a suitable food vehicle to fortify with vitamin A. For Cambodia, fortification of rice with iron and zinc could be an effective strategy to improve the micronutrient status of the population if no other food vehicles are available.

A Call to Action to Bring Safer Parenteral Micronutrient Products to the U.S. Market.

The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) started an intensive review of commercially available parenteral vitamin and trace element (TE) products in 2009. The chief findings were that adult multi-TE products currently available in the United States (U.S.) provide potentially toxic amounts of manganese, copper, and chromium, and neonatal/pediatric multi-TE products provide potentially toxic amounts of manganese and chromium. The multivitamin products appeared safe and effective; however, a separate parenteral vitamin D product is needed for those patients on standard therapy who continue to be vitamin D depleted and are unresponsive to oral supplements. The review process also extended to parenteral choline and carnitine. Although choline and carnitine are not technically vitamins or trace elements, choline is an essential nutrient in all age groups, and carnitine is an essential nutrient in infants, according to the Food and Nutrition Board of the Institute of Medicine. A parenteral choline product needs to be developed and available. Efforts are currently under way to engage the U.S. Food and Drug Administration (FDA) and the parenteral nutrient industry so A.S.P.E.N.'s recommendations can become a commercial reality.

Legislative frameworks for corn flour and maize meal fortification.

Corn flour and maize meal fortification can benefit the consumer when the added nutrient contents are in amounts appropriate to address nutrient gaps. Legislative instruments (standards and regulations) are needed to provide guidance to the producers and food control authorities. We reviewed a number of national standards and regulations of fortified corn flour and maize meal and identified constraints; contrary to current belief, the practice of using minimum contents or ranges of nutrients has caused confusion, misinterpretation, and conflict, and should therefore be abandoned. On the basis of the findings, a model of fortification legislation is proposed, in which the additional content and the expected average nutrient content in a final product are recommended as the main parameters for quality control and enforcement. For labeling, the average content, or one adjusted to the expected content of the product at the market, can be applied. Variation in micronutrient contents should still be checked to ensure homogeneity but with adherence to clear procedures of sampling and testing, which should be part of the standards and regulations.

Stability of key micronutrients added to fortified maize flours and corn meal.

Maize is a dietary staple in many countries. Although nutritious in many ways and a good source of energy, typical maize lacks several key micronutrients (MNs) that are often added to maize meals or flours to enhance nutritional value. Many factors affect MN stability in maize products, including uncontrolled conditions during distribution, long storage times, and MN premix composition. Consumer preparation also affects the final MN content of food. This review summarizes research relating to MN stability during processing, transport, storage, and meal preparation, focusing on those MNs most often added to maize and maize-based foods. Significant losses in B vitamins (B1, B2, B3, B6, B9, and B12) occur during manufacturing, distribution, and cooking. Added minerals (e.g., iron, zinc, calcium) are generally retained, although phytates in corn may affect bioavailability. Vitamins A and D3 are recent additions to fortification premixes for maize and are not well studied. Although there have been numerous studies of MN fortification in wheat flour, maize has not been as thoroughly examined, so recommendations are not as well supported. Future investigations should include well-designed and executed studies of the most labile MNs added to maize flours and meals, and their fate during all steps of processing, shipping, and preparation.

EURRECA-Evidence-based methodology for deriving micronutrient recommendations.

The EURopean micronutrient RECommendations Aligned (EURRECA) Network of Excellence explored the process of setting micronutrient recommendations to address the variance in recommendations across Europe. Work centered upon the transparent assessment of nutritional requirements via a series of systematic literature reviews and meta-analyses. In addition, the necessity of assessing nutritional requirements and the policy context of setting micronutrient recommendations was investigated. Findings have been presented in a framework that covers nine activities clustered into four stages: stage one "Defining the problem" describes Activities 1 and 2: "Identifying the nutrition-related health problem" and "Defining the process"; stage two "Monitoring and evaluating" describes Activities 3 and 7: "Establishing appropriate methods," and "Nutrient intake and status of population groups"; stage three "Deriving dietary reference values" describes Activities 4, 5, and 6: "Collating sources of evidence," "Appraisal of the evidence," and "Integrating the evidence"; stage four "Using dietary reference values in policy making" describes Activities 8 and 9: "Identifying policy options," and "Evaluating policy implementation." These activities provide guidance on how to resolve various issues when deriving micronutrient requirements and address the methodological and policy decisions, which may explain the current variation in recommendations across Europe. [Supplementary materials are available for this article. Go to the publisher's online edition of Critical Reviews in Food Science and Nutrition for the following free supplemental files: Additional text, tables, and figures.].

The development and implementation of quality assurance programs to support nutritional measurements.

The National Institute of Standards and Technology administers quality assurance programs devoted to improving measurements of nutrients and related metabolites in foods, dietary supplements, and serum and plasma samples. These programs have been developed in collaboration with the National Institutes of Health to assist measurement communities in their efforts to achieve accurate results that are comparable among different laboratories and over time. Targeted analytes include micronutrients, botanical markers, nutritional elements, contaminants, fatty acids, and vitamin D metabolites.

[Enriched and functional foodstuffs: similarities and differences].

A comparison of fortified and functional foods on such parameters as destination, food group, the principles of enrichment with vitamins and/or macro- and micronutrients, doses and forms of vitamins and minerals, hygienic regulations of micronutrients usage and content in the final product, regulatory and technical documentation, duration of application, effectiveness, labeling, information for consumers has been carried out. Insufficiency and the need to improve the regulatory framework for functional foods are noted.

The power of vitamins.

Although a healthy, varied diet should be sufficient for the majority, certain population groups are at risk of micronutrient deficiencies, particularly young women of childbearing age, whose diets are commonly micronutrient poor and whose requirements increase peri-conceptually and throughout pregnancy and lactation. Infants and young children are also vulnerable to micronutrient deficiencies, associated with the high nutritional demands of rapid growth alongside the transition from milk to solids during weaning. The DH and NICE recommend i) periconceptual folic acid supplementation ii) vitamin D supplementation during pregnancy and lactation, for breastfed infants over 6 months of age (> 1 month if at high risk of deficiency), in those taking less than 500ml infant formula and for all 1-5 year olds iii) vitamin A supplementation during infancy and early childhood. The vitamin and mineral supplement industry is vast, with a third of the UK population and half of children being reported to be taking micronutrient supplements, although it is predominantly by those who do not need them. Guidance on suitable micronutrient supplementation from health professionals, supported by dietitians if required, is therefore likely to be welcomed by many families.

Selenium exposure in subjects living in areas with high selenium concentrated drinking water: results of a French integrated exposure assessment survey.

BACKGROUND: Selenium is an essential element which can be toxic if ingested in excessive quantities. The main human exposure is food. In addition, intake may be boosted by consumption drinking water containing unusual high selenium concentration. OBJECTIVE: We measured the individual selenium level of people exposed to selenium concentration in drinking water greater than the maximum recommended limit which is 10 µg/L. METHODS: We carried out a prospective cohort study on 80 adults (40 exposed subjects i.e. living in the involved area and 40 non-exposed ones i.e. living elsewhere) in western France. We used three different approaches: (1) direct measurement of ingested selenium by the duplicate portion method, (2) dietary reconstitution with a food frequency questionnaire (FFQ) and (3) evaluation of the individual selenium status by measuring the selenium content in toenail clippings. Analyses were performed by inductively coupled plasma-mass spectrometry. The association between toenail selenium concentration and area of residence was analyzed using linear regression with repeated measurements. RESULTS: We estimated selenium intake from FFQ at 64±14 µg/day for exposed subjects as opposed to 52±14 µg/day for the non-exposed ones. On the basis of 305 duplicate diet samples, average intake was estimated at 64±26 µg/day for exposed subjects. Area of residence (p=0.0030) and smoking (p=0.0054) were independently associated with toenail selenium concentration. CONCLUSION: Whatever method used for estimating selenium intake, the selenium level in this studied area with high selenium concentrated drinking water is much lower than in seleniferous areas.

Systematic review of safety and tolerability of a complex micronutrient formula used in mental health.

BACKGROUND: Theoretically, consumption of complex, multinutrient formulations of vitamins and minerals should be safe, as most preparations contain primarily the nutrients that have been in the human diet for millennia, and at safe levels as defined by the Dietary Reference Intakes. However, the safety profile of commercial formulae may differ from foods because of the amounts and combinations of nutrients they contain. As these complex formulae are being studied and used clinically with increasing frequency, there is a need for direct evaluation of safety and tolerability. METHODS: All known safety and tolerability data collected on one complex nutrient formula was compiled and evaluated. RESULTS: Data were assembled from all the known published and unpublished studies for the complex formula with the largest amount of published research in mental health. Biological safety data from 144 children and adults were available from six sources: there were no occurrences of clinically meaningful negative outcomes/effects or abnormal blood tests that could be attributed to toxicity. Adverse event (AE) information from 157 children and adults was available from six studies employing the current version of this formula, and only minor, transitory reports of headache and nausea emerged. Only one of the studies permitted a direct comparison between micronutrient treatment and medication: none of the 88 pediatric and adult participants had any clinically meaningful abnormal laboratory values, but tolerability data in the group treated with micronutrients revealed significantly fewer AEs and less weight gain. CONCLUSIONS: This compilation of safety and tolerability data is reassuring with respect to the broad spectrum approach that employs complex nutrient formulae as a primary treatment.

The marketing of dietary supplements in North America: the emperor is (almost) naked.

BACKGROUND: Many different dietary supplements are being sold in North America. The quality of the evidence supporting their efficacy covers a wide spectrum: Some are based on solid science (such as vitamin D and fish oil), whereas with most supplements there is little or no supporting evidence. Types of supplements commonly sold include exotic fruit juices (such as goji juice) and single herbs or mixture of herbs. Common claims made in support of particular supplements are that they are rich in antioxidants, induce detoxification, stimulate the immune system, and cause weight loss. Supplements are commonly sold through health food stores and by multilevel marketing. Sales may be promoted using bulk mail ("junk mail"), spam e-mails, and Web sites. A large part of marketing is based on claims that are blatantly dishonest. CONCLUSIONS: Whereas supplements for which good supporting evidence exists generally cost around $3-$4 per month, those that are heavily promoted for which there is little supporting evidence cost about $20-$60 per month. The major cause of this problem in the United States is weakness of the law. There is an urgent need for stricter regulation and for giving better advice to the general public.

Micronutrientes y enfermedades crónicas: ¿hacia donde apunta la evidencia científica? / Micronutrients and chronic diseases: which way is the scientific evidence pointing to?

Los estudios observacionales han demostrado, de manera consistente, una asociación positiva entre el consumo de dietas ricas en frutas y vegetales, y un menor riesgo de enfermedad cardiovascular, cáncer, enfermedad cerebrovascular y otras enfermedades crónicas. El consumo de suplementos de vitaminas antioxidantes ha ido en aumento, bajo la premisa de que estos podrían ayudar a prevenir o curar enfermedades crónicas. Sin embargo, a pesar de la gran cantidad de investigaciones que se han realizado en este campo, no se ha logrado esclarecer realmente el papel que la suplementación con estos micronutrientes pueda estar ejerciendo en la patología de esas enfermedades. El Instituto Nacional de Salud de los Estados Unidos establece, que no existe, suficiente evidencia científica para promover o desestimular, el uso de suplementos multivitamínicos para la prevención de las enfermedades crónicas. Los datos emergentes cuestionan los beneficios reales que los suplementos antioxidantes puedan tener en los sujetos con un adecuado estado nutricional, y sugiere que su consumo podría no ser seguro en comparación con las vitaminas y minerales contenidos naturalmente, en los alimentos. Los meta-análisis realizados, con estudios randomizados no han logrado demostrar efectos benéficos de la suplementación con multivitaminas sobre la mortalidad por enfermedades crónicas, y más bien, algunos análisis han sugerido que los B-catorenos, la vitamina A y la vitamina E podrían aumentar el riesgo de muerte.

Observational studies have consistently demonstrated a positive association between high fruits and vegetables intake and a reduced risk of heart disease, cancer, cerebrovascular disease, and other chronic diseases. Under the premise that vitamin and mineral supplements can have thesame effects of those naturally found in food, many people are using them to prevent or treat chronic diseases. But in spite of intensive research, the benefitial effect of antioxidant supplements is still not clear. The US National Institute of Health states that there is not enough evidence torecommend or discourage the use of multivitamin supplements to prevent chronic diseases. Growing scientific data questions the benefitial value of supplementing with antioxidant vitamins,in well nourished population and raises the possibility that they may not be safe compared with vitamin consumption within a healthy diet. Meta-analyses of randomized trials have failed todemonstrate that supplementations with antioxidant vitamins can have benefitial effects on mortality. Even more, some analyses suggested that β-carotenes, vitamin A or vitamin E can increase the risk of death.

Quality criteria for micronutrient powder products: report of a meeting organized by the World Food Programme and Sprinkles Global Health Initiative.

Distribution of micronutrient powder (MNP), also known as Sprinkles", is becoming a preferred strategy for addressing micronutrient deficiencies. In response, different formulations are being developed, different producers manufacture MNP and several organizations coordinate distribution. However, as yet, the supply of MNP as well as experience with large-scale MNP programs is limited. To facilitate expansion of MNP use such that acceptability and compliance are high and effectiveness maintained, product quality, of both powder and packaging, good advocacy among decision makers, and providing good information to the target population are crucial. A meeting was organized in Toronto by the Sprinkles Global Health Initiative and the World Food Programme to review and reach consensus on quality criteria for composition, manufacturing, packaging, and labeling of MNP propose guidelines for wide-scale production, and discuss MNP program experience. It was recognized that the durability of some of the more sensitive micronutrients in their powdered form in the harsh climatic conditions of many countries has implications for formulation, packaging, storage, and handling of the MNP product. A question-and-answer manual would greatly facilitate program design and implementation. It was agreed to form an interim Technical Advisory Group to prepare for formation of a Technical Advisory Group with agreed-upon tasks and responsibilities. The MNP manufacturing manual of the Sprinkles Global Health Initiative can continue to be used, with reference to the recommendations from the Toronto Meeting outlined in this paper. Meanwhile, the Sprinkles Global Health Initiative will not place any encumbrances on production using its manual; however, the brand name Sprinkles" will stay protected under various trademark laws.