Challenges in translating scientific evidence into mandatory food fortification policy: an antipodean case study of the folate- neural tube defect relationship

Objective: To identify challenges in translating scientific evidence of a  nutrient and health relationship into mandatory food fortification policy.
Design: A case study approach was used in which available evidence  associated with the folate–neural tube defect relationship was reviewed against the Australia New Zealand Food Regulation Ministerial Council's Policy Guideline for mandatory food fortification. Results: Three particular challenges were identified. The first is knowing when and how to act in the face of scientific uncertainty. The second is knowing how to address the special needs of at-risk individuals without compromising the health and safety of the population as a whole. The third is to ensure that a policy is sufficiently monitored and evaluated. Conclusions: Despite the availability of compelling evidence of a relationship between a particular nutrient and a health outcome, a definitive policy response may not be apparent.  Judgement and interpretation inevitably play significant roles in influencing whether and how authorities translate scientific evidence into mandatory food fortification policy. In relation to the case study, it would be prudent to undertake a risk–benefit analysis of policy alternatives and to implement nutrition education activities to promote folic acid supplement use among the target group. Should mandatory folate fortification be implemented,  comprehensive monitoring and evaluation of this policy will be essential to know that it is implemented as planned and does more good than harm. In relation to mandatory food fortification policy-making around the world,  ongoing national nutrition surveys are required to complement national policy guidelines.

Food fortification : the evidence, ethics and politics of adding nutrients to food

This research book presents a critical analysis of mandatory food fortification as a technology for protecting and promoting public health. Increasing numbers of foods fortified with novel amounts and combinations of nutrients are being introduced into the food supplies of countries around the world to raise populations’ nutrient intakes. Three topical food fortification case studies representing the different public health rationales for adding nutrients to food were assessed for their public health benefits, risks and ethical considerations: Universal salt iodisation (USI) to help prevent iodine deficiency disorders; mandatory flour fortification with folic acid (MFFFA) to help prevent neural tube defects; and mandatory milk fortification with vitamin D (MMFVD) to help prevent vitamin D deficiency. These assessments found that whereas USI performs strongly as a public health intervention, MFFFA and MMFVD are associated with more risks and less ethical justification than an alternative policy option. Food fortification can be a blunt policy response to complex policy problems. The findings highlight that the primary predictor of a mandatory food fortification policy’s benefits, risks and ethics is its ability to address the underlying cause of the policy problem. The analysis of the policy-making processes for each case study found that certain powerful actors use their influence to determine what counts as evidence in policy processes to privilege food fortification activities over alternative policy options. Policy-making frequently was notable for the low prominence it afforded ethical considerations and its lack of public engagement. Priority activities to help strengthen policy processes and outcomes are suggested.

Evidence synthesis and translation for nutrition interventions to combat micronutrient deficiencies with particular focus on food fortification

Over two billion people suffer from micronutrient deficiencies. Food fortification is a prominent nutrition intervention to combat such deficiencies; however, its effectiveness, risks, and ethical implications vary depending on the contexts associated with the deficiency it is addressing and the circumstances with its implementation. The aim of this research was to analyse the profile of nutrition interventions for combating micronutrient deficiency with particular focus on food fortification reported in existing systematic reviews (SRs), guidelines and policy statements, and implementation actions for nutrition. A review of secondary data available from online databases of SRs, guidelines and policy statements, and implementation actions, categorised as either "nutrition-specific interventions" (NSpI) or "nutrition-sensitive interventions" (NSeI), was conducted. Currently, there is evidence available for a diversity of food fortification topics, and there has been much translation into action. Indeed, food fortification and micronutrient supplementation interventions and NSpI more broadly dominate the profile of interventions for which there were SRs, guidelines, and policy statements available. The findings demonstrate that, although there is a rational linear relationship between evidence synthesis and translation in formulating policy and actions to combat micronutrient deficiencies, the various nutrition interventions available to help combat micronutrient deficiencies are not equally represented in the evidence synthesis and translation processes. Effective and safe policies and actions to combat micronutrient deficiencies require decisions to be informed from a body of evidence that consists of evidence from a variety of interventions. Into the future, investment in making available a higher number of SRs, guidelines and policy statements, and actions of NSeI is indicated.

Mandatory folate fortification - will benefits outweigh risks?

The article considers the concerns raised about the implementation of mandatory food fortification in Australia. Mandatory food fortification, the compulsory addition of nutrients to food products, is a powerful policy approach for public health nutrition. The danger in exposing every Australians to increased amounts of nutrients is discussed. Mandate folate fortification is being assessed by Food Standards Australia New Zealand due to the increased cases of neural tube defects in Australia.

Folate fortification : a case study of public health policy-making

This thesis investigates the use of scientific evidence in the process of making public health policy. A case study located within a food regulation setting is used. The aim is to test theory against this case study. The outcome is a theoretical understanding of the use of scientific evidence in the policy-making process in a food regulation setting. Food regulation can influence food composition and food labelling and thereby affect the population's dietary intake. Frequently there are contested values, beliefs, ideologies and interests among stakeholders regarding the use of food regulation as a policy instrument to effect public health outcomes. The protection of public health and safety, taking into account evidence based practice, is generally employed by food regulators as the priority objective during the policy-making process to adjudicate among the competing expectations of stakeholders. However, this policy objective has not been clearly defined and is vulnerable to interpretation and application. The process by which folate fortification policy was made in Australia, in response to epidemiological evidence of a relationship between folate intake during the periconceptional period and reduced risk of neural tube defects, was analysed as a case study of the policy-making process. The folate fortification policy created a precedent for both food fortification and subsequently health claims policy in Australia. A social constructivist method was used to analyse the case study. The method involved deconstructing the food regulatory system into three levels; decision-making process; procedural; and political environment. Data aligned with each level of analysis was collected from 22 key informant interviews, documentary sources, field notes and surveys of both a random sample of the Australian population's knowledge of folate and use of folic acid-containing supplements (n = 5422), and the implementation of folate fortified food products into stores (n = 60). The insights that emerged from each of the three levels of analysis were assessed iteratively to identify a pattern of interrelationships associated with the policy-making process within the food regulatory system. The identified pattern was interpreted against existing theory to gain a theoretical understanding of the public health policy-making process in this political setting. The central argument of this thesis extends Sabatier and Jenkins-Smith's Advocacy Coalition Framework theory to a food regulation setting. The argument is that within the contemporary political climates of neoliberalism and globalisation, a coalition between corporate interests and the values of scientists with a positivist-reductionist approach to public health research is privileged so as to invoke certain scientific evidence to, in turn, legitimise food regulation policy decisions. The theory will help to inform policy-makers about how and why the public health policy objective in a food regulation setting is interpreted and applied. This will contribute to improving policy practice intended to effect public health outcomes. It is concluded that irrespective of the quantity and quality of the scientific evidence that is being made available, scientific evidence cannot be assumed to speak for itself Policy-making is an inherently political and value-laden process and the potential for politically motivated interpretation and application of otherwise value-neutral scientific evidence can undermine the investment in its generation. From this perspective, evidence based practice, far from liberating policy-making from political influence, can itself become part of the problem rather than the solution. Nevertheless, rational evidence based practice is an ideal to strive for and a series of recommendations is proposed to help make the use of evidence in current food regulation policy processes more transparent and democratic.

Fortification. Folic acid and spina bifida. Is it safe? Is it wise? Is it right?

Food fortification takes many forms. The example discussed here is unusual, because in many countries now it is required by law: the fortification of flour with the B vitamin folic acid, or MFFFA for short. Voluntary fortification of various food products was first used to help prevent and control child and maternal anaemia associated with folate deficiency (1). In the mid-1990s, policy-makers in various countries began considering using mandatory fortification under a novel policy paradigm, that fortification was needed to increase the folic acid intake and protect the health status of people who had a special requirement for this nutrient, irrespective of the folate status of the population as a whole.

Profiling national mandatory folic acid fortification policy around the world

Mandatory food fortification “occurs when governments legally oblige food producers to fortify particular foods or categories of foods with specified micronutrients” [1]. Because mandatory food fortification exposes everyone in the population who consumes the fortified food(s) to raised levels of the specified micronutrient, it is one of the most powerful policy instruments available to influence dietary intake and population health outcomes. Many national food regulatory authorities have established policy guidance on mandatory food fortification. From an international perspective, the Codex Alimentarius Commission (Codex) provides principles for the addition of essential nutrients to foods [2]. According to these Codex principles, mandatory food fortification with additional vitamins and minerals is recommended where there is proven public health and nutrition need (Note: these principles are under review at the time of writing).

Anaemia in pregnant women before and after the mandatory fortification of wheat and corn flours with iron

Objective: To estimate the frequency of anaemia in pregnant women before and after the fortification of flours with Fe. Design: Retrospective study developed from secondary data obtained from medical records. Setting: Two health units in Rio de Janeiro, Brazil. Subjects: Socio-economic, demographic, obstetric and Hb concentration data were collected of 778 pregnant women attending prenatal care. Two study groups were created: the first referred to the period before fortification (G1, n 391), including women whose parturition happened before June 2004; and the second referred to the period after fortification (G2, n 387), including women whose last menstrual cycle happened after June 2005. The Hb cut-off point adopted for anaemia diagnosis was <11.0 g/dl. Results: In linear regression models, when Hb concentration was expressed as a dependent variable, women in G2 presented Hb concentration 0.26 g/dl and 0.36 g/dl higher during the second and third trimesters of pregnancy, respectively, compared with G1. In logistic regression models where the dependent variable was anaemia during the second and third trimesters, it was verified that being a member of G2 was a protective factor against anaemia in the third trimester. Regarding the presence of anaemia at any gestational moment, it was verified that being a member of G2 represented a protective factor against anaemia during pregnancy. Conclusions: Results indicate the protective effect of the fortification of flours with Fe in the fight against gestational anaemia, contributing to prevention and control of this nutritional disorder among pregnant women.

Towards the biofortification of banana fruit for enhanced micronutrient content

In Uganda, vitamin A deficiency (VAD) and iron deficiency anaemia (IDA) are major public health problems with between 15-32% of children under 5 years of age showing VAD and 73% being anaemic. This is largely due to the fact that the staple food crop of the country, banana, is low in pro-vitamin A and iron, therefore leading to dietary deficiencies. Although worldwide progress has been made to control VAD and IDA through supplementation, food fortification and diet diversification, their long term sustainability and impact in developing countries such as Uganda is limited. The approach taken by researchers at Queensland University of Technology (QUT), Australia, in collaboration with the National Agricultural Research Organization (NARO), Uganda, to address this problem, is to generate consumer acceptable banana varieties with significantly increased levels of pro-vitamin A and iron in the fruit using genetic engineering techniques. Such an approach requires the use of suitable, well characterised genes and promoters for targeted transgene expression. Recently, a new banana phytoene synthase gene (APsy2a) involved in the synthesis of pro-vitamin A (pVA) carotenoids was isolated from a high â-carotene banana (F’ei cv Asupina). In addition, sequences of banana ferritin, an iron storage protein, have been isolated from Cavendish banana. The aim of the research described in this thesis was to evaluate the function of these genes to assess their suitability for the biofortification of banana fruit. In addition, a range of banana-derived promoters were characterised to determine their suitability for controlling the expression of transgenes in banana fruit. Due to the time constraints involved with generating transgenic banana fruit, rice was used as the model crop to investigate the functionality of the banana-derived APsy2a and ferritin genes. Using Agrobacterium-mediated transformation, rice callus was transformed with APsy2a +/- the bacterial-derived carotene desaturase gene (CrtI) each under the control of the constitutive maize poly-ubiquitin promoter (ZmUbi) or seed-specific rice glutelin1 (Gt1) promoter. The maize phytoene synthase (ZmPsy1) gene was included as a control. On selective media, with the exception of ZmUbi-CrtI-transgenic callus, all antibiotic resistant callus displayed a yellow-orange colour from which the presence of â-carotene was demonstrated using Raman spectroscopy. Although the regeneration of plants from yellow-orange callus was difficult, 16 transgenic plants were obtained and characterised from callus transformed with ZmUbi-APys2a alone. At least 50% of the T1 seeds developed a yellow-orange coloured callus which was found to contain levels of â-carotene ranging from 4.6-fold to 72-fold higher than that in non-transgenic rice callus. Using the seed-specific Gt1 promoter, 38 transgenic rice plants were generated from APsy2a-CrtI-transformed callus while 32 plants were regenerated from ZmPsy1-CrtI-transformed callus. However, when analysed for presence of transgene by PCR, all transgenic plants contained the APsy2a, ZmPsy1 or CrtI transgene, with none of the plants found to be co-transformed. Using Raman spectroscopy, no â-carotene was detected in-situ in representative T1 seeds. To investigate the potential of the banana-derived ferritin gene (BanFer1) to enhance iron content, rice callus was transformed with constitutively expressed BanFer1 using the soybean ferritin gene (SoyFer) as a control. A total of 12 and 11 callus lines independently transformed with BanFer1 and SoyFer, respectively, were multiplied and transgene expression was verified by RT-PCR. Pearl’s Prussian blue staining for in-situ detection of ferric iron showed a stronger blue colour in rice callus transformed with BanFer1 compared to SoyFer. Using flame atomic absorption spectrometry, the highest mean amount of iron quantified in callus transformed with BanFer1 was 30-fold while that obtained using the SoyFer was 14-fold higher than the controls. In addition, ~78% of BanFer1-transgenic callus lines and ~27% of SoyFer-transgenic callus lines had significantly higher iron content than the non-transformed controls. Since the genes used for enhancing micronutrient content need to be expressed in banana fruit, the activity of a range of banana-derived, potentially fruit-active promoters in banana was investigated. Using uidA (GUS) as a reporter gene, the function of the Expansin1 (MaExp1), Expansin1 containing the rice actin intron (MaExp1a), Expansin4 (MaExp4), Extensin (MaExt), ACS (MaACS), ACO (MaACO), Metallothionein (MaMT2a) and phytoene synthase (APsy2a) promoters were transiently analysed in intact banana fruit using two transformation methods, particle bombardment and Agrobacterium-mediated infiltration (agro-infiltration). Although a considerable amount of variation in promoter activity was observed both within and between experiments, similar trends were obtained using both transformation methods. The MaExp1 and MaExp1a directed high levels of GUS expression in banana fruit which were comparable to those observed from the ZmUbi and Banana bunchy top virus-derived BT4 promoters that were included as positive controls. Lower levels of promoter activity were obtained in both methods using the MaACO and MaExt promoters while the MaExp4, MaACS, and APsy2a promoters directed the lowest GUS activity in banana fruit. An attempt was subsequently made to use agro-infiltration to assess the expression of pVA biosynthesis genes in banana fruit by infiltrating fruit with constructs in which the ZmUbi promoter controlled the expression of APsy2a +/- CrtI, and with the maize phytoene synthase gene (ZmPsy1) included as a control. Unfortunately, the large amount of variation and inconsistency observed within and between experiments precluded any meaningful conclusions to be drawn. The final component of this research was to assess the level of promoter activity and specificity in non-target tissue. These analyses were done on leaves obtained from glasshouse-grown banana plants stably transformed with MaExp1, MaACO, APsy2a, BT4 and ZmUbi promoters driving the expression of the GUS gene in addition to leaves from a selection of the same transgenic plants which were growing in a field trial in North Queensland. The results from both histochemical and fluorometric GUS assays showed that the MaExp1 and MaACO promoters directed very low GUS activities in leaves of stably transformed banana plants compared to the constitutive ZmUbi and BT4 promoters. In summary, the results from this research provide evidence that the banana phytoene synthase gene (APsy2a) and the banana ferritin gene (BanFer1) are functional, since the constitutive over-expression of each of these transgenes led to increased levels of pVA carotenoids (for APsy2a) and iron content (for BanFer1) in transgenic rice callus. Further work is now required to determine the functionality of these genes in stably-transformed banana fruit. This research also demonstrated that the MaExp1 and MaACO promoters are fruit-active but have low activity in non-target tissue (leaves), characteristics that make them potentially useful for the biofortification of banana fruit. Ultimately, however, analysis of fruit from field-grown transgenic plants will be required to fully evaluate the suitability of pVA biosynthesis genes and the fruit-active promoters for fruit biofortification.

Investigating the association between sun exposure and folate degradation in the human body

This thesis is the first study to investigate the associations between sun exposure and folate degradation in a group of childbearing age women in a high UV environment. It examined whether the degree of sun exposure experienced by women influenced blood folate levels following a period of folic acid supplementation and found a strong significant relationship between increased sun exposure and folate degradation. This relationship has strong implications for public health and the thesis has provided a foundation for further research in this area.

The effectiveness of dietary counselling versus oral nutrition supplements in improving nutritional intake in malnourished patients with Chronic Obstructive Pulmonary Disease (COPD)

The evidence for nutritional support in COPD is almost entirely based on oral nutritional supplements (ONS) yet despite this dietary counseling and food fortification (DA) are often used as the first line treatment for malnutrition. This study aimed to investigate the effectiveness of ONS vs. DA in improving nutritional intake in malnourished outpatients with COPD. 70 outpatients (BMI 18.4 SD 1.6 kg/m2, age 73 SD 9 years, severe COPD) were randomised to receive a 12-week intervention of either ONS or DA (n 33 ONS vs. n 37 DA). Paired t-test analysis revealed total energy intakes significantly increased with ONS at week 6 (+302 SD 537 kcal/d; p = 0.002), with a slight reduction at week 12 (+243 SD 718 kcal/d; p = 0.061) returning to baseline levels on stopping supplementation. DA resulted in small increases in energy that only reached significance 3 months post-intervention (week 6: +48 SD 623 kcal/d, p = 0.640; week 12: +157 SD 637 kcal/d, p = 0.139; week 26: +247 SD 592 kcal/d, p = 0.032). Protein intake was significantly higher in the ONS group at both week 6 and 12 (ONS: +19.0 SD 25.0 g/d vs. DA: +1.0 SD 13.0 g/d; p = 0.033 ANOVA) but no differences were found at week 26. Vitamin C, Iron and Zinc intakes significantly increased only in the ONS group. ONS significantly increased energy, protein and several micronutrient intakes in malnourished COPD patients but only during the period of supplementation. Trials investigating the effects of combined nutritional interventions are required.

Estimating the burden of disease attributable to iron deficiency anaemia in South Africa in 2000

OBJECTIVES To estimate the extent of iron deficiency anaemia (IDA) among children aged 0 - 4 years and pregnant women aged 15 - 49 years, and the burden of disease attributed to IDA in South Africa in 2000. DESIGN The comparative risk assessment (CRA) methodology of the World Health Organization (WHO) was followed using local prevalence and burden estimates. IDA prevalence came from re-analysis of the South African Vitamin A Consultative Group study in the case of the children, and from a pooled estimate from several studies in the case of the pregnant women (haemoglobin level < 11 g/dl and ferritin level < 12 microg/l). Monte Carlo simulation-modelling was used for the uncertainty analysis. SETTING South Africa. SUBJECTS Children under 5 years and pregnant women 15 - 49 years. OUTCOME MEASURES Direct sequelae of IDA, maternal and perinatal deaths and disability-adjusted life years (DALYs) from mild mental disability related to IDA. Results. It is estimated that 5.1% of children and 9 - 12% of pregnant women had IDA and that about 7.3% of perinatal deaths and 4.9% of maternal deaths were attributed to IDA in 2000. Overall, about 174,976 (95% uncertainty interval 150,344 - 203,961) healthy years of life lost (YLLs), or between 0.9% and 1.3% of all DALYs in South Africa in 2000, were attributable to IDA. CONCLUSIONS This first study in South Africa to quantify the burden from IDA suggests that it is a less serious public health problem in South Africa than in many other developing countries. Nevertheless, this burden is preventable, and the study highlights the need to disseminate the food-based dietary guidelines formulated by the National Department of Health to people who need them and to monitor the impact of the food fortification programme.

Micronutrients: dietary intake v. supplement use

Whilst clinical deficiency of micronutrients is uncommon in the developed world, a suboptimal intake of certain micronutrients has been linked with an increased risk of chronic diseases such as CVD and cancer. Attention has therefore focused on increasing micronutrient status in order to theoretically reduce chronic disease risk. Increasing micronutrient status can involve a number of approaches: increasing dietary intake of micronutrient-rich foods; food fortification; use of supplements. Observational cohort studies have demonstrated an association between high intakes of micronutrients such as vitamin E, vitamin C, folic acid and beta-carotene, and lower risk of CHD, stroke and cancer at various sites. However, randomised intervention trials of micronutrient supplements have, to date, largely failed to show an improvement in clinical end points. The discordance between data from cohort studies and the results so far available from clinical trials remains to be explained. One reason may be that the complex mixture of micronutrients found, for example, in a diet high in fruit and vegetables may be more effective than large doses of a small number of micronutrients, and therefore that intervention studies that use single micronutrient supplements are unlikely to produce a lowering of disease risk. Studies concentrating on whole foods (e.g. fruit and vegetables) or diet pattern (e.g. Mediterranean diet pattern) may be more effective in demonstrating an effect on clinical end points. The present review will consider the clinical trial evidence for a beneficial effect of micronutrient supplements on health, and review the alternative approaches to the study of dietary intake of micronutrients.