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).

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.

Knowledge about folate and the contribution of nutrient supplements to the intake of folic acid and vitamin B12 in Australian adults in 1995 and 1996

The present paper reports knowledge about folate and the contribution of supplements to the intake of folic acid and vitamin B12 in Australian adults during 1995 and 1996. Data were obtained from two population survey monitor surveys conducted in a sample of 5422 adults in 1995-96. The surveys were designed to complement food intake data from the 1995 National Nutrition Survey and to provide an estimate of total folate intake prior to the implementation of voluntary fortification of foods with folic acid. The proportion with knowledge about folate increased with education level and socioeconomic status and was greater in women than men. It was also greater in those who were married, and in those residing in Western Australia and the Australian Capital Territory than in other states and territories. Five per cent of men and 10% of women had taken a supplement containing folio acid on the previous day. The equivalent figures for vitamin B12 were 7.5% for men and 12.5% for women. On average, intake of folic acid from supplements was 11 micro g per day for men and 28 micro g per day for women and intake of vitamin B12 was 2.6 micro g per day for men and 4.5 micro g per day for women. For individuals who consumed a supplement containing folic acid on the day before the survey the median folic acid contribution was 200 micro g. In 1995 and 1996 only one in two adult Australians had heard of folate and only one in ten women of child-bearing age had taken a supplement containing folic acid.

Dietary counseling to increase natural folate intake: a ransomized placebo-controlled trial in free-living subjects to assess effects on serum folate and plasma total homocysteine.

BACKGROUND: The association between vascular disease and elevated plasma total homocysteine (tHcy) concentrations is caused, in part, by inadequate intakes of dietary folate. Increasing folate intake either through supplements or foods naturally rich in folates has been shown to decrease tHcy concentrations. OBJECTIVE: The aim of this study was to determine whether a similar reduction in tHcy was possible in free-living persons receiving dietary counseling. DESIGN: The study included a 4-wk placebo-controlled dietary intervention trial in which participants consumed either unfortified breakfast cereal (control group) or an extra 350 micro g folate derived from food/d (dietary group). Serum folate and tHcy concentrations in both groups were measured before and after the intervention period, and the concentrations in the dietary group were also measured 17 wk after the intervention period. RESULTS: During the 4-wk intervention, mean dietary folate intake in the dietary group increased from 263 (95% CI: 225, 307) to 618 micro g/d (535, 714), resulting in a mean increase in serum folate of 37% (15%, 63%) and a decrease in tHcy from 12.0 (10.9, 13.3) to 11.3 micro mol/L (10.2, 12.5). A further decrease in tHcy occurred in the dietary group during follow-up, with a final tHcy concentration of 9.7 micro mol/L (8.8, 10.8). CONCLUSIONS: Increasing natural folate intake improved folate status and decreased tHcy concentrations to an extent that may significantly reduce the risk of vascular disease. Dietary modification may have advantages over folic acid fortification because the altered food-consumption patterns lead to increased intakes of several vitamins and minerals and decreased intakes of saturated fatty acids.

Assessment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial.

Objective: To determine the minimum effective dose of folic acid required to appreciably increase serum folate and to produce a significant reduction in plasma total homocysteine (tHcy).

Design: Double-blind, randomised placebo-controlled intervention trial.

Setting: Community-based project in a New Zealand city.

Subjects: Seventy free living men and women with tHcy10 µmol/l. Mean age (range) was 58 (29-90) y.

Interventions: Daily consumption over 4 weeks of 20 g breakfast cereal either unfortified (placebo) or fortified with 100, 200 or 300 µg folic acid. Dietary intake was determined by weighed diet records and consumption of commercially fortified products was avoided.

Main outcome measures: Plasma tHcy and serum folate concentrations.

Results: Average serum folate concentrations (95% CI) increased significantly in the treatment groups relative to the control group by 28(9-51)%, 60(37-87)% and 79(51-114)% for supplementation with 100, 200 and 300 µg folic acid, respectively. A reduction in tHcy was observed, being 16(8-22)%, 12(4-18)% and 17(9-24)% in the three treatment groups, respectively.

Conclusions: A regular intake of as little as 100 µg folic acid per day was sufficient to lower tHcy in persons at the upper end of the normal range for tHcy. Low-level fortification may also be appropriate for lowering the risk of neural tube defects given that, when aggregated from all sources, the total intake of folic acid may be sufficiently high to adequately improve the folate status of young women.

Comparative effects of tuna oil and salmon oil on liver lipid metabolism and fatty acid concentrations in rats

The comparative effect of tuna oil (TO) and salmon oil (SO) on the plasma and liver lipid and fatty acid compositions in Sprague Dawley rats was investigated. The total triacylglycerol (TG) and total cholesterol (TC) concentrations in liver was significantly decreased in the TO group; TG level in liver was also significantly decreased in the SO group. The mRNA expression of HMG-CoA reductase in liver was significantly down-regulated in the TO and SO groups relative to the control group. The plasma TG and TC were decreased in TO, but not in SO; plasma low-density lipoprotein and very low-density lipoprotein levels in TO and SO were decreased compared with the control group. The total n-3 polyunsaturated fatty acid (PUFA) in plasma and liver phospholipids was significantly elevated in the TO and SO. Docosahexaenoic acid (22:6n-3) and eicosapentaenoic acid (20:5n-3) in tissues were significantly increased in the TO and SO, respectively. In this study, TO had a more beneficial effect on liver TC and plasma TG, TC, high-density lipoprotein in rats than SO. The likely mechanism for lowering liver and plasma cholesterol by n-3 PUFA is to suppress the mRNA expression of gene encoding HMG-CoA reductase responsible for cholesterol biosynthesis.

PRACTICAL APPLICATIONS

The beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) from fish and fish oil on human health is derived from their role in modulating membrane lipid composition and affecting metabolic and signal-transduction pathways. In the present study, we demonstrated that n-3 PUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from tuna and salmon oils can be effectively incorporated into tissue membranes. Tuna oil rich in DHA has more beneficial effect on liver total cholesterol (TC) and plasma triglyceride, TC and HDL in rats than salmon oil, which is rich in EPA. The present data could provide information for the potential application of fish oils as components of functional food, and selected for fortification with different fish oils.

Comparison of different maximum safe levels in fortified foods and supplements using a probabilistic risk assessment approach

Different European institutions have developed mathematical models to propose maximum safe levels either for fortified foods or for dietary supplements. The objective of the present study was to compare and check the safety of these different maximum safe levels (MSL) by using a probabilistic risk assessment approach. The potential maximum nutritional intakes were estimated by taking into account all sources of intakes (base diet, fortified foods and dietary supplements) and compared with the tolerable upper intake levels for vitamins and minerals. This approach simulated the consequences of both food fortification and supplementation in terms of food safety. Different scenarios were tested. They are the result of the combination of several MSL obtained using the previous models. The study was based on the second French Individual and National Study on Food Consumption performed in 2006–7, matched with the French food nutritional composition database. The analyses were based on a sample of 1918 adults aged 18–79 years. Some MSL in fortified foods and dietary supplements obtained independently were protective enough, although some others could lead to nutritional intakes above the tolerable upper intake levels. The simulation showed that it is crucial to consider the inter-individual variability of fortified food intakes when setting MSL for foods and supplements. The risk assessment approach developed here by integrating the MSL for fortified foods and dietary supplements is useful for ensuring consumer protection. It may be subsequently used to test any other MSL for vitamins and minerals proposed in the future.

Iron and zinc nutrition in the economically-developed world : a review

This review compares iron and zinc food sources, dietary intakes, dietary recommendations, nutritional status, bioavailability and interactions, with a focus on adults in economically-developed countries. The main sources of iron and zinc are cereals and meat, with fortificant iron and zinc potentially making an important contribution. Current fortification practices are concerning as there is little regulation or monitoring of intakes. In the countries included in this review, the proportion of individuals with iron intakes below recommendations was similar to the proportion of individuals with suboptimal iron status. Due to a lack of population zinc status information, similar comparisons cannot be made for zinc intakes and status. Significant data indicate that inhibitors of iron absorption include phytate, polyphenols, soy protein and calcium, and enhancers include animal tissue and ascorbic acid. It appears that of these, only phytate and soy protein also inhibit zinc absorption. Most data are derived from single-meal studies, which tend to amplify impacts on iron absorption in contrast to studies that utilize a realistic food matrix. These interactions need to be substantiated by studies that account for whole diets, however in the interim, it may be prudent for those at risk of iron deficiency to maximize absorption by reducing consumption of inhibitors and including enhancers at mealtimes.

Fish oil replacement in current aquaculture feed : is cholesterol a hidden treasure for fish nutrition?

Teleost fish, as with all vertebrates, are capable of synthesizing cholesterol and as such have no dietary requirement for it. Thus, limited research has addressed the potential effects of dietary cholesterol in fish, even if fish meal and fish oil are increasingly replaced by vegetable alternatives in modern aquafeeds, resulting in progressively reduced dietary cholesterol content. The objective of this study was to determine if dietary cholesterol fortification in a vegetable oil-based diet can manifest any effects on growth and feed utilization performance in the salmonid fish, the rainbow trout. In addition, given a series of studies in mammals have shown that dietary cholesterol can directly affect the fatty acid metabolism, the apparent in vivo fatty acid metabolism of fish fed the experimental diets was assessed. Triplicate groups of juvenile fish were fed one of two identical vegetable oil-based diets, with additional cholesterol fortification (high cholesterol, H-Chol) or without (low cholesterol, L-Chol), for 12 weeks. No effects were observed on growth and feed efficiency, however, in fish fed H-Col no biosynthesis of cholesterol, and a remarkably decreased apparent in vivo fatty acid b-oxidation were recorded, whilst in LChol fed fish, cholesterol was abundantly biosynthesised and an increased apparent in vivo fatty acid b-oxidation was observed. Only minor effects were observed on the activity of stearyl-CoA desaturase, but a significant increase was observed for both the transcription rate in liver and the apparent in vivo activity of the fatty acid D-6 desaturase and elongase, with increasing dietary cholesterol. This study showed that the possible effects of reduced dietary cholesterol in current aquafeeds can be significant and warrant future investigations.

Among vitamin B12 deficient older people, high folate levels are associated with worse cognitive function: combined data from three cohorts

Folate fortification of food aims to reduce the number of babies born with neural tube defects, but has been associated with cognitive impairment when vitamin B12 levels are deficient. Given the prevalence of low vitamin B12 levels among the elderly, and the global deployment of food fortification programs, investigation of the associations between cognitive impairment, vitamin B12, and folate are needed.

Environmental and genetic determinants of vitamin D insufficiency in 12-month-old infants

We aimed to investigate the relationship between genetic and environmental exposure and vitamin D status at age one, stratified by ethnicity. This study included 563 12-month-old infants in the HealthNuts population-based study. DNA from participants' blood samples was genotyped using Sequenom MassARRAY MALDI-TOF system on 28 single nucleotide polymorphisms (SNPs) in six genes. Using logistic regression, we examined associations between environmental exposure and SNPs in vitamin D pathway and filaggrin genes and vitamin D insufficiency (VDI). VDI, defined as serum 25-hydroxyvitamin D3(25(OH)D3) level ≤50 nmol/L, was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Infants were stratified by ethnicity determined by parent's country of birth. Infants formula fed at 12 months were associated with reduced odds of VDI compared to infants with no current formula use at 12 months. This association differed by ethnicity (P;bsubesub;= 0.01). The odds ratio (OR) of VDI was 0.29 for Caucasian infants (95% CI, 0.18-0.47) and 0.04 for Asian infants (95% CI, 0.006-0.23). Maternal vitamin D supplementation during pregnancy and/or breastfeeding were associated with increased odds of infants being VDI (OR, 2.39; 95% CI, 1.11-5.18 and OR, 2.5; 95% CI, 1.20-5.24 respectively). Presence of a minor allele for any GC SNP (rs17467825, rs1155563, rs2282679, rs3755967, rs4588, rs7041) was associated with increased odds of VDI. Caucasian infants homozygous (AA) for rs4588 had an OR of 2.49 of being associated with VDI (95% CI, 1.19-5.18). In a country without routine infant vitamin D supplementation or food chain fortification, formula use is strongly associated with a reduced risk of VDI regardless of ethnicity. There was borderline significance for an association between filaggrin mutations and VDI. However, polymorphisms in vitamin D pathway related genes were associated with increased likelihood of being VDI in infancy. © 2014 Elsevier B.V. All rights reserved.

Dietary micronutrients and in vivo n-3 LC-PUFA biosynthesis in Atlantic salmon

Aquaculture, and in particular Atlantic salmon culture, is expected to deliver n. -3 long-chain polyunsaturated fatty acid (n. -3 LC-PUFA) rich products. Nevertheless, the availability of n. -3 LC-PUFA rich raw materials for aquafeed is dwindling, and at an ever increasing market price. Thus, there is the need to better understand the in vivo n. -3 LC-PUFA biosynthetic capabilities of cultured fish to enable the possible maximization of dietary 18:3n. -3 (ALA) bioconversion to 20:5n. -3 (EPA) and 22:6n. -3 (DHA). The cofactors and coenzymes involved in this metabolic pathway have so far received limited research attention. In this study, juvenile Atlantic salmon were fed an ALA-rich diet with no, normal, or over-fortified inclusion of those micronutrients reported to be essential cofactors (iron; zinc; magnesium) and coenzymes (riboflavin; biotin; niacin) for the fatty acid elongase and desaturase enzymes. The results showed that reduced dietary inclusion of these micronutrients impaired the normal n. -3 LC-PUFA biosynthetic capabilities of fish, whereas the over fortification did not provide any additional benefit. This study provides new knowledge on micronutrients and lipid metabolism interactions in a commercially important cultured species, and is envisaged to be a useful contribution towards developing more sustainable and commercially viable aquafeed for the future.Statement of relevance. This work is the continuation and extension of a previous study (Lewis et al., 2013, Aquaculture 412/413, 215-222) in which we explored the physiological roles and potential effects of micronutrients on fatty acid metabolism in cultured fish. The present study differed from the previous in the blend of minerals and vitamins used, the species, the fatty acid composition of the test diet, and the inclusion also of a negative control. The results are most interesting, showing that riboflavin (B2), biotin (B7), and niacin (B3), Iron (Fe), Magnesium (Mg) and Zinc (Zn) are all required for proper fatty acid bioconversion, but also that a dietary over-fortification does not translate into proportional improved bioconversion.

A question mark on iron deficiency in 185 million people of Pakistan: its outcomes and prevention

Micronutrient deficiency especially the iron deficiency is the bane of our lives, affecting all strata of society. Unfortunately, the women during pregnancy, adolescence, and children are under this curse particularly in developing countries like Pakistan. It is one of the biggest reasons of complications during pregnancy and malnourished children under five years of age. Maternal death, still-births, and underweight births are most common consequences of iron deficiency and these outbreaks as iron-deficiency anemia in Pakistan. Disastrous nature of iron deficiency requires an urgent call to eradicate it. Hence, the solution should not be frail comparing with the huge economic loss and other incompatibilities. Flour fortification, supplementation, dietary diversification, and especially maternal education are possible solutions for combating this micronutrient deficiency.