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Folic acid fortification: The current global state of play

By Lynda Searby

- Last updated on GMT

The fortifiers and the non-fortifiers - who is doing what when it comes to folic acid and neural tube defects? © iStock.com / eyegelb
The fortifiers and the non-fortifiers - who is doing what when it comes to folic acid and neural tube defects? © iStock.com / eyegelb

Related tags: Folic acid fortification, European union, Uk, Eu, Neural tube defects

To date 75 countries globally have implemented mandatory fortification programmes for folic acid with the aim of preventing neural tube defects (NTDs) in babies. Yet despite growing calls from NGOs, health experts and researchers, the 28 EU member countries are notably absent from the list. 

Whether there should be mandatory fortification of folic acid across the EU has been hotly debated for some time, with regulatory agencies across the bloc pondering the idea of introducing national guidelines for fortification of foods with the pro-vitamin. 

NutraIngredients rounds up mandatory and voluntary folic acid fortification efforts in Europe and beyond. 

The UK: Fortification on the cards?

The only EU country moving in the direction of mandatory fortification is the UK.

Currently, UK flour is enriched with nutrients such as iron, calcium carbonate and thiamin (vitamin B1) and there is strong support for adding folic acid to this list.

The Scientific Advisory Comittee on Nutrition (SACN) and food standards groups including the Food Standards Agency in Scotland and Northern Ireland have recommended mandatory fortification of flour with folic acid and the decision is now in the hands of UK health ministers.

The Scottish government is strongly committed to mandatory fortification and, in the absence of firm commitment from Westminster, is taking steps towards mandatory fortification on a Scotland-only basis. 

Ireland: Voluntary approach failing

Ireland came close to implementing mandatory flour fortification on the back of a recommendation by the Food Safety Authority of Ireland (FSAI) in 2006.

Three years later, the programme was halted when mandatory flour fortification was deemed unnecessary. Instead, voluntary fortification was pursued to bring NTD rates down.

However, according to a study published last year in the Journal of Public Health​, the percentage of fortified foods​ has since decreased, and the incidence of neural tube defects is increasing​.

According to Professor Helene McNulty, director of the Northern Ireland Centre for Food and Health (NICHE), this has put the spotlight back onto mandatory fortification.

“Ireland is probably the closest country to the UK (within Europe) in terms of considering mandatory folic acid fortification.

"The decision is now in the hands of the government health minister,”​ she told NutraIngredients. 

Rest of Europe and Asia: Resistant to fortification

In other European countries, mandatory fortification looks unlikely to happen any time soon, with most governments preferring to rely on public health recommendations for folic acid intakes as a means of preventing NTDs.

Advice differs between countries, although the majority follow the World Health Organisation (WHO) guidance of a healthy diet plus a folic acid supplement of 400 micrograms per day from preconception (4-12 weeks) until the end of the first trimester of pregnancy (8-12 weeks).

Three European countries - Finland, France and Sweden - consider supplementation unnecessary if a healthy diet is adhered to.

Singapore and Taiwan have taken a similar stance, and Asian countries in general are unlikely candidates for mandatory folic acid fortification, with fortification efforts focused on other nutrients.  

The US: Where it all started

The US became the first country to introduce mandatory folic acid fortification in 1998, a policy which has resulted in a decline in NTDs.

According to data from the US Centers for Disease Control and Prevention, NTD prevalence decreased by 36% after fortification, although prevalence was 21% higher among Hispanics.

This led to an FDA announcement last week that the mandate would be extended to include corn masa flour - a staple in Hispanic diets. 

Successful mandatory fortification programmes have also been documented in other countries including Canada, Costa Rica, Chile and South Africa, resulting in significant increases in blood folate concentrations and 25-50% reductions in the prevalence of NTD-affected pregnancies. 

FFI Network Grain_Fortification_Legislation_April_2016
Mandatory cereal grain fortification with vitamins & minerals 2016 (source: Food Fortification Initiative)Red = wheat flour; green = wheat flour and maize flour; orange = wheat flour and rice; blue = wheat flour, maize flour and rice; yellow = rice 

Post-Soviet states embrace fortification

The former Soviet Union countries have also proved willing adopters of mandatory fortification. Turkmenistan was one of the first countries to fortify its flour supplies in 2006, a policy that has resulted in lower NTDs.

Other post-Soviet countries including Kazakstahn, Kyrgyzstan and Uzbekistan have since followed suit, and others, such as Tajikistan and Georgia, are planning to implement mandatory fortification. 

Australia and New Zealand: Differences down under

In 2009, Australia and New Zealand jointly agreed on mandatory fortification.

However, whilst Australian millers have been adding folic acid to wheat flour used for breadmaking at a dose of 2–3 mg per kilogram since 2009, just one month before the planned introduction of folic acid fortification the New Zealand government announced it would not be going ahead with the deal signed by the two countries two years earlier.

The government’s minister of health said further research was needed and the decision was deferred. In 2012 the government made a decision to continue with voluntary fortification of bread with folic acid rather than making it mandatory. 

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Folic acid fortification, MTHFR and NTDs

Posted by Helene McNulty, Anne Molloy, Mary Ward, Kristina Pentieva,

It is entirely incorrect to state that ‘folic acid fortification is causing a huge problem’ for people with a common mutation in the MTHFR gene (i.e. the MTHFR C677T polymorphism) and the explanation in relation to unmetabolized folic acid is misrepresented (comments posted 28 April and 03 May) and inaccurate in that folic acid requires the enzyme DHFR, not MTHFR. Folic acid provides a highly stable and bioavailable form of the vitamin folate, and is also the only vitamin form which is proven to reduce the risk of neural tube defects (NTD). As researchers who have dedicated our scientific careers to investigating folate and related B vitamins we find both statements to be untrue. It is our view, based of years of research in the field, that THE biggest public health concern in this area is that preventable NTDs are not being prevented in many countries globally (including most of Europe) because of inadequate uptake of folic acid supplement usage, as recommended, by women of reproductive age, for various reasons, and a delayed response by many governments to introduce mandatory (population-wide) folic acid fortification to provide protection to those women not reached through folic acid supplementation.

We would like to make the following points:
1. Current folic acid recommendations to prevent NTD are based on the strongest scientific evidence possible (the randomized clinical trial; RCT);
2. Those RCTs were conducted using the ‘cheaper’ folic acid (not methylfolate) and while it is likely that methylfolate taken orally would provide benefit in preventing NTD we cannot assume that this is the case. It would be unethical therefore to conduct such a trial i.e. to randomly assign women, in a future study, to receive an unproven alternative to folic acid given that folic acid has been proven to prevent NTD.
3. There is no evidence that folic acid is problematic specifically for the people worldwide (10%) with 2 copies of the variant MTHFR gene mentioned above (i.e. those with the co-called TT genotype); in fact many are of the view that these people have higher requirements, compared to the general population, because of their impaired folate metabolism. For example, the European Food Safety Authority (EFSA) in its recent report, factored in the higher folate requirements of people with the TT genotype in MTHFR by revising dietary folate recommendations. Readers should note that the first reference quoted in relation to high folic intake and MTHFR was on mice engineered to have a genetic deficiency in MTHFR. Extrapolation to the MTHFR 677CT genotype in humans is speculation. The second reference, on pregnant women, acknowledges that women with TT genotype have lower serum folate. The third does not refer to MTHFR at all.
4. Rather than warning women with the TT genotype against the use of folic acid on the basis of risk of miscarriage, they should arguably be specifically targeted for folic acid supplementation because they are more at risk of this and a number of adverse pregnancy outcomes linked with low folate, including: Decreased embryo viability; Increased incidence of aneuploidy (abnormal no. of chromosomes in the cell); Recurrent pregnancy loss; Spontaneous abortion; Pre-term delivery; Low birth rate.

Finally, the fourth reference quoted does indeed give a balanced overview of the potential dangers of very high folic acid consumption and is worth reading. It concludes ‘The potential adverse effects that might arise from folic acid fortification are complex and could lead to a “fear of folate” if not dealt with carefully’. In our view, it is highly important to monitor folic acid fortification practices but equally, highly irresponsible to scare-monge

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Slow absorption causes unmetabolised folic acid accumulation in blood

Posted by Kerry Mackinsey,

It is simplistic to say that with a MTHFR mutation folic acid is simply absorbed more slowly. Because of reduced enzyme capacity saturation occurs more quickly, resulting in significant unmetabolised folic acid entering the systemic circulation. This is increasingly showing up in research as potentially deleterious.
The CDC article given as reference in the comment below does not explain this (perhaps they do not understand this?). It also mentions only one of the MTHFR variants but there are more and a compound homozygote will have even less capacity to metabolise folic acid quickly enough to prevent unmetabolised folic acid accumulating in the blood.
High levels of folic acid in the blood are becoming implicated in a range of other health issues eg increased breast and colorectal cancer,increased malaria risk, reduced natural killer cell cytotoxicity, masking of vitamin B12 deficiency and more. High levels of folic acid are also thought to inhibit MTHFR function even in those without a mutation in this gene. See below some references regarding these and other concerns. For more information also see the citations listed in these papers.
Am J Clin Nutr 2015 101:646-658; Am J Clin Nutr 2015 102:848-857; Br J Nutr. 2007 Oct 98(4):667-75; Prev Nutr Food Sci. 2014 Dec 19(4):247–260;

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MTHFR and folic acid

Posted by Sarah Zimmerman,

People with the MTHFR mutation can absorb folic acid; they simply absorb it more slowly than others. Thus the number of people with the MTHFR mutation is not a reason to avoid foods fortified with folic acid. See the last paragraph here: http://www.cdc.gov/ncbddd/birthdefectscount/faq-folic-ntd.html. Methylfolate is not a good alternative for fortification because it is not stable when heated, and most foods are cooked or baked.

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