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U.K. will fortify flour to prevent birth defects, joining long list of other countries

In 2013 at the Scottish Parliament in Edinburgh, 9-year-old Ella Chambers of Glasgow spoke to politicians from her wheelchair. Ella has spina bifida, a birth defect that occurs when the embryonic neural tube does not close properly during the first month of pregnancy. She and her family were campaigning for the U.K. government to mandate fortification of flour with folic acid, a synthetic form of the B vitamin folate that can prevent many such defects. Ella’s mother had taken folic acid supplements—but not until she knew she was pregnant, by which point the damage was done.

The United Kingdom studied and wrangled over the issue for another 8 years. Finally, last month, the country announced it would begin the mandatory addition of folic acid to white flour. New Zealand made a similar announcement in July. The U.K. decision, the culmination of a long campaign that included pro-fortifica­tion recommendations by government science advi­sers in 2006 and again in 2017, puts the country in line with 80 or so others, including the United States, Canada, and Australia, many of which made the change decades ago.

“I couldn’t believe they had actually done it,” says Ella, now 17, of the U.K. move.  “It was a bit of a shock—in a good way.”

“There’s nothing that can help Ella,” who is paralyzed from her chest down and has learning difficulties, says her mother, Melanie Chambers. The family has worked with Spina Bifida Hydrocephalus Scotland to promote fortification. “But other families hopefully won’t have to go through what we have.”

Yet the nations of the European Union are not following suit. For reasons that include a wariness about unnatural ingredients in food, they have steadfastly declined to mandate flour fortification. The average prevalence of neural tube defects (NTDs) in 19 European countries is about 10 for every 10,000 pregnancies, notably higher than in others where fortification is required. (The figure is seven per 10,000 pregnancies in the United States.)

“Europe is really dragging the chain,” says Lyall Thurston, a veteran New Zealand activist whose 38-year-old son has spina bifida. “It’s incredibly sad. Because the science and the research is there.”

The power of folic acid
The prevalence of neural tube defects dropped notably in the years after these countries began to fortify flour with folic acid. The European Union does not require fortification and the United Kingdom just decided to do so.
GRAPHIC: K. FRANKLIN/SCIENCE; DATA: European Commission; National Center on Birth Defects and Developmental Disabilities/U.S. Centers for Disease Control and Prevention

Babies with NTDs are born without brains or with their spinal cords protruding from their backs, the former killing them and the latter often causing lifelong disability. Many pregnancies are terminated when an NTD is diagnosed. An estimated 70% to 80% of cases are due to inadequate folate, an essential nutrient that promotes DNA synthesis and is present in leafy greens, liver, lentils, and other dietary sources.

Back in 1991, Nicholas Wald, now a professor of preventive medicine at University College London, and colleagues showed that folic acid supplements taken before and during early pregnancy substantially reduced NTDs. Folic acid is a synthetic form of folate that is better absorbed than the natural form and more effective in preventing NTDs. Because the neural tube closes by 28 days after conception, before most women know they are pregnant, starting in the 1990s many countries aimed to boost the nutrient value for everyone. They required companies to add folic acid to white flour. (In the United States, “enriched” rice, pasta, and cornmeal are also fortified.) The numbers of pregnancies affected by NTDs dropped in every country studied.

But no EU nation joined them. Fortification “has not been considered justified” by the scientific evidence, says an official of the European Commission. Even targeted supplementation isn’t uniformly urged by European policies, most of which date to the 1990s. In a survey published in 2016, only three of 20 countries recommended that all women of childbearing age take a daily folic acid pill. Although 11 countries recommended folic acid supplementation by women planning a pregnancy, none specified that they should start 12 weeks before conceiving, the time needed to attain optimal protective levels, according to work published since 2000.

Such measures are inadequate in any case, fortification advocates say. They note that about 50% of pregnancies are unplanned and many women, particularly disadvantaged ones, don’t know they need supplements.

The result is an elevated rate of NTDs in much of Europe—in Bulgaria, for example, 22 of every 10,000 pregnancies are affected. The rate is lower in a few countries such as Italy (5.4), perhaps because of diet or widespread use of folic acid supplements by women before becoming pregnant.

Pressure to fortify in Europe may have been muted because most affected fetuses are identified by antenatal screening and terminated, health experts say. Across 19 EU countries that are full members of a European Commission registry, 80% of affected pregnancies were terminated in recent years. (In the United States, an estimated 23% to 42% are terminated.)

Compared with many other countries, “Europe has very good access to terminations,” says Vijaya Kancherla, an epidemiologist at the Center for Spina Bifida Prevention at Emory University. “There are not as many babies born with these conditions, so they don’t see them and they think there is no problem.”

Kancherla adds that many Europeans “see anything added to food as … not natural, as being dangerous to the body. Which is not true for folic acid.”

Some European experts are wary of potential adverse effects from excessive folic acid intake in the general population. That’s what the German Federal Institute for Risk Assessment (BfR) wrote in a 2017 report rejecting mandatory fortification. BfR recommended folic acid intake be boosted only in the target group of women. “The benefits of folic acid for a relatively small group must be weighed against the possible disadvantages for a large part of the population,” the report argued.

Adverse effects have been seen at very high doses of folic acid, in excess of 5 milligrams daily, or 36 times the amount added to a 100-gram serving of fortified white bread in the United States. In the 1940s, some people with vitamin B12 deficiency given very high doses of folic acid to treat anemia developed irreversible neuropathies. More recent studies have hinted at cognitive impairment in the elderly and growth promotion of existing cancers. But other studies have found that folic acid protects against some cancers. “Strong biological and mechanistic premises connecting [high folic acid levels] to adverse health outcomes are lacking,” a 2019 National Institutes of Health workshop concluded.

“We have had folic acid fortification in the U.S. for [23] years and we haven’t seen skyrocketing rates of colon cancer or other conditions,” adds Philip Lupo, an epidemiologist at Baylor College of Medicine.

Irwin Rosenberg, a physician and nutritionist who is a professor emeritus at Tufts University, says he’s worried about excess folic acid from supplements in the United States, where supplements are popular and largely unregulated. But he’s not concerned about fortified flour. The potential adverse effects of fortification are so weak that they “really should not have been used … as an argument against fortification,” he says.

“The evidence against folic acid [fortification] is really weak,” agrees Rima Obeid, a clinical biochemist at Saarland University Hospital in Homburg, Germany. “The problem is you don’t have [a] political interest” in getting it done.

Possible toxicity from folic acid is the last thing on the mind of Katya Kovacheva, of the Medical University, Pleven, in Bulgaria, who runs the country’s only birth defects registry. “I have drawn attention to the high prevalence of NTDs in our country … unfortunately without a response from the authorities,” she says.

Michael Turner, a professor of obstetrics and gynecology at University College Dublin, says lobbying authorities country by country is unlikely to yield results. “I would make a heartfelt cry for all European countries … to come together to standardize mandatory food fortification in Europe. There needs to be a pan-European solution to this.”

Source: Science Mag