Does New Zealand need folic acid fortification?

On the 8th of July 2021 the New Zealand government decided to finally give into the pressure to legislate for mandatory fortification of wheat flour with folic acid. Several times before the government had been asked to do this, but given the relatively small number of people who stand to benefit from this type of mass medication, the action had always been hard to justify. 

Let’s start with the good news: Organic sourdough bread is a great source of folate and fibre. And even if the mandatory fortification will come into effect, organic flour will be exempt from it. So for those of you, who don’t want to pollute your bodies with synthetic chemicals, please know that at Bread & Butter Bakery we will continue to bake with flour that is not laced with chemicals and we will continue to use our ancient method of slow long sourdough fermentation, thus adding additional natural folate to our loaves.   Read on to find out more on my take on the problem with mandatory fortification …. 

“What’s the problem with mandatory folic acid fortification?”, you might ask. 

For starters one should do a risk-benefit analysis of the proposal and ask, what the net benefit of mass administration of synthetic folic acid would be. Sadly this was not presented in the government’s statements. So I am going to try and explain the issue and the risks involved here. It requires a bit of biology and biochemistry, so I apologise, if it gets a little technical.

Folate is the natural vitamin that is part of the vitamin B group of vitamins. It is naturally present in many foods. Folate is required for the body to make DNA and RNA [the molecules that store our genetic information, authors note] and metabolise amino acids necessary for cell division. As humans cannot make folate, it is required in the diet, making it an essential nutrient. The recommended adult daily intake of folate is 400 micrograms. [Wikipedia]. Folic acid is the stable synthetic form of folate that gets converted to folate inside our bodies. 

Because a baby forming during pregnancy is in a constant state of growth and therefore DNA replication, pregnant women need a higher amount of folate in their daily diet to support their baby’s development compared to the non-pregnant population. A lack of sufficient folate in pregnant woman has been linked to Spina Bifida, a neural tube defect (NTD) where the spinal cord of the baby does not fully form. Each year approximately 0.012% of births are affected, or in other words in New Zealand an estimate of seven babies per year are born or are prematurely aborted because of this condition, resulting in miscarriage.

Studies conducted by the Vitamin Research Group in the early 1990s (1) have concluded that supplementation of folic acid pre-pregnancy leads to significant reduction in NTDs. But given that nearly 50% of all pregnancies are unplanned and the high levels of folate are especially critical in the first 28 days of pregnancy, when many women don’t even know that they are pregnant, pre-pregnancy voluntary supplementation seems difficult. Hence various governments have mandated fortification of grain products with folic acid since the late 1990s and in the countries that have done so (US, Canada, Chile, Australia and a few others) frequency of NTDs has decreased since. 

So does this oblige us in New Zealand to follow? 

What are the risks of folic acid fortification?

To understand the risks it is necessary to delve a little deeper into the biochemistry of the folate metabolism in our bodies. Folate plays an essential role in the human body as a major coenzyme in one-carbon metabolism, including DNA synthesis. Synthetic folic acid (pteroylmonoglutamic acid, short PteGlu) is very stable under the majority of conditions (i.e. temperature and pH), and is the vitamer used for supplements and food fortification. However, since PteGlu is not a natural form of folate, it requires additional metabolic steps before it can be used by our bodies. The rate at which our bodies are able to convert PteGlu is extremely low and, therefore, to be effective the synthetic form has to be taken in high dosage. Administration of high concentrations of the synthetic form of this vitamin can lead to its accumulation in the bloodstream (2). This unmetabolised PteGlu has the potential to accelerate DNA break-down (3). 

Entry of synthetic PteGlu into folate metabolism. PteGlu, pteroylmonoglutamate or folic acid; DHFR, dihydrofolate reductase; SHMT, serine hydroxymethyltransferase; MTHFR, methylenetetrahydrofolate reductase; MS, methionine synthase; DMG, dimethylglycine; BHMT, betaine-homocysteine methyltransferase; SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine; Hcy, homocysteine (Figure from: Contemporary Issues Surrounding Folic Acid Fortification Initiatives. Jeong-Hwa Choi,1,5 Zoe Yates,2 Martin Veysey,3 Young-Ran Heo,4 and  Mark Lucock1, Prev Nutr Food Sci. 2014 Dec; 19(4): 247–260.)

Some research seems to indicate that chronic exposure to a high level of folate leads to increased folate consumption required to meet the elevated metabolic demand, a positive feedback loop, meaning for the people, who are not currently pregnant – approximately 98% at any given time – increased exposure to folic acid could disrupt their natural folate cycle and lead to downstream effects that could mess with other natural functions of our bodies. (4)

Have any negative effects of mandatory folic acid supplementation been found?

Here are a few that I could find:

Early studies in Norway and the US suggested that maternal use of folic acid supplements decreased risk of Autism Spectrum Disorders (ASD). However, recent studies also suggested that ASD occurrence is increasing with time, and increased intake of maternal folic acid supplements might be partially responsible for it. A study in the US analyzed data from the Center for Disease Control for 1994~1999 and concluded that the use of maternal folic acid supplements increased the risk for ASD by approximately 2.5 times. (6)

Folic Acid fortification also seems to interrupt the natural Vitamin B12 metabolism and mask deficiencies in this vitamin (11). 

There are other studies that suggest that folic acid fortification leads to elevated levels of colorectal cancer (5), that it leads to a reduction in cytotoxicity of natural killer cells, a group of immune cells that mediate our response to pathogens like viruses and bacteria (7). 

And the potential for unmetabolised synthetic folic acid to be genotoxic, meaning the unmetabolised folic acid has a potential to interfere with DNA directly and thus may lead to higher levels of mutation and thus an elevated risk of various forms of cancer (8). 

There seems to be an increased risk of twin births (9).

Also high concentrations of synthetic folic acid might interfere with epilepsy medication (10), 

Another study suggests that higher maternal folate levels led to higher rates of adiposity and higher insulin resistance in their children. (11)

According to one study, pregnant women who were administrated a PteGlu supplement during their pregnancy showed the presence of unmetabolized PteGlu in their milk and low milk folate binding protein synthesis. The effects on the babies have not been studied. (12)

The list could probably be extended. I am by no means an expert in this field. But suffice to say that artificially increasing the levels of an essential vitamin by means of mandating that everybody take elevated levels of a synthetic product without fully understanding the metabolic pathways and multitude of factors that are at play at any given time bears massive risks of causing other unintended problems down the line. 

Given that only 2% of the population are pregnant at any given point in time and only 0.012% of the pregnancies are actually affected by the potential effects of low folate this means that only 2-3 in 1,000,000 people would benefit. Or looking at it the other way 999,997 people have to take a potentially risky synthetic additive in their food, with no apparent benefit to them, so that three people can benefit. Is this justifiable?

While there is an apparent giant discrepancy of benefit on a population basis, you  might still argue that every life is valuable and if we can prevent one baby from being born with a potentially deadly disorder, we should still do it. The cost of this intervention will be born by everyone to a small degree and therefore one could potentially justify it. If it was unequivocally beneficial and there were no risks for others attached to the intervention this might be so. But given the above mentioned apparent risks, one should also ask, what are the alternatives? 

Why do we have to fortify flour at all?

After all, folate naturally occurs in foods and natural folate does not seem to come with the same risks as the synthetic version of it. 

The main reason that wheat products are singled out as the culprits that need to be enhanced artificially is that the majority of wheat products consumed in the anglophone world are produced from highly refined white wheat flour. This flour is produced by stripping away the outer husk of the wheat kernel, which contains most of the nutrients, including all of the natural folate (13). So it is our propensity to eat white, sugary bread rather than nutritionally more valuable whole foods that have created this problem. Instead of fortifying a nutritionally low quality product with a synthetic additive of questionable benefit, why doesn’t the government mandate that all bread should contain a certain proportion of wholemeal or wholegrain flour?

Furthermore baker’s yeast – Saccharomyces – as well as several other strains of wild yeasts produce folate during the fermentation process (14). They do it however rather slowly, meaning it takes more than an hour (the time factory made conventional supermarket bread is fermented for) and optimal fermentation times for high rates of folate production seem to be at least 12 hours of fermentation. So again, one could also solve this issue by mandating that all bread has a minimum fermentation time of 12 hours. This would add folate even to white flour products that have been stripped of their natural folate. 

What would the benefits of these interventions be? 

Potentially they would be manifold, since we know that people, who eat a diet high in processed foods and low in fibre and wholefoods, not only suffer from two in a million chance of bearing a child that is born with Spina bifida, but also from a multitude of other illnesses and conditions that are caused by bad nutrition. What would the cost benefit analysis of this intervention look like? 

If the government was actually serious about doing something that would benefit the people’s overall health and was honestly committed to improving people’s lives, rather than window dressing the issue and in the process nonchalantly overlooking the fact that the main beneficiaries of their intervention are certain chemical and pharmaceutical companies, they would not give into public health measures of such minute benefits. 

Again, the good news is that organic sourdough bread is one great source of folate and fibre. And the even better news in all this is that organic flour will be exempt from the mandatory fortification. So for those of you, who don’t want to pollute your bodies with synthetic chemicals, please know that at Bread & Butter Bakery we will continue to bake with flour that is not laced with chemicals and we will continue to use our ancient method of slow long sourdough fermentation, thus adding additional natural folate to our loaves.   

Literature cited in this article:

(1) Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991 Jul 20; 338(8760):131-7.

(2) The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. Bailey SW, Ayling JE. Proc Natl Acad Sci U S A. 2009 Sep 8; 106(36):15424-9. 

(3) Inhibition of pig liver methylenetetrahydrofolate reductase by dihydrofolate: some mechanistic and regulatory implications.[Biochemistry. 1979]

 (4) Is folic acid good for everyone? A David Smith 1, Young-In Kim, Helga Refsum. [Am J Clin Nutr. 2008]

(5) Folate and colorectal cancer: an evidence-based critical review. Kim YI. Mol Nutr Food Res. 2007 Mar; 51(3):267-92.

(6) Autism, seasonality and the environmental perturbation of epigenome related vitamin levels.[Med Hypotheses. 2013]

 (7) Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. Troen AM  et al, J Nutr. 2006 Jan; 136(1):189-94.

(8) Methyltetrahydrofolate inhibits photosensitization reactions and strand breaks in DNA. Offer T, Ames BN, Bailey SW, Sabens EA, Nozawa M, Ayling JE. FASEB J. 2007 Jul; 21(9):2101-7.

(9) Higher rate of multiple births after periconceptional vitamin supplementation. Czeizel AE, Métneki J, Dudás I. N Engl J Med. 1994 Jun 9

(10) Folic Acid and Epilepsy. Morrell MJ Epilepsy Curr. 2002 Mar; 2(2):31-34.

(11) Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study. Yajnik CS et al. Diabetologia. 2008 Jan; 51(1):29-38.

(12) Unmetabolized folic acid and total folate concentrations in breast milk are unaffected by low-dose folate supplements. Houghton LA, Yang J, O’Connor DL. Am J Clin Nutr. 2009 Jan; 89(1):216-20.

(13) https://www.laucke.com.au/knowledge-base/distribution-of-nutrients-in-the-grain

(14) Production of folate in oat bran fermentation by yeasts isolated from barley and diverse foods. M. Korhola, R. Hakonen, K. Juuti, M. Edelmann, S. Kariluoto.  Journal of applied Microbiology. June 2014

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