It seems highly likely that flour could be fortified with folic acid next year in the UK, a decision that has lagged behind other European countries for years. Yet did we hold back for good reason and what are the potential pros and cons of this? This insight post discusses.

Folate Forms.
First up, before we delve into the ins and outs of fortification strategies it’s important to recognise that there are several different folate forms.

Folate – this is a general term for a group of water soluble B-vitamins, and is also known as B9. Dark green leafy vegetables such as broccoli, spinach, kale and whole grains can provide folate though the bioavailability of these tends to be poor.

Folic acid – this refers to the oxidized synthetic compound used in dietary supplements and food fortification.

5-methyltetrahydrofolate (5-MTHF) or L-methylfolate – this is the pure stable crystalline form of the naturally-occurring predominant form of folate. This type of water-soluble B-vitamin plays a key role in central metabolic pathways, e.g., cell division and repair.

Requirements May be DIFFERENT.
This is very important to consider. For example, individuals who have previously had a neural-tube defect (NTD) affected pregnancy or those with diabetes may require up to 5 mg per day. There is also growing evidence that obese women could well have higher requirements of this nutrient. Equally, women with underlying polymorphisms in genes related to folate metabolism can benefit from 5-MTHF instead of folic acid

Folate requirements.

  • Healthy women – 0.4 mg/day
  • Women with diabetes – 5mg/day
  • Women who have had a previous NTD-affected pregnancy – 5mg/day
  • Women with obesity – 0.4mg/day ↑

Other recent work suggests that 0.4mg-0.8mg per day could be enough, as intake above ∼1 mg does not show an increase in absorption. However, in this work it is recommended that maternal folate status should be assessed. Bearing this in mind, should requirements first be updated become fortification strategies go ahead? – the last report was in 2006.

Genetic Polymorphisms Should be Considered.
The MTHFR 677TT genotype polymorphism (when the base code in DNA changes) is present in 10-22% of the European population. These individuals have an increased risk of delivering infants with neural tube defects. Obviously, the key issue here is screening to make women aware that they have this polymorphism. These individuals have lower folate levels and are less responsive to folic acid.

The dihydrofolate reductase (DHFR) 19-bp deletion polymorphism occurs when a mutated enzyme has a limited ability to reduce folic acid. This condition is associated with higher levels of unmetabolised folic acid in the blood.

Take Home Points.

  1. Will supplementation strategies become confused? One concern is that if flour is fortified with folic acid will supplementation strategies become confused? This poses more of a risk than a strength.
  2. Would women of childbearing age eat enough of these flour fortified foods to generate an effect? For example, are we actually moving away from eating breads and lowering our carbohydrate intake?
  3. What about those with higher requirements and those with polymorphisms? For some individuals with higher requirements, the amount of folic acid delivered via flour may not even touch the sides. Carriers of certain polymorphisms in genes related to folate metabolism or absorption have an increased benefit from 5-methylTHF intake instead of folic acid.
  4. Is folic acid the best folate form for everyone? There is growing evidence that naturally occurring 5-MTHF has valuable advantages over synthetic folic acid – it is well absorbed and its bioavailability is not affected by metabolic defects.
  5. What about the masking of vitamin B12 deficiency? Using 5-MTHF instead of folic acid also reduces the potential for masking haematological symptoms of vitamin B12 deficiency.
  6. And what about ‘unmetabolised folate?’ – do we know enough? Use of 5-MTHF also prevents the potential negative effects of unconverted folic acid in the peripheral circulation also known as ‘unmetabolised folate’.

Concluding Points.
All in all, clearly we don’t want to see babies born with cleft lip and palate, hydrocephalus or neural tube defects. Yet is flour fortification really the best strategy for everyone? I tend to stick with the idea that in the ideal world pregnancies should be planned. In addition, we would also screen for genetic polymorphisms. Where I am slightly confused, is around the idea that we were moving into the era of personalised nutrition, yet this seems to go against this? Hence, we all could well be consuming extra folic acid, whether we are pregnant or not, and whether we like it or not.  Finally, if we were to fortify flour should it not be with 5-MTHF?

Related references.
Dolin CD et al. (2018) Folic Acid Supplementation to Prevent Recurrent Neural Tube Defects: 4 Milligrams Is Too Much. Fetal Diagn Ther 44(3):161-165

Scaglione F & Panzavolta G (2014) Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica 44(5):480-8.

Obeid R et al. (2013) Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects? J Perinat Med 41(5):469-83.

Derbyshire (2011) Nutrition in the Childbearing Years. Wiley Blackwell, West Sussex. pp. 34-36.

SACN (Scientific Advisory Committee on Nutrition) (2006) Folate and Disease Prevention. The Stationary Office: London.