Folic acid fortification, friend or foe?

3 minute read – fact checked ✓

I wanted to share my thoughts regarding the UK Government’s recent announcement to fortify flour with folic acid (1), also known as vitamin B9, discussing arguments for and against the measure. But first, I would like to lay down a disclaimer, by saying that the contents you will read below, although fact-checked and accurate, is not intended as medical or nutritional advice, and so therefore you should still follow the recommended advice of the UK Government or your healthcare professional for that matter.

The UK government recently announced that Folic acid will be added to non-wholemeal wheat flour across the UK to help prevent life-threatening spinal conditions in babies (1), estimating that adding folic acid will mean foods made with flour such as bread, will actively help avoid around 200 neural tube defects each year – around 20% of the annual UK total. Currently, the NHS strongly recommends women who may become pregnant or are planning to get pregnant take a 400 micrograms folic acid tablet every day before pregnancy and until they are 12 weeks pregnant (2). This advice will continue but due to 50% of pregnancies in the UK being unplanned, the UK government is taking action to increase folic acid intake nationally to help protect more babies, especially where a pregnancy is unplanned and supplements are not taken early enough.

The rationale for folic acid fortification is that it is estimated that over 99% of British households buy bread and over a quarter of all groceries in the four biggest supermarkets contain flour, making adding folic acid to flour-based products a simple way to increase folate levels for tens of millions of people across the UK (1). Conversely, flour fortification could also encourage people to consume more refined flour produce which could increase the risk of obesity and metabolic complications, which places folic acid fortification of refined flour at odds with the UK Government obesity campaign (3).

Folate is a key nutrient required for an essential biochemical process in the body known as methylation, involved in a variety of processes such as red blood cell production, estrogen metabolism, cellular energy etc. DNA methylation is a crucial epigenetic modification of the genome that is required for DNA production. However, excessive (hypermethylation) of CpG promotor regions of DNA, could lead to a functional loss of tumour suppressor genes and could result in colorectal cancer (7) as discussed in one of my previous posts (8). However, there is no evidence suggesting that supraphysiological long-term folate supplementation (or increased intake via fortification) could increase cancer risks.  In my opinion, folate status is best achieved via a healthy wholefood diet (fig 1) rich in folate foods (9) with occasional supplementation with methylated 5-methyltetrahydrofolate (5-MTF) which the natural and active form of Vitamin B9 (folate), or a low-dose B-vitamin complex supplement two or three times a week to avoid potential single nutrient interactions, whilst always prioritising a food-first approach.

Folic acid fortification can indeed increase folate status (4), but (synthetic) folic acid could also mask laboratory diagnosis of Vitamin B12 deficiency by correcting anemia, whilst allowing neurological manifestations to progress (5). Additionally, excess (synthetic) folic acid could lead to increased unmetabolised folic acid products (fig 2) and could potentially increase the risks of adverse health outcomes such as cancer by promoting tumour progression, although the evidence is definitely controversial and conflictive (6). Conversely, supplementing with 5-MTF, could potentially reduce the formation of unmetabolised folic acid products and in theory reduce the risks of adverse health outcomes (6). Food fortification with folic acid could also raise issues of potential drug-nutrient interactions, such as patients on Methotraxtate who are not recommended to ‘supplement’ with folic acid as it can interfere with the pharmacodynamics and pharmacokinetics of the medication (11). Folic acid fortification could also interfere with zinc absorption by forming zinc-folic acid complexes in the GI tract (12). Despite these nuances, folic acid food fortification would be a good way to improve folate status in the general population.

But one should also consider whether absolutely everyone of all ages and gender would need increased folate by consuming fortified flour, if the onus is simply to improve maternal folate status to reduce the risks of neural tube defects. Food fortification also raises ethical considerations regarding whether trying to support one aspect of health, may justify ‘medicating’ the entire flour-eating population with folic acid, which could be especially concerning for those individuals already supplementing with higher doses of folate or folic acid for any other health reasons.  Additionally, it could also be argued that improving overall diet quality and nutrient diversity should be a key goal, which could allow for a more holistic approach to (excuse the pun!) kill two birds with one stone by improving general health and folate status.  On an individual and personalised level, stratification by determining genetic single nucleotide polymorphisms for folate metabolism and methylation status, as well as homocysteine levels (10), could also provide for a more evidence-based approach and better justify individual needs for folic acid supplementation, increasing patient safeguarding and reducing the risks of adverse health outcomes.

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