Why Do We Need Folate?

What is folate?

Folate is an essential B vitamin sometimes known as vitamin B9, folacin or pteroylmonoglutamic acid. It’s essential to the body so DNA and RNA can be created, and to metabolise amino acids required for cell division^[1]. Cells divide for several reasons including to replace dead and damaged cells and for growth.

What foods are high in folate?

Folate occurs naturally in a wide variety of foods of both plant and animal origin; great food sources include the following:

• Spinach
• Brussel sprouts
• Cabbage
• Broccoli
• Beans and legumes
• Yeast and beef extracts
• Oranges and fresh orange juice
• Wheat bran and other whole grains
• Poultry
• Pork
• Shellfish
• Liver
• Huel products

Some foods are also fortified with additional folic acid. Folic acid is used to treat folate-deficiency anaemia, additionally it’s advised as a supplement for women who are trying for a baby^[2-4].

The main role of folate is to function as a coenzyme where it supports the metabolism of energy, DNA and the synthesis of five amino acids including the essential amino acid methionine^[5]. As folate is essential in DNA metabolism, it is involved with gene expression and cell differentiation where it has a role in preventing the development of cancer^[6]. Folate’s function is closely linked to that of vitamin B12^[5].

Recommended intake levels of folate

The EU Nutrient Reference Value for folate is 200μg per day^[7]. This level provides enough to prevent folate deficiency and for adequate levels of folate in red blood cells. Typical intakes in the UK are 240μg, so by consuming a varied diet the NRV is easily met^[8].

Sometimes when looking at folate intake, the preferred unit of measurement is Dietary Folate Equivalent (DFE)^[9]. For example, the US Daily Values (DVs) are based on this^[10]. DFE reflects the higher bioavailability of the folic acid supplement form compared to that of food folates^[11]. The following indicates how DFEs are calculated:

• 1μg of food folate = 1μg DFE
• 1μg of folic acid in fortified food or as a supplement consumed with food = 1.7μg DFE
• 1μg of folic acid supplement consumed on an empty stomach = 2μg of DFE

Can you get too much folate?

Although no adverse effects have been associated with the consumption of large amounts of folate from food, there have been concerns regarding very high intakes of supplementary folic acid. Both the EU and the US have provided a tolerable upper limit recommendation of 1,000μg per day, a level based on intakes from supplementation and fortification^[12]. Naturally occurring folate from foods has no tolerable upper limit^[12].

Levels of folic acid significantly higher than the tolerable upper limit are at risk of masking megaloblastic anaemia caused by an underlying vitamin B12 deficiency. Moreover, it is advised for people aged over 50 years or those with a history of bowel cancer not to take folic acid supplements containing more than 200μg per day^{[2, 13, 14]}.

Deficiency of folate

Severe deficiency of either folate or vitamin B12 can lead to megaloblastic anaemia a condition that features a low number of large red blood cells called megaloblasts^[15]. Symptoms include tiredness, heart palpitations, shortness of breath, sore tongue, change in colour of skin or hair, irritability and possibly changes in behaviour, especially so in children^[16]. There is a complex interaction between folate and vitamin B12, and also with both vitamin B6 and iron to some degree, so that deficiency of one may mask a deficiency of another^[5]. Megaloblastic anaemia caused by a dietary deficiency or impaired metabolism of vitamin B12 is known as pernicious anaemia, whereas megaloblastic anaemia caused as a result of folate intake or metabolism is known as folate-deficiency anaemia^[15].

Folate deficiency is most commonly a result of inadequate dietary intake^[5]. Deficiency can also be due to an increased requirement for folate as a result of the body excreting more than usual or from alcoholism or smoking^{[5, 17-21]}. There are a number of medications that interfere with folate metabolism; these include aspirin, ibuprofen, some anti-epileptic drugs and some oral contraceptives when taken in large doses^{[22, 23]}. There is also research indicating that the effects of excessive UV light, like tanning beds, can be associated with deficiency^[24].

Additionally, a defect in the enzyme homocysteine methyltransferase or a deficiency of vitamin B12 may lead to a ‘methyl-trap’ of tetrahydrofolate (THF). THF is a derivative of folate that occurs in metabolism. In this condition, THF is converted to methyl-THF, and this cannot be metabolised and leads to subsequent folate deficiency anaemia^[25].

Absorption of folate takes place in the small intestine, and when in intestinal cells it binds to specific receptor proteins. Inflammatory intestinal diseases, such as Crohn’s disease, coeliac disease, colitis or chronic enteritis, may be associated with a reduced activity of these proteins required for folate absorption so may contribute to folate deficiency^[5].

Folic acid supplementation

The most common supplementary form is folic acid which, is synthetically derived and used to treat folate-deficiency anaemia^[3]. As discussed above, caution should be taken to avoid excessive amounts of folic acid supplements.

Studies have shown that women who are trying to conceive and supplement with additional folic acid have a massive reduction in the risk of babies being born with neural tube defects (NTDs) like spina bifida^[26]. The advice is for women to take 400μg of folic acid supplements whilst they are trying for a baby until week 12 of pregnancy^[4]. Low blood levels of folate during the early stages of pregnancy have been cited to be the cause of more than 60% of the incidences of NTDs in babies^[26-28].

Another form of folate that’s available as a supplement and an alternative to folic acid is L-methylfolate, also known as L-5-methyltetrahydrofolate, which is often naturally derived. This form has been shown to have comparable activity, bioavailability and absorption to folic acid and has the advantage of both not interacting with certain drugs and offering some protection against problems regarding vitamin B12 deficiency^[29-33].

MTHFR gene mutation: folate vs. folic acid

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme produced from the MTHFR gene, which is involved in the metabolism of the amino acid homocysteine via a number of processes that also involves THF, folate and vitamin B12^[34]. When homocysteine isn’t metabolised correctly, it can build up in the blood vessels and cause inflammation which can be involved in the disease process of cardiovascular disease (CVD) like heart disease and stroke^[35]. A high level of homocysteine, known as hyperhomocysteinemia, is a risk factor for CVD and has also been linked to impaired kidney function^{[36, 37]}. This may happen due to a deficiency in folate or vitamin B12, either as a result of inadequate dietary intake of either vitamin, or from an impaired metabolism from thyroid hormone insufficiency, kidney disease, certain medications or from a genetic origin^[38]. High levels of homocysteine may also be associated with increased cancer risk^[39-41] and can mask vitamin B12 status^{[42, 43]}.

There are two main variants of a mutation that can occur to the MTHFR gene and these, in more extreme cases, can lead to a build-up of homocysteine in the blood or high levels in the urine known as homocystinuria. The two mutations are the C677T polymorphism and the rarer A1298C, and there are sub-variants of each^[44]. People can have a full or partial mutation, and as many as 30 to 40% of North Americans and Europeans have the presence of C677T polymorphism^[45]. Not everyone with the full mutation has elevated homocysteine levels, although for women with the MTHFR gene mutation there is the increased risk of NTDs in their children^[46].

People with an MTHFR gene mutation may benefit from a higher than normal intake of dietary folate or from supplementing with L-methylfolate. This is because food-derived folate and L-methylfolate are metabolised in a way so they will not accumulate in the body^[47]. Therefore, in people with a low vitamin B12 status, that’s not a result of a poor dietary intake, the advice is to avoid folic acid fortified foods and supplements, in preference for L-methylfolate supplements^{[48, 49]}.

Folate in Huel

In Huel Powder v3.0, over 20% of the folate is provided by the main ingredients, mainly the oats and flaxseed. In Huel Black Edition, around 12% of the folate is from the main ingredients, mainly the flaxseed, In Huel Ready-to-drink, around 20% of the folate is from the main ingredients, again, mainly the oats, flaxseed and also brown rice flour. The Huel Hot & Savoury ingredients provide around 25% of the total folate. The forms of additional folate used in all Huel products are types of L-methylfolate based on the advantages that this form has over folic acid.

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