Folate

When most people hear “folic acid” they think about the need to supplement with it before and during pregnancy. This is because of the well-publicized link between maternal folate status and neural tube defects in newborns. Since more than 50% of pregnancies are unplanned, and the neural tube forms in the first 4 weeks of pregnancy, supplementing with folate after confirming pregnancy could be a bit too late. That’s why in Canada the folic acid fortification of foods was initiated in 1998 and since then the incidence of neural tube defects has decreased by 46%.

Along with vitamins B12 and B6, folate is essential for the synthesis, repair and methylation of DNA.  It is also important in maintaining healthy levels of homocysteine (Hcy).

Moderately elevated levels of Hcy have been found to increase the risk of brain shrinkage, cognitive impairment, and dementia in the elderly.  High levels of Hcy are also correlated with cardiovascular disease and specifically with heart attacks and strokes, and they may contribute to the development of inflammation, and disorders in cholesterol metabolism.  Although genetics can have a significant effect on Hcy levels, it seems that in the majority of cases high levels are due to low vitamin levels or intake.

Folate can come from dietary sources and supplementation.  Some of the major sources of dietary folate are dark green leafy vegetables, fruits, grains, legumes, and dairy products.  The main dietary sources of folate in developed countries are foods that are fortified with synthetic folic acid. Synthetic folic acid has been associated with possible adverse effects, such as masking symptoms of vitamin B12 deficiency and possibly increasing the risk of some cancers.  Consuming synthetic folic acid from supplements or fortified foods, however, is more effective at increasing blood and tissue folate levels than consuming high-folate foods. That’s not to say that consuming dietary folate is not beneficial, just that it may not be adequate in someone who might be folate deficient.

Some research has suggested that high levels of folate may be correlated with various cancers.  This is controversial and making sense of this research is complicated primarily by two things:

  1. Folate levels can be measured either in the serum or in the red blood cell (RBC) and then that there are several different ways that these levels are measured. RBCs retain folate from the time that they are produced through their 120-day life span, so RBC folate levels indicate long-term folate status. The serum levels can change more quickly with folate intake.
  2. The high folate cut-off levels of most of the studies might not be that high and might just be clinically normal levels

What the studies do seem to indicate is that folic acid intake is correlated to lower levels of birth defects, including cardiovascular defects, cleft palate, limb defects, urinary tract malformations, and congenital hydrocephalus. Levels of folate intake that are within the recommended daily intake levels have also been associated with lower levels of colorectal, prostate, breast, and lung cancer in the general population.

There is a portion of the population that has a form of the gene that codes for the enzyme MTHFR C677T that can impair the metabolism of folate and lead to levels of serum folate that are 10–25% lower than in others without that gene variant. This could impact laboratory measures of RBC folate in this population. It’s also interesting to note that there is evidence that in the population with that gene variant, supplementation with 5-MTHF but not with folic acid can lead to increases in 5-MTHF in the cerebrospinal fluid.  This is relevant because some of these people may develop neurological symptoms that can be corrected with 5-MTHF.

Some of the folate in foods is lost by the heat from cooking or by dissolving into the water used to boil them. There is a trade-off, however, as the cooking may also increase the bioavailability, or how much is available for the body to use, of the folate, depending on what form it is in.  There are two major forms that are used in food fortification and supplementation: folic acid and 5-MTHF. The form traditionally added to food is the folic acid form and 5-MTHF is the form that easily utilized within the body. Studies using radio-labelled forms of 5-MTHF and folic acid have shown that levels of folate in the blood are about 50% lower with folic acid than with 5-MTHF for the first couple of hours after oral administration. This could be due to the liver’s affinity for folic acid, as well as several other factors which can affect the bioavailability of folate, including the presence of absorption inhibitors, such as EGCG found in green tea, the pH of the digestive tract, and the genetic variations mentioned earlier. As mentioned earlier, synthetic folic acid can mask the symptoms of a B12 deficiency but the 5-MTHF form of the vitamin is not likely to do so.

As a general guideline, you should make sure that you get adequate levels of folate, preferably in the 5-MTHF form, and don’t take too much, because the possible adverse effects of having too much are unknown. If you’re interested you can also get genetic testing to determine the influence of your particular genetics on your folate status.

 

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