Many of you are familiar with the concerns about folate deficiency …. doctors recommend taking enough folate to avoid neural tube defects, poor pregnancy outcomes, anemia, and cancer. Folic acid has been promoted by public health departments and is a regular part of most diets because of flour fortification. But now there are concerns about the effect of too much folic acid…. actually too much unmetabolized folic acid.
Folic acid refers to the synthesized, oxidized compound that was discovered in the 1940s. It is what you find in cheap dietary supplements and food fortification. In the liver, folic acid is converted by the enzyme, dihydrofolate reductase, to the usable form, tetrahydrofolate. When this mechanism is overwhelmed or too slow, folic acid can build up in the serum, as unmetabolized folic acid (UMFA).
Folate refers to the water-soluble B-vitamin that we find naturally in whole foods. Folates found naturally in food include 5-methyltetrahydrofolate (5-MTHF), 10-formyltetrahydrofolate, and 5-formyltetrahydrofolate.
Folic acid must be converted to its active forms to be used by the body. This is a multi-step biochemical process that occurs in the intestines and liver. In the presence of intestinal or liver dysfunction this conversion may not occur sufficiently enough to meet the body's needs. Furthermore, up to 60-percent of the U.S. population may have a genetic enzyme defect that makes it difficult for them to convert folic acid into active 5-MTHF. For these individuals and many others, 5-MTHF supplementation may be a more effective method of folate repletion.*
Some studies have shown that folic acid intake is associated with cancer progression and growth (colorectal, breast, prostate). High UMFA might be responsible for these negative effects. As little as 300 to 400 mcg of folic acid can elevate serum UMFA, while consumption of naturally occurring folates does not increase UMFA. The evidence suggests that it is the synthetic form of the vitamin (folic acid) that causes problems and that natural folates (in food) are not problematic.
While there is increasing concern about adverse health effects of excess folic acid intake and high UMFA, high 5-MTHF may not be desirable either. It could actually be that the cancer-promoting effect of folic acid is due to supraphysiologic levels of tetrahydrofolate (THF), the bioactive form of the vitamin. 5-MTHF could also increase THF. Therefore, either high 5-MTHF levels or high UMFA levels may be contraindicated in patients with cancer risk.
The bottom line is that when it comes to folic acid, too little or too much could lead to problems. It isn’t wise to give high doses of folic acid (or folate) to patients without evidence that they need it. Testing 5-MTHF can help us determine your personal need for folate.
Dangers of too little folate
- Neural tube defects
- Megaloblastic anemia
- Poor pregnancy outcomes
- Neuropsychiatric disorders
- Atherosclerosis (high homocysteine)
- Increased risk of cancers
Dangers of too much folic acid
- Cancer progression and growth (colorectal, breast, prostate)
- Pernicious anemia (masks the detection)
- Interferes with anti-folate medications
- Suppresses the immune system
- Contraindicated with cerebral folate deficiency
The old adage, “everything in moderation,” probably holds true, not just for folate but for all nutrients. We can’t say all vitamins are good and we can’t say all vitamins are bad; there are many factors that determine if a vitamin is good or bad, and at what quantities for a given individual. Having to sort through all of these complexities for each patient reminds us of the wisdom of individualized medicine! Dr Carnahan now offers Testing UMFA and 5-MTHF which can help determine if you what the right amount is for YOU!
References
- Kim YI. Folic acid fortification and supplementation–good for some but not so good for others. Nutr Rev. Nov 2007;65(11):504-511.
- Bailey RL, Mills JL, Yetley EA, et al. Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged > or =60 y in the United States. Am J Clin Nutr. Aug 2010;92(2):383-389.
- Kelly P, McPartlin J, Goggins M, Weir DG, Scott JM. Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. Am J Clin Nutr. Jun 1997;65(6):1790-1795.
- Powers HJ. Folic acid under scrutiny. Br J Nutr. Oct 2007;98(4):665-666.
- Solomons NW. Food fortification with folic acid: has the other shoe dropped? Nutr Rev. Nov 2007;65(11):512-515.http://www.metametrixinstitute.org
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7 Comments
“The evidence suggests that it is the synthetic form of the vitamin (folic acid) that causes problems and that natural folates (in food) are not problematic.”
Hi can you reference this evidence?
Yes, this is true! You can’t usually do harm from folic acid content of food 🙂
I find the article really confusing, with folate and folic acid basically being used interchangeably despite them being totally different animals. A clear distinction should be made that folic acid is synthetic and only found in cheaper supplements; whereas folate is natural found in nature, whole foods and in better supplements (as eg. L-5-MTHF, Metafolin). It was also my understanding (via. Ben Lynch) that folate is safe, whereas folic acid is the only form that causes UMFAs and poses a cancer risk/danger.
I use 2 pumps a day of Methylation Cream because I have a MTHFR gene mutation. In your opinion, is this methylation cream safe to use or not. Thanks
Hi Ozden,
I generally use oral supplements but for many creams are a good option.
Warmly
Dr Jill
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