FASCINATION WITH FOLATE

By Alice R. Laule, M.D.

Folic acid is one of the B vitamins. Although we don’t usually hear it associated with its number, it is “B-9.” Most commonly it is found in foliage, hence the name folate. Many people have heard about its associated with neural tube defects, specifically spina bifida. For almost two decades now it has been a stern admonition to expectant mothers that they should take folic acid as a supplement. What is not always made clear is that the folic acid levels must be adequate by day 26 of pregnancy, certainly during the entire first trimester, to reduce the incidence of spina bifida. Since too few pregnancies in the US are that carefully planned, women of child bearing age should all be taking folic acid.

      Oddly, folic acid is a vitamin that is better absorbed as a supplement than it is from its food source. Probably because of the need for folate for the health of any rapidly dividing tissue, such as the lining cells of the gut, it is actually more poorly absorbed the more deficient a person is. There is no toxicity, and it can be given in large amounts. The RDA is 400 mcg. (0.4 mg) daily. Because it works hand in glove with vitamin B-12, and in fact they share many of their duties in the body, taking folic acid can mask a B-12 deficiency. Therefore, the FDA does not allow folic acid to be manufactured in dosages larger than 800 mcg per tablet. It is dangerous to mask a B-12 deficiency, since serious, permanent neurological defects can occur.  However, nutritionally oriented physicians sometimes want to give patients dosages as high as 10,000 mcg. (10 mg) daily to treat certain folic acid deficient conditions, such as abnormal PAP smears and elevated homocysteine.

It has been clinically apparent for years that such high doses are needed. Other than poor absorption in the gut, why might such elevated doses be necessary?

     The human genome project has helped give us some answers. Bear with me — you know I’m a science geek. I find this fascinating, and I’ll try to make the scientific part palatable.

      For folic acid to be fully active in the body, it has to be changed by an enzyme called MTHFR. The name is actually “methylene tetrahydrofolate reductase.” You can see why it gets shortened to MTHFR. The end product, the fully activated folate, is called tetramethylhydrofolate. We’ll shorten that to TMG folate for simplicity’s sake.

     One more term  — the methyl group (CH3). A methyl group is a very important biochemical structure, one we could not live without. It consists of one carbon and three hydrogen atoms. TMH folate has four methyl groups hanging off it. Folic acid that we take as a supplement has no methyl groups, Folinic acid, the food form, has two methyl groups. However, it needs all four CH3’s to be fully active. That enzyme we talked about, the MTHFR, is the tool out body uses to hang all those methyl groups in place around the folic acid molecule. Only then, as TMH folate, is it able to do all its jobs in the body.

     What the human genome project discovered is that 7% of people don’t make an MTHFR that works very well, because there is a tiny glitch in the gene that codes for it, and 3% of people make an MTHFR that doesn’t work at all. Without MTHFR, we can take folic acid all day long and in huge quantity, but the stuff will never get methylated, so it remains inactive. It’s analogous to having a lovely Christmas tree, and a whole bunch of ornaments, but no ornaments hangers, or only bent ones. With no way to hang the ornaments, you can’t have a decorated tree.  With no way to hang methyl groups off the folic acid, you can’t have it performing any of its functions in the body.

And what are the functions of folic acid? They are many, and I do not want to list every one of them. Here are a few key ones.  Folic acid helps as a methyl donor for proper neurotransmitter function, so it effects behavior.  A fully methylated folic acid protects the DNA from free radical damage (it specifically protects the guanosine part of the base pairs). It is essential for normal cell division, so between the DNA protection and the cell division function, you can see it might be important in cancer as well as any problem where cell division has gone wrong.

It helps form blood cells properly. Along with B-12, it makes methionine (helpful for detox) out of homocysteine, thus lowering homocysteine levels, which in turn lowers heart disease risk.

            Symptoms of deficiency of folic acid are cramps, irritability, fatigue, depression; signs are weight loss, hair loss, anemia, elevated homocysteine, reduced vision, changes in the lining of the mouth or the surface of the tongue, and others. Deficiency is found in children who won’t eat anything green, teens with a fast food diet, alcoholics and the elderly.

     I actually see this in young people who come to me with a normal eyes, but inability to see well. A multi-vitamin supplement, or a B-vitamin complex will restore their vision in 6-8 weeks. I used to order a complete neurological workup, but now find I just need to supplement their nutrition. It surely saves the parents a big chunk of money. A vitamin pill costs a lot less than an MRI.

     I also see this in adults with depression and fatigue. The serum folate will be normal, but that does not indicate if the folic acid is activated and functioning. A biochemical in the urine known as FIGlu indicates folic acid function. If it does not normalize with ordinary folic acid supplements, my next step is to give TMH folate as a supplement. Before TMH folate was available, I would load people up with lots and lots of folic acid, in the 10 mg. range, and hope to get some response. Now that is no longer necessary. I seldom request a genomic test for MTHFR mutation. That testing is readily available, but expensive.

     I previously mentioned the use of folic acid in the presence of an abnormal PAP smear.  Human papilloma virus (HPV) causes abnormal PAP smears and cervical cancer by causing difficulty with cell division. Since folic acid normalizes cell division, it may be that HPV causes more abnormal cells in the uterine cervix predominantly in folic acid or MTHFR deficient women. For decades nutritionally oriented physicians have given women with this problem 10 mg. of folic acid daily for 3 months. Before the availability of TMH folate as a supplement, I used to do the same thing. To date,  I have never had a PAP smear

to normalize with this routine. Now I am using TMH folate 800-1600 mcg daily, and getting the same results. I believe there is a relationship between folate, MTHFR, and cervical cancer. Perhaps one can stay benign with B-9. (Sorry, couldn’t help myself.) Of course,  high grade abnormal PAP smears that indicate cancer is already present should be treated more aggressively.

     Folate is a powerful nutrient, so eat your greens. Call us if you have questions about folate. The only caveat here is — if you are on Dilantin or Methotrexate, do ask your physician before taking high dose folic acid supplements. 

      Here’s to your health!

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