by Lawrence Wilson, MD

© February 2014, The Center For Development


Folate or vitamin B9 is an essential vitamin. Among other functions, it is required to convert the toxic amino acid homocysteine into the vital amino acid, methionine. The body then uses methionine to make proteins and other important compounds. High levels of homocysteine, on the other hand, are associated with cardiovascular disease. A natural form of folate is found in cooked vegetables in large quantities, especially cooked dark green vegetables. In fact, the name folate comes from the word foliage, or green leaves of plants. About half of the world's population has a copying or transcription defect that causes reduced activity of the enzyme that converts folic acid to the active form of the vitamin. This is not exactly a genetic defect. It is a copying problem. The important difference is explained below. If those with the copying defect do not eat enough cooked greens about 1.5 cups of cooked greens three times weekly - they can develop fatigue, depression and other symptoms. The situation is being blown way out of proportion on some websites. This article seeks to simplify and clarify the problem and how to handle it.


Because this is a little confusing, I want to clearly state the different forms of vitamin B9 that are available, their sources, and how well they work:
1. Folate. This form of the vitamin is found in natural foods. If you get enough of it in your diet, which is not hard, you will overcome any copying defect you may have. One needs to eat at least 1.5 cups of cooked greens about three times weekly to obtain enough to overcome almost any copying or so-called genetic defect. On a nutritional balancing diet, you should be getting a lot more than this because one needs to eat a cup or more of dark greens every day.
Folate is also found in meats, eggs and other foods, but not as much. Some folate can also be made in the intestinal tract of human beings.
2. Folic acid. This is a synthetic form of folic acid that is widely used in B vitamin supplements. It must go through a few steps to be converted to the active form of the vitamin, which is called L-methylfolate. This is a problem for some people with an MTHFR defect.
3. Folinic acid. This is an intermediary step in the conversion of folic acid to the active form of the vitamin.
4. L-Methyl folate. This is a supplemental form of folate that is well-utilized by those with the copying defect.


Every enzyme and protein in our bodies is made by a multi-step process involving gene transcription. Basically, a section of DNA (deoxyribonucleic acid) that gives the coded information to make folate, for example, is split into two parts. Then a mirror image copy of the DNA is made using a substance called RNA or ribonucleic acid. This involves an enzyme called RNA transferase, which is a zinc-dependent enzyme. Another enzyme that is involved at times, is RNA polymerase, and this, too is a zinc-dependent enzyme. This means that if a person's body is low in zinc, which is very common today, then the copying process may not work correctly. Also, if some other chemical or metal such as copper or mercury blocks the action of zinc, even if you have enough zinc, the zinc-dependent enzymes will not work correctly.
The mirror image copy of the DNA is like a clay mold that is used to make a metal part, for instance. From the RNA mold or mirror image copy, another mirror image copy of that blueprint is made which becomes the desired protein or enzyme. Our bodies go through this copying procedure thousands of times every second in order to make all of our enzymes and proteins.
Copying problems. The problem is that in the copying process, mistakes occur on a regular basis. Some "proofreading" or quality control on the copying occurs, but mistakes sill occur. When these happen, the enzyme or protein does not work as well.
Now let us discuss the problem that can occur with folate. The final production of the active form of folic acid requires an enzyme called MTHFR or methylenetetrahydrofolate reductase. To be technical for a moment, this enzyme converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. About 50% of the world population seems to have various copying errors, also called transcription errors, that reduce the amount or potency of MTHFR. This is our problem.
Severe copying defects of the enzyme are very rare, with only about 50 cases worldwide. These people have 0-20% production of the MTHFR enzyme. Most of these people are very ill with developmental delays, very high homocysteine levels, neurological disorders and other serious symptoms.
However, researchers have identified about 50 other variants of the MTHFR enzyme, which are called polymorphisms. These will affect the amount and effectiveness of the MTFHR enzyme, and thus affect one's health if one does not ingest enough folic acid in cooked vegetables.


Note that these variants or polymorphisms are not exactly genetic defects, as most websites suggest. That is, the genes are not defective and one's DNA is not defective. However, the production of the enzyme from the gene is defective for some reason. This is called a copying error or transcription error. The word transcribe means to copy.
Among the most likely reasons for the copying errors and thus variants of the enzyme are zinc deficiency and the presence of toxic metal poisoning such as mercury and copper toxicity. Copper, for example, directly antagonizes or blocks the action of zinc in some cases. This is critical to understand because these copying problems can be reversed, at least in some cases.


Another confusing feature of the MTHFR problem is that everyone has two MTHFR genes. At this time, doctors believe that about 10% of the population have a variant in the expression of both genes. When the problem affects both genes, it is called a homozygous problem, and this is more severe.
Another 40% have a variant in the expression of just one of the genes. This is called a heterozygous defect, which creates a milder block to the conversion of folate to the active form of the vitamin.


These can include fatigue, depression, cardiovascular disease, and other more vague complaints such as aches and pains and other symptoms.


1. This is not exactly a genetic defect. It is better described as a mild genetic variant or weak expression of the gene needed to make MTHFR. It is a problem with RNA and protein synthesis, which is highly dependent upon proper nutrition and can be ruined by toxic metals.
2. The likely cause of these defects is toxic metal poisoning, especially with mercury and copper. This is so common today it is almost universal.
3. The problem is much more common in slow oxidizers. Most slow oxidizers are low in zinc, and often have copper imbalances and mercury toxicity, no matter what any type of test reveals. All tests that I know of – blood, urine, feces, hair – are not reliable enough methods to test for copper imbalance. Slow oxidizers also seem to need more B-complex vitamins, including folate.
4. One need not buy a special supplement to overcome possible MTHFR problems. This is not clear from many websites on this subject. Most people can just eat more folate in their diet.
5. The problem can be overcome in all cases by eating about 1.5 cups of well-cooked dark greens every other day. These foods include spinach, kale, Swiss chard, mustard greens and perhaps other greens. Eating the food, rather than taking a special supplement, has several advantages:
     A. One cannot easily ingest too much of the cooked greens, but one can take too much of the supplements.
     B. The foods provide dozens of other critical nutrients we all need today, while the supplements do not.
6. One can also overcome the copying error involving MFTHR by taking a supplement of folinic acid or methyl folate. Standard synthetic folic acid supplements may work, but not as well. The dosage needed is higher.
7. Testing for MTHFR defect is possible, but rather costly at about $200.00. A much less expensive option is to eat more cooked greens or take a little folinic acid as a supplement and see if one feels better.
These supplements are available at health food stores, or there are prescription drug versions available such as Deplin, for example.


In some people, folinic acid is quite a stimulant. This is very important to know. If one has a four lows pattern on a hair mineral analysis, do not take folinic acid. It can make the four lows pattern worse.
I am not sure at this time if this supplement will make a fast oxidizer worse, but it is possible.
In contrast, eating plenty of cooked dark green vegetables is perfectly safe, as far as I know.


Both TMG (trimethyl glycine) and folate will increase methyl groups in the body. However, folate has other effects because folate is involved in energy production, amino acid production and other activities.
Taking extra niacin will oppose the action of folinic acid by causing a reduction in methyl groups. This is why taking a balanced B-complex is often better than taking isolated B vitamins. However, niacin is extremely yin and I do not recommend high-dose niacin, ever. Also, most B vitamins, including folate and niacin, will generally worsen the health of those in fast oxidation and those in four lows pattern.
CBS. This copying error causes high levels of homocysteine, and in severe and rare cases causes homocysteinuria. This is associated with elevated cholesterol, and many other health conditions. CBS stands for cystathionine beta-synthase.
COMT. This RNA copying error affects catechol-O-methyltransferase. This is one of several enzymes that degrades catecholamines such as dopamine, epinephrine, and norepinephrine. As a result, a problem with this error can cause a varying degree of irritability, agitation, anxiety and other symptoms associated with a high level of catecholamines.
As with the MTHFR copying error above, in most cases, CBS and COMT problems are not exactly genetic defects. They are best described as a mild genetic variants or weak expression of certain genes. They are a problems with RNA and protein synthesis, which is highly dependent upon proper nutrition and can be ruined by toxic metals.
We are researching whether a nutritional balancing program will reduce the negative effects of these RNA copying errors. I suspect that it will, but more research is needed.

All information in this article is for educational purposes only. It is not for the diagnosis, treatment, prescription or cure of any disease or health condition.