For individuals with health problems that are difficult to diagnose, one of the most common causes is folate deficiency.
In 1941, the food form of folate was first discovered in green leafy vegetables (folate from the Latin word for leaf, folium). Since then, hundreds of studies have shown the benefits of naturally occurring folate, while none show any harm. Folate, a critical nutrient, is primarily found in raw, fresh spinach, beef, and other green vegetables such as brussels sprouts.
Some researchers think that low dietary folate levels due to reduced vegetable and fruit intake adversely affected our genes giving rise to a genetic variant, which then impairs our ability to metabolize folic acid. This was one of the arguments that led to fortification of flour with synthetic folic acid.
But recent studies have been demonstrating the potential ill effects of long-term synthetic folic acid intake. Part of the problem is that too many people are getting too much because so many processed foods are fortified with this chemical. In fact, current levels of synthetic folic acid are in excess by as much as twice the target set for fortification.
Genetic Polymorphism
This genetic problem is called the C677TT genotype, “T” variant, or polymorphism, and its occurrence is relatively new at such high levels in the population. It’s particularly a common problem seen in difficult patients who appear unresponsive to many therapies.
What began as a mutation seen in very few individuals a generation ago is now common. (Each parent supplies genes to their child, and the polymorphism is passed on when one or both parents have the genetic variant in their chromosomes).
Today, many millions of the world’s population has the polymorphism, with geographic and ethnic variation. For example, U.S. Hispanics and Southern Europeans have frequencies above 40 percent, with other European populations (including British and Irish) and U.S. whites between 30 and 36 percent. Lower incidences are seen in U.S. blacks, and Asian populations (14 and 11 percent, respectively).
How much does this polymorphism affect folate metabolism? Significantly. If two parents have the genetic variant, and pass both to the offspring, they are “homozygous” (meaning they received the variant from both parents), and their ability to convert folic acid to the natural folate (5MTHF) is reduced by 70 percent. Children who receive the variant from one parent have a 35 percent reduction.
- Those with the polymorphism may particularly be vulnerable to brain dysfunction. This is due to the inability of folic acid to get into the brain (it can’t cross the blood-brain barrier), while natural folates can. This places these individuals at increased risk for depression, mood and behavioral problems, schizophrenia, bipolar disorder, and other brain problems.
- Folates are also vital in the regulation of red blood cells, and the polymorphism can lead to folate-deficient or megaloblastic anemia (where the cells are abnormally large). Since red blood cells carry oxygen, low folate can impair physical activity and be associated with fatigue. Symptoms may be more noticeable at higher altitudes, where oxygen uptake is already lower. In athletes it can significantly reduce performance.
- The polymorphism appears to also increase the risks of intestinal dysfunction, including Crohn’s disease and ulcerative colitis. This is because natural folates play such crucial roles in various areas of the intestinal tract.
About half the general population carries at least one type of polymorphism.
Blood Tests
Along with other assessments, blood tests may be very useful to help determine folate-related problems. Here are some tests your health practitioner may perform:
- Homocysteine. This is one of the most common and accurate measures of folate status.
- Genetic test for C677T. Three potential results are negative (normal), heterozygous (one variant), and homozygous (two variants).
- Red blood cell count (including indices). This measures the quantity and quality of the cells and helps rule out anemia.
- Unmetabolized folic acid (not performed by all laboratories).
- Fasting serum folate and erythrocyte folate. (Most laboratories don’t differentiate between synthetic folic acid and 5MTHF.)
Many people have health problems associated with folate insufficiency or deficiency. The first factor in addressing these conditions is to assure sufficient amounts of natural folate from food are being consumed. In many cases, it’s also important to know if the genetic polymorphism exists, and whether the body is using adequate amounts of folate as indicated by homocysteine levels. This information can easily be obtained from blood tests. The second consideration is supplementing the diet as necessary.
Dietary Supplement Options
For people with higher folate needs, those who can’t/won’t eat sufficient amounts of healthy food, two types of dietary supplements are helpful.
The body’s most useful folate, 5MTHF, is available as a dietary supplement. This may be the most useful supplement for those with the polymorphism. Many nutrition-oriented health professionals use this nutrient, but it’s more difficult to find in stores. 5MTHF also would be the best folate form to use in fortification of processed foods, but that is unlikely due to higher costs.
Another form of folate, also available as a dietary supplement, is folinic acid. It too converts to 5MTHF in the body but some folinic acid is used in different biochemical pathways, especially in the synthesis of DNA and regulation of genetic materials. Clinicians sometimes use folinic acid as a dietary supplement along with 5MTHF, for brain-related problems and other conditions. (Patients taking the drug metholtrexate, used to treat rheumatoid arthritis and various cancers, significantly reduces folate in the body, and are often given high doses of folinic acid without adverse affects. Many NSAIDs also have antifolate activities, reducing the body’s level of folate.)
Whether you are folate deficient or not, eating folate-rich foods is essential to maintaining healthy folate levels in the body.
