Science has well established that adequate folate intake from the consumption of folate-rich foods is essential for health. Folate aids the complete development of red blood cells, reduces levels of homocysteine in the blood, and supports proper nervous system development and function.
Tetrahydrofolate (THF) is the useable form of folate the cells need for their functions. Natural folates, found in foods, are utilized in the small intestine. Folic acid must undergo initial reduction and methylation in the liver, and then converted to the THF form; this requires a specific enzyme absent or impaired in up to 60% of the population. The low activity of this enzyme in the human liver, combined with a high intake of folic acid, may result in elevated levels of un-metabolized folic acid entering the systemic circulation; Leading to a whole host of health problems plaguing modern society.
Human exposure to folic acid was non-existent until its chemical synthesis in 1943. Upon the addition of synthetic folic acid to food by government mandate in 1989, the US has seen a rise in autism, infertility, autoimmune disease and cancers. Research has reported the presence of un-metabolized folic acid in the blood following the consumption of folic acid supplements or fortified foods. The presence of un-metabolized folic acid in the blood is associated with decreased natural killer cytotoxicity. Natural killer cells aid in tumor cell destruction, which implies that excess folic acid, may promote existing premalignant and malignant lesions.
Other issues with a high intake of folic acid, include, un-metabolized folic acid could mask a vitamin B12 deficiency which can harm central nervous system function. Many studies have shown association between elevated folic acid, low B12 and cognitive decline.
Excellent sources of dietary folate include green vegetables, beets, and lentils. The highest levels of folate are found in duck and calf liver…chooses organic of course if you indulge.
The Importance of avoiding Folic Acid
Modern science has shown us recently that supplementation or over supplementation does not mitigate or negate the potential damage we know synthetic folic acid can cause. We now know that supplementing with the proper forms of Methylated B vitamins can help restore health. It has been shown that most individuals with “MTHFR family” family mutations will likely tolerate small amounts (estimated as 100-200 mcg weekly) in enriched foods. However high amounts of folic acid in supplements AND enriched and fortified foods can be detrimental to health. The following are the exact pathways affected by high dose folic acid.
Folic Acid Inhibits DHFR (dihydrofolate reductase) Gene-
DHFR gene is implicated in cervical adenocarcinoma
Folic acid can build up in the cell leading to un-metabolized folic acid and immune dysfunction.
Un-metabolized folic acid is problematic for women undergoing in vitro fertilization.
Evidence shows increased possibility of conceiving multiple embryos; leading to a higher rate of risk and possible loss
In Patients with Coronary artery disease and Stent placement un-metabolized folic acid can cause inflammation and stent occlusion
Patients being treated for malaria, arthritis, psoriasis, and cancers, un-metabolized folic acid may reduce the response to related anti-folate drugs
Ireland reported that un-metabolized folic acid is detected in cord blood from infants at birth including full-term and premature infants.
A report shows that aged female mice fed with diet containing high folic acid have significantly lower number of natural killer (NK) cells in their spleens with decreased cytotoxicity immune function.
MTHFR deficiency may amplify cancer risk.
Folic Acid Blocks Natural Folates
Causing a MTHFR deficiency which results in liver cell destruction and those cells lose their ability to accommodate lipid disturbance resulting in changes in phospholipid / lipid metabolism and altered membrane integrity.
Why is The Methylation Important?
The methylation cycle is important because it takes the nutrients from our food (and supplements) and utilizes them to make the energy our bodies need to work optimally. It also supports the manufacturing of healthy cells and neurotransmitters. Methylation is a key component in the removal of toxins and foreign invaders like bacteria and viruses. When methylation is optimal, the body is full of energy, When it is poor or impaired, your body will feel fatigued, depressed, irritable, susceptible to infections, and achy.
Proper methylation is important for mitochondrial function and energy production. Low mitochondrial function and low methylation can lead to low energy, low thyroid function, decreased memory, and Lyme disease to name a few.
Poor methylation can cause
Low neurotransmitter levels, which can lead to anxiety and depression,
Poor immune function, which lead to high incidence of allergies, asthma, and eczema as well as a higher probability of bacterial infections
Poor liver detoxification, which impairs toxin removal
Problematic fertility, including risk of miscarriage, and neural tube defects
There is a delicate balance to methylation and all pieces must be working properly for the optimal result. The proper outcome would be production of glutathione, a major antioxidant and protector of cells.
The methylation pathway starts with MTHFR. Research indicates that approximately 60% of the US population has at least one MTHFR mutation. This means that the bulk of the population cannot process and convert Folic acid to MTHF to some degree. These MTHFR mutations can increase your risk for certain medical conditions. One of the best and easiest treatments is to avoid folic acid by avoiding processed or enriched foods.
Another beneficial treatment is to minimize stress in your life and in your cells. Because of the delicate balance between methyl donors and adrenal hormones it is likely under stress you will feel worse.
Things to Avoid
- Alcohol (all wine, beer and liquor)
- Candida/ Yeast die off, from having and treating yeast
- Antibiotics (especially in the “floxin” family)
- Nitrous oxide gas (used at the dentist)
- Foods that cause sensitivities or allergies
- Toxins in the environment (pesticides, radiation, EMFs, etc)
- Heavy metals (like mercury and aluminum)
- Elevated cortisol (stress hormone)
More than MTHFR
Of course there are hundreds of genes and mutations that affect methylation, knowing which mutations you have will help your practitioner guide you toward better health.
Other SNPs (single nucleotide polymorphisms—genes that tell us of a specific action) such as MTHFR’s “cousins” MTR, MTRR, BHMT help shortcut through the methylation cycle and uses choline instead of folate and B12 to add methyl groups into the energy cycle. This May indicate that tolerance to Adenosyl or Hydroxy B12 may be better than Methyl B12. 5-MTHF (methylfolate) and MB12 (methylcobalamin) are utilized to convert homocysteine into methionine. Then the MTRR uses methionine to make SAMe or S-Adenosyl Methionine. SAMe protects DNA and cells, and manufactures neurotransmitters and other substrates responsible for over 40 important metabolic reactions. The final enzyme in this process is called CBS; CBS is the “garbage disposal” for the removal of homocysteine and ammonia and the manufacture of glutathione. Glutathione is the “KING” anti-oxidant, so any SNPs effecting CBS can make for increased oxidative stress and higher ammonia levels, leading to fatigue.
As a review….Important enzymes and their function
MTHFR – Methylenetetrahydrofolate reductase. Converts folic acid to methylfolate
MTR – Methionine Synthase. uses methylfolate (folate) and methylcobalamin (B12) to turn homocysteine into methionine
MTRR – Methionine Synthase Reductase creates SAMe and makes energy in the mitochondria
BHMT – Betaine/homocysteine methyltransferase. “shortcut” in the liver and kidneys that can also make methionine from choline
CBS – Cystathionine beta synthase. “garbage disposal” Removes homocysteine from the MTR/MTRR cycle and converts it into glutathione
Where to start? At the beginning of course…
Folate and Pre- Pregnancy and Pregnancy
Should you feel compelled to supplement or are of childbearing age and wish to have children in the future, always look for “5-methyltetrahydrofolate” or “L5-MTHF” as your folate source. Avoid products that say “folic acid”, or use the word “enriched” or “fortified” on the label. Make sure to check your multivitamin, because most will contain folic acid and not folate. It is important to also make sure there is adequate B12 for proper absorption too.
Women of child bearing age planning to have children should consume between 800 and 1200 mcg of folate per day for several months before the start of pregnancy. Please note oral contraceptives deplete folate stores so be sure to supplement “L5-MTHF” for several months after stopping hormonal birth control before becoming pregnant. During a pregnancy, you should be supplementing with 600-1200 mcg of folate per day, depending on your dietary intake.
5-MTHF has its important advantages compared to synthetic folic acid in the rest of the population too. It is well absorbed even when there are pH changes in the gut. It is bioavailable and is not affected by metabolic defects and the use ofL 5-MTHF instead of folic acid in treating MTHFR reduces potential of masking symptoms of vitamin B12 deficiency. It reduces interactions with other medications, prevents the formation of un-metabolized folic acid in blood circulation, and overcomes metabolic defects caused by MTHFR polymorphism.
We now know identifying and treating MTHFR and other mutations can directly modify cancer risk, or indirectly modify cancer risk through interaction with folate and other nutritious components in folate metabolism.
We now know identifying and treating MTHFR and other mutations can improve and enhance fertility.
We now know L5-MTHF Is More Effective than Folic Acid (A report suggests that 5-MTHF increases plasma folate more effectively than folic acid irrespective of mutations of MTHFR.)
We now know avoiding fortified flour or cereal, processed drinks, enriched foods and supplements containing folic acid, the risk of consuming too much is greatly reduced or eliminated.
We now know that Folate plays a critical role in the prevention of chromosome breakage and damage of DNA.
So in conclusion watch out for anything “enriched’ or “fortified” choose “methyl-folate” over folic acid and “eat your greens!”