MTHFR is not a term we always hear and yet, over 40% of the population is affected with some form of its gene mutation. MTHFR stands for methylenetetrahydrofolate reductase, a type of metabolic pathway gene which plays an integral role in the production of the MTHFR enzyme. This enzyme is crucial in processing amino acids, the conversion of homocysteine to methionine, and the metabolism of folate into its active form. Because of this, individuals with MTHFR may have 70% lesser methyl-folate in their bodies compared to those without the mutation.
At the moment, there are a total of 34 mutations in the MTHFR gene. Variations in the MTHFR gene can lead to a number of genetic disorders like spina bifida, homocystinuria, and anencephaly. It is also associated with cardiovascular disease, neurological disorders, cancer, leukemia, and diabetes, among others. Patients with common MTHFR variants also have elevated homocysteine levels which have been studied as a risk factor for numerous diseases.
MTHFR and Digestive Diseases
Although there is no direct relationship between MTHFR and digestive diseases, abnormal methyl levels may affect tissue repair, stress response, inflammation, and cellular integrity. These may all affect the gut and increase the likelihood of developing IBS, GERD, SIBO, diarrhea, bloating, and other symptoms. MTHFR is also one of the many possible culprits for the development or progression of gallbladder, pancreatic, and liver diseases.
Methylation Cycle and its Effects
Before we go on about the possible ways MTHFR may affect our gallbladder health, it is important for us to have a basic understanding of methylation, a basic process affected by the gene mutation.
Methylation is a complex process that involves the binding of a methyl group (made up of 3 hydrogen and 1 carbon atom) to another molecule. One of the main enzymes involved in the methylation cycle is the MTHFR enzyme which converts folic acid to methylfolate. The problem for individuals with the MTHFR gene mutation is that their ability to turn folic acid into folate is decreased significantly. This means that the mutation impairs the body’s ability to produce sufficient methyl groups to support the following:
- Immune response
- Inflammatory response
- Neurotransmitter formation
- DNA production
- Cellular energy
- Histamine metabolism
- Estrogen metabolism
- Fat metabolism
Molecules Affected by Methylation
Aside from negatively affecting those biological processes, a number of important molecules cannot be effectively produced by the body with insufficient methyl donors.
- Coenzyme Q10
- Nitric Oxide
- many more
MTHFR Gene Mutation May Cause a Slew of Problems
Given the impact of the MTHFR gene mutation to methylation, it can definitely give rise to a number of health conditions. Health problems linked with MTHFR include:
- Neurologic disorders like depression, anxiety, bipolar disorder
- Cardiovascular diseases like heart attacks, stroke, and embolism
- Cancer like gallbladder, colon, and pancreatic cancer as well as leukemia
- Autoimmune diseases like diabetes and Hashimoto’s
- Pregnancy and congenital anomalies like recurrent miscarriages and neural tube defects in babies such as spina bifida
- Developmental disorders like autism
For individuals with gallbladder, liver, and gastrointestinal issues, it is possible that the MTHFR gene has a hand in the development and progression of these conditions. Here are the reasons why:
a. MTHFR affects the body’s ability to detoxify.
Our body has built-in cleaning mechanisms. However, because of the mutation of the MTHFR gene, many of these natural processes cannot efficiently be completed. For one, glutathione and metathione are depleted because of the abnormal methylation cycle. Second, methylation imbalance slows down estrogen detoxification. Whether estrogen levels are elevated from hormone replacement therapy, birth control, or pregnancy, this female hormone needs to be metabolized properly and flushed from the body daily. The more estrogen we are exposed to, the more methyl groups we need to break it down. This is especially difficult for those with MTHFR.
b. Methylation issues affect the bile
When our body is full of toxins, our liver health is on the line. If our liver cannot detoxify properly, then the bile which is manufactured in the liver and circulated/re-circulated in the body will definitely be affected. Impaired methylation also depletes methionine, affecting bile flow and toxicity. Methionine administration improves bile salt conjugation with taurine, thereby making the bile less toxic.
Aside from methionine, folate also helps the bile. It increases bile flow, bile acid synthesis, and bile acid secretion. However, in people with MTHFR, the body’s ability to breakdown folic acid into a usable form is affected.
Another bile-related mechanism affected by MTHFR gene mutation is the level of phosphatidylethanolamine (PEMT) in the body. Phosphatidylethanolamine, a type of phospholipid, is created in the liver during methylation and it is for the gallbladder and liver. It plays a crucial role in the secretion of lipoproteins in the liver. Some studies also prove that PEMT increases cholesterol solubility in bile. The creation of PEMT uses up a lot of methyl groups and therefore, individuals with MTHFR gene mutations may have a hard time producing enough of this phospholipid. PEMT deficiency may impair cellular growth and overall cellular energy production. It has been implicated in neurodegenerative disorders, metabolic syndromw, cardiovascular disease, and tumor development.
Decreased bile flow as well as having more toxic, fat-soluble bile, may increase the risk of developing gallstones and other gallbladder diseases.
c. It is related to pancreatic and gallbladder cancer development
DNA breakage, chromosomal loses, and the loss of methyl groups from the DNA molecule (also called DNA hypomethylation) induces carcinogenesis and accelerates cancer development. In individuals with methyl group deficiency, these cellular irregularities are common.
A 2003 study on the progression of gene hypermethylation in gallstone disease concluded that methylation issues may contribute to tumor formation within the chronically-inflamed gallbladder. Another study proposed that MTHFR A1298C mutation may increase the risk of gallbladder cancer. Lastly, an experiment with 974 middle-aged Japanese men showed that elevated homocysteine levels, common among MTHFR patients, are also associated with gallstones and increased likelihood for cholecystectomy.
When bile acids become dysregulated, they can become cytotoxic. The presence of abnormally high levels of toxic bile acids coupled with a pro-inflammatory shift in the gut flora profile may also contribute to the development of cancer due to DNA damage, cell death, and increased cell proliferation.
Aside from its relationship with gallbladder cancer, MTHFR, abnormal methylation, and hyperhomocysteinemia are all implicated in the development of breast, colorectal, pancreatic, and liver cancer.
d. It is linked to NAFLD
There is a long list of possible reasons for the development of non-alcoholic fatty liver disease (NAFLD); the most common among them are avoidable causes like unhealthy habits and bad diet. Unfortunately, the development risk and severity of NAFLD may also be genetic.
In a study involving 286 human subjects with and without NAFLD, it was concluded that MTHFR C677T and A1298C mutations were common in NAFLD patients than in the healthy control group. Other related studies about elevated homocysteine levels and abnormal methylation capacity of the liver also both conclude that individuals with MTHFR are more predisposed to NAFLD compared to other people without the same genetic profile.
e. Abnormal methylation may affect brain health
Methylfolate is very important in the brain development. So if there is not enough methyl in the body or if folic acid cannot be synthesized into a useful form, the brain is affected. This is true not just for unborn babies but for developing children and adults as well. Numerous experiments have already linked MTHFR and conditions affecting mental health like depression, schizophrenia, and brain fog. Folate is the primary vitamin involved in the formation of dopamine, norepinephrine, and serotonin, important neurotransmitters for normal brain function.
Methylation’s effect on our natural inflammatory and immunity response make it even worse for our mental health. That is why some studies have proven that methylfolate supplementation (not to be mistaken as synthetic folic acid) helps those with depression. A 2012 study published in the American Journal of Psychiatry suggest taking as much as 15 mg of methylfolate supplement daily for significant effect. An individual suffering from depression or anxiety may start with 7.5 mg and gradually increase the dosage every day to maximize the amount that goes through the blood brain barrier. Though this amount is significantly higher the recommended daily dosage, it is still way below 50 mg which is identified as the safety limit for daily dosage. Supplementation will also have a significant positive effect on gastrointestinal function as mediated by the mind-gut connection.
There is no other way to know if you have problems with MTHFR but to have genetic testing. However, this test is rarely recommended. A number of organizations like the The American Congress of Obstetricians and Gynecologists (ACOG), American Heart Association, College of American Pathologists, the American College of Medical Genetics, and the American Heart Association advise against MTHFR gene testing unless absolutely necessary. This is because they believe that results have minimal impact on a person’s medical management. Since it is an issue of genetics, there is no technology or treatment available at the moment for the reversal of the mutation.
If your blood test shows you have high fasting blood homocysteine levels, then it is best to consult a naturopath or a holistically-oriented MD. Despite the number of people possibly afflicted by this mutation, there are a few main-stream medical practitioners who are well-informed about MTHFR.
Whether you know for sure that you have MTHFR gene mutation or not, the recommended treatment for MTHFR won’t do you any harm. There is no recommended treatment but a healthy lifestyle would definitely help in managing it.
- Steer clear of environmental toxins.
- Quit smoking.
- Exercise regularly.
- Eat more green, leafy vegetables and strive to go organic as much as possible.
- Manage your stress.
Though there is no cure for MTHFR mutation, there are a few natural supplements that you can try to help support your body’s methylation cycle.
a. B Vitamins
The B vitamins, especially B2, B6, and B12, can support the body’s needs during the methylation cycle. B vitamins are also effective supplements for digestion and metabolism .
b. Natural Folate
Try food sources and supplements with natural folate. Take methylfolate or folic acid. Folate is required for cellular function, amino acid metabolism, detoxification, and the formation and maturation of red blood cells, white blood cells, and platelets.
Glutathione is not called the master antioxidant for nothing. For a list of glutathione benefits, read here .
d. Phosphatidylcholine (PC)
PC supplementation lowers homocysteine (HCY) levels in the blood while increasing methyl donors, helping improve the body’s methylation.
Choline is one of the important methyl donors in the body. When folate levels are too low, it is very important that the body has enough cholate to pick up the slack.
Betaine helps lower homocysteine levels. In an animal study, betaine has been used to rescue MTHFR mice from postnatal death by supplementing their mothers. Betaine may also help protect the brain from biochemical and developmental anomalies.
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