MTHFR, Oxidative Stress and Glutathione

Glutathione and MTHFR are both important parts of the body’s system for maintaining homeostasis. The complex way the biochemicals of the body interact, means that a problem with one important biochemical will often affect others. In the case of MTHFR anomalies, the inability of the MTHFR enzyme to do its job effectively increases the work load for glutathione, with less than pleasant consequences.


MTHFR Anomalies Create Oxidative Stress

Oxidative stress is damage to the cells of the body by free radicals. Many diseases associated with aging are caused by oxidative stress, as are a number of other health problems. People who have MTHFR anomalies have high levels of oxidative stress.

This is because MTHFR anomalies cause high levels of homocysteine, and homocysteine creates the free radicals that cause oxidative stress.


Oxidative Stress Lowers Glutathione Levels

Glutathione is one of the body’s most powerful anti-oxidants. One of glutathione’s main jobs in the body is to seek out and neutralize free radicals before they can do any damage. Glutathione also helps repair cells and DNA that have already been damaged by free radicals.

When there are more free radicals (which is another way of saying ‘high oxidative stress’) glutathione gets used up faster than usual. If it gets used up fast enough, the body isn’t able to keep up and glutathione levels drop. Then, free radicals are able to damage cells throughout the body, creating the symptoms of oxidative. Low glutathione levels also mean there isn’t enough available to repair damage to cells or help with the other things the body uses it for, like clearing heavy metal.


MTHFR anomalies → high homocysteine → more free radicals → high oxidative stress + low glutathione → many health problems

What is Oxidative Stress?

Oxidative stress has become something of a health buzz-word in recent years. It is getting blamed for everything from heart problems, to cancer, to aging. Yet for all the talk, not many people know what oxidative stress is.

Oxidation is surprisingly familiar. We see it all the time. We just don’t don’t usually call it oxidation. When we cut an apple in half and it turns brown, that is oxidation. When iron rusts, that’s oxidation. Oxidation also happens inside the body. Just like iron rusting and apples going gooey, oxidation inside the body causes damage. This damage is what doctors call oxidative stress.

But… let’s back up a bit. Just what is oxidation? Well, it starts with oxygen. Oxygen is unbalanced. Each oxygen atoms has seven electrons, in a space that is able to fit eight electrons. So oxygen is constantly ‘stealing’ electrons to fill that last spot and make itself balanced. This is called oxidation.

Oxygen isn’t the only chemical that causes oxidation; it’s just the best known. Many other chemicals do the same thing. Free radicals are chemicals inside the body that cause oxidation. Some free radicals come from outside the body, some are created inside the body. All of them cause problems.

Oxidative Stress
All of the cells in the body, and all the pieces of the cells, are made of chemicals that are held together by electrons. When a free radical steals an electron from the cell membrane, it damages the cell and might create a hole in the membrane. Over time, free radicals do more and more damage to different parts of the cell. This damage hurts the cell, and prevents the cell from doing its job. Eventually, the damage will cause the cell to die. This is oxidative stress.

If enough of your cells die, organs in your body will develop problems, and you will get sick. Many lung conditions are caused by oxidative stress, because lungs need to deal with free radicals from the environment and from inside the body. Of course, its not just the lungs that can be damaged by oxidative stress. Every organ in the body is susceptible to oxidative stress, and most of what we think of as ‘signs of aging’ are actually the results of long-term oxidative stress on the body.

Thankfully, the body doesn’t take oxidative stress lying down. There is an extensive system for combating and controlling oxidative stress. Free radicals that are created inside the body are carefully controlled and converted into other chemicals or flushed from the body. Special chemicals called ‘anti-oxidants’ are made by the body just to give extra electrons to free radicals and prevent them from causing oxidative stress. Cells constantly repair and fix damage done by the free radicals that the body isn’t able to stop in time.

When everything goes well, the body’s defenses against oxidative stress are very effective. Over time, damage does accumulate, but very slowly. When the body is able to protect against oxidative stress, people stay healthy and don’t develop diseases associated with old age early in life. Most people will develop one or two of the age associated diseases, and stay generally healthy until they die.

Unfortunately, many things can cause problems for the body’s defenses. There are more free radicals in the environment than ever before, so people are being exposed to higher amounts of external free radicals, which makes it harder for the body to protect itself. Many people don’t eat a healthy diet with enough anti-oxidants, so the body may not have everything it needs to protect itself. Finally, some genetic conditions can change the balance of free radicals and anti-oxidants, crippling or overwhelming the body’s defense.

How Does Oxidative Stress Relate to MTHFR?
MTHFR anomalies increase the amount of oxidative stress on the body. At first, researchers weren’t sure why this happened. There was no reason they could see for MTHFR anomalies to cause high levels of oxidative stress, and they couldn’t find any other reason for the high oxidative stress in people with MTHFR anomalies. For a few years, all they could say was that yes, MTHFR causes oxidative stress.

In 2009, a study was published in the Proceedings of the National Academy of Sciences of the United States (PNAS) which finally explained how MTHFR causes oxidative stress. This study found that homocysteine creates free radicals, the chemicals that cause oxidative stress. And researchers have known for years that MTHFR anomalies create high levels of homocysteine. So MTHFR anomalies don’t cause oxidative stress directly, but the increase in oxidative stress is a secondary effect, caused by the high levels of homocysteine.

Unfortunately, when levels of oxidative stress get high, the body doesn’t have enough anti-oxidants to prevent significant damage from occuring. Many people with MTHFR anomalies develop age-related diseases at unusually young ages, or are increased risk for age-related diseases as they get older.

A further affect of high levels of oxidative stress is the decrease in the amount of glutathione available to the body. Glutathione is one of the most important anti-oxidants, and when oxidative stress is high, like when a person has an MTHFR anomaly, glutathione levels drop. Since glutathione also clears heavy metals from the body, this can also lead to long term heavy metal poisoning, and it’s associated problems.

What Kinds of Health Problems are Caused by Oxidative Stress?
Oxidative stress causes a wide variety of health problems. Some of the most common ones can be:

  • Kidney damage
  • Cataracts
  • Ischemic bowel disease
  • Hardening of the arteries
  • Cancer
  • Diabetes
  • Alzheimer’s Disease
  • Asthma
  • Hyperoxia
  • Rheumatoid Arthritis
  • Angioplasty
  • Psoriasis


More on the connection between MTHFR, oxidative stress, and glutathione.

What Health Problems Do MTHFR Anomalies Aggravate?

MTHFR anomalies can have a wide variety of effects. This is partly because of the widespread impact on MTHFR on the body’s metabolism, and partly because each anomaly has slightly different effect, leading to different health problems. In addition, the effects of MTHFR can vary depending on a person’s environment, lifestyle or other metabolic anomalies.

In this article you will find a brief introduction to some of the health problems that MTHFR causes. If you or someone you love is dealing with several of these health problems, especially if there is no clear cause for their illness, it is probably worthwhile to look into getting tested for MTHFR anomalies.

Health Problems Caused by MTHFR
Autism: MTHFR 677 and MTHFR 677/1298 both carry an increased risk of autism. Mothers with MTHFR who do not take folate supplements during pregnancy may be more likely to have children develop autism.

Birth defects: MTHFR 677 is associated with an increased risk of birth defects including neural tube defects and cleft lip.

Cardiovascular disease: One of the most common causes of death, cardiovascular disease affects millions of people world wide. Cardiovascular disease is associated with MTHFR 677.

Hypertension: Elevated blood pressure is more strongly associated with MTHFR 677 than other forms of cardiovascular disease.

Chronic fatigue syndrome: In 2011 it was discovered that there is a virus associated with CFS, and treatments are finally being developed. However there is also a relationship between CFS and MTHFR 1298. Perhaps the MTHFR anomaly in some way prevents the body from fighting off the virus.

Deep venous thrombosis (DVT): Deep vein thrombosis is the medical term for when a blood clot forms in a major vein and blocks blood flow to large parts of the body. Untreated, DVT is potentially fatal. Most often these blood clots form in the legs. MTHFR 677 is associated with an increased risk of developing DVT.

Dementia: Many people, as they get older, slowly lose cognitive functions. Their memory becomes weaker; their judgment and behavior become erratic, they have difficulty speaking or can’t think clearly. Most of the time dementia is a symptom of another illness, such as brain cancer. Sometimes dementia develops for no apparent reason. When no other cause for dementia may be found, in these cases MTHFR 1298 may be a factor.

Depression and anxiety disorders: MTHFR 1298 interferes with serotonin production. Low levels of serotonin are a frequent cause of mental health problems such as anxiety and depressive disorders.

Elevated homocysteine: Homocysteine is an amino acid that is produced by the body when breaking down proteins. High levels of homocysteine are associated with and believed to cause a number of health problems. People with MTHFR 1298 are likely to have high homocysteine levels.

Fibromyalgia: Frequently referred to as ‘fibro’, fibromyalgia is a chronic pain syndrome with no known cause. It frequently occurs alongside chronic fatigue syndrome. Fibro is more common among people with MTHFR 1298.

Heavy metals: People with all MTHFR polymorphisms have trouble clearing heavy metals. This can lead to heavy metal poisoning and the many health problems high levels of heavy metals in the body can cause.

Irritable bowel syndrome (IBS or spastic colon): A bowel disorder associated with cramping, pain, unusual bowl movements and is usually triggered by eating specific foods. IBS is more frequent in people who have MTHFR 1298.

Migraines: Migraines are a specific kind of headache which include pain focused behind the eyes, light sensitivity, ‘auras’ or visual effects, and other symptoms. Many people who have migraines find they are triggered by specific foods, stress and environmental factors. Some kinds of migraines are associated with MTHFR 677.

Oxidative Stress: Techinically, oxidative stress isn’t a health problem in the sense of a disease or medical disorder. Oxidative stress is damage done to the body by free radicals, and over time it leads to a wide variety of additional health problems.

Parkinson’s disease: Parkinson’s is a nervous disorder which interferes with the nerves and slowly destroys both fine and gross motor control. It is also frequently painful. People with the 1298 MTHFR polymorphism are more likely to develop Parkinson’s disease.

Peripheral neuropathy: Peripheral neuropathy is the medical term for when the nerves throughout the body stop functioning properly. This condition is a part of several poorly understood nervous disorders, including multiple sclerosis. MTHFR 677 is associated with increased risk of peripheral neuropathy.

Pre-eclampsia: Pre-eclampsia is a pregnancy complication which develops sometimes when a mother’s blood pressure is very high for an extended period of time. If untreated pre-eclampsia develops into eclampsia, which can lead to early labor and is potentially dangerous for both mother and baby. Mothers with MTHFR 677 are more likely to develop pre-eclampsia.

Renal failure (Acute kidney failure): The kidneys are responsible for filtering the blood, removing wastes and concentrating urine. Sudden (or acute) kidney failure is more likely in people who have any of the MTHFR polymorphisms.

Schizophrenia: Schizophrenia is a mental disorder whose symptoms include paranoia and hallucinations. It occurs more frequently in people who have MTHFR 677.

Stillbirth: A stillbirth is when a fetus dies of natural causes after the 20th week of the pregnancy. Early spontaneous abortion is when the fetus dies of natural causes before the 20th week. Women with MTHFR 677 are more likely to experience a stillbirth or multiple early spontaneous abortions.

Stroke:  When blood flow to an area of the brain is suddenly cut off, parts of the brain are damaged. This is what is known as a stroke. A stroke may occurs when a blood clot forms inside the brain and cuts off blood flow, or when something else interferes with the flow of blood through the brain. An increased risk of stroke is associated with MTHFR 677.

Tetrahydrobiopterin problems: Tetrahydrobiopterin is an amino acid that plays several important roles tin the body’s function. Some people have a deficiency in tetrahydrobiopterin. These deficiencies may cause a variety of neurological problems. Tetrahydrobiopterin problems are more common among people with MTHFR 1298.

Researchers are still working to determine why the MTHFR anomaly may cause these problems. In time, they may find other health problems that are also related to MTHFR. Not everyone who has MTHFR problems will have these health issues, and many people who have some of these health problems do not have an MTHFR anomaly. Having an MTHFR anomaly increases the risk of developing these health problems, but other factors determine whether or not anyone will have a specific health problem. For instance, someone with an MTHFR anomaly will have difficulty clearing heavy metal from their body; but if they are not exposed to heavy metals, they will not get heavy metal poisoning.