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

Understanding Homocysteine

Homocysteine is an amino acid that comes from animal protein. Normally the human body keeps the level of homocysteine low by constantly converting it into other amino acids. The MTHFR enzyme converts homocysteine to methionine through a process called ‘remethylation’. Sometimes something goes wrong, and the levels of homocysteine become higher than they should.

What health problems does homocysteine cause?
When homocysteine levels get too high, people often develop vascular disease. Many researchers believe that high levels of homocysteine cause vascular disease, but they haven’t determined how this happens. Some of the vascular disease problems that happen when people get high levels of homocysteine are hardening of the arteries, formation of blood clots, stroke and dementia. Several other medical problems may develop over time, especially if homocysteine levels are extremely high. When homocysteine levels in the blood are higher than they should be, it is called hyperhomocysteinaemia.

Homocysteine also causes oxidative stress. Homocysteine increases the levels of free radicals in the body, putting more stress on the body and lowering the levels of important anti-oxidants like glutathione.

What causes hyperhomocysteinaemia?
A number of things can cause homocysteine levels to rise. B12 and folate are both used in converting homocysteine to other amino acids. If a person has a deficiency in either B12 or folate, the body cannot convert homocysteine and the levels will rise. Some medications can cause high levels of homocysteine, especially medications that interfere with folate. There are several medical conditions that can lead to high homocysteine levels as well. The 677 MTHFR anomaly is one of several genetic conditions that can cause high homocysteine levels.

How does 677 MTHFR cause high homocysteine levels?
The 677 MTHFR anomaly creates a change in the MTHFR enzyme. The MTHFR enzyme created by the 677 anomaly is known as TL-MTHFR. Remember that the MTHFR enzyme converts homocysteine into another amino acid? The TL-MTHFR version works only half as well as the regular MTHFR enzyme. This means that only half the homocysteine is being converted to methionine, and a lot of homocysteine is being left behind to cause health problems.

If I have hyperhomocysteinaemia do I have 677 MTHFR?
Maybe. There are a lot of things that can cause high homocysteine levels. If you have high homocysteine levels you might want to get tested for MTHFR to be sure, and you should definitely talk with your doctor about other possible causes.