Oxidative Stress

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 Glutathione?

If you keep up with the latest nutrition advice, you may have heard of glutathione. Glutathione has become popular in recent years as an important anti-oxidant that is found in some fruits. It is actually one of the body’s most important anti-oxidants, but it does a lot more then just clear out free radicals. In fact, glutathione is involved in a great deal of the body’s metabolism.

So, Just What Is Glutathione?
Glutathione is a small molecule made of three amino acids – the pieces that proteins are built from. The technical term for this kind of molecule is a ‘tri-peptide’.

What Does Glutathione Do?
Glutathione is a very busy molecule. It:

  • Is an antioxidant, protecting the body against free radicals and oxidative stress
  • Helps process medications
  • Processes and protects against carcinogens
  • Clears heavy metals from the body
  • Helps build DNA
  • Helps build proteins

As you can see, glutathione does a lot of important things. Luckily, the body is normally very good at keeping levels of glutathione high enough to take care of everything it needs to. For most people, glutathione will quietly do its job without any problems for their entire lives.

What Happens if the Body Doesn’t Have Enough Glutathione?
When there isn’t enough glutathione, a person has a glutathione deficiency. When a glutathione deficiency develops, then the body isn’t able to protect itself against oxidative stress, process medications, clear heavy metals or protect itself from carcinogens. Some of the health problems that can develop or worsen when this happens include:

  • Alzheimer’s disease
  • Parkinson’s disease
  • liver disease
  • cystic fibrosis
  • sickle cell anemia
  • cancer
  • heart disease
  • stroke
  • diabetes

What Causes Glutathione Deficiency?
Several things can cause a gluthathione deficiency.

Genetic problems in glutathione production: Sometimes something prevents the body from making enough glutathione. There are some rare genetic polymorphisms that directly interfere with the body’s production of glutatione, and some more common polymorphisms on what is called the ‘transulfuration pathway’ and can also lead to a glutathione deficiency. MTHFR is not included in these genetic polymorphisms. MTHFR does not interfere with the production of glutathione.

Poor Nutrition: The body needs animal protein to create glutathione. It cannot manufacture glutathione from plant protein or other sources. However glutathione is already present in a number of fruits. In order to avoid a glutathione deficiency it is important to eat either animal protein or fruits high in glutathione.

The body is good at maintaining healthy levels of glutathione – a few days without fruit or animal protein now and then won’t cause problems, bu one or the other should be a regular part of your diet.

High levels of oxidative stress: Oxidative stress is the only thing researchers have found which is Able to cause a sudden drop in glutathione levels.

MTHFR causes high levels of oxidative stress, which can lead to glutathione deficiency and all the health problems it causes.

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

The Connection Between Heavy Metal and MTHFR

MTHFR is a genetic condition, heavy metal poisoning is, like all poisoning, caused by something outside the body. Which makes it a bit surprising that MTHFR increases the risk of heavy metal poisoning. How can a genetic condition effect whether or not a person is poisoned?

The connection is a bit convoluted, but very much real. Basically, MTHFR anomalies destroy the body’s ability to protect itself from heavy metal. A person with an MTHFR anomaly will get sick from amounts of heavy metal that normally aren’t dangerous, because their body is not able to get rid of the heavy metal.

How the Body Deals with Heavy Metals
Many things need to happen before a person develops symptoms of heavy metal poisoning. The first, and most important, is they need to be exposed to a lot of heavy metals. Someone who is never exposed to heavy metals will never get heavy metal poisoning. Unfortunately, our world is full of heavy metals. Mercury is found in sea food, lead in some paints; commercial fertilizers have zinc, nickle and cadmium, even cars spread heavy metal, in the dust from tired and brake pads.

Luckily, the body has ways of dealing with and getting rid of heavy metals. Glutathione, in the liver, clears heavy metal from the blood stream and urine carries it out of the body. If there is more heavy metal than can be carried away by the urine, it is taken up by hair follicles and grows out of the body with our hair. In extreme cases, heavy metal will be ‘stored’ in fat cells. This puts the heavy metal in a place where it can’t hurt the body, but means the heavy metal is still there, and if the person loses weight, the heavy metal will flood their system.

The human body is not very good at getting rid of heavy metals. The systems for getting rid of heavy metals can be easily overwhelmed with relatively small amounts of heavy metals. This is why things like lead in paint and drinking water are so dangerous. The body can keep up with normal heavy metal exposure, but any excess quickly becomes a problem. When no more heavy metal can be shoved out of the body through urine and hair growth, or packed into fat cells, the heavy metal stays in the blood stream, and people get sick.

Glutathione, MTHFR and Heavy Metals
Glutathione is the key to the body’s defense against heavy metals. Anything that interferes with glutathione or reduces the amount of glutathione available immediately increases the risk of heavy metal poisoning. However, removing heavy metals is something of a secondary job for glutathione. It is a major factor in several parts of the metabolism, and gets used for a lot of different purposes. Normally, the body does a very good job of keeping level of glutathione stable. By making sure there is always enough glutathione, the body insures that all the jobs glutathione is needed for can get done, including clearing heavy metals.

There are really only two things can really reduce glutathione levels. One is a genetic polymorphism that interferes with the production of glutathione, the other is high levels of oxidative stress (aka, lots of free radicals). Oxidative stress is the connection between MTHFR anomalies and heavy metal poisoning.

MTHFR anomalies create high levels of oxidative stress. Oxidative stress is just as much a poison as heavy metals are, and clearing oxidative stress from the body is one of glutathione’s most important jobs. However, when the levels of oxidative stress get too high, the body can’t keep up, and glutathione levels start dropping. If you are exposed to heavy metals while the body has low levels of glutathione, the heavy metals will stay in your body. Without glutathione, the heavy metals can’t be cleared out of the blood steam and gotten rid of. This can lead to heavy metal poisoning.

MTHFR anomalies → high oxidative stress → low glutathione
Low glutathione + heavy metal exposure → heavy metal poisoning

Many people without any MTHFR anomalies develop heavy metal poisoning every year. And many people with MTHFR anomalies never develop heavy metal problems. However, people who have MTHFR anomalies can develop symptoms of heavy metal poisoning far more easily, and with far less heavy metal exposure, than people who do not have MTHFR anomalies.

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.