There are numerous theories for the cause and symptoms triggering fibromyalgia and CFS. One theory, now gaining some traction, should be explored in more detail–certainly doctors should be testing their patients for Methylation Cycle Block.
Excerpt taken from my new 5th edition Treating and Beating Fibromyalgia and Chronic Fatigue Syndrome book.
A New Theory of Cause:
Glutathione Depletion and Methylation Cycle Block
Methylation is a key biochemical process essential for the proper function of almost all of your body’s systems. It occurs billions of times every second and is believed to operate in every cell. It helps repair your DNA on a daily basis, and it helps protect against plaque formation, arterial occlusion, heart disease, heart attack, and stroke. Methylation regulates moods and inflammation, and it helps recycle molecules needed for detoxification. It also facilitates the production of CoQ10 and carnitine, two important chemicals for energy.
When the methylation cycle is blocked, important biochemical functions are not carried out properly. A methylation block leads to a block in the folate metabolism, to which it is intimately linked, and this interferes with synthesis of new DNA and RNA, among other important effects. Perhaps the greatest problem with a methylation-cycle block is that neither the immune system nor the detox system can operate properly. If the methylation cycle remains blocked for an extended period of time, infections and toxins can be expected to build up in the body. Not good.
Methylenetetrahydrofolate reductase ( MTHFR) is a common genetic variant that causes a key enzyme in the body to function at a reduced rate. There are over fifty known MTHFR variants, and it is associated with a variety of chronic illnesses, including fibromyalgia and CFS/ME.
Rich van Konynenburg, PhD, has spent a number of years piecing together an interesting theory, one that is gaining momentum among functional medicine doctors, known as glutathione depletion and methylation cycle block. Dr. van Konynenburg proposes that in order to develop CFS/ME, a person must have When this person then is also subjected to some combination of long-term physical, chemical, biological, or psychological/emotional stressors, glutathione levels are lowered to the point that a block occurs in the methylation cycle.
This lowering of glutathione levels also simultaneously removes the normal protection that glutathione provides to vitamin B12 and allows the accumulation in the body of toxins (probably mercury, chiefly) that can interfere with the utilization of this vitamin. His hypothesis further proposes that the lowering of glutathione levels means that the level of methylcobalamin (a special form of natural vitamin B12) is too low to support the methionine synthase reaction, and it therefore becomes chronically blocked. This produces a vicious cycle that causes CFS/ME to become a chronic condition.
Those with MTHFR do usually have very low glutathione levels. This makes them more susceptible to stress, including toxins that overwhelm an already poorly functioning detoxification system, leading to more stress. Glutathione is the body’s primary antioxidant and a potent detoxifier. These folks simply can’t detoxify the chemicals they are exposed to on a daily basis. As time goes on, they find they become more and more chemically sensitive. They have “funny” (not so funny, really) reactions to meds, aversions to strong odors, and seemingly random sensitivities.
Rich van Konynenburg’s idea is that ineffective methylation is a major cause of fatigue. There are many possible reasons for this connection, but some become obvious when we look at the many different functions of methylation:
- to produce vital molecules such as CoQ10 and carnitine.
- to switch on DNA and switch off DNA by activating and deactivating genes.
When viruses attack our bodies, they take over our own DNA in order to replicate themselves. If we can’t switch DNA/RNA replication off, then we become more susceptible to viral infection. This “switching” role is also essential for protein synthesis. And proteins, of course, make up our hormones, neurotransmitters, enzymes, and immune factors and are fundamental to good health.
- to determine the rate of synthesis of glutathione, which is essential for detoxification.
- to produce myelin for the brain and nervous system.
- to control sulphur metabolism of the body, not just glutathione but also cysteine, taurine, and sulphate. This is an important process for detoxification.
- to serve as part of folic-acid metabolism. This also switches on synthesis of new DNA and RNA.
- to assist in normal immune function.
The methylation cycle is essential for cell-mediated immune function, and blockages here will mean that infections will not be adequately dealt with.
Factors that Affect Your Methylation Process
- Genetics: Like an estimated 20 percent of us, you could be genetically predisposed to high homocysteine levels, which affect your methylation process.
- Poor diet: B vitamins come from eating leafy greens, beans, fruit, and whole grains to get adequate levels of vitamins B 6 and B 12, betaine, and folate. Egg yolks, meat, liver, and oily fish are the main dietary sources of vitamin B 12, so long-term vegan diets can also be a problem. Plus, certain compounds can raise levels of homocysteine and deplete the B vitamins: excess animal protein, sugar, saturated fat, coffee, junk food, and alcohol.
- Smoking depletes vitamin B 6.
- Decreased stomach acid: Aging and other conditions can reduce stomach acid, and therefore absorption of vitamin B 12.
- Malabsorption: Conditions like digestive diseases, food allergies, and even aging can reduce absorption of nutrients.
- Other conditions: These include hypothyroidism, kidney failure, having only one kidney, cancer, and pregnancy.
- Medications: Drugs like acid blockers, methotrexate (for cancer and arthritis and other autoimmune diseases), oral contraceptives, HCTZ (for high blood pressure), and Dilantin (for seizures) can all affect levels of B vitamins.
The overall effect here is that if the methylation cycle doesn’t work, the immune system malfunctions, the detoxification system malfunctions, the antioxidant system malfunctions, and our ability to heal and repair is reduced.
Measuring Your Own Methylation Process
To find out if your methylation process is optimal, ask your doctor for the following tests:
- Complete blood count: Red blood cells with a mean corpuscular volume (MCV) greater than ninety-five can signal a methylation problem.
- Homocysteine: The normal level is less than thirteen, but the ideal level is likely between six and eight.
- Serum or urinary methylmalonic acid: This is a more specific test for vitamin B 12 insufficiency. Your levels may be elevated even if you have a normal serum B 12 or homocysteine level.
- Plasma blood test: Along with the above, I use this test from Doctor’s Data that measures six primary indicators of methionine metabolism.
I strongly encourage you not to embark on treating MHTFR without the help of a functional medicine doctor trained in MHTFR. When your body starts to detox properly, which is the goal of correcting MHTFR, you’ll most likely have die-off reactions from the killing of unwanted viruses, bacteria, yeast, etc. These reactions can be severe and at best, very uncomfortable. It is best to work with a health-care professional who can walk you through the process slowly but surely. The first step in this treatment, however, is to be properly These reactions can be severe and at best, very uncomfortable. It is best to work with a health-care professional who can walk you through the process slowly but surely. The first step in this treatment, however, is to be properly tested. If you’ve only been in the traditional medical world, I bet you’ve not been properly tested.