Methylation? What exactly is methylation? It is an overlooked, extremely important biochemical reaction and an essential biochemical reaction that takes place in every single cell of our body. Without methylation, we would cease to exist. It is estimated that a billion methylation reactions occur in our bodies every second! It is probably the second most important biochemical reaction in the human body besides oxidative reactions which are responsible for producing energy in our cells. Furthermore, the methylation process in our bodies is interlinked to several other important biochemical reactions. As a matter of fact, you can think of these biochemical pathways as a machine that contains several gears that intermesh with each other. If one gear is not functioning or out of line it effects all the other gears. So, essentially if the methylation cycle or pathway is not working properly it has widespread effects in the function of the body and can have multiple symptoms that go along with this dysfunction. Many of these symptoms or health issues may appear to be totally unrelated. However, they may be all stemming from an improper functioning methylation cycle/pathway. Some signs of poor methylation can lead to autism, ADD/ADHD, allergies, arthritis, chronic fatigue, cancer, dementia, diabetes, fibromyalgia, migraines, seizures, thyroid problems and many more. We will list others later but, as you can see it covers a wide range of conditions that do not seem to be directly related.
On a biochemical basis methylation is the transfer of what is referred to as a methyl group. A methyl group is simply a carbon atom with three hydrogen atoms attached (see diagram to right). This may seem to be impossible that such a small molecule can have such an effect on the body. However, methylation does significantly change the function and structure of enzymes, proteins, carbohydrates, fats, and our nuclear material in our chromosomes known as genes.
Influences of Methylation:
- Production of DNA and RNA which are our genetic building blocks.
- Turns on and off and stabilizes our genes.
- Production of neurotransmitters.
- Production of myelin which is a fatty insulator around our nerves.
- Regulation of our immune system and inflammation.
- Effects the fluidity of our cell membranes and production of important phospholipids.
- Control and breakdown of our hormones
- Production and repair of proteins throughout the body.
- Detoxification and removal of heavy metals.
- Allergic reactions via histamine.
CONDITIONS ASSOCIATED WITH METHYLATION
The list here is very extensive because methylation has such extensive effects on the body.
- Advanced aging
- Allergies and increasedhistamine
- Birth defects
- Chronic fatigue
- Cancer (breast, ovarian, brain, colon, liver etc.)
- Down Syndrome
- Heart Disease
- High blood pressure
- Irritable Bowel (Crohns, ulcerative colitis)
- Leaky gut
- Metal toxicity
- Neural tube defects
- Renal failure
- Rheumatoid arthritis
- Sleep disorders
METHYLATION AND OTHER PATHWAYS
There are several interrelated biochemical pathways/cycles inside of your cells. You can think of these pathways as gears in a machine that are all meshed together, as seen in the schematic below. This is why impaired methylation can have such widespread and profound effects on our health.
The methylation cycle also known as the methionine/ homocysteine cycle is vitally important. This is where the main methyl donor is produced called SAMe. This is part of the cycle that assist in DNA production which is essential for cell division and DNA/gene expression. It is involved in protein and neurotransmitter production. It is responsible for creating compounds for cell membrane repair and fluidity. Lastly, it is responsible for the production of glutathione. This is the main antioxidant in the human body.
The folate cycle is important for DNA and RNA synthesis, repair and stabilization. This allows proper cell growth and cell division. It is particularly important for red blood cell production. It should be noted that there is a very important enzyme called MTHFR that affects all these cycles. Genetic defects of this enzyme can have significant effects on human health.
The BH4 cycle is responsible for production of many neurotransmitters like serotonin. It decreases free radical production, maintains blood vessel function via nitric oxide. Lastly, it is linked to the urea cycle to help remove ammonia which is a protein byproduct.
COFACTORS AND MTHFR ENZYME
As was mentioned before it is essential that these cycles run smoothly and efficiently. All of these cycles rely on proteins called enzymes. Without the proper functioning of these enzymes, our health will suffer. These enzymes can be affected by the lack of cofactors, inflammatory changes and genetic mutations.
Cofactors are compounds that bind with the enzyme to help activate and regulate enzyme activity. Many cofactors are vitamin and mineral derived. The methylation cycles require, biotin, betaine, vitamins B2, B6 and particularly the activated form of B12 called methylcobalamin. This is not to be confused with the common supplemental form called cyanocobalamin which is inactive. The metallic minerals needed are zinc, magnesium and molybdenum.
Genetic mutations of the key enzyme MTHFR can lead to a number of health issues already listed. It is estimated that 45-50% of the US population has some defect in one of the two major genes affecting the MTHFR enzyme. Special genetic testing can be performed on the blood or via tissue mouth swab to determine the likelihood and severity of methylation problems. These tests are available in our office.
Lastly, many of these enzymes are sensitive to inflammatory changes. The inflammation may come from diet, environmental toxins, and other forms of oxidative stress.
This is a compound that is part of the “main” methylation cycle. It often becomes elevated with dysfunction of the methylation cycle. This is not good as homocysteine when elevated causes significant damage to the blood vessels throughout the body leading to atherosclerosis and cardiovascular disease. As a matter of fact, homocysteine measured in your blood is 10 times more accurate in determining the likelihood of cardiovascular disease than cholesterol, triglycerides or the “bad” cholesterol called LDL.
The increasing atherosclerosis or plaque buildup, begins to cause, heart, kidney and brain dysfunction due to decreased oxygen and nutrient delivery. These are very vascular organs so they are particularly sensitive to these vascular changes. The vascular changes associated with increased homocysteine can accelerate the formation of blood clots, elevated blood pressure, stroke, diabetes, peripheral neuropathy, retinopathy, preeclampsia, osteoporosis and osteoarthritis. Note that homocysteine also becomes elevated after menopause.
The genetic mutation C677T for MTHFR is associated with increased homocysteine levels. However, regular exercise and the proper nutrients can reduce homocysteine levels.
SAMe and METHYLTETRAHYDROFOLATE (MTHF)
S – adenosylmethionine also known as SAMe is an extremely important component of the methylation cycle. It is one of the prime compounds that donates methyl groups. It is a major compound for detoxification at the level of the liver and the liver contains about 80% of all the SAMe in our bodies.
Several studies have found this to be more effective in treating depression than most anti-depressants. It is readily prescribed in Europe.
SAMe is also involved with Co enzyme Q production, decreases histamine from allergic reactions, helps with protein production especially for muscles, repair and stabilization of DNA and joint cartilage. It has been shown to be as effective as NSAIDs in reducing joint and fibromyalgia pain.
The next major methyl donor is methyl tetrahydrofolate (MTHF). Many people cannot produce this compound due to genetic factors. MTHF is essential for decreasing homocysteine and producing SAMe Again, making sure inflammation is reduced and other genetic imbalances are addressed, these substances can improve health significantly.