What is methylation? In simple terms it is a process in which certain chemicals called methyl groups or methyl donors are added to various constituents of proteins, DNA and other molecules. These are needed to keep them in good ‘working’ condition.
For example, if the brain chemical serotonin is not methylated it will become inactive which in turns leads to depression. This is just one of the many ‘chemicals’ in the body that need to be methylated and if they are not can lead to serious health consequences.
Another important chemical that requires the methylation process is homocysteine. Homocysteine is a by product of an important amino acid – methionine – and is what remains when methionine is used to methylate your proteins and DNA. Homocysteine needs to be methylated to convert it back to methionine. If methyl donors are not available, the conversion back to methionine is hampered, producing elevated homocysteine. Both undermethylation and overmethylation can cause distressing symptoms. If either of these conditions are present, there are nutritional therapies to help correct the imbalance.
Undermethylation is characterized by low levels of serotonin, dopamine, and norepinephrine, high whole blood histamine and elevated absolute basophils. However, the connection between high histamine and elevated absolute basophils (ABC) did not appear in one significant study Ph[/glossary].D., BCLD, Hugh D. Riordan, M.D., Sharon Neathery, MT(AMT), Chad Krier, ND, DC.].
This population has a high incidence of seasonal allergies, OCD tendencies, perfectionism, high libido, sparse body hair, and several other characteristics. They usually respond well to methionine, SAMe, calcium, magnesium, omega-3 essential oils (DHA & EPA), B-6, inositol, and vitamins A, C, and E. They should avoid supplements containing folic acid. In severe cases involving psychosis, the dominant symptom is usually delusional thinking rather than hallucinations. They tend to speak very little & may sit motionless for extended periods. They may appear outwardly calm, but suffer from extreme internal anxiety.
Aggressive methylation therapy can be very successful, but usually involves a very slow response. Typically, treatment with methionine, calcium, magnesium, B-6, etc requires about 2 months before the patient before any progress is evident — and 6-12 months are required for all of the benefits to be attained. Please note that whole blood histamine is a marker for innate methylation tendency, but is not an indicator of wellness or the degree to which undermethylation has been overcome. Undermethylated patients can become quite well without their histamine lab results changing at all.
One way to speed up the process of recovery is to use SAMe supplements in the beginning. Undermethylated patients usually report nice progress after the first week or two. SAMe is quite expensive, and can be gradually replaced by methionine after a couple of months.
Nearly all severely undermethylated persons have low serotonin levels and present with a history of depression, internal anxiety, and OCD. Many have a history of perfectionism and high accomplishment in the early years. Unfortunately this population also has a tendency for non-compliance with any treatment.
The late and great Carl Pfeiffer would occasionally resort to use of the anti-histamines Benedryl or Dilantin in high-histamine persons who were slow to respond. Avoidance of folate supplements is essential for most undermethylated persons, an exception being autism.
Some practitioners like to tinker with the SAM cycle to promote conversion of homocysteine to methionine, but this can deplete the cystathione pathway and result in deficiencies of glutathione, cysteine, etc. Some persons have
a genetic enzyme weakness which can disrupt the SAM cycle.
Undermethylated adults typically require 2,000 – 3,000 mg/day of methionine for several months to see good results. Also, augmenting nutrients such as calcium, magnesium, B-6, and zinc are essential.
TMG generally provides some benefits to undermethylated persons, but tends to make oxidative stress protections worse by diminishing the amount of homocysteine which converts via the cystathione pathway of the SAM cycle.TMG certainly is a promising nutrient for such persons, and adding some cysteine or glutathione can overcome the cystathione pathway deficit.
Personally, I believe the use of SAMe is the quickest way to help an undermethylated, high-histamine person.
Signs, symptoms & indicators of Methylation, Insufficient
Paying attention to detail
Being stubborn
Helped by antihistamine
No effect with/worse by benzodiazapines
B complex makes me feel worse
Poor pain tolerance
Light/minimal body hair
Excess/abundant saliva in mouth
Being detached from reality
Being an antisocial person
Strong sexual desire
No difficulty achieving orgasm
Conditions that suggest Methylation, Insufficient
Trichotillomania
Trichotillomania has been associated with OCD and undermethylation. If you can confirm the presence of undermethylation, the patient should benefit from (1) aggressive doses of l-methionine, calcium, magnesium, along with augmenting nutrients zinc, B-6, Inositol, Vitamin A & C and (2) strict avoidance of folic acid, choline, DMAE, and copper supplements. [Willam Walsh, Ph.D., past senior scientist, Pfeiffer Treatment Center www.hriptc.org]
Histadelia (Histamine High)
Elevated histamine and/or elevated basophils indicate undermethylation. [Willam Walsh, Ph.D., past senior scientist, Pfeiffer Treatment Center www.hriptc.org]
Depression
More than 40% of all clinically depressed men are undermethylated and benefit from therapies which enhance methylation. Another 15% or so are overmethylated and need to head for the other goal line…… namely avoidance of methylating supplements and use of folate therapy. [Willam Walsh, Ph.D., past senior scientist, Pfeiffer Treatment Center www.hriptc.org]
Risk factors for Methylation, Insufficient
SAMe use
Recommendations for Methylation, Insufficient
Key
| Strong or generally accepted link |
| Proven definite or direct link |
| Highly recommended |
| Reasonably likely to cause problems |
| Avoid absolutely |
Glossary
Protein
Compounds composed of hydrogen, oxygen, and nitrogen present in the body and in foods that form complex combinations of amino acids. Protein is essential for life and is used for growth and repair. Foods that supply the body with protein include animal products, grains, legumes, and vegetables. Proteins from animal sources contain the essential amino acids. Proteins are changed to amino acids in the body.
DNA
Deoxyribonucleic acid, the large molecule that is the main carrier of genetic information in cells. DNA is found mainly in the chromosomes of cells.
Serotonin
A phenolic amine neurotransmitter (C10H12N2O) that is a powerful vasoconstrictor and is found especially in the brain, blood serum and gastric membranes of mammals. Considered essential for relaxation, sleep, and concentration.
Amino Acid
An organic acid containing nitrogen chemical building blocks that aid in the production of protein in the body. Eight of the twenty-two known amino acids are considered "essential," and must be obtained from dietary sources because the body can not synthesize them.
Methionine
Essential amino acid. Dietary source of sulfur and methyl groups. Important for proper growth in infants, nitrogen balance in adults, healthy nails and skin and the synthesis of taurine, cysteine, phosphatidylcholine (lecithin), bile, carnitine and endorphins. It is an antioxidant nutrient and lipotropic agent which promotes the physiological utilization of fat.
Dopamine
A neurohormone; precursor to norepinephrine which acts as a stimulant to the nervous system.
Noradrenaline
(Norepinephrine): A catecholamine hormone secreted from the adrenal medulla and post-ganglionic adrenergic fibers in response to hypotension or emotional stress.
Histamine
A chemical in the body tissues, produced by the breakdown of histidine. It is released in allergic reactions and causes widening of capillaries, decreased blood pressure, increased release of gastric juice, fluid leakage forming itchy skin and hives, and tightening of smooth muscles of the bronchial tube and uterus.
Basophil
The basophils account for about 1% of the granulocyte count (60 to 75% of the white blood cells). They release chemicals such as histamine and play a role in the inflammatory response to infection.
Allergy
Hypersensitivity caused by exposure to a particular antigen (allergen), resulting in an increased reactivity to that antigen on subsequent exposure, sometimes with harmful immunologic consequences.
Calcium
The body's most abundant mineral. Its primary function is to help build and maintain bones and teeth. Calcium is also important to heart health, nerves, muscles and skin. Calcium helps control blood acid-alkaline balance, plays a role in cell division, muscle growth and iron utilization, activates certain enzymes, and helps transport nutrients through cell membranes. Calcium also forms a cellular cement called ground substance that helps hold cells and tissues together.
Magnesium
An essential mineral. The chief function of magnesium is to activate certain enzymes, especially those related to carbohydrate metabolism. Another role is to maintain the electrical potential across nerve and muscle membranes. It is essential for proper heartbeat and nerve transmission. Magnesium controls many cellular functions. It is involved in protein formation, DNA production and function and in the storage and release of energy in ATP. Magnesium is closely related to calcium and phosphorus in body function. The average adult body contains approximately one ounce of magnesium. It is the fifth mineral in abundance within the body--behind calcium, phosphorus, potassium and sodium. Although about 70 percent of the body's magnesium is contained in the teeth and bones, its most important functions are carried out by the remainder which is present in the cells of the soft tissues and in the fluid surrounding those cells.
Essential Oil
Volatile terpene derivative responsible for the odor or taste of a plant.
DHA
Docosahexanoic Acid. A metabolite of the omega-3 fatty acid alpha-linolenic acid.
EPA
Environmental Protection Agency. Also: Eicosapentanoic Acid. A metabolite of the omega-3 fatty acid alpha-linolenic acid.
Vitamin B6
Influences many body functions including regulating blood glucose levels, manufacturing hemoglobin and aiding the utilization of protein, carbohydrates and fats. It also aids in the function of the nervous system.
Inositol
Usually considered part of the vitamin B complex. It is thought that along with choline, inositol is necessary for the formation of lecithin within the body. Involved in calcium mobilization.
Folic Acid
A B-complex vitamin that functions along with vitamin B-12 and vitamin C in the utilization of proteins. It has an essential role in the formation of heme (the iron containing protein in hemoglobin necessary for the formation of red blood cells) and DNA. Folic acid is essential during pregnancy to prevent neural tubular defects in the developing fetus.
Hallucination
A false or distorted perception of objects or events, including sensations of sight, sound, taste, smell or touch, typically accompanied by a powerful belief in their reality.
Anxiety
Apprehension of danger, or dread, accompanied by nervous restlessness, tension, increased heart rate, and shortness of breath unrelated to a clearly identifiable stimulus.
Glutathione
A natural sulfur-bearing peptide formed from the linking of three amino acids: glutamic acid, cysteine and glycine. Glutathione acts as an antioxidant and detoxicant and is involved with the selenium-containing enzyme glutathione peroxidase. Glutathione is also involved in amino acid transport across cell membranes.
Cysteine
A nonessential amino acid but may be essential for individuals with certain diseases or nutritional concerns. Cysteine is a sulfur-bearing amino acid with antioxidant properties. It is important for keratin synthesis, a protein found in skin, hair and nails and is a component of coenzyme A and glutathione.
Enzymes
Specific protein catalysts produced by the cells that are crucial in chemical reactions and in building up or synthesizing most compounds in the body. Each enzyme performs a specific function without itself being consumed. For example, the digestive enzyme amylase acts on carbohydrates in foods to break them down.
Milligram
(mg): 1/1,000 of a gram by weight.
Zinc
An essential trace mineral. The functions of zinc are enzymatic. There are over 70 metalloenzymes known to require zinc for their functions. The main biochemicals in which zinc has been found to be necessary include: enzymes and enzymatic function, protein synthesis and carbohydrate metabolism. Zinc is a constituent of insulin and male reproductive fluid. Zinc is necessary for the proper metabolism of alcohol, to get rid of the lactic acid that builds up in working muscles and to transfer it to the lungs. Zinc is involved in the health of the immune system, assists vitamin A utilization and is involved in the formation of bone and teeth.
TMG
Tri-methyl-glycine. After supplying a methyl group, TMG becomes di-methyl-glycine. DMG, a natural component of animal and plant metabolism, positively influences the immune response in laboratory animals and humans and boosts physical and mental performance.
Vitamin A
A fat-soluble vitamin essential to one's health. Plays an important part in the growth and repair of body tissue, protects epithelial tissue, helps maintain the skin and is necessary for night vision. It is also necessary for normal growth and formation of bones and teeth. For Vitamin A only, 1mg translates to 833 IU.
Choline
A lipotropic substance sometimes included in the vitamin B complex as essential for the metabolism of fats in the body. Precursor to acetylcholine, a major neurotransmitter in the brain. Choline prevents the deposition of fats in the liver and facilitates the movement of fats into the cells. Deficiency leads to cirrhosis of the liver.
Copper
An essential mineral that is a component of several important enzymes in the body and is essential to good health. Copper is found in all body tissues. Copper deficiency leads to a variety of abnormalities, including anemia, skeletal defects, degeneration of the nervous system, reproductive failure, pronounced cardiovascular lesions, elevated blood cholesterol, impaired immunity and defects in the pigmentation and structure of hair. Copper is involved in iron incorporation into hemoglobin. It is also involved with vitamin C in the formation of collagen and the proper functioning in central nervous system. More than a dozen enzymes have been found to contain copper. The best studied are superoxide dismutase (SOD), cytochrome C oxidase, catalase, dopamine hydroxylase, uricase, tryptophan dioxygenase, lecithinase and other monoamine and diamine oxidases.
pH
A measure of an environment's acidity or alkalinity. The more acidic the solution, the lower the pH. For example, a pH of 1 is very acidic; a pH of 7 is neutral; a pH of 14 is very alkaline.