Methylation

What is methylation?

Methylation and glutathione

Causes of methyl imbalance

Tests for dysfunctional methylation

What is histadelia / under-methylation?

Symptoms of histadelia / under-methylation

Treatment of histadelia / under-methylation

What is histapenia / over-methylation?

Symptoms of histapenia / over-methylation

Treatment of histapenia / over-methylation

References

What is methylation?

Methylation is the addition of a single carbon and three hydrogen atoms (called a methyl group) to another molecule. Almost every biochemical reaction in the body involves methylation. In contrast, demethylation is the removal of methyl groups.

If you have a shortage of methyl groups or your methylation cycle is somehow compromised, numerous processes in your body are affected and you can get sick.

Methylation is involved in many processes, such as:

• Brain chemistry. The production of neurotransmitters and the balancing of brain chemistry.
• Detoxification. The removal of hormones, chemicals and heavy metals.
• Energy production.
• Glutathione production and recycling. Glutathione is the body's master antioxidant.
• Hormone production, stress (fight-or-flight) response.
• Healing, repair and reproduction. Genetic expression and the repair of DNA. The repair of cells damaged by free radicals.
• Immune function and inflammation. Regulating the immune response, controlling T-cell production and fighting infections.

Methylation and glutathione

Glutathione is an important antioxidant that prevents cellular damage caused by reactive oxygen species. In addition, glutathione contains sulphur groups, which are sticky compounds that adhere to toxins and heavy metals before excretion.

A healthy body makes sufficient glutathione from the amino acids cysteine, glycine and glutamine. It can also recycle glutathione via methylation using methyl donors like vitamin B12, folate, betaine and other nutrients. Under normal conditions, your body makes and recycles enough glutathione to handle all the toxins that you're exposed to. However, if you have a high toxic load or suffer from under-methylation (histadelia), you may benefit from the treatments suggested below.

Optimal methylation is important for everyone, but improving methylation is especially important if you have an autoimmune condition. Methylation plays a central role in the production and recycling of glutathione, the body's master antioxidant. Glutathione also reduces inflammation and assists other antioxidants like vitamins C, E and lipoic acid.

Glutathione optimal diet:

• Glutathione precursors. Eat foods that are high in the amino acids required to make glutathione - cysteine, glycine and glutamate. The richest sources are meats, poultry, fish, egg yolks and dairy. Matured cheeses are a good source of glutamates, as is fish sauce.
  
  For vegetarians, the best sources are quinoa and buckwheat. Small amounts of some of the three amino acids are found in banana, beans, bell peppers (capsicum), broccoli, Brussels sprouts, cauliflower, cabbage, cucumber, garlic, kiwi fruit, mushrooms, onions, peas, pumpkin, spinach, tomatoes (ripe) and walnuts. Soy products are a good source, but are not recommended as a food in Grow Youthful.
• Sulphur-rich foods. Sulphur is a key component of glutathione, so ensure you get sufficient sulphur-rich foods such as garlic, onions and cruciferous vegetables (brassica) like broccoli, cauliflower, cabbage, watercress and bok choy.
• Selenium. Selenium plays an important role in the production of glutathione. The best food source is Brazil nuts. Eat just one or two per day.

Causes of methyl imbalance

Here are the possible causes of over-methylation (histapenia) and under- methylation (histadelia).

• Imbalance of the gut biome, deficiency of certain bacteria or fungi.
• Dietary imbalance or deficiency.
• Elevated histamine.
• Histamine intolerance.
• Insufficient sunlight, both on your skin and in your eyes. Dawn is the most important sunlight to see every day that you can. Morning sunlight, from dawn until 10am, is the most beneficial. Get it in your eyes (by not wearing sunglasses and being outside), and on your skin if you possibly can, even in winter. Sunlight affects your gut biome, digestive system, the entire hormonal system, and the ability to process sulphur.
• Pyroluria is often associated with methyl imbalance.
• Hormonal imbalance, typically high estrogen.
• MTHFR is an enzyme (methylenetetrahydrofolate reductase) that regulates the methyl cycle. The MTHFR gene is necessary for its creation. If the gene is abnormal, the methyl cycle may function abnormally. MTHFR gene polymorphism is directly associated with both poor methylation and over-efficient methylation.

Tests for dysfunctional methylation

Are you suffering from being over-methylated (Histapenia) or under-methylated (Histadelia)? Both over and under methylation can cause a variety of symptoms including mental distress and psychological disorders. It is important not to try to diagnose yourself from the list of conditions below, because many of the symptoms overlap and treating the wrong condition will end up doing more harm than good.

Histamine test using either blood plasma or urine.

Basophil blood test. If a histamine test shows levels to be high, then a basophil blood test is required to confirm histadelia as opposed to histamine intolerance.

The best way to confirm that you truly have a methylation problem is to get a MTHFR gene test. This is a simple blood or saliva test kit that can be ordered online, or done by your health practitioner. It will analyse the underlying methylation problem.

What is histadelia / under-methylation?

Histadelia, also known as under-methylation is a genetic, metabolic and biochemical condition in which too much histamine is produced because too few methyl groups are there to break down excess histamine. The body makes a compound called SAM-e (S-Adenosyl methionine) to donate methyl groups. Those suffering from histadelia have low levels of SAM-e. The consequence is elevated blood histamine levels that have an effect on mental and physical health. Histamine is involved in allergies and inflammation, and high levels of histamine can cause unwanted inflammatory responses. Histamine also acts as a neurotransmitter which is why imbalances can affect brain chemistry. (1, 2)

Symptoms of histadelia / under-methylation

Bear in mind that if you are suffering from histadelia you may not experience all the symptoms listed below. Your symptoms will depend upon your particular genetic polymorphisms of the MTHFR gene as well as other factors. Here is a collective list of symptoms that people with under-methylation tend to exhibit.

• High blood histamine, causing allergic and inflammatory reactions ranging from itching, hives, runny nose, sneezing to asthma, period pain, shortness of breath and elevated oestrogen levels.
• Fast metabolism, high production of body heat.
• Frequent colds (influenza).
• High basophil count (2). This is usually associated with inflammation, infections and allergic reactions.
• Low serotonin.
• High homocysteine, directly in proportion to the degree of under-methylation.
• Low zinc.
• Low copper.
• High heavy metal levels. Proper methylation detoxifies the body of heavy metals and some other toxins. If a person is under-methylated, detoxifying may be inhibited.
• Headaches.
• Heavy perspiration, heat intolerance.
• High libido.
• Insomnia, difficulty sleeping.
• Anorexia nervosa.
• Lean body type with little body and facial hair. Large ears, hands or feet with longer fingers or toes.
• Muscle cramps or pains.
• Nausea. Easily nauseated.
• Higher blood pressure (hypertension) and tendency to cardiovascular disease.
• Respiratory and seasonal allergies. The under-methylator's elevated level of histamine may lead to more pronounced allergic reactions, particularly during seasonal transitions. Allergic rhinitis.
• Excessive production of stomach acid, saliva and tears.
• Low pain tolerance. Poor tolerance to any kind of pain.
• Aging more quickly than necessary.
• Autoimmune conditions.
• Cancer, increased risk.
• Chronic Fatigue Syndrome.
• Diabetes, increased risk.
• Digestive problems.
• Alzheimer's disease, increased risk.
• Miscarriages, infertility and problems in pregnancy, increased risk.



The under-methylator's personality / mental state

• Competitive. Histadelics tend to be extremely competitive in sports, business and other facets of life. Being competitive is a notable signal that a person may have insufficient methylation.
• Impulsive behaviour and a racing mind.
• Short concentration. Difficulty maintaining focus for a prolonged period.
• Inner tension. Histadelics may appear calm on the outside but may be filled with inner tension.
• Perfectionism and control. Not satisfied unless tasks are perfectly completed in accordance with their specific methodology.
• Social isolation. Some people may isolate themselves from others and prefer to be left alone, especially while working. Shyness.
• Addictions or an addictive personality. Using drugs and alcohol to counter blood histamine and provide a lift is common in high-histamine people. Sugar addiction is also common. High tolerance of addictive substances.
• Strong-willed.
• Aggressive.
• Self-motivated. They may be highly self-motivated in work, learning and other achievement, not needing any outside inspiration or encouragement to complete their tasks.
• Anxiety / panic attacks.
• Depression. People with histadelia do not at first seem to be depressed, looking like they are motivated and successful. They are often creative and have good ideas but suffer a constant inner tension and uncertainty about the success of their current projects and ventures. They cannot switch off their racing mind, and eventually their depression leads to crying and suicidal thoughts.
• Obsessive compulsive disorder and / or ritualistic behaviour. Rigid schedules and specific daily rituals to which they must adhere.
• Phobias. Irrational fears.
• Bi-polar disorder.
• Autism and other neurological disorders.
• Delusions. Poor perception of reality leading to delusions or beliefs that aren't based in reality. Psychosis. Schizophrenia.
• Oppositional defiant disorder (ODD).

Treatment of histadelia / under-methylation

Treatment normally takes 8 to 12 months before the patient feels noticeably better. The correct diet can be highly effective and successful over the long-term.

• Avoid high-histamine foods like fermented dairy products such as cheese (especially aged), yogurt, sour cream, buttermilk, and kefir. Avoid fermented vegetables, such as sauerkraut and kimchi. Avoid pickles or pickled vegetables and other foods. Avoid kombucha, and cured or fermented meats, such as salami and fermented ham.
• Small intestinal bacterial overgrowth (SIBO) and / or intestinal bacterial issues. Kefir and sauerkraut are two of the best sources of probiotic microorganisms, but because they are high-histamine foods they should be used with caution until you are aware of how they affect your body.
• Folic acid levels may be abnormally high in those with histadelia, so avoid high-folic acid foods like leafy green vegetables, citrus fruits, beans, cereals and grains, and rice. Avoid taking B Complex vitamins, especially vitamin B9 (folic acid).
• Histadelia causes low levels of calcium, magnesium, methionine and Vitamin B6, so consider them for supplementation. Other micronutrients that may need supplementation are choline, omega-3 fatty acids, SAM-e, vitamins B6 and B12, vitamin C and zinc. It is best to get trusted professional advice concerning supplementation, as it can be complex depending on your specific conditions.
• Copper may be deficient, or it may be in the body but in a bio-unavailable form (copper toxicity).
• Avoid alcohol, energy drinks, black tea, green tea, mate tea.
• Avoid gluten.
• Stress reduction, meditation.
• Exercise. In addition to being a stress outlet, exercise also boosts your glutathione levels and enables detoxification.
• Sleep. Get sufficient and good sleep. Studies show that lack of sleep can deplete glutathione.

What is histapenia / over-methylation?

Over-methylation (histapenia) is the polar opposite of under-methylation. Histapenia occurs when the level of methyl groups is too high. Methyl groups are very active in the brain, and high levels lead to overproduction of serotonin, norepinephrine and dopamine. This can cause problems such as reduced motivation, reduced libido, weight gain and confusion.

Histapenics often have:

• Elevated levels of serotonin.
• Low levels of histamine. It is unnecessary to use an over-the-counter antihistamines.
• Low basophil count, meaning less likelihood of allergic reactions. (2)
• High copper.
• Low zinc.

Symptoms of histapenia / over-methylation

Here is a list of possible symptoms. Understand that you will not exhibit every symptom on the list and that the severity of each symptom is highly subject to individual variation. There is even an overlap between some of the symptoms listed below and some of the symptoms of histadelia, so it is difficult to diagnose one or the other just based on symptoms. Before undergoing any treatment, it is best to get a definitive diagnosis.

• ADHD.
• Anxiety and panic attacks.
• Some writers suggest that Histapenics are more right brain dominated, being more artistic and musical.
• Depression, often displayed in lack of motivation and accomplishment.
• Dry skin.
• Food sensitivities. Highly sensitive to certain foods and / or chemicals.
• Frustration. Being easily frustrated when this is not justified.
• High pain tolerance.
• Low libido.
• Low motivation. Not competitive. Being a low achiever.
• Nervousness.
• Obsessions. Unlike histadelia, these obsessions are not usually accompanied by compulsions.
• Overweight.
• Paranoid thoughts or auditory hallucinations.
• Restless legs syndrome.
• Self-imposed isolation.
• Self-harm and self-mutilation.
• Sleep disorders.

Treatment of histapenia / over-methylation

I recommend that you use a health professional to decide which if any supplements are required for your specific needs. You probably will not notice any changes overnight, but may gradually feel better over the course of 3 to 6 months.

Supplements for histapenia:

• DMAE
• Folic Acid (Folate)
• Niacinamide (vitamin B3)
• Omega-3 fatty acids
• Vitamin B6
• Vitamin C
• Vitamin E
• Zinc

References

1. Jackson J A, Riordan H D, Neathery S, Revard C. Histamine Levels in Health and Disease. Journal of Orthomolecular Medicine, 1998, 13(4), 236-240.

2. Jackson J A, Riordan H D, Neathery S, Krier C. Blood Basophils and Histamine Levels in Patients. Journal of Orthomolecular Medicine, 2006, 21(2), 107-108.