Introduction

New research about methylation since 2005 has displaced vitamins and minerals in explaining how the body works.  Linking vitamin C to scurvy or vitamin D to ricketts may prevent these diseases but does not give us a complete bio-chemical explanation.  This article explains the chemical links between vitamins and diseases with methylation and its importance to health. Costello: Vit Bs & Methylation  2001  Understanding methylation helps you become aware of the effect your diet and lifestyle have on methylation.

Although many factors impact disease risk, a growing body of research and clinical experience suggests genetically-targeted nutritional supplementation may have far-reaching health benefits.

Methylation

Oh .... what is methylation?  Methylation is a biochemical process that occurs in every cell in our body occurring billions of times/second. Methylation involves methyl groups. We are finding out now that if you can have enough methyl groups [CH₃] in your diet, you can start removing or chelating out some of the bad toxins. Syed: Methylation & air pollution 2013

For example, Methyl groups like Betaine [ illustration on right ], or trimethylglycine (TMG).  Betaine is found in beets.  It's a carbon with three hydrogens [H].

When methylation is working, you’ll feel full of energy, in a good mood and you will feel generally well. When it is not working, you will feel tired, depressed, irritable, run-down, susceptible to infections, foggy-brained, and just plain “toxic.”  DR. Doni Wilson  Juicing with beet, carrot and celery gives you a methylate properly !

The surprise finding in this article was that B vitamins are essential for Methylation. Skokawa: B 3 & preventing cancer  2009  Although we have been brain washed to think of vitamins as being the big determiners of health, new research points a finger at methylation as being more important than vitamins. Mehtylation explains why our bodies may not be able to absorb nutrients and supplements more readily, why we may be predisposed to constipation, cancer, diabetes, heart disease, asthma and other disorders. Methylation requires that all the nutrients and enzymes work together in unision.  You probably think that methylation does not apply to you; however, read on because knowing about methylation could improve or save your life.

"Methylation is a biochemical process involved in almost all of your body's functions! What is methylation? Without getting too technical, methylation is the addition of a single carbon and three hydrogen atoms [called a methyl group = CH₃] to another molecule. The removal of a methyl group is called demethylation. Think of billions of little on/off switches inside your body that control everything from your stress response and how your body makes energy from food, to your brain chemistry and detoxification. That's methylation and demethylation." Corey: Methylation & health 2015

Methylation explained by Dr.Mark Hayman

What's the big deal with Methylation?

It should be obvious by now that body disorders reflect the person’s ability to properly detoxify, repair tissue damage and fight infections.  This explains the severe symptoms that come and go in some people, and why some folks herx [feel sick] so badly and others don’t.

Without methylation there is no life. Methylation: SAME

• Affects fetal development, brain function
• Regulates gene expression
• Preserves the fatty cell membranes; serves as the methylating agent in the synthesis of:
 Various hormones and neurotransmitters - including SEROTONIN
 MELATONIN, NOREPINEPHRINE (adrenaline)
 NOREPINEPHRINE. DOPAMINE, and HISTAMINE
 DNA/RNA
 Protein
 Creatine (an important energy reservoir in muscle tissue)
 Phospholipids

The process of methylation turns genes on and off; this means it affects your DNA or genetic code. The ability to methylate helps you process toxins and hormones. For example, estrogen… you make it in your body, and you also get it from xenobiotics [ chemicals in shampoos, pesticides, herbicides, plastics and more ]. If you can’t break down estrogen and get it OUT of your body, you could develop all sorts of disorders. Cohen: Methylation & diseases 2014

Methylation also plays a role in making and breaking down various neurotransmitters, such as energy producing epinephrine and sleep producing melatonin. Most people are concerned about making enough neurotransmitters. If there’s a problem breaking neurotransmitters down, then they will hang around in excess which may cause unwanted issues such as seizures, insomnia, panic attacks and fits of rage to name a few. Cohen: Methylation & diseases 2014

Consider the people who might have a methylation problem: Children with autism, anyone with a seizure disorder, neurological condition, Alzheimer’s disease, cancer, severe Lyme disease, chronic infections, low T cells or reduced NK cells, diabetes, allergies, fertility issues, miscarriages, cardiovascular disease, chronic fatigue, anxiety or any psychiatric illness.   Cohen: Methylation & diseases 2014  Williams: Methyl Gp regulation 2007   Pandika: methylation & asthma 2015

Other research has clearly linked impaired methylation with B vitamins and autoimmune conditions.  Richardson methylation & vit B connection 2003  Costello: Vit Bs & Methylation  2001  Skokawa: B 3 & preventing cancer  2009  "Reductions in rat growth rates accompanying B vitamin deficiencies are consistent with the importance of B vitamins in cellular energy metabolism. Other adverse events observed in our study include hair loss, weakness, loss of appetite, inflammation, dermatitis, and bloody discharge. Necropsy showed reductions in liver and heart development, and absence of the thymus."  Riordan: Vit B study 2012

Corey has reinterpreted genetic disorders and impaired methylation as linkages to various body processes below:   Corey: Methylation & health 2015  Williams: Methyl Gp regulation 2007

• The stress (fight-or-flight) response
• The production and recycling of glutathione — the body's master antioxidant
• The detoxification of hormones, chemicals and heavy metals
• The inflammation response
• Genetic expression and the repair of DNA
• Neurotransmitters and the balancing of brain chemistry
• Energy production
• The repair of cells damaged by free radicals
• The immune response, controlling T-cell production, fighting infections and viruses and regulating the immune response

Methylation defects reduce the person’s ability to properly detoxify, repair the damage and fight the infections.  This explains the severe symptoms that come and go in some people, and why some folks herx [feel sick] so badly and others don’t.

If you lack vitamins and minerals, your ability to drive the methylation pathway is limited. Why? Because these nutrients are needed to help make the most active form of folate in your body known as methylfolate. These include:  Cohen: Methylation & diseases 2014

• Zinc
• B2/riboflavin
• Magnesium
• B6/pyridoxine
• B12/methylcobalamin
Folate [ from food or folinic acid ]

B vitamins are involved in Methylation.  Vitamins B2, B6, B12 are needed for this biochemical process. SAMe is also a supplement that supports methylation.  Costello: Vit Bs & Methylation  2001

People with a methylation difficulty have trouble eliminating poisons.  These build up in the body and that is what contributes to many health concerns. An example of such poison blockage is high levels of acetylaldehyde, a potent neurotoxin released when drinking alcoholic beverages.  Detoxifying acetylaldehyde allows methylation to clear this alcohol poison and that should help reduce symptoms of drunkeness.

If you can’t methylate properly, you cannot produce CoQ10, carnitine, creatine or ATP [energy]. You will also have nerve pain termed “neuropathy.” That’s because the methylation process helps make the protective wrapping around your nerves.

Methylation Cycle:

There are four cornerstones to the methylation cycle and on each cornerstone sit four molecules namely homocysteine, methionine, S-adenosylmethionine (SAMe) and S-adenosylhomocysteine. Each of these molecules leads into the next one by means of enzymes. The important co-factors that allow this to happen are the B vitamins such as folic acid, vitamin B12 and vitamin B6.

The methylation cycle is animated in the video below:

Video:  7:36 mns

Source: Caledonia

In converting from S-adenosyl methionine into S-adenosyl homocysteine, a methyl group is given up and this can be used to stick on to other molecules - hence the name, the methylation cycle. However, there is a particular bio-chemical glitch here. In order for the methylation cycle to work these B vitamins have to be in their activated form, namely methylcobalamin, folinic acid and pyridoxyl-5-phosphate.

In order to get cobalamin [ vitamin 12 ] into methylcobalamin, the methylation cycle has to be working. So if this cycle has crashed completely, the body can't make methylcobalamin in order to get it up and running again. As an example: vitamin B12 deficiency is often found in vegetarians and this can predispose them to cardiovascular disorders. Woo: B12 deficiency & CVD 2014

Since this cycle is so fundamental to other biochemical cycles including trans-sulphuration and folate metabolism, it has to change the vitamin B6, folinic acid and cobalamin into the active forms necessary for the methylation cycles to work. This means that in order to get this cycle up and running initially we have to prime the pump with the activated vitamins. Hopefully once the methylation cycle is up and running, it can start other bio-chemical processes functioning and get the body to work properly.

Methyl Group

To better understand methylation, we need to understand the methyl group.  A methyl group [Me] is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms — CH₃. [ illustrated by diagram on right ] Such hydrocarbon groups occur in many organic compounds [ compound represented by symbol 'R' in diagram ]. It is a very stable group in most molecules.  Methyl group is the chemistry that makes methylation work. Williams: Methyl Gp regulation 2007

The methyl group has numerous helpers that help make methylation work.  The methyl group turns the chemical switches on or off.  Understanding the methylation cycle starts with methyl enzymes activating or stopping body processes from working.  These enzymes include: Lynch: Histamine Intolerance, MTHFR and Methylation 2015

• MTHFR – stands for Methylenetetrahydrofolate reductase. It converts folic acid to methylfolate [5MTHF]
• MTR – Methionine Synthase uses methylfolate (folate) and methylcobalamin [B12] to turn homocysteine into methionine
• MTRR – Methionine Synthase Reductase creates SAM [SAMe] and electrons that make energy in the mitochondria
• BHMT – The backup system in the liver and kidneys that can also make methionine from choline and TMG
• CBS – Removes homocysteine from the MTR/MTRR cycle and converts it into cysteine and glutathione

Epigenetics

Another component of making methylation work is the link to genetics, or epigenetics.  Epigenetics is the study of factors that influence whether genes are turned off [silenced] or on [activated] when cells are replicated.

Turning genes on and off means it affects your DNA or genetic code. An example of such genetic coding are small non-coding MicroRNAs [miRNA]. These regulate gene expression.  Recent evidence suggests that miRNA expression may be implicated in a wide variety of genetic defects as noted below: Syed: Methylation & air pollution 2013   Cohen: Methylation & diseases 2014  Methylation, folate and birth defects  Krakowsky Nutrition impacting epogentrics 2015  Skokawa: B 3 & preventing cancer  2009   Stidley Methylation, food & smoking 2019  Woo: B12 deficiency & CVD 2014

• Diabetes
• Fibromyalgia/Chronic Fatigue Syndrome
• Cancer
• Pulmonary Embolism
• Addictive Behavior, even alcoholism
• Insomnia
• Autism or down’s syndrome
• Frequent miscarriages
• Bipolar or manic depression
• Allergies or Multiple Chemical Sensitivities
• Atherosclerosis
• Spina Bifida or Cleft Palate or Neural Tube Defects
• Multiple Sclerosis and other Autoimmune Disorders
• Hashimoto’s or Hypothyroidism (visit The Thyroid Summit online)
• ADD or ADHD
• Dementia/Alzheimer’s
• Schizophrenia
• Anxiety
• Neuropathy
• Lyme Disease*
• Chronic Viral Infections

* Usually in severe cases, the symptoms are due to toxin build-up; please note the methylation defect does not cause Lyme, which is a tick-borne illness. But the infection causes ammonia, quinolinic acid, acetylaldehyde, etc..

Nutrients affect people differently, depending on genetic variation. "One size does not fit all!" We have different genetic backgrounds, different life styles, and so on. You may need to get a DNA test to determine which genes may be affecting your methylation.  Science has discovered that there is a connection between diet and the epigenome [ Chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring. ].  Just as mapping our gene variations gives us a window into our personalized medical needs, so might a profile of one's unique epigenome. Formed through a lifetime of experiences beginning in the womb, our epigenome may provide a wealth of information about how to eat better.

Enter the future field of nutrigenomics [ how the foods we eat interact with our genes to affect our health ], where nutritionists take a look at your methylation pattern and design a personalized nutrition plan. It can help us understand how to eat or which supplements to use based on our genetic profile.  Berardi:Nutrigenomics & Dr El-Sohemy 2008  Krakowsky Nutrition impacting epogentrics 2015  Your informed doctor can already tell a lot about the your disease risk by looking at your family health history and doing a DNA test.  But .... the medical application of this information is somewhat controversial as the evidence for such application may not be all that complete. Pavlidis: Nutrigenomics controversy 2015  So you may have difficulty at this time finding out how the foods you eat interact with your genes and health. In spite of such limitations, you should not give up discussing with your health care provider the possibility of methylation and nutrigenomics helping you. 

Toxin build-up

People with a methylation difficulty have trouble eliminating poisons and toxins.  Toxins build up in the body and that is what contributes to many health concerns.  Today we are exposed to a variety of environmental poisons that are absorbed into our body by inhaling them, absorbing these through the skin or ingesting them in our food.  Syed: Methylation & air pollution 2013   Pandika: methylation & asthma 2015   Stidley Methylation, food & smoking 2019

The "body burden" of chemicals, as tested by the Atlanta-based Centers for Disease Control and Prevention every two years, has found that the average American now [ 2010 ] has 116 synthetic compounds in his or her body. Smith: chemicals make Y sick

"It is common knowledge that 80% to 90% of most chronic health conditions are triggered by toxins. Toxins are carcinogens which cause damage to our DNA, and brain function, cause cells to divide faster than their normal rate, thus causing all kinds of cancer, as well as neurological disorders and so forth." Paull team: Toxins

The ability to methylate helps you process toxins and hormones. For example, estrogen… you make it in your body, and you also get it from xenobiotics [ chemicals in shampoos, pesticides, herbicides, plastics and more ] if you can’t break down estrogen and get it OUT of your body, you could develop all sorts of disorders. Cohen: Methylation & diseases 2014

Another example of toxicity are high levels of acetylaldehyde, a potent neurotoxin released by the yeast infection Candida, and also a by-product of drinking alcohol [even red wine] is an example of a body toxin that blocks methyation in the body.

If you can’t methylate properly, you cannot produce CoQ10, carnitine, creatine or ATP [energy]. You will also have nerve pain termed “neuropathy.” That’s because the methylation process that normally helps make the protective wrapping around your nerves is blocked.

These few examples of toxin build-up in the body and that methylation can remove these from the body tells us that the body has a natural detoxification process.  You do not need to use detox diets to cleanse your colon, although these may help.  Instead, concentrate on cleansing the body of toxins by activating methylation.

Opening up the methylation road block helps clear your body of poisons and that should help reduce illness symptoms. Methylation challenges the traditional ways we have been led to believe we should detoxify; like fasting and ingesting special foods.

It All Starts With Your Gut

"High-quality probiotics are incredibly important to people with a methylation problem because if you let Candida overrun your gut, you get excessive amounts of Candida’s toxin called acetylaldehyde. I should tell you that acetylaldehyde is also a break down product of drinking alcohol. So job one is to repair the digestive tract and stop drinking alcohol. Optimize gut flora. The less candida you have, the less acetylaldehyde. You may have yeast overgrowth and not even know it. People who have been drinking a long time have been mugged of thiamine and probiotics."  Cohen: Methylation & diseases 2014

Dr. Andrew Rostenburg - Gut Origin of Methylation problems video: 19:05 mns.

Source: Caledonia 

We understand getting sick from outside our body, like getting a virus that causes flu or a chemical toxin; or we can get sick from the inside, like an organ not functioning properly. But what we were not aware is that feelings of discomfort and illness may be related to the bacteria in our digestive system.  We can get sick from the the wrong kind of bacteria or when the proper balance of good and bad bacteria in the body is disrupted.    You may find a very good and easy to understand article by two medical doctors, Kay Judge and Maxine Barish-Wreden, from Sacramento, California, about how obesity may be linked to the bacteria in our gut. Judge: gut germs linked to obesity 2013

Researchers since 2000 have discovered that there are over 400 good and bad bacteria living in the large intestine or colon.  If the normal balance of 80 - 85% good and 15 - 20 % bad bacteria is disrupted, then the bad bacteria multiply and can cause many of our illnesses and diseases.  Today, most of us show the reverse ratio; therefore, it’s no coincidence that the incidences of chronic and degenerative diseases have multiplied dramatically since World War II.  Common everyday symptoms of not feeling good [ intestinal dis-balance of bacteria ] are bloating, abdominal cramping, constipation and diarrhea. Sorochan: Immune digestive link 2013

The good news is that changes to the mix of microbes in the digestive tract have already successfully treated disorders and illnesses like leaky gut syndrome, stomach ulcers, inflammatory bowel disease and Crohn's disease. Sorochan: Immune digestive link 2013   Restoring the healthy balance of  80%good and 20% bad bacteria in the gut will help methylation.

And now, a little information about histamine and Homocysteine

Histamine and Homocysteine are both part of the methylation cycle.

Histamine:  As an integral part of the immune system, histamine is involved in immune system disorders,  allergies, regulates physiological functions in the gut and acts as a neurotransmitter.  Histamine is involved in the inflammatory response and has a central role as a mediator of pruritus [ itchy skin ].  As part of an immune response to foreign pathogens, histamine is produced by basophils and by mast cells found in nearby connective tissues. Histamine increases the permeability of the capillaries to white blood cells and some proteins, to allow them to engage pathogens in the infected tissues. Histamine is also regulated by methylation. In order to determine the actual functional methylation status in the body, whole blood histamine must be measured. Histamine levels correlate with the functionality of the methylation process. Histamine and methyl are inversely related to one another. That is to say, if whole blood histamine is low, the individual will be over-methylated and if it is high, they will be under-methylated. The protocols to treat the two conditions are different.

Homocysteine:  Once a SAMe molecule [ part of the methylation cycle ] loses its methyl group, it breaks down to form homocysteine, which is potentially toxic if it builds up within cells.  SAME

SAMe or S-Adenosyl methionine:  is found in almost every tissue and fluid in the body. SAMe circulates in the blood naturally and acts as a 'methyl donor'.  SAMe donates a methyl group [ CH₃ ] to another molecule to make that molecule bio-active!  Most SAMe is synthesized from the amino acid, methionine, and consumed in the liver. SAMe activates cellular methylation reactions.  U Maryland: SAMe   Examine: SAMe information 2015  NCCIH: SAMe 2013   Other methyl donors include: folate, B12, TMG [Betaine], DMG and DMAE; as well as some vegetables like onions, garlic and beets.

S-Adenosylmethionine (SAMe) is involved in many important processes. SAMe plays a role in the immune system, maintains cell membranes, and helps produce and break down brain chemicals, such as serotonin, melatonin, and dopamine. It works with vitamin B12 and folate (vitamin B9). Being deficient in either vitamin B12 or folate may reduce levels of SAMe in your body. U Maryland: SAMe   Examine: SAMe information 2015  NCCIH: SAMe 2013

Homocysteine, which is like a bad drunk of metabolism, is the result of a missing a methyl group. When you start looking at the bad estrogen, toxins and homocysteine, they are missing methyl groups. If you have enough methyl groups in your diet, you can start chelating out some of these bad toxins.  People who eat raw food have a lot of methyl groups in their diet, especially if they drink vegetable beet juice and eat goji berries.  Borscht is made with beets and other vegetables and it is the methyl group betaine found in beets that restores detoxification and makes you feel good. 

Cholesterol-lowering medication is a result of the whole theory that believes that high cholesterol is associated with imminent heart attack. Half the people who have a heart attack have normal cholesterol, but all people who have a heart attack have elevated homocysteine – so elevated homocysteine is a better marker than cholesterol for predicting heart disorders.  If you review your homocysteine levels, then you will know how close you are to a heart attack.   Homocysteine is by definition missing a methyl group. So if you take stuff that is able to methylate, like beets, goji berries and B vitamins, then you naturally bring down homocysteine. Research shows us that if you have adequate vitamin B6, vitamin B9 and vitamin B12 in your diet, then your homocysteine goes down.  Wolfe: New info Methylation  2011

Lastly, methylation can regulate your immune system. If you have a shortage of methyl groups, or your methylation cycle is interrupted, any or all of these immune processes can become compromised, and you could get sick. Research has clearly linked impaired methylation with autoimmune conditions.   Richardson: ethylation & immune system    Corey: Methylation & health 2015

Testing for how well the methylation works: We don't have a simple test to see how well the methylation cycle works. What we can do is measure levels of homocysteine and SAMe. If these were elevated this would show a blockage in one part of the pathway. Indeed, a raised homocysteine would be a major risk factor for arterial disease, almost certainly because this represents blockages in the methylation cycle. However, one could have a normal homocysteine and normal SAMe but blockages elsewhere in the system, which would still impair the ability to methylate. So there is no simple test.  McNill: Methylation  2015

Treatment Suggestions video: 5:31 mns

Foods rich in methyl groups:  [ The list below is incomplete but a quick reference. ]

 Beets
 Borscht soup
 Dark green leafy vegetables
 Spinach
 Romaine lettuce
 Broccoli
 Spirulina

Here is a list of foods rich in methyls from University of Utah:

 Methyl donors in the column on the left are nutrients involved in a biochemical process called methylation, in which chemicals are linked to proteins, DNA, or other molecules in the body.  The foods supplying these nutrients are in the middle column.  The column on the right explains briefly the role of nutrients.  Dietary intake of methyl donors has been shown to affect the risk of developing a number of diseases, including heart disease and cancer.  ATS: Food & methyl donors 2014  Han: Diet & methyl doners 2013

Here is a helper web-site that is free, sets up a custom program for you, complete with a menu, exercise goals, a shopping list, and helps you loose weight. You need to do the rest: Get Healthy

Final last words:  If you have an auto-immune disease or disorders like lupus, psoriasis, arthritis, autism, digestive disorders, continuous constipation, memory problems, obesity, diabetes, itchy skin, cannot sleep,  migraine headaches or other disabilities, then your methylation is not working properly.  You should consult with an informed health care provider and a bio-chemist to help turn the appropriate switches on or off.  Search for an experienced methylation therapist in your area.

In light of the information presented in this article, activating methylation can be a game changer for everyone. It will change the way medicine is practiced!

ALERT:  Your feedback on this article is most appreciated. Thank you: E-mail author

Go to main menu