The methylation cycle:

We are living in exciting times when new knowledge of epigenetics is opening doors to disease prevention and management. We can no longer trust “one size fits all” protocols. We must address each individual’s unique genetics and exposures to create a bioindiviualized programs. Epigenetics is a breakthrough in how we address disease and emotional dysfunction!

Methylation is a process critical for creating and maintaining DNA and new cells. It involves adding chemicals called “methyl groups” to proteins, DNA and other molecules. Methylation is important for the entire life process. It affects detox, aging, and survival. Dysfunction in methylation affects new cell synthesis which can contribute to autoimmunity. When genes are not methylated it can trick the immune system into reacting against itself.

Individuals with genetic methylation mutations have difficulty making regulatory T cells. T cells help the body control the B cells and prevent autoimmune antibodies. If you are not making adequate T cells, then you may end up with auto immune antibodies. Methylation also plays a role in the ability of the immune system to recognize foreign bodies. If it does not recognize foreign bodies, it cannot respond to them. In this way, assisting the function of the methylation cycle could be a key in managing autoimmune disease.

SAMe (S-adenosyl methionine) is the most active methyl donor in the body. If we don’t have enough SAMe or if it cannot be recycled properly, we can see issues of neurotransmitter imbalance, difficulty with detoxification, issues with the formation of myelin surrounding the nerves and cellular energy generation.


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1st cycle

The first cycle involves the amino acid methionine. The purpose of this cycle is to

convert homocysteine into methionine. Methionine is the building block of protein. Excessive homocysteine is related to heart disease, stroke, liver damage and Alzheimer’s. Therefore, it’s necessary to convert homocysteine into methionine. The end process of methionine cycle is the elimination of toxins from the body. Genetic mutations can cause a block in the normal process of methylation. We will discuss this in detail along with alternatives later

2nd cycle

The second cycle of methylation is the folate cycle. Folate is the B vitamin from leafy greens and beans. It is essential to break down folate so that it can be used for neurotransmitter balance and detox. The folate cycle and the methionine cycle connect to each other like two gears. B12 is a critical factor to connect and drive the first methionine cycle and the second folate cycle.

3rd cycle

The third cycle in the methylation ,is the BH4 cycle. BH4 regulates positive feelings and is related to serotonin and dopamine. Your body converts tryptophan to serotonin using BH4. Serotonin makes you feel confident and satisfied. Lack of serotonin causes depression. BH4 also helps turn the amino acid tyrosine into dopamine. Dopamine gives the satisfaction from achievement. Imbalances of dopamine cause ADD/ADHD and a lack of dopamine causes Parkinson’s. Mutations in the methylation cycle affect BH4 levels. BH4 is further compromised by environmental toxins such as Mercury, Lead and Aluminum. The addition of a bacterial infection (such as Lyme) can create the perfect storm.

4th cycle

The forth and final cycle of methylation i
s the urea cycle. The urea cycle helps rid the body of ammonia through urine. Lack of BH4 not only affects Serotonin and Dopamine but it also affects this urea cycle. The BH4 cycle helps reduce oxidation so lack of BH4 can cause the urea cycle to create neurological inflammation.

Using nutrition or supplementation to balance the methylation cycle helps regulate the off / on switch of epigenetics. While your DNA will not change, your epigenetics can change. Epigenetics gives your body a way to compensate for inherited diseases. This is why you are not a victim of your genetic makeup. Knowledge is the key.

The term “methyl group” refers to a group of molecules which is critical for health and well being. These methyl groups move around the body to turn genes on or off. This is critically important. Methyl groups serve as a mechanic for your DNA. Imagine if your mechanic quit. Over time there would be an accumulation of issues. The methylation cycle can have blocked areas that can be bypassed through the use of nutrition and supplements. There is no point to learn about your genes if you have no way to correct mutations. Thankfully we do have ways to address these blocks. Just as we might take alternative routes to avoid construction we can take advantage of alternative pathways.

By changing the function of the methylation pathways you can even affect future generations. Epigenetics is the second change for your own health as well as that of your ancestors. This also helps explain how identical twins with the same DNA can have different health conditions. Infections, environmental toxins and stress affect our epigenetics. We cannot always control infections so we must do our best to avoid toxins and reduce stress in our lives.


Methylation is highly dependent on B vitamins.


You are probably aware that there are several B vitamins that make up B-complex. If an individual has mutations in MTR, MTRR, or MTHFR they will have to chose B12 and Folate carefully and according to their genetics. It is important however to establish a base support of the remaining B-vitamins. These include: Thiamin, Riboflavin, Niacin, Vitamin B6, Pantothenic Acid, and Biotin. Seeking Health, a supplement company, creates a product called “B-minus” which is an easy way to establish a B-complex base prior to adding B12 or folate.

The ultimate goal is to get the methylation cycle functional as described, however, this can initially cause an excessive detox reaction. For this reason it is smart to first address the short cut to help restore methylation.


If there is a block in the B12 juncture, between the methionine cycle and the folate cycle, you can bypass this juncture through a shortcut. This shortcut goes directly through the Methionine cycle. To help transform homocysteine directly into methionine we can use compounds called “phospholipids”. These include:

DHA Docosahexaenoic acid PS Phosphatidylserine
PC Phosphatidylcholine
PE Phosphatidylethanolamine PI Phosphatidylelinositol

Ask a knowledgable practioner about using phospholipids as they can be a way to jumpstart methylation prior to addressing B12.

We can also use TMG (Trimethylglycine) as a method to shortcut the methylation cycle. Our body makes TMG but this can be disrupted due to heavy metal toxicity. Beetroot juice is a good source of TMG. Whenever possible let food be your medicine!


Between the Methionine and Folate cycles we find the B12 at the junction of the gears. As a reminder the Methionine Cycle has the purpose of transforming homocysteine into methionine. A critical mineral involved in B12 absorption is lithium. Adding B12 before addressing lithium will further deplete this critical mineral.

The American College of Nutrition suggests that 83% of our population is lithium deficient. This can be measured through hair and blood tests.

Average intake is recommended at 650-3100 micrograms with therapeutic doses up to 2700 mg. Please seek the guidance of a qualified Functional Medicine Doctor before attempting therapeutic dosing. If you are taking thyroid medication or iodine you may need more lithium.

Prior to adding B12 it’s important to be sure you have adequate Lithium because it is essential for B12 transport. If we add B12 prior to Lithium we will further deplete lithium supplies. Lithium is important for emotional control and reduces aggressiveness.

As more B-12 is added, you will also need to assure adequate lithium support. This is a missing link in B-12 supplementation.

(as a side note: data indicates many people with Lyme disease are low in Lithium)


Once you have jump started methylation using the shortcut, and supported lithium, we can slowly start to add the proper form of B12. To do this we need an individuals full genetic picture.

B12 is called Cobalamin. B12 is water soluble so it doesn’t stay in the body for long. It is important for energy, memory and for healthy red blood cells. Lack of B12 is well documented to cause a vast range of neurological disorders. It is easily depleted through poor diet, alcohol, medication and aging. Vegetarians often lack B12.

The most common form of B12 we find in supplements is Cyanocobalamin.

Cyanocobalamin contains a cyanide molecule and must be converted in the body. It will first be converted to Hydroxy B12 and the body must get rid of the toxic cyanide molecule. It is frequently found in supplements because is it the most stable and least expensive. I do not recommend this form of B12 for anyone.

Methyl B12 is another common form but it cannot be tolerated by everyone. Those with COMT genetic mutations should avoid Methyl B12 because they have difficulty with excess methyl groups. Those who cannot tolerate caffeine will also want to avoid Methyl B-12.

Hydroxycobalamin or Hydroxy B12 is most easily used by the body. It is less common because it is difficult to work with and more difficult to keep in the active form. It is also more expensive. This is the form of B12 those with COMT mutations should take and I recommend it for everyone who is sensitive or chronically ill.

Adenosyl B12 is also a smart addition to Hydroxy B12 because it is helpful for cellular energy. It is typically added in smaller doses because it is not as versatile.

If you have not yet done your genetic testing and you are suffering with chronic illness I recommend you start with Hydroxy B12. B12 does not absorb easily in the gut, taking it sublingually by mouth is a preferred method. Even better, try to hold it in your mouth for 90 seconds.


The other B vitamin that we need to address in the methylation cycle is B-9 called Folate. Folate is important for neurotransmitter balance as well as detoxification.

The most popular form of folate you will find in supplements is Folic Acid. Folic Acid is of no use until it can be broken down. Individuals with MTHFR mutations cannot break down folate normally and may need a form called L-5 methyl THF. Even worse, unmetabolized folic acid can stay in your bloodstream for months and block or clog folate receptors. This makes those receptors unable to bind and utilize other forms of folate. This issue of blocking folate receptors is quite serious.

98% of those with Autism have the MTHFR gene mutations and it is also very commonly found with those with Chronic Lyme disease. This affects the ability to detox effectively.

About 45% of the population has the MTHFR C677T gene mutation. Because the MTHFR gene mutation is very common, Folic Acid should be generally avoided in my opinion. That may seem drastic, but new evidence in the field of methylation suggests avoiding Folic Acid completely, is wise for everyone. Folic Acid is synthetic and is not beneficial for anyone. I also encourage you to avoid processed food that is labeled as “enriched” or “fortified” because this means it’s “enriched” with folic acid. As always, the preferred source of vitamins is though food. Folate is found in leafy greens and beans. Your body knows what to do with food.

When supplementing with L-5 MTHF, it’s important to start out very slowly with low doses and gradually increase. This pathway is involved in detoxifying infections, toxins and heavy metals. If we open the pathway too quickly a healing crisis could occur.

As you can see the process of supplementing for genetic mutations should be done slowly and in layers. This is not a process that should be rushed. When we supplement for mutations we are supplementing for the “worst case scenario”. The goal is always to life a lifestyle that keeps your mutations in the “off” position.


About the Author OriginalRx

Original Rx is not "alternative" medicine...its original. A bioindividualized approach to wellness addresses your unique body and needs.

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