Methylation Enhancement

Below are a few all-natural tips to improve your methylation pathways. (1)

1. Eat healing greens.

Eating dark leafy green veggies daily provides you with natural folate (a methyl donor), necessary for proper methylation. Make sure to get a minimum of two cups of these healing foods daily.

2. Get B vitamins and folate.

B vitamins are methyl donors, especially folate, B6, B12 and riboflavin. Sources of B vitamins include fish, eggs, dark leafy greens, asparagus, almonds, sunflower seeds and walnuts.

3. In your diet is imperfect, support methylation with supplements, in particular magnesium and zinc. Never take folic acid supplement though, new research confirmed its nefarious effects, much better to get folate (B-9) via whole plant based foods.

4. Take probiotics.

Remember, the good bugs help produce and absorb B vitamins and folate.

5. Reduce chronic and toxin intake.

These toxic “splinters” burden your liver and un-necessarily use up methyl groups.

 Boosting Glutathione

In addition to making sure your methylation is operating at full capacity, you can increase your glutathione levels with the following strategies as both pathways are inter-related

1. Eat healing proteins.

Eating foods that are high in the glutathione precursors — cysteine, glycine and glutamate — will boost your glutathione. For those in need of a quick fix, wild omega-3 small fish will do the trick.

2. Eat sulfurous foods.

Sulfur is a key component of glutathione, so eating enough sulfur-containing foods is vital. Sources include garlic, onions and cruciferous vegetables like kale, broccoli, cauliflower, cabbage, watercress and bok choy.

3. Protein powder, maybe, for a quick fix if a totally holistic lifestyle is too difficult.

Undenatured whey protein powder boosts glutathione levels by converting cysteine into glutathione. If you’re allergic to whey (which comes from dairy), try a hypoallergenic rice protein powder. Take one or two scoops of protein powder per day in water, juice or smoothie.

4. Take selenium.

Selenium plays an important role in the production of glutathione. Take 200 to 400 mcg per day if holistic diet is deficient.

5. Optimize your antioxidants.

Vitamins CD and E all encourage higher glutathione levels.

6. Move your body.

Besides reducing stress and depression, exercise also boosts your glutathione levels and improves detoxification.

7. Get enough sleep.

Studies show that lack of sleep can deplete glutathione. Make sure you get between seven and 10 hours of sleep nightly.

8. Take herbs to support glutathione.

Studies show that milk thistle can boost glutathione levels. Take 100 to 300 mg daily or just eat.

9. Spice it up.

Curcumin raises glutathione levels in the liver — one more good reason to use this anti-inflammatory spice! Or, you can take a curcumin supplement.

Avoiding toxins, lowering your stress, healing your GI and consuming foods and supplements that support methylation and glutathione can enhance your body’s ability to naturally detoxify and heal.

If the reader needs clarification, the Institute offers workshops and coaching sessions to help guide you through the healing process.


Hacking Nutritional Support for Methylation

Here are some of the important ones that you can get through diet and, for some, you might need add some supplementation.

For folate, eat uncooked green vegetables, and for you beef liver lovers, it’s the top source. Folate requires active transport across the intestinal mucosa, so if you have IBS or other gut problems, you might not be absorbing enough.

Vitamin B12 (aka cobalamin) is the yin to folate’s yang – both are required at a critical point in the methylation cycle. If you’re a vegetarian, you will need to supplement regardless of genetic variants because it is found in highest quantities in animal products. Some supplements use cyanocobalamin, but if you have the MTRR genetic variant, you might want to consider methylcobalamin if your blood levels stay low after supplementing.

Vitamin B6 in it’s coenzyme form is involved in more than 100 enzyme reactions, mostly concerned with protein metabolism. Pyridoxal 5′ phosphate (PLP) and pyridoxamine 5′ phosphate (PMP) are the active coenzyme forms of vitamin B6. PLP is involved in the metabolism of one-carbon units, carbohydrates, and lipids. Tuna is the best source, followed by spinach, cabbage and bok choy. Go easy on the cooking since prolonged heat can degrade B6. Inflammation can lead to low B6 levels.

Mind your zinc levels. I could do a whole separate post on the role of zinc in immune health! Oysters, red meat, sesame and pumpkin seeds and lentils rank highest as food sources, but phytates bind zinc and will limit it’s absorption from grains, legumes, nuts and seeds. Another reason to soak them before using. GI disease, diabetes, and liver disease can decrease zinc absorption.

Choline is not a vitamin, but considered an essential nutrient. Humans only synthesize a small amount, so we all need to bump our dietary or supplement intake. If you don’t consume or supplement enough folate, the body draws on choline to recycle homocysteine, reducing the amount that can be used to produce phosphatidylcholine, and essential to keep your cell membranes fluid and functional. Shrimp, eggs and scallops top the list of food sources. If supplementing, the best type of choline is up for debate. You can search for those discussions. Citicoline is recommended by Dr. Bredesen for the ReCODE protocol.

Consider using a nutrition tracker, like MyFitnessPal or Chron-o-meter, for a short while to see if you are getting enough micronutrients. They can be tedious to use, but eye-opening. And make sure to test your blood levels and see if you are within range before deciding to supplement. In addition, prescription drugs, other supplements and aging can impact your ability to absorb and utilize vitamins. If you’re looking for specific foods that can boost specific nutrients, I like to use

And lastly, if you go back to the large Seeking Health diagram, you can look for other co-factors that could potentially be tweaked.

Hacking Genetic Variants

Supplementation might be needed with some of these genetic variants. Work with your doctor to get the appropriate labs done, and always start with low doses and work up to a level that works for your target range. For that reason, I do not recommend amounts because they should be based on your individual needs, except for a comment on where to start with methylfolate, mostly driven by personal experience. Some doctors may suggest higher doses, so I’m suggesting a starting point.


Start any B supplementation regime with methyl-B12 first, especially if your labs show low B12 status. This avoids a potential “methylfolate trap” where methylfolate can’t get converted due to lack of B12. For more on that, see
Use a methylated version of folate. This allows you to bypass the less efficient process of converting dietary folates to their active form. Too much methylfolate is a problem, too, so start low (400 mcg/day or less), and go up slowly. Side effects of too much methylfolate include irritability, insomnia, anxiety, headaches, migraines, palpitations, sore muscles and achy joints. If you feel any of these symptoms after taking folate, try taking 50-100 mg of niacin as nicotinic acid. Niacin is broken down by SAM, so it’s a good way to use up excess SAM (from excess folate).

It is also important to use methylfolate with MTHFR variants because there is competition between “active” folate and “inactive” folic acid. So, it’s best to avoid vitamins or processed food products with folic acid.
A Perspective on Systemic Nutrition and Nutritional Genomics

“Dietary folate and folic acid supplements compete with L-methylfolate at the blood-brain barrier. Unmetabolized folic acid is unable to cross the blood brain barrier and may become bound to folate binding receptors on the membrane, blocking absorption of the active form, L-methylfolate (Zajecka, 2007.)”
Avoid Nitrous Oxide gas at the dentist. This study shows that patients with a homozygous MTHFR 677C>T or 1298A>C mutation are at a higher risk of developing abnormal plasma homocysteine concentrations after nitrous oxide anesthesia.

Avoid Methotrexate. The analysis highlighted a significant association of 677C>T polymorphism with overall MTX toxicity, hepatotoxicity, hematological toxicity, and neurotoxicity. It also revealed an association with MTX toxicity in patients with rheumatoid arthritis.

Avoid Lamisil. “It was later noted that Lamisil’s mechanism of action interferes with cells’ methylation cycle, which we suspect compromises cellular function in people with the methylenetetrahydrofolate reductase genetic mutation.”

Check for hypothyroidism. In hypothyroid conditions, the hepatic activity of MTHFR is decreased.
Other Genetic Hacks

With the remaining genetic variants, I have not found many direct studies testing specific treatments. So, if you want to treat any of the following, here’s a starting point and feel free to check the Seeking Health diagram for other substrates and co-factors and go from there. N=1!


Test your folate, B12 and zinc levels. Supplement as needed to get within range.

Take care using methotrexate for rheumatoid arthritis if you have the A2756G G variant. This genotype was associated with MTX-induced accelerated rheumatoid nodulosis (MIARN). (

You might want to look at B12 metabolism genes, too, such as transcobalamin II (TCN2), which is essential for the uptake of vitamin B12 from the intestine. With variants, sublingual B12 might work better to bypass intestinal absorption.

Common variants of FUT2 are associated with plasma vitamin B12 levels












What is going on here?
This is a classic balancing act between how much methylation is ideal.

You can see exactly how fast the balance can shift.

First, the client is obviously undermethylated due to his symptoms so his doctor appropriately addressed it through prescribing methylfolate and methylcobalamin.

The only issue is the doctor did not realize how effective methylation is at supporting neurotransmitters and thyroid hormone production.

So what happened is the gentleman decided to skip his methylfolate and methylcobalamin dose, take a lot of niacin (which is a methyl ‘sponge’) and he immediately tanked his methyl groups which caused symptoms of undermethylation.

Then, upon restarting the methylfolate and methylcobalamin, and maintaining his current dosage of medications, he felt great for a few hours.

Then anxiety hit due to excessive neurotransmitter production and likely thyroid hormone production.

So – in order to quiet those symptoms, I told him about how niacin works and how to take it and his anxiety decreased almost immediately.

MTHFR protocol for anyone.

Genetics, lifestyle, diet, medications all play a role in how much methylfolate and methylcobalamin are needed – and these amount can change daily as well.

Finding a doctor that understands this is critical – or you will have a difficult time regaining health – and maintaining it.

Why Niacin??!
You’re likely wondering why niacin was so effective at reducing this gentleman’s anxiety.

I’ll let you in on the secret and wonderful actions of biochemistry.

Niacin restored his mood in two ways – at least the two three ways that I am familiar with:

  1. Nicotinic acid (Niacin USP) requires SAMe to be metabolized. SAMe is a major methyl donor. Thus, when one consumes niacin, SAMe gets used up and methyl donors drop. Thereby excessive methylation goes away.
  2. Nicotinic acid also supports the elimination of glutamate. Many with elevated levels of glutamate do not do well with methylfolate or any type of folate until the levels of glutamate are balanced.
  3. Niacin supports the feedback inhibition of the IDO1 gene which feeds into the kyurenine pathway. This pathway can deplete one’s tryptophan levels which makes them low in serotonin. The niacin slows the loss of tryptophan by pushing it towards serotonin formation.


stories and experiences of undermethylation and overmethylation.


quick question that I can’t make sense of- Niacin turns down methylation. So, why is it suggested by many to supplement it (sometimes at considerably high dosages) for depression and Lyme disease? I have also read about using it against Candida. How would this work??
Grateful for your help in my healing : )

    • Niacin helps reduce nitric oxide, also helps increase serotonin levels and also supports Complex 1 of the mitochondria. Not sure why good against candida.

      In exercise

      High intensity exercise has been shown to result in reduced DNA methylation in skeletal muscle.[52]Promoter methylation of PGC-1α and PDK4 were immediately reduced after high intensity exercise, whereas PPAR-γ methylation was not reduced until three hours after exercise.[52] 

      By contrast, six months of exercise in previously sedentary middle-age men resulted in increased methylation in adipose tissue.[53] One study showed a possible increase in global genomic DNA methylation of white blood cells with more physical activity in non-Hispanics.[54]

      ab Barrès R1, Yan J, Egan B, Treebak JT, Rasmussen M, Fritz T, Caidahl K, Krook A, O’Gorman DJ, Zierath JR (2012). “Acute exercise remodels promoter methylation in human skeletal muscle”. Cell Metabolism. 15 (3): 405–411. doi:10.1016/j.cmet.2012.01.001. PMID22405075.





DNA methylation modifies the human genome, and can be a cause of many diseases. Read more below to learn how it affects your health.



Types of Methylation

1) DNA Hypermethylation

2) DNA Hypomethylation

3) DNA Demethylation


Methylation in humans affects the cytosine (C) nucleotide. It is the process by which a methyl group (a carbon atom with 3 hydrogen atoms attached to it) connects to the cytosine nucleotides (R).

DNA methylation causes a crucial modification to the genome that is involved in regulating many cellular processes. These processes include chromosome structure and stability, DNA transcription, and embryonic development (R).

In normal cells, it ensures the proper regulation of gene expression and gene silencing (R).

Types of Methylation

1) DNA Hypermethylation

A healthy body has a certain level of methylation. Irregular and over-methylated DNA can change a gene, preventing it from producing what it’s meant to. Changes in the placement of methyl groups can cause diseases (R).

Some researchers have even used the amount of methylation in certain genes as a biological clock, as it occurs in individual genes is proportional to age. The implications include, but are not limited to:

•Causes cancer

•Lowers immune system function

•Damages brain health

•Lowers energy and exercise

•Quickens aging

It can inactivate certain tumor-suppressor genes and stop the expression of MRNAs that play a role in tumor suppression (R).

Additionally, external, environmental factors can alter methylation. In other words, while abnormal methylation in DNA can replicate itself and be passed down, this balance can also be altered by everything around us (R).

2) DNA Hypomethylation


If there is not a high enough level of methylation in the body, it can cause genomic instability and cell transformation (R).

3) DNA Demethylation

DNA demethylation can also play a role in the formation of tumors. It happens in early embryos and is essential for stem cells to be able to differentiate into different cell types (R).

Demethylation removes the modification of the nucleotides from DNA (R).


•The most striking feature of vertebrate DNA methylation patterns is the presence of CpG islands, that is, unmethylated GC-rich regions that possess high relative densities of CpG (R).

•However, a significant fraction of all human CpG islands is prone to progressive methylation in certain tissues during aging (R).

•Cytosine deaminases carry out demethylation, converting 5mC to thymine, followed by T-G mismatch repair that specifically replaces thymine with cytosine (R).

•TET family hydroxylases oxidizing 5mC may also participate in active DNA demethylation (R).

•Either transcription persists leading to restoration of the unmethylated CpG island flanked by methylated non-island-flanking DNA, or other mechanisms extinguish transcription in the embryo and this invites de novo methylation of the CpG island and its flanks (R).

process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging and carcinogenesis. (3

Two of DNA’s four bases, cytosine and adenine, can be methylated. Cytosine methylation is widespread in both eukaryotes and prokaryotes, even though the rate of cytosine DNA methylation can differ greatly between species. (4)




Reference and Precision Notes

(1) A methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms — CH3. In formulas, the group is often abbreviated Me. Such hydrocarbon groups occur in many organic compounds. It is a very stable group in most molecules.

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