Start Here for MTHFR and Methylation
If you are looking for information on methylation and the MTHFR gene, this is where to start.
If you are looking for information on methylation and the MTHFR gene, this is where to start.
My MTHFR Protocol
This 7-page quick guide to optimizing your MTHFR status using foods and supplements is available to Masterpass members. Subscribe to one of the paid options now and you will immediately get it emailed to you in the welcome email and can always access it from the bottom of each email or from the ebooks menu.
If the box above says “upgrade to paid,” you need to upgrade to receive the protocol.
If the box says “subscribed,” you are a Masterpass member. Masterpass members can download it any any time here.
An Introduction to Methylation
Methylation is profoundly important to our physical, mental, and emotional health. To properly discuss it, we should first define it.
You and I, and everything that lives upon the face of the earth, are made primarily of organic molecules, which are strings of carbon atoms that are bound mostly to hydrogen, but are sometimes bound to other atoms, such as nitrogen, oxygen, and sulfur. A single carbon atom that attaches to such a molecule at one point and is otherwise bound only to hydrogen is known as a “methyl group.” Methylation is the transfer of these methyl groups and is also known as one-carbon metabolism.
Most of your methylation is used to synthesize two molecules: creatine and phosphatidylcholine.
Creatine is best known for boosting muscular strength. Bodybuilders take it as a supplement to build muscle and many kinds of athletes take it to boost their power and performance. Less well known, creatine helps you make the stomach acid you need to digest your food, provides the energy you need to absorb the nutrients in your food, powers sperm as they swim up the vaginal canal, fuels the regeneration of healthy skin, and helps you see and hear.
Phosphatidylcholine is a critical constituent of your cell membranes throughout your body, but is especially important to helping you remove fat from your liver. Without enough of it, we are more vulnerable to fatty liver disease, which afflicts an estimated 70 million Americans. This fat-moving function also helps move bile, which is critical to gall bladder health and is essential to the digestion of fats and the absorption of fat-soluble vitamins.
Phosphatidylcholine also serves as a precursor for acetylcholine. Acetylcholine is a neurotransmitter with many roles. In the brain, it supports cognitive performance during tasks that require sustained attention. In your muscles, it's what stimulates contraction and lets you push, pull, lift, throw, and move in whatever other way pleases you.
Methylation has many other roles as well. It helps get rid of histamine, best known for its contribution to allergic reactions. In the brain, it acts to make you mentally more flexible, and helps prevent you from ruminating on negative thought patterns that may contribute to anxiety and depression. In the liver, it contributes to detoxification of foreign chemicals and heavy metals. Our cells are constantly altering the expression of our genes according to the demands of our environment, and methylation is one of the key tools they use to do it.
There is such a thing as too much methylation. For example, too much methylation in the brain can make you so mentally flexible that you become too easily distracted and have difficulty focusing. It may also make you drowsy or interfere with your ability to break established habits. Too much methylation also seems to shorten lifespan.
So, we need to have proper balance. To achieve that balance, we use the amino acid glycine as a buffer of excess methyl groups. If we get a lot of methyl groups but not much glycine, we run the risk of running low in glycine, and this can hurt our detoxification system, destabilize our blood sugar, interfere with our sleep, weaken our bones, and make our skin age faster.
The best way to balance this system is to get plenty of everything, things that supply methyl groups on one hand and glycine as a buffer of the excess on the other.
These are the key nutritional players in the methylation system:
Methionine is an amino acid found in all proteins, but which is especially rich in animal products. After being activated using ATP, the fundamental energy currency of the cell, methionine becomes the universal methyl donor.
Once activated methionine donates its methyl group, it becomes homocysteine. Homocysteine needs to be recycled back to methionine so methylation can continue, and homocysteine itself is thought to be harmful by contributing to cardiovascular disease.
Vitamin B12 and folate (vitamin B9) recycle homocysteine back to methionine. They take the methyl group from the metabolism of amino acids that we get from dietary protein.
Alternatively, betaine (trimethylglycine, TMG), which is mainly derived from choline, recycles homocysteine back to methionine.
Several other B vitamins, mainly thiamin (vitaminB1), riboflavin (vitamin B2), niacin (vitamin B3), and pyridoxine (vitamin B6), support B12 and folate in recycling methionine, even though they themselves are not methyl donors.
Glycine is our buffer for excess methyl groups.
A number of minerals are needed to support the enzymes involved in this system: iron, phosphorus, sulfur, magnesium, potassium, zinc, and possibly cobalt. Vitamin A is also needed to produce the enzyme involved in using glycine as a methyl buffer.
The MTHFR Protocol
This 7-page quick guide to optimizing your MTHFR status using foods and supplements is available to Masterpass members. Subscribe to one of the paid options now and you will immediately get it emailed to you in the welcome email and can always access it from the bottom of each email or from the ebooks menu.
If the box above says “upgrade to paid,” you need to upgrade to receive the protocol.
If the box says “subscribed,” you are a Masterpass member. Masterpass members can download it any any time here.
Searchable Databases Related to Methylation
Balancing Methionine and Glycine in Foods: The Database
Consuming Creatine in Foods and Supplements
Articles Related to Methylation
How Energy Deficiency Hurts Methylation
Lipoic Acid Saps Methyl Groups
Why Would Someone Not Tolerate Methyl Donors Even If They Need Them?
Glutathione Intolerance: Getting to the Bottom of It
Your “MTHFR” Is Just a Riboflavin Deficiency!
Alex Leaf: Supplement riboflavin to fix the MTHFR polymorphism
Does Choline Deficiency Contribute to Fatty Liver in Humans?
Meeting the Choline Requirement — Eggs, Organs, and the Wheat Paradox\
Beyond Good and Evil: Synergy and Context with Dietary Nutrients
When SAMe Helps, Consider Magnesium and Your Metabolic Rate
Should We Avoid Animal Protein to Optimize Methylation?
Podcast Episodes Related to Methylation
Methylate Your Way to Mental Health With Dopamine
Why You Need Glycine: A Panel Discussion
Creatine: Far More Than a Performance Enhancer
Why You Should Manage Your Riboflavin Status and How to Do It
Niacin, Part 1: What It Is and Why You Need It
Nutrition in Neuroscience (Parts 2 and 4 are most relevant to methylation): Part 1, Part 2, Part 3, Part 4
Chris Masterjohn Lite Episodes Related to Methylation
What EVERYONE Should Be Doing About Methylation
Folate: You Can Freeze Your Liver But Not Your Veggies
Supercharge Your Folate With Pastured Egg Yolks and Sprouted Legumes
Getting Enough B12: Vegans, Omnivores, and Everyone In Between
How to Know If You Need to Care About Your MTHFR
This is the Blood Work You Should Get for MTHFR
Does Methylfolate Make You Angry or Depressed?
DON'T Use Niacin to Buffer Excess Methyl Groups
Why I Don't Believe in “Undermethylators” and “Overmethylators”
DON'T Use Histamine To Assess Methylation Status
Your MTRR Genes and Vitamin B12
What to Do About Your COMT Genes
Sometimes Synthetic Folic Acid Is Better Than Natural Food Folate
5 Ways to Help With Glutamate Sensitivity and Glutamate Dominance
Collagen Before Your Workout For Tendon Health
Glycine With a Meal for Blood Sugar
Oxalates — Should You Be Concerned About Collagen?
The MTHFR Protocol
This 7-page quick guide to optimizing your MTHFR status using foods and supplements is available to Masterpass members. Subscribe to one of the paid options now and you will immediately get it emailed to you in the welcome email and can always access it from the bottom of each email or from the ebooks menu.
If the box above says “upgrade to paid,” you need to upgrade to receive the protocol.
If the box says “subscribed,” you are a Masterpass member. Masterpass members can download it any any time here.
I'm 42, and have an 81% decrease on my methylfolate score. I started this protocol a few weeks ago, and:
* my RHR is down to high 40s-mid 50s from the mid-60s;
* I haven't had a brain fog episode once -- very exciting to be able to do my business books whenever I have time, and not during a mysterious window of opportunity;
*HRV is is trending up;
*No more bouts of dyspnea;
*Energy and exercise tolerance has greatly improved;
*100% O2 sat for the first time in about two years. I live at altitude.
I feel like I have my life back. Thanks, Chris.
FROM MORIAH MEYER:
Chris,
Please read the journal article titled “ Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial”.
https://doi.org/10.3945/jn.115.216739
I am interested to see your thoughts on this statement detailing how creatine supplementation can ultimately inhibit MTHFR: “therefore, an increase in SAM from creatine supplementation would result in inhibition of MTHFR, decreased synthesis of 5-mTHF, alleviated inhibition of GNMT, and ultimately, decreased SAM, increased SAH, and increased homocysteine”.
Studies have also shown that supplementation of creatine results in significant decreases of glycine. (I apologize, I do not have the DOI for this but I am sure you can find a similar study). Might this be harmful for MTHFR individuals who have some reliance on the glycine-buffer system?
As someone with MTHFR supplementing creatine, the negative impact on my health that resulted prompted me to research more into it. I wonder if this is an appropriate recommendation. I understand the logic that since a large portion of methylation goes towards synthesizing creatine, supplementing it would free up methyl groups and ultimately ease the burden of the methylation cycle. However, I do not think it is as straightforward as this and may be a dangerous recommendation. “Unexpectedly, creatine supplementation (alone or in combination with l-arginine) was associated with an 11–20% increase in homocysteine concentration (p < 0.05), which was not attributable to worsened renal function, providing evidence against an effect of creatine on decreasing methylation demand.” https://doi.org/10.1177%2F1358863X08100834