MTHFR Protocol - Chris Masterjohn, PhD

A well-functioning MTHFR is profoundly important to our mental and physical health. It calms our anxiety; it improves our mental flexibility, helping us avoid getting stuck on negative thoughts; it calms the inflammation that can result from allergic reactions or histamine present in our food; it supports healthy digestion; it keeps our liver in tip-top shape so it can clear out toxins and keep our blood sugar stable; and it keeps our muscles energetic, strong, and powerful.
MTHFR mutations

MTHFR does all these things by helping us make methylfolate, a critical part of the methylation system. If you have a poorly functioning MTHFR, this is not the diagnosis of a disease or a sentence to poor health. It just means you need to adapt your food and supplements to better support your genetics. This protocol is meant to support the nutritional needs of someone with any of the genetic variations that hurt MTHFR activity. By default, the amounts of foods and nutrients are meant for someone with the genetic variation known as C677T +/+, but I will be providing instructions for further tailoring it to your own genetics and your own response to foods and supplements. The essentials are presented first, then how to get the nutrients from foods or supplements, then some information on personalizing the protocol and tailoring it to your own unique needs.

The Essentials 

Here are the most essential components of the protocol: 

  • 5 milligrams per day (mg/d) of riboflavin (vitamin B2). Riboflavin helps improve the ability of MTHFR to make methylfolate. 
  • 500 milligrams of trimethylglycine (TMG) taken twice a day. TMG acts as an alternative to methylfolate and helps you get around a poorly functioning MTHFR. 
  • 5 grams of creatine per day. Creatine helps reduce the need for methylfolate. 
  • 400-600 micrograms per day (mcg/d) of dietary folate equivalents (DFE) from food with an optional addition of 400 mcg DFE supplemental methylfolate taken twice a day. Folate should be spread out across meals as much as possible to ensure there is always some methylfolate present in your system. 
  • 3 grams of glycine per meal. Glycine helps stabilize the methylation system, preventing swings back and forth in mood, mental state, and energy. Low methylfolate levels lead to glycine loss, so glycine is here to replace what is lost.

How to Get the Essentials from Food and Supplements 


To hit the riboflavin target with food, mix and match five of the following each and every day: 28 grams of liver; 56 grams of kidney, heart, or almonds; or 200 grams of red meat, cheese, eggs, salmon, mushrooms, seaweed, sesame, wheat germ, or wheat bran. You can pile up on one or two rather than mixing and matching broadly, but you shouldn’t exceed eight ounces of liver per week. While high-dose riboflavin supplements are generally safe, when using supplements it is best to keep the dose near the target unless you have a good reason to go higher. Riboflavin is best as free riboflavin or simply as “riboflavin” rather than as riboflavin 5’-phosphate. The easiest way to get a riboflavin supplement close to the 5 mg target is to use a liquid supplement instead of tablets or capsules. A quick search will reveal several brands that have a liquid supplement with 6.5 mg riboflavin per dropper. 

Trimethylglycine (TMG) and Choline 

TMG has “glycine” in its name but is fundamentally different from the “glycine” that is listed at the bottom of the essentials. It is actually much more related to choline. In food, we mostly eat
choline rather than TMG, but we convert the choline to TMG in order to support methylation. You can meet the 1000 mg of TMG from food with either TMG, choline, or both. You can hit the target by mixing and matching seven of the following each and every day: 
  • Mainly providing choline: 1 tablespoon of lecithin; 40 grams of beef liver; 44 grams of veal liver; 62 grams of turkey liver; 71 grams of chicken liver; 143 grams of salmon; 135 to 285 grams of most meat, fish, or shellfish; 172 grams of flax seeds; 185 grams of pistachios, quinoa, amaranth, or pinto beans; 215 grams of pumpkin or squash seeds, or cashews; 250 grams of pine nuts, edamame, buckwheat, sunflower seeds, peanuts, or almonds. 
  • Mainly providing TMG: 24 grams of quinoa; 25 grams of wheat germ; 37 grams of wheat bran; 44 grams of raw lambsquarters; 57 grams of canned beets; 83 grams of dark rye flour; 105 grams of frozen spinach; 112 grams of raw beets; 140 grams of whole wheat flour; 143 grams of raw kamut. 
The best supplement to take to support methylation is TMG, which usually comes in 500 mg capsules.


You can hit the target by eating two pounds of muscle meat (that is, “regular” meat and not organ meats) per day cooked rare, and three pounds of muscle meat per day if cooked between medium and well done. However, high intakes of meat raise your need for glycine. If you choose to eat 2-3 pounds of meat per day, you should calculate your protein intake, and, for every 100 grams of protein, add an additional three grams per day of glycine, over and above the dose recommended above. Alternatively, you can supplement with creatine using any creatine monohydrate, which comes in powders or capsules. Many brands use “Creapure,” which is the purest creatine on the market. 


The folate requirement can be met with two to three 100-gram servings of liver, legumes, or leafy greens, measured raw. Add one more serving for pregnancy or lactation; add one more if you always cook your plant foods; and add another if you always throw out the cooking water when you cook your plant foods. Don't wash veggies after cutting and don't trust frozen veggies or canned beans.
The default supplement to use is 400 ug DFE methylfolate, also known as 5-MTHF or L-5-MTHF, or L-5-methyltetrahydrofolate, taken twice a day.  


There are several ways to get 3 grams of glycine: 10 grams of gelatin, 10 grams of collagen, 3 grams of glycine powder, or one cup of bone broth listed as containing 10 grams of protein.

The Many Other Nutrients You Need 

While this protocol focuses on the essential nutrients whose requirements are altered by low MTHFR activity, many other nutrients are needed in the background to keep the methylation system operating smoothly. These include thiamin (vitamin B1), niacin (vitamin B3), pyridoxal (vitamin B6), vitamin A, and a lot of the minerals: iron, phosphorus, sulfur, magnesium, potassium, zinc, and possibly cobalt. This protocol will operate most effectively when you are meeting your needs for all of your essential vitamins, minerals, and fatty acids, as well as your needs for protein, carbohydrate, fat, and calories. If you don’t have any particular dietary restrictions, here are some simple rules of thumb to follow to make sure you hit your targets for all your essential nutrients:
  • Diversify your protein among meat, fish, shellfish or other invertebrates, eggs, and dairy. Get a half gram to a gram of protein per pound of bodyweight (if overweight, reduce this to your ideal bodyweight), which for a 150-pound person would be 75-150 grams of protein. Most people have plenty of wiggle room within this range, but if you are trying to lose body fat, gain muscle, or meet athletic goals, you should aim for the higher side of the range (and in some cases higher). 
  • Make an effort to eat “nose to tail” by utilizing parts of the animals we’ve been neglecting in our society. For example, try eating liver once a week and using bones to make broths, gravies, and sauces or eating the edible bones found in canned fish. 
  • Get about 1000 milligrams of calcium per day, which is easiest to get from several daily servings of dairy or edible bones, such as the ones found in canned fish. 
  • Diversify your carbohydrates among legumes, whole grains, starchy tubers, and fruits. 
  • Eat a large volume (several cups per day) of vegetables, diversifying them across colors with an emphasis on red, orange, yellow, and green. Always include dark green vegetables in the daily mix. 
  • Include foods or supplements that aid in digestion at every meal. Examples include ginger, lacto-fermented vegetables, kombucha, raw apple cider vinegar, Swedish bitters and digestive enzyme supplements. The reasoning behind this one is simple: all those nutrient in your food are only useful if you digest your food well, breaking it down fully and absorbing everything it has to offer.



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