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
Riboflavin
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
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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, although I’ll be sending you an email soon about some alternatives.
Creatine
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
Folate
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
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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. I will send you an email soon about some alternatives
Glycine
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, Copyright © Chris Masterjohn, 2021-2023. All rights reserved.
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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
For a more detailed look at each of the essential vitamins, minerals, and fatty acids, see my Vitamins and Minerals 101 Cliff Notes, where all the key insights about these nutrients over my last 15 years of research are all collected into one place in a 27-page PDF.
How to Personalize This Protocol
First, obtain a genetic analysis from 23andMe or Ancestry, and run it through my free choline calculator. This will look at multiple genes besides just MTHFR that impact your methylfolate levels
Your results will give you a suggested choline intake. This can replace the 1000 mg of TMG or choline listed as a default within this protocol
Click on “Advanced Stuff” and scroll down to your “Methylfolate Score.” You can divide the result you get by 75 and then multiply that decimal by the doses of the other nutrients listed in this protocol. If your score is less than a 75% decrease, the adjusted doses should be lower than those in this protocol. If it is more than a 75% decrease, the adjusted doses should be higher.
Under “Advanced Stuff” if your PEMT is listed as +/- or +/+, you should get at least a portion of choline requirement from phosphatidylcholine If it is +/-, aim to get at least 25% of your choline from phosphatidylcholine, and if it is +/+, aim to get at least 50% of your choline as phosphatidylcholine. Phosphatidylcholine is the main form of choline found in food, and the foods listed in the Choline section under “Mainly providing choline” can be counted towards your phosphatidylcholine requirement When obtaining phosphatidylcholine from supplements, the easiest way to get it is from lecithin, where one tablespoon provides about 135 mg of choline. If using a phosphatidylcholine supplement, you need to multiply the dose of “phosphatidylcholine” in the supplement by 0.13, because phosphatidylcholine is only 13% choline.
Here are a few other tips for personalizing this protocol:
● If your MCV consistently comes back high on a complete blood count (CBC) ordered by your doctor, you may do better with folinic acid instead of methylfolate
● If methylfolate makes you angry or depressed, or causes other symptoms you associate with “overmethylation,” you may need to increase the amount of glycine in the protocol to better stabilize your methylation system. Additionally, you may benefit from starting with a very small amount of methylfolate, adjusting to it over the course of one to four weeks,
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This is an educational resource and is not to be construed in any way as medical or nutritional advice
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and then slowly building up The best way to do this is with Holistic Health liquid 5-MTHF, where you can start with one drop providing 72 ug, and work up by one additional drop every one to four weeks Further details can be found in, “Why Would Someone Not Tolerate Methyl Donors Even If They need Them?”
○ If you need to dilute the liquid methylfolate, spread the drops out as evenly across the day as possible. If even one drop causes problems, you can dilute it down to 7 2 ug per drop by mixing one drop with ten drops of olive oil or another edible oil you use If doing this, work under as little light as possible (or best, under a red light), don’t take longer than needed, and don’t mix it more than is needed to make it homogeneous Make this in small batches, and store the diluted liquid away from light and preferably in the refrigerator until used up
● If you have symptoms associated with low acetylcholine levels, such as poor learning and memory, an inability to perform under conditions of sustained, focused attention, or poor muscular power, consider meeting 50% or more of your choline requirement with alpha-GPC Doses of this supplement that help boost brain power are 600-1200 mg/d Alpha-GPC is only 40% choline, so multiply that dose by 0.4 to see how much choline you are getting from it
The Ultimate Personalization
While your genetics and response to different types of foods or supplements help you personalize this protocol beyond using simply the average requirements taken from research studies, the ultimate personalization is to manage your nutrients using lab tests that tell us exactly what is going on in your body on any given diet and supplement regime.
Proper testing gets you results much faster than tinkering through trial and error
The most useful blood tests specific to methylation are homocysteine, the Genova Methylation Panel, serum and red blood cell folate, serum B12, and blood and urine methylmalonic acid.
Your methylation system will operate most effectively, however, when you take the proper approach to testing your status for all of the essential nutrients.
My comprehensive approach to managing nutritional status with lab tests, signs and symptoms, and dietary analysis, can be found in Testing Nutritional Status: The Ultimate Cheat Sheet.
Copyright © Chris Masterjohn, 2021-2023. All rights reserved.
This is an educational resource and is not to be construed in any way as medical or nutritional advice
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