MTHFR and Homocysteine By The Numbers

These past few weeks we’ve gone over some general information about MTHFR and homocysteine, the link between methionine and homocysteine, and the new information about MTHFR, homocysteine, and Covid-19. What we haven’t talked about is Homocysteine testing and parameters – what is normal, what isn’t, and what is considered normal but maybe shouldn’t be.

Testing Homocysteine

Homocysteine tests are simple blood tests that can be ordered by your doctor. It must be performed fasting for accurate results. Any protein you eat before your test can skew the numbers because methionine in your food may cause a temporary rise in homocysteine. The best way to ensure a blood test is fasting is to schedule your blood test early in the day before you have eaten anything. 8 – 12 hours of fasting (like you would get overnight) is best for the most accurate results.

“Normal” Levels

The current medical standard in the U.S. is a normal range from 5 – 15 umol/L (that is micro mols/Litre). Anything above 15 micro mols/L is considered high, or hyperhomocysteinemia. There is a growing body of evidence that the normal level should be adjusted:

  • A study published in the New England Journal of Medicine shows that carotid artery thickening and stenosis risk begins to increase for men by 9.2 umol/L (although the risk for women seems to remain stable until 11.4 umol/L). Both of these are significantly lower than the 15 umol/L that is considered normal.
    • Risk increases at 9.2 umol/L
  • A meta-analysis published in the Journal of the American Medical Association shows that a 3 umol/L decrease in homocysteine leads to an 11% lower risk of ischemic heart disease and a 19% lower risk of stroke.
  • A strong linear relationship exists between homocysteine levels and death in patients with coronary disease. The lowest risk group has homocysteine below 9 umol/L and the risk increases from there both within what is considered the normal level and outside of it.
    • Homocysteine <9 umol/L = 3.4% risk of death
    • Homocysteine 9 umol/L – 14.9 umol/L = 8.6% risk of death
    • Homocysteine >15 umol/L = 24.7% risk of death.
    • Risk increases at 9 umol/L
  • The study we discussed last week dealing with homocysteine levels as a predictive marker for worse outcomes with Covid-19 also showed an increased risk for pathological lung changes on CT at 8 umpl/L
    • Risk increases at 10.58 umol/L

If The “Normal” Levels aren’t Ideal, What Is?

All of the risks for negative health outcomes seems to be lowest around the 6 – 8 umol/L mark, so we’re going to call that “Optimal.” This is an estimation based on the research that we talked about above. Joe Pizzorno (a legend in the natural wellness community), estimates the ideal range to be 5.0 to 7.0. Ben Lynch, the epigenetic expert, estimates ideal to be between 6 to 9 umol/L.

If Homocysteine Is So Bad, Why Aren’t We Aiming for Zero?

Too much homocysteine is bad for sure, and with MTHFR and homocysteine that is the direction we usually trend, but remember that homocysteine is absolutely essential. If your homocysteine is too low (hypohomocysteinemia), then there are also health consequences. Without homocysteine you can’t make glutathione, which is one of your main defenses against oxidative stress. Without glutathione, things would go sideways pretty quickly.

Homocysteine is also the precursor for something called alpha-ketobutyrate, which is a vital ingredient in the process that makes cellular energy. Very few studies are done about low homocysteine levels (I mean VERY few. I can count them on two hands). By far the most interesting one shows a link between low homocysteine and peripheral neuropathy. It states that fully 41% of people with low homocysteine have peripheral neuropathy, which is hugely significant.

In my opinion, this implies that the lack of glutathione and consequent difficulty with free radicals is leading to higher levels of inflammation and nerve damage. Ben Lynch put forward a similar theory on his website here, and Joe Pizzorno, here.

I wouldn’t be surprised to see a link between low homocysteine and chronic fatigue, as well, although the research has never been done.

The bottom line is that we need homocysteine, but too much of it becomes a big problem. Aim for 6 – 8ish micro mols/L. Next week we’ll talk about ways to lower your homocysteine levels if they’re too high.

Has your homocysteine ever tested too low? I”d love to hear your comments here, or in Genetic Rockstars, our amazing MTHFR community.

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Methionine, MTHFR, and Homocysteine.

The link between MTHFR and homocysteine is clear – if you aren’t familiar with that part of the picture, you can brush up with last week’s topic. The link between methionine and homocysteine is clear as well since they loop together in the methionine cycle with dietary methionine converting into homocysteine as a by-product, then being recycled back to methionine using MTHFR.

It’s easy to get into a situation where you assume methionine is “good” and homocysteine is “bad,” but actually for MTHFR, methionine itself is a double-edged sword.

Recommended Intake of Methionine

When it comes to suggested protein intakes per day, it’s pretty hotly debated and the criteria are updated every few years. Generally, requirements for infants are much higher (according to intake in mg/kg body weight) than those of children, and children are in turn higher than those of adults. Again, this is based on an mg/kg measure and not an absolute number.

  • Infants (3-4 months) – 58 mg/kg body weight/day
  • Children 2 years old – 27 mg/kg body weight/day
  • Children 10-12 years old – 22 mg/kg body weight/day
  • Adults – 13 mg/kg body weight/day.

This means for the average 150 pound (or 68 kg) adult, the daily requirement for methionine is 884 mg. That is found in 100 g (or 3.5 oz) or less of a lot of meats. This means that while vegetarians are probably getting the right amount, most meat eaters are significantly overdoing it.

Recommended Daily Protein Intake

This data is also debated, but the best researched reference data from the World Health Organization is below.

AgeProtein intake in grams/kg body weight/day
Infant1.2-1.4 g/kg body weight/day
Children0.8 – 0.97 g/kg body weight/day
Adolescents0.67 – 0.79 g/kg body weight/day
Young Adult0.75 g/kg body weight/day
Adult0.6 g/kg body weight/day
Elderly0.75 g/kg body weight/day
Pregnant0.92 g/kg body weight/day
LactatingBasic rate plus 15 g per day for the first 6 months, 12 g per day thereafter.

This works out to about 46 grams per day for the average woman and 56 grams per day for the average man. In the west, we tend to overdo protein. Most American adults eat about 100 g of protein per day, which is twice the recommended amount. Not only that, the latest trends in nutrition mean that 60% of Americans report that they are trying to increase their protein intake according to the Hartman Group.

Food Sources of Methionine

Methionine is an amino acid, which is the building block of protein, so naturally, it is high in protein-rich foods. The top ten categories of foods according to my food data are:

FoodMethionine
per 100g
Methionine per 6 ozSimilar Foods
Ground Turkey931 mg1583 mgChicken breast, thigh, drumstick.
Beef (skirt steak)905 mg1539 mgOther cuts of beef, lamb, veal, buffalo
Tuna885 mg1505 mgGrouper, salmon, snapper, tilapia, mahi mahi
Lean Pork Chops850 mg1445 mgPork ribs, lean ham, pork bratwurst,
Firm Tofu211 mg532 mgEdamame, soybean sprouts, soy milk
Milk88 mg431 mgYogurt, buttermilk
Low fat ricotta284 mg528 mgParmesan, gruyere, Swiss (other cheeses)
Brazil nuts1124 mg1914 mgHemp, squash, pumpkin, chia, sesame seeds.
Large white beans146 mg196 mgNavy, kidney, black beans.
Quinoa96 mg133.5 mgTeff, wild rice, kamut.

So… Too Much Protein?

In the West, we love our protein. We’re all working on building muscle and improving our lean bodyweight… Except that in reality, most of us aren’t. Most of us are actually working on holding down our office chair and staring at a screen. Still, we’re obsessed with the idea of being fit and lean so we overconsume in different ways than we used to. Most of us eat more than we need in general, and those of us who are “working on our health” are especially prone to working to get too much protein This, of course, leads to the modern issues of obesity and heart disease,

For people with an MTHFR issue, this takes on an added dimension because eating more protein means adding more burden to the methionine (or methylation) cycle and hence the MTHFR enzyme which ties methylation into the folate cycle. Remember how those two cog together like gears?

the MTHFR lifestyle matters because of the way these cycles all interconnect.

Extra protein means your folate cycle has to work harder, your body needs more active folate and more methyl donors, and homocysteine is going to build up. We already talked about how bad homocysteine is when it builds up.

Plus, Lower Methionine Intake Might Mean You Live Longer

Research has long shown that calorie-restricted diets are effective in promoting lifespan. Meaning, the people who eat less usually live the longest, even to the fact that some of the humans with the longest life spans on record have gone through periods of food shortage. Further research has found that limiting methionine intake specifically extends lifespan. That is with or without actual calorie restriction. Also, intermittent fasting, which is one of my favorite health hacks, is a great way to actually have minor calorie restrictions without too much fuss.

Also, methionine restriction is showing promise as a therapeutic approach to limiting the growth of certain types of cancer. This isn’t because methionine is bad – it’s essential for human growth, development, and healthy functioning. We do get more than we need, but also cancer cells have fewer ways to adapt to methionine limitation, while healthy cells can protect themselves better.

In a fascinating study, researchers are also limiting methionine with the use of an oral medication that breaks down methionine (called an oral methionase) to treat Covid-19. The RNA of the coronavirus needs to be methylated, using SAMe, in order to initiate viral replication. Limiting methionine (which limits SAMe) interferes with that step and so slows the viral replication and can potentially reduce viral load. This generally makes me wonder about all of us MTHFR folks and Covid-19. Do we have a survival advantage because it’s harder for us to produce SAMe? Also, should people supplementing with SAMe consider taking a break if they’re in a high-risk situation for COVID?

Even though we are obsessed with getting more protein – I mean, who doesn’t have jerky in their purse right now? We are clearly overdoing it. Reducing protein intake, specifically methionine, would help us all live longer, healthier lives. But it is especially important for MTHFR folks.

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THWT! Trailer, and a bonus P.S.A. about Covid-19, from my four-year-old daughter, Sabrina.

Hello, I’m delighted to welcome you to the To Health With That! podcast where we’ll break one BIG health topic, like hypertension, type II diabetes, or this season’t choice – MTHFR mutation, into small bite-sized pieces of ten minutes or less. I’m your host, Naturopathic Doctor Amy Neuzil.

In Season One, we’ll focus on the MTHFR mutation– a topic that is near and dear to my heart. But you, dear listeners, will choose the topics for Season Two and beyond. If you know you have questions about the MTHFR mutation and want me to answer them in the podcast and also play your lovely voices on the air, then go here and click the +MESSAGE button under the logo. Or, you can email me at thwtpodcast at gmail.com (I’m writing it like that so that I don’t get approximately one million spam emails every 24 hours.) The first episode will air on June 21, just in time for father’s day. Not that it’s so father’s day relevant.

To Health with That! Naturally Healthy In No Time.

P.S.A. On Coronavirus from my 4-year-old daughter, Sabrina.

It’s Sabrina here. I’m Sabrina. I’m talking for the Coronavarirus, but I’m not sure if you can go out. It’s not safe to go out without a mask because if you make one that’s okay and if you buy one that’s okay. But, if you don’t have one and you can’t buy one and you can’t make one, that’s not good–you can’t go to the store. Bye! I’m Sabrina.

This is Sabrina, with a recently rescued chipmunk (rescued from the jaws of our Boxer/Lab, Tiki, no less.
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