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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MTHFR and Homocysteine – The Basics

High homocysteine is often the first indication of an MTHFR issue, and it’s certainly the one that doctors take the most seriously. There is a good reason for this. Homocysteine is implicated in heart disease including heart attack and stroke, so it shouldn’t be taken lightly. 

What is Homocysteine?

Homocysteine is an amino acid that is made within your body as a part of methionine metabolism. Amino acids are the basic building blocks of protein, and we take in amino acids every time we eat protein-containing foods.

We need homocysteine in order to make ATP, our cellular energy, and also to make cysteine and ultimately glutathione, which is our master antioxidant. The problem comes when levels get too high, and this happens when your body is unable to recycle homocysteine back into methionine.

The primary recycling pathway relies on the MTHFR enzyme, as well as active folate and B12. There is a secondary pathway called the BHMT pathway that ramps up when homocysteine levels start to rise and this relies on other methylators like betaine, trimethylglycine (TMG), and choline. 

Why does Homocysteine Get High?

As usual, there are a number of reasons and many of them are related to MTHFR.

  • MTHFR compromise – your body recycles homocysteine into methionine in an MTHFR-dependent process. It requires the active form of folate for the process so if your MTHFR is running slowly or inefficiently then homocysteine levels can build up causing inflammation and damage.
  • Folate deficiency – Whether or not you have an MTHFR issue, if you don’t have folate then the recycling doesn’t happen either.
  • B2 or B12 deficiency – Like folate, these vitamins are necessary for methionine recycling, and not having enough of them can raise your homocysteine to an unhealthy level.
  • Too Much Protein intake – This is certainly a first-world problem and a bigger one recently with everyone doing fad diets from Keto to Atkins to Paleo. If you’re taking in higher levels of methionine than your body can easily process, then homocysteine is going to build up. Also, meats and dairy have some naturally occurring homocysteine in them. We’ll talk more about the methionine situation next week.
  • Other medical conditions – thyroid disease, rheumatoid arthritis, and diabetes are linked to higher homocysteine levels.
  • Medications that decrease folate absorption – proton pump inhibitors, birth control pills, antifolate agents, and some anticonvulsant medications interfere with folate absorption or metabolism.
  • High coffee intake – I am sorry to say, high coffee intake is also linked to elevated homocysteine.

What Does Homocysteine Do That’s So Bad?

So many things. Homocysteine is vital, of course, but in this situation, too much of a good thing becomes toxic.

  1. Inflammation – Inflammation is the most well-documented issue to do with homocysteine. It is specifically damaging to cell membranes and the lining of your blood vessels, which is part of why it is so linked to heart disease.
  2. Clotting – Clotting in the blood vessels can lead to heart attack, stroke, pulmonary embolism, and deep vein thrombosis, none of which are good. This is thought to be due to a combination of factors. One is that nitric oxide metabolism is compromised and so blood vessels aren’t able to dilate properly. The other is that thromboxane A2 (TXA2) activity is increased in both blood vessels and platelets, possibly because of a higher free radical burden. This promotes clotting.
  3. Neurological issues – High homocysteine levels are implicated in a number of neurological disorders including stroke and Alzheimer’s disease, but extending to disorders like epilepsy, Parkinson’s, multiple sclerosis, and ALS. The research is unclear in terms of whether homocysteine is actually a causative factor in its own right or just a marker of low B-vitamin status.
  4. Fractures –  Research shows that homocysteine significantly increases fracture risk and it appears to be independent of other risk factors, but it is unclear whether or not B vitamin supplementation decreases that risk.
  5. Microalbuminuria – Microalbuminuria is an abnormal protein in the urine and it indicates a high future risk of cardiovascular disease as well as kidney dysfunction. Every 5 umol/L increase in homocysteine levels is associated with an increased risk of developing microalbuminuria.
  6. Atherosclerosis – As a consequence of the increased inflammation in your arteries, your body is more likely to lay down arterial plaque to protect itself. This isn’t the direction you want to go. High blood pressure – possibly because of the issues with blood vessel dilation, blood pressure and homocysteine go hand in hand. High homocysteine increases the thickness of arterial walls, reduces the elasticity of arteries, and increases the production of stiffer collagen fibers in the vascular system. 
  7. Pregnancy complications – High homocysteine levels have been implicated in spontaneous abortion, placental abruption, and preeclampsia. 

Is There Anything Good About Homocysteine at All?

Homocysteine is certainly an issue for MTHFR folks, but it’s also incredibly helpful for us as a biomarker. Testing your homocysteine gives you an easy way to see if your methylation is becoming unbalanced at the moment. While it’s a small silver lining, it’s still a good one.

We’ll talk more about the role of methionine in this conversation as well as testing homocysteine and optimal levels in the next couple of weeks.

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Detoxification for MTHFR, Revisited

MTHFR and detoxification are intimately linked. Having a methylation issue impairs detox of many substances including heavy metals and hormones to name a few, but also when those branches of detoxification are impaired it can generally affect the speed at which other substances are able to be eliminated.  So actively supporting those elimination pathways is a huge part of the MTHFR lifestyle. The problem is that anybody who has ever had a hangover, knows that being toxic comes with symptoms. Sadly, lots of people who have done cleanses also know that cleansing too quickly can come with symptoms.

I can certainly say first hand that doing an intense cleanse is fraught with difficulty. When I was a student, well before I knew anything about MTHFR or it’s consequences or that I have it, a good friend was bulk ordering cleanse kits at a discount.  This is the sort of weird geekery that we engaged in as students. Anyway, the cleanse involved a limited diet that tapered down to a total water fast over the course of six weeks along with heavy-duty liver pushers, clay as a binder, and a massive dose of fiber.  I won’t go into the gory details, but right around week four a good friend sat me down and said, very earnestly, “If you don’t stop this cleanse, I am personally locking you in your apartment to preserve everyone else’s sanity.”

I actually broke that fast with an entire large extra cheese and pepperoni pizza and an order of breadsticks by myself, which is even funnier if you had seen me in person because I’m 5’2 and 105 lbs soaking wet. Quite honestly, the pizza was blissful and the only part of that cleanse that was worth the price of admission.  The problem was, that for my body the cleanse was WAY too intense and it pushed my liver to liberate toxins that my system had no way of actually eliminating, and so they rattled around turning me into quite literally a toxic human.

Interestingly, when we refer to someone as “toxic” emotionally, they are usually a pretty good picture of what a person who is toxic physically looks like.  Angry, lashing out, generally spewing hatred and unpleasantness. Internally they might also have a headache, some mild (or severe) nausea, and be constipated. Their skin could be itchy, they might (eek!) produce some weird odors. It’s all pretty gross and, well, toxic. 

The symptoms of being toxic and needing a detox are much the same as the symptoms that occur if you’re trying to detox too quickly.  I know, for the small handful of you who are listening who have experimented with an overly-eager cleanse before, this was a lightbulb moment. The rest of you are probably saying, “so what?”

The reason this matters is that if you’re truly on a path towards balancing your methylation, then you’re going to get to the point where you start incorporating gentle detox into your routine more frequently, and invariably when people start doing gentle detox regularly and see how much better it makes them feel, they try to push the envelope with heavier-hitting detox. 

So let’s talk about steps toward mitigating those toxic symptoms.  We’ll go through a little flow chart.

  1. Are you having symptoms spontaneously (like you’re just toxic) or have you been actively detoxifying?
  2. If you’re just toxic, it’s time to implement some gentle detox strategies and give your body a cleaner diet for a couple of weeks or for good.
  3. If you’ve been detoxing, it sounds like you’re pushing your body a bit too hard. Here’s how to handle that.
    1.   First, Stop taking any supplements involved with the detox. Your body needs a break.
    2. The next big priority is to get your bowels moving because if you can’t physically eliminate things, then they’re hanging around inside of you and that is a genuinely horrible thought. This may mean a one-off dose of a laxative tea or even a glycerine suppository. Whatever you do, make sure you poop.
    3. Also, adding in some detox-type activities that don’t go through your liver or bowels can be a really helpful thing. This is using a sauna or sweating it out in any way you can, doing castor oil packs, taking Epsom salts baths, and that type of thing. 
    4. Keep a very simple, clean diet (fruits and veggies, rice, broth, fresh juices, lots and lots and lots of water. No alcohol, refined sugars, or processed foods, until the symptoms have passed, will help too.
    5. Sleep more – as much as you physically can, and generally give your body a break. 

MTHFR-safe detoxes.

In general, I warn MTHFR folks away from detox kits unless they are a pro with detoxes and can read their body’s signs and symptoms effectively and know how to counter any adverse reactions. But just because we can’t do prepackaged kits very well, doesn’t mean we can’t detox.

Intermittent Fasting

 I love intermittent fasting. Love it with a passion. It’s easy, it’s safe, and it’s extremely well researched in all kinds of areas, but especially in promoting longevity. It’s just about the simplest and most effective health hack out there. Here’s how you do it.

  • 24-hour Fast: For a 24 hour fast, have dinner like usual, skip breakfast, lunch, and snacks the next day and drink plenty of water with a little bit of lemon in it (or plain if you’re not into lemon). Around the same time as you had dinner the night before, have a healthy, simple dinner. That’s it! It’s literally the easiest possible health-boost because there is less effort involved than you take on a normal day. 
  • 36-Hour Fast: For a 36 hour fast, have dinner the night before, skip all food the day of the fast and drink a ton of water or lemon water.  Get up the next morning (which is roughly 36 hours later) and eat a healthy breakfast. Done!

Clean Week

This is a great tool to use quarterly, and it can be as simple or as intense as you feel ready for that quarter. A simple clean week could be stripping your diet down to fresh fruits and veggies, rice, broth, and some gentle herbal detox teas. Take out some of the foods we tend to lean on that might not be the best – the grains, processed foods or packaged foods, refined sugars. During this week it’s important to rest more, be more mindful of toxin avoidance, and I like to take it as an opportunity to go inward – do a bit of journaling, clear out some clutter, that sort of thing. If you want to get more intense about it you can do a full juice cleanse, liquid diet, or alternate between juice only days and fasting days. This is a completely customizable tool.

Modified Month

This is exactly what it sounds like, and can be a really helpful format to use if you have a habit that you know is taking a toll. A modified month is like taking a reset on a bad habit – if you’ve watched your sugar cravings ramp up (like mine have) during covid, it could be a great idea to do a modified month over the summer in which everything else is mostly the same, but you cut out the sugar and sweets. Lots of people do modified months with events like Dry July or Sober October. Also, a modified month can be a great way to work on improving a good habit instead of eliminating a bad one. What about Active August or Hydrated… Shmydrated. I don’t have a rhyme for that one.

Detox can be as simple and small or as large and complex as you want to make it, and just because you did a big complex one last time doesn’t mean you need to do that again. Take your stress level and your life chaos into account when you’re planning this.

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What To Expect When You’re Breaking A Mental Bad Habit

Last week we started our conversation about the “bad habit” component, called neuroplasticity, of depression, anxiety, intrusive thoughts, and obsessive or compulsive thoughts. This is, of course, only part of the picture. Neurotransmitter balance is a factor along with the often overlooked physical contributors to depression and other states.


We discussed three main methods for breaking mental bad habits. Those are:

  1. The Fantasy
  2. The Stop and Drop
  3. The Distraction

When you’re first trying this, it can be really helpful to try all three strategies at different times to see what works the best for you. You’ll know it works when you are able to pop yourself out of your mental bad habit – to feel different in your body and to let go of whatever thought pattern it is that you’re working on.

Stages of Resolution With Mental Bad Habits

  1. Learning. In this phase, you’re actually learning to pay attention to your thoughts and that takes more time than you would think. You may find a particular “warning” signal for you – it could be a behavior (like when I’m starting to feel this way I always log on to Facebook and click links that make me angry or I start craving XYZ food. It could also be a physical feeling – a headache in a particular place, a clenching in your belly, pain in your neck or shoulders. It could also be something more subtle like tuning into your mood more frequently.
  2. Out of Control. This phase feels like you’re moving backward. You’ve started tuning in and now you’re actually noticing how much your brain does this thing and it’s a ton! It will seem like your brain is a wild horse racing ahead of you, and it feels like the bad habit is happening more, not less.  That is a GREAT sign because the reality is that you aren’t doing the bad thing more, you’re just noticing more and that is the first step to actually changing it. This can take a few months of diligent attention, but don’t get discouraged – you’re doing it and you’re making progress.
  3. Quietening. In this phase, you start to make tangible progress and you’ll notice that the mental bad habit becomes softer somehow. Quieter.  The thoughts/feelings are still there and they still affect you, but you’re learning to let them go more quickly and it’s easier not to get pulled in by them. 
  4. Maintenance. This phase is amazing.  One day you’ll notice your mental bad habit pop up and the first thought you’ll have is “Oh! I haven’t seen that for a while.” and you’ll dismiss it and move on. This is the phase where you have the freedom to move on to something else because that bad habit is mostly gone.  It’s a good idea to still take proactive action when it pops up, but it is popping up so much less frequently that it becomes almost a curiosity when it’s there.

Great! So I’ll be mentally healthy by next week, right?

Absolutely not. I would love to say it was easy and took no time or effort, but that would be a bald-faced lie. It’s a challenge and it takes time. You’ve probably had this mental bad habit for years if not for your entire adult life, so it will take some time to break it too. And some time doesn’t mean a couple of weeks, it means months and maybe even a year. This isn’t quick, but it is SO. WORTH. IT.

Does This Work Every Time?

This works every time if you stick with it, and when there isn’t some other major imbalance. If your serotonin is actually so low it’s living in the sub basement, then this will still help fix the habit part of it, but it won’t completely normalize the serotonin (but it will bring it up – research shows these techniques are associated with higher levels of both serotonin and melatonin). Although, every day we’re learning more about what this can actually accomplish.

What IS This Witchcraft? It’s Mindfulness.

Yup. That thing that hippies and new-agey types do. Also, everybody who studies neurology and neuroscience of any sort, because as it turns out the effects are so powerful as to be almost unbelievable.

Among the many documented effects of any form of mindfulness are:

  • Increased wellbeing
  • Reduced cognitive reactivity (so external things don’t affect you so much)
  • Reduced inflammation
  • Reduced reactivity of the autonomic nervous system (you don’t get an adrenaline spike every time something bad happens)
  • Higher serotonin
  • Higher melatonin
  • increased telomerase activity (anti-aging)
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