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

Methylation, Detoxification, and the Glamorous MTHFR Lifestyle.

I’m picturing sequins and feathers and beautiful women in luscious red dresses and martini glasses with skewers of exotic fruit. Okay, so maybe it’s not that glamorous, but there IS an MTHFR lifestyle. We’ll get to that in a minute.

This is EXACTLY what the MTHFR lifestyle is like. In my dreams..
Amazing photo Photo by Boluwatife TheSalt from Pexels

First, The Detox Part…

Detoxification sounds like a thing we do after a raging party or a week-long trip to Vegas. In reality, it isn’t. It’s something we do CONSTANTLY. We detox after drinking water, breathing air, eating food, exercising, during sleep and just from the entirely normal body processes that happen every day. This isn’t reserved for when you’ve added something to your body that is known to be toxic, it’s as constant as death and taxes.

You can, of course, “do a detox,” which usually means taking a few days out of your life and really pushing your body to clean house, by either fasting or eating a very simple clean diet, supporting your liver with herbs or supplements, ramping up the fiber or other gut sponges like clay or charcoal, and doing detox activities like Epsom salts baths and saunas to sweat it out. “Detoxing” in this way is also dependent on methylation, but I’m talking about the far more simple every-day housekeeping that your body needs to do.

Why Do We Need Methylation To Detox?

Methylation is actually one of the main pathways your body uses to eliminate certain toxins. Detoxification of most substances happens in three phases, a few substances need all three, most need two and some need only the first phase.

  • Phase I – Modification. In this phase, the original toxins are modified to make them more reactive and polar. This is so that we can do more things to them – like making them water-soluble (if they’re fats) or getting them into the right state to attach something else to them so we can actually chuck them out. Note that phase I often makes these chemicals more active, and they’re usually still small enough to cross cell membranes so if they can’t move on to Phase II, they can hang around doing damage – sometimes even more damage than the original substance itself. This largely happens through the Cytochrome P450 pathway, which we don’t need to discuss here.
  • Phase II – Conjugation. This phase attaches a charged molecule (like a methyl group, for instance), in order to make the molecule less biologically active and also allow it to be actively transported out. There are six different phase II reactions, one of which is methylation.
  • Phase III – Further Modification and Excretion. Many toxins are excreted after Phase II, but a few need this additional step.

What Happens in Methylation?

To be clear, this does not use the MTHFR enzyme directly, it uses the product of the MTHFR enzyme, which is SAM-e. In methylation reactions your body takes the mutant-mickey-mouse-head methyl group off of SAM-e and attaches it to the toxin so that the toxin can be eliminated. For MTHFR folks, SAM-e might not be as plentiful as it should be, because there is a bottleneck through the MTHFR enzyme.

The chemistry-intense process of toxin methylation, made ridiculously simple.

What Type of Toxins Need to Be Methylated?

There are many, but the ones of most concern are heavy metals. These include arsenic, mercury, selenium (which is toxic with too much exposure, but necessary in small amounts) and cadmium.

That Doesn’t Seem Like A Lot – What Is The Problem?

As with every other body system, chemical pathways and enzymatic reactions have the bad habit of interconnecting – meaning the products or function of one pathway ends up being necessary for the action of another. This is how MTHFR messes up your urea pathway (how we detox ammonia and make urine) and any pathway that needs glutathione (the master antioxidant. They don’t call it that for no reason.) We’ll have to get to glutathione another week because this is getting a bit heavy.

Okay, So… The Urea Pathway.

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

As you can see in this diagram, the urea pathway uses end products of the BH4 pathway, which needs methylation to work. If methylation is bottlenecked, BH4 is in short supply, and the toxic waste ammonia builds up because your body can’t convert it to urea, which is eliminated in your urine. Ammonia causes neurological inflammation. At very high levels (usually only seen in actual liver failure – not so much with MTHFR mutations) ammonia overload can lead to seizures, coma, and death.

What Is The MTHFR Lifestyle?

It sounds like it could be so good. And honestly, for people with MTHFR mutations it does make life much better, but it’s not so glamorous. We will talk about it at great length in other posts, but here are some of the basics.

We will talk about all of this in detail – I promise.

An Interesting Aside About Sweating It Out

There has been lots of debate over the usefulness of sweating during therapeutic detox, with naysayers, like this article in the New York Times, claiming that such a tiny amount of toxin elimination is effectively meaningless.

Dr. Schwarcz compared it to someone sitting in a bathtub worrying about drowning. Removing a dropper-full of water from the tub will theoretically reduce the risk — because the chance of drowning is lower in less water — but getting rid of so little water will be effectively meaningless.

Dr. Joe Schwartz, Chemistry professor, McGill University. Cited from above linked NYT article.

Interestingly, the article also acknowledges that heavy metals and BPA from plastics have been detected in sweat.

A systematic review, published in the Journal of Environmental Public Health, compiled research studies on arsenic, cadmium, lead and mercury excretion in sweat. This shows a clear documentation within the research of the ability of your body to eliminate these substances through sweat.

Arsenic, cadmium, lead, and mercury may be excreted in appreciable quantities through the skin, and rates of excretion were reported to match or even exceed urinary excretion in a 24-hour period. 

Sears ME, Kerr KJ, Bray RI. Arsenic, cadmium, lead, and mercury in sweat: a systematic review. J Environ Public Health. 2012;2012:184745. doi:10.1155/2012/184745

Clinically, I have seen therapeutic sweating as part of a larger protocol to be highly beneficial for many clients, helping them to improve their energy levels, reduce brain fog, decrease sensitivity reactions and improve their overall health, but on the evidence pyramid, things we observe in clinical practice are always on the low end, because there are so many uncontrolled variables. Those people might have improved because of sweating AND other things we were working on, or solely because of the other things we were working on, or because of something entirely different. This is why, when I’m talking about things I’ve observed in clinical practice, I’m very careful to specify. Also, in terms of my categories of evidence, I’d give the whole sweating it out concept a C. This means there is a combination of some research and clinical evidence, but not definitive proof.

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