This whole week’s topic stemmed from a call-in question from Jane Turner that piqued my curiosity, so thanks, Jane! Here’s the question:

I just found out that I’m an MTHFR mutant… I have some pain issues, and I was wondering how NSAIDs or other pain medications that are tempting to use might be influenced by MTHFR, and if there are better choices that I should be considering?

– Jane Turner on the To health with that! Podcast

This is so relevant because pain is an experience that is shared by a lot of MTHFR folks. We have a higher tendency toward inflammation than average and that can be a big source of physical and structural pain, but we also have tendencies towards altered neurochemistry and with some neurochemical imbalances, the perception of pain is also heightened. Just to add to that, many of us MTHFR folks have a tendency to push ourselves to extremes – extreme competition athletics (especially in undermethylators), extreme expressive athletics like dance (in both over and under methylators), and extremes of ignoring self-care in favor of artistic, professional or athletic goals ( in both over and under methylators). Add to this all of this the sensitivities and toxicities which can contribute additionally to inflammation, pain is part of the MTHFR experience.

MTHFR and Pain Medications

Let’s start this off by saying, as I so often find myself doing, that research is limited. Very limited. We will go through different pain medications individually.

What is the risk of MTHFR mutations and pain medications?
In the case of pain medications and MTHFR mutations, what are the risks associated with them?

MTHFR and Tylenol

Tylenol (or paracetamol, or acetaminophen) is one of the most common pain killers used globally and is sold in most places without a prescription. The exact mechanism of action isn’t known, but it may act to reduce prostaglandins in the brain, thus decreasing the sensation of pain. It is not like most commonly sold pain medications, an NSAID (which stands for non-steroidal anti-inflammatory) because it is not known to be strongly anti-inflammatory.

Tylenol has been shown to reduce levels of glutathione, which could be part of why Tylenol overdose is one of the most common causes of fatal poisonings worldwide. This could also present more sensitivity for MTHFR mutants than for other folks. With an MTHFR mutation, our glutathione production is compromised to varying degrees (via the BH4 pathway). Glutathione production depends on many factors, not just MTHFR so this isn’t a cause for total avoidance, more just a cause for caution about prolonged or high-dose use. There is absolutely no research on Tylenol specifically with MTHFR – literally not one study, so it isn’t a well-documented issue. This is more of a theoretically potential issue, but something to be aware of if you take Tylenol on a regular basis. Also, it’s good to consider other factors that can deplete glutathione, like smoking or alcohol use.

MTHFR and NSAIDS – Ibuprophane, Naproxen Sodium, Etc…

Again, not even one study exists on this topic. I did stumble across a fascinating study about residual NSAIDs in water supplies increasing oxidative stress in a tiny water creature called Hyalella, but it would be hard to leap to any conclusions from that. At the end of the day, this one is a big unknown.

As far as I’m aware there aren’t any specific risks to MTHFR folks with this category of medications, but of course, all medications should be treated with caution.

MTHFR and Opiates

Opiates, especially lately in North America, have been the topic of extensive research because there is such a huge potential for abuse and also fatal overdose. As pain medications, opiates are highly effective and overlap into psychiatric and mental/emotional pain relief, which makes them especially helpful to many people. Unfortunately, there is a higher risk of opiate dependency for people with MTHFR polymorphisms, and research is only beginning to explore MTHFR as a factor in other addictions.

The unfortunate fact with opioids, is that many of the people with addictions started out with legitimate pain, and legitimate reasons to take legitimate medications. This isn’t the shadowy criminal underworld, this is just people looking for answers to medical problems.

There is a lot of controversy surrounding MTHFR and pain medications - are opiates really worth the risk?
MTHFR and pain medications – are opiates worth the risk?

MTHFR and Aspirin

This area is absolutely fascinating. Aspirin is a pain medication, of course, but also a well-known blood thinner. While there isn’t any research on aspirin medication for pain in MTHFR folks at this moment, there is some great research on aspirin for MTHFR families who have a history of repeat miscarriages. This study compared treatment with 100 mg aspirin + 5 mg folic acid daily with 100 mg aspirin + 5 mg folic acid + low molecular weight heparin (another, stronger anticoagulant). It showed a significant difference between the groups – with the triple therapy group having more positive pregnancy outcomes than the double therapy group. My only complaint is that the control group (the group that receives no therapy) were women without a history of repeat miscarriages or MTHFR mutations, so it’s difficult to see how much of an improvement from baseline it is for both groups.

This also suggests to me that micro-clotting, which is thought to be the mechanism that is interfering with these pregnancies in the first place, might be more of a routine issue for MTHFR folks than we realize. A similar study was done in women who were not tested for MTHFR mutations, which found that both aspirin and aspirin + heparin were effective in increasing pregnancy outcomes.

MTHFR and pain medications - the benefits of aspirin might surprise you
If you have MTHFR gene mutations and take pain medications, you might be surprised to learn how beneficial aspirin can be

Aspirin may also reduce the risk of colorectal cancer in MTHFR mutants, but the evidence, in this case, is really mixed.

MTHFR and Nitrous Oxide

Nitrous Oxide is not a conventional pain therapy, but it is used as an anesthetic, often for dental procedures or other minor surgeries. This is a really interesting case and it deserves its own post because there is a lot of information, but the quick and dirty version is that Nitrous oxide is not the best choice for MTHFR folks because it lowers plasma vitamin B12 concentrations (this study has a great discussion of how exactly that happens), which can, in turn, raise homocysteine levels. Elevated homocysteine and low B12 are factors that a lot of MTHFR mutants struggle with anyway, so this is doubly bad for us. Bad enough to be fatal in the most extreme cases, and also to cause blood clotting and it’s secondary effects (like heart attack and stroke).

For MTHFR-safe options for pain management, look for fewer drug-based treatments and more hands-on pain control methods. We’ll do a whole post about it in the future, but the most well-documented and researched therapies are:

  • Therapies that break up fascial adhesions like gua-sha, myofascial therapy, fascia scraping and any bodywork technique like Rolfing.
  • Light therapies like 660 – 670 nm/850 nm red light therapy
  • Cognitive behavioral therapy for chronic pain
  • Acupuncture
  • Cold laser therapy
  • Magnet therapy
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