Gene mutations are caused by environmental factors (think radiation & chemicals), or by errors that occur during natural replication.
We all have them.
Some gene mutations become hereditary. Like other genetic characteristics, we give them to our kids.
Genetic mutations can have complex consequences.
For example, there's evidence that a genetic mutation enabled early humans to process plant-based foods, allowing for expansion of the fish-based diet that had previously kept them tethered to bodies of water in central Africa.
This mutation enabled migration across the continent, which created cultural diversity as we know it today. It also (eventually) created the diseases of civilization for descendants of these early Africans (I might be one), which we are now trying to heal by returning to our ancestral eating patterns.
Pretty profound consequences for a mutation in one little gene cluster.
Advances in genomic analysis enables us to access huge amounts of data about possible mutations in our 24,000 genes.
It's nice to think that somewhere in this superabundance of highly-individualized scientific information, there might be answers to some of the challenging health questions we've been asking.
Of all the data generated through genomic analysis, the MTHFR gene mutation is getting the most attention.
MTHFR the current darling of the alternative health care world.
The MTHFR gene is involved in the methylation cycle, as described by Rory Linehan in part 1 of this post
Considering the primacy of the methylation cycle for our health, it makes sense that it is being targeted as an intervention point. Unfortunately, what we don't yet know about how to address specific genetic mutations outweighs what we do know, and it’s inevitable that we'll make mistakes along the way.
The best we can do is continue to refer to emerging research, conduct informed experiments & share the results with each other. That's the spirit this post is offered in.
Treating the MTHFR Mutation
The problem: blanket prescriptions for supplements are being issued on diagnosis of the (very common) MTHFR gene mutation, but many people aren't responding well to this approach.
Chris Kresser addresses this phenomenon in a podcast:
"Impaired methylation is fairly common. That’s because a relatively high percentage of the population, 45% of the population, is heterozygous for an MTHFR mutation, which, in layperson’s terms, means almost half the population has a genetic mutation that reduces the activity of the MTHFR enzyme up to between 20% and 40%. That alone doesn’t mean that the enzyme won’t function well. I want to emphasize that. I see a trend out there that really disturbs me, which is that people are getting genetic tests, and then taking supplements only on the basis of their genetic results. I think there’s really nothing in the research literature to support that. Genes load the gun and environment pulls the trigger, as I’ve said before. Genes can tell you what kind of methylation issues you’re predisposed to having, your specific genetic profile. But it can’t tell you how you’re actually methylating or whether you need methylation support. I just want to emphasize that, because I’ve been seeing that there are these companies now where you can run your genetic profile through them, and they spit back a list of supplement recommendations. I have a big problem with that. It’s a huge pet peeve of mine right now. I see a lot of people doing potential damage to themselves by just following those recommendations based only on the results of their gene profile."
Turns out a number of Autoimmune Protocol (AIP) bloggers have experienced this first-hand:
Mickey blogs with Angie Alt at Autoimmune Paleo.
She says: "This is a huge topic considering how popular MTHFR is in the community right now. A lot of people are really jumping to conclusions and engaging in treatment that has not been proven to be clinically significant, and in some cases, quite harmful. I have a compound heterozygous mutation (one of each), and supplementation created histamine issues from being over methylated. Diet and avoiding toxins go a long way in treating most of the population with these mutations.”
Rory blogs at The Paleo PI. He had to sleuth his own solution after being prescribed an inappropriate supplement based on the diagnosis of the MTHFR mutation:
"I also have an MTHFR mutation and at one stage was supplementing with P5P . It ended up doing much more harm than good, causing some real bad inflammation, as my CBS enzyme (later in the methylation cycle) has its own mutation causing me to process sulphites too fast. This caused a massive build-up of sulphites between CBS and SUOX (the next enzyme in the cycle) as my SUOX runs at standard pace. Having some luck now with getting my CBS back to a normal pace."
(Warning: Once you start down genomic analysis rabbit hole, you almost need to learn a whole new language!)
Matthew doesn't blog (I do!) But he does have autoimmune conditions which he is managing through personalized (n=1) experimentation methods.
He was prescribed Methylfolate by his Functional Medicine Doctor based on his heterozygous MTHFR C677T gene mutation. Methylfolate can cause side-effects, many of which mimic Matthew's existing symptoms (irritability, insomnia, sore muscles, joint pain and nausea), so it took a while to figure out that the supplementation was actually making things worse. He abandoned that treatment. After studying his genetic report & doing his own research, he discovered that he was also homozygous for the MTHFS gene mutation. As a result he was prescribed Folinic Acid, but experimental treatment with Folinic Acid resulted in excruciating intestinal pain, so that treatment was abandoned as well.
Matthew has to be careful to implement only one treatment at a time, both to determine how a new protocol affects him & because he tends to experience all the gnarly side-effects for any given treatment. He’s in experimental treatment recovery mode right now, and to date hasn't found an effective treatment, other than a nutrient-dense diet (he remains on a low-FODMAP version of the Autoimmune Protocol).
Angie blogs with Mickey Trescott at Autoimmune Paleo. She comments on the successful treatment of her own MTHFR mutation:
"I have the most severe form of this mutation, but my blood work looks so awesome that I am basically "outdoing" it. I take a simple methylated B vitamin & eat right. Case closed. Having the super bad version of the mutation & Birth Control pills did not mix (life improved immensely when I stopped Birth Control). And I have labs that show my B-12 was in the tank at Celiac diagnosis, shot through the roof with supplements (not methylated forms), then when I switched to methylated it evened out nicely. Oh! And after I started methyl Bs, my skin (acne) finally cleared! My liver could detox better, is my assumption. Still not resolved: infertility. But I am sure that is more than just MTHFR."
Joanna blogs at Conscious Autoimmunity. She has also experienced success with supplementation, as part of a constellation of strategies:
"Careful supplementation has helped me HUGELY (along with a host of other things, like the Autoimmune Protocol. Having a Functional Medicine doctor who is aligned with my health goals has been invaluable. I do understand that our bodies are amazingly adept at self-regulating when we look after them properly. For me, the interesting thing about all of this is the 'bio-individuality' for us all.
The starting point for me was recognising alarmingly low levels of Vitamin D when investigating 23 years of a chronic skin condition, Hidradenitis suppurativa (HS) and a self diagnosed suspicion that gluten was not my friend.
Further testing indicated compound Heterozygous MTHFR, Pyrrole disorder and severe gut dysbiosis (I had pretty serious periodontal issues, too.)
I'd had chronic acne as a teenager and have since learnt that I was not good at managing stress. I think working out the right MTHFR/Pyrrole combo of supplements has mainly positively affected the quite severe anxiety I never really acknowledged I had until it wasn't there anymore. I'm just more 'zen' about things. Which doesn't sound like much, but has REALLY affected my quality of life.”
There is no standard approach to effectively the impacts of the MTHFR gene mutation, and automatic prescriptions based on diagnoses of the mutation can be detrimental.
Some people find that supplements, in the right dose and correct combination are effective. Laura Matheos found this sweet spot for her daughter.
Working with a knowledgeable health practitioner is key.
We are complex systems attempting to heal ourselves inside complex systems. As such, some approaches to treatment may be generally applicable (including an anti-inflammatory diet like the Autoimmune Protocol) but an individualized approach to supplementation seems to be required.
SAD to AIP in SIX
The safest way to manage any gene mutations is through nutrition and lifestyle.
SAD to AIP in SIX is a an online program, created by Angie Alt and facilitated by trained, certified coaches, that supports the process of transitioning to the Autoimmune Protocol (AIP) over 6 weeks. Every detail of the diet and lifestyle changes required for the AIP occurs at a manageable pace.
Enrollment for SAD to AIP in SIX is open 5 times a year.