Transcription
Hi everyone, my name is Dr. Robin Lewis. I am a naturopathic physician practicing here in Vancouver, British Columbia, Canada. Today, I want to talk to you about something that I have been getting a lot of questions about in practice. This is in part due to the Gary Brea episode on Joe Rogan's podcast, but this is by no stretch a new concept in medicine.
What I'm going to talk to you about today is methylation. Methylation is the process of adding or removing methyl groups inside the body, and these very unique chemical reactions are very important for a wide variety of different things inside the body. For example, methylation issues have been linked to heart disease, mood disorders, neurological disorders, issues with detoxification, and pain. There are a lot of different things that methylation has its hands in, and that is what I want to talk to you about today.
Like anything, you can have too much methylation or too little methylation. When you hear people talking about this, they're generally referring to undermethylation, and that is largely due to the fact that about 40 to 60% of the population here in North America have a genetic variation that would dampen someone's ability to methylate to varying degrees, depending on your genetics and also depending on your environment.
There are two different ways this can go about, but I will be focusing mostly on the undermethylation problem because that is more often what's happening in the environment, whereas overmethylating usually has more to do with supplements, which is something that I will talk about. I'm going to focus a lot on the undermethylation issues because that's more prevalent in the population.
I also want to mention that this is going to be a two-part series. In part one, I really want you to get a foundational understanding of what methylation is, how it's affecting your body, and how you can test for it so you can tell if this is even something you need to worry about. Then, in part two, I'm going to talk about some of the therapies because this is a really nuanced topic, and the therapies that are geared towards helping do come with some side effects that you need to be aware of. These things need to be implemented properly; otherwise, you can end up feeling sicker rather than better.
All right, so first things first: what is methylation? This, again, is a biochemical reaction that happens inside the body, and it affects almost every single body system that you can imagine. It happens billions of times per second and has a role in repairing your DNA, regulating homocysteine (which has a huge impact on cardiovascular disease), recycling molecules needed for detoxification (so getting toxins out of the body), and regulating your mood and inflammation. The point I'm trying to make is that it does a lot of things inside the body.
Now, if we focus on a couple of specific examples, it'll make itself really clear just how important this is. One example of an extremely important role of methylation is to methylate our DNA. This is essentially what we call epigenetics, which means that we can turn certain genes on and off using methylation groups—adding and removing methylation groups to our DNA. Just because you have a gene for something, it doesn't necessarily mean it's going to turn into a physical reality. That gene needs to be turned on in order for it to translate into something that you see, feel, or that affects your health.
Take the BRCA gene, for example. The BRCA gene is highly correlated with different types of breast cancer and ovarian cancer. It does not mean that if you have the BRCA gene, you are absolutely going to get those things. If you have a means of turning those genes off, there is a better chance of you never developing these diseases, even if you have this highly unfavorable genetic variation. So that's one of the roles of methylation.
Another big role of methylation in the body is detoxification—getting toxins out of the body. One of our main methylators, something called SAMe (S-adenosylmethionine), which I will describe a little bit more later, is really important for helping replenish our glutathione, which is our master antioxidant. This glutathione molecule will help work with the liver to process chemicals and get them out. It will also help us replenish our other antioxidants, like vitamin C. Glutathione is incredibly important in the body, and people who have methylation issues will often be very sensitive to chemicals in their environment because they can't process and get those chemicals out as efficiently as someone who doesn't have this issue.
This is a pretty big deal because, I don't know if you're aware, but we are constantly inundated with various different environmental toxins, whether that be through our food or pollution in the air. The point is, we are exposed to a lot of things, and we have mechanisms inside our body to get rid of those things so they don't stay in the body and create more problems. But if you have problems with detoxification, that's going to make it a really hard challenge to get those things out. So methylation plays a huge role in this.
The last example I want to give you is how methylation plays a role in regulating some of our neurochemicals that play a role in things like anxiety, depression, ADHD, and so on. SAMe, that molecule I was just referring to, has a huge impact on our enzyme called COMT (catechol-O-methyltransferase). This enzyme will help deactivate things like dopamine and our adrenaline hormones inside the body. So when we're finished with these hormones, this enzyme will help deactivate those chemicals so that they don't create things like overstimulation and other mood disorders.
Again, this is just one example of how methylation is affecting our mood, our detox, and other aspects of our health. These are just some examples of how methylation is affecting our health and some of the roles it has inside the body.
Now let's go into why or how you develop methylation issues in the first place. I like to break this into two main categories: genetic and environmental—the classic gold nature versus nurture debate. Both of these things play a role, and I'm going to start by talking about the genetics.
Now, we all have genetic variations that can give us advantages or disadvantages, and over the years, they have found quite a few different genes linked to methylation. This includes things like the MTHFR, MTR, and COMT. There are many different genes that they're studying, and more, I'm sure, will come down the pipeline as this is an ever-evolving science. But there are certainly some of these genes that get more airtime than others, and the MTHFR is by far the most talked about. This likely has to do with the fact that it's really common in the general population.
This gene stands for methylene tetrahydrofolate reductase, and it is an enzyme that has a role in converting folate into its active form of five-methyl tetrahydrofolate. I know it's a mouthful, but this is essentially taking inactive B9 and converting it to active B9. Interestingly enough, a lot of our B vitamins actually have to go through an activation in order for them to be used in the body. This is also a really good example of why it's important to know what's in your supplements because a lot of these cheaper forms of B vitamins will give you the inactive form. For those people who don't have this genetic variation, that's okay; they can convert it. But for the people who do have this problem, they are not going to be able to take that cheaper supplement and convert it inside the body into something that they can actually use.
I also want to highlight that having this enzyme working well and having your active B9 levels adequate has a heavy influence on other compounds like B12 and that SAMe molecule. This is why you will often see all three of those things going into methylation protocols, as they are all very interconnected and heavily influence each other.
So the MTHFR gene does affect directly B9, but indirectly it's affecting a lot of other compounds. Circling back to the genetics, there are two main variations in that MTHFR gene: the first being the C677T variant and the second being the A1298C variant. For each of these genetic changes, you can either have one or two copies of this variation. That's how it always works with genes; you have a copy from your mom and a copy from your dad. Of course, if you have one of these genetic variations, then it will put you at a reduced function of this enzyme. But if you have two genetic variations, then the two compound together, and the problem is worse.
For example, approximately 20 to 40% of the population is heterozygous for the C677T variation. Heterozygous refers to one bad copy, so they have one of these variations, not two. Having one of these reduces the function of that enzyme by up to 35%. Now, if you are homozygous, meaning you have two of these variations, then it can reduce the function of that enzyme by up to 75%. Of course, that is a massive reduction, and you can only imagine how much that influences the body.
So that's just one of the variations of one of the genes. The A1298C variant can reduce the enzyme to a similar degree, but the A1298C variant is a little less common in the general population. As you can tell, these genetic variations are very common, and they can present on a spectrum depending on how many bad copies you have of how many genes. For some people who are perhaps heterozygous, they only have one of these copies; they might be able to get by for a while. Or if you are even homozygous but you're living a life that is very healthy and you're taking the supplements and stuff like that, you might also get by.
But what you'll often see in practical life is that these people will start presenting with a lot of these peculiar symptoms that perhaps have to do with detox or mood or whatever. They only really start to present with symptoms when the demand goes up. This is where we kind of get into more of the environmental things that can deplete this system. If you have a genetic variation, you are incredibly susceptible to the environmental things that can deplete methylation, and for some people, those are the moments where you might actually start to present with symptoms.
This then begs the question: what increases our demand for methylation? What increases our demand for B9, B12, and SAMe? Because even in people who don't have these genetic variations, they can start to present similarly to these people if the demand is high enough. So it's really important to identify these things.
The first thing I want to talk about is medications. There are certain medications that will deplete our methylators, our B9, and our B12. As you can see from this list, there are quite a few, and this is not even really a complete list. A really good example is something like metformin. This is an incredibly common medication that is given to people who have type 2 diabetes. Now, for most things, it's really good, but it does tend to deplete your B12. So as we can refer back to that diagram, that could perpetuate this issue. If you have one of these genetic variations, you will likely be more sensitive to that medication and more likely to develop side effects from the low B12 because the system was already burdened to begin with.
So identifying different medications that can be perpetuating the problem is really important. And it's not just medications; different supplements can also eat through our methylators. A really good example of this is niacin, and they will actually give this to people who are overmethylating to help with that response. But there are certain supplements out there that can do it as well.
Toxins in our environment, as I mentioned before, the SAMe is really important for replenishing our glutathione and our antioxidants. They need to clean up all these things we're exposed to. So again, if we're exposed to more, the demand goes up, and this is also seen in high stress. Yes, stress kills everything. The more stressed we are, the more sleep-deprived we are. There are certain farming practices that are depleting our soils of these nutrients, which is a way of getting a deficiency of nutrients. This again is going to burden the system if you're low in things like B9 and B12 and all of those things that should be coming into our diet. If you don't have good nutrition or if you're eating nutrient-depleted foods, then that's an issue as well.
So yes, there are a lot of different things that can create a methylation issue if the demand is high enough, and there can definitely be a cumulative effect. If you have a combination of these things, we do need to set aside some time to talk about how to test for these things, and I will be brief.
The first, most obvious thing is to get some sort of genetic testing. They usually do this as a cheek swab. There are many different types of genetic testing kits out there, run through different programs or different companies. I personally used one based out of Ontario called Love My DNA because they have a very good variety of markers that they assess. Really, that's ultimately what I'm looking for: how many of these markers do these tests look at, and how easy are these tests to interpret? They should always be interpreted by a doctor for you so you can take it into context and know what to do with that information.
Yes, genetically testing for these variations is massively important. You can also look at nutrient testing, so assessing your B12 levels, for example. That's one way to assess the system. Mind you, there are lots of things that can create a B12 deficiency, so it doesn't directly tell you it's a methylation issue, but it's a part of the methylation pathway. That's one thing you can look at.
The other big one would be testing something called homocysteine because homocysteine will go up in individuals with these genetic variations, or eventually, it will go up. Not everyone who has the MTHFR genetic variation will have high homocysteine; perhaps they're living a very healthy lifestyle and can kind of get by. But if you do have something like homocysteine getting elevated and flagged in your blood work, I would argue that it's a good opportunity and a good idea to go get your genes tested because that could be a root cause of the high homocysteine, which is very damaging to our blood vessels and our cardiovascular system.
So ultimately, it's the genetic test that for sure tells you about this high probability of reduced function of these enzymes. But yes, there are other markers you can look at to assess the collateral damage of being an undermethylator.
Okay, so that's probably a good place to stop. I am again going to do a part two where I dive more into how to treat, supplements to look at, and things to consider when you're taking some of these methylators. But again, they are something that can have side effects if you're not implementing them properly. So that'll be in part two. Thank you again for listening. If you have any questions, by all means, please comment them below, and I thank you for your continued support.