Nitric Oxide, MTHFR, and NOS3

MTHFR is well known for causing heart health issues. It’s directly responsible for raising homocysteine levels, it’s implicated in troublesome blood clotting, and it’s indirectly responsible for making it harder to make adequate nitric oxide.

All of this is compounded if you have MTHFR and another gene SNP called NOS3.

What is Nitric Oxide?

Nitric oxide is the primary substance responsible for keeping your blood vessels open and relaxed so that blood can flow through easily. Without it, your blood vessels tighten and constrict, which drives up blood pressure and reduces oxygenation of your tissues. The primary function of your blood is to carry oxygen to all of the muscles, organs, and tissues that need it, and nitric oxide helps make that happen.

Nitric oxide also helps to keep your platelets, those tiny flakes in your blood that make up blood clots, nice and smooth and slippery. It inhibits platelet aggregation and adhesion, and even helps to destabilize any small clots that have formed.

Blood that clots when you’re injured are a good thing – they keep you from losing too much blood. Blood clots that happen for no reason, are deadly. That is what lies underneath the bulk of the heart attacks and strokes out there. You want blood that is smooth and free of clots.

Nitric oxide also helps with the growth and formation of new blood vessels.

Why Does MTHFR Affect Nitric Oxide?

MTHFR is part of the folate cycle, turning inactive folate into the active form, which is 5-LMTHF. The folate cycle needs to spin in order for a linked pathway, the BH4 pathway, to also spin. The BH4 pathway is most known for neurotransmitter formation because this is where we see serotonin and dopamine formation. BH4 is also necessary for nitric oxide synthesis. There is a detailed pathway document in the show notes, if you really want to dive in, but suffice to say if MTHFR is sluggish, then nitric oxide synthesis is also sluggish.

Let’s Talk NOS

NOS stands for nitric oxide synthease and there are three different forms, depending on where they are located in your tissues. NOS1, is also called neuronal NOS (or nNOS). NOS2 is also called iNOS, or inducible NOS, and NOS3 is epithelial NOS, or eNOS. eNOS, or NOS3 is extremely important here because it is most represented in the epithelium, which lines your blood vessels and so has the greatest direct impact on vessel dilation as well as clotting.

Nitric oxide is made from arginine, which is one of the building blocks of protein, and so that matters for proper functioning, as does calcium. Under normal circumstances, NO synthesis is dependent on the level of calcium within the cell and so that must be adequate. NO synthesis can also be influenced by injuries, such as shear stress, that require changes to blood flow.

NOS “Uncoupling”

There are many factors, mostly implicated in heart disease, that can set up a bad situation with your NOS. These factors include diabetes, ongoing high blood pressure, high cholesterol, aging, and metabolic syndrome and they all lead to higher percentages of oxygen radicals, which can in turn cause NOS to break off of BH4, or “uncouple” and bond with a reactive oxygen species. This establishes a cascades of enhanced free radical production that does nobody any good. This is part of why your doctor is so eager to treat diabetes, high blood pressure, and cholesterol before they have a chance to do long-term damage.


The NOS3 gene SNP, as you might have guessed, has its biggest consequences in heart and cardiovascular health, but also influences some tissues that rely heavily on constant, tightly regulated blood flow like your brain or a developing fetus. It is especially likely to create problems in situations with overlapping pathology, like NOS3 Gene SNP with diabetes, which also decreases circulation.

Common signs of NOS3 problems:

  • Chest pain with exertion or away from it
  • Cold hands and feet (poor circulation)
  • High blood pressure
  • Erectile dysfunction
  • Migraines
  • Stroke
  • Chronic sinus issues
  • Blood clots
  • Congenital heart defects (in babies born from mothers with untreated NOS3 polymorphisms)
  • Arteriosclerosis or hardening of the arteries
  • Preeclampsia in pregnancy (this is also a risk with MTHFR alone).
  • Family or personal history of Alzheimer’s disease.

Supporting a NOS3 Polymorphism

There are many ways you can support nitric oxide synthesis in your body, with or without a NOS3 gene SNP. Here are just a few:

  • Eliminate Folic Acid – folic acid causes a decrease in BH4, which is bad for your nitric oxide synthesis and your neurotransmitter production (also, your methylation).
  • Hum! – eNOS is highly expressed in your sinuses, and humming causes a 15-20 x increase in nitric oxide synthesis in those tissues. This is part of why breathing through your nose at night is so important for tissue oxygenation. A wonderful study published in the journal Medical Hypothesis showed that not only will strong humming for an hour every evening clear up nasal blockages and sinus infections, it also increases your functional nitric oxide.
  • Eat a low glycemic index diet – lowering your blood sugar fluctuations as well as your blood sugar in general will help your NOS, your heart, and your risk of diabetes in the long term. This means that every meal and snack should have a balance of proteins, good fats, fiber, complex carbs and sugars. A big pop or candy bar in the middle of the afternoon with no real food to back it up is the opposite of this.
  • Breathe through your nose– talk with your doctor about mouth breathing (Especially at night), try mouth taping, and make sure any larger issues like deviated septum get addressed. Deep breathing exercises for one minute three times per day can really help as well.
  • Exercise – exercise is great for everything and a healthy NOS3 is no exception.
  • Stop smoking and stay away from chemicals – chemicals in your environment can impair your NOS function by reducing the amount of BH4 produced, as well as impacting glutathione levels and NOS needs support from glutathione so it doesn’t get into the uncoupling situation.
  • Good dietary sources of arginine, calcium, and B2. Arginine comes from high protein foods like meat, dairy, and legumes which you will be eating more of with a low glycemic index diet. Calcium also comes from dairy, dark ark leafy greens, and broccoli. Riboflavin can be found in eggs, liver, lamb, mushrooms, spinach and almonds.

Whether you have a NOS3 polymorphisms or not, supporting a healthy nitric oxide function is crucial for a healthy heart, brain, and sinuses. It is especially important if you have an MTHFR polymorphism because we do have tendencies toward compromise in this area. Plus, most of the steps here overlap with the MTHFR lifestyle – so if you do the MTHFR lifestyle plus some deep breathing or humming, you’re there.

Share with friends:

S2E32: Glutathione Review with gene SNPs GGS, and GGT.

We haven’t discussed glutathione in a while, but MTHFR’s effects on glutathione production are of major consequence in the health of all of us MTHFR folks. While a sluggish methylation typically leads to a sluggish glutathione production, there are some particular gene SNPs that have a far greater impact. The most notable are GGS, GGT, GST and GPX.

Glutathione – The Master Antioxidant

Glutathione is an antioxidant just like vitamin C or vitamin E and it helps to scavenge free radicals and stop them from damaging your vital tissues. It is considered your “master antioxidant” because it also recycles other antioxidants, like vitamin C, so they can be used again. Kind of like an antioxidant double-whammy.

In addition to antioxidant function, glutathione is vital for a number of different detoxification reactions, specifically phase II detox reactions called glutathione conjugation. This type of reaction is necessary for some herbicides and pesticides with xenobiotic compounds known as “persistent organic pollutants”, or “POPs.” Mercury detoxification, especially from your brain, is dependent on glutathione.

Also, tylenol which in spite of being a common over the counter drug worldwide, is also the #1 leading cause of fatal overdoses. Tylenol, also called acetaminophen or paracetamol, needs glutathione to be detoxified. Remarkably, the life-saving hospital treatment for tylenol overdose is a glutathione IV, which saves an incredible number of lives but only if it is administered quickly.

If all of that weren’t enough, glutathione is vital for the function of your mitochondria. Your mitochondria power your cells, quite literally supplying the energy required for the rest of the cell to work. Creating this energy, however, leads to an extremely high burden of reactive oxygen species, or free radicals. If the mitochondrial glutathione isn’t enough to keep this in balance, then cellular energy production falters, leaving cells without the proper fuel to function. As you can imagine, this makes for a chronically tired, worn-down body.

Lastly, glutathione is vital to appropriate cellular death. Cellular death may be something that sounds like a thing you don’t want, but let me assure you – appropriate death for cells is actually crucial to your survival. Cells that do not die appropriately, in addition to adding a burden to your body, boosting inflammation, and creating an unhealthy internal environment, lead directly to cancer. Cancer is, quite literally, a cell that won’t die and reproduces without check. Glutathione is one of your body’s internal defenses against such cells.

Gene SNPs that Affect Glutathione Production – GSS and GGT

GSS stands for glutathione synthetase, and this gene encodes for one of the main enzymes involved in the actual manufacture of glutathione. As you might guess, SNPs affecting this gene tend to reduce the amount of glutathione produced by the body and so manifest in a reduced capacity to detoxify mercury and persistent organic pollutants, and has been implicated in some heavy hitting chronic disorders such as COPD and ALS.

Outside of this, however, this SNP has not received much research attention and so there is a lot we don’t know. Information on different SNPs and the level of glutathione impairment isn’t out there yet, so watch for this one in emerging research over the next few years.

GGT stands for gamma-glutamyltransferase and there are a number of different varieties of this gene and enzyme, so we see GGT1 through 7. This enzyme also is not well studied, but is another essential step in the formation of glutathione. There is some evidence that risk of acute pancreatitis is higher in smokers with a polymorphism in GGT1, Outside of that, however, this area is largely unexplored in humans.

I think it is entirely possible that these genes will be found to be consequential in future research, but at the moment that data just does not exist.

Natural Ways to Boost Glutathione

There are some great natural ways to boost glutathione that we covered in more detail in Season 1, Episode 14: Glutathione and MTHFR. That episode also covered known diseases linked to low glultathione. Some of the best ways to boost glutathione include:

  • Whey protein
  • Omega-3 fatty acids
  • Foods high in selenium like brazil nuts
  • Riboflavin
  • Vitamin C
  • Vitamin E
  • Alpha-lipoic acid
  • phytonutrients from fruits and veggies
  • Brassica veggies specifically – including broccoli, cauliflower, kale, cabbage, and brussels sprouts.
  • Herbs including rosemary, turmeric, milk thistle, and ginkgo biloba, green tea
  • Fruits and vegetables that actually contain glutathione including: asparagus, avocado, cucumber, green beans, and spinach.

Thank you so much for listening and next week we’ll talk about two well-explored genes that affect glutathione, called GST and GPX.

Share with friends:

S2E31: COMT Fast

The COMT fast picture, as you can imagine, is the flip-side of COMT slow. This enzyme works too well, eliminating crucial substances before they have the chance to act. The most well researched polymorphism that contributes to this picture is the COMT Val158Met Val/Val pattern, but again total COMT activity is additive across all the COMT polymorphisms and is best determined by symptoms and personality.

Signs and Symptoms of Fast COMT

In terms of neurotransmitters, low dopamine, epinephrine, and norepinephrine looks like:

  • Lack of enthusiasm
  • Relaxed, laid-back personality
  • Low motivation
  • Difficulty remaining focused on one task
  • Addictive tendencies.

These neurotransmitters do double-duty as stress hormones and so we also see:

  • Suddenly shine in stressful situations, like they are at their best under pressure.
  • Stimulation-seeking – want lots of noise, lights, chatter in the work environment, and chaos to get their neurotransmitters fired up.
  • Sleep easily
  • Tendency toward restless legs and constipaton
  • Typically better with caffeine or other stimulants.

COMT also affects estrogens – meaning it lowers them – and so people with fast COMT often have:

  • Dry skin
  • More prone to osteoporosis
  • Often started their menses later than their peers
  • Symptoms related to low estrogen such as .moodiness, irregular periods, absent periods,
  • Lower tendency toward hormonal cancers including breast and prostate. 
  • Potentially lower sex drive

Remember that other gene SNPs can affect these same neurotransmitters,  and hormones, but if you have this symptom pictures then addressing the situation is appropriate no matter what your gene report says.

The COMT fast genotype carries with it some superpowers as well. On a surface level, the COMT variants get divided into Warrior and Worrier pictures.  COMT fast, because of the lower level of stress hormones, falls into the warrior category.

We say warrior, because stressful situations truly do make people with the COMT fast genotype shine. While others are overwhelmed or overstimulated, these folks are in the zone, at peak performance, and completely on-point. COMT fast folks are well suited to working in emergency rooms, the trading floor on Wall Street, or possibly on the race track. They also have a gift in terms of shifting between topics or areas of focus quickly. None of us are good at multitasking, but COMT fast folks can switch between tasks and activities with ease. This remarkable skill is called cognitive flexibility.

Managing a Fast COMT

Step 1: Balance Your Methylation.

As we discussed, the COMT enzyme is dependent on healthy methylation, so the first thing you would do in this situation, just like in COMT slow, is to optimize your methylation. Get your basic B vitamins, find the best B12 for you, and add a methylation driver like 5-LMTHF or SAMe. Optimize your doses of those things based on how you actually feel and how your symptoms look on a symptom tracker. If you don’t have one yet, you can get a free symptom tracker by signing up for the newsletter at

Keep in mind that with a fast COMT your neurotransmitters are naturally low and pushing methylation drivers in this case can make a huge and immediate difference to your mood and affect. Getting good methylation drivers into the works will help tremendously.

Step 2: Optimize Your Diet

Protein boosts dopamine, which is exactly what you want with fast COMT. In a fast COMT situation eating a high protein diet will keep those flagging neurotransmitters up for a good mood and focus. Focus on a higher protein meal at breakfast, and lunch, and have a moderate protein dinner so the neurotransmitters don’t interfere with sleep.

Adding in high magnesium foods helps as well because magnesium is one of the best nutrients for a fast COMT. Look for dark green leafy veggies, low-fat dairy, nuts, and legumes. The magnesium will also balance the tendency toward constipation, muscle cramps, and restless legs.

Step 3: Stimulate

Such a big part of this picture involves stress hormones, and so balancing the helps to optimize performance. This means:

  • Like the slow COMT counterparts, declutter your home and keep it tidy. A calm, chaos-free environment reduces stress hormones, which is not as crucial for COMT fast folks, but it also makes focus easier.
  • Interrupting work with activities that give your brain a dopamine boost, like video games or a quick burst of exercise. Just make sure you’re keeping it in check because these things can become addictive in low-dopamine brains.

Step 4: Balance the Hormones.

As I said last week, balancing hormones is an entire podcast series in itself. Still there are a few things you can do in low hormone states as well:

  • Seed cycling. It’s too much to get into right here, but here’s a link to a detailed article. It’s a lovely way to help balance and regulate hormones safely.
  • Herbal medicines. Shatavari, black cohosh, and red clover are all known to boost estrogens in a relatively safe way, but it is best to work with a knowledgeable practitioner.
  • Exercise to build muscle mass and reduce fat. Dropping estrogens can decrease lean muscle mass and gaining muscle mass helps to balance and regulate all of your hormones.

Thanks so much for listening today and next week we’ll review glutathione before we talk about some of the SNPs that can affect levels. Please subscribe so you don’t miss any episodes and if you like what we’re doing here, I’d really appreciate it if you’d leave a review. Thanks so much!

Share with friends:

S2E30: Slow COMT

This week, let’s talk about our first of two COMT pictures. COMT slow. Remember, this means the COMT enzyme is less efficient than normal so the catecholamines it is supposed to break down stay in circulation longer. This leads to high neurotransmitters including dopamine, norepinephrine, and epinephrine. It also means high levels of hormones, including stress hormones, which are really those same neurotransmitters when they operate outside of the brain, and also estrogens.

This is not dependent on one COMT polymorphism, but rather the sum of all COMT polymorphisms but again I want to caution you against assuming you know what is going on based on a piece of paper. A genetics report can only show you the genes as written, and not the ways your body has activated or silenced those genes (which is called epigenetics) – that can only be observed in real life. So if you’re trying to determine if your COMT is fast or slow, the most helpful thing to look at is personality and symptoms.  Also, there is research showing that the presence of estrogen may inhibit the COMT enzyme further, meaning that women with slow COMT would be more strongly affected than men.

Signs and Symptoms of Slow COMT

In terms of neurotransmitters, high dopamine, epinephrine, and norepinephrine looks like:

  • Enthusiasm
  • Exuberance
  • Self-confidence. 
  • Ability to focus for long periods of time
  • Workaholism

These neurotransmitters do double-duty as stress hormones and so we also see:

  • Difficulty calming down in stressful situations
  • Dislike of overstimulation – lots of noise, lights, chatter in the work environment, chaotic or messy spaces.
  • Hard time falling asleep
  • Easy irritability
  • Often worse with caffeine or other stimulants.

COMT also affects estrogens and so people with slow COMT often have:

  • Glowing skin
  • Strong bones
  • Often started their menses younger than their peers
  • Symptoms related to high estrogen such as fibroids, PMS, and fibrocystic breasts.
  • Higher tendency toward hormonal cancers including breast and prostate. 
  • Higher estrogen status is generally harder to see in men, but in extreme cases it can cause swelling of breast tissue, erectile dysfunction, and delayed puberty but milder cases may be harder to detect.

Remember that other gene SNPs can affect these same neurotransmitters,  and hormones, but if you have these symptom pictures then addressing the situation is appropriate no matter what your gene report says.

The COMT Slow genotype carries with it some superpowers as well. On a surface level, the COMT variants get divided into Warrior and Worrier pictures.  COMT slow, because of the high level of stress hormones, falls into the worrier category.

That doesn’t sound like a superpower, but stick with me. People with slow COMT actually have higher levels of dopamine in their prefrontal cortex, which is associated with executive function, decision making, understanding consequences, impulse control, coordinating complex behaviors, and creativity. 

In studies, higher dopamine in this area of the brain allowed people to excel at these tasks, especially in creativity. Those with the COMT Val158Met Met/Met allele (COMT slow) showed greater abilities in divergent thinking, meaning they were able to create more different  solutions to a given problem in a short amount of time than someone without that polymorphism.

So while those of us with the COMT slow variant (you can’t see it but my hand is up here), have the potential to feel stress more acutely than our COMT fast counterparts but we can also think of 50 ways to solve a problem in no time at all.

Interestingly, the slow COMT state also has better cognitive stability, meaning the ability to stay focused on a task for long periods of time, where COMT fast is better at flipping between tasks effectively.

Managing a Slow COMT

Step 1: Balance Your Methylation.

As we discussed last week, the COMT enzyme is dependent on healthy methylation, so the first thing you would do in this situation, just like in COMT fast, is optimize your methylation. Get your basic B vitamins, find the best B12 for you, and add a methylation driver like 5-LMTHF or SAMe. Optimize your doses of those things based on how you actually feel and how your symptoms look on a symptom tracker. You can get a free symptom tracker by signing up for my newsletter at

Keep in mind that with a slow COMT your neurotransmitters look a lot like you’re on small doses of uppers all the time and so overdoing your methylation drivers can take that away, flipping your COMT slow to a COMT fast, and frankly nobody likes anything that downs their uppers. So beware of taking too much or pushing this process too hard. We’ve got to be flexible and responsive in dosing methylation drivers and not get stuck on a target amount we’re “supposed” to take.

Step 2: Optimize Your Diet

Protein boosts dopamine, which is something that you don’t need if you’ve got a slow COMT. Especially at night when you’re trying to get to sleep. Focus on a higher protein meal at breakfast, but lower at lunch and dinner. Slow COMT folks do best with a veggie and carb weighted dinner.

Adding in high magnesium foods helps as well because magnesium is one of the best nutrients for a slow COMT. Look for dark green leafy veggies, low-fat dairy, nuts, and legumes. Fortunately, these are also foods that are high in natural folate, so you’re eating them anyway, right?

Boost your fiber. Help your body to eliminate those excess estrogens by eating lots of fiber that can help to bind them in your gut and make sure they get eliminated.

Step 3: Calm.

Such a big part of this picture involves high stress hormones, and so minimizing stress is crucial to keeping balance. This means:

  • Declutter your home and keep it tidy. A calm, chaos-free environment helps reduce stress hormones.
  • Go for quiet environments or soothing background music when you’re trying to focus or wind down.
  • Meditate, take a minute to breathe deeply, or try the technique Martha Beck outlines in this episode of her Bewildered podcast with Rowan Mangan.

Step 4: Balance the Hormones.

While balancing hormones is an entire podcast series in itself, there are a few constants. I mentioned fiber in the diet section and if there is only one thing you can do, fiber should be it. Otherwise:

  • Seed cycling. It’s too much to get into right here, but here’s a link to a detailed article. It’s a lovely way to help balance and regulate hormones safely.
  • Bump up your broccoli. Broccoli and other cruciferous veggies like cabbage, brussels sprouts, cauliflower, and kale specifically help to detoxify estrogen. If you’re going for bonus points, then look to broccoli sprouts for the win.
  • Avoid plastics and pesticides, many of which mimic estrogen in your body. Getting these artificial estrogens out will help your body deal with your natural estrogens more easily.

Thanks so much for listening today and next week we’ll dive right in to the COMT fast picture. Please subscribe so you don’t miss any episodes and if you like what we’re doing here, I’d really appreciate it if you’d leave a review. Thanks so much!

Share with friends:

S2E28: COMT and MTHFR.

To kick off our series on other polymorphisms, I’m starting with another heavy-hitter that is deeply entwined with MTHFR.  This polymorphism is also in a gene that codes for an enzyme by the name of catechol-O-methyltransferase.

I’m hoping that right off the bat, you noticed the word “methy”l in there as part of the enzyme name. That is important in terms of how it ties in with MTHFR. So let’s break this name down.

Catecholamine = the group of compounds that this enzyme acts on. In fact, it metabolizes these substances as part of the break-down process.” Catecholamines are a very important group of hormones, many of which do double duty as neurotransmitters, that have a similar structure and are all highly biologically active.  They include dopamine, norepinephrine, epinephrine, and a group of estrogenic compounds called catecholestrogens.

It doesn’t take a vast wealth of biomedical knowledge to know that an enzyme that affects stress hormones, neurotransmitters, and estrogens is going to matter. Really matter.

Catechols are also found in foods, drinks, and supplements and the COMT gene can change the way we respond to those as well. Coffee, beer, buckwheat, green and black tea, chocolate, peppermint, parsley, thyme and many other fruits, vegetables, and herbs all contain catechols. In terms of supplements, EGCG (from green tea), green coffee-bean extract, rutin, and quercetin.

A quick note on the supplements – they generally act as COMT inhibitors, which can be a good thing if your COMT is overly fast, but not so good if you have a slow COMT.

As for the next part of the name, “O-methyltransferase” – this refers to the specific action taken at this particular step in the breakdown process. We’re transfering a methyl group to a particular location (designated “O”). And by methyl group, I mean from a SAMe, made by your MTHFR.  So if your MTHFR is limping along, then COMT is by  nature compromised because there isn’t enough SAMe or enough methyl donors to go around.  So these two enzymes are highly tied together. This is also a big part of why MTHFR folks often have issues with estrogens.

There is one other breakdown pathway for these neurotransmitters, which is via the MAO series of enzymes, all of which can also have polymorphisms, so there is a lot of symptom overlap between COMT and MAO mutations.

It may sound like COMT isn’t important because it isn’t about formation of these products, it’s about breakdown, but in reality, breakdown is just as important.  Overly efficient breakdowns means that the substance is cleared too quickly and you don’t get all the benefit, while breakdown that is too slow means the substance hangs around for too long doing damage. 

There are several COMT mutations and they have additive effects to make the overall activity of the enzyme either faster or slower than the wild type genetics. The most studied so far is COMT Val158Met.

COMT Val158Met (or rs4680, or G158A because genetics can’t keep its names straight).

This is a really interesting polymorphism because it can take a person either faster or slower, depending on it’s presentation. In the next two weeks we’ll dive into the idea of faster and slower and what that means for the person experiencing it.

Met/Met = estimated to be 40% slower than “wild type”

Val/Met = intermediate activity

Val/Val = faster than average COMT activity

There are other COMT polymorphisms as well, but I do want to caution you from trying to figure out your fast/slow status from a genetic report. The symptoms and signs of fast and slow COMT are very clear and easy to see and they’re far more accurate than us doing theoretical math on gene SNPs. Remember that genes can actually have a polymorphism, but they can also act like they have a polymorphism because of nutrition, lifestyle, and epigenetic factors so the most important factor in figuring out whether you’re fast or slow is your symptoms and personality.


There is a really strong link between your MTHFR status (and more importantly, how well you’re methylating) and your COMT activity. Remember the O-methyltransferase part? Well, we can only transfer methyl groups if we have methyl groups and in order to have a healthy supply, methylation needs to be happening well.

This might sound simple, but it essentially means that healthy COMT function depends entirely on healthy methylation, so without doing your methylation background you can work on COMT until you’re blue in the face and it isn’t going to fix things.

This also means that if you’re pushing methylation too hard – say you’re taking great big doses of methyl folate or SAMe and (somehow) tolerating it well but not really needing it? That has the potential to push your COMT into too-fast territory.

The supplements that can push COMT too fast are:

  • methyl-cobalamin (this is one that I see people take far too much of really frequently).
  • betaine / TMG
  • 5-LMTHF or methyl folate
  • SAMe

You’ll notice these are all the drivers of methylation and your big methyl donors.

COMT, also needs a cofactor and that is magnesium. Just like MTHFR needs B2, or riboflavin, to do anything at all, COMT needs magnesium. Fast or slow, this is a great addition to your routine, especially at bedtime because magnesium is physically and mentally relaxing.

Thanks so much for listening and next week we’ll dive into the COMT slow personality type and picture and also what you can do if you have COMT slow. Thanks so much for listening, and if you might be interested in a 6 Weeks to Amazing MTHFR course and workbook, then you’d better get into Genetic Rockstars or sign up for the mailing list at right now.

Share with friends:

S2E27: MTHFR and Other Gene SNPs

This week I want to start a mini-series of talks  about other gene SNPs with or without MTHFR.

I actually want to start it out with a disclaimer, and this is something that you’ve heard me say before, but it bears repeating.  

You are more than your genetic report, and just because you have a polymorphism in a gene doesn’t actually mean that it’s causing problems in real life.

We like linear ideas in medicine because they’re easy to get our heads around. Linear ideas like this polymorphism does this concrete thing in a predictable and repeatable way. The truth, however, is that most of the genes we are talking about are part of a complex web of overlapping functions. There are loops and redundancies and always, always, at least 15 ways to do the same thing. This means that linear in medicine is largely a myth. It’s a popular myth, but a big fat lie none the less. In truth, all of these processes are more like a web and pulling one strand might lead to a tension on the other side of the web, might pull four or five unexpected places, and might have no impact because of other strands that are being pulled at the same time. The tremendous forces that shaped and designed your body have had eons to perfect it, so you are far more vast and strange than you have ever believed yourself to be.

I feel like Ben Lynch summed this up really clearly in his book Dirty Genes. He gets really clear that genes can BE “dirty” in that they have polymorphisms of some kind, or that they can ACT “dirty,” meaning they’re perfectly average wild-type genes but some environmental or life stressor is causing them to act like they have polymorphisms.  LIkewise, genes with polymorphisms can ACT “clean” if your lifestyle and nutrition around that gene are optimized.  

This acting clean is precisely why we’re talking so much about balancing methylation, because balancing your methylation means your MTHFR polymorphism becomes silent – the MTHFR gene is now acting “clean.”

This is really important for two reasons.The first, is that it’s easy to get caught in the trap of trying to fix a piece of paper and disregarding your symptoms and how you feel as a human in the process.  What I mean by this is that people start to take supplements for gene SNPs, even when it’s unnecessary and cumbersome becasue they’re paying more attention to what the genetic report says than to what they feel in real life.

You are more than your genetic report

What you feel in real life always trumps genetic reports, always.  It’s entirely possible to have a gene SNP that is normalized already by nutrition and lifestyle so it isn’t causing harm, but taking a supplement for that gene might cause harm in that pathway or elsewhere.

The other reason is that not all of us have genetic reports.  It’s entirely possible to work on the symptoms that you’re having that sound like a “dirty” gene without actually knowing what the gene SNP is on paper.  At the end of the day, what’s on paper isn’t the point. The thing we’re working on is how you feel as a human.

So each week we’ll discuss a different polymorphism, the symptoms you might see with that polymorphism and some beginning steps about how to work with that.  Also, we’ll talk about how it relates to the MTHFR gene because MTHFR really is foundational to all of this.

What I do want to make clear is that following the basic steps to balance your methylation will help you to balance 85% of the rest of this as well.  There are a few particulars that might take extra steps, but if you’re following the plan, you’re already working on all of the cycles that interconnect with the methylation pathway. You are already working on everything relating to folate, methylation, glutathione, neurotransmitter formation, and circulation via nitric oxide.  Balancing methylation even helps with many detoxification-related processes and hormone balance.  So if you’re following the plan, you’re 85% of the way there and now you just need to refine with details. 

That is exactly why the foundations of this journey are so important. What are the foundations, you might ask? The foundational steps are:

If you’ve done those things you are 85% and possibly even more of the way there. After that, it’s all little detail things but a solid foundation is set.

So, for the next three months, buckle your seatbelts because we’re going to start a whirlwind tour of commonly tested gene SNPs, what they do, and how to work with them.

Thank you so much for listening today and if you haven’t already joined Genetic Rockstars, consider doing so. Helping other people to heal has been shown to increase your own rate of healing across a variety of physical and mental health conditions and MTHFR is no exception. The biggest thing you can do for yourself is to share your story, laugh and cry with other MTHFR folks, and be there for your healing community.

Share with friends:

S2E27: What is Really Going On With MTHFR Basic State?

Basic state is something that we’ve talked about before, but I want to dive a little bit deeper into why I feel it’s important when other fantastic practitioners, like Dr. Ben Lynch, aren’t really into it. Honestly, there is no right answer here.  So let’s look a little more closely.

The idea of over and under-methylators came originally from the research of Dr. Walsh from the Walsh Research Institute.The main thrust of his research was that mental and emotional disorders often stem from an imbalance or deficiency of nutrients in the brain. 

This research was not based on genetics and had nothing whatsoever to do with the MTHFR polymorphism, or any polymorphisms in the histamine pathway. It was based on Dr. Walsh’s clinical observations over years of working with vast numbers of patients. The terms “overmethylator” and “undermethylator” were his own and based on what he theorized was happening. The names, in my opinion, are a bit misleading because we don’t actually know what is happening with the genetics or if the DNA is really overmethylated or undermethylated. Hopefully, that research will happen eventually, but it certainly hasn’t happened yet.

The reason I like using basic states as a guidepost, is because it’s an easy way, especially in the beginning of your MTHFR journey, to guess how you might respond to certain supplements and drugs for mental health.  This can be hugely helpful because we all have a tendency to dive into the deep end with this, and believe me – taking a big dose of methylfolate if your body isn’t ready for it can scare you off of taking methylfolate for a very long time. 

Also, since the basic state is based on observable personality traits, allergies, and measurable signs and symptoms, we’re not looking at just one gene. We’re looking at how the totality of a person’s genes plays out in real life, because how they look on paper isn’t always how they act and how they act is what really matters at the end of the day.

Also, this is something that can be determined without any genetic testing, without any specialized help from practitioners and without the need for any fancy interventions at all. That makes it extremely valuable because for every one  person who thinks they have an MTHFR polymorphism who is working with a knowledgeable practitioner, there is another hundred who are doing this on their own.

For that, basic state is invaluable. Also, I love the fact that it’s based on what is called phenotype, or genetic expression, not genotype, or genes as they’re written. What that means, is that elements like personality traits or high or low histamine, represent the way all of your genes come together to express, which is by far more valuable information clinically than the actual gene polymorphisms themselves. 

There are so many genes involved in each pathway – when you look at actual gene expression, or phenotype, you’re seeing the way all the genes come together, which is more relevant than just the status of one gene or another. Also, all of your genes express or don’t express depending on a variety of factors including lifestyle, nutritional status, other health factors and even your mother’s health status while you were in utero. It’s far more complicated than just this or that gene, but looking at who you are as a person and how your personality expresses is actually a great way to sum up this information.

Knowing your basic state can give you some well informed starting places in terms of how you will respond to supplements, pharmaceutical drugs, and even the types of doses you might expect to be optimal. It isn’t 100% accurate, but it gives you a better idea of starting places than you would otherwise have. Still always start low and go slow, but knowing your basic state can speed up the process of discovery. 

The MTHFR Basic State Mirror Image

When you’re trying to determine your own basic state, it’s most helpful to think of them as flip-sides of the same coin with opposite traits on either side.  Your basic state will come down to how many traits you have from each side.

For instance, the traits of overachievement and perfectionism show a subtle but important difference. Both under and over-methylators express these traits, but undermethylators tend to be perfectionistic and overachieve in all areas, where overmethylators hyperfocus on the areas that are important to them and let the rest slide.

There is a very important difference in allergic response as well. High histamine type allergies and sensitivities are like classic hay-fever, where you open a window and the pollen instantly makes your eyes stream and starts the sneezing.  That is an undermethylation, high-histamine type reaction. Overmethylators, on the other hand, show more chronic allergies and sensitivities – the low-grade headache, neck tension, entire season with a blocked nose that doesn’t particularly change whether you’re indoors or out. That is a low-histamine sensitivity pattern. Also, overmethylators tend more toward chemical and food sensitivities, where undermethylators tend more toward histamine intolerance in foods.

High, for everythingAchievement and DriveHigh for the thing that matters to them, low for other things
Typically follows rules and social norms wellRules and guidanceFollows rules that make sense to them, disregards others. Follows the beat of their own drum.
Typically pushes for achievement in everything they doAchievementPushes for achievement in the things that matter to them, but not interested in other things
High histamine and seasonal allergiesHistamineLow or normal histamine with chronic allergies/sensitivities
Typically lowerPain ToleranceTypically higher
Often intolerant to histamine in foods, but less often to foods themselves.Food reactionsTypically has sensitivities to specific foods and chemicals
High fluidity (saliva, tears, etc…)FluidityLow fluidity (saliva, tears, etc…)
The MTHFR Basic State Mirror Image

At the end of the day, trying to decipher the big picture by looking at each particular gene SNP can lead to a really messy situation in which you can end up taking supplements that look good on paper, but aren’t actually addressing the issues you have in real life.  This is far less likely to happen if you’re working with a good practitioner, but sadly I’ve seen some practitioners fall victim to this mentality as well. Even worse, you can end up taking one supplement for each gene SNP and getting completely overwhelmed by a cumbersome protocol that costs a lot of money and time, but doesn’t get you anywhere.

If you’re looking for a MTHFR basic state refresher, you can follow this link to learn more about the idea in general. Here’s a link to dive deeper into the undermethylator picture and here’s one for overmethylators.

Thank you so much for listening today, and if you haven’t done so already, check out the show notes at There are resources, downloads, links to research, and best of all an email list where you can sign up to be sure you’re the first to hear about exciting new courses, free resources, and other great things.

Share with friends:

Supplements for Depression with MTHFR

MTHFR and depression are intimately linked. We’ve spoken about this before, and if you want to brush up, take a look at Season 1 Episode 8 where we explored the link between the MTHFR mutation and neurotransmitter formation via the BH4 pathway. The quick and dirty version is that when methylation isn’t working optimally, then the pathway that makes many of your major neurotransmitters, including serotonin, melatonin, dopamine, epinephrine, and norepinephrine gets stalled out too.

Season 1 Episode 33 was also all about MTHFR and depression, specifically the entirely fixable causes of depression that your doctor will typically overlook. This whole episode was about steps you can take at home to manage depression. Balancing your methylation is obviously a cornerstone, but there are so many other factors involved that are entirely in your hands.

Another great one to review is Season 1 Episode 34, where we talked about the component of depression that is quite simply a mental bad habit. The part that feels like falling into a rut mentally where your brain travels over the same tracks, the same complaints, the same problems without questioning them or without breaking those patterns. Also, Season 1 Episode 35 in which we talk about some great techniques for breaking those bad habits.

The part of depression we haven’t talked about yet is the supplement part and this is something that people ask me about all the time. At the end of the day, sometimes we really do need a pill to take the edge off while we’re making these other changes. Often, the supplement helps us to have the mental and emotional energy TO make other changes. So let’s talk about a few good options that are typically pretty safe for MTHFR folks and typically well-tolerated.

Some Amazing Depression Supplements We Won’t Be Talking About

There are some great supplements for depression that we won’t talk about today, mostly because we’ve talked about them before at great length. One of the best natural treatments for depression is, of course, balancing methylation using a good folate source or SAMe and a good B12 source. Since those are things we talk about pretty much every week, I’m going to assume you’ve got those covered. For most of my clients, balancing methylation – whether it’s through 5-LMTHF, folinic acid, food sources of natural folate, or SAM-e – is the cornerstone of their depression relief. That doesn’t mean it’s the only thing they need to do, but it’s certainly the foundation.

Another effective supplement for depression that we’ve talked about before is St. John’s Wort. We dove into that one at some length in Season 1 Episode 46 on the link between MTHFR and serotonin. Also, omega-3 fatty acids and fish oils are extremely well studied for depression and we’ve also talked about those at great length because they boost the effectiveness of B vitamins in MTHFR mutation (Season 1, Episode 42). Just remember that if you’re using fish oils for depression you may need a higher dose than the one listed on the bottle.

Saffron For Depression

Saffron is best known as a spice, adding brilliant yellow color and subtle flavor to Middle Eastern food and haute cuisine. Like most other highly-colored spices it’s absolutely packed with antioxidants, carotenoids, and biologically active compounds. In research and clinical practice, saffron shows major benefits for those with depression and it is thought that this could be through some serotonin-boosting mechanism, possibly similar to SSRI medications in which the saffron keeps serotonin in the synapse longer, basically making the same amount of serotonin do twice the work.

In fact, when compared to the actions of SSRI medications, saffron was found to be just as effective for major depressive disorder as these commonly prescribed pharmaceuticals.

Given that this is thought to directly affect serotonin levels, it is best to talk with your doctor before starting saffron if you are already taking an antidepressant medication because there may be an interaction between them.

Saffron is typically dosed around 30 mg per day in research studies.

NAC for Depression

NAC or N-acetyl cysteine is something that we have talked about before as a precursor to glutathione, which is one of your body’s key antioxidants. It is actually precisely because of this function that it is so useful for depression. People with depression are more likely to have higher levels of oxidative stress, inflammation, and inflammatory cytokines like C-reactive protein, tumor necrosis factor-alpha (TNF-a), and interleukin-6 (IL-6). By helping to moderate the inflammation, NAC actually eases symptoms of depression as well.

It is thought that NAC helps to regulate glutamine and dopamine levels in the brain and demonstrates a great ability to both cross the blood-brain barrier and also to increase levels of glutathione within the brain and central nervous system. NAC also shows promise for use with addiction and substance abuse issues.

NAC is actually an amino acid and so it is best taken on an empty stomach. If it is taken with food, then it competes with other amino acids for absorption. The doses typically used for depression are between 2 and 2.4 g/day. This can be divided into two or three doses depending on what is easiest for you to manage.

Rhodiola for Depression

Rhodiola is well known as a supplement for helping to get core energy back in situations of adrenal fatigue or exhaustion. This is because of its action as an adaptogen, and that adaptogenic ability is also thought to be the reason it helps with depression.

Studies have linked hypothalamic-pituitary-adrenal axis dysregulation (or HPA axis dysregulation for less of a mouth full), with depression. HPA axis dysregulation is exactly what is happening in clinical cases of adrenal fatigue or exhaustion. It describes a state of over-reactivity and subsequent burn-out of this vital neuro-endocrine system.

In a study that compared the effectiveness of Rhodiola to the common antidepressant Sertraline, the Rhodiola was shown to be effective, but not quite as effective as the antidepressant, but also far better tolerated with fewer side effects.

The typical dose of Rhodiola for depression is around 340 mg per day. There are other adaptogenic herbs as well, all of which may have similar benefits for depression. These include licorice root, ginseng, American ginseng, schizandra, and ashwagandha.

Thank you so much for listening, and if you’re interested in a 6-weeks to health with MTHFR course, make sure to sign up for the mailing list at and keep listening to the podcast for more info.

Share with friends:

MTHFR Questions – Specific products and Marmite.

This week, I’d like to get to some questions that listeners have been kind enough to leave on the website and within the community.

The first comes from Liana O and she says “Specific 5-L-methyltetrahydrofolate supplement recommendations and dosing, please?”

This is actually a really common question, and I’m probably not going to answer in a way that is satisfying because everyone is so different. Also, the products available to people vary so widely that the best I can give is guidelines.  In terms of people first starting on this journey, the absolute best, easiest, and most painless way to start is with a multivitamin that doesn’t have any folate or B12.

To my knowledge, there is only one such product on the market, which is made specifically for MTHFR  and by a fellow MTHFR mutant. It’s called Optimum Start by Seeking Health. This is a great product, and Seeking Health will ship internationally from their website, which is great, but as everyone who isn’t in the US knows, international shipping for something like this often makes it cost-prohibitive. I do have an affiliate account with Seeking Health, so if you’re ordering products I would so appreciate it if you’d do it via the link from to support the work I’m doing here.

Outside of that, there are a number of great multivitamins with low doses of methyl folate that can be really great for a starting place. One of my favorites is the Smarty Pants kids multi gummy.  It has a mere 37.5 mcg methyl folate per gummy. This won’t give you an adequate dose of everything else you need, but if you’ve had trouble with methylated folates before, it can still be a great way to start. Smarty Pants also has some great adult gummy vitamins that can be a good way to ramp up your intake slowly because typically the dose is split between 4 gummies, and also gummies are easy to cut in halves or quarters.

If you prefer capsules, look for high-quality multivitamins that have multiple capsules in the dosage and are made for adolescents or teenagers so the doses per capsule aren’t high. Some examples are junior nutrients from Pure Encapsulations, which has 100 mcg folate per capsule.  Thorne Research multi-encap is also a good choice at 130 mcg folate per capsule.  
In general, I prefer to buy from companies that follow good manufacturing practices and who sell primarily through practitioners. This includes companies like Thorne Research, Integrated Therapeutics, Pure Encapsulations, Xymogen, and NuMedica.  Divinci Labs also makes some nice products, as does Jarrow. 

At the end of the day, what matters most is local availability, even if it’s via amazon or a similar mail order service, and ingredients. Always look for doses on the low end of the spectrum, especially with methyl folate and B12. You can add in higher doses of those ingredients separately, which is the best strategy because it gives you more flexibility overall.

I know this seems like a non-answer to this question, but the most important to find something that works for you individually.

The second question is from Tim and is quite honestly, sending me on a bit of a hunt. He asks….

So, even though Marmite says it has Folic Acid, you’re saying it’s actually NOT Folic Acid, is that correct? You have me so scared of Folic Acid that I don’t want to be eating it. Thanks.

Now, you all know of my obsession with Marmite. It is a yeast extract quite similar to the one that was used in the initial research that found folate to be an important nutrient for pregnancy. Outside of being a huge fan, I have also always been under the impression that it was unfortified and that all the folate present was directly linked to the natural byproducts of the yeast.  I am at this moment, fearful that I might actually be mistaken about this.

These two pieces of information aren’t the same. But why? The answer is yet to be found.

I have a question pending with Unilever, the current manufacturers of marmite, but so far it remains unanswered. The label information is somewhat frustrating. The Food Standards Agency, which is the UK’s food regulation authority, also has a folic acid fortification program with wheat flour, but I can not find out whether or not the terms “folic acid” and “folate” are considered to be equivalent legally. If anybody from the UK can shed some light on that matter for me, I’d appreciate it.

I do know that the bottle in my pantry lists the ingredients as Yeast extract, Salt, Dehydrated Carrots, Spice Extracts, Dehydrated Onions. And that’s all. There is no mention of additional vitamins or fortification, which in Canada is a legal requirement. The label is definitely following Canadian guidelines otherwise, as it has all information in both official languages.

I called the information number on my bottle and left a message, which has yet to be answered.

Also, I “spoke” with the marmite website chatbot and I hate to say, the chatbot listed ingredients that I don’t see on my label. According to the marmite bot, it includes vitamins and one of those is folic acid. Sigh.

So, obviously, this still requires some investigation because if there is folic acid on there, why isn’t it on my label? Also – how much is actually in there? Is the entire 100 mcg dose listed as the amount per 8 g serving folic acid? It’s all a bit confusing.

I will certainly update you when I hear from Unilever and also from the Canadian helpline because the contradiction in information doesn’t make sense. It could be that there is a difference in the formulas depending on the country, but it seems like the label would be easier to change than the product.

To address the second point in the question, Tim mentions the fear of folic acid. This is something I want to talk about because while I”m not a fan of folic acid, the problems actually occur when it’s folic acid in high doses. Small amounts just slowly labor on in the process of being converted to something useful like 5-LMTHF, but they do eventually get there. So a small amount of folic acid isn’t going to be a problem if you’re just getting it from one source, like marmite, which still has good natural folates as well.

When it becomes a problem is when it’s the only source and you’re getting it everywhere. All the fortified grains, your multivitamin, some prescriptions, etc… Then is when we see folic acid building up and also folic acid gumming up the works of the methylation pathway. There is probably a safe threshold, but to my knowledge, that research really doesn’t exist yet. So at this point, minimizing intake is the safest bet.

Are There Other Yeast-Based Products Like Marmite?

Since Marmite is now in uncertain territory, I will give you some options. One of my favorites is nutritional yeast. It has a delicious cheesy-nutty-umami flavor and is easy to sprinkle on popcorn, add to sauces, sprinkle over veggies, or use as an additional flavor burst in things like salad dressings.

Like everything else with food, it’s a bit complicated. If your package doesn’t mention anything, then it is likely fortified, which means they’ve added extra B12, folic acid, and probably a few other B vitamins to the mix. This is kind of standard and so if they just say it’s a good source of B vitamins, then they’ve probably done this. Also, the fortification gives the flakes a bright yellow color – more like a true yellow.

Nutritional yeast is available unfortified as well, but you have to hunt for it. I can’t find unfortified at any of my local stores, but I can on amazon so I order a big bag once a year and that’s that. The unfortified tastes just as good but the color is a bit more gentle – more of a buttery yellow rather than a bright yellow.

If you have some in your pantry right now, check the color – I’ll put a picture below so you can compare.

Thanks so much for listening today and thanks Liana and Tim for the great questions. Make sure you’re signed up for the email list so you’re the first to know about upcoming courses.

Share with friends:

Checking In With Progress On The MTHFR Journey

Let’s check in with what is going on so far. If you’ve been following the process this season, you will have noticed that I haven’t really addressed what we’re doing in a while, so let’s touch base.

There are some reasonably long stretches in the MTHFR journey in which we aren’t really changing things, doses are just staying the same, and it might seem like not much is happening. The reality, in fact, is that lots of things are happening in your body but none of it needs additional input from you.

This phase of the journey is what I like to call “Burning Through The Backlog.” When you first start diet changes and methyl folate or SAMe or whatever workaround you’re using, you see the immediate activation of the methyl cycle and some immediate health changes. Usually, that feels like a better mood, less anxiety, etc… After that initial balancing phase, the progress slows down but it isn’t because your body has stopped doing things.

This part of the process involves unpacking your body’s to-do list. All of the things it couldn’t do in the past because methylation just wasn’t happening fast enough. It’s a time of more subtle change where neurotransmitters are slowly coming into balance, toxins are slowly being eliminated, inflammation is slowly decreasing and oxidative stress is balancing out. Even your hormones and energy levels are being influenced in this process

How To Make Sure You’re Burning Through The Backlog Efficiently – Check Your Basics

In this phase, it’s easy to forget some of the basics so the first thing I want you to do this week is to take a look at things you should be doing and tighten up where needed.

  • Folic Acid – Make sure folic acid is out of your diet and supplements and isn’t creeping back in without you noticing.
  • Balanced Diet With Natural Folates – Get lots of fruits and veggies, as much fiber as you can pack in, moderate protein, and plenty of good food sources of natural folate like lentils, black beans, spinach, asparagus, dark green leafies, avocados, marmite, and any kind of bean or pea you feel like eating.
  • Multivitamin – Keep up with the background of other B vitamins – this is usually in the form of a good basic multivitamin. All of the processes that are happening now, from neurotransmitter formation to detoxification, to energy production, to balancing your oxidative stress and reducing inflammation needs a good solid basis of all the B vitamins.
  • Sleep and Rest – I really enjoy the paradox presented by this particular issue. Most of my clients say they would love more sleep and rest, but it’s always the hardset possible thing to actually accomplish. Just keep trying to work actual sleep and actual rest into your schedule.
  • Moderate Exercise – because generally, MTHFR folks do best with regular exercise, but not extreme exercise. Ironically, there are lots of us who are professional athletes and serious competitive athletes, but for those people it’s important to make sure methylation is balanced and to compensate adequately for the extra damage being done to their bodies.
  • Detox Support – since detoxification is such a huge part of Burning Through The Backlog, it’s important to give your body the support it needs. This can be in the form of gentle detox teas, castor oil topically, sweating it out, extra dietary fiber, or some mish-mash of all of these things. We’ve done posts on detox support before as well.

Burning Through The Backlog Efficiently – Optimizing Your Dose Of Methylation Drivers

The supplement or supplements you’re taking that specifically support methylation should be dose-checked occasionally. Maybe quarterly in this whole process. This could include any one of the following supplements:

  • 5-LMTHF or another form of methylated folate
  • Folinic Acid
  • SAMe

These supplements are all pushing the methylation cycle forward and so may need an occasional check-in to see if you’re still on the right dose. Usually, this means trying to increase your dose to see how you feel.

Generally, in this process, you increase by the smallest increment you can and make sure you’re using your symptom tracker for a couple of weeks before and after so you can see if there are small changes that you might not notice otherwise. If you feel fine with the higher dose, that’s great. Keep using the higher dose unless you start to get symptoms that indicate that your dose is too high. If you get symptoms right away or within the first two weeks then go back to your original dose.

Symptoms That Your Dose Is Too High

Typically too high a dose of anything that drives methylation feels hyper-caffeinated. It’s anxious, restless, can’t settle down, fidgetty, has a racing heart, or feels like all-out panic. If you’re noticing any of that – even if it’s a small change, then your balance will be better with a slightly smaller dose.

What About Other Supplement Routines?

For some people, taking supplements that take an alternate route through the methylation pathway, rather than methylation drivers, is the best path forward. Especially if you’re starting out from a kind of messy health place. These are supplements like methionine or choline. Methionine just gives you more of the raw ingredients to make SAMe and choline cuts through the middle of the methylation cycle as a viable short-term work around. These are great band-aids, but probably not the thing you want to be relying on for the long-term. If you are looking for long-term solutions but really can’t manage any of the true methylation drivers – methylfolate, SAMe, or folinic acid – then choline is the better of these two options. You still need the other B vitamins, and as much natural dietary folate as you can manage.

Moving forward, it’s a good idea to check in with your body quarterly to see if your dose is sufficient or if you’re getting enough for your body’s needs right now. Your dose will always be somewhat dynamic. Eventually, you will actually catch up with all of the things on your body’s internal to-do list and need a far lower dose, so watch for those anxious/hyper symptoms and keep it on your radar that your best dose might need to decrease too.

Thank you so much for listening today and give some thought to joining us in Genetic Rockstars – the MTHFR community. This month we’re talking about some of the links between MTHFR and histamine, and it’s a great way to meet people who understand what you’re going through and who have great information to share.

Share with friends: