How Do You Know When Your Methylation is Balanced With MTHFR?

It’s great to talk about “balancing your methylation” and finding your right folate dose, but how do you know when you’re actually there? This question matters a lot because I’ve seen so many clients who are on a constant upward trend with their methylfolate dose – always pushing to take more simply because they can tolerate it.

The point is, do you need it? Is it helping you? This isn’t a contest in which the person who takes the most methylfolate wins a prize, this is about listening to your body and finding balance – balance meaning not too much and not too little. This goes for MTHFR folks, but also people without an MTHFR polymorphism, because you don’t have to have MTHFR to have imbalanced methylation.

So where is this elusive magical place in which balance is reached? It may not be nearly as elusive, nor as magical as you’re thinking.

Does Balanced Methylation Mean All My Symptoms Are Gone?

Goodness, I wish it did. It usually means most symptoms are better, and some of them are gone, but all of your symptoms being gone is not actually realistic. We’re all human and human bodies are built differently for lots of reasons. One of those is MTHFR, but each human has hundreds of polymorphisms along with a whole life history of pathogens, traumas, nutritional factors, lifestyles, and varying degrees of self-care. Balancing methylation can’t compensate for all of that, it just takes a big chunk out of the bottom.

Having said that, the process of balancing your methylation usually helps people tremendously – decreasing anxiety, softening depression, improving sleep, reducing inflammation, normalizing hormones and generally getting things closer to where they should be.

What Is The Easiest Way To Tell If My Methylation Is Balanced?

There are two great ways. The first is to look at the work you’re doing around methylation. The second is to look at your labs.

Caring For Your Methylation

You know you’re at a place where your methylation is balanced when these things are happening:

  • You understand the signals your body gives you when it needs more support and when you’re taking too much methylation support
  • You respond appropriately to those signals
  • You aren’t hitting major walls coming from detox symptoms or up and down methylation crashes
  • Your symptoms are slowly but surely softening and resolving. THey may not be fully resolved, but you’re on an upward trajectory. Some of this just takes time.
  • Your body’s basic needs are regularly met – you’re getting good nutrition, good sleep, gentle exercise.

I see the same panic-stricken look on many faces when I say this, especially from folks at the beginning of their journey. Don’t worry – this all becomes clear over time and this is a journey that takes time. In good news, the best way for it to all unfold, is softly. This is a lot like pregnancy in that you can’t really rush it – it’s best to just support the process. For everyone who has just muttered something grumpy under their breath, the next section is more concrete. I promise.

Ok – So What About Lab Work?

Basic bloodwork can tell you a lot about what your body is doing at that moment. Values that are most specific to methylation are:

  • Serum Folate
  • Serum B12
  • Serum homocysteine

There are also some tests that are suggested on various MTHFR forums that I am less inclined to use including:

  • Serum MMA
  • RBC Folate
  • Urine MMA
  • Urine FIGLU

We’ll go through the tests I use one by one. The tests I am less inclined to use we’ll cover in a different post.

Serum Folate Test

This is the standard folate testing t and sadly doesn’t differentiate between useful folate that is bioavailable and folic acid or worse, unmetabolized folic acid. So this test will tell us if there is an overt folate deficiency, but not much else. Still, knowing if you have a folate deficiency matters with MTHFR. Levels below 4 mcg/L indicate a folate deficiency, but outside of that, the guidelines are vague. I don’t like to see the numbers creep too high either and >8 mcg/L can also be a red flag for over-supplementation, or for high lingering folic acid and unmetabolized folic acid in the blood.

Serum B12 Test

This test measures levels of B12 in the serum and is reasonably accurate, but has a broad reference range. The reference value is typically 180 – 914 ng/L and anything in there is considered normal. Anything below 180 ng/L is considered to be deficient. Because it is such a broad range, I tend to look at anything even close to 180 ng/L with suspicion. Remember reference ranges give us the average numbers where people begin to experience symptoms, but that doesn’t mean it’s the ideal number for you, so aim for the middle of the range (somewhere between 450 – 650 ng/L). Also, if you test normal but still have symptoms of B12 deficiency, then extra supplementation could be warranted.

Serum Homocysteine Test

We’ve talked a lot about serum homocysteine and there is a normal range and also an optimal range. If you’re outside of normal, then obviously there’s a problem, and for MTHFR folks it’s a good idea to aim for optimal. The normal range is 5 – 15 umol/L with optimal being 6 – 9 umol/L (in my opinion. Follow the link to see my reasoning.) Homocysteine, remember is an inflammatory marker in the blood that is a direct measure of how well you’re methylating methionine and so is the clearest measure of MTHFR function.

Are There Other Tests?

There are other tests, namely serum MMA, urine MMA and urine FIGLU. These tests are less commonly used and deserve a post of their own when we have more time. I find the serum folate, serum B12 and homocysteine to be the most useful of the bunch.

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Lowering Homocysteine with MTHFR

As with everything to do with MTHFR, balancing your methylation and boosting your B vitamins, especially B2, folate or 5-LMTHF, and B12, is the first step. Balance your methylation! There are some other things you can look into as well.

MTHFR Isn’t The Only Cause of High Homocysteine

Of course, our focus is MTHFR, but high homocysteine has other causes as well and the sad truth is, you can have fleas and ticks on the same dog. That is one of my favorite Texas expressions. What I mean by that is that just because you have MTHFR, doesn’t mean you don’t have to also watch out for other causes of high homocysteine. It’s important to manage those too. Other Causes of high homocystein (or hyperhomocysteinemia) include:

  • Poor diet
  • Poor lifestyle
  • Smoking
  • Diabetes
  • Rheumatoid Arthritis
  • Thyroid imbalance
  • Chronic inflammatory diseases
  • Celiac disease
  • Crohn’s disease
  • Long-term use of corticosteroids
  • Prescription medications
    • methotrexate (because it lowers folate)
    • metformin (long term use because it interferes with B12 absorption)
    • hydrochlorothyazide
    • Fibrate type cholesterol-lowering medications
    • Levodopa
    • Anti-epileptic drugs (long-term use)
    • Possibly nicotinic acid or niacin, but research is very conflicted.

If you have one of these underlying conditions or are taking a medication known to elevate homocysteine, then working on that condition or talking with your physician about the medication can be a great place to start. Outside of that, let’s talk about useful steps.

The MTHFR Plan to Lower Homocysteine To Optimal

  1. Balance your methylation – I’ve said it already, but the first step is always boosting your methylation cycle because this is where we tend to stall out with MTHFR. This means following the To Health With That! Plan. Eliminate folic acid, add a methylation-friendly B complex, then add 5-LMTHF, or folinic acid, or whatever workaround you are using if you don’t tolerate folate. If you aren’t familiar with the plan you can start to walk through it here.
  2. Limit your protein intake – The more protein (and consequently methionine) you take in, the more homocysteine your body makes. There’s a full article about the methionine and homocysteine link here.
  3. Quit smoking – As though you needed one more reason why smoking is bad for your health. But yes, smoking raises your homocysteine levels.
  4. Take a look at your alcohol intake – alcohol blocks folate absorption, and so increased drinking can raise your homocysteine levels. This is probably mitigated by extra folate intake, but possibly not.
  5. Balance your coffee intake – As much as it pains me, too much coffee has consequences and high homocysteine is one of them.
  6. Zinc – zinc is a cofactor in some of the enzymes involved in the recycling of homocysteine to methionine, and so zinc deficiency can increase homocysteine levels while zinc supplementation can help to improve beneficial conversion.
  7. NAC – NAC, or N-acetyl cysteine, has been shown to lower homocysteine levels as well as folate supplementation in studies.
  8. Fish oils – in a magical synergy, fish oils + B vitamins work better together than they do apart.
  9. Make sure there aren’t other underlying causes – If you’re doing everything right and your homocysteine still isn’t where you want it to be, it matters to talk to your doctor about other underlying causes. If you’re living the perfect lifestyle, but you still have a low thyroid, then fixing your thyroid is probably the only thing to bring your levels back to balance.

Don’t forget that every little step you take towards getting healthy, counts. They all add together to contribute to your state of health, today. So every little step you take in the right direction, matters. Don’t get discouraged if things don’t move right away, just keep trying.

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MTHFR and Homocysteine – The Basics

High homocysteine is often the first indication of an MTHFR issue, and it’s certainly the one that doctors take the most seriously. There is a good reason for this. Homocysteine is implicated in heart disease including heart attack and stroke, so it shouldn’t be taken lightly. 

What is Homocysteine?

Homocysteine is an amino acid that is made within your body as a part of methionine metabolism. Amino acids are the basic building blocks of protein, and we take in amino acids every time we eat protein-containing foods.

We need homocysteine in order to make ATP, our cellular energy, and also to make cysteine and ultimately glutathione, which is our master antioxidant. The problem comes when levels get too high, and this happens when your body is unable to recycle homocysteine back into methionine.

The primary recycling pathway relies on the MTHFR enzyme, as well as active folate and B12. There is a secondary pathway called the BHMT pathway that ramps up when homocysteine levels start to rise and this relies on other methylators like betaine, trimethylglycine (TMG), and choline. 

Why does Homocysteine Get High?

As usual, there are a number of reasons and many of them are related to MTHFR.

  • MTHFR compromise – your body recycles homocysteine into methionine in an MTHFR-dependent process. It requires the active form of folate for the process so if your MTHFR is running slowly or inefficiently then homocysteine levels can build up causing inflammation and damage.
  • Folate deficiency – Whether or not you have an MTHFR issue, if you don’t have folate then the recycling doesn’t happen either.
  • B2 or B12 deficiency – Like folate, these vitamins are necessary for methionine recycling, and not having enough of them can raise your homocysteine to an unhealthy level.
  • Too Much Protein intake – This is certainly a first-world problem and a bigger one recently with everyone doing fad diets from Keto to Atkins to Paleo. If you’re taking in higher levels of methionine than your body can easily process, then homocysteine is going to build up. Also, meats and dairy have some naturally occurring homocysteine in them. We’ll talk more about the methionine situation next week.
  • Other medical conditions – thyroid disease, rheumatoid arthritis, and diabetes are linked to higher homocysteine levels.
  • Medications that decrease folate absorption – proton pump inhibitors, birth control pills, antifolate agents, and some anticonvulsant medications interfere with folate absorption or metabolism.
  • High coffee intake – I am sorry to say, high coffee intake is also linked to elevated homocysteine.

What Does Homocysteine Do That’s So Bad?

So many things. Homocysteine is vital, of course, but in this situation, too much of a good thing becomes toxic.

  1. Inflammation – Inflammation is the most well-documented issue to do with homocysteine. It is specifically damaging to cell membranes and the lining of your blood vessels, which is part of why it is so linked to heart disease.
  2. Clotting – Clotting in the blood vessels can lead to heart attack, stroke, pulmonary embolism, and deep vein thrombosis, none of which are good. This is thought to be due to a combination of factors. One is that nitric oxide metabolism is compromised and so blood vessels aren’t able to dilate properly. The other is that thromboxane A2 (TXA2) activity is increased in both blood vessels and platelets, possibly because of a higher free radical burden. This promotes clotting.
  3. Neurological issues – High homocysteine levels are implicated in a number of neurological disorders including stroke and Alzheimer’s disease, but extending to disorders like epilepsy, Parkinson’s, multiple sclerosis, and ALS. The research is unclear in terms of whether homocysteine is actually a causative factor in its own right or just a marker of low B-vitamin status.
  4. Fractures –  Research shows that homocysteine significantly increases fracture risk and it appears to be independent of other risk factors, but it is unclear whether or not B vitamin supplementation decreases that risk.
  5. Microalbuminuria – Microalbuminuria is an abnormal protein in the urine and it indicates a high future risk of cardiovascular disease as well as kidney dysfunction. Every 5 umol/L increase in homocysteine levels is associated with an increased risk of developing microalbuminuria.
  6. Atherosclerosis – As a consequence of the increased inflammation in your arteries, your body is more likely to lay down arterial plaque to protect itself. This isn’t the direction you want to go. High blood pressure – possibly because of the issues with blood vessel dilation, blood pressure and homocysteine go hand in hand. High homocysteine increases the thickness of arterial walls, reduces the elasticity of arteries, and increases the production of stiffer collagen fibers in the vascular system. 
  7. Pregnancy complications – High homocysteine levels have been implicated in spontaneous abortion, placental abruption, and preeclampsia. 

Is There Anything Good About Homocysteine at All?

Homocysteine is certainly an issue for MTHFR folks, but it’s also incredibly helpful for us as a biomarker. Testing your homocysteine gives you an easy way to see if your methylation is becoming unbalanced at the moment. While it’s a small silver lining, it’s still a good one.

We’ll talk more about the role of methionine in this conversation as well as testing homocysteine and optimal levels in the next couple of weeks.

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