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.

Share with friends:

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.

Share with friends:

MTHFR and Depression

Depression is a common thread among all humans – this isn’t limited to MTHFR folks in any way, but as folks with an MTHFR variant, balancing methylation can be an effective way of tackling depression that is often overlooked by doctors and practitioners.

We always hear about neurotransmitters and depression, so much so, that I feel we overlook the fact that there are any other possible contributors. The assumption becomes that if you’re depressed, your neurotransmitters must be off somehow and if we can fix those neurotransmitters, we can fix the depression.

The problem is, this theory doesn’t actually pan out for a lot of people – especially MTHFR people. A drug that boosts the activity of serotonin in the brain should work, but often doesn’t. It has a lot of merit to explore other cuases of depression as well – especially when so many of them are fixable.

MTHFR does, of course, affect neurotransmitters via the BH4 pathway, but my experience clinically has been that balancing all of the other things goes farther than pills for neurotransmitters in most people (there are some highly notable exceptions, of course.)

Many factors play into depression and some of these are related to MTHFR, and some aren’t.

  • Low Folate and Vitamin B12 Status – This link holds true whether the person in question has an MTHFR issue or not. Lower nutritional status regarding folate and B12 means a higher risk of depression. Also, higher serum B12 and folate are shown to predict better treatment outcomes.
  • MTHFR? – It is clear that lower folate levels can increase the risk of depression, and that MTHFR can increase the risk of lower folate levels, but it isn’t absolutely clear if MTHFR increases the risk of depression independently from folate status.  There are several ways that it could – MTHFR polymorphisms have an impact on neurotransmitter formation, and also on DNA methylation, which can boost depression by itself.
  • C677T Status? – Again, this is questionable. This meta-analysis shows a link between C677T status and depression, but the fascinating thing is that another study shows that the strength of the link changes in different geographical areas. This could be due to local changes in diet, but it could also represent a big wild-card factor that tells us we have a lot to learn in this area.
  • High homocysteine – Of course high homocysteine could be a result of low folate status, but there is a clear link between homocysteine and depression (and, don’t forget, a link between MTHFR and homocysteine.)
  • Inflammation – In a classic chicken-or-egg scenario, inflammation and depression are terminally linked. If inflammation rises, so too does depression and likewise, if depression worsens, so too does inflammation. With MTHFR we do have a greater tendency toward both, so it matters to keep your inflammatory processes in check.
  • Oxidative stress – Oxidative stress is your body’s total level of reactive oxygen species (free radicals). Studies show that people with higher levels of markers for oxidative stress also have higher levels of depression and poorer responses to treatment. With MTHFR, we have the potential to have lower glutathione, which is the master antioxidant, meaning we may have higher levels of oxidative stress.
  • Insulin Resistance and Blood Sugar Issues – Research is mixed in this area. There is a clear link between depression and diabetes, but insulin resistance, which is one of the stepping stones on the path to type 2 diabetes, is less clear. The immediate and obvious link between blood sugar fluctuations and mood, is much less difficult. As anyone with a hungry toddler can tell you, the jump between hungry and “hangry” is a short one. Again, with MTHFR we do have a slightly increased tendency towards blood sugar issues, insulin resistance, and ultimately diabetes.
  • Hormones – Again, the links here aren’t clear. Low estrogen in women is linked to perimenopausal depression. Low Testosterone in men is likewise linked to depression. High estrogen presents mood and behavior shifts, and high progesterone brings on the waterworks (between naps). What is clear is that balanced hormones certainly lead to better and steadier moods, where fluctuations or abnormalities might put us into the roughs. MTHFR is, of course, involved in hormone regulation and processing, so righting the balance can be a highly productive step.
  • Sleep – A giant link exists between sleep quality and depression, and most of us have firsthand experience of that (is anybody else’s household entirely grumpy if their sleep is interrupted?)
  • Sedentary Lifestyle – There isn’t particularly a link between MTHFR and sedentary lifestyles, which is great news. There is, however, a big link between sedentary behavior and depression and also between exercise and improved quality of life mentally, emotionally, and physically. This isn’t an MTHFR issue in any way, but I would feel remiss if I left it out of the causes of depression list.

Each of the factors above is measurable and trackable and highly treatable, with or without an MTHFR mutation. Each of those factors can be worked on independently, but also any step toward a healthier lifestyle is going to help in many of those areas.

For example, balancing your methylation (which for us MTHFR folks usually means either taking a good form of folate or if we don’t tolerate folate, then finding a good work-around) will help to raise folate levels, lower homocysteine, and reduce both inflammation and oxidative stress. So one change is influencing four big contributing factors to depression. Does that mean balancing your methylation is going to fix your depression completely? Not necessarily, but it does get us closer to the goal and also improve your chances of responding better to other therapeutic interventions as well.

So from this list, we have a number of natural treatments for depression:

  • Folate, high folate diet, and anything that will help you to balance your methylation
  • B12
  • Exercise
  • Any kind of sleep therapy
  • Lower glycemic index diet for blood sugars
  • Reducing inflammatory foods
  • Antioxidants – especially the ones that cross the blood-brain barrier
  • Anything that will help you balance your hormones
  • Any anti-inflammatory

Every one of those is a book in and of itself, but seriously that is a lot of options to try, and all of them will lead to greater health regardless.

There are also two special factors that we haven’t talked about yet. One pertains more strongly to MTHFR folks, and the other is just a human-nature problem.

  • Childhood Trauma – A significant portion of depression in adults stems from childhood trauma, and unfortunately, people with the MTHFR mutations may be more susceptible to life-long depressive tendencies from childhood traumas than average. This is fixable, but it will take some work. This could be self-guided help through spiritual seeking, prayer, meditation, and self-healing techniques. It could also be professional help in the form of therapy, hypnosis, EMDR, or a myriad of other options.
  • Habit – This conversation is really neglected and so next week’s topic is going to be about expanding the habit idea and giving you some life hacks that you can start to practice at home, but any mental state, no matter what else contributes to it, has the potential for a habit component. This could be depression, anxiety, obsessive thoughts, intrusive thoughts, whatever. And sometimes you have to train yourself to break the habit in the same way that you would with any other bad habit.

I feel like all of this could appear daunting, but if you look at it another way, it also opens up so many opportunities for healing that are often overlooked. It can be incredibly discouraging when your doctor runs out of options for depression, but chances are they haven’t even scratched the surface of this list. Typically doctors look at sleep, blood sugar, and neurotransmitters in terms of depression. You now have the opportunity to dive deeper.

Share with friends: