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:
Chronic inflammatory diseases
Long-term use of corticosteroids
methotrexate (because it lowers folate)
metformin (long term use because it interferes with B12 absorption)
Fibrate type cholesterol-lowering medications
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
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.
Quit smoking – As though you needed one more reason why smoking is bad for your health. But yes, smoking raises your homocysteine levels.
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.
Balance your coffee intake – As much as it pains me, too much coffee has consequences and high homocysteine is one of them.
Fish oils – in a magical synergy, fish oils + B vitamins work better together than they do apart.
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.
These past few weeks we’ve gone over some general information about MTHFR and homocysteine, the link between methionine and homocysteine, and the new information about MTHFR, homocysteine, and Covid-19. What we haven’t talked about is Homocysteine testing and parameters – what is normal, what isn’t, and what is considered normal but maybe shouldn’t be.
Homocysteine tests are simple blood tests that can be ordered by your doctor. It must be performed fasting for accurate results. Any protein you eat before your test can skew the numbers because methionine in your food may cause a temporary rise in homocysteine. The best way to ensure a blood test is fasting is to schedule your blood test early in the day before you have eaten anything. 8 – 12 hours of fasting (like you would get overnight) is best for the most accurate results.
The current medical standard in the U.S. is a normal range from 5 – 15 umol/L (that is micro mols/Litre). Anything above 15 micro mols/L is considered high, or hyperhomocysteinemia. There is a growing body of evidence that the normal level should be adjusted:
A study published in the New England Journal of Medicine shows that carotid artery thickening and stenosis risk begins to increase for men by 9.2 umol/L (although the risk for women seems to remain stable until 11.4 umol/L). Both of these are significantly lower than the 15 umol/L that is considered normal.
A strong linear relationship exists between homocysteine levels and death in patients with coronary disease. The lowest risk group has homocysteine below 9 umol/L and the risk increases from there both within what is considered the normal level and outside of it.
Homocysteine <9 umol/L = 3.4% risk of death
Homocysteine 9 umol/L – 14.9 umol/L = 8.6% risk of death
Homocysteine >15 umol/L = 24.7% risk of death.
Risk increases at 9 umol/L
The study we discussed last week dealing with homocysteine levels as a predictive marker for worse outcomes with Covid-19 also showed an increased risk for pathological lung changes on CT at 8 umpl/L
Risk increases at 10.58 umol/L
If The “Normal” Levels aren’t Ideal, What Is?
All of the risks for negative health outcomes seems to be lowest around the 6 – 8 umol/L mark, so we’re going to call that “Optimal.” This is an estimation based on the research that we talked about above. Joe Pizzorno (a legend in the natural wellness community), estimates the ideal range to be 5.0 to 7.0. Ben Lynch, the epigenetic expert, estimates ideal to be between 6 to 9 umol/L.
If Homocysteine Is So Bad, Why Aren’t We Aiming for Zero?
Too much homocysteine is bad for sure, and with MTHFR and homocysteine that is the direction we usually trend, but remember that homocysteine is absolutely essential. If your homocysteine is too low (hypohomocysteinemia), then there are also health consequences. Without homocysteine you can’t make glutathione, which is one of your main defenses against oxidative stress. Without glutathione, things would go sideways pretty quickly.
Homocysteine is also the precursor for something called alpha-ketobutyrate, which is a vital ingredient in the process that makes cellular energy. Very few studies are done about low homocysteine levels (I mean VERY few. I can count them on two hands). By far the most interesting one shows a link between low homocysteine and peripheral neuropathy. It states that fully 41% of people with low homocysteine have peripheral neuropathy, which is hugely significant.
I wouldn’t be surprised to see a link between low homocysteine and chronic fatigue, as well, although the research has never been done.
The bottom line is that we need homocysteine, but too much of it becomes a big problem. Aim for 6 – 8ish micro mols/L. Next week we’ll talk about ways to lower your homocysteine levels if they’re too high.
Of course in a pandemic we all want to know how it might affect us specifically, with all of our genetic differences. That research takes time and money and usually comes after the big stuff (like how does this spread and why does it kill people.)
In good-ish news, Covid-19 has now officially been around long enough for some of the smaller, more specific areas of research to be done. This includes the very first steps on research into the interplay between homocysteine, MTHFR and covid 19.
This particular study came about because there have been big differences in COVID disease severity, in particular in the death rate, between different geographic areas as well as between the genders. The study I am talking about was published in November 2020 in a journal called Medical Hypotheses, which is not peer-reviewed research, but rather includes important theoretical papers, so I do want to emphasize that this information is theoretical and has not been formally researched yet.
At the date of publication of this research, Covid-19 was associated with an 8.8% mortality rate in those above 60 years of age, and 0.46% for patients aged below 60 years old. Countries with the highest mortality rates are Italy, Spain, France, Iran, and the USA. A recent report from Italy showed that the vast majority of those infected who were critically ill were older men, 68% of whom had at least one comorbidity. The worldwide mortality rate is higher among men almost by a factor of two.
Mortality rate Male:Female = 1.7:1
In Italy, high rates of ICU admission, ICU mortality, and overall mortality have been seen and the deaths from COVID-19 are often associated with high neutrophils, high levels of pro-inflammatory cytokines, abnormal coagulation tests, and disseminated inter vascular coagulation.
The most common comorbidities among the most critically ill were:
The article goes on to summarize the high points of MTHFR:
The MTHFR enzyme is the most important in the methionine pathway.
It regulates fundamental processes such as DNA repair, neurotransmitter function, and membrane transport.
The C677T mutation has been suggested to be protective against certain cancers including colon and acute lymphatic leukemia.
The mutation leads to a thermolabile variant of the MTHFR enzyme in which the dissociation rate of the cofactor Flavin Adenine Dinucleotide (FAD) (this is from B2) is increased, thus reducing the activity of the MTHFR enzyme by 50% or more.
In people with a medium skin tone, the function of the MTHFR enzyme is largely preserved as long as they have sufficient dietary folate intake.
With insufficient folate intake, the production of 5-LMTHF is reduced, which leads to the accumulation of the key metabolite, homocysteine, to toxic levels.
MTHFR is the most common genetic cause of hyperhomocysteinemia.
Low folate status resulted in significantly higher levels of homocysteine in men.
Research suggests that the C677T mutation is associated with a significantly increased risk of coronary artery disease only in homozygous men.
Other risk factors for the development of high homocysteine are:
chronic kidney failure
cancers of the breast, ovary, and pancreas
Acute High Homocysteine
In addition to the risks of high homocysteine that we have talked about before, an acute high homocysteine situation can be triggered, independent of folate status, when a systemic inflammatory process is triggered (like, for instance, by a virus). This process boosts inflammation and releases a tremendous amount of reactive oxygen species (free radicals), which can overwhelm your antioxidant defense systems. This is potentially an even greater issue in MTHFR folks because we have the potential for lower glutathione than average. This whole ugly cascade activates something called nuclear transcription factor (or NF-kB), which accelerates viral replication in SARS Co-V. The study also cites a case report in which glutathione supplementation led to a rapid symptom improvement in two cases of Covid-19.
Interestingly, COVID-19 patients’ plasma homocysteine levels show predictive value for the progression of pathological findings on chest CT. This means the higher the patient’s homocysteine is, the more likely they are to show damaging changes in their lung tissue on a chest CT scan. Also, these changes began to show at a lower homocysteine level than the one that is usually used as a medical reference. Negative changes began to show at 10.58 umol/L rather than the 15 umol/L that is normally recognized as a “high” value.
What Do We Do About High Homocysteine, MTHFR and Covid-19?
This study makes some suggestions.
Patients at high risk with Covid-19, such as the elderly with comorbidities, should also be screened for high homocysteine.
Those with 8 umol/L Homocysteine or above should implement a folate-rich whole foods diet (fruit, vegetables, whole grains, good protein sources.)
These individuals should also add 5-MTHF supplementation.
Folic acid should be avoided by these individuals as supplementation can have the opposite of the desired effect, especially in individuals with the MTHFR polymorphism. This is thought to be because unmetabolized folic acid accumulates, which inhibits MTHFR and also folic acid competes at binding sites with 5-MTHF.
B6, B12, and B2 should be added as well as they are cofactors for the MTHFR enzyme, or in the methionine pathway.
Supplements with demonstrated anti-viral properties can be added, including vitamins A, C, D, E, selenium, zinc, iron, and omega-3 fatty acids.
Strong antioxidants including vitamin C and glutathione have shown positive results for Covid-19 outcomes.
At the end of the day, it looks like taking care of yourself appropriately for MTHFR and following the positive steps to balance your methylation that we have been talking about, is actually the best defense for those of us with MTHFR against the worst of the outcomes with Covid-19. Taking positive steps to manage your MTHFR doesn’t mean that you won’t get Covid-19, but hopefully, it will help to reduce your risk of dying from Covid-19. Keep in mind that this study represents a well-researched theory, and it has yet to be proven in clinical trials.
The link between MTHFR and homocysteine is clear – if you aren’t familiar with that part of the picture, you can brush up with last week’s topic. The link between methionine and homocysteine is clear as well since they loop together in the methionine cycle with dietary methionine converting into homocysteine as a by-product, then being recycled back to methionine using MTHFR.
It’s easy to get into a situation where you assume methionine is “good” and homocysteine is “bad,” but actually for MTHFR, methionine itself is a double-edged sword.
Recommended Intake of Methionine
When it comes to suggested protein intakes per day, it’s pretty hotly debated and the criteria are updated every few years. Generally, requirements for infants are much higher (according to intake in mg/kg body weight) than those of children, and children are in turn higher than those of adults. Again, this is based on an mg/kg measure and not an absolute number.
Infants (3-4 months) – 58 mg/kg body weight/day
Children 2 years old – 27 mg/kg body weight/day
Children 10-12 years old – 22 mg/kg body weight/day
Adults – 13 mg/kg body weight/day.
This means for the average 150 pound (or 68 kg) adult, the daily requirement for methionine is 884 mg. That is found in 100 g (or 3.5 oz) or less of a lot of meats. This means that while vegetarians are probably getting the right amount, most meat eaters are significantly overdoing it.
Recommended Daily Protein Intake
This data is also debated, but the best researched reference data from the World Health Organization is below.
Protein intake in grams/kg body weight/day
1.2-1.4 g/kg body weight/day
0.8 – 0.97 g/kg body weight/day
0.67 – 0.79 g/kg body weight/day
0.75 g/kg body weight/day
0.6 g/kg body weight/day
0.75 g/kg body weight/day
0.92 g/kg body weight/day
Basic rate plus 15 g per day for the first 6 months, 12 g per day thereafter.
This works out to about 46 grams per day for the average woman and 56 grams per day for the average man. In the west, we tend to overdo protein. Most American adults eat about 100 g of protein per day, which is twice the recommended amount. Not only that, the latest trends in nutrition mean that 60% of Americans report that they are trying to increase their protein intake according to the Hartman Group.
Food Sources of Methionine
Methionine is an amino acid, which is the building block of protein, so naturally, it is high in protein-rich foods. The top ten categories of foods according to my food data are:
Methionine per 100g
Methionine per 6 oz
Chicken breast, thigh, drumstick.
Beef (skirt steak)
Other cuts of beef, lamb, veal, buffalo
Grouper, salmon, snapper, tilapia, mahi mahi
Lean Pork Chops
Pork ribs, lean ham, pork bratwurst,
Edamame, soybean sprouts, soy milk
Low fat ricotta
Parmesan, gruyere, Swiss (other cheeses)
Hemp, squash, pumpkin, chia, sesame seeds.
Large white beans
Navy, kidney, black beans.
Teff, wild rice, kamut.
So… Too Much Protein?
In the West, we love our protein. We’re all working on building muscle and improving our lean bodyweight… Except that in reality, most of us aren’t. Most of us are actually working on holding down our office chair and staring at a screen. Still, we’re obsessed with the idea of being fit and lean so we overconsume in different ways than we used to. Most of us eat more than we need in general, and those of us who are “working on our health” are especially prone to working to get too much protein This, of course, leads to the modern issues of obesity and heart disease,
For people with an MTHFR issue, this takes on an added dimension because eating more protein means adding more burden to the methionine (or methylation) cycle and hence the MTHFR enzyme which ties methylation into the folate cycle. Remember how those two cog together like gears?
Extra protein means your folate cycle has to work harder, your body needs more active folate and more methyl donors, and homocysteine is going to build up. We already talked about how bad homocysteine is when it builds up.
Plus, Lower Methionine Intake Might Mean You Live Longer
Research has long shown that calorie-restricted diets are effective in promoting lifespan. Meaning, the people who eat less usually live the longest, even to the fact that some of the humans with the longest life spans on record have gone through periods of food shortage. Further research has found that limiting methionine intake specifically extends lifespan. That is with or without actual calorie restriction. Also, intermittent fasting, which is one of my favorite health hacks, is a great way to actually have minor calorie restrictions without too much fuss.
In a fascinating study, researchers are also limiting methionine with the use of an oral medication that breaks down methionine (called an oral methionase) to treat Covid-19. The RNA of the coronavirus needs to be methylated, using SAMe, in order to initiate viral replication. Limiting methionine (which limits SAMe) interferes with that step and so slows the viral replication and can potentially reduce viral load. This generally makes me wonder about all of us MTHFR folks and Covid-19. Do we have a survival advantage because it’s harder for us to produce SAMe? Also, should people supplementing with SAMe consider taking a break if they’re in a high-risk situation for COVID?
Even though we are obsessed with getting more protein – I mean, who doesn’t have jerky in their purse right now? We are clearly overdoing it. Reducing protein intake, specifically methionine, would help us all live longer, healthier lives. But it is especially important for MTHFR folks.
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.
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.
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.
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.
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.
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.
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.
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.
MTHFR and detoxification are intimately linked. Having a methylation issue impairs detox of many substances including heavy metals and hormones to name a few, but also when those branches of detoxification are impaired it can generally affect the speed at which other substances are able to be eliminated. So actively supporting those elimination pathways is a huge part of the MTHFR lifestyle. The problem is that anybody who has ever had a hangover, knows that being toxic comes with symptoms. Sadly, lots of people who have done cleanses also know that cleansing too quickly can come with symptoms.
I can certainly say first hand that doing an intense cleanse is fraught with difficulty. When I was a student, well before I knew anything about MTHFR or it’s consequences or that I have it, a good friend was bulk ordering cleanse kits at a discount. This is the sort of weird geekery that we engaged in as students. Anyway, the cleanse involved a limited diet that tapered down to a total water fast over the course of six weeks along with heavy-duty liver pushers, clay as a binder, and a massive dose of fiber. I won’t go into the gory details, but right around week four a good friend sat me down and said, very earnestly, “If you don’t stop this cleanse, I am personally locking you in your apartment to preserve everyone else’s sanity.”
I actually broke that fast with an entire large extra cheese and pepperoni pizza and an order of breadsticks by myself, which is even funnier if you had seen me in person because I’m 5’2 and 105 lbs soaking wet. Quite honestly, the pizza was blissful and the only part of that cleanse that was worth the price of admission. The problem was, that for my body the cleanse was WAY too intense and it pushed my liver to liberate toxins that my system had no way of actually eliminating, and so they rattled around turning me into quite literally a toxic human.
Interestingly, when we refer to someone as “toxic” emotionally, they are usually a pretty good picture of what a person who is toxic physically looks like. Angry, lashing out, generally spewing hatred and unpleasantness. Internally they might also have a headache, some mild (or severe) nausea, and be constipated. Their skin could be itchy, they might (eek!) produce some weird odors. It’s all pretty gross and, well, toxic.
The symptoms of being toxic and needing a detox are much the same as the symptoms that occur if you’re trying to detox too quickly. I know, for the small handful of you who are listening who have experimented with an overly-eager cleanse before, this was a lightbulb moment. The rest of you are probably saying, “so what?”
The reason this matters is that if you’re truly on a path towards balancing your methylation, then you’re going to get to the point where you start incorporating gentle detox into your routine more frequently, and invariably when people start doing gentle detox regularly and see how much better it makes them feel, they try to push the envelope with heavier-hitting detox.
So let’s talk about steps toward mitigating those toxic symptoms. We’ll go through a little flow chart.
Are you having symptoms spontaneously (like you’re just toxic) or have you been actively detoxifying?
If you’re just toxic, it’s time to implement some gentle detox strategies and give your body a cleaner diet for a couple of weeks or for good.
If you’ve been detoxing, it sounds like you’re pushing your body a bit too hard. Here’s how to handle that.
First, Stop taking any supplements involved with the detox. Your body needs a break.
The next big priority is to get your bowels moving because if you can’t physically eliminate things, then they’re hanging around inside of you and that is a genuinely horrible thought. This may mean a one-off dose of a laxative tea or even a glycerine suppository. Whatever you do, make sure you poop.
Also, adding in some detox-type activities that don’t go through your liver or bowels can be a really helpful thing. This is using a sauna or sweating it out in any way you can, doing castor oil packs, taking Epsom salts baths, and that type of thing.
Keep a very simple, clean diet (fruits and veggies, rice, broth, fresh juices, lots and lots and lots of water. No alcohol, refined sugars, or processed foods, until the symptoms have passed, will help too.
Sleep more – as much as you physically can, and generally give your body a break.
In general, I warn MTHFR folks away from detox kits unless they are a pro with detoxes and can read their body’s signs and symptoms effectively and know how to counter any adverse reactions. But just because we can’t do prepackaged kits very well, doesn’t mean we can’t detox.
I love intermittent fasting. Love it with a passion. It’s easy, it’s safe, and it’s extremely well researched in all kinds of areas, but especially in promoting longevity. It’s just about the simplest and most effective health hack out there. Here’s how you do it.
24-hour Fast: For a 24 hour fast, have dinner like usual, skip breakfast, lunch, and snacks the next day and drink plenty of water with a little bit of lemon in it (or plain if you’re not into lemon). Around the same time as you had dinner the night before, have a healthy, simple dinner. That’s it! It’s literally the easiest possible health-boost because there is less effort involved than you take on a normal day.
36-Hour Fast: For a 36 hour fast, have dinner the night before, skip all food the day of the fast and drink a ton of water or lemon water. Get up the next morning (which is roughly 36 hours later) and eat a healthy breakfast. Done!
This is a great tool to use quarterly, and it can be as simple or as intense as you feel ready for that quarter. A simple clean week could be stripping your diet down to fresh fruits and veggies, rice, broth, and some gentle herbal detox teas. Take out some of the foods we tend to lean on that might not be the best – the grains, processed foods or packaged foods, refined sugars. During this week it’s important to rest more, be more mindful of toxin avoidance, and I like to take it as an opportunity to go inward – do a bit of journaling, clear out some clutter, that sort of thing. If you want to get more intense about it you can do a full juice cleanse, liquid diet, or alternate between juice only days and fasting days. This is a completely customizable tool.
This is exactly what it sounds like, and can be a really helpful format to use if you have a habit that you know is taking a toll. A modified month is like taking a reset on a bad habit – if you’ve watched your sugar cravings ramp up (like mine have) during covid, it could be a great idea to do a modified month over the summer in which everything else is mostly the same, but you cut out the sugar and sweets. Lots of people do modified months with events like Dry July or Sober October. Also, a modified month can be a great way to work on improving a good habit instead of eliminating a bad one. What about Active August or Hydrated… Shmydrated. I don’t have a rhyme for that one.
Detox can be as simple and small or as large and complex as you want to make it, and just because you did a big complex one last time doesn’t mean you need to do that again. Take your stress level and your life chaos into account when you’re planning this.
Last week we started our conversation about the “bad habit” component, called neuroplasticity, of depression, anxiety, intrusive thoughts, and obsessive or compulsive thoughts. This is, of course, only part of the picture. Neurotransmitter balance is a factor along with the often overlooked physical contributors to depression and other states.
When you’re first trying this, it can be really helpful to try all three strategies at different times to see what works the best for you. You’ll know it works when you are able to pop yourself out of your mental bad habit – to feel different in your body and to let go of whatever thought pattern it is that you’re working on.
Stages of Resolution With Mental Bad Habits
Learning. In this phase, you’re actually learning to pay attention to your thoughts and that takes more time than you would think. You may find a particular “warning” signal for you – it could be a behavior (like when I’m starting to feel this way I always log on to Facebook and click links that make me angry or I start craving XYZ food. It could also be a physical feeling – a headache in a particular place, a clenching in your belly, pain in your neck or shoulders. It could also be something more subtle like tuning into your mood more frequently.
Out of Control. This phase feels like you’re moving backward. You’ve started tuning in and now you’re actually noticing how much your brain does this thing and it’s a ton! It will seem like your brain is a wild horse racing ahead of you, and it feels like the bad habit is happening more, not less. That is a GREAT sign because the reality is that you aren’t doing the bad thing more, you’re just noticing more and that is the first step to actually changing it. This can take a few months of diligent attention, but don’t get discouraged – you’re doing it and you’re making progress.
Quietening. In this phase, you start to make tangible progress and you’ll notice that the mental bad habit becomes softer somehow. Quieter. The thoughts/feelings are still there and they still affect you, but you’re learning to let them go more quickly and it’s easier not to get pulled in by them.
Maintenance. This phase is amazing. One day you’ll notice your mental bad habit pop up and the first thought you’ll have is “Oh! I haven’t seen that for a while.” and you’ll dismiss it and move on. This is the phase where you have the freedom to move on to something else because that bad habit is mostly gone. It’s a good idea to still take proactive action when it pops up, but it is popping up so much less frequently that it becomes almost a curiosity when it’s there.
Great! So I’ll be mentally healthy by next week, right?
Absolutely not. I would love to say it was easy and took no time or effort, but that would be a bald-faced lie. It’s a challenge and it takes time. You’ve probably had this mental bad habit for years if not for your entire adult life, so it will take some time to break it too. And some time doesn’t mean a couple of weeks, it means months and maybe even a year. This isn’t quick, but it is SO. WORTH. IT.
Does This Work Every Time?
This works every time if you stick with it, and when there isn’t some other major imbalance. If your serotonin is actually so low it’s living in the sub basement, then this will still help fix the habit part of it, but it won’t completely normalize the serotonin (but it will bring it up – research shows these techniques are associated with higher levels of both serotonin and melatonin). Although, every day we’re learning more about what this can actually accomplish.
What IS This Witchcraft? It’s Mindfulness.
Yup. That thing that hippies and new-agey types do. Also, everybody who studies neurology and neuroscience of any sort, because as it turns out the effects are so powerful as to be almost unbelievable.
Among the many documented effects of any form of mindfulness are:
Reduced cognitive reactivity (so external things don’t affect you so much)
Reduced reactivity of the autonomic nervous system (you don’t get an adrenaline spike every time something bad happens)
Depression and anxiety are common problems for humans. So common that almost all of us will experience one or the other or both in our lifetimes. In truth, both depression and anxiety are normal and healthy reactions to life stressors, grief, and trauma and they have their uses in terms of survival and adaptation. The problem comes, then, when they linger beyond their useful time.
The Neurotransmitter-Only Myth
In modern medicine we tend to compartmentalize and idealize situations in which we can blame a problem on one concrete and measurable thing. Like serotonin. Serotonin is a great thing to blame in medicine. Not only is it concrete and measurable, but we have drugs to change how it is used and processed and therefore, it’s “fixable.” That is all nice and neat and it would be perfect, if this strategy actually worked. Like, really worked.
I am not at all suggesting that this is a bad route of treatment for depression – it’s actually a pretty good one and lots of people see improvement of their symptoms and sometimes even resolution with a drug that affects serotonin, like an SSRI. But, lots of people don’t, which means we have a ways to go.
Last week, we talked about other factors that can lead to depression, and those are generally physical states. These are typically also pretty straightforward to address and will often bump a person from meh, to good. That is tremendous. But what about what is left?
Mental Bad Habits, Also Known As Neuroplasticity
The factor in troubled mental health that I feel is most overlooked is the bad habit factor. Unfortunately, this is a giant factor in our mental health because there is an important survival-related brain function that prioritizes neural pathways that we use frequently, which we call “neuroplasticity.”
Neuroplasticity is part of the way your brain learns what is important to you. The pathways between neurons that you use most frequently get strengthened and prioritized because they matter to you.
Picture it like a path through tall grass. The first time you walk through the tall grass and weeds you have to push through weedy tangles, the plants pull at your legs and they’re so close together that you can feel resistance as you walk. The fifth time you walk the same path, you notice the plants are trampled in that area, there is a natural space opening up and walking is easier. The five hundredth time, there is a dirt trail there where the plants have stopped growing because the path is traveled so frequently. It’s clear and easy and there is no resistance.
Your brain is exactly the same way – the more you use a certain pathway, the easier it becomes to continue to use that pathway. This principle applies to many mental states that could be considered mental bad habits.
Guilty or self-reproaching thoughts.
Lack and scarcity
This also applies to many mental states that can be considered mental good habits.
Now, does this mean that if you focus on retraining your brain that a lifetime of depression and anxiety can disappear? In all honesty, I think it does, but it also takes a significant amount of work, and sometimes there really are nutritional deficiencies, physical problems, or neurotransmitter imbalances that need to be corrected as well.
Breaking A Mental Bad Habit
There are three techniques that I think are incredibly helpful in breaking a bad habit. The key to all of these is experimenting to see what seems to work best for your particular bad habit, and then repeating the technique over and over again. Mostly, this boils down to practice. So here are the techniques to choose from:
Say your issue is catastrophizing or anxiety and you get into a place of “what if.” “What if I lose my job and I can’t keep up with the bills and I have to choose between keeping the house or …” We all have these thoughts sometime and they are largely unproductive. This isn’t when most people do effective planning, this is just when they spin out into fear and anxiety. So, here’s what you do.
Notice you’re spinning out. This is actually the hardest part because if you get into this thought frequently, it often runs in the background without you placing any attention on it.
Choose something awesome instead. With the above job-loss fantasy (which is in most cases just a fantasy), replace it with an opposite fantasy. “What if I win the lottery and buy my own jet and …”
Enjoy it for a minute. Really get into the replacement fantasy. Figure out what you would do, imagine how it would feel waking up every day knowing that you can do whatever you want. Think of all the things you could enjoy.
Repeat. Every time you notice anxious thoughts, do this same thing. It takes practice, but you will notice the anxious thoughts coming less frequently, feeling less emotionally compelling, and vanishing more quickly.
The Stop and Drop
This is my personal favorite, just because it’s a nice gap in a crowded mental landscape. Again, the hardest part is noticing your mind.
Notice you’re having a mental bad habit. If you’re doing your mental bad habit – judging yourself, feeling bad about something, obsessing, the first step is always to notice you’re doing it. This means recognizing the thought or feeling in the moment.
Stop. In that moment stop what you’re doing for a few seconds, take a deep breath, and notice your body, your hands, your shoulders, the physical feeling that goes with your mental bad habit. Usually, people notice clenched jaws, fisted hands, bunched-up shoulders, clenched belly, that sort of thing. Let your body relax.
Drop. Take another deep breath and keep your body relaxed and let the thoughts just drop. You don’t really have to do anything with the thought, just let it finish and go away and don’t choose to pick it up right away.
Repeat. Again and again and again. This isn’t quick, but it is so effective. You are literally training your brain and just like training a dog or a horse, it’s all about persistence and repetition.
I learned this technique when my little girl was an early toddler and it applies to adult brains too.
Notice your brain is in a bad place. Again, this first step is the hardest but if you start to pay attention, you will start to catch yourself in places you don’t want to be.
Choose a distraction. Find your own version of a toddler distraction. Something your brain likes to do that isn’t a mental bad habit. It could be a book, a funny youtube video, or a quick game of some kind. Something that is mentally compelling enough to distract you entirely from that thought.
Do your distraction for 1 – 3 minutes. It helps to set a timer so you don’t get lost in your distraction because that isn’t helpful either, but use your distraction as a way to bump your brain out of an unhealthy pattern. I’m not suggesting you binge watch Friends to stop your depression because ultimately, that isn’t the point. Distracting yourself for twelve hours straight really only counts as one episode of distraction. The key is to repeat at short intervals.
Repeat. Every time you notice your bad habit, give yourself a quick distraction. It will happen
A Note About Recognizing How You’re Feeling In the Moment
This is actually the hardest part because at the end of the day, the mind is a wild landscape and it’s not actually under much control. Your mind mostly does it’s own thing and you actually tune in selectively. Tuning in more often means you’ll have to learn the signals your mind gives you. A big part of this process will be noticing the trigger thoughts, feelings and body sensations that actually tell you your mind is in a dark place.
Lots of what goes on in your mind stays in the dark corners, never really coming to your attention except maybe as a sour feeling in your stomach, tense shoulders, or the sinking feeling that you’ve done something wrong and you’ll never be good enough. All of those things start in your mind even if you don’t hear or listen to the thoughts. It’s especially hard to see if you’re in that state almost constantly. Just keep trying. Even if you notice it twice a day, that’s a huge step forward.
If you really don’t ever notice it, then set alarms for yourself to practice one of the above techniques randomly. Take 2-3 minutes out of your day as often as you can – even hourly while you’re awake. It all adds up and stopping any thought and replacing it with something either entirely neutral, like the stop and drop or joyful, like the fantasy, makes a difference in the tracks your brain will follow.
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
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
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.
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.
Undermethylation, as we have discussed, is the most common state according to the research of Dr. Carl Pfeiffer in his book Nutrition and Mental Illness, An Orthomolecular Approach To Balancing Body Chemistry. Undermethylation really isn’t one state – it’s a tendency based on your genes, lifestyle, stressors, diet, and environment. Undermethylation is also a tendency that flows in a spectrum, from very mild symptoms to far more severe ones.
If you’re not sure if you’re an undermethylator, methylation neutral, or an overmethylator then visit this post for a comparative chart. As with everything else, even the most severely undermethylated person will have some associated traits and not others – this is all very individual. The biggest constants are high achievement/perfectionism, seasonal allergies, and depression.
Undermethylators Are Blessed With Many Positive Traits.
High drive to achieve
There Can Be A Darker Side:
Obsessive-compulsive traits or disorder
Undermethylation Can Lead to Physical or Medical Issues
Seasonal and inhalant allergies – this picture is dominated by high histamine and this is one of the most common problems even in relatively moderate or healthy undermethylation.
Headaches – these could be hormonal, allergic, stress-related, or migraine.
Addictions – softer addictions like workaholism in more healthy situations, which can progress to harder addictions.
Depression – depression is very common in this group and it can be quite severe.
At The Extreme End of Pathology Undermethylators Can Be Prone To:
Paranoia, delusions, or phobias – the FBI or CIA is after them, their neighbor is an alien, etc….
Denial of or tendency to hide illness – illness just doesn’t go with perfection very well.
Hearing voices – Dr. Pfeiffer estimated this to be 5-10% of this group.
Nutritional Tendencies In Undermethylation
Bad Reactions to B Vitamins – not every undermethylator experiences this, but many do. B vitamins, especially folate and B12, can cause bad reactions.
Often low calcium and/or magnesium
Often low methionine
Often low B6
Often low serotonin – can be extremely low
Often low melatonin – made from serotonin, so tracks along with it.
Medication and Supplement Reactions in Undermethylation
This represents what is typical for the group, but drug and nutrient reactions can be very personal, so this is a general guideline and not a certainty. This information is both from Dr. Pfeiffer’s book (see above), this article, and my own experience with clients.
Typically Good Reaction
Typically Bad Reaction
SSRI medications (although may still be troubled by side effects)
Folic Acid, Folate, Folinic Acid, 5-LMTHF
SAMe, DMG or TMG (all methyl donors)
St John’s Wort, melatonin
Calcium and magnesium (1:1 ratio), zinc
Antioxidants – A, C, E, alpha-lipoic acid, resveratrol, ECGC, etc…
High folate foods including dark green leafy veggies and beans/pulses
Omega-3 fatty acids
Finding your best path forward is still a bit of trial and error, but this can give you some starting points. Remember, all of this depends not only on your MTHFR polymorphism, but all the other polymorphisms you might have (of which there are likely hundreds if not thousands) so be patient with yourself when you’re finding the best nutrients for your body.