Undermethylation Myths, MTHFR & the Folate Debate

70% of those with mental health conditions have a methylation imbalance. Methylation is an important biochemical process, in which methyl is added to particular molecules. Our ability to methylate impacts the expression of our genes, our ability to detoxify and our vulnerability to inflammation.
In this short episode I address the following:
* What is MTHFR and more specifically undermethylation (UM)?
* What is the incidence of (UM) in various brain disorders, including depression?
* How is it diagnosed?
* How common are MTHFR variants?
* Does having an MTHFR variant mean you have UM?
* Is folate good for everyone? Who is it not good for?
* What foods are high in folate?
* What are the concerns about high folate taken throughout an entire pregnancy?
* Has there been an increase in UM?
For further information on Undermethylation see previous episode and in blogpost at CourtneySnyderMD.com.
Also related to this topic is podcast and blogpost:
Undermethylation & Strengthening the Right Brain in a Left Brain World
Medical Disclaimer:
This podcast is for educational purposes and not intended or implied to be a substitute for professional medical advice, diagnosis or treatment for either yourself or others, including but not limited to patients that you are treating (if you are a practitioner). Consult your own physician for any medical issues that you may be having.
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[@newmexicodreams5633]

You had me at " holistic psychiatrist".

[@vjr5261]

The description of symptoms is me.

[@courtneysnydermd-holisticp3072]

I hope you found this helpful....it describes many of us.

[@Shakedown24Seven]

Always great to hear your work. Thanks a bazillion, Courtney 👍🏽

[@courtneysnydermd-holisticp3072]

Thank you. I really appreciate that.

[@StarHarvestOfficial]

So glad to see you back Dr Snyder!

[@courtneysnydermd-holisticp3072]

Thank you so much! (I've been taking some time to think about more effective (and sustainable) ways for me to share information.)

[@1disney100]

Hello! I had major blood work done and showed extremely low folic acid levels. does this suggest I am a underfolate type ? Also, when I started taking methylfolate, I felt really normal for a few days, but then developed all the negative side effects (anger, depression, headache ect) so I stopped it for now. Does this sound like underfolate or high? Thankyou!

[@courtneysnydermd-holisticp3072]

Hello! I wouldn't use folic acid levels or a reaction to folate to assess methylation Instead we use symptoms, traits and a whole blood histamine (from LabCorp) and/or a methylation profile. Most people with low serotonin symptoms (usually depression and/or anxiety) and undermethlation are high in folate, but it is possible to be undermethylated and have low folate A negative reaction to folate could be due to promoting detoxification. Thank you for your questions. I hope something here is helpful.

[@jeanpaultongeren125]

I'm looking for some Holistic Psychiatrist here in Amersfoort, Holland.

[@courtneysnydermd-holisticp3072]

Hello. You might look at the Walsh Research Institute website. The practioner list has doctors in Europe. They won't necessarily be Holistic Psychiatrists, but they will know how to evaluate and address methylation as I'm describing in this video.

[@vash-747]

Good morning! For those who are under methylated, with high homocysteine, could they take methylated folic acid for a period? How much TMG approximately daily? Thanks. I look forward to the next updates!

[@courtneysnydermd-holisticp3072]

Good evening! Thank you...If folic acid is used in a Walsh protocol (which often isn't necessary because we have other tools) to bring down homocysteine, it is normally not the methylated form. I don't find that I need to use TMG very much either, but depending, it could be 500 twice a day. If you are asking for yourself (or someone you are treating), I wouldn't recommend this or know if that would even be a good idea. Thank you for commenting.

[@vash-747]

Thanks for the reply! To decrease homocysteine, what is used?

[@mojjt]

Is organic acid test valid for vitamin B definiencies?

[@courtneysnydermd-holisticp3072]

I am just seeing your question. I don't necessarily use it for that reason, though, from my perspective, it can be helpful for B2. For B12 and folate (if I check those) I use bloodwork. I don't do testing for B6 as it is highly unreliable. I look more at symptoms for that.

[@mojjt]

@@courtneysnydermd-holisticp3072 Thank you very much!

[@lyndsey.malaniamarie]

Hi Dr courtney. I'm diagnosed undermethylator by blood histamine test. Currently, I have folate deficiency and low rbc and rdw. Folates make my mental health worse. Taking Tmg seems to help. Is there any suggestion you have to get the deficiency remedied. Chronic fatigue is a huge symtom of mine. Right now I take 400mcg of folinic acid with minimal bad effects. I can feel a little lower motivation and sadness occur. But the recommended is 5mg folic acid for 3months. I don't know how to get my stores back up.

[@courtneysnydermd-holisticp3072]

Most but not all people who are undermethylated have higher folate levels. (and thus are already dealing with depressed serotonin activity). Reactions to folate can be for other reasons beyond what I discuss in this video. Because it can help promote detoxification, sometimes that is what is causing symptoms. Methylation aside - in those with chronic complex illness (including chronic fatigue, fibromyalgia, CIRS, mast cell activation), many higly sensitve patients don't easily tolerate folate until toxins - often biotoxins such as mold toxins are addressed and then when we do use folate, we start out very low and usually do not get to high doses. Obviously I don't know if any of this applies to your situation, but I mention it to emphasize that side effects from folate can be for other reasons. Thank you for commenting.

[@Tanya-my4uo]

Hello, Dr. Snyder. Children with autism have undermethylation from neurotransmiter tests and most have increased serotonin, some have increased dopamine in addition to serotonin. They have anxiety, depression, they are not cognitive. You are talking about low serotonin, you mean like activity or an indicator in tests? Also, these children have high histamine, often high b12, which means it circulates in the serum and does not enter the cell. They have mutations in their genes MTHFR, MTRR, MRR, COMT, SUOX, VDR. Is folate given in this case? It is clear that methyl donors are not enough, but folate is also increased in blood serum.What is your opinion? Thanks!❤

[@courtneysnydermd-holisticp3072]

Hi. Thank you. There are more complexities to your question than I will be able to effectively address here. You are correct - I am referring to neurotransmitter activity as opposed to measures of neurotransmitters. I do rely more on symptoms, traits and nutrient levels that impact neurotransmitter activity, as opposed to neurotransmitter testing, which I don't use. Added folate in those who are undermethylated and with evidence of low serotonin activity, can further lower serotonin in the synapse by effecting the expression of serotonin reuptake receptors (which is very separate from the benefit of folate in the methylation cycle). Despite those on the AS being undermethylated (almost always), we do find benefit from folate, especially those who appear to be more autistic. I'm less inclined to use if for those on the high functioning end of the spectrum. If folate is used for these individuals, it would be with caution and watching if symptoms of anxiety, depression, even rigidity seemed to increase. Some of us would argue that biochemically, there are significant differences between autism and high functioning autism. Though I wasn't a fan of the name "Asperger's," it did make a distinction.

[@Tanya-my4uo]

​@@courtneysnydermd-holisticp3072Tank you!❤

[@rhondadeitenbeck30]

Meta Folate NOT Folic Acid. Methyl B12 not just B12

[@courtneysnydermd-holisticp3072]

Thank you. I'm not sure if this is a question or a comment. I'm glad to respond if you can elaborate.

[@rhondadeitenbeck30]

@@courtneysnydermd-holisticp3072 I have the MTHFR mutation that caused me to develop pernicious anemia. I was forced to seek help outside of the traditional doctor patient relationship because my doctor was just ordering cyanocobalamin shots with folic acid supplements. Of course that didn’t help at all. I have been taking Metafolate and methyl B12 along with grass fed beef liver. My symptoms are gone. You need a methyl donor. Nothing helps without it.

[@Truerealism747]

Drs just want to give amitriptyline I do not want to take those I've had those but make you put on to much weight and want to find best alternative for pain fatigue depression due to symptoms from the Asperger's add

[@catarunverma7525]

Hey, Courtney. I have mthfr A1298c heterogeneous mutation. I had symptoms of low mood, anxiety and ocd. I get severe anxiety from methylfolate, though it improves my mood. After trying folic acid and folinic acid , i got depressive symptoms. I tried sam e in 200 mg twice a week for 2 weeks. It gave me anger, irritability and depression. Also it raised my homocysteine. After that the moment i took methylfolate, p5p and methylb12, my mood improved. Not sure what to do.

[@catarunverma7525]

I took seeking health folinic acid and b12 to reduce hcy, which it effectively reduced in 10 days from 20 to 15. Still high. But got depressive symptoms. Will these depressive symptoms subside automatically as I have stopped folinic acid ? Please answer. I never had such symptoms in my life except after taking Sam e. Not sure of any other mutation, but my poor tolerance to stress indicate comt.

[@courtneysnydermd-holisticp3072]

There can be many variables so some of what I'll say may not be relevant for you. When someone is undermethylated (which you wouldn't want to assume based on having an MTHFR snp) we do aim to bring homocysteine down below 10 before starting to using SAMe or methionine. There are a number of tools we use that often allow folate to be avoided, including B12, B6 (P5P), TMG, and L-Serine. Again, I can't recommend these for you specifically. Intolerance of SAMe would make me think of high homocysteine, candida and/or mold but even overmethyation (though I would expect there to be symptoms to be fitting with that).

[@catarunverma7525]

Thanks a lot for such nice explanation. Is bad reaction to Sam e can also because of the fact that it has to be taken with methylated b vitamins, otherwise it raises hcy levels and/or there can be a possible slow comt ? I also remember having candida issues before taking sam e. Also, for folate part, should I not even complete daily rda requirement of dietary folate ? I will get tested for serum folate soon.

[@courtneysnydermd-holisticp3072]

You're welcome. Normally we assure homocysteine is not elevated prior to starting SAMe and if it is, we focus on bringing that down first. When people have mold and or candida they may not tolerate SAMe until those are getting addressed. Without having evaluated you, I wouldn't be informed enough to know what you should do or to advise you on your specific care.

[@Caribe78]

histamine intolerance is under or over?

[@courtneysnydermd-holisticp3072]

Hello....If you mean intolerance of histamine in food, that could be due to a DAO insufficiency, which is not invovled in methylation. There are a number of factors that impact histamine. Methylation is one. It is needed to break down histamine, so if someone is undermethylated they may have more issues.

[@RachelWilliams-hn1fc]

Hi Dr Courtney. I had a bad reaction to folinic acid that resulted in a lot of these symptoms made worse and severe brain fog, but it’s been several weeks now and the symptoms are still there. I believe I am an undermethylator. How can I rebalance my methylation in this case? Is there anything to counteract the effects of folate on someone like me?

[@courtneysnydermd-holisticp3072]

Hi Rachel. You might listen to the video on Undermethylation where I discuss how we address this from a brain health standpoint. As I mention in this video, many of those who are undermethylated with low serotonin activity will have a further decrease in serotonin activity with folate supplements. They usually have very high levels of folate already and we recommend avoiding any added forms of folate. I can't say why you are having your specific effects from it and I can't make recommendations, but normally we wouldn't be giving it in cases as I mentioned (as opposed to trying to counter the effects). Sometimes, however, someone doesn't have a methylation issue. They simply can't tolerate it because it is promoting detoxification too quickly and they have to work with lower doses. Again, I wouldn't know if that is the case for you.

[@catarunverma7525]

Hey Rachel, have your brain fog reduced or subsidised? I too got brain fog after taking tetrafol plus containing 😢methyl folate. I took only two doses of 2.8 mg. Before that, I had took it in May, June regularly. Hi doc courtney any guidance from your end ?

[@Truerealism747]

B9 gives me.indigestion

[@dougmann66]

Is inositol ok for lower serotonin under mentholate?

[@courtneysnydermd-holisticp3072]

Inositol actually raises serotonin levels. It can be helpful for anxiety and insomnia people with undermethylation, however, I think of it as being more supportive than the nutrients that I mentioned.

[@dougmann66]

@@courtneysnydermd-holisticp3072 awesome thanks 👍

[@dougmann66]

@@courtneysnydermd-holisticp3072 the reason for my curiosity is I read that sodium valpro can deplete inositol ! 🌞

[@Leoninmiami]

Thank you for this. It cleared up some misconceptions I had regarding B vitamins.

[@courtneysnydermd-holisticp3072]

You're very welcome.

[@shaquibalikhan6151]

can we be suffering from undermethylation without MTHFR mutation ?

[@courtneysnydermd-holisticp3072]

Yes. There are a number of genes that impact methylation beyond MTHFR. Great question. Thank you.

[@shaquibalikhan6151]

my homocysteine is 20 umol/L. my b12 is low as compared to protein intake i have. i have all the symptoms of under methylation that u have mentioned in the video. what is the diagnosis for this ? and cure . i have been suffering since long .

[@courtneysnydermd-holisticp3072]

@@shaquibalikhan6151 I'm unable to diagnose and provide treatment recommendation when I have not seen someone as a patient. The Walsh Research Institute has a resource map with doctors nationally and internationally. Many people who are undermethylated have problems with absorption. But even with that, dietary interventions are often insufficient to meet the nutrient needs when someone is having a nutrient imbalance such as undermethylation. Separately, we normally try to bring the homocysteine down to less than 10 prior to starting supplements like SAMe or methionine. I hope something here is helpful.

[@lindsayblest]

Sorry asparagus Brussels sprouts and avocado are “also high” in what? Folate? Methyl?

[@courtneysnydermd-holisticp3072]

folate

[@avaelizabeth4808]

I was own the Walsh protocol for years and my copper levels and other labs got worse than when instated .

[@courtneysnydermd-holisticp3072]

Thank you for sharing this. I'm curious if you or your doctors were able to figure out why.

[@dougmann66]

Thanks for your wonderful service dr ! ⭐⭐⭐⭐⭐

[@courtneysnydermd-holisticp3072]

Thank you!

[@Spectre2434]

What tests are most reliable for this ? Could it be implicated in spastic paraplegia?

[@courtneysnydermd-holisticp3072]

We use a whole blood histamine (LabCorp) and/or a methylation panel (Doctor's Data), but more we are looking at brain symptoms and traits. I don't have experience with spastic paraplegia, but it does look like there is some research at least related to the MTHFR gene - "Although severe MTHFR deficiency is a rare cause of complicated spastic paraparesis in adults, it should be considered in select patients...." - JAMA 2014 article - Severe Methylenetetrahydrofolate Reductase Deficiency Clinical Clues to a Potentially Treatable Cause of Adult-Onset Hereditary Spastic Paraplegia (available online)

[@courtneysnydermd-holisticp3072]

Part of this assessment is also checking homocysteine levels.