March of Dimes and most medical providers recommend folic acid supplementation for up to a year preconceptually to prevent neural tube birth defects. I’m wondering if you support that recommendation
Thank you for this question. I'm all for folic acid to prevent neural tube defects, fitting with the CDC and what I see on the March of Dimes website (where they recommend adding supplementation 30 days before conception and for the first 12 weeks of pregnancy for most women (not high risk). I'm glad to look at other references that suggest up to one year before conception. I'm not seeing that on their website.
Wow I can so relate to all this. I'm homo for C677T and any form of folate makes me depressed 😔 I live in South Australia. Please tell me where a can get professional help 🙏
Thank you for commenting on this. From a Walsh (Research Institute)/brain perspective, we actually look at the outcome of all the methylation genes as opposed just MTHFR. Sometimes people have other SNPs that can offset the impact of the MTHFR. Another difference is if someone is undermethylated and has low serotonin activity (such as depression or anxiety - which is very common in my practice), we would actually avoid any type of folate (methylated or not). I do think most functional medicine doctors (who are not brain-focused), however, would agree with what you are saying. Thanks again.
My 21 year old struggles with debilitating low energy/ fatigue. She also has significant anxiety. Recently realized she has MTHFR polymorphism (C677T heterozygous), and issues with low b2, high ferritin, low iron. Just ordered an MTHFR b complex supplement that includes methyl folate. Is this a bad idea?
About 40% of the population is heterozygous. Debilitating fatigue would make me wonder if something else is going on. Normally I assess methylation in conjunction with copper, zinc and consider if toxins such as mycotoxins (very common) or gut microbial imbalances are at play. Fitting with the Walsh approach (which I have posts on) - to assess the impact of all the methylation genes together, (and not just MTHFR), I use a whole blood histamine (methylation helps remove histamine). If someone is undermethylated and has low serotonin symptoms, folate can make them feel worse. We typically use SAMe instead. But again, normally we are looking at more variables than the presence of MTHFR. I hope something here is helpful.
Yes, you’re right, my daughter does have other health issues (history of Lyme and mold illness, MCAS - much better since we dealt with the mold, multinodular thyroid with normal thyroid hormone levels, and a muscle channelopathy that causes episodes of weakness. Most things are either resolved (Lyme and mold), or somewhat controlled (everything else), but no one has an answer or treatment for the terrible fatigue. I will go back and read your information. Thank you for your input!
Hi, I couldn’t find the blog post about “the role of the NMDA receptor in methylation imbalances” as you referred in this article, would it be possible to share the link?
Hi. Great question. I don't have a newsletter on that yet, though have one in the works. Those with undermethylation can have high activity at the NMDA receptor. Symptom-wise this can look like addiction or OCD tendencies. NAC is a supplement does a lot of things, but one is that it can decrease activity at the NMDA receptor.
https://juniperpublishers.com/gjidd/GJIDD.MS.ID.555841.php This is a very interesting study that shows NMDA receptor dysfunction is appearent in ADHD patients. What can people with ADHD do to improve this function? You mentioned NAC supplement can reduce the activity of NMDA receptor.
But in the research it says ADHD patients already have reduced activity "reduced expression of NR1/NR2 impairs the dopaminergic system which is closely associated with the regulation of attention and reward processing and further contributing to the symptoms of ADHD." so wouldn't it further reduce the NMDA receptor activity in this case?
A whole blood histamine test showed a low histamine level (25). But I had been taking a LOT of niacin for several weeks. (Didn't take niacin for 12 hours before the test though). I'm a little concerned now that the niacin lowered the blood histamine , making me think I'm an over-methylator when I'm not. I don't want to take folic acid if I'm actually an undermethylator. Niacin has been a life-saver to me, though, for anxiety. Up to 3 grams a day.
Hi. I wouldn't expect niacin to lower histamine. If anything, it would more likely to increase histamine. There are a lot of medications that can lower a whole blood histamine level. Another situation in which the histamine level is not reliable, is when someone has a DAO insufficiency,. We don't know why, but they often will paradoxically have a low histamine level. You may already know this, but we do use niacinamide in overmethylation (with B12 and folic acid). It can also be helpful for those who have a slow COMT and/or MAO causing high dopamine activity. Thank you for commenting and sharing your experience.
total body histamine by chronically depleting storage levels.11
I want to start taking folinic acid but I am hesitant because, of the characteristics listed above for under-methylation, I fit every one except addictive tendencies and seasonal allergies. However, I am empathetic, have strong artistic interests and musical ability, and have food sensitivities. I want to make sure the blood histamine level places me firmly in the over-methylating category before I start experimenting with nutrients other than niacin.
Thank you for sharing that article. Really interesting. I'll need to see if Dr. Walsh has commented on this. Typically, we rely more heavily on symptoms than on the whole blood histamine and people don't need to have all of them. I do see many undermethylated people who are highly creative and many who have food sensitivities. When someone has a mixed picture (which I personally have as well), I think about undermethylation with a slow COMT and/or MAOA variant. I have a podcast on these 2 variants if you haven't heard it. Thank you again for sharing that.
I only just read this today because it was linked to another blog that comes up on my feed. Fascinating. It caused me to wonder about a couple of things: (1) can excess folate cause irritability and (2) although perhaps not seen a lot in psychiatry, might there be a relationship between UM and seizure disorders?
Hi. 1) yes, especially for those who are undermethylated and already low in serotonin activity. 2) there could be a relationship (depending on what other symptoms or traits are present)., but more often, I think of cardiovascular disease, autoimmunity and cancer being more common with methylation imbalances. Thank you for joining the conversation!
I’m not sure which way to go in order to help my son. He is a 22 year old varsity athlete, and university student. He has been struggling greatly over this past year. It started with a major break up and the death of his grandmother. He has a lot of physical and mental stress from being a high level athlete. He is a 4th year university student who has never liked school and really struggles to apply himself academically. If it wasn’t for football, I doubt he would be in university. He has always been quiet and somewhat antisocial. He is extremely driven in sports and is also very sensitive to criticism. He is has never been a pleaser which certainly didn’t help him going through school. He has always been kind and likes to help the underdog.
This past year he started getting Ds and even failed a course. Normally he gets Cs and Bs. He seems very depressed. He has one more year of university to complete his degree but wants to drop out. He has even said he wants to take a break from football which has been his passion since he was a little boy.
I have done all of our family’s genetics. Owen is homozygous for the variants in COMT, MTHFR, DRD2, NBPF3, SLC23A1(B6), SLC30A8(zinc), GC(vitamin D) FUT2(B12), heterozygous for MAOA, ANKK1, and Homozygous for the normal allele of TPH2 and 5-HTTLPR.
He is the only one in our family with the slow version of COMT. My other 3 children have been diagnosed with ADHD. We tested Owen and he didn’t get a diagnosis, I’m assuming because of the slow COMT. However he struggled to focus and get motivated for school even though I know he has the intelligence. This past year he started using his siblings Vyvanse occasionally to help him get through his studies. I have also noticed that he started using cannabis as well, which is odd for him because he is so tuned into health and nutrition because of football. I now realize how detrimental Vyvanse is for him because of slow COMT and I am making an assumption that this along with the breakup and death has put him in a very bad place mentally and emotionally.
I desperately want to help him, he is struggling so much. But I am so confused as to the path to take because of his undermethylation, slow COMT, low dopamine and normal serotonin.
He has agreed to stop taking and I am hoping this will alleviate his need for cannabis. Should I try SAMe or TMG and stay away from methyfolate because of his very low mood? If it was just a slow COMT, that would be one thing, but add in undermethylation and low production of dopamine and fewer dopamaine receptors, and depressed mood….I am having a hard time trying to figure the hierarchy. I don’t want to give folate because of his depressed mood. I’m now even concerned about the amount of protein he consumes. But he needs to eat a lot of protein to preform in football.
I’m sorry this is so long, but I am just looking for some guidance in which is the most important gene to support first. I’m now thinking that because of how well we eat (tons of leafy greens, grassfed beef, chicken etc) this may have actually been detrimental for him as well. Any direction would be greatly appreciated. ❤️
I'm sorry your son is struggling. Without evaluating someone, I'm able to give an informed response. I would say, however, that I don't tend to treat snps, because we never know if they are being expressed or not. I consider them (if someone has their variants) in the bigger picture of their symptoms, brain related nutrient levels, evidence of inflammation, toxicity and stress/trauma. For anyone with brain symptoms however, I do check the basic Walsh lab
that involve a few specific nutrient levels that have been found to contribute to brain symptoms (methylation is just one). I have a post on the labs that I use. Separately, when college student start to struggle, one of the first things I think of is mold toxicity from their dorm or apartment. I have also seen individuals with mold toxicity from cannabis. Mold toxicity (which is very common) can cause it's own symptoms, but also impact the expression of various snps. Mold toxin testing is also referenced on that post about lab testing. If you want to message me the state you are in, I can share some clinical resources.
Thank you Courtney. We live in New Brunswick, Canada. I will look at the Walsh labs, I bought the book. As far as mold and dorm rooms, he lives at home. He attends the university that just happens to be in our town. We built our home about 18 years ago and have never had any water damage. He also gets his cannabis from the government agency store I wouldn’t think mold would be an issue, but of course it is possible. My hypothesis is that he started taking 30mg of Vyvanse last fall. His girlfriend of 3 years broke up with him ( which he did not want and was devasted) and his grandmother died who he was very close with. I was thinking that all the things I just mentioned along with being a Captain of his football team with a very toxic culture and school stress was too much for his slow COMT and poor methylation to handle. It was a few months later that we noticed him smoking cannabis, he was never a cannabis smoker before….maybe the odd time at a party or something. I feel he was trying to self medicate whatever was going on in his head. As I mentioned, we eat really well (organic, grassfed, free range, gluten and dairy free, lots of vegetable etc). We also supplement with a Seeking Health Multi vitamin, vitamin D, omega 3 and magnesium. So I didn’t figure he would be deficient in micronutrients. We did do an organic acids test and his vitamin C, folate and glutathione were low. He did suffer from a lot of GI issues such as Candida and SIBO but we cleared those up with the help of our Naturopath last spring. He also has been practicing meditation and yoga for a couple of years now. I guess that’s why I thought that the combination of Vyvanse, slow COMT and undermethylatin might have created a real mess inside his head. I explained this to him and he stopped the Vyvanse and cannabis and just wants to find balance again. He is just really depressed, crying, very emotional, tired and having a hard time getting his school work done. He had to summer courses because he failed for the first time ever and is currently not eligible to play football in the fall….which is adding more stress to him. I appreciate you taking the time and I realize you haven’t evaluated him, I just feel so helpless as his mother watching him struggle. I have ideas of somethings that I think could help, but at the same time, I’m afraid to make it worse if I am wrong. I am definitely not giving him methylfolate and will support methylation other ways. I also just bought ‘Dirty Genes’ and am looking forward to diving into that book.
Christine. As you read Nutrient Power and Dirty Genes, you'll notice that they are in opposition when it comes to addressing brain symptoms (especially as relates to Undermethylation). I find the Walsh approach to be much more impactful when it comes to brain health. When high stress is a seeming trigger, pyrroles would be an important consideration. If you are not already familiar, Dr. Walsh will list the symptoms in Nutrient Power. I also just a couple of newsletters on recently on Pyrroles. Best to you and your son. Courtney
March of Dimes and most medical providers recommend folic acid supplementation for up to a year preconceptually to prevent neural tube birth defects. I’m wondering if you support that recommendation
Thank you for this question. I'm all for folic acid to prevent neural tube defects, fitting with the CDC and what I see on the March of Dimes website (where they recommend adding supplementation 30 days before conception and for the first 12 weeks of pregnancy for most women (not high risk). I'm glad to look at other references that suggest up to one year before conception. I'm not seeing that on their website.
Wow I can so relate to all this. I'm homo for C677T and any form of folate makes me depressed 😔 I live in South Australia. Please tell me where a can get professional help 🙏
Hi Carl. Biobalance is a group in Australia who are aligned with the Walsh Research Institute. They have several providers. Here is their website:https://www.biobalance.org.au/find-a-bbh-trained-doctor/
Good article! I'm passionate about this one. Doctors still don't treat it properly.
Hollistic medicine is way ahead on this one. There are big differences between folate (additive to foods) and methylfolate as supplements.
Look at both genes C677T and A1298C.
There are more severe version of MTHFR mutations, in a subset of people that are less common - heterzygous, homozygous, and compound heterozygous.
https://www.dietvsdisease.org/mthfr-c677t-a1298c-mutation/
Thank you for commenting on this. From a Walsh (Research Institute)/brain perspective, we actually look at the outcome of all the methylation genes as opposed just MTHFR. Sometimes people have other SNPs that can offset the impact of the MTHFR. Another difference is if someone is undermethylated and has low serotonin activity (such as depression or anxiety - which is very common in my practice), we would actually avoid any type of folate (methylated or not). I do think most functional medicine doctors (who are not brain-focused), however, would agree with what you are saying. Thanks again.
My 21 year old struggles with debilitating low energy/ fatigue. She also has significant anxiety. Recently realized she has MTHFR polymorphism (C677T heterozygous), and issues with low b2, high ferritin, low iron. Just ordered an MTHFR b complex supplement that includes methyl folate. Is this a bad idea?
About 40% of the population is heterozygous. Debilitating fatigue would make me wonder if something else is going on. Normally I assess methylation in conjunction with copper, zinc and consider if toxins such as mycotoxins (very common) or gut microbial imbalances are at play. Fitting with the Walsh approach (which I have posts on) - to assess the impact of all the methylation genes together, (and not just MTHFR), I use a whole blood histamine (methylation helps remove histamine). If someone is undermethylated and has low serotonin symptoms, folate can make them feel worse. We typically use SAMe instead. But again, normally we are looking at more variables than the presence of MTHFR. I hope something here is helpful.
Thanks so much for your reply.
Yes, you’re right, my daughter does have other health issues (history of Lyme and mold illness, MCAS - much better since we dealt with the mold, multinodular thyroid with normal thyroid hormone levels, and a muscle channelopathy that causes episodes of weakness. Most things are either resolved (Lyme and mold), or somewhat controlled (everything else), but no one has an answer or treatment for the terrible fatigue. I will go back and read your information. Thank you for your input!
Hi, I couldn’t find the blog post about “the role of the NMDA receptor in methylation imbalances” as you referred in this article, would it be possible to share the link?
Hi. Great question. I don't have a newsletter on that yet, though have one in the works. Those with undermethylation can have high activity at the NMDA receptor. Symptom-wise this can look like addiction or OCD tendencies. NAC is a supplement does a lot of things, but one is that it can decrease activity at the NMDA receptor.
Would be great to read this article when you publish it, thanks
https://juniperpublishers.com/gjidd/GJIDD.MS.ID.555841.php This is a very interesting study that shows NMDA receptor dysfunction is appearent in ADHD patients. What can people with ADHD do to improve this function? You mentioned NAC supplement can reduce the activity of NMDA receptor.
But in the research it says ADHD patients already have reduced activity "reduced expression of NR1/NR2 impairs the dopaminergic system which is closely associated with the regulation of attention and reward processing and further contributing to the symptoms of ADHD." so wouldn't it further reduce the NMDA receptor activity in this case?
A whole blood histamine test showed a low histamine level (25). But I had been taking a LOT of niacin for several weeks. (Didn't take niacin for 12 hours before the test though). I'm a little concerned now that the niacin lowered the blood histamine , making me think I'm an over-methylator when I'm not. I don't want to take folic acid if I'm actually an undermethylator. Niacin has been a life-saver to me, though, for anxiety. Up to 3 grams a day.
Hi. I wouldn't expect niacin to lower histamine. If anything, it would more likely to increase histamine. There are a lot of medications that can lower a whole blood histamine level. Another situation in which the histamine level is not reliable, is when someone has a DAO insufficiency,. We don't know why, but they often will paradoxically have a low histamine level. You may already know this, but we do use niacinamide in overmethylation (with B12 and folic acid). It can also be helpful for those who have a slow COMT and/or MAO causing high dopamine activity. Thank you for commenting and sharing your experience.
Thank you for your reply. It is very helpful. This is where i got the idea:
http://orthomolecular.org/library/jom/2002/pdf/2002-v17n01-p017.pdf
Further, Hoffer suggested
that daily intake of niacin gradually lowers
total body histamine by chronically depleting storage levels.11
I want to start taking folinic acid but I am hesitant because, of the characteristics listed above for under-methylation, I fit every one except addictive tendencies and seasonal allergies. However, I am empathetic, have strong artistic interests and musical ability, and have food sensitivities. I want to make sure the blood histamine level places me firmly in the over-methylating category before I start experimenting with nutrients other than niacin.
Thank you for sharing that article. Really interesting. I'll need to see if Dr. Walsh has commented on this. Typically, we rely more heavily on symptoms than on the whole blood histamine and people don't need to have all of them. I do see many undermethylated people who are highly creative and many who have food sensitivities. When someone has a mixed picture (which I personally have as well), I think about undermethylation with a slow COMT and/or MAOA variant. I have a podcast on these 2 variants if you haven't heard it. Thank you again for sharing that.
I only just read this today because it was linked to another blog that comes up on my feed. Fascinating. It caused me to wonder about a couple of things: (1) can excess folate cause irritability and (2) although perhaps not seen a lot in psychiatry, might there be a relationship between UM and seizure disorders?
Hi. 1) yes, especially for those who are undermethylated and already low in serotonin activity. 2) there could be a relationship (depending on what other symptoms or traits are present)., but more often, I think of cardiovascular disease, autoimmunity and cancer being more common with methylation imbalances. Thank you for joining the conversation!
Thank you very much!
I’m not sure which way to go in order to help my son. He is a 22 year old varsity athlete, and university student. He has been struggling greatly over this past year. It started with a major break up and the death of his grandmother. He has a lot of physical and mental stress from being a high level athlete. He is a 4th year university student who has never liked school and really struggles to apply himself academically. If it wasn’t for football, I doubt he would be in university. He has always been quiet and somewhat antisocial. He is extremely driven in sports and is also very sensitive to criticism. He is has never been a pleaser which certainly didn’t help him going through school. He has always been kind and likes to help the underdog.
This past year he started getting Ds and even failed a course. Normally he gets Cs and Bs. He seems very depressed. He has one more year of university to complete his degree but wants to drop out. He has even said he wants to take a break from football which has been his passion since he was a little boy.
I have done all of our family’s genetics. Owen is homozygous for the variants in COMT, MTHFR, DRD2, NBPF3, SLC23A1(B6), SLC30A8(zinc), GC(vitamin D) FUT2(B12), heterozygous for MAOA, ANKK1, and Homozygous for the normal allele of TPH2 and 5-HTTLPR.
He is the only one in our family with the slow version of COMT. My other 3 children have been diagnosed with ADHD. We tested Owen and he didn’t get a diagnosis, I’m assuming because of the slow COMT. However he struggled to focus and get motivated for school even though I know he has the intelligence. This past year he started using his siblings Vyvanse occasionally to help him get through his studies. I have also noticed that he started using cannabis as well, which is odd for him because he is so tuned into health and nutrition because of football. I now realize how detrimental Vyvanse is for him because of slow COMT and I am making an assumption that this along with the breakup and death has put him in a very bad place mentally and emotionally.
I desperately want to help him, he is struggling so much. But I am so confused as to the path to take because of his undermethylation, slow COMT, low dopamine and normal serotonin.
He has agreed to stop taking and I am hoping this will alleviate his need for cannabis. Should I try SAMe or TMG and stay away from methyfolate because of his very low mood? If it was just a slow COMT, that would be one thing, but add in undermethylation and low production of dopamine and fewer dopamaine receptors, and depressed mood….I am having a hard time trying to figure the hierarchy. I don’t want to give folate because of his depressed mood. I’m now even concerned about the amount of protein he consumes. But he needs to eat a lot of protein to preform in football.
I’m sorry this is so long, but I am just looking for some guidance in which is the most important gene to support first. I’m now thinking that because of how well we eat (tons of leafy greens, grassfed beef, chicken etc) this may have actually been detrimental for him as well. Any direction would be greatly appreciated. ❤️
Hi Christine,
I'm sorry your son is struggling. Without evaluating someone, I'm able to give an informed response. I would say, however, that I don't tend to treat snps, because we never know if they are being expressed or not. I consider them (if someone has their variants) in the bigger picture of their symptoms, brain related nutrient levels, evidence of inflammation, toxicity and stress/trauma. For anyone with brain symptoms however, I do check the basic Walsh lab
that involve a few specific nutrient levels that have been found to contribute to brain symptoms (methylation is just one). I have a post on the labs that I use. Separately, when college student start to struggle, one of the first things I think of is mold toxicity from their dorm or apartment. I have also seen individuals with mold toxicity from cannabis. Mold toxicity (which is very common) can cause it's own symptoms, but also impact the expression of various snps. Mold toxin testing is also referenced on that post about lab testing. If you want to message me the state you are in, I can share some clinical resources.
Courtney
Thank you Courtney. We live in New Brunswick, Canada. I will look at the Walsh labs, I bought the book. As far as mold and dorm rooms, he lives at home. He attends the university that just happens to be in our town. We built our home about 18 years ago and have never had any water damage. He also gets his cannabis from the government agency store I wouldn’t think mold would be an issue, but of course it is possible. My hypothesis is that he started taking 30mg of Vyvanse last fall. His girlfriend of 3 years broke up with him ( which he did not want and was devasted) and his grandmother died who he was very close with. I was thinking that all the things I just mentioned along with being a Captain of his football team with a very toxic culture and school stress was too much for his slow COMT and poor methylation to handle. It was a few months later that we noticed him smoking cannabis, he was never a cannabis smoker before….maybe the odd time at a party or something. I feel he was trying to self medicate whatever was going on in his head. As I mentioned, we eat really well (organic, grassfed, free range, gluten and dairy free, lots of vegetable etc). We also supplement with a Seeking Health Multi vitamin, vitamin D, omega 3 and magnesium. So I didn’t figure he would be deficient in micronutrients. We did do an organic acids test and his vitamin C, folate and glutathione were low. He did suffer from a lot of GI issues such as Candida and SIBO but we cleared those up with the help of our Naturopath last spring. He also has been practicing meditation and yoga for a couple of years now. I guess that’s why I thought that the combination of Vyvanse, slow COMT and undermethylatin might have created a real mess inside his head. I explained this to him and he stopped the Vyvanse and cannabis and just wants to find balance again. He is just really depressed, crying, very emotional, tired and having a hard time getting his school work done. He had to summer courses because he failed for the first time ever and is currently not eligible to play football in the fall….which is adding more stress to him. I appreciate you taking the time and I realize you haven’t evaluated him, I just feel so helpless as his mother watching him struggle. I have ideas of somethings that I think could help, but at the same time, I’m afraid to make it worse if I am wrong. I am definitely not giving him methylfolate and will support methylation other ways. I also just bought ‘Dirty Genes’ and am looking forward to diving into that book.
Christine. As you read Nutrient Power and Dirty Genes, you'll notice that they are in opposition when it comes to addressing brain symptoms (especially as relates to Undermethylation). I find the Walsh approach to be much more impactful when it comes to brain health. When high stress is a seeming trigger, pyrroles would be an important consideration. If you are not already familiar, Dr. Walsh will list the symptoms in Nutrient Power. I also just a couple of newsletters on recently on Pyrroles. Best to you and your son. Courtney