Good stuff, I have experienced similar results after starting the MTHFR protocol. It’s been 2 years now and results are permanent. I will add that all of my inflammation and joint pain has gone away as well. I’m a little older than Beth C. So that was an issue for me as well.
When you combine any you increase the probability but you should think of A1298C as a little tax that doesn't reach magnitude on its own to be a major issue but could combine with anything in the pathway to compound the effect.
What is the specific connection between inefficient methylation and OCD???
I'm a nutritionist in NZ and I see clients all the time with a long history of OCD, who have B12 below 300 OR around 900 (poor absorption?), low folate (around 30), elevated homocysteine (8-20), sometimes elevated (but not crazy high) liver enzymes, and low Alk Phos indicating low Zn. And horribly low iron.
Many have tested positive for an MTHFR variation.
Many have a history of being vegan or vegetarian, which made everything worse until they started eating meat again. Some have extra complications from mold toxicity, recurring strep infections, long Covid....(neuroinflammation).
I always encourage more B12, folate, zinc, and choline foods, supplemental methylated Bs, Zn, high doses of Mg, OCD-specific psychotherapy, and liver support (no caffeine or booze, dandelion, the B vitamins of course) and sometimes limiting gluten, depending on their presentation.
Some clients make great progress, others less so (though compliance is a likely factor).
The iron is a tricky one, as many have a history of strep infections, so their low iron seems more a consequence of inflammation (and I don't want to feed the bacteria!)
Any pearls of wisdom you'd be happy to share on the mechanism of compromised methylation in OCD and what I may be missing would be so appreciated. I am also an OCD survivor myself - nutrition made a HUGE difference.
Hi again Chris, I just listened to this and took notes (I was focused!!) OMG. Mind blown. I will never look at OCD the same way again. I think you are really on to something here. BTW, I think my OCD recovery experience was so similar to yours...being vegetarian messed me up so much, physically and mentally. Bringing in animal foods and fats (and magnesium, liver support, and eventually B vitamins and other things) gave me my life back. I have never had genetic testing but I have Italian roots...99% sure I have an MTHFR variation and maybe a COMT one too. Golly, thank you so much for breaking down the complexity of methylation, HUMANIZING it, and sharing your brain with us all. I have learned a lot. Thank you.
Hey Chris, thanks very much for the reply, have been exploring your library but had not listened to this yet...will check it out now!
I knew there was a role for dopamine dysregulation in OCD but you describe it in a way that I can relate to, as an OCD survivor (not being able to let go) - I have read that you have lived experience, too. Anyway, off to listen now. Thanks again!
I have Mediterranean G6PD, tested at 0.8 (ref range 8.8-16.6) i.e. 5-10% normal activity. (Squarely the bottleneck in my Pentose Phosphate Pathway) In addition to poorly recycling glutathione and making limited ATP, I'm also not making NADPH for MTHFR...?
AND... my MTHFR is impaired. (C677T +/+)
Supplementing with megadose B-2 for a long time (300-400mg 2x/day) seems to help. (Does riboflavin vs R5P matter?)
Been using a few different B Complex supplements that have 50-100mg Niacin. (Does niacinamide vs inositol hexaniacinate matter?) They have 400-500mcg B12. (Does methylcobalamin vs dibencozide matter?)
Trying to sort this all out while also figuring out copper, zinc, my iron overload, and my potential manganese overload.
SLC19A1 folate transport polymorphism should be added as research states that solving MTHFR in this case is not enough. Also, some research from 2023 states that this transporter impacts thiamine. I have both, main MTHFR homoz and SCL19A1 homoz. Finally, Impaired Function of Solute Carrier Family 19 Leads to Low Folate Levels and Lipid Droplet Accumulation in Hepatocytes. Vitamin D works as an expression agonist, so I’m supplementing 5.000 UI/d. Should RBC folate be checked? Should SAMe be used? Should higher folate dose than 800mcg be used? Thank you.
I agree that the folate transporter polymorphism matters, but this was not intended as a comprehensive list of relevant genes. Rather, it is a comprehensive list of nutrients that impact MTHFR activity, with the biochemical reasons being illustrative and not comprehensive.
Hi Dr. Masterjohn! Quick question, would you recommend a RhoGAM shot for an RH-negative pregnant woman (second pregnancy—first pregnancy was an RH-positive baby) with a positive Coombs test? Or would you decline the RhoGAM? Looking for resources as I’d like to avoid it but I am not sure what to do! Have heard that people with RH-negative blood are likely to have MTHFR. Thank you for your time!
I'm very sorry for the delay. Right now I need to nourish BioOpt till its on its feet. Then I will systematically attack all loose threads, including the book and the unfinished MWM Energy Metabolism class.
Lifesaver!
Good stuff, I have experienced similar results after starting the MTHFR protocol. It’s been 2 years now and results are permanent. I will add that all of my inflammation and joint pain has gone away as well. I’m a little older than Beth C. So that was an issue for me as well.
Thanks Chris,
Scott F.
Awesome1
Would A1298C homozygous with BHMT 02,04,08 combination cause methylation issues?
When you combine any you increase the probability but you should think of A1298C as a little tax that doesn't reach magnitude on its own to be a major issue but could combine with anything in the pathway to compound the effect.
I have done the MTHFR protocols pretty thoroughly, testing my homocysteine and lactate,I had improved markers but never felt any better really.
I was always intolerant to tiny amount of methylfolate, even in the presence of glycine and B2.
Recently my doctor prescribed a vitamin for MTHFR called “Enlyte” I was reluctant to try it given the amounts on the label.
But I ended up being shocked at how well it worked for my mood, sleep, etc with no adjustment period.
I called them to ask about why this is and received a pretty basic answer.
Any idea why this is so effective? I had tried every ingredient in here before together with little response.
Link to ingredients below
https://www.folatehealth.com/_files/ugd/22d2d5_2a77c747faaa4d31b55a930746770f6b.pdf
Either because of the very high dose, or because you needed one of the other nutrients, as it's almost a multivitamin.
What is the specific connection between inefficient methylation and OCD???
I'm a nutritionist in NZ and I see clients all the time with a long history of OCD, who have B12 below 300 OR around 900 (poor absorption?), low folate (around 30), elevated homocysteine (8-20), sometimes elevated (but not crazy high) liver enzymes, and low Alk Phos indicating low Zn. And horribly low iron.
Many have tested positive for an MTHFR variation.
Many have a history of being vegan or vegetarian, which made everything worse until they started eating meat again. Some have extra complications from mold toxicity, recurring strep infections, long Covid....(neuroinflammation).
I always encourage more B12, folate, zinc, and choline foods, supplemental methylated Bs, Zn, high doses of Mg, OCD-specific psychotherapy, and liver support (no caffeine or booze, dandelion, the B vitamins of course) and sometimes limiting gluten, depending on their presentation.
Some clients make great progress, others less so (though compliance is a likely factor).
The iron is a tricky one, as many have a history of strep infections, so their low iron seems more a consequence of inflammation (and I don't want to feed the bacteria!)
Any pearls of wisdom you'd be happy to share on the mechanism of compromised methylation in OCD and what I may be missing would be so appreciated. I am also an OCD survivor myself - nutrition made a HUGE difference.
Thank you Chris, for all you do!
See here:
https://chrismasterjohnphd.substack.com/p/043-methylate-your-way-to-mental
Hi again Chris, I just listened to this and took notes (I was focused!!) OMG. Mind blown. I will never look at OCD the same way again. I think you are really on to something here. BTW, I think my OCD recovery experience was so similar to yours...being vegetarian messed me up so much, physically and mentally. Bringing in animal foods and fats (and magnesium, liver support, and eventually B vitamins and other things) gave me my life back. I have never had genetic testing but I have Italian roots...99% sure I have an MTHFR variation and maybe a COMT one too. Golly, thank you so much for breaking down the complexity of methylation, HUMANIZING it, and sharing your brain with us all. I have learned a lot. Thank you.
Hey Chris, thanks very much for the reply, have been exploring your library but had not listened to this yet...will check it out now!
I knew there was a role for dopamine dysregulation in OCD but you describe it in a way that I can relate to, as an OCD survivor (not being able to let go) - I have read that you have lived experience, too. Anyway, off to listen now. Thanks again!
Excellent material here!
I have A1298C +/+ and PEMT 5465G>A +/+.
What methylation score would this combination have?
What do you think of Dr. Gregory Russel-Jones theory on selenium/iodine/molybdenum and b2/12 deficiency as the cause of methylation issues?
I do not follow him and what I’ve seen from him seems myopic and dangerous to me.
Trying to wrap my head around NADPH and MTHFR...
I have Mediterranean G6PD, tested at 0.8 (ref range 8.8-16.6) i.e. 5-10% normal activity. (Squarely the bottleneck in my Pentose Phosphate Pathway) In addition to poorly recycling glutathione and making limited ATP, I'm also not making NADPH for MTHFR...?
AND... my MTHFR is impaired. (C677T +/+)
Supplementing with megadose B-2 for a long time (300-400mg 2x/day) seems to help. (Does riboflavin vs R5P matter?)
Been using a few different B Complex supplements that have 50-100mg Niacin. (Does niacinamide vs inositol hexaniacinate matter?) They have 400-500mcg B12. (Does methylcobalamin vs dibencozide matter?)
Trying to sort this all out while also figuring out copper, zinc, my iron overload, and my potential manganese overload.
SLC19A1 folate transport polymorphism should be added as research states that solving MTHFR in this case is not enough. Also, some research from 2023 states that this transporter impacts thiamine. I have both, main MTHFR homoz and SCL19A1 homoz. Finally, Impaired Function of Solute Carrier Family 19 Leads to Low Folate Levels and Lipid Droplet Accumulation in Hepatocytes. Vitamin D works as an expression agonist, so I’m supplementing 5.000 UI/d. Should RBC folate be checked? Should SAMe be used? Should higher folate dose than 800mcg be used? Thank you.
I agree that the folate transporter polymorphism matters, but this was not intended as a comprehensive list of relevant genes. Rather, it is a comprehensive list of nutrients that impact MTHFR activity, with the biochemical reasons being illustrative and not comprehensive.
Hi Dr. Masterjohn! Quick question, would you recommend a RhoGAM shot for an RH-negative pregnant woman (second pregnancy—first pregnancy was an RH-positive baby) with a positive Coombs test? Or would you decline the RhoGAM? Looking for resources as I’d like to avoid it but I am not sure what to do! Have heard that people with RH-negative blood are likely to have MTHFR. Thank you for your time!
This is outside my knowledge base, sorry.
Does methylation have anything to do with having higher blood pressure? It runs in my family.
It can.
this is a great summary of a very intricate topic.
On a different note
I bought the pre-book of your Vitamins and Minerals but haven't received it. Do you have an update on this?
I'm very sorry for the delay. Right now I need to nourish BioOpt till its on its feet. Then I will systematically attack all loose threads, including the book and the unfinished MWM Energy Metabolism class.