Please read the journal article titled “ Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial”.
I am interested to see your thoughts on this statement detailing how creatine supplementation can ultimately inhibit MTHFR: “therefore, an increase in SAM from creatine supplementation would result in inhibition of MTHFR, decreased synthesis of 5-mTHF, alleviated inhibition of GNMT, and ultimately, decreased SAM, increased SAH, and increased homocysteine”.
Studies have also shown that supplementation of creatine results in significant decreases of glycine. (I apologize, I do not have the DOI for this but I am sure you can find a similar study). Might this be harmful for MTHFR individuals who have some reliance on the glycine-buffer system?
As someone with MTHFR supplementing creatine, the negative impact on my health that resulted prompted me to research more into it. I wonder if this is an appropriate recommendation. I understand the logic that since a large portion of methylation goes towards synthesizing creatine, supplementing it would free up methyl groups and ultimately ease the burden of the methylation cycle. However, I do not think it is as straightforward as this and may be a dangerous recommendation. “Unexpectedly, creatine supplementation (alone or in combination with l-arginine) was associated with an 11–20% increase in homocysteine concentration (p < 0.05), which was not attributable to worsened renal function, providing evidence against an effect of creatine on decreasing methylation demand.” https://doi.org/10.1177%2F1358863X08100834
I'm 42, and have an 81% decrease on my methylfolate score. I started this protocol a few weeks ago, and:
* my RHR is down to high 40s-mid 50s from the mid-60s;
* I haven't had a brain fog episode once -- very exciting to be able to do my business books whenever I have time, and not during a mysterious window of opportunity;
*HRV is is trending up;
*No more bouts of dyspnea;
*Energy and exercise tolerance has greatly improved;
*100% O2 sat for the first time in about two years. I live at altitude.
Chris, great MTHFR pdf! Any chance that you can add Family Tree DNA to the choline calculator? I tried using citicoline the other day and got heart palpitations, ugh, trying to figure out how this happened.
Thank you. This is a great page. I’m going to point a lot of people here. I found out about five years ago that I am homozygous C677T, it really explained a lot. As soon as I read a list of symptoms I knew I had it, as I had 90% of them, and the others had all been present in my family history over and over. I have strokes, non BRCA breast cancer, heart disease on one side of the family, and heart disease and prostate cancer on the other side. That day I found out about MTHFR genes for the first time, despite studying genetics at university in the 90s and going to numerous doctors over the preceding 15 years to try and explain my seemingly unrelated (and somewhat debilitating) symptoms. I ordered a gene test and high strength methylated B vitamins that very day. Within a week on the vitamins and avoiding folic acid, my numerous symptoms had vanished, some (like extreme tiredness) I’d had my entire life. I studied a lit online, and ended up treating myself, after one doctor after researching for 2 hours on the internet having never heard of it told me I had a mild form and I was oversupplementing. Both of these were incorrect, I have one of the most severe forms 25% of normal MTHFR function, and supplementing was making me feel human for the first time in my life. The blood tests were clearly reflecting the buildup of fake “vitamins” I was unable to metabolise. She was gobsmacked when I told her I had cured all my symptoms including moderate depression by just taking B vitamins in the proper (active, methylated) form. I had gone to her for support, thinking she would actually take me seriously, my first experience with a medical professional besides myself (a scientist) trying to explain MTHFR to them. My IVF doctor who’d been unwittingly poisoning me with high dose folic acid for several years, claimed the standard treatment protocol was high dose folic acid. I told her no I will be taking methylfolate from now on, and she then claimed it’s exactly the same, and handed me a prescription for 5mg folic acid as I left. I did not fill that prescription, having thrown out all the folic acid in the house previously.
Finally found the missing piece of the puzzle, I was able to get and stay pregnant after about a year of high dose B vitamins (Methylguard Plus to start with at full dose 5mg folate and 3mg B12). I’ve since worked out how to avoid side effects, I have heterozygous COMT also, and was quite nauseous and headachy to begin with. I take electrolytes and eat with food, and take 10mg niacin lozenges as needed. I should’ve started on a much lower dose, but I stayed on the high dose even after I found this out as I was finally MTHFR symptom free (apart from side effects) for the first time I can remember. I was practically leaping out of bed each morning, and my severe joint pains and peripheral neuropathy had disappeared. I later found a more comprehensive B Complex with all the B vitamins in their correct forms. I also put my nearly three year old on a chewable B12/B9/B6 by Jarrow and he’s a lot happier and back to sleeping all night again which he started at 10 weeks old when I was solely breastfeeding. He didn’t sleep well at all having to have some formula over his first year, it was impossible to get a folic acid free formula especially as he was born as our first lockdown began with its panic buying, but it’s hard anyway to find. He was born with a very minor sacral dimple, no other outward signs of his at least heterozygosity for C677T mutation. I don’t know about his other parent, as he was an anonymous clinic donor. I plan to get him tested, but I’m waiting as the best/cheapest way I found was basic Ancestry DNA on sale, and I don’t want to reveal his paternal ancestry too soon.
There is lot of good stuff here. But I am deeply puzzled by the emphasis on Choline by Chris. Because this reveals what I think is a great contradiction in Choline. Bear with me here:
Quick background – I have undermethylation and also suffer from OCD.
In couple of studies done on OCD people, it was found that their brains showed above average increase in Choline or had positive correlation to choline. Which means, if I am interpreting it correctly, that perhaps OCD sufferers should stay away from choline.
Here is the BIG KICKER – Usually people with OCD, especially my kind of OCD (Pure OCD/intrusive thoughts) also happen to be undermethylated, and vice versa.
I am wondering if I am interpreting anything wrong here given what seems to be a contradictory role of choline.
At the end, should I consider supplementing with or eating food rich in choline, given that I have both undermethylation and OCD? (And I suspect there are lot of people like me around)
When I supplement choline I get really, really pale stool – I presume from fat which has been exported from the liver, but then can’t be burnt off. It happens with choline bitartrate, alpha-GPC, betaine HCl and lecithin (though the latter makes me feel really good, at least in the short term). I then start having symptoms of mineral deficiencies etc.
I’ve tried adding carnitine, which doesn’t really help, and makes my hypothyroid symptoms worse. Lipase enzymes also don’t help. I also get paler stool from B12 (I take an adenosyl/methyl mix) and folate (folinic acid or 5MTHF) and fat-soluble vitamins. I’d love to know of any ideas of what might help. Creatine seems to be helping a bit but gives me symptoms of excessive levels of bile acids (which are really messing up my teeth) – which I think is probably due to increased B6 need. I suspect that low creatine may be causing low stomach acid which is causing poor fat digesiton.
Hello Chris, I’m heterozygous A1298C. My b12 and folate are low. B12 is 258 and Folate is 7.9. Back in 2017, I had great number s b12 was 660 and folate 20. I wasn’t supplementing at all and I haven’t changed my eating habits much. I’m assuming stress kicked my gene into the “on” position. I struggle taking any and all supplements but especially anything methylated. I am homozygous for the COMT gene and suspect this is the reason I can’t take methyl supplements. Any advice?
I have decided to take Betaine HCL + Pepsin in order to better digest my proteins. I saw your comment that it does contain trimethylglycine, so this counts toward our glycine requirements. QUESTION: If I’m taking more Betaine HCL now, will that possibly throw things off by getting TOO MUCH glycine or betaine? Because I was already doing this protocol and I don’t know if I’ll end up getting too much in total of choline/betaine/glycine. At what point is doing all of the things in earnest “too much”??
I do know that glycine and phosphatidyl choline as supplement greatly helped me.
I have been following this protocol with good results.
-adding dried beet powder and creatine powder to smoothies
-Adding additional beets or beet juice sometimes
-taking 2 scoops, about 4 Tbsp. collagen per day.
-B Complex to get the riboflavin (no folate or B12 in my current one). Added B6.
-6 capsules of liver per day
-cannot eat eggs right now. Taking one phosphatidyl choline supplement per day.
-cannot eat grains, legumes, or nuts right now. (autoimmune)
Is there a product that combines these supplements together that you could recommend so I don’t have to take a handful of vitamins on top of the handfuls I already take?
MTHFD1 +/+, MTHFR c677T +/+, VDR taq +/-. She takes pyridostigmine which is an acetylcholinesterase inhibitor to control dizziness from having POTS. She still suffers from fatigue. Which supplements should she take based on her genetics to help with this?
Chris, the ON creatine you recommend is no longer made with creapure. I would suggest recommending a different version.
Here is quote from customer service:
—
Hello-
Thanks for choosing ON! We have decided to stop using Creapure in the product. It was a company decision to move in a different direction from branded creapure to non-branded. By moving to non-branded we are able to secure multiple suppliers of creatine, which gives us a robust supply chain. It also guarantees that we always have enough creatine as an ingredient so that we can continue to produce our micronized creatine products. We use high quality micronized creatine that has been approved through our high Quality standards and specifications. Our creatine is made of 100% Pure Creatine Monohydrate.
I have started taking spinach powder in a protein shake daily because of my mthfr etc issues with folate. Do you know if this process retains the folate? ( as it’s pointless doing it if not. )
FROM MORIAH MEYER:
Chris,
Please read the journal article titled “ Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial”.
https://doi.org/10.3945/jn.115.216739
I am interested to see your thoughts on this statement detailing how creatine supplementation can ultimately inhibit MTHFR: “therefore, an increase in SAM from creatine supplementation would result in inhibition of MTHFR, decreased synthesis of 5-mTHF, alleviated inhibition of GNMT, and ultimately, decreased SAM, increased SAH, and increased homocysteine”.
Studies have also shown that supplementation of creatine results in significant decreases of glycine. (I apologize, I do not have the DOI for this but I am sure you can find a similar study). Might this be harmful for MTHFR individuals who have some reliance on the glycine-buffer system?
As someone with MTHFR supplementing creatine, the negative impact on my health that resulted prompted me to research more into it. I wonder if this is an appropriate recommendation. I understand the logic that since a large portion of methylation goes towards synthesizing creatine, supplementing it would free up methyl groups and ultimately ease the burden of the methylation cycle. However, I do not think it is as straightforward as this and may be a dangerous recommendation. “Unexpectedly, creatine supplementation (alone or in combination with l-arginine) was associated with an 11–20% increase in homocysteine concentration (p < 0.05), which was not attributable to worsened renal function, providing evidence against an effect of creatine on decreasing methylation demand.” https://doi.org/10.1177%2F1358863X08100834
I'm 42, and have an 81% decrease on my methylfolate score. I started this protocol a few weeks ago, and:
* my RHR is down to high 40s-mid 50s from the mid-60s;
* I haven't had a brain fog episode once -- very exciting to be able to do my business books whenever I have time, and not during a mysterious window of opportunity;
*HRV is is trending up;
*No more bouts of dyspnea;
*Energy and exercise tolerance has greatly improved;
*100% O2 sat for the first time in about two years. I live at altitude.
I feel like I have my life back. Thanks, Chris.
thanks!
Hi Chris.
I made a comment on youtube about not getting an email with pdf.
You wrote you will send my profile to substack tech support?
Thanks
Chris, great MTHFR pdf! Any chance that you can add Family Tree DNA to the choline calculator? I tried using citicoline the other day and got heart palpitations, ugh, trying to figure out how this happened.
This is great! Thanks Chris
FROM JODY:
Thank you. This is a great page. I’m going to point a lot of people here. I found out about five years ago that I am homozygous C677T, it really explained a lot. As soon as I read a list of symptoms I knew I had it, as I had 90% of them, and the others had all been present in my family history over and over. I have strokes, non BRCA breast cancer, heart disease on one side of the family, and heart disease and prostate cancer on the other side. That day I found out about MTHFR genes for the first time, despite studying genetics at university in the 90s and going to numerous doctors over the preceding 15 years to try and explain my seemingly unrelated (and somewhat debilitating) symptoms. I ordered a gene test and high strength methylated B vitamins that very day. Within a week on the vitamins and avoiding folic acid, my numerous symptoms had vanished, some (like extreme tiredness) I’d had my entire life. I studied a lit online, and ended up treating myself, after one doctor after researching for 2 hours on the internet having never heard of it told me I had a mild form and I was oversupplementing. Both of these were incorrect, I have one of the most severe forms 25% of normal MTHFR function, and supplementing was making me feel human for the first time in my life. The blood tests were clearly reflecting the buildup of fake “vitamins” I was unable to metabolise. She was gobsmacked when I told her I had cured all my symptoms including moderate depression by just taking B vitamins in the proper (active, methylated) form. I had gone to her for support, thinking she would actually take me seriously, my first experience with a medical professional besides myself (a scientist) trying to explain MTHFR to them. My IVF doctor who’d been unwittingly poisoning me with high dose folic acid for several years, claimed the standard treatment protocol was high dose folic acid. I told her no I will be taking methylfolate from now on, and she then claimed it’s exactly the same, and handed me a prescription for 5mg folic acid as I left. I did not fill that prescription, having thrown out all the folic acid in the house previously.
Finally found the missing piece of the puzzle, I was able to get and stay pregnant after about a year of high dose B vitamins (Methylguard Plus to start with at full dose 5mg folate and 3mg B12). I’ve since worked out how to avoid side effects, I have heterozygous COMT also, and was quite nauseous and headachy to begin with. I take electrolytes and eat with food, and take 10mg niacin lozenges as needed. I should’ve started on a much lower dose, but I stayed on the high dose even after I found this out as I was finally MTHFR symptom free (apart from side effects) for the first time I can remember. I was practically leaping out of bed each morning, and my severe joint pains and peripheral neuropathy had disappeared. I later found a more comprehensive B Complex with all the B vitamins in their correct forms. I also put my nearly three year old on a chewable B12/B9/B6 by Jarrow and he’s a lot happier and back to sleeping all night again which he started at 10 weeks old when I was solely breastfeeding. He didn’t sleep well at all having to have some formula over his first year, it was impossible to get a folic acid free formula especially as he was born as our first lockdown began with its panic buying, but it’s hard anyway to find. He was born with a very minor sacral dimple, no other outward signs of his at least heterozygosity for C677T mutation. I don’t know about his other parent, as he was an anonymous clinic donor. I plan to get him tested, but I’m waiting as the best/cheapest way I found was basic Ancestry DNA on sale, and I don’t want to reveal his paternal ancestry too soon.
FROM KRIS:
There is lot of good stuff here. But I am deeply puzzled by the emphasis on Choline by Chris. Because this reveals what I think is a great contradiction in Choline. Bear with me here:
Quick background – I have undermethylation and also suffer from OCD.
In couple of studies done on OCD people, it was found that their brains showed above average increase in Choline or had positive correlation to choline. Which means, if I am interpreting it correctly, that perhaps OCD sufferers should stay away from choline.
Here is the BIG KICKER – Usually people with OCD, especially my kind of OCD (Pure OCD/intrusive thoughts) also happen to be undermethylated, and vice versa.
I am wondering if I am interpreting anything wrong here given what seems to be a contradictory role of choline.
At the end, should I consider supplementing with or eating food rich in choline, given that I have both undermethylation and OCD? (And I suspect there are lot of people like me around)
FROM KT:
When I supplement choline I get really, really pale stool – I presume from fat which has been exported from the liver, but then can’t be burnt off. It happens with choline bitartrate, alpha-GPC, betaine HCl and lecithin (though the latter makes me feel really good, at least in the short term). I then start having symptoms of mineral deficiencies etc.
I’ve tried adding carnitine, which doesn’t really help, and makes my hypothyroid symptoms worse. Lipase enzymes also don’t help. I also get paler stool from B12 (I take an adenosyl/methyl mix) and folate (folinic acid or 5MTHF) and fat-soluble vitamins. I’d love to know of any ideas of what might help. Creatine seems to be helping a bit but gives me symptoms of excessive levels of bile acids (which are really messing up my teeth) – which I think is probably due to increased B6 need. I suspect that low creatine may be causing low stomach acid which is causing poor fat digesiton.
FROM JONAH LAMONDA:
I have c677t homozygous gene
Should I take regular glycine or tmg or both?
FROM SARA BENTON:
Hello Chris, I’m heterozygous A1298C. My b12 and folate are low. B12 is 258 and Folate is 7.9. Back in 2017, I had great number s b12 was 660 and folate 20. I wasn’t supplementing at all and I haven’t changed my eating habits much. I’m assuming stress kicked my gene into the “on” position. I struggle taking any and all supplements but especially anything methylated. I am homozygous for the COMT gene and suspect this is the reason I can’t take methyl supplements. Any advice?
FROM RACHEL LAKEWOOD CO:
Chris,
I have decided to take Betaine HCL + Pepsin in order to better digest my proteins. I saw your comment that it does contain trimethylglycine, so this counts toward our glycine requirements. QUESTION: If I’m taking more Betaine HCL now, will that possibly throw things off by getting TOO MUCH glycine or betaine? Because I was already doing this protocol and I don’t know if I’ll end up getting too much in total of choline/betaine/glycine. At what point is doing all of the things in earnest “too much”??
I do know that glycine and phosphatidyl choline as supplement greatly helped me.
I have been following this protocol with good results.
-adding dried beet powder and creatine powder to smoothies
-Adding additional beets or beet juice sometimes
-taking 2 scoops, about 4 Tbsp. collagen per day.
-B Complex to get the riboflavin (no folate or B12 in my current one). Added B6.
-6 capsules of liver per day
-cannot eat eggs right now. Taking one phosphatidyl choline supplement per day.
-cannot eat grains, legumes, or nuts right now. (autoimmune)
-do take mushroom powders regularly
FROM SEBASTIAN:
Is there a product that combines these supplements together that you could recommend so I don’t have to take a handful of vitamins on top of the handfuls I already take?
FROM CHRIS:
My daughter is SLC19a1 +/+,
MTHFD1 +/+, MTHFR c677T +/+, VDR taq +/-. She takes pyridostigmine which is an acetylcholinesterase inhibitor to control dizziness from having POTS. She still suffers from fatigue. Which supplements should she take based on her genetics to help with this?
FROM GREG:
Chris, the ON creatine you recommend is no longer made with creapure. I would suggest recommending a different version.
Here is quote from customer service:
—
Hello-
Thanks for choosing ON! We have decided to stop using Creapure in the product. It was a company decision to move in a different direction from branded creapure to non-branded. By moving to non-branded we are able to secure multiple suppliers of creatine, which gives us a robust supply chain. It also guarantees that we always have enough creatine as an ingredient so that we can continue to produce our micronized creatine products. We use high quality micronized creatine that has been approved through our high Quality standards and specifications. Our creatine is made of 100% Pure Creatine Monohydrate.
Have a great day!
Consumer Affairs Rep 05269
Optimum Nutrition/ABB Performance
—
Thanks for your work Chris!
-Greg
FROM TONY:
Hi Chris,
I have started taking spinach powder in a protein shake daily because of my mthfr etc issues with folate. Do you know if this process retains the folate? ( as it’s pointless doing it if not. )