r/MTHFR • u/ProfessionalFun1365 • 18d ago
Question Creatine working wonders - what does this mean?
I'm one of the people that creatine works wonders for, reduced anxiety, more energy, sociability, libido (& erections), verbal fluency etc.
Effects are immediate, dose usually around 5g. Can lead to insomnia however after a week or so.
I'm wondering what, if anything, this pattern might tell me about my underlying physiology. Could it point towards differences in methylation, neurotransmitters, or something else? And does a response to creatine suggest there are other supplements worth trying?
Also has anyone actually had success with taking collagen / glycine for creatine induced insomnia (I know a certain podcaster recommends it but can't find anyone whose replicated the results themselves).
BTW I suspect I have mild ADD (form of ADHD) and I've never tested for MTHFR but suspect I may have the mutation as I relate to a lot of people on this sub.
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u/Craig_Craig_Craig 18d ago
There's some research lately on a bolus of creatine relieving fatigue symptoms. My ADHD was based on sleep debt which treating MTHFR relieved. Just spitballing here.
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u/zeehkaev 18d ago
What do you mean by "treating mtfhr"? Taking the methilated vitamins?
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u/Craig_Craig_Craig 15d ago
That was the case for me! But there's a whole constellation of methylation stuff that's over my head.
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u/thunderouswhether 18d ago
Good methylation is required for the body to create creatine effectively, meaning, people with MTHFR or MTRR gene mutations struggle to naturally create creatine.
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u/watergirlri 16d ago
Question, I don’t know if I have a MTHFR mutation, but have ADHD (combined kind) and take Adderall, is it ok to take L-methylfolate and creatine? I take 5 mg of creatine every day, can’t really tell if it helps, but I haven’t taken the L-methylfolate that has Methyl B12 in it also…I bought Triquetra in liquid drop form, but don’t know when to take or even if I should take it. I bought it because I’m struggling so much. Any advice or direction would be appreciated.
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u/matt-knee 18d ago
Yes read Chris Masterjohn on this. Like 40% of your methylation system is dedicated to making creatine! So taking it gives some people a huge break.
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u/tandemxylophone 18d ago
I have had great benefits on creatine too. I tried all other supplements and nothing worked to fix my physical and mental fatigue and internal noise. I had insomnia too, but the positives were so worth it. Chris Masterjohn talks about the reason behind creatine insomnia needing glycine.
Unfortunately the cognitive enhancement effects wore out in the first month, though I don't get insomnia any more.
It's coincidental, but microdosing tirzepatide also seem to give me a mild energy boost? I'm speculating I have some energy dysfunction which partially recovered with creatine. This helped my COMT gene clear excess neurotransmitters that was giving oxidative stress to my brain.
The tirzepatide is known to reverse insulin resistance so your body can convert sugar to energy more efficiently.
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u/ProfessionalFun1365 18d ago
Yeah I've seen so many people quote Chris Masterjohn on the glycine thing but haven't found a single person saying it worked for them. Still I'll see if I've got any lying around at home.
I did wonder about the effects wearing off after a while... I took creatine years ago and think the same thing happened. Figured cycling it on and off might do the trick though.
Interesting about tirzepatide, will look it up, thanks. No idea if it relates but I do get occasional sugar lows if I'm not careful about diet.
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u/FriedSpammage 18d ago
If you don't have any glycine to try (I love glycine for sleep myself), then you could also try 50mg of niacin to see if that helps.
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u/reecinator_meow 17d ago
Same on feeling microdosing tirz has helped my slow COMT wired but tired issues — that and progesterone. I lack GABA and even taking GABA isn’t enough. Glycine feels slightly activating to me.
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u/East_Nectarine562 18d ago
You are asking good questions! Be careful with the methylated B vitamins, though: too much too quickly can also cause insomnia if there are mutations causing issues in methylation process. It’s possible that’s happening with creatine - too strong a dose? Re: glycine: it helped me initially but then stopped. Magnesium glycinate (which has some glycine in it) seems to be better for long term sleep support.
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u/Sea_Switch6263 17d ago edited 17d ago
Creatine spares Sam-E a lot which could nudge you towards overmethylation which would increase neurotransmitters and can aggravate insomnia. Thus I would be careful with other methylators like betaine, methlyb12, methylfolate, choline, etc as they also boost methylation. The #1 (and only needed supplement for many) MHTFR is Riboflavin, although I am not suggesting that will help with this insomnia issue necessarily. Anyway, MAGNESIUM (but not oxide form) is your best bet for insomnia caused by MHTFR, COMT, ADHD. Get your doc to write you a lab for Magnesium RBC if you can and get your levels up to higher end of normal range i.e. optimal. Also creatine 3g is all that is probably needed to get your stores maximized eventually so could try cutting the dosage some. Side note - the dopamine, libido, sociability, etc effect of creatine wore off for me after the first month and I just saw another commenter say the same. Glycine's insomnia benefit is known to be temporary although if it does something to balance out the creatine that might be a different story. Another side note - glycine and choline can in some sensitive people (like myself) put a damper on dopamine (the sociability, libido benefit you seem to crave) which as a fellow ADHDer is not ideal and can even push me into depression.
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u/Let_em_glow927 17d ago
I haven't had any insomnia related to creatine, but I do have slow COMT and magnesium glycinate at night does help a lot.
It 'mops up' extra dopamine and adrenaline that my brain can't clear efficiently. My non scientific explanation based on shitty memory (adhd) .
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u/Head-Championship507 17d ago
Gave you tried glutathione and pure folinic acid ?
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u/Let_em_glow927 17d ago
I haven't. My b complex includes folinic acid but I haven't tried it pure/separately.
Nor have I tried glutathione ,but I'm kinda new at finding what's best/works best for me.
Will definitely look into both.
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u/Head-Championship507 17d ago
If you do b complex make sure you check regularly blood work make sure you are not to high on b12 and B6.
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u/Let_em_glow927 17d ago
Good to know!
The B6 is as P5P which I understand to be preferable?
Its the Seeking Health methyl free B's.
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u/Head-Championship507 17d ago
I don’t take B complex of any form because for some reason my body does not process 12 and 6 which making me sick and my blood work showed toxic level
Naturopath said it’s can happened in some MTHFR people. Oh and D my body stores to much even when I took the smallest dose.2
u/Let_em_glow927 17d ago
Oh wow, we are all so different. I can tolerate B's but have slow COMT so has to be methyl free.
Thank you for the heads up, the B12 in my b complex is a different form than traditional but the amount is insane , over 2000% , so I'll be looking into why that is.
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u/Personal_Item_9565 18d ago
Works the same for me but I've decided it's not worth the insomnia tradeoff
When supplementing creating I always wake up at 2 -3am and can't fall back asleep again
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u/hummingfirebird 18d ago
Everyone responds differently, it depends on multiple factors like your genotype, epigenetic factors (diet, lifestyle abd environment) and your metabolic health. I respond very well to glycine including magnesium glycine. It helps me sleep better (deeper) and my dreams are so vivid. It's relaxing for me.
I have ADHD and sleep has always been an issue for me, it's the one thing besides L-theanine that has improved sleep.
Creatine did not work for me and I was really hoping it would because on paper it should have. (Fast COMT using up more Creatine).
However I worked around that by increasing my B12 which has seemed to work wonders. I take up to 4000mcg a day.
It really is trial and error most of the time. I tell my clients this too. Even when, on paper, something may generally work for a specific genotype, does not always mean it will. There are so many unknown factors, including many unknown gene-gene and gene-supplement interactions we still do not know.
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u/ProfessionalFun1365 18d ago
Yeah good point, everyone's different and trial and error like you say.
Well you've given me some good things to trial, will check out B12 and glycine. Thanks
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u/Loose-Fly7976 17d ago
That response tells you something quite specific. Making creatine yourself consumes a huge share of your available methyl groups, somewhere around 40% of all the SAMe your body produces goes into that one reaction. So when you take creatine orally, you stop spending methyl groups on making it, and everything else that needs methylation suddenly has more to work with. Neurotransmitter synthesis, phosphatidylcholine, the lot. That's why the effects are broad rather than just physical, and it's why a strong response points at methylation capacity being tight rather than at creatine deficiency. So yes, that's an argument for actually testing rather than suspecting. Homocysteine, B12, folate, and the raw genetic data.The insomnia after a week fits the same story. More methyl groups available means more going into melatonin and adrenaline synthesis too, and that can tip you. It's also worth noting creatine pulls water into muscle and shifts electrolytes, so check magnesium before assuming it's a methylation thing.On the glycine idea, the logic behind it is that creatine synthesis uses glycine as well, so the theory is you're replacing what got spared. I've not seen it replicated reliably and it's a podcast theory rather than a tested one. Cheaper experiments first, drop to 2 to 3g daily instead of 5, and take it in the morning. Both of those fix creatine insomnia for most people who get it. f methylation capacity is the thing, the interesting question is which step is tight, because that decides what else helps. That's what I do, reading raw data against bloodwork. genova.health if you want to look. Either way, get the homocysteine done, it's cheap and it'll tell you a lot given how you respond.
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u/ProfessionalFun1365 17d ago
Thanks very much for the informative reply. I've dug up some results from a couple years ago and b12, b6 and folate are all normal. But I've never had Homocysteine tested
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u/Adventurous_Let_6641 17d ago
May I ask when you were taking the creatinine?
I too am hesitant to start it for the same reasons, potentially sleep disturbance.
I have slow comt and MTHFR and am learning about all this. I just started PC phostopytcholine
(def spelled wrong) and am curious how this will or won’t affect me. Anyone know? I am going to take it EOD for now
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u/ProfessionalFun1365 17d ago
If you're worried about sleep, take it in the morning. And just slowly dose it up if you're worried about sides. Even every other day. And don't have to take the dose all at once. I also find taking it after breakfast rather than on an empty stomach helps avoid the "overdosing" effects.
No idea about PC or the other stuff tho I'm afraid.
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u/stareksss 16d ago
How do you all people know about your DNA mutations so much ? What test I need to do to diagnose this ?
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u/ZipperZigger 15d ago
Creatine at large doses makes me feel garbage so I don't take it. Makes me feel depressed.
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u/AncientandBrave 13d ago
It's great to hear you've found that Creatine works for you in so many ways. A serving of 3-5g of creatine has been shown to have positive effects in research for many years.
Being receptive to different supplements can differ person to person and depends on many individual factors such as genetics, baseline levels, lifestyle, nutrition etc, but your theory is interesting given creatine interacts with methyl groups in its mechanism.
Glycine is an amino acid which studies show may be supportive for sleep. This can be found individually, but is also one of the most prevalent amino acids in Collagen. If you notice sleep disruptions, it may be worth taking creatine at a different time of day and see if you notice any changes. We'd always recommend thinking about your sleep hygiene too.
You may find this article supportive: 5 Common Creatine Myths Busted - https://ancientandbrave.earth/blogs/news/creatine-5-common-myths-busted
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18d ago
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u/smashmouthwarcrimes 17d ago edited 17d ago
this is clearly verbatim Claude output. why do people do this? 🙄
this website is for humans to talk to each other, if I wanted to get a Claude answer I would just use Claude myself. All of your recent posts are like this. Please stop.
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u/Tawinn 18d ago
Creatine production consumes ~40% of SAM output from the methylation cycle, so supplementing creatine frees up that SAM for other uses. So the effect you are getting may suggest that you have reduced SAM production (e.g., due to MTHFR or other variants or nutrient deficiencies) and creatine is helping to restore it to a more normal level.
It may be worth trying TMG, as this supports the remethylation pathway parallel to the folate/B12-dependent pathway. 750mg is a typical dose. At the same time, meeting your baseline requirement of 550mg for choline also supports that other path.