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Overmethylation and weight gain (MTHFR)

Messages
48
Why is Overmethylation associated with weigh gain and difficulty in losing it? What causes the weight gain and difficulty in losing weight for Overmethylators? Is it linked to low histamine?

Does anyone understand the process enough to explain it?
Thanks
 
Messages
48
Methylation has been infiltrated by a great deal of quackery, attributing pretty much every symptom imaginable to undermethylation or overmethylation, and sometimes both at the same time. I very much doubt there's any connection with weight gain.

It may well be.. I'll deduce from that, that there is no connection.
What makes you think that it's quackery? Did Ray Peat say it?
 
Messages
19
Location
Bath, England
i do not understand the process but have been overmethylated for a while - i trialed niacin yesterday and after a few doses of 50mg every few hours, my lethargy, dulled brain, negative thoughts went, also my feeling of being a lot heavier went to. i definitely had a heavier bottom half. and i slept really well last night which i hadn't been able to do in about a month. i thought i had low cortisol (had this a few years ago and had to go on daily adrenal support for a couple of years) and had tried adrenal cortex but that didn't help . i am also on NDT for my hypothyroidism and bhrt for my menopause. i wish i knew what was going on but thank god for nicotinic acid. i did not think i was overmethylating as i am not following the protocol at the moment. i did have a very stressful 6 month run up to the end of last year.
 
Messages
45
Location
Northern Virginia
I wonder about this connection too!! Every time I have an overmethylation episode, I gain about a pound. And it doesn't go away no matter how much I exercise or how clean I eat. It is seriously frustrating. I have spent hours and hours researching but no real answers...
 
Messages
1,478
I think the main problem is that we don't know enough to make broad sweeping statements like " over methylation causes weight gain". It's too far removed from the end process to attribute definitively attribute cause? It's probably riding on the back of hypothyroidism studies ?

My test of quackery is to find 5-10 separate pieces of research that points in the same direction. If they exist it's worth looking into further, if not then I'm afraid .......To make it substantive I would like to see clinical research with patient studies, but that isn't always available. I dismiss books as being fiction unless there is clear references to research. Phrases like "it is believed that....." Or " many believe " or "it is thought". Generally can be interpreted as " I don't have any research to back this point up"

The fact that you can't find anything substantive gives you the answer I think?
 
Messages
48
I wonder about this connection too!! Every time I have an overmethylation episode, I gain about a pound. And it doesn't go away no matter how much I exercise or how clean I eat. It is seriously frustrating. I have spent hours and hours researching but no real answers...

I know how your feel. I slipped into this after a serious bout of stress 10 years ago and haven't been able to lose a pound since.. All thyroid hormones are at optimal levels so I'm stumped. Running 65 km a week and gym have done nothing for my weight. If anything I've got fatter.
 
Messages
48
I think the main problem is that we don't know enough to make broad sweeping statements like " over methylation causes weight gain". It's too far removed from the end process to attribute definitively attribute cause? It's probably riding on the back of hypothyroidism studies ?

My test of quackery is to find 5-10 separate pieces of research that points in the same direction. If they exist it's worth looking into further, if not then I'm afraid .......To make it substantive I would like to see clinical research with patient studies, but that isn't always available. I dismiss books as being fiction unless there is clear references to research. Phrases like "it is believed that....." Or " many believe " or "it is thought". Generally can be interpreted as " I don't have any research to back this point up"

The fact that you can't find anything substantive gives you the answer I think?

I agree that there's a lack of evidence out there. Unfortunately without lateral thought we will be waiting forever for the answers we require to become profitable (otherwise who's going to pay for it). I'm a bit of a cynic too so I do require some proof. If I can relate the pseudo science to my on issues in some way or another then I'm getting further than the doctors can get me.

Thanks for your response.
 
Messages
45
Location
Northern Virginia
I know how your feel. I slipped into this after a serious bout of stress 10 years ago and haven't been able to lose a pound since.. All thyroid hormones are at optimal levels so I'm stumped. Running 65 km a week and gym have done nothing for my weight. If anything I've got fatter.

That sounds exactly like me....thyroid meds are optimal, and I feel like my exercise (regular weight training and cardio) level is about right. I think inflammation may be the real culprit - sigh...
 
Messages
45
Location
Northern Virginia
I know how your feel. I slipped into this after a serious bout of stress 10 years ago and haven't been able to lose a pound since.. All thyroid hormones are at optimal levels so I'm stumped. Running 65 km a week and gym have done nothing for my weight. If anything I've got fatter.

So, here's some info to chew on: Oxidative stress and inflammation appear to be closely interlinked in obesity, although it is difficult to establish the temporal sequence of their relationship. Here's the reference - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676851/
 

Basilico

Florida
Messages
948
I think the main problem is that we don't know enough to make broad sweeping statements like " over methylation causes weight gain".

My husband is an overmethylator and has been lean and muscular for most of his life.

He has always been an extremely healthy eater who never eats fast food, fried/junk food, or much in the way of desserts or snacks. He also has been active in sports and weightlifting for most of his life.

I think eating habits and activity levels are far more important than methylation status.
 
Messages
1,478
My husband is an overmethylator and has been lean and muscular for most of his life.

He has always been an extremely healthy eater who never eats fast food, fried/junk food, or much in the way of desserts or snacks. He also has been active in sports and weightlifting for most of his life.

I think eating habits and activity levels are far more important than methylation status.

Completely agree. I wasn't particularly athletic or into fitness, but was strong, had high stamina, was aerobically active and ate a clean balanced diet before I got ill.

I think the true cause of weight gain for me was the fact that I stopped moving as much and didn't cut down my calories enough. I also think that as my Krebs cycle got screwed up my carb consumption became too high for what I could process and I started laying down more of my carbs as fat. I've lost a bit of the weight by consuming less than 1900 calories per day and reducing my carbs to 100-150g.
 
Messages
516
I tried to figure this out a few times but it's impossible to get a clear picture.

On one hand, histone and DNA methylation factually affects the browning of white adipose tissue and expression of brown adipose tissue (http://www.jbc.org/content/early/2015/08/25/jbc.M115.662650 + several others). Even worse, if some PGC-1α promoters get too methylated it could stop thyroid from working (https://www.ncbi.nlm.nih.gov/pubmed/24622795). (PGC-1α is "the master regulator of mitochondrial biogenesis" in wikipedia's opinion).

It looks damning but you can't say much about what dietary methyl groups will do in relation to that if anything. The methylation of some other promoters does the exact opposite, those just stand out the most. In articles they mostly blame palmitic acid for everything (figures).

The closest you get to saying that dietary methyl groups contribute to fat gain is from the liver effects of SAMe:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336596/
If you increased the export of VLDL and it's malformed on top that has potential to affect fat mass (sure this is NAFLD but I bet you're not flaunting your liver health).

In a general way liver methylation cycle is tied to liver lipid handling. I don't know the extent to which it happens in other tissues. Maybe someone has better information, but they're not posting it...
 
Messages
45
Location
Northern Virginia
I tried to figure this out a few times but it's impossible to get a clear picture.

On one hand, histone and DNA methylation factually affects the browning of white adipose tissue and expression of brown adipose tissue (http://www.jbc.org/content/early/2015/08/25/jbc.M115.662650 + several others). Even worse, if some PGC-1α promoters get too methylated it could stop thyroid from working (https://www.ncbi.nlm.nih.gov/pubmed/24622795). (PGC-1α is "the master regulator of mitochondrial biogenesis" in wikipedia's opinion).

It looks damning but you can't say much about what dietary methyl groups will do in relation to that if anything. The methylation of some other promoters does the exact opposite, those just stand out the most. In articles they mostly blame palmitic acid for everything (figures).

The closest you get to saying that dietary methyl groups contribute to fat gain is from the liver effects of SAMe:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336596/
If you increased the export of VLDL and it's malformed on top that has potential to affect fat mass (sure this is NAFLD but I bet you're not flaunting your liver health).

In a general way liver methylation cycle is tied to liver lipid handling. I don't know the extent to which it happens in other tissues. Maybe someone has better information, but they're not posting it...

Will definitely check out the references you mentioned! My weight was holding pretty steady until this methylation nightmare started about a year ago. Thanks!
 
Messages
45
Location
Northern Virginia
Why is Overmethylation associated with weigh gain and difficulty in losing it? What causes the weight gain and difficulty in losing weight for Overmethylators? Is it linked to low histamine?

Does anyone understand the process enough to explain it?
Thanks

Hi Dominover. I never forgot this thread you started and wanted to give you a positive update.

I've been working with a Naturopath who's specialty is translating genetic testing. I told him of my frustration with gaining weight with every overmethylation episode and my inability to lose any fat regardless of exercise or diet. He said, well, you're dealing with a lot of inflammation (thank you genetics!), and when the body is inflamed, it will not allow you to lose fat.

He recommended I try intermittent fasting. This is the best thing that has ever happened for me. I've actually lost 17 lbs since Thanksgiving 2017. I cannot believe it. And what have I given up? A glass of milk at bedtime - that's it. I stopped taking my bedtime pills (magnesium, probiotics, and progesterone) with a glass of milk. I still drink milk during my window of eating - FYI.

I try and reach 16 hours of fasting and feel so much better. Still have to be careful about eating too much folate rich food - sigh. I realize not everyone can do intermittent fasting, and from my research, some folks genetics and/or medical issues don't allow for it. But for me it has been a true miracle. I hope it can be helpful for you too!!
 

bjl218

Senior Member
Messages
145
Location
Chelmsford, Massachusetts
Can someone define what you mean by being an "overmethylator"? Are you basing this on your genetics, blood histamine levels? When you talk about "overmethylating episodes" is this an episode due to taking methylation supplements or just something that happens to you every now and then because of your own particular body chemistry? I'm so confused between the definition of "overmethylation" I see used in orthomolecular medicine and what I see written by people like Ben Lynch.
 
Messages
45
Location
Northern Virginia
This discussion refers to hypermethylation brought on by too many methyl donors. For me, thanks to MTHFR, COMT & CBS issues, too many methyl donors, like folate, cause me to experience the following: increased heat/ hot flashes, headache, tinnitus, body aches, insomnia, and something else I'm forgetting. Many people experience a lot of anxiety when having a hypermethylation episode. It's a miserable, immediate form of inflammation. And, yes, this is the overmethylation that Ben Lynch discusses.

I'm so sensitive to methyl donors that I do not take any form of folate as a supplement, nor TMG, not Folinic Acid. I often have hypermethylation episodes after eating too much folate rich food - like salads.

I totally understand your question as the word overmethylation is used by different factions...