Overmethylation and weight gain (MTHFR)

[HamandRyeSandwiches]

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...

Hi Carnation4000. I'm new here...although I've lurked in the background for a long time as a very interested party. I am struggling with similar problems as you...MTHFR, COMT, CBS, overmethylation, weight gain that won't budge, inflammation, and the symptoms you listed above. I wanted to reply because the above symptoms sound like salicylate sensitivity to me (inc loss of memory!). Since I'm new here I don't know if this is a hot topic...or not on the radar. I discovered that I had a very severe case of sal poisoning 1.5 years ago...and it's made a HUGE difference for me getting off Mediterranean foods. I will gladly share more information if it would be helpful to you.

 

[Carnation4000]

Hi Carnation4000. I'm new here...although I've lurked in the background for a long time as a very interested party. I am struggling with similar problems as you...MTHFR, COMT, CBS, overmethylation, weight gain that won't budge, inflammation, and the symptoms you listed above. I wanted to reply because the above symptoms sound like salicylate sensitivity to me (inc loss of memory!). Since I'm new here I don't know if this is a hot topic...or not on the radar. I discovered that I had a very severe case of sal poisoning 1.5 years ago...and it's made a HUGE difference for me getting off Mediterranean foods. I will gladly share more information if it would be helpful to you.

In all my research I haven't seen anything about salicylate sensitivity. But at this point, I wouldn't be surprised to find out that there's yet another thing causing issues for me. I would be glad to see what information you have! Thanks!

 

[HamandRyeSandwiches]

In all my research I haven't seen anything about salicylate sensitivity. But at this point, I wouldn't be surprised to find out that there's yet another thing causing issues for me. I would be glad to see what information you have! Thanks!

This is a great website that explains alot. www.salicylatesensitivity.com

Salicylates aren't just in plants anymore. Because they are a natural preservative they are in 90% of pack aged foods (in the form of HFCS), and many personal and home care products.

You can know if you're sensitive pretty quickly by removing from your diet. If so, your symptoms will begin to go away within one day.

 

[Carnation4000]

Thanks so much! Will definitely take a look.

 

[Tunguska]

I don't really want to post here, but I just wanted to point out, because this confuses the hell out of people and it's actively setting people back: methylation can in fact be tied to weight gain. A subset of people will notice direct effects from this. One thing that happens is that the liver exports fat using methionine/TMG/methylation/choline/phosphatidylcholine and this will accumulate in tissues (through VLDL/LDL/tryglycerides/lipase). Essentially there's a caloric balance between the liver and the other tissues such as the abdominal fat. If you interrupt this process without burning the calories, then you get fatty liver instead.

There is a second process that contributes to weight gain, which is that methionine contributes to polyamine synthesis. This is explained elsewhere and I won't bother trying explain it, because I'm not an authority on it.

There are additional processes tied to sulfur amino acids (which is basically methylation) which are either tied to the above or not properly explained in traditional clinical circles yet. Here is a notable example in rats: https://www.ncbi.nlm.nih.gov/pubmed/23154184

 

[HamandRyeSandwiches]

I don't really want to post here, but I just wanted to point out, because this confuses the hell out of people and it's actively setting people back: methylation can in fact be tied to weight gain. A subset of people will notice direct effects from this. One thing that happens is that the liver exports fat using methionine/TMG/methylation/choline/phosphatidylcholine and this will accumulate in tissues (through VLDL/LDL/tryglycerides/lipase). Essentially there's a caloric balance between the liver and the other tissues such as the abdominal fat. If you interrupt this process without burning the calories, then you get fatty liver instead.

There is a second process that contributes to weight gain, which is that methionine contributes to polyamine synthesis. This is explained elsewhere and I won't bother trying explain it, because I'm not an authority on it.

There are additional processes tied to sulfur amino acids (which is basically methylation) which are either tied to the above or not properly explained in traditional clinical circles yet. Here is a notable example in rats: https://www.ncbi.nlm.nih.gov/pubmed/23154184

Thank you! I know this is a big question, but how do we stop the weight gain if we have the poor methylation gene mutations? Any ideas?

 

[Tunguska]

I don't know any research showing those genes having associations with weight gain.

The general solution is specific amino acid restriction. Methionine restriction and BCAA restriction can have positive effects (BCAAs in blood correlate with obesity with some functional links [mice] [humans] [etc], unclear the contributions of leucine vs valine vs isoleucine), with neutral or lowered calories, or to prevent weight gain from excess calories.

You may not even eat that much to begin with, so you can do the opposite (rather both) and supplement Arginine (+ a iNOS inhibitors to prevent worsening disease, POTS/inflammatory/other), Glycine, and moderate Lysine (somewhere between 3:1 and 1:1 Arg:Lys in total with diet) to promote the synthesis of Creatine and Carnitine at the expense of histone methylation, polyamine synthesis and even methylation-PEMT-backed phospholipid synthesis (that one is tricky, you don't want to compromise phospholipid synthesis too much, yet the regulation may be tight, so in theory you add low uridine dose and moderate choline with meals and avoid polyunsaturated fats which associate more with the PEMT pathway products).

Just do not confuse the water-weight altering effects of these compounds with fat mass, and this will not help if you don't mind calories at all. If disease symptoms worsen, stop them one by one, starting with the Arginine. For vitamins folate from vegetables or maybe folinic acid, hydroxycobalamin might make sense here but I haven't researched that angle much. B6/P5P for the homocysteine. Be careful if your homocysteine was already high but there are contributions both ways from a protocol like this so can't predict the net effect. This is obviously not an established protocol so take it with grains of salt and adapt it to you. Not motivated to write more here, good luck.

 

[Tunguska]

Note the amino supplements are really intended to work together with the methionine restriction. But some people don't eat that much protein or methionine to begin with, and theoretically the MTHFR/MTRR/IIRC mutation might lessen the need to restrict by some percent.