Folate can make some undermethylaters worse

[DogLover]

I've seen this question pop up a few times "why does folate make me worse?" I've found this simple explanation:

Epigenetics is essentially the study of how external factors (like nutrition, stress, oxidative damage, etc…) influence the way our genes express themselves. Folate and folic acid, according to the Walsh Research Institute, have an epigenetic effect on the SERT transporter. The SERT transporter helps to reuptake serotonin after it’s been released. SERT is the target for many pharmaceutical antidepressants (SSRIs, or Selective Serotonin Reuptake Inhibitors). SSRIs work because they interfere with SERT and so serotonin stays active longer, which means you get more benefit from this happy neurotransmitter. Methylfoate, folate from foods and folic acid, while they increases serotonin production through BH4, also increase SERT via an epigenetic effect. This means they help your brain to clear out serotonin faster, thereby reducing the amount of serotonin that is available for you to use. Essentially this makes folate the anti-anti-depressant. Sigh.

http://dramyneuzil.com/methylfolate-makes-depression-worse-how-is-this-possible/

 

[xena]

Hi I've been noticing this for the past couple of years. Ie- folate causing worsening depression. However, this only started happening since I tried a low sulfur diet for my CBS mutation. I believe this depleted my glycine or collagen levels since my skin stopped healing properly during this period. Glycine is the body's natural buffering system for extra methyl groups and allows us to appropriately regulate methylation. I believe this maybe the proximate cause of why the folate is causing depression in some of us in the "overmethylator" subtype. It would explain for example why the SERT is being inappropriately regulated- maybe it's being methylated incorrectly because our bodies don't have enough glycine to prevent this. Based on a quick Google, there is research showing that the level of DNA methylation of SERT affects mental health issues.

Eg. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203012/

Chris Masterjohn had several good short videos about this- not SERT but the overmethylator/undermethylator issue.

Even small amounts of green vegetables used to worsen my mood causing severe depression for weeks until I take niacin. Fortunately it's gotten way less extreme and I can usually tolerate some veggies now. However- extra methyl donors in the form of egg yolks can cause depression again. Again the niacin helps.

I've also experimented with Walsh's key recommendation of Sam-e. I found that it helps the depression in the short term but actually badly exacerbates the problem in the long run. When I would stop the dam-e, even after a day I would get extremely severe depression, worse than before. I believe this is because plain Sam-e depletes the glycine reservoir further.

The other Walsh recs: I have also found the inositol helpful but it exacerbates calcium in the cells and drives up my anxiety. Ditto on the plain calcium. The magnesium is somewhat helpful, especially with b6. St John's wort helps as does 5 htp.

This hypothesis predicts that balancing your glycine reservoir and methyl donors could help. I've tried to do that by not eating more methyl donors in the form of choline or betaine, or too methionine from meat. This generally helps me avoid the severe folate depression. I also take b2 daily about 20 mg since it's been shown to nearly normalize the function of the mthfr enzyme. Mthfr activity is important to preserve glycine levels so at this point I'm trying take enough folate and b2 on a daily basis to build up my glycine reservoir. Btw- it took me a while to build up b2 intake, initially it caused very bad reactions. See the b2 I love you thread.

Directly taking collagen has been helpful I think with the depression but it's tricky for me because it exacerbates my oxalate levels. Glycine I try to take but unclear if it is helping.

Summary: be cautious with the methionine/sam-e and other methyl donors potentially using up too much glycine if you have folate induced depression. Try to build up your glycine levels through taking b2 + b9 to the extent you can. Take collagen or glycine if you can tolerate it.

 

[DogLover]

@xena

Thanks for the input. Just wondering, have you ever taken an Organic Acids Test?

 

[xena]

@xena

Thanks for the input. Just wondering, have you ever taken an Organic Acids Test?

I think I have?

 

[Sophiedw]

Hey @xena, did your collagen problems recover? What do you think helped? Do you still take inositol?

 

[xena]

Hey @xena, did your collagen problems recover? What do you think helped? Do you still take inositol?

which aspect of them? I don't take inositol anymore, no

 

[Sophiedw]

@xena here you say that the folate gave you anxiety and at the same time your skin stopped healing. Did the skin start healing any better at any point? Thank you

 

[xena]

@xena here you say that the folate gave you anxiety and at the same time your skin stopped healing. Did the skin start healing any better at any point? Thank you

yes- it doesn't give me anxiety anymore. or... to put it another way it takes like 1000s of times more methyl donor to provoke anxiety. my skin did start healing better once i stopped that low sulfur diet. over time, as my inflmmation dropped and body healed, my tolerance for methyl donors has improved. i made a big improvement recently when i introduced gaba powder. ive tried gaba before but for whatever reason it made a huge difference in improving my tolerance for methyl donors- i think it has reduced inflammation and helped heal my gut

 

[Sophiedw]

Awww amazing very happy to hear that. Do you take all the methylation supps like sam-e tmg etc?

 

[xena]

Creatine... more effective. B2. Folate as needed. B12

 

[GreenMachineX]

Hi I've been noticing this for the past couple of years. Ie- folate causing worsening depression. However, this only started happening since I tried a low sulfur diet for my CBS mutation. I believe this depleted my glycine or collagen levels since my skin stopped healing properly during this period. Glycine is the body's natural buffering system for extra methyl groups and allows us to appropriately regulate methylation. I believe this maybe the proximate cause of why the folate is causing depression in some of us in the "overmethylator" subtype. It would explain for example why the SERT is being inappropriately regulated- maybe it's being methylated incorrectly because our bodies don't have enough glycine to prevent this. Based on a quick Google, there is research showing that the level of DNA methylation of SERT affects mental health issues.

Eg. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203012/

Chris Masterjohn had several good short videos about this- not SERT but the overmethylator/undermethylator issue.

Even small amounts of green vegetables used to worsen my mood causing severe depression for weeks until I take niacin. Fortunately it's gotten way less extreme and I can usually tolerate some veggies now. However- extra methyl donors in the form of egg yolks can cause depression again. Again the niacin helps.

I've also experimented with Walsh's key recommendation of Sam-e. I found that it helps the depression in the short term but actually badly exacerbates the problem in the long run. When I would stop the dam-e, even after a day I would get extremely severe depression, worse than before. I believe this is because plain Sam-e depletes the glycine reservoir further.

The other Walsh recs: I have also found the inositol helpful but it exacerbates calcium in the cells and drives up my anxiety. Ditto on the plain calcium. The magnesium is somewhat helpful, especially with b6. St John's wort helps as does 5 htp.

This hypothesis predicts that balancing your glycine reservoir and methyl donors could help. I've tried to do that by not eating more methyl donors in the form of choline or betaine, or too methionine from meat. This generally helps me avoid the severe folate depression. I also take b2 daily about 20 mg since it's been shown to nearly normalize the function of the mthfr enzyme. Mthfr activity is important to preserve glycine levels so at this point I'm trying take enough folate and b2 on a daily basis to build up my glycine reservoir. Btw- it took me a while to build up b2 intake, initially it caused very bad reactions. See the b2 I love you thread.

Directly taking collagen has been helpful I think with the depression but it's tricky for me because it exacerbates my oxalate levels. Glycine I try to take but unclear if it is helping.

Summary: be cautious with the methionine/sam-e and other methyl donors potentially using up too much glycine if you have folate induced depression. Try to build up your glycine levels through taking b2 + b9 to the extent you can. Take collagen or glycine if you can tolerate it.

I have the opposite problem it seems. My skin doesn't heal and nails don't grow if I don't take folate, but taking folate revs me up too much and gives anxiety. I just started taking glycine so hopefully that helps. I'm getting about 5g now. Hope that's enough.

 

[GreenMachineX]

I have the opposite problem it seems. My skin doesn't heal and nails don't grow if I don't take folate, but taking folate revs me up too much and gives anxiety. I just started taking glycine so hopefully that helps. I'm getting about 5g now. Hope that's enough.

This didn't work out for me. When I started taking collagen, I was up all night jumping out of my skin.