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TMG was eye opening + need advice

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29
Hi everyone,

I'm new to this site and there's a ton I will need to learn over the next few years, but I since I responded very well to TMG supplement (3000 mg/ day) and I have some methylation mutations along with chronic fatigue syndrome, I figure I can get some improvement now whilst I spend some time learning more about how to optimize my health.

To give you a brief overview of my condition, I am a 27 year old male. I progressed into a chronic fatigue state about 5 years ago. I don't believe it was caused directly by an illness or infection, although I was often sick throughout my life. I knew something was wrong when I would work one day of manual labour (or a bodybuilding session at the gym) and be unable to work/ workout for the next week due to sore muscles. The fatigue hasn't lifted over the years. I've lived with it everyday and it's impacted my career/ relationships/ social life.

The CFS started around the time I was put on an SSRI for anxiety/ low-level to moderate depression. The SSRI really helped the moodiness and anxiety (life-changing actually) but it worsened my fatigue. I would often sleep 12 hours. Fast forward to 2015, on the advice of a really, really good psychologist, I sought an ADD-Inattentive type diagnosis and was officially diagnosed by a psychometrist and put on Adderall. The stimulant medication was, again, a life-changing moment for me, and it helps a lot with the ADD symptoms and SOME fatigue, but the core CFS is still there.

So two days ago, I tried the TMG supplement and was very surprised by my reaction. I not only experienced increased energy, but:
-My head felt clear, noticeable also on awakening
-I've been sleeping less hours and waking easier
-My life-long stuffy nose from allergies has never been clearer despite allergy shots + sprays (I can finally BREATHE)
-My foggy/ cloudy vision from the CFS (hard to explain) has cleared up and I can see facial expressions better as I go throughout my day, see farther and more clearly into the distance, and my accommodation (looking from one object to another) is immediate as opposed to delayed before the TMG ( i.e. if I were working on the computer and a colleague walked into the room, if I looked at him/her it would be foggy/ vaguely cloudy at first).
-Speech improvement. Clearer pronunciation. Speaking takes less effort and drains me less. This was a surprise. I've since learned that DMG/ TMG are helpful to facilitate speech in people with Autism.
-I also experienced a mild-moderate feeling of WELLNESS on the TMG - this is also hard to explain but it's more than just a lifting of fatigue. I take wellbutrin and Adderall and although they relieve fatigue, that icky, ill, yucky feeling in the head and body (like when you have a low-level flu) was still there. But the TMG kind of removes that ill feeling a little bit which was a big surprise and proved to me a good chunk of my symptoms are more than just psychological, but are also biological.

Anyways, before I delve into all the information here, I was wondering if somebody could help me get on the fast-track to recovery with some advice on supplementation. I will list my genetic mutations below and what I think (through the research I've done thus far) are the appropriate supplements to take for each:

MTHFR C677T AG +/- : methylfolate

MTRR A66G AG +/- & MTRR A664A AG +/- : b12 hydroxycobalamin (COMT V158M & VDR Taq both negative)

BHMT-02 CT +/- & BHMT-08 TT +/+ : sunflower lecithin

MAO A R297R TT +/+ : SSRI or 5-htp

VDR BSM TT +/+ : Vitamin D3

In addition to this, I will continue with the TMG and also add in a little Sam-e since I seem to really respond to that as well (when I tried it a couple years ago but stopped once I was diagnosed with ADD and wanted to have a pure trial of stimulant medication).

Is methylation supplementation as simple as taking the above supplements? Is there something I'm missing ? Is there a direction somebody could kindly point me in to take my improvement even further ?

I really appreciate any feedback. I thank you all in advance as I wouldn't have even heard of methylation without this forum and others like it!!

Best,

Pheenix997
 
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29
Also, how can I know if I'm over- or under-methylating? I forgot that having the mthfr mutation could mean either. So is response to TMG, Same, ssris etc. A good indication? I do get side effects from ssris such as sleepiness and brain fog, but I function better with it.
 

Paralee

Senior Member
Messages
571
Location
USA
I think over or undermethylation isn't that simple, or at least that's what I read when I first got into this. I've read that parts of you can be overmethylating and parts undermethylating at the same time. I wish I understood more too, so I will be following this.
 

Aroa

Senior Member
Messages
109
Location
Spain
Hi @Pheenix997 !!!

I am quite new in this, as you are, and trying to understant all the methylation stuff.

As for the SSRI, I remember in the Fluge y Mella PDH thread, people saying that SIRT4 inhibits the PDH complex, and that SIRT4 was increased by SSRI, and that would be the reason why ME people often react badly to SSRI.
I experienced that bad reaction as well when my doctor put me on SSRI, as here is the standard protocol together with GET :bang-head: to treat ME/CFS.

I am currently doing meditation to get my mind under control and left SSRI. There are also some people who are doing well with 5 HTP.

Good luck and thank you for sharing your experience with TMG!!!!
 
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15,786
MTRR A66G AG +/- & MTRR A664A AG +/- : b12 hydroxycobalamin
MTRR A664A doesn't have much impact at all. MTRR A66G only has a significant impact if homozygous. So there's no indication of B12 being necessary due to those mutations. However many people do find it beneficial for other reasons.

BHMT-02 CT +/- & BHMT-08 TT +/+ : sunflower lecithin
BHMT-02 has no impact. BHMT-08 is reported backwards by Yasko and Genetic Genie. There's no indication that those SNPs would require any action.

MAO A R297R TT +/+ : SSRI or 5-htp
This SNP doesn't do anything, hence doesn't indicate any need for an intervention.

VDR BSM TT +/+ : Vitamin D3
VDR BSM has little impact, and is unlikely to indicate a need for D3. But supplementing Vitamin D can be a good idea anyhow, especially when far from the equator, in the winter, and/or chronically ill.
 

Aroa

Senior Member
Messages
109
Location
Spain
@Valentijn ,

Thank you for your answer.

Is there in your opinión any SNP - of those identified by Dr. Yasko that impact the methylation - that you think should have a negative effect on it ?

Besides the ones identified by Dr. Yasko, are there any others you consider to be critical for the methylation?

Thank you !!!!!
 
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15,786
Is there in your opinión any SNP - of those identified by Dr. Yasko that impact the methylation - that you think should have a negative effect on it ?
MTRR A66G (+/+ only), MTHFR C677T, and MTHFR A1298C.

Besides the ones identified by Dr. Yasko, are there any others you consider to be critical for the methylation?
A list of links depending on the gene are at http://forums.phoenixrising.me/inde...e-and-host-of-other-issues.42339/#post-684881
 
Messages
29
Thanks for the reply @Valentijn !

What about the MTHFR677 +/- gene. What supplements would you recommend for this? I know you can't give a definitive answer obviously but there's so much information here to digest that it's hard to know where to begin...

So after the first few good days on TMG I get waves of a sick feeling, like sleepy and run down. But then I'd get a wave of calm energy, feeling "switched on" and more alert to life. It's been weird. I'm thinking the recent negative symptoms are the result of detox?

Here's what I'm currently taking:
Methylfolate 2000 mcg
MethylB12 2000 mcg
Same 200 mg
TMG 3000 mgs
And a whole bunch of other stuff (Vitamin B6, Zinc, P5P, Vitamin D, turmeric, Milk Thistle, Glutathione etc.)
 
Messages
15,786
What about the MTHFR677 +/- gene. What supplements would you recommend for this?
MTHFR C677T results in a 35% reduction in enzyme function. But because the MTHFR mutations are extremely common, the average person has a 30% reduction in function. Hence having only that MTHFR mutation would make you pretty normal in that regard.

It is associated with increased risks related to reduced folate levels, however, primarily in regards to birth defects in a pregnant mother with that mutation. A couple studies show that eating a diet with a decent amount of veggies, or supplementing a normal amount of folic acid (400-800mcg) is sufficient to fully correct for the increased risks.

A lot of people have problems when supplementing too much folate in combination with B12. So it might help to cut back to a normal dose of folate, such as what you'd get from a multivitamin or B-complex.
 
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29
Hmm ok maybe I'll cut back. I'm looking for CFS relief however, so I was hoping this methylation thing would help. TMG - my God - certainly did the first few days. My vision problems were corrected, it was amazing. Does this response indicate anything?

Thanks so much for your responses it means a lot...
 
Messages
29
Hi @Pheenix997 !!!
As for the SSRI, I remember in the Fluge y Mella PDH thread, people saying that SIRT4 inhibits the PDH complex, and that SIRT4 was increased by SSRI, and that would be the reason why ME people often react badly to SSRI.
I experienced that bad reaction as well when my doctor put me on SSRI, as here is the standard protocol together with GET :bang-head: to treat ME/CFS.!!
Hey there !!

What was your bad reaction to the SSRI? Just fatigue and brain fog or anything else ? The problem for me is it works SO well on my anxiety and makes me more comfortable socially. The fatigue and brain fog reaction I assumed was also due to the fact that I had undiagnosed ADD (I actually have it, not just saying I do), as serotonin activity lowers dopamine. I was actually experiencing some Parkinsonian symptoms (delay in initiating movement; at 22 years old!!!) which made me really think ok something is not right here.

After experimenting with changes from dropping the SSRI for a year to only trying wellbutrin and/or adderall I find I'm at my best on all of them. It sucks but I can't increase one neurotransmitter without intolerable side effects from lack of the other.

The fact that I do have multiple mild neuro chemical imbalances is part of the reason I'm interested in getting my methylation to work better to synthesize more neurotransmitters, so that eventually I can wean off or at least lower the doses of what I'm taking.
 
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29
I think it might also be useful to say my Blood B12 levels were 306 pmol/L (range is > 133) or 414 pg/ml. It looks like I am not deficient, but i've also read that blood values may not be a true indication of how much is being used in cells.

I do notice more energy on all of these supplements. Every week I am going to titrate the methylb12 and methylfolte to see if I get greater reduction in CFS symptoms. I don't have much to lose at this point. I know @Valentijn you said 400-800 mcg folate daily is enough to make up for the MTHFR polymorphism, but perhaps in reality, due to my extreme symptoms of fatigue, I could use much more.
 
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15,786
I'm looking for CFS relief however, so I was hoping this methylation thing would help.
I've seen little indication that methylation has any impact on core ME/CFS symptoms. People still get PEM, are still house-bound are bed-bound, etc.

Every week I am going to titrate the methylb12 and methylfolte to see if I get greater reduction in CFS symptoms. I don't have much to lose at this point. I know @Valentijn you said 400-800 mcg folate daily is enough to make up for the MTHFR polymorphism, but perhaps in reality, due to my extreme symptoms of fatigue, I could use much more.
Fatigue has little to do with ME/CFS. If that's your primary symptom, you may need to talk to your doctor about investigating further for the cause. ME/CFS is character by Post-Exertional Malaise (PEM), which means that muscular, neurological, and/or immunological symptoms, etc, get badly exacerbated starting approximately 24 hours after exertion. That can involve full body pain (not just in the over-used muscles), ataxia, low blood pressure, swollen lymph nodes, etc.

I'm not sure what methylation has been shown to do for chronic fatigue. But in an ME/CFS study, there were some initial improvements which disappeared over time.
 
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1,478
I would also add that a sign of CFS is brain fog after exertion (cognitive or physical) but also brain fog throughout the day. If you just have brain fog you could well be just b12 deficient. Have you tested for pernicious anaemia etc? B12 supplementation helped me reduce brain fog. You do need folate though for this to work but probably not necessarily in the ratio you have above. I'm not sure whether excessive folate is the key for everyone. I certainly get by with a lot less than others have here. I've never tried taking SAMe or tmg since i seem to be ok taking just the b12, folate, b2/b6 for methylation (with a little help from creatine). Trying to take multiple supplements is a tricky thing. I would recommend the basics first going low and slow before trying anything too clever with tmg etc. Look into magnesium as well, which can help.
 

Aroa

Senior Member
Messages
109
Location
Spain
What was your bad reaction to the SSRI? Just fatigue and brain fog or anything else

I was more fatigued, so that before I was able to walk for 10-15 minutes most days, but after SSRI couldn´t.

The fact that I do have multiple mild neuro chemical imbalances is part of the reason I'm interested in getting my methylation to work better to synthesize more neurotransmitters, so that eventually I can wean off or at least lower the doses of what I'm taking.

It makes a lot of sense to me!

The fact is that many people here noticed improvements on methylation protocol, so I think it is worth trying. I do not know whether it is due to the fact that you may be correcting metabolism imbalances that are proved to exist in ME/CFE. This imbalances are also affected by genetics. And that´s why is not that easy to know what supplements will be effective for everyone.

I started already with "all in one" multivitamins and 5 days ago introduced Hydroxy B12, and I noticed quite an improvement on this last one, although it is too short to say it.

I follow the advice : Start Low and Go Slow
 
Messages
29
I was more fatigued, so that before I was able to walk for 10-15 minutes most days, but after SSRI couldn´t.

That sounds a lot like my reaction to it. But it helped my anxiety so much which enabled me to function better. So I've stayed on it at a very low dose.
 
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29
Fatigue has little to do with ME/CFS. If that's your primary symptom, you may need to talk to your doctor about investigating further for the cause. ME/CFS is character by Post-Exertional Malaise (PEM), which means that muscular, neurological, and/or immunological symptoms, etc, get badly exacerbated starting approximately 24 hours after exertion. That can involve full body pain (not just in the over-used muscles), ataxia, low blood pressure, swollen lymph nodes, etc.

I will say that TMG initially was making me much better able to workout in the gym with a NORMAL level of fatigue, not the breathless, pale, faint feeling I'd normally have. All stimulants have this effect for me, though.

And I use the word fatigue to efficiently and practically communicate the umbrella of CFS symptoms. I have CFS believe me. PEM, definitely. My psychologist I was once seeing differentiated it from dysthymia for me, and was the one who said I had CFS. Sometimes it's difficult to stand up straight whilst going to the washroom. Just terrible. It's severely slowed down my life and I've suffered for it in all areas.
 
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1,478
I will say that TMG initially was making me much better able to workout in the gym with a NORMAL level of fatigue, not the breathless, pale, faint feeling I'd normally have. All stimulants have this effect for me, though.

And I use the word fatigue to efficiently and practically communicate the umbrella of CFS symptoms. I have CFS believe me. PEM, definitely. My psychologist I was once seeing differentiated it from dysthymia for me, and was the one who said I had CFS. Sometimes it's difficult to stand up straight whilst going to the washroom. Just terrible. It's severely slowed down my life and I've suffered for it in all areas.

Forgive me if this is old news for you but have you had your diagnosis through a medical GP as oppose to the psychologist? Your visits to the gym makes me think that there might be another reason for the fatigue that might be more treatable? Apologies if you have had all the screening tests just thought I would ask. It's quite unusual to be able to do any aerobic activity at all without PEM. I guess gym is quite genetic and could mean stretching or carefully heart rate managed resistance training?
 
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15,786
I will say that TMG initially was making me much better able to workout in the gym with a NORMAL level of fatigue, not the breathless, pale, faint feeling I'd normally have.
This could be due to orthostatic intolerance or another form of dysautonomia, not necessarily ME/CFS.