MTHFR mutations

[patty2292]

That would be my thinking. Sam-E is a methyl donor, so may be over driving things. If you still feel sick try putting the brakes on methylation with some niacin.
If that doesn't help there are two options left.

_http://www.pvmhmr.org/5-depression/article/13034-major-depression-serotonin-precursors-same

Safety and Dosing

Dosing for SAMe is typically between 800mg/day and 1600mg/day. SAMe is very safe at recommended dosages. Because it is essentially a protein, it has no real side effects other than gastrointestinal upset and the possibility of triggering mania in people with bipolar disorder.

SAMe increases the risk of developing a rare condition called serotonin syndrome (or serotonin toxicity) that produces mental confusion, agitation, headache, shivering, sweating, hypertension, tachycardia (fast heart rate), and other symptoms. Check with your health care provider before incorporating SAMe into your therapy.

The dose i was introduced was 400mg/day. But the symptoms suddenly hit me a day or two after the introduction. My thoughts where as you said basically; that it was showing me the problems that my immune system was fighting... But it also showed me the weakness of my immune system overall. I went the doctors today to see what it was, and she advised it was just a viral infection that was giving me the flu/cold like symptoms. I also mentioned it could be a detox reaction, but she didnt buy it... As expected .

Lastly is you may now be experiencing a detox reaction. Methylation needs to be working well to produce any glutathione.
So try some NAC, and possibly some EDTA/ALA (see heavy metal protocols).
...
*edit to add* Thinking further, it could be that your immune system is waking up and taking care of business. Especially if it's reduced your stress levels.
It's probably best to avoid SAM-e though. You could try reintroducing it again once symptoms have disappeared.
If it's genuinely a cold, get some zinc, selenium, b6, vit D along with vit C.

Its probably necessary for me to mention that for the past 2 weeks ive been doing coffee enema's. Once a week, and it was also around the second one that i felt the symptoms (also when i introduced Sam-e). The coffee enema is something that should be producing alot of Glutathione from what ive read, so again this could be a heavy detox reaction to multiple things at once.
Ive also been doing a very high pro-biotic dose and digestive aid protocol that has improved my digestion a hell of alot. This is also a big contributing factor to my enhanced mood and well-being. Im taking multiple strains of strong pro-bi's several times a day, with slippery elm and glutamine pre meals. Along with panc-enzymes and betain HCL. Its something that i looked into, and decided to go very fast on to repopulate the gut while doing the methylation protocol. As the odd pro-bi here and there just didnt seem to do anything, and was wasting alot of money with no outcome. Carb count/pre-biotic intake has gone up, and i am definitely not in keto, but its really helping me to heal the internal distress and malabsorbtion issues. So the high carb count hasnt created any negative effects so far.

So i think if i look at it all, including the enema, mass methylation supplementation and also digestive aids, it could be a very very likely chance that is a combination of my immune system kicking in, possible heavy metal detox and die off reactions all at once. Ive never felt neck/shoulder pain and stiffness like this. And i never EVER get headaches, never mind migraines. Saying that, i only ever get ill once a year. This is normally in the midst of winter when im exposed to cold for too long.

Ive cut all protocol for the past two days, and do feel slightly better. Although the upper body tension is still very noticeable. But i havnt been taking any immune system boosting aid, apart from Vit-C. So that will be my next point of action. I will also introduce the B-Vitamin supplements today and avoid the Sam-e as i clearly can not handle the amount of gas it was giving.

But overall, even though i am experiencing negative reactions, that glimpse of sheer clarity and mental focus with no anxiety/stress was worth this backlash. So im going to continue to experiment with other co-factors like TMG once im back on track.

 

[RedFox]

Glad you are feeling better. Sounds like you should avoid the SAM-e all together if it was giving you gas.

But overall, even though i am experiencing negative reactions, that glimpse of sheer clarity and mental focus with no anxiety/stress was worth this backlash. So im going to continue to experiment with other co-factors like TMG once im back on track.

Yeah the clarity is pretty amazing!
A few things came to mind that may be useful.
Firstly, try some magnesium, and broth. I've noticed that when I reached a certain point with this protocol, my body started using up electrolytes and other minerals quickly, especially when it was repairing the nervous system.
You may also find that you don't need to take as large a dose of supplements as before - I've found I've had to drop my dose for supplements quite considerably. It seems my body is way more efficient than it was before. The tiny RDA you get on vitamins is plenty now.

 

[RedFox]

Just saw this on sott

http://www.sott.net/article/301142-10-health-tips-for-anyone-with-a-MTHFR-gene-mutation

[..]Key functions these donated methyl group are:

Protecting DNA and RNA. If DNA is not protected it is susceptible to damage by viruses, bacteria, heavy metals, solvents and other environmental toxins. Over time if this damage becomes significant and could even result in cancer.
Reducing histamine levels (see this article) Sometimes the common methyl-donor, SAMe can help reduce histamine levels.
Protecting cell membranes. The methyl group donated by SAMe helps build phosphatidylcholine which then gets incorporated into the walls of all your cells. If these cell membranes become damaged and weak, the cells become fragile and harmful things may enter the cell. If they are unable to carry in useful nutrients, they will die. Excessive cell membrane damage can lead to serious medical conditions, such as multiple sclerosis.[..]

Could you try some phosphatidylcholine and see what happens? If you get the same symptoms it's most likely a virus that the body now has the ability to defend against.
It could also be cell death from DNA damage I guess, and the body is now ridding itself of damaged cells.

 

[patty2292]

Glad you are feeling better. Sounds like you should avoid the SAM-e all together if it was giving you gas.

I implied that gas as in acceleration... Sorry if it wasnt very clear. Poor choice of words !

Firstly, try some magnesium, and broth. I've noticed that when I reached a certain point with this protocol, my body started using up electrolytes and other minerals quickly, especially when it was repairing the nervous system.
You may also find that you don't need to take as large a dose of supplements as before - I've found I've had to drop my dose for supplements quite considerably. It seems my body is way more efficient than it was before. The tiny RDA you get on vitamins is plenty now.

Ive been having alot of salt water through the day with my liquid potassium. Its helped with the headaches, but i also sort of feel like my body needs it really. I normally despise the taste.
Also having alot more magnesium before bed, 4x my normal dose, and surprisingly it hasn't effected my stool like it used to if i took too much.

Could you try some phosphatidylcholine and see what happens? If you get the same symptoms it's most likely a virus that the body now has the ability to defend against.
It could also be cell death from DNA damage I guess, and the body is now ridding itself of damaged cells.

So taking phosphatidylcholine will replace the action/process of Sam-e initially?

 

[Carl]

Could you try some phosphatidylcholine and see what happens? If you get the same symptoms it's most likely a virus that the body now has the ability to defend against.
It could also be cell death from DNA damage I guess, and the body is now ridding itself of damaged cells.

So taking phosphatidylcholine will replace the action/process of Sam-e initially?

As far as I know choline should help the conversion of homocysteine back to methionine through the TMG pathway, which would then translate into more SAMe as long as Magnesium and sleep are adequate.

 

[patty2292]

Could you try some phosphatidylcholine and see what happens? If you get the same symptoms it's most likely a virus that the body now has the ability to defend against.
It could also be cell death from DNA damage I guess, and the body is now ridding itself of damaged cells.

As far as I know choline should help the conversion of homocysteine back to methionine through the TMG pathway, which would then translate into more SAMe as long as Magnesium and sleep are adequate.

Im running around and cant seem to find much information that i can digest on the way choline is beneficial in all of this. From what i can see its not mentioned much by Dr. Yasko, but it is in the diagrams directly relating to the TMG pathway. So im guessing its some kind of nutritional support to feed into a certain pathway to bypass a mutation?

Ive ordered it anyway, as there seems to be other benefits, but i just cant seem to grasp the direct relation for it in all of this. Suppose i will just be my own guinea pig come monday!
Still waiting on the TMG supplement to be delivered, shame it didnt come before the sam-e!

 

[RedFox]

I've been thinking about your reactions, and this is the best working hypothesis I have right now:

http://stevenenninger.com/articles/2014/5/31/why-youre-not-getting-better-understanding-mthfr

Active folate is required to activate our defensive T cells. This immune reaction is one of the first lines of defense against bugs (virus and bacterial) invading our system.

http://www.drkendalstewart.com/wp-content/uploads/2011/09/Methylation-Overview-for-Professionals-10.11.pdf

Methylation and the Immune System
New T cell synthesis is needed in order for T cell clones to expand and respond properly to an immune assault. T cells are needed to help to control the B cells and to balance TH1 and TH2 responses. If there are methylation cycle problems or mutations, you may have trouble making the bases that are needed for new DNA synthesis. If you cannot make new DNA, then you cannot make new T cells and as a result you may lack immune system regulatory cells.
The immune system has the B cell "arm" that makes antibodies, known as humoral immunity and the T cell "arm" known as cellular immunity. If you are having trouble making new T cells, in particular,
T suppressor cells, then the immune response may become more heavily weighted in the direction of B cells. B cell skewed individual has the ability to respond by making antibodies (or autoantibodies) in high numbers to attempt to overcome the T cell deficiency that fights infection. B cell clones expand to be available for the future. This scenario creates a somewhat greater need for new DNA synthesis.
Methylation also plays a role in the ability of the immune system to recognize foreign bodies or antigens that it needs to respond to. Research has shown that methylation is decreased in humans with auto immune conditions. Impaired methylation of T cells may be involved in the production of auto antibodies. Studies from patients with systemic lupus erythrematosis (SLE) have shown that their T cells are undermethylated. As proper methylation function is restored, immune system regulation should slowly recover.

That is, your immune system has woken up and is now fighting something that has been lurking for years perhaps?

Could you try some phosphatidylcholine and see what happens? If you get the same symptoms it's most likely a virus that the body now has the ability to defend against.
It could also be cell death from DNA damage I guess, and the body is now ridding itself of damaged cells.

As far as I know choline should help the conversion of homocysteine back to methionine through the TMG pathway, which would then translate into more SAMe as long as Magnesium and sleep are adequate.

Im running around and cant seem to find much information that i can digest on the way choline is beneficial in all of this. From what i can see its not mentioned much by Dr. Yasko, but it is in the diagrams directly relating to the TMG pathway. So im guessing its some kind of nutritional support to feed into a certain pathway to bypass a mutation?

Ive ordered it anyway, as there seems to be other benefits, but i just cant seem to grasp the direct relation for it in all of this. Suppose i will just be my own guinea pig come monday!
Still waiting on the TMG supplement to be delivered, shame it didnt come before the sam-e!

Have attached a picture of the Choline/TMG side of methylation.
If the mthfr side is weak/taxed, the Choline/TMG side probably takes the strain, which means that your body is depleted of choline for use in other areas. i.e. cell membranes, especially nerve cells.

*edit* looking at the diagram, perhaps the SAM-e was overdriving the production of homocysteine, and the conversion of that couldn't cope?
*edit* If you where over producing homocysteine, you may find you get hot and angry easily.

 

[patty2292]

Thanks for that Redfox, makes it all a lot clearer as to what happened.

Me and Carl after looking at the full diagram, along with the exert of the description of it lead me to the same conclusion you hit: sam-e was causing a build up of homocysteine that couldn't go anywhere.

I'm back on the supplements with no sam-e, and now taking choline along with them. I'm slowly feeling that mind clarity and less anxiety again after some b12.
Coming into work I also noticed my high body temperature so it's good that you mentioned that aswell!

 

[Justin]

Thanks Huxley

Thought it may be worth mentioning (on the COMT side of things - neurotransmitter breakdown)

http://resqua.com/100001600189727/what-does-the-comt-gene-mutation-mean

Red or purple berries and herbs:
The COMT enzyme processes the colors red and purple so that consuming red or purple herbs or foods and drinks actually slows this enzyme down further. This is a side issue from those with the CBS having difficulty processing phenols. For those with a complete COMT mutation, the simple act of eating too many delicious summer fruits and herbs often leads to more neurotransmitter peaks and valleys. For some, this leads to roller coaster mood or “dopamine swings,” while for others it translates toward more nor- epinephrine surges and restlessness or anxiety. Even so, the synthetic phenols used as coloring agents are even more problematic. *Many become irritable or agitated and struggle with insomnia, and/or develop flushed, red cheeks and ears. In many cases, those with a complete mutation are more sensitive to berries and may develop allergies to them.

Additionally, headaches, insomnia, and heat intolerance are also commonly seen in those with phenol sensitivities. This may be considerably aggravated in the presence of a CBS defect, as it impacts the PST enzyme (please see phenol discussion).

So if you have a MTHFR mutation and normal COMT (slower filling of the methyl bucket, and normal emptying speed) you'll tend to have lower neurotransmitter levels.
One thing that I seem to have done for years is self medicate with berries. Berry tea works just as well.
Berries use up COMT and slow the breakdown of neurotransmitters. Do watch that they don't make you anxious though, that can be a sign of too many neurotransmitters.

This is interesting. I have the COMT ++ version and generally have a bad reaction to these sorts of foods. I bought a bottle of pomegranate juice the other day and drank maybe 2 swallows before I started to feel weird. Mostly I've learned to avoid them altogether, but never knew why exactly - I guess I assumed it was fructose that was the culprit.

 

[Turgon]

Thanks Huxley

Thought it may be worth mentioning (on the COMT side of things - neurotransmitter breakdown)

http://resqua.com/100001600189727/what-does-the-comt-gene-mutation-mean

Red or purple berries and herbs:
The COMT enzyme processes the colors red and purple so that consuming red or purple herbs or foods and drinks actually slows this enzyme down further. This is a side issue from those with the CBS having difficulty processing phenols. For those with a complete COMT mutation, the simple act of eating too many delicious summer fruits and herbs often leads to more neurotransmitter peaks and valleys. For some, this leads to roller coaster mood or “dopamine swings,” while for others it translates toward more nor- epinephrine surges and restlessness or anxiety. Even so, the synthetic phenols used as coloring agents are even more problematic. *Many become irritable or agitated and struggle with insomnia, and/or develop flushed, red cheeks and ears. In many cases, those with a complete mutation are more sensitive to berries and may develop allergies to them.

Additionally, headaches, insomnia, and heat intolerance are also commonly seen in those with phenol sensitivities. This may be considerably aggravated in the presence of a CBS defect, as it impacts the PST enzyme (please see phenol discussion).

So if you have a MTHFR mutation and normal COMT (slower filling of the methyl bucket, and normal emptying speed) you'll tend to have lower neurotransmitter levels.
One thing that I seem to have done for years is self medicate with berries. Berry tea works just as well.
Berries use up COMT and slow the breakdown of neurotransmitters. Do watch that they don't make you anxious though, that can be a sign of too many neurotransmitters.

This is interesting. I have the COMT ++ version and generally have a bad reaction to these sorts of foods. I bought a bottle of pomegranate juice the other day and drank maybe 2 swallows before I started to feel weird. Mostly I've learned to avoid them altogether, but never knew why exactly - I guess I assumed it was fructose that was the culprit.

If you're having a reaction like that, you could also be sensitive to blood sugar spikes from the pomegranate juice. Even though I haven't gotten my tests back, I suspect I have an MTHFR mutation, so I've decided to simply supplement with L-Carnitine, CoQ10, phosphatidyl choline and eating a lot of lettuce for increased naturally occurring folate to help with my energy levels. I'm not sure if there's been an overall increase in energy but I do feel better about myself generally speaking and less rigid in thinking.

 

[RedFox]

This is interesting. I have the COMT ++ version and generally have a bad reaction to these sorts of foods. I bought a bottle of pomegranate juice the other day and drank maybe 2 swallows before I started to feel weird. Mostly I've learned to avoid them altogether, but never knew why exactly - I guess I assumed it was fructose that was the culprit.

The amount of sugar in those drink will make you feel weird prety quickly, so I agree with Turgon. Generally a good idea to avoid sugar!

 

[monotonic]

We were at our local health market today and we found the Mercola B12 and vitamin D sprays on clearance, so we decided to try them out. The B12 spray uses methylcobolamin. After using it I experienced a strange mental state of being extremely irritated at every little annoyance. It reminded me of times in my childhood when I would explode with rage, times when I also could have been taking B vitamins. Not sure what to think of this?

I notice a lot of other people have noticed a similar problem:

http://www.health24.com/Experts/Question/vitamin-b-makes-me-angry-and-violent-20090319

 

[RedFox]

The following from the phoenix rising forum may be of help:
_http://forums.phoenixrising.me/index.php?threads/mb12-made-me-feel-angry.11856/

I think this is due to an increase in the excitotoxicity of the neurons that have NMDA glutamate receptors. When methionine synthase is first stimulated using B12 and folate, it converts more of the homocysteine into methionine, so that less enters the transsulfuration pathway to support glutathione synthesis. Glutathione therefore drops initially on this type of treatment, and that impacts the ability of the astrocytes in the brain to import glutamate and convert it to glutamine for recycle back to the neurons. The glutamate level in the synapses thus stays too high, and that causes too much stimulation of the NMDA receptors, raising the state of excitotoxicity. Anxiety, insomnia and nervousness are symptoms of excitotoxicity.

This should calm down as the methylation cycle recovers and more homocysteine is available to go to glutathione synthesis. In the meantime, I have suggested that using some liposomal glutathione might help. The new acetyl glutathione that is supplied by Allergy Research Group might also be a possibility. I haven't had much feedback on this yet, so can't say for sure if it will work.

There are several other supplements that may help with excitotoxicity. Among them are magnesium, taurine, progesterone cream, GABA, theanine, Valerian root and some others. Dr. Yasko has suggested these in her book "Autism, Pathways to Recovery."

 

[LQB]

We were at our local health market today and we found the Mercola B12 and vitamin D sprays on clearance, so we decided to try them out. The B12 spray uses methylcobolamin. After using it I experienced a strange mental state of being extremely irritated at every little annoyance. It reminded me of times in my childhood when I would explode with rage, times when I also could have been taking B vitamins. Not sure what to think of this?

I haven't noticed particular irritation but sublingual B12 before bed definitely robs me of sleep, so I confine it to daytime.

 

[monotonic]

Thanks. I hope it does calm down over time because it can be dangerous. It's one of those deceptive states of mind where you feel great and it just seems like everyone else is an idiot and you need to start breaking things and you have bizarre fantasies. And after it has passed the feeling good part seems to persist without the irritation. I'll reduce the dose, and maybe some NAC will also help.