methylation in people with bipolar

[mike1127]

Has anyone here with bipolar tried any of the methylation protocols? I just started with one of the active B12 forms, adB12, and it is doing wonders for my fatigue and brain fog. However, it's not good for my bipolar... it increases the racing thoughts I have almost all the time in the mixed-state-bipolar condition I deal with. I started with 1.25 mg dibencozide and worked up to 2.5 mg/day after a week. I'm backing off, though. Taking a few days off and restarting at 1.25 mg.(Oh, it also increased irritability.)

I'm looking at other reasons that I could be compounding the bipolar. For instance, I might be producing too much epinephrine and norepinephrine when I start up methylation because I'm taking an SNRI. Maybe I need to cut back on that before ramping up methylation.

Mike

 

[Beyond]

You might have success adding Lithium orotate to the mix, its actually a methylation supplement on top of popular for bipolar.

 

[Charles555nc]

NAC has shown improvement in symptoms for people with biploar disorder. I actually gave it to my mother who has always been emotionally unstable most of her life and she become much more pleasant and rational. I take 2400mg in the morning (worked up to this dose) and two hours later I take 1600mg methyl folate (which NAC burns up), Had a herx reaction and improvement in symptoms. It kills a form of c. pneumoniae, which I had tested positive to.

My body didnt attack the c pneumoniae until I got on low dose naltrexone, which gave me improvement in symptoms but a raging case of Rosacea. I took a LDN break and slowly started it again, months later. I am convinced that alot of people with immune issues have a problem with c pneumoniae, an infection that starts in the lungs and spreads throughout the body (including the brain). C pneumoniae makes extensive use of biofilms, which makes it almost completely immune to antibiotics.

NAC "breaks up mucus" which means it helps with COPD and breaks up biofilms, so I recently added 3 grams of MSM (also antibiofilm) and 4 grams of vitamin c a day- hit another herx with lots of achyness today. My face looks better too.

 

[caledonia]

Adenosylcobalamin doesn't contain methyl groups. It works on the mitochondria. So you're not producing the neurotransmitters needed to fix the bipolar mood swings. I'm not sure of the mechanism that would increase mood problems.

It would be really good to know what your SNPs are. If you haven't done 23andme testing yet, I suggest doing it. You may have COMT/VDR SNPs which will cause mood swings if you don't take the right forms and amounts of B12.

Some people need lithium to help process B12. The lithium amounts in supplements are a lot lower than what's used for bipolar medicine.

 

[mike1127]

I just read my first post and realized I left something out. I did try mb12 after a few days on adb12, and the mb12 is what caused irritability (2 days at 250 mcg). I stopped the mb12 for now. ab12 on the other hand causes a powerful good mood, but that might not be acting on neurotransmitters, but rather causing a good mood just by reducing the muscle pain and fatigue that normally makes me cranky.

Yes, lithium as prescribed for bipolar is something like 1200 mg/day, while the supplement might give you 10 mg. But, still, it's worth a try. However, I think that looking for the COMT mutation, as you suggest, and treating that properly (by the way, how do you treat the COMT mutation naturally?) would be more effective on the bipolar.

Oh, sorry, I should mention the reason I suspect the COMT mutation is that I get a lot of benefit for bipolar mania (actually mixed state) by taking risperdal, which blocks the action of dopamine. This suggests I make too much dopamine, and it also suggests that starting up methylation is going to produce even more of excess of dopamine which is going to break down into epinephrine and cause irritability.

Mike

 

[mike1127]

Does 23andme show you the COMT/VDR SNPs? Because $99 is a lot better than the $499 testing sold by Holistic Health.

 

[Valentijn]

Does 23andme show you the COMT/VDR SNPs? Because $99 is a lot better than the $499 testing sold by Holistic Health.

23andMe is missing one of the Holistic Health SNPs - VDR Fok-1. But 23andMe has at least 7 relevant VDR SNPs which Holistic Health doesn't have. Likely 23andMe has more relevant SNPs for COMT as well.

 

[stridor]

These things are complicated. I am stable, without medication and I am 75% finished chelating mercury and suspect that I was "Mad as a Hatter". Bipolar disorder is partly due to a problem with the astrocytes in the brain. Checking the 3rd level of the dorsolateral prefrontal cortex, one finds many fewer astrocytes and the ones remaining are enlarged - no one knows how well they are functioning.
If we agree that this finding is significant then we can look at the function of the astrocytes to see if there are treatment options. We find that they produce the lion's share of glutathione for the neurons. There is a good working theory that includes low glutathione in the production of bipolar symptoms. People with methylation problems produce less glutathione - it all makes sense. What else? Astrocytes are involved in conversion of T4 to T3 in the brain. We note that the areas with the highest T3 receptor site concentrations are in the limbic (emotions) and norepinephrine (activation) areas of the brain - both involved in Bipolar. We note that there has been some success treating rapid-cyclers with thyroid meds...even when their peripheral blood tests are normal. The Astrocytes are also involved with the breakdown of glutamate which is neurotoxic is not dealt with. Too much can cause anxiety and other symptoms.
NAC should help but many of us do not tolerate it. Esp those with CBS issues. The best way to increase glutathione is by just fixing methylation and getting enough B2, Vit C and E to recycle it.
I attribute part of my success to taking thyroid meds in spite of my blood tests. I keep my T4 and T3 pegged at the tippy-top of normal range.
During my sickest I used nicotine patches which are neuroprotective in rats for glutamate toxicity. I no longer need it. I do take lithium orotate which is neuroprotective 10 mg/day
I think I will stop now. Hope that this helps. I think thyroid is your next avenue. Do some research and see what you think. brad

 

[Beyond]

Amazing comment stridor. I assume you chelated with ALA? On a side note, I took large doses of NAC in the past with my homozigous CBS C69T and had no bad reaction that I could notice. Maybe it was the brand, that was crappy, I dont know...

 

[mike1127]

Thanks for the comments everyone. I got my 23andMe results. I would be interested in how these affect my course of action in restarting methylation. I really struggle with irritability and insomnia on a daily basis, and generally speaking supplements that improve my energy level and mood also tend to worsen my irritability and insomnia, especially methyl b12. Also, how these results would affect trying to address bipolar.

COMT V158M +/+
COMT H62H +/+
VDR Bsm +/-
VDR Taq +/-
ACAT1-02 +/-
MTHFR C677T +/-
MTRR K350A +/-
BHMT-02 +/-
BHMT-04 +/+
BHMT-08 +/-
CBS C699T +/+
SHMT1 C1420T +/+

 

[caledonia]

Thanks for the comments everyone. I got my 23andMe results. I would be interested in how these affect my course of action in restarting methylation. I really struggle with irritability and insomnia on a daily basis, and generally speaking supplements that improve my energy level and mood also tend to worsen my irritability and insomnia, especially methyl b12. Also, how these results would affect trying to address bipolar.

COMT V158M +/+
COMT H62H +/+
VDR Bsm +/-
VDR Taq +/-
ACAT1-02 +/-
MTHFR C677T +/-
MTRR K350A +/-
BHMT-02 +/-
BHMT-04 +/+
BHMT-08 +/-
CBS C699T +/+
SHMT1 C1420T +/+

Thanks for getting your SNPs done and posted. This explains a lot about why you've been struggling with methylation.

You have all three First Priority mutations, so you have some work to do before you may be able to tolerate folate and B12. The mutations are SHMT, ACAT and CBS. For SHMT, you take folinic acid. For ACAT, bile salts and possibly some other stuff. Or Yasko has an all in one supplement for ACAT and BHMT. You have both of those, so this supplement would be suitable. It's kind of expensive though.

SHMT and ACAT are known as "leaky gut" genes, so it would be a good idea to check for that and treat that first. Some signs of leaky gut are multiple food intolerances/allergies. Candida and other gut bugs can cause this. You can do a test for intestinal permeability, or do a Doctors Data Comprehensive Stool Analysis to see what bugs you might have (good and bad) and the overall status of your gut. If there are problems then do a 4R gut rebuilding program to fix your gut.

Yasko says that you should supplement for SHMT and ACAT while working on the gut, otherwise treatments might not be as effective.

Ok, then onto CBS. You should check to see if this is expressed first. Some people have this SNP and don't need to treat for it, others do. If you're getting a stress/anxiety reaction from methyl supps, suspect CBS. Other signs are high ammonia, or consistently high sulfur on urine sulfate strips. For treatment, you do ammonia and sulfur lowering supps and a diet. I successfully used Heartfixer's CBS program except for I didn't do the Yasko RNA supps and I did the Free Thiol diet instead of a low sulfur diet. The Free Thiol diet is easier to do and it still works.

It's going to take many months if you need to do a gut program and a CBS treatment, so you're going to need a lot of patience. But each step should bring some improvements.

Then finally onto methylation. You have MTHFR C677T, so some methylfolate for that. Only one MTRR, so maybe a bit of B12, but not as much as someone who has MTR and a bunch of MTRR SNPs like me. You may even be able to skip B12 supplementation as long as you're not taking huge amounts of folate (due to methyl trapping).

You have almost the worst COMT/VDR combo, so for that Yasko suggests hydroxycobalamin and adenosylcobalamin to prevent mood swings. So - stay away from methylcobalamin!

You have all the BHMTs which is the secondary shortcut methylation pathway, so some TMG for that.

The combination of blocks in the primary pathway (MTHFR) and secondary pathway (BHMT) would certainly put a damper on your ability to methylate properly, thus problems with neurotransmitters and mood issues.

I have links to everything I mentioned in my signature, so check those out.

ps. If you decide to taper off the SNRI, be extremely cautious, so you don't get into a horrible withdrawal syndrome by going too fast. Doctors don't know about this and will give you too fast of a taper schedule. The best way to taper is 10% of the previous dose every 3-6 weeks. I'm tapering off Zoloft and actually going a bit slower than that - 10% every 8 weeks. It's going to take me 3 years to get off. Check out the Paxil Progress forum for more info.

 

[stridor]

Interesting about the NAC. It is also possible that as I have mercury toxicity that the single thiol was dragging Hg around. I keep trying it as it makes sense from a certain perspective to do that.
Like some with ME/CFS, I identify with the autistic community. I am aware that a portion have high cysteine and I have also wondered it that was possible.
I have 4 hetero CBS. I have a lot of problems with sulphite to sulphate conversion as well and while not tested I suspect SUOX. I have been able to return sulphur foods to my diet but these also made my symptoms worse for quite a while.

 

[Valentijn]

COMT V158M +/+
COMT H62H +/+
VDR Bsm +/-
ACAT1-02 +/-
MTHFR C677T +/-
MTRR K350A +/-
BHMT-02 +/-
BHMT-04 +/+
BHMT-08 +/-
CBS C699T +/+
SHMT1 C1420T +/+

I've crossed out the SNPs which have no research indicating that they have any impact on their genes.

MTHFR C677T +/- reduces methylfolate production to 65% of normal. SHMT1 aggravates that. Hence methylfolate supplementation is strongly indicated.

MTRR K350A is likely to result in slowed activity recycling B12 for MTR. B12 supplementation can help with that. But having the slow versions of COMT and VDR might mean that you don't tolerate additional methyl groups very well, hence hydroxoB12 might be a safer bet than methylB12, especially if you want to try higher doses.

BHMT-08 can cause homocysteine to get a little elevated, but since you have the faster version of CBS C699T, it probably isn't a problem. Contrary to some who have either not read or badly misread the research, CBS C699T +/+ is not capable of causing any problems.

I'm afraid I don't know how any of this interacts with bipolar. For irritability and difficulty sleeping (brain won't shut down), I've found that glutamate is the likely culprit in my case, and taking N-acyteylcysteine (NAC) has been helpful. Basically the NAC combines with glycine and glutamate to form glutathione, thus lowering glutamate and creating a very beneficial substance in the process. Some people need glycine instead of, or in addition to, NAC.

SUMMARY:
Methylfolate is probably needed, and hydroxoB12 may help as well. It also might be worthwhile to give NAC and/or glycine a try.

 

[stridor]

Not to belabour my point - just want to finish my thought....In the 1800's the symptoms of hypothyroid and hyperthyroid were considered to be mental illnesses. The similarity of hypothyroidism/depression and hyperthyroidism/ mania was not lost on them. Once the function of the thyroid gland was elicited, and it was noted that it did not reside within the cranial vault, this idea was largely abandoned. That was a mistake IMO.
When you tie in methylation and thyroid - Dr Lynch has videos on this which I haven't had time to watch yet - then consider the bipolar/thyroid connection, I think that there is enough here to warrant some attention. It is quite likely that methylation can contribute to the diagnosis of Bipolar in more than one way (thinking about BH4 for one) but I contend that this will be one of the main pathways. At least for those with rapid-cycling.
Coincidence or otherwise, I identify thyroid treatment with affective stability. That was Jan 2011. I continued to have the type of depression (no cycling) associated with ME/CFS until the introduction of mB12 and mfolate in Aug 2012.

 

[Beyond]

The evidence against "psychiatric/psychological illness" is growing larger. In reality we are talking about physiological (and treatable) conditons mosly, with emotional components IMO. It is sad how much suffering has been inflicted to people with toxic drugs and useless psycho-babble who could have been/be treated.

 

[stridor]

Yes, I think that you are right. I consider it along the same lines as other conditions - I'll pick cirrhosis. There is a physiological component that establishes a disease process but eventually the disease grows legs of its own and continues even if you remove the causative agent. I could have picked seizures as well, I suppose.
Whatever the cause, neurons die, cellular architecture changes and impairment can lead to more impairment. For example, one of the theories for schizophrenia includes glutamate toxicity and loss of neurons changing the way dopamine is regulated and then dopamine in access also becomes neurotoxic. Once some of these balls start to roll, they are hard to stop.
Like you suggest, early targeted treatments that deal with the underlying trigger could form the basis of treatment someday. And the world will be a better place.

 

[Beyond]

http://www.sciencedirect.com/science/article/pii/S0306987702002943

Now that there is evidence to support the hypothesis that fibromyalgia may be due to thyroid hormone resistance, four major questions appear addressable. First, can a simple biomarker be found to help diagnose it? Second, what other syndromes similar to Fibromyalgia may share a thyroid-resistant nature? Third, in non-genetic cases, how is resistance acquired? Fourth, what other methods of treatment become available through this new understanding?
Preliminary evidence suggests that serum hyaluronic acid is a simple, inexpensive, sensitive, and specific test that identifies fibromyalgia. Overlapping symptom complexes suggest that chronic fatigue syndrome, Gulf war syndrome, premenstrual syndrome, post traumatic stress disorder, breast implant silicone sensitivity syndrome, bipolar affective disorder, systemic candidiasis, myofascial pain syndrome, and idiopathic environmental intolerance are similar enough to fibromyalgia to merit investigation for possible thyroid resistance.

 

[mike1127]

stridor, I'm not familiar with thyroid meds. What specifically do you take?

Beyond, psychotherapy is very helpful and has been shown to change the brain. It's a problem when psychotherapy is thought of as the only way to correct a "disorder," but many therapists consider themselves to be helping strong people to grow emotionally and spiritually in ways that weren't possible in their families of origin. Psychotherapy has been absolutely essential for me. In fact there is no way I could recover physically without it. And it has changed my brain.

The important thing is to explore all avenues... to avoid thinking of my problems as only about biochemistry, or only about mental habits or psychological structure.

I have taken several psych meds for years, and they saved my life... but I may be in for a hard road trying to get off of them. I take Risperdal, a dopamine blocker, for the bipolar. I take Cymbalta, an SNRI.

 

[Beyond]

Everyone can have a different experience. For me, the around 10 psychologists and psychiatrists I have gone to have been between useless and humiliating. The psych meds I have tried (Trazadone,Fluoxetine, Diazepam, maybe something else) have always failed at correcting my psychological problems and gave me scary side effects.

Hehe I guess I am a bit of an extremist mike, I know someone in the right moment can have a positive impact in you, I just havent seen that with psychotherapists or the like. I see these people capable of changing your life more like couples, friends or family. And it is true some people benefit from meds, but overall they arent good compared with natural (non-toxic) alternatives.

 

[stridor]

I take dessicated thyroid and it is called "Thyroid" here in Canada. So, in other words, ground up pig thyroid glands. ` I take 90 mg/day and as well I take 50 mcg of Synthroid at bedtime.
You are right of course. Scans show that psychotherapy can help to change brains. BDNF (brain-derived-neurotrophic factor) is important for brain maintenance, new connections between neurons and in certain parts of the brain the growth of new neurons. It can be increased 4 ways: exercise, certain medication (lithium for example), learning something new -could be CBT or it could be a new language...whatever. For the life of me, I can't remember what the 4th thing was...oh well.
I am not critical of you taking meds one tiny bit. The truth of the matter is that if they worked for me, I wouldn't be here right now. Every med worked for varying periods of time (divalproex, lithium, quetiapine, olanzapine, clonazapam, bupropion, lorazapam, lamictal and maybe others) - but none could hold me. I either had an atypical Bipolar (and such might be the case if the symptoms were driven by mercury) or I had an evolving illness. Supportable as my symptoms worsened after 40 when glutathione levels start to drop....which would allow the symptoms secondary to mercury oxidation to surface.
My decision to go it alone has cost me most of my retirement savings.