X-Men Mutant Protocols: A1298C Homozygous

[Jorlev]

Anyone aware of A1298C-Ho being associated with low Carnitine? If so, what might be the connection?

 

[Jorlev]

Anyone know of studies done that link A1298C-Ho to low BH4?
Very hard to get my MDs to investigate without proof of the connection.

 

[Jorlev]

Question for anyone with, or knowledge of MTHFR 1298C HMZ issues:
I know that Aluminum blocks BH4 synthesis. Have a water test done and it notes acceptable limits of <50 ppb.
I got a reading of 18 ppb. The question is, though this may be acceptable for the average person, is 18 ppb enough to
affect someone with MTHFR 1298C HMZ? Anyone know a way to remove aluminum from water?
These reading are from water filtered with a Zero Water filter.

 

[Paulf]

Desperately seeking a protocol for 1298 homozygous. Started myself on Methyl Folate months ago. I take Methyl Life 40 mg per day and Methyl Support which I find effective. Also Hydroxocobalamin approx 4 to 8 mg per day. I realize that these are high dosages but it takes this much for me to feel affects. I no longer suffer from lack of attention and fatigue during the day. However I still cannot get a good night of rest. I sleep at most 5.5 to 6 hours. I am also MAO-A + and take some 5-htp to bolster seratonin at night but my mind is still racing and wakes me up at 3am and it’s very difficult to get back to sleep. I believe that lack of BH4 production may be the cause. Perhaps gabba production is being affected? I have found a supply of BH4 and will try to supplement directly. Please if there is anyone out there who is homozygous 1298 and has serious sleep issues share with me what works to solve this. I have tried EVERY sleep med, and EVERY herbal supplement (including Dr. Teitlebaum’s Sleep Revitalization Formula), hypnosis, acupuncture, and many many others. My lack of sleep leaves me with stiff muscles during the day.

 

[Critterina]

Desperately seeking a protocol for 1298 homozygous. Started myself on Methyl Folate months ago. I take Methyl Life 40 mg per day and Methyl Support which I find effective. Also Hydroxocobalamin approx 4 to 8 mg per day. I realize that these are high dosages but it takes this much for me to feel affects. I no longer suffer from lack of attention and fatigue during the day. However I still cannot get a good night of rest. I sleep at most 5.5 to 6 hours. I am also MAO-A + and take some 5-htp to bolster seratonin at night but my mind is still racing and wakes me up at 3am and it’s very difficult to get back to sleep. I believe that lack of BH4 production may be the cause. Perhaps gabba production is being affected? I have found a supply of BH4 and will try to supplement directly. Please if there is anyone out there who is homozygous 1298 and has serious sleep issues share with me what works to solve this. I have tried EVERY sleep med, and EVERY herbal supplement (including Dr. Teitlebaum’s Sleep Revitalization Formula), hypnosis, acupuncture, and many many others. My lack of sleep leaves me with stiff muscles during the day.

Paulf,

I'm hetero A1298C, and my serious sleep issues were due to muscle wasting, so I can't speak from your perspective.

I did want to point out, though, that the MAO A variant slows down the breakdown of serotonin. So, assuming you have enough BH4 (which may be a faulty assumption), you end up with more serotonin due to the MAO A variant. Unless you test low for tryptophan, I'm not sure the 5-HTP is doing you any good.

I keep reading that BH4 supplementation should be held off until you get the other cycles working. It sounds like you may still have some fine tuning to do, so go slow. Especially since you take the 5-HTP.

Tight muscles - how is your potassium? Does your heart race? Does drinking coconut water help?

Have you tried GABA? Have you tried reducing your supplements to 80% of what you're taking, now that you've been on them a while, and see if your attention and fatigue change? To me it sounds like you're over-revving your system and it's just not able to come down enough to sleep. What causes that I don't know.

I don't think anyone can really give you a protocol. Read and ask questions and learn. Experiment, but go slow. BEst wishes for a good night's sleep!

 

[Paulf]

Critterina

Thank you for this helpful response to me - a newbie. I have just made a donation to support this site and I will put future Amazon.com purchases through the Phoenix Rising link in Sasha’s July 19.

Here are my answers to your questions:

I did want to point out, though, that the MAO A variant slows down the breakdown of serotonin. So, assuming you have enough BH4 (which may be a faulty assumption), you end up with more serotonin due to the MAO A variant. Unless you test low for tryptophan, I'm not sure the 5-HTP is doing you any good.

You may be right. I have been dabbling with the seratonin precursors based on Dr. Amy Yasko’s theory that mood swings result from the backing up of seratonin to the point where one’s system “shuts off” production. Production recommences once levels become overly depleted. Yasko’s protocol for MAO A calls for supplementing with small amounts of 5-HTP throughout the day. In my case I find my mood during the day is fine. My theory is that I and the other members of my family who have the same mutation suffer from our Seratonin being “shut off” at night. For 20 years each of us wake between 1:30 am to 4:30 am with minds racing. I find the time release 5-htp so far to provide the best result in lengthening sleep duration and improving restorative sleep. But to your point it isn’t a solution. It does not feel “normal” to me. I feel drugged. I still wake up but it’s somewhat easier to get back to sleep. I do still feel that “something is missing in my head”. I don’t feel the drowsy urge to get back to rest even though I am physically and mentally exhausted. My brain is trying its hardest to push through the chemical and race just the same and the anxiety I feel is only being masked.

I keep reading that BH4 supplementation should be held off until you get the other cycles working. It sounds like you may still have some fine tuning to do, so go slow. Especially since you take the 5-HTP.

I am not sure which other cycles need attention. I no longer lack an ability to focus. I can think more clearly. I do not suffer from anxiety or panic attacks. From a symptoms perspective I am doing so much better but still have the one remaining item is sleep - which the 5-HTP is meant to address. I only want to use BH4 during illness when body stores are most taxed. I don’t even know if BH4 is the solution - in case it is but there is a better solution you and others can help me find then THANK YOU.

Tight muscles - how is your potassium?
I have never had potassium levels checked only magnesium which has historically been low. Since May of this year I have been taking a supplement containing 300 mg magnesium and 200 mg potassium because I sweat profusely and want to protect my electrolytes. I recently had a hair analysis done which showed a high level of potassium but a low level of magnesium for their respective reference ranges. At the same time I had a urine analysis done which showed a very low level of potassium being excreted and normal levels of magnesium. Could this mean my body was in fact deficient in potassium and has been “sucking it up as fast as I can injest it”?

My theory on the tight muscles is two fold. A1298C mutation screws up Nitric Oxide levels resulting in tightened unrelaxed muscles. And, the lack of proper deep sleep is resulting in shortage of growth hormone / body repair at night.

Does your heart race?

I have indeed been suffering from heart racing particularly in the evening. Today I believe this comes from exhaustion. I do not sleep well but drive myself as hard as I can, with my new mental clarity during the day. I previously saw a cardiologist and he chalked it up to the adderrall I was taking at the time. I no longer take adderrall but I still do get heart racing (albeith much less severe) in the evening and in the middle of the night at times.

Does drinking coconut water help?

I will give that a try - thanks for the suggestion.

Have you tried GABA?

Yes and no. I tried it years ago and it did absolutely nothing. If you know of a particular brand or method of ingesting it I will try it please share? In the past Ambien has helped me to stay asleep - but it is a completely physically unrestorative sleep - equivalent to not sleeping at all. Xanax like Ambien which works in the Gaba receptor realm was extremely effective for me. I explored with my doctors the possibility of taking Xanax permanently in low dose. Their concern which came to be realized was that I would grow tolerant and require increasing amounts. I found the withdrawal to be severe and when combined with Adderall which I was taking at the time (my doctors initially though I had ADHD) - I became a bit of a monster - totally uninhibited and fearless. I cannot go back there again. I looked into experimenting again with Gaba as a supplement instead. I learned that Gaba does not cross the blood brain barrier except when binded with another chemical that does - which I assumed explained my lack of success with Gaba as a supplement the first time around. Phenibut is a Gaba compound that will cross the BBB. I have never tried it. I have a bottle and only want to resort to it as an emergency measure when sleep is essential for a next day presentation or meeting. I hear this substance is addictive and cannot be a long-term solution for me (if in fact it is effective). If I could have a Xanax-like induced sleep - with no chemical residual in the morning this would be a solution. My theory is that the 1298 mutation which results in BH4 deficiency causes a shortage in supply of all the neurotransmitters including Gaba. Seratonin and Gaba are both needed for proper sleep. I can get the Seratonin fixed with 5-htp but not the other.

Have you tried reducing your supplements to 80% of what you're taking, now that you've been on them a while, and see if your attention and fatigue change? To me it sounds like you're over-revving your system and it's just not able to come down enough to sleep. What causes that I don't know.

Thanks for the suggestion. I did cut the supplements in half yesterday and will do the same today. It’s worth a try. I have been supplementing since May and have not cut back in order to test whether the benefits that have accrued to me might extend to better sleep at night on lower dosages. My experience with awful sleep has been with me for 2 decades.


I don't think anyone can really give you a protocol. Read and ask questions and learn. Experiment, but go slow. BEst wishes for a good night's sleep!

Thanks for the tips. Any suggestions from those with a 1298 mutation on what has helped for sleep and muscle aches is worth listening too. I have searched and been reading for a very long time now.

 

[Critterina]

Paulf,

I'm a newbie, too. So please take EVERYTHING I say with caution. Verify it for yourself. Experiment on yourself gently. I got my 23andMe results late July and joined PR after that.

I'm not convinced the muscles are anything but low potassium, and heart racing can be part of that too, I think. I know it's not your main problem, but if we can separate it out, it might give us a better picture.

Too much potassium isn't good either. MY story this week: my legs were tight from a short hike on Saturday, so I had three 8.4 oz boxes of coconut water (533 mg K each) on Sunday and Monday with meals, and my blood pressure Tuesday was 98/58. Last time it was like 138/76. So, it did help my legs, but probably 2 boxes would have been fine. That's what I mean by 'go slow'. Now if I'll only practice what I preach.

So, I'm hoping the reason you did such a drastic cut to your supplements yesterday was because you couldn't cut the pill in smaller pieces. Did you notice any difference?

I'd like to respond to more, but no time now. There's a post that helped me - have you seen it? http://forums.phoenixrising.me/inde...ylation-and-healing.21725/page-17#post-338867 If that's not the first post on the first page, sorry, I'm still figuring out how to's. Read the first page of this post (not all 17 of them!) and see if what Freddd says about potassium getting low when you take a lot of MTHF makes sense. Also look up symptoms of hypokalemia (that means low potassium) and hyperkalemia.

One last thought. Branch chain amino acids make ALL the difference with my sleep. My issues are different (perhaps poor protein digestion?), and when I'm awake in the night my mind is not racing. But, it's not like there's a lot of chance they'd hurt anything but your wallet to try them. I use Source Naturals and do what it says on the bottle. I got results the first day, relapsed when I ran out, the first day I was out. I think I'm an odd bird and it probably won't help you, but I thought I'd mention it, just in case. Make your own decision.

 

[Paulf]

Just an update. My PDoc referred me to an endocrine MD after taking a testosterone reading. I am now on injections for low testosterone. I feel better during the day - fewer muscle aches - better mood. DHEA and Pregnenolone have been very low always and can only be taken to normal levels when supplementing.

Are there any 1298 Homozygotes out there who can relate to this?

Also still hoping someone can chime in on their 1298 sleep remedy if there is one to be found. My pDoc put me on gabapentin but this did not help.

 

[Freddd]

Desperately seeking a protocol for 1298 homozygous. Started myself on Methyl Folate months ago. I take Methyl Life 40 mg per day and Methyl Support which I find effective. Also Hydroxocobalamin approx 4 to 8 mg per day. I realize that these are high dosages but it takes this much for me to feel affects. I no longer suffer from lack of attention and fatigue during the day. However I still cannot get a good night of rest. I sleep at most 5.5 to 6 hours. I am also MAO-A + and take some 5-htp to bolster seratonin at night but my mind is still racing and wakes me up at 3am and it’s very difficult to get back to sleep. I believe that lack of BH4 production may be the cause. Perhaps gabba production is being affected? I have found a supply of BH4 and will try to supplement directly. Please if there is anyone out there who is homozygous 1298 and has serious sleep issues share with me what works to solve this. I have tried EVERY sleep med, and EVERY herbal supplement (including Dr. Teitlebaum’s Sleep Revitalization Formula), hypnosis, acupuncture, and many many others. My lack of sleep leaves me with stiff muscles during the day.

Hi Paulf,

Lack of sufficient MeCbl in the brain can cause a multitude of sleep disorders. Lack of sufficient L-carnitine fumarate and AdoCbl can cause sleep disorders. HyCbl is generally partially effective on 30 out of 300 or so active b12 deficiency symptoms that can respond to the deadlock quartet. The stiff muscles can also clear up with the deadlock quartet and has been one of the listed symptoms for 9 years.

 

[kakrpa]

Have u had cortisol levels tested? Before I did genetic testing (a1298 heterozygous), I met with a naturopath for diff testing. Results re cortisol came back showing a remarkable rise in cortisol during the night, peaking at about 7am. She asked if I frequently woke up in the middle of the night, or had trouble sleeping. I don't, but I'm more of a heavy sleeper, so this cortisol level may impact a light sleeper more severely. No idea if this helps, but I hope u get the answers and sleep u need!
p.s. for a1298c'rs, I started taking 7.5mg deplin about two weeks ago and noticed a positive diff the first day. At first thought it was just placebo, but am beginning to think otherwise. I'll keep on it and see if the trend continues.

Just an update. My PDoc referred me to an endocrine MD after taking a testosterone reading. I am now on injections for low testosterone. I feel better during the day - fewer muscle aches - better mood. DHEA and Pregnenolone have been very low always and can only be taken to normal levels when supplementing.

Are there any 1298 Homozygotes out there who can relate to this?

Also still hoping someone can chime in on their 1298 sleep remedy if there is one to be found. My pDoc put me on gabapentin but this did not help.

 

[kakrpa]

Forgot to mention that I've been taking Seriphos (amazon) since receiving my wacky cortisol results. It has definitely calmed me to an extent, and I believe it's doing 'something', lol, though I'm not familiar with its exact biochemical function. HTH!

Have u had cortisol levels tested? Before I did genetic testing (a1298 heterozygous), I met with a naturopath for diff testing. Results re cortisol came back showing a remarkable rise in cortisol during the night, peaking at about 7am. She asked if I frequently woke up in the middle of the night, or had trouble sleeping. I don't, but I'm more of a heavy sleeper, so this cortisol level may impact a light sleeper more severely. No idea if this helps, but I hope u get the answers and sleep u need!
p.s. for a1298c'rs, I started taking 7.5mg deplin about two weeks ago and noticed a positive diff the first day. At first thought it was just placebo, but am beginning to think otherwise. I'll keep on it and see if the trend continues.

 

[trollo]

I don't remember off the top of my head but I am pretty sure the video lecture discusses the lithium connection. But again one of my takeaways was the inflammation stress put on the biopterin vs neopterin production which can be huge.

I think where the jury is still out is if methylfolate truly is a cofactor for production of BH4 or instead about the recycling from BH2 (which is known in the literature). Dr Yasko and others in her court emphatically claim that methylfolate upregulates the primary production path for BH4 but to my knowledge there is no scientific research that conclusively shows this to be the case. Regardless methylfolate will bolster BH4 levels whether by recycling or by indirect mechanisms. I am not arguing with the clinical observations. Just being careful to jump to conclusions on the precise biochemical mechanism.

And yes it does cross the BBB.

Here is a research article regarding oral BH4 for PKU patients:
http://www.biopku.org/pdf/fiege.pdf

I think you re wrong. The Yasko theory is that MTHFR interact with THE RECYCLING of BH4 not the direct production (there are several recycling pathways, like the well known DHFR), and in fact i think THIS is a yasko theory. At least i m not able to find any validation about a connection between MTHFR activity and BH4 recycling. You said that this is "known in literature", please can you share this literature with me??? I m looking for it since a few monthes without success.

 

[trollo]

Also about pushing the BH4 production through 5 mthf or directly with BH4 or biopterin, i found out this studiy, i think everybody should have a look to it...
http://biopku.org/pdf/choi58.pdf
I think it could be dangerous unless there is a test that prooves we have lower bh4 levels than normal

 

[sutton08]

That is taken from the Yasko handbook almost verbatim.

I had forgotten about the lithium connection. The actual mechanism involving MTHFR and BH4 is in dispute. Not everyone buys Yasko's theory on this. I am undecided.

HB12 is a poor surrogate for lowering peroxynitrites. I think the jury is out if lowering or raising NO is a good or a bad thing dependent on how one deals with peroxynitrites and other nitrogen radicals.

The link to glutamine and ammonia is also a matter of controversy. Yasko et all typically forbid glutamine. Yet like the author (Helen) I find glutamine to be beneficial. Yucca is promising for my own testing but for some reason induces reflux in me (? not sure?).

I believe mb12 is superior to hb12 for almost any scenario. If someone has COMT -/- then maybe they just can't stand too high a level of mb12. I have a hard time reconciling hb12 for any reason.

Again one of the biggest missing elements is inflammation. If bad enough it will trump most of the other measures taken.

Here it is explained in a lecture: http://vimeo.com/31010898

dbkita,
I just registered at this forum...I am homozygous 1298c and have also been curious as to why yucca doesn't agree with me either (reflux). I've been treating my CFS/autoimmune condition(s) for 2+ years with diet and supplements and was excited about trying yucca, but I find that I can't really tolerate it. Have you figured anything out since this post?

 

[kel88]

No one tryed BH4/kuvan? Why should directly supplemental with BH4 be a problem? Low bh4 is the problem right with a1298c so why not direclty take the BH4?

In going to try it myself! Its such a shame that i dont find people who teyed kuvan! Only one at autisme page...

 

[garyfritz]

@Paulf, I'm ++A1298C and I have sleep issues related to muscles. Not the same as yours, but maybe there are some similar origins. My issues manifest as muscle twitching -- I used to totally tear the bed apart from about 1-5am because I was thrashing like a fish out of water. This is combined with mental agitation, sometimes a wired can't-sleep state, sometimes a nightmarish semi-conscious state.

My miracle was B12. I take large doses of methyl B12, adenosyl B12, and methyl folate. (Currently about 1.5 mg methyl and 4.5 mg adenosyl, effective absorbed dose -- might take 20-30mg or more methyl B12 to get 1.5 mg absorbed with sublinguals.) If I don't get enough B12, I'll wake up wired and probably twitching. I can lay there like that for hours -- it won't resolve on its own. Then I can take some B12 and within a few minutes I feel an "aaahhhh" reaction. The tension drains out of my body, my muscles relax, and almost immediately I fall asleep.

I also take 100mg 5HTP to help me go back to sleep if I wake in the night.

And BTW I've also always been borderline low testosterone, with most of the resulting symptoms. My MD put me on testo troches for a while, maybe 10-15 yrs ago, but never injections.

 

[kel88]

@garyfritz you dont have CBS mutations or well? Because you can take that much "methyldonors"??
I will also take large amounts of methyl b12 but im unable because of the CBS homozygous mutation

 

[garyfritz]

Yes @kel88, I am ++ CBS A13637G. I don't understand the interactions, but B12 has never been a problem for me. Quite the opposite -- it gives me relief from a number of symptoms.

 

[kel88]

@garyfritz whatare youre other mutations? Or only CBS?

 

[garyfritz]

See my sig...