Ativan, l-theanine, serotonin, gelatin, glycine, glutamate, etc.!

[Mary]

THE FIRST FOUR POSTS IN THIS THREAD HAVE BEEN MOVED FROM THE THREAD Third Annual Community Symposium on the Molecular Basis of ME/CFS Sponsored by OMF - DISCUSSION BECAUSE THEY WERE OFF-TOPIC

I took Ativan for 11 years for sleep. I started at 0.5 mg and after a couple of years went up to 1 mg., middle of the night. I liked it a lot! unfortunately of course it is addictive and I had reached a point where I was going to have to increase my dose again, which was not good. Also I'd read about the connection between benzos and Alzheimer's. So I weaned off of it, which was difficult. The Ativan did nothing to help with ME/CFS - with PEM or anything else, just sleep.

@Rufous McKinney - I found high dose vitamin C to be very helpful in getting off of Ativan. It helps with neurotoxicity caused by excess glutamate. For awhile I was taking vitamin C round the clock - every couple of hours I would take 2,000 mg or so, even during the night. https://www.ncbi.nlm.nih.gov/pubmed/25701025 Unfortunately this much vitamin C ended up making me acidic (got extra achey and tired) but I countered that with baking soda.

Taurine might also be helpful for you. https://www.ncbi.nlm.nih.gov/pubmed/15003996

I also take 5-htp, l-theanine (see post below), niacin, inositol, glycine, lots of magnesium glycinate and melatonin. Boron is supposed to help with magnesium utilization.

I have a few more suggestions re sleep, but am afraid of hijacking this thread so if you have more questions re sleep, send me a PM.

 

[SlamDancin]

L-theanine can also raise glutamate and so I’m not sure it’s a great option for pwME.

Not to knock what works for you @Mary but I’d be very wary of taking 5-htp as well. It’s not good for metabolism and pwME may already have high brain serotonin to begin with.

Glycine is good but research from Harvard on metabolites in ME shows increased Proline turnover which means collagen usage for energy most likely. Most pwME May benefit more from a Collagen hydrosylate or Gelatin which has high Proline, no tryptophan (unlike all other proteins) and almost 3g of Glycine per serving.

 

[Mary]

L-theanine can also raise glutamate and so I’m not sure it’s a great option for pwME.

I've read that too, but I think it's good to at least try it as it very well may help. And if it worsens insomnia, then stop it of course.

Not to knock what works for you @Mary but I’d be very wary of taking 5-htp as well. It’s not good for metabolism and pwME may already have high brain serotonin to begin with.

I started taking 5-htp in 2004 - it helped almost immediately with sleep so I've been taking it ever since. I had already been sick since 1998 with ME/CFS. As to whether I still need it, I don't know. It might be worth an experiment to stop it for awhile and see what happens. You might want to read about BCAAs which interestingly are supposed to counter the effects of high tryptophan in the brain and help with something called "central fatigue" caused by excess tryptophan. BCAAs have cut my PEM by more than half. There are some links to articles about BCAAs and tryptophan in this thread.

Most pwME May benefit more from a Collagen hydrosylate or Gelatin which has high Proline, no tryptophan (unlike all other proteins) and almost 3g of Glycine per serving.

I tried gelatin and did badly with it sleepwise and figured out it was the glutamate in the gelatin which I was reacting to. I had read about its high glycine content so thought it would be perfect, but unfortunately the insomnia it caused was bad. But plain glycine has been very effective for me. Actually it ended up also helping my detox pathways get working properly - but that's another story.

 

[SlamDancin]

@Mary Thanks for the well thought out response but I just want to correct a couple things and clarify.

BCAA’s, Tyrosine, Phenylalanine all compete and different ratios of the three result in changes in plasma and brain serotonin and catecholamines. Simply taking BCAA’s will lower catecholamines and so you would need to supplement Tyrosine or Phenylalanine in order to not lower DA and NE, something that I personally find is not helpful. Also when it comes to BCAA’s, @Hip explained why Isoleucine may be more effective than Leucine, and Valine concerns me because I’ve read it can raise plasma endotoxin levels. BCAA’s may also be antimetabolic. Again, it’s a PEM buster for you keep it up but things could always be better.

https://www.ncbi.nlm.nih.gov/m/pubmed/31349924/?i=9&from=5-htp

Now this might have been the paper I was remembering on 5-htp. Not only is it anti-metabolic, pro fibrotic, it can possibly do pretty severe brain and BBB damage.

Collagen contains Glutamic acid you are correct there. About 900mg a serving if I’m not mistaken. There’s probably more than that in the meat, eggs, poultry, dairy and gluten you eat though. We clearly need Proline and apparently run through that faster than Glycine and collagen is the best way to get Proline. If you take L-Proline itself it activates NMDA receptors. Seemingly the best way to deal with any neurotoxicity from the glutamic acid and L-Proline would be to take in collagen form where the Glycine should help to balance inhibitory and excitatory signaling.

Have you ever tried Quiatepine for sleep? In low doses it’s simply a H1 antagonist and and an alpha1–adrenergic antagonist. No harmful mechanisms involved and it’s much less toxic than 5-htp alone. I sleep well almost every night with it.

In general Serotonin is not a healthy molecule and when it’s supraphysiologically given like that with 5htp it tends to cause damage in every organ it’s found. Of course a minimum amount is needed for brain and gut function. I would imagine if you aren’t taking Tyrosine or Phenylalanine, that because Serotonin generally antagonizes dopamine and because the BCAA’s are depleting it’s production, that your DA/NE functioning is suffering because of these supplements.

I’m not a fan of Serotonin at all and in pwME Dopamine and NE have been found to be low, or have lower transporter function or lower signaling in the case of dopamine (also seen as higher prolactin) and so just please give this some all some thought about whether it’s necessary or possibly more harmful than the Ativan was.

 

[Mary]

Simply taking BCAA’s will lower catecholamines and so you would need to supplement Tyrosine or Phenylalanine in order to not lower DA and NE

What are DA and NE?

Also when it comes to BCAA’s, @Hip explained why Isoleucine may be more effective than Leucine,

I tried isoleucine with no benefit after reading @Hip's post on it.

As I posted earlier, gelatin did cause bad insomnia for me. I was very sensitive to anything related to glutamate or MSG. However, I don't know about collagen and will give it a try. I might have the same issues with it - it has to do with free vs. bound glutamate (they discuss that here: https://chriskresser.com/beyond-msg-could-hidden-sources-of-glutamate-be-harming-your-health/) But on the off-chance I can tolerate the collagen, and perhaps the glycine content will help offset the glutamate, I'm willing to give it a go, not least because of vanity! (possible better skin, hair, etc. )

. I would imagine if you aren’t taking Tyrosine or Phenylalanine, that because Serotonin generally antagonizes dopamine and because the BCAA’s are depleting it’s production, that your DA/NE functioning is suffering because of these supplements.

Again, what is DA/NE functioning? The BCCAs btw have helped several people on the board here with their functioning. Perhaps we should take tyrosine with it, I'll have to read more about it

Re Quetiapine (Seroquel) for sleep - I'll take my chances with 5-htp any day! Seroquel killed my mother. She was elderly (92) and had dementia, and despite a black box warning, the idiot doctor prescribed it for her anyway. She collapsed and was in the ER within 24 hours. She never really recovered and died 5 weeks later. It's an antipsychotic. She wasn't psychotic by the way. She was elderly and frail and couldn't have hurt a fly. Why he gave her that I have no idea. Some doctors should not be allowed to prescribe meds. It's like operating heavy machinery and you have to know what you're doing in order to avoid major damage. I have no desire to take something like that. I have an extremely low tolerance for prescription meds anyways (cannot take prescription anti-depressants).

 

[Moof]

I'm so sorry to hear what happened to your mum, @Mary, that's a shocking story. That type of med should never be given to elderly people.

I think DA is dopamine and NE is norepinephrine, by the way. I take BCAAs, and my neurotransmitters seem to work fine – thanks to the supplements, I'm as well as I have been since the 1970s. I don't take high doses of anything, BCAAs included, but I've taken them every day for a couple of years now. They're the only thing I've ever found that make a significant difference to my energy, stamina, and PEM, without causing side-effects.

 

[Mary]

I'm so sorry to hear what happened to your mum, @Mary, that's a shocking story.

Thanks @Moof! I'm sure it's not an isolateD incident. I think doctors routinely ignore black box warnings. I had to argue with a couple of them when they wanted to give me a fluoroquinolone for a routine UTI and an old established med worked just fine.

I think DA is dopamine and NE is norepinephrine, by the way.

Thank you for the clarification! I'll do some more reading on this (when I get the energy! ) Actually I've had nothing but good results from the BCAAs, so won't be without them!

 

[YippeeKi YOW !!]

@Mary

I was very sensitive to anything related to glutamate or MSG. However, I don't know about collagen and will give it a try

I'd approach collagen with great care. A good prequel, as it were, is: if you tolerate bone broth with no issues, than collagen may be OK for you. But it's a particularly intense form of glutamate, made from the bones, sinews, skin, connective tissue and other by-products of the meat industry, all hydrolyzed and powdered into an over-hyped and not cheap supplement. It doesnt matter if it's collagen peptides or collagen protein, it'll have the same negative effect on you if you're sensitive to glutamates.

I was sad to have to give up my gelatin cocktail for all of your reasons: I needed help with sleep, and anything that would help hair and skin was waaaaay welcome. I took me a minute to figure out what was causing my fairly standard free-glutamic acid reaction, but once I did, I sorrowfully left it behind.

Seroquel killed my mother.

Some doctors should not be allowed to prescribe meds.

Oh Lordy, I couldnt agree more. I'll take it a step further: some Drs shouldn't be licensed as Drs. Drs prescribed haldoperidol for my mother, frail and battling colon and liver cancer that her Dr had somehow missed for 2 or 3 years before I was able to wrench her away and to a kind, honest, and concerned Dr, sadly, too late. Luckily I checked her daily meds two times, sometimes three times, a day. After that, it no longer appeared in her medical records (she was in an extended care facility at the time, that I was trying desperately to get her out of), and it wasn't til a year or so after she died that I began to realize that just because they didnt record it didnt mean that they weren't still sneaking it in. I was with her 10 to 12 hours a day, but that still left a lot of time for medical mischief.

I think doctors routinely ignore black box warnings.

It's not so much that they ignore them, altho they do, but that they're so flocking arrogant that they just know that they know better. Or maybe they just don't care.

I'm so sorry that your story is so similar to mine. I'll never get over the guilt I feel, or the belief that I let mama down.

 

[Mary]

if you tolerate bone broth with no issues, than collagen may be OK for you. But it's a particularly intense form of glutamate, made from the bones, sinews, skin, connective tissue and other by-products of the meat industry, all hydrolyzed and powdered into an over-hyped and not cheap supplement. It doesnt matter if it's collagen peptides or collagen protein, it'll have the same negative effect on you if you're sensitive to glutamates.

I don't know if I tolerate bone broth. It's not something I make. But thanks for the warning! I will keep it in mind. I'm not as sensitive to MSG as I was a few years ago, I think maybe due to a couple of things: (1) I stopped pantothenic acid which depletes taurine - I had taken PA for YEARS - and taurine is needed to deal with msg toxicity! So I stopped the pantothenic acid as soon as I learned this and I now take 500 mg. taurine before bed. (2) I've been off of lorazepam for sleep for a couple of years now so I think my system has calmed down a bit. So I think collagen will be a good test. I'll go slow - and I know what to look for!

I'll never get over the guilt I feel, or the belief that I let mama down.

I'm so sorry to hear about your mother too! And you should not feel guilty - you didn't let her down, you did everything you could to help her. I'm just aghast at the number of incompetent doctors. I have to be careful because I start resenting all of them, and have to remember there are some very good ones. But we all have to watch out for ourselves and can't take anything any of them say blindly without checking.

 

[Rufous McKinney]

I don't know if I tolerate bone broth. It's not something I make.

Its not difficult to make your own, it just means your gonna be looking at bones. And they get hard to find. Especially with marrow. Used to be free, funny now.

I can get grass fed bone broth frozen..its pricey. Makes less mess in the kitchen.

 

[SlamDancin]

@Mary To be fair Mary, I’m talking about specifically low dose Seroquel, which to my knowledge and experience with doesn’t have any antipsychotic effects, only sedative. Wikipedia asserts the same and my doctor agrees. It’s a whole other beast in doses around 100mg which is the lowest prescribed dose for anti-psychotic effects. I take 12.5 mg - 25 mg. I’d really reconsider the 5-htp but I won’t badger you about it. The other posters above got it. BCAA’s can lower brain serotonin, dopamine and norepinephrine. *Can* and YMMV but I take 1.5mg-3mg Tyrosine everyday and some days 5g Isoleucine.

@YippeeKi YOW !! I’m really disappointed to hear that about hydrolyzed collagen being excitotoxic. Are there any studies that discuss this? I don’t quite know how else to rebuild collagen without the necessary aminos but I’ll check into the bone broth situation and see how feasible that is. Appreciate the info about that.

 

[Mary]

Collagen contains Glutamic acid you are correct there. About 900mg a serving if I’m not mistaken. There’s probably more than that in the meat, eggs, poultry, dairy and gluten you eat though. We clearly need Proline and apparently run through that faster than Glycine and collagen is the best way to get Proline. If you take L-Proline itself it activates NMDA receptors. Seemingly the best way to deal with any neurotoxicity from the glutamic acid and L-Proline would be to take in collagen form where the Glycine should help to balance inhibitory and excitatory signaling.

A big difference between getting glutamic acid in gelatin or collagen, vs. meat, eggs, poultry etc., is the form of gltuamic acid. When eaten in food, it's bound to other amino acids and is absorbed more slowly. In a free hydrolyzed form, it's absorbed much more quickly and that's where a lot of the problems come from. See http://www.missionheirloom.com/understanding-glutamate and https://chriskresser.com/beyond-msg-could-hidden-sources-of-glutamate-be-harming-your-health/

 

[YippeeKi YOW !!]

@SlamDancin , @Mary
I'm with Mary on the Seroquel. It's an anti-psychotic, no matter what the dose, The calming, sleep-inducing effect comes with a potentially high price tag, ie, akathisia, Parkinson’s-like tremors and movement abnormalities, weight-gain, high blood sugar, new or worsening diabetes and, in rare cases, heart arrhythmias that can cause sudden cardiac death. Quetiapine and other “atypical” antipsychotics were linked in a fairly recent Canadian Health study to all the above and a few extras, including an increased risk of sleep apnea —breaks in breathing during sleep. There's more but that should be enough.

It's a hard pill to swallow, but we need to be aware that Drs are often encouraged, energetically, by pharmaceutical companies to use various medications for off-label, non approved purposes that have little to do with our well-being, and almost no concern for the potential pitfalls and damages to patients who are already in less than perfect shape.

It's really good that it works for you, but do keep an eye out for any new and unusual developments in your system, and be aware of it's potentialities when recommending it as a solution for poor or bad sleep.

hydrolyzed collagen being excitotoxic.

Anything hydrolyzed is, almost by definition, excitotoxic, since hydrolyzation breaks the bonds between naturally occurring amino acids and turns them into little free-standing stealth bombs, unbalanced by the natural co-factor effect of their binding to other aminos, as @Mary stated above. There are innumerable studies supporting this, and I dont have the energy right now to search them out for you. Just google some key words, and you should have a night's worth of reading material, tho I wouldnt do that before bedtime. Maybe tomorrow morning, yes? It should be a real eye-opener .

I don’t quite know how else to rebuild collagen without the necessary aminos but I’ll check into the bone broth situation and see how feasible that is.

I had the same problem. After a whole lotta research, I settled on non-defatted desiccated beef liver from New Zealand, and then added desiccated bone marrow, also from New Zealand. Both are incredibly good sources of a range of vitamins and minerals in their natural forms, amino acids also in their natural form, and 6 caps is the equivalent of 1 or 2 ounces of the natural substance involved (liver and bone marrow, in this case). I filled in the need for sufficient protein with mozzarella cheese, and other un-aged cheeses, since for quite a while, I couldn't eat much of anything without reacting to it.

I wouldn't recommend bone broth if you're dealing with excitotoxic reactions, but we're all different, so YMMV. Here's a link to my post today (#34 on pg. 2) regarding all this, or at least part of this:

https://forums.phoenixrising.me/threads/glycine-advice-please.75449/page-2#post-2233551

Give some thought to the desiccated liver. I have to separate it from the capsules, which are gelatin based, because otherwise I'll have an unpleasant reaction after a few days of piling all that glutamate into my system.

Yeah, I know. The Princess and the Pea. Tedious, but it be what it be.

 

[S-VV]

@YippeeKi YOW !! What do you take to counter glutamate/NMDAR? I take 1 gram a day of magnesium bisglycinate, but it's not enough.

I'm wary of direct receptor blockers or GABA agonist, since the receptors will just over or under-regulate respectively.

I have lots of trouble falling asleep and wake up with a racing heart 6 hours later. Sometimes I will use an antihistamine or gabapentin, but I develop tolerance extremely quickly. Like if I take gabapentin to sleep, by the following morning my peripheral neuropathy is worse.

 

[S-VV]

I'm going to try l theanine, which will either hydrolize into glutamate and ethylamine or block NMDAR and glutamine uptake , which is somewhat rate limiting for glutamate synthesis.

 

[YippeeKi YOW !!]

@S-VV

@YippeeKi YOW !! What do you take to counter glutamate/NMDAR? I take 1 gram a day of magnesium bisglycinate, but it's not enough.

It's as I stated above: when I first started using mg gly for the anxiety, I went as high as 1200 - 1800 mgs a day in larger separated doses with no visible or beneficial effect. It was only whenI I brke that down in mini-doses at frequent and regular intervals, that I was able to block NMDR receptors and ccalm the glutamate storms. Initially, and for probably 6 months, I used 50 mgs every 30-60 mins, depending on how bad the excitotoxic response was. This did the trick, tho not overnight.

I'm wary of direct receptor blockers or GABA agonist, since the receptors will just over or under-regulate respectively.

I agree, esp re GABA agonists. I found no adverse responses to the large mini-dosing of mg gly, even tho it does function as an NMDA blocker. It accomplishes that largely by blocking the release of calcium into an already battered, weakened system by blocking its uptake in the NMDA receptors.

I'm going to try l theanine

L-theanine bit me on the butt bigly, and sent my anxiety and excitotoxic responses into frenzied overdrive. You might want to start slow and low til you know how it's gong to affect your system, yes?

 

[Mary]

@SlamDancin - I just wanted to give you an update. Your posts got me thinking about collagen and partly because of its purported skin benefits and also because I'm no longer as extremely sensitive to msg and glutamate as I used to be, I've started taking a collagen product and am not reacting badly to it. My muscle testing indicates it's good for me, and I've been able to cut my BCAAs in half.

I've only been taking it a little over a week, but so far so good - another DIY lab experiment! So thanks for the recommendation.

btw, grounding or earthing is helping my sleep - you might want to look into this, it might get you off the Seroquel! (I think I feel as strongly about Seroquel (if not more) as you do about 5-htp.)

fwiw, I think it's likely that my earlier extreme sensitive to msg and glutamate in all their iterations was caused by taking pantothenic acid for many years. I originally needed it at one time many years ago, and just kept taking it. Well, it depletes taurine I found out, and taurine is what helps us with glutamate excitotoxicity. So I stopped the pantothenic acid when I learned this (about 3 or 4 years ago) and my extreme msg/glutamate sensitivity has greatly lessened.

 

[YippeeKi YOW !!]

fwiw, I think it's likely that my earlier extreme sensitive to msg and glutamate in all their iterations was caused by taking pantothenic acid for many years.

It's more likely that it was as a result of Dr prescribed medications that screw bigly with GABA/Glutamate balance, and leaves us, for some reason, at the mercy of anything MSG related, at east until time and tide (ane getting off those meds) heals that.

The pantothenic acid, while quite possibly a contibuting factor, probably wouldnt be able to do that damage on its own, but who knows? Not a scientist here, so go with your gut.

 

[Mary]

It's more likely that it was as a result of Dr prescribed medications that screw bigly with GABA/Glutamate balance, and leaves us, for some reason, at the mercy of anything MSG related, at east until time and tide (ane getting off those meds) heals that.

The pantothenic acid, while quite possibly a contibuting factor, probably wouldnt be able to do that damage on its own, but who knows? Not a scientist here, so go with your gut.

Well, there are several sources which say that pantothenic acid blocks production or metabolism of taurine, so I have little doubt it was a contributing factor. But my 11 years on lorazepam for sleep I'm sure didn't help either! I've been off it now I think for around 2 years, I've lost track.

In any event, I am tolerating collagen peptides now and having mustard or a little bit of soy sauce with dinner no longer keeps me awake until 3:00 a.m.!

 

[YippeeKi YOW !!]

In any event, I am tolerating collagen peptides now and having mustard or a little bit of soy sauce with dinner no longer keeps me awake until 3:00 a.m.!

Definite signs of successful healing, and congrats, esp on the courage to slowly trial a few things that used to guarantee extended, extreme discomfort. It ain't easy !!!

Lorazepam is one of the worst GBA/Glute scramblers, so you really had a rough road there. I'm so glad that the worst is in the rear-view mirror

Like you, I've found, by trial and error, that I can now tolerate a few of the many things were absolute poison three years ago. I think both of our GABA/Glute systems are normalizing, which would be absolutely fab !!!