11 replies to this topic

[Diesel]

I've been suffering from REM sleep behavior sleep disorder (RBD) for many years now. According to research, RBD is triggered by low-grade inflammation of the hypothalamus and brainstem causing increased REM and loss of muscle atonia, respectively. It's most often associated with neurodegenerative disorders, but it can also be idiopathic.

There are no sleep studies in my country, so I went out of my way to try the drugs commonly indicated for such a disorder, namely melatonin and clonazepam, but they weren't that effective.

I decided to target the inflammatory response itself. I came to the conclusion that these neuroinflammatory states are triggered by toll-like receptors, TLR2 and TLR4, which produce cytokines such as IL-6, TNF-α, and IL-2 via the microglia and astrocytes. Nigella sativa oil produced a modest decrease of symptoms at high dose which wasn't enough but was a step in the right direction.

I looked up substances that decrease neuronal TLR2 and TLR4 mRNA expression and there were two substances that did just that: Candesartan and lipophilic statins (Lovastatin, Simvastatin, and Atorvastatin). I'm averse to statin use since many recent studies show an increased risk of worsening or triggering Parkinson's disease, although those studies are not conclusive and further studies are needed to confirm this, I'm afraid I can't risk using a statin. I currently manage my dyslipidemia through lifestyle changes and a strict diet.

As for Candesartan, my hypertension is stage 1 so I can't take a dose high enough to have a significant effect on TLR expression. Glycyrrhizin is synergistic with it but chronic intake would mess up my HPA axis due to 11β-hydroxysteroid dehydrogenase inhibition.

I'm at my wit's end. Any suggestions would be appreciated.

Edited by Diesel, 12 March 2018 - 11:35 PM.

[Ames]

First, I'm not a doctor. See a doctor.

 

While your willingness to dive into and treat according to the research is commendable, my personal experience is that trying to hit disorders with a less specific tool, so to speak, often works the best. At least as a first measure. You can waste a lot of time and energy trying to treat with overly specific best guesses when something much less specific ultimately takes care of the issue. 

 

If I were you, what I would do is take 1.5 - 2 grams of vitamin C each morning to reduce general inflammation in the brain. This will work to a degree. It absolutely works for vascular issues in the brain. I know from experience. The key is consistency. If you ever have ischemia, for instance, start taking vitamin C. It works.

 

Two, I would take 500 mg of Taurine before 1-2 hours before sleep. You can take it at bedtime instead, but I find it smoother if taken a little before. Though, it will be harder hitting if taken before bed. I've only gotten a mild side effect, if taken too often right before bed, in a slight constriction headache upon waking. But that isn't common and I usually need to be taking it often, at that time of night, for it to occur once.

 

You can also take it during the day instead, depending on ultimate preference. Experiment with both times. The key is consistency over weeks. Sometimes taking a few days off, after 2-3 weeks, can help recover some lost potency. Overall, its a pretty consistent substance over time.

 

You can take 1000 mg, which will likely make you groggy in the morning (if taken before bed) and perhaps cause some reversable word retrieval issues during the day (if taken during the day). Though, the sedating effect will be much greater at night to the point that I don't prefer it (note, I use "sedating" non-clinically - Taurine tends to make you sleep if you need to but can actually reverse tiredness in the morning if taken then - its great that way).

 

I prefer 500mg and some time (a few weeks) to allow it to work.  

 

What you are trying to do is use a non-specific implement in Tuarine to generally (and relatively gently) cause a calming effect that will hopefully become a least semi-permanent over-time for whatever is over-active. I find that Taurine works well for this method. Its also the best (smoothest) sleep aid I've ever taken, and family members who I cant get to take anything else agree. 

 

If i gets rid of the issue for a while and it later comes back, just repeat the method. The Taurnine is the most important part. The vitamin C is only for good measure, and you can take or exclude that at your will.

 

It might be worth a shot. Give it time to work and stay consistent. The effect should build over time.

Edited by golgi1, 10 June 2018 - 06:10 AM.

[csimon02]

Check out this case study on extended release melatonin.

https://www.ncbi.nlm...0/?i=3&from=rbd sleep

[csimon02]

Another possibility, CBD oil.

https://www.ncbi.nlm...ubmed/24845114/

[Ames]

While anything is possible, I disagree that it is likely that melatonin or CBD oil would likely work for the OPs issues. He's not having issues falling asleep. He doesn't have a melatonin deficiency. I don't think that getting involved a dirty GABA effecting cannabis compound (CBD) is a good path either. Taurine acts relatively benignly on and cleanly at GABA. Cannabis compounds tend not to be so side effect free. Just my opinion.

 

My recommendations come from extended use with both substances for neurological complaints. In my experience, Taurine tends to have a medium to long term calming effect within deeper brain structures, over time and consistent use . If the OP has such inflammation, consistent relatively low dose Taurine supplementation may help. Melatonin acts more like a neurohormone with withdrawal symptom risk. My experience with Cannabis compounds, to include CBD, is that their dirty nature can lead to extremely long acting withdrawal symptoms. Think many years. This specific aspect of cannabis compounds is compounded by the fact that a person can take them indefinitely and not realize there is much of a problem (except for chronically low dopamine perhaps). This can translate to years of use that can lead to real problems should they ever want to stop in full.

Edited by golgi1, 11 June 2018 - 04:10 AM.

[John250]

I know that MK-677 will induce extreme deep state sleep but I’m not sure if that would make your symptoms worse or improve them.

[csimon02]

Diesel, have you found success? Have you tried fasting Or intermittent fasting? The is Lots of supporting data for the anti-inflammatory effects of fasting.

[micro2000]

Low dose naltrexone? Ibudilast?

[Mind_Paralysis]

Hmm... a tricky question, this one.

 

I must admit that you know a lot more than me about these inflammatory states, and RBD, than me! But, judging from the inflammatory cytokines you mentioned, then some antidepressants may actually be useful - many AD's are known to cause disruptions in sleep though... on the other hand, you have increased REM-sleep, yes? So, this may not be such a bad thing then...

 

Anyways, when you mentioned the hypothalamus I immediately started thinking about one perticular compound: BUPROPION! : D

 

It affects the hypothalamus specifically, it's rather unusual as an antidepressant as such. It decreases TNF-alpha and interferon-gamma, but sadly I don't see that you mentioned IG as a marker elevated in RBD? The effect may then be limited. What is clear though, is that Bupropion definitively alters sleep-structure! Whether or not that would be in a good way for you, remains to be seen.

 

A curious note btw... apparently some of that effect on inflammatory cytokines is supposedly through the inhibition of prostaglandins?? The reason it's curious, is because Prostaglandins are lipids... Prostaglandin inhibitors such as NSAID's are apparently also useful for hypotension, which is certainly a plus.

 

The bad note though, is that Bupropion could of course increase your blood-pressure through it's NDRI-effects...

 

I also had a look into Lewy Body Dementia, since RBD can sometimes evolve into that, as one grows older, and I sadly must say that some of the things here looked problematic... There's mention of decreased activity of the Dopamine Transporter in the disease, and Bupropion inhibits DAT... There's also mention of how Anticholinergic compounds can worsen sleep-behaviour, and Bupropion is an anticholinergic. (different receptors than what they mention though, not muscarinic, but nicotinic) So, best read up a lot on Bupropion and it's possible effects on people with both RBD and Lewy-Body dementia, if you decide to use it.

 

Very curious this... I almost feel as if there's some kind of underlying connecting thread in your diseases... lipids and RBD and the lewy bodies... HMMm! Have you looked into Alpha-Synuclein? Do you have Parkinsons or Dementia in your family?  Apparently Alpha-Synuclein is expressed a lot in the Thalamus, which borders the Hypothalamus - could there be a connection? I dunno'... but it's interesting, certainly.

 

Anyways, there's something called APOCYNIN, which could possibly be useful here... it inhibits NOX, which is a result of alpha-synuclein - and RBD seems to be connected to Dopamine, and since dopamine disturbances can be seen in both Lewy-Body Dementia and Parkinsons, then perhaps there might be something to it, yes?

 

 

It would be helpful if you could test yourself, do a full blood-panel for every inflammatory marker of BRD, to see which markers are specific to YOU - that way, would be able to select anti-inflammatory compounds which are more likely to work, even without the two drugs you cannot take.

 

 

My take though, is that you need something to put you to sleep after becoming fully awake, yet more healthy, from Bupropion - so, let's take a look at the hypothalamus! = ) Here's an old favourite of mine, Alpha-2-agonist - perhaps Dexmedetomidine

combined with gabapentin is something you could take in the evening? Along with Apocynin.

 

 

Anyways, in short, test this:

 

1. Bupropion in the morning

2. Dexmedetomidine + Apocynin in the evening

 

 

 

References:

------------------

Analgesic and anti-inflammatory activities of bupropion in animal models

https://www.ncbi.nlm...les/PMC4314873/

 

https://en.wikipedia...i/Prostaglandin

Researchers find simple blood test could help depression patients find right treatment

https://www.ctvnews....tment-1.3350590

(different disease, yes, but the basic idea may be possible to apply to any number of diseases)

 

NADPH oxidase 1, mediates alpha-synucleinopathy in Parkinson’s disease

https://www.ncbi.nlm...les/PMC3501265/

(NOX-1 inhibitors might be useful in lowering the effects of alpha-synuclein - look into those, they're anti-inflammatories, yes?)

 

https://en.wikipedia.org/wiki/Apocynin

 

Neuronal ensembles sufficient for recovery sleep and the sedative actions of α2 adrenergic agonists.

https://www.ncbi.nlm...pubmed/25706476

 

https://en.wikipedia...Dexmedetomidine

[csimon02]

Delete

Edited by csimon02, 14 August 2018 - 07:02 PM.

[csimon02]

Delete

Edited by csimon02, 14 August 2018 - 07:01 PM.

[csimon02]

Since Parkinsons and Rbd are related, I'll put this link here. Blood pressure med propranol causes increased risk of parkinsons and albuterol reduces risk. Did you say you are on bp meds?

http://blogs.science...rkinsons-puzzle