Pereise1

The Cure For Narcolepsy

94 posts in this topic

Just read most of this --- fascinating stuff guys. 

 

I have posted about my personal "trial" on this forum into intermittent fasting the last 3 or so years of my life. It has been a game changer. I don't know all of the mechanisms behind it though, only theories. 

The histamine stuff is very interesting. On my bad nights when I can't fall asleep (which is always odd) I often take a benadryl. Sometimes I have a hangover effect, but often it works pretty well and I wake up feeling rested. 

Edit: Walking 30 - 40 min in the afternoon has worked wonders well. I get a lot of light in then which helps reset my clock. Most of my day is spent in an office which doesn't help with the whole "natural lighting" thing. 

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@Nocturne Hope I can provide a few answers, Orexin is involved in a lot more than just wakefulness:

1. One of the major input sites from Orexin is the Tuberomammillary Nucleus, a major site of histaminergic neurons. As is the case with all neurotransmitters/peptides, histamine has more than one function, being critical in the maintenance of wakefulness. That's why certain N medications have CNS histamine activating actions, such as (ar)modafinil and pitolisant. Histamine in the CNS has many more roles than histamine released from mast cell activation (allergy, inflammation). One of the important actions it has is activating arginine-vasopressin (AVP), a hormone that signals the body to retain water. A dysfunction in releasing AVP, as is seen in mold illness or general histamine or cholinergic dysfunction, means retaining less water and constant dehydration. So less orexin = less CNS histamine = less AVP/hydration:

Quote

 

Abstract

The hypothalamic neurotransmitter histamine (HA) induces arginine vasopressin (AVP) release when administered centrally. We studied and characterized this effect of HA with respect to receptor involvement. In addition, we studied the possible role of hypothalamic histaminergic neurons in the mediation of a physiological stimulus (dehydration) for AVP secretion. Intracerebroventricular administration of HA, the H1-receptor agonists 2(3-bromophenyl)HA and 2-thiazolylethylamine, or the H2-receptor agonists amthamine or 4-methyl-HA stimulated AVP secretion. The stimulatory action of HA on AVP was inhibited by pretreatment with the H1-receptor antagonist mepyramine or the H2-receptor antagonist cimetidine. Twenty-four hours of dehydration elevated the plasma osmolality from 298 +/- 3 to 310 +/- 3 mmol/liter and increased the plasma AVP concentration 4-fold. The hypothalamic content of HA and its metabolite tele-methyl-HA was elevated in response to dehydration, indicating an increased synthesis and release of hypothalamic HA. Dehydration-induced AVP secretion was lowered when neuronal HA synthesis was inhibited by the administration of (S) alpha-fluoromethylhistidine or when the animals were pretreated with the H3-receptor agonist R(alpha)methylhistamine, which inhibits the release and synthesis of HA, the H1-receptor antagonists mepyramine and cetirizine, or the H2-receptor antagonists cimetidine and ranitidine. We conclude that HA, via activation of both H1- and H2-receptors, stimulates AVP release and that HA is a physiological regulator of AVP secretion.

 

As for the urticaria, can't really help much there as I haven't heard of increased allergies from Narcolepsy.

2. Hypoxia, or a faulty response to hypoxia, seems to be common to Narcolepsy. Here's a pair of studies that speak of the role of orexin in breathing: 

http://www.sciencedirect.com/science/article/pii/S0306452210015587 ("Hypocretin-1 (orexin A) prevents the effects of hypoxia/hypercapnia and enhances the GABAergic pathway from the lateral paragigantocellular nucleus to cardiac vagal neurons in the nucleus ambiguus")

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2049199/ ("The neurohormone orexin stimulates hypoxia-inducible factor-1 activity")

Despite orexin having a role, the following study seems to suggest that it may have more to do with our HLA type (genetic) as opposed to simple orexin destruction. Either way, there's definitely a scientific basis to faulty breathing being a part of Narcolepsy:

Quote

Narcolepsy is a debilitating sleep disorder characterized by excessive daytime sleepiness, cataplexy and intrusive rapid–eye movement sleep. Deficits in endogenous orexins are a major pathogenic component of the disease. This disorder is also associated with the gene marker HLADQB1*0602. Orexins as hypothalamic neuropeptides have multiple physiological functions, and their primary functions are regulation of the sleep–wake cycle and feeding. Evidence from animal studies using orexin knockout mice and focal microdialysis of an orexin receptor antagonist at the retrotrapezoid nucleus and medullary raphe in rats demonstrated that orexins also contribute to respiratory regulation in a vigilance state–dependent manner, as animals with orexin dysregulation have attenuated hypercapnic ventilatory responses predominantly in wakefulness. These findings are consistent with the notion that the activity of orexinergic neurons is higher during wake than sleep periods. Orexin neurons seem to be a pivotal link between conscious and unconscious brain functions in animals. The human model of hypocretin deficiency is patients with narcolepsy–cataplexy. In contrast to the findings suggested by animal studies, we found significant decreases in hypoxic responsiveness, but not in hypercapnic responsiveness, in narcoleptics, and further analysis indicated that decreased ventilatory responses to hypoxia in human narcolepsy–cataplexy is in relation to HLA-DQB1*0602 status, not hypocretin deficiency. This is confirmed by the fact that the hypoxic responsiveness was lower in HLA positive versus negative controls. Unlike in mice, hypocretin-1 is not a major factor contributing to depressed hypoxic responses in humans. Species differences may exist.

3. Have you had any continuous exposure to mold or water damaged buildings? A lot of what you're describing, like the loss of smell, is more typical of mold illness than Narcolepsy. It took me a while, not until I started supplementing intranasal Orexin-A, that I realized that a lot of my symptoms were part of my mold illness and not from my narcolepsy, like constant sinus issues, altered smell, and strange allergic symptoms. Also, as @HBr mentioned, it'd help to know what meds you're on at the moment. Amphetamine also lowers aldosterone, which is another hormone involved in hydration, and can usually be helped by having some licorice tea every once in a while. Hope some of that info helped.

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22 hours ago, NetiNeti said:

Just read most of this --- fascinating stuff guys. 

 

I have posted about my personal "trial" on this forum into intermittent fasting the last 3 or so years of my life. It has been a game changer. I don't know all of the mechanisms behind it though, only theories. 

The histamine stuff is very interesting. On my bad nights when I can't fall asleep (which is always odd) I often take a benadryl. Sometimes I have a hangover effect, but often it works pretty well and I wake up feeling rested. 

Edit: Walking 30 - 40 min in the afternoon has worked wonders well. I get a lot of light in then which helps reset my clock. Most of my day is spent in an office which doesn't help with the whole "natural lighting" thing. 

I've wanted to try intermittent fasting for a while, as there's a lot of evidence that it's great for wakefulness, metabolism, autoimmunity, and a host of other things. Unfortunately, my inconsistent schedule and lack of willpower have gotten in the way every time. It should definitely help with helping cure Narcolepsy one day, as it increases ghrelin which upregulates orexin. And yes, the natural light is a massive help, the days I'm most tired are also the days I get the least natural light I.E. work days.

As for the insomnia, I'd personally avoid benadryl/diphenhydramine at all costs due to it's dirty anticholinergic effects and implication in Alzheimer's pathogenesis. If histamine seems to be a problem in getting to sleep, I'd personally go with Feverfew, which is a potent 5-HT2A antagonist ( + slow wave sleep), lowers histamine, and is a potent neuro anti-inflammatory (https://examine.com/supplements/feverfew/). Alternatively, you can try lavender, which lowers histamine and acetylcholine without affecting the receptors. Same with Stinging Nettle.

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@Pereise1 Thanks for the feedback. I will look into Feverfew. I've been using it so long not (intermittently) I haven't really questioned it much.

 

I would defiantly recommend fasting. The first 3-6 months are the hardest as your body learns to adjust to the new way of eating. Now its completely fine. That plus a lower carb diet have been game changers. 

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12 hours ago, Jacky said:

Is anyone tracking body temperature changes - if so what are you using??!!

Can't say I am, although I'm aware that I always feel hot. Strangely, if it's cold enough to lower my internal body temperature, it takes forever for my body to warm up again, although it's still less annoying than the heat so it's still a welcome change. The Lateral Hypothalamus regulates body temperature so it's not surprising there would be some related problem. Haven't really looked into ways of lowering this unfortunately.

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29 minutes ago, NetiNeti said:

@Pereise1 Thanks for the feedback. I will look into Feverfew. I've been using it so long not (intermittently) I haven't really questioned it much.

 

I would defiantly recommend fasting. The first 3-6 months are the hardest as your body learns to adjust to the new way of eating. Now its completely fine. That plus a lower carb diet have been game changers. 

It's probably the best thing for me I haven't actually tried yet. I have massively lowered my carb intake over the last few years and it definitely helps with my symptoms. Sigh... one day I'll be able to rough it and finally start intermittent fasting. Too many things going on right now though.

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1 hour ago, Pereise1 said:

It's probably the best thing for me I haven't actually tried yet. I have massively lowered my carb intake over the last few years and it definitely helps with my symptoms. Sigh... one day I'll be able to rough it and finally start intermittent fasting. Too many things going on right now though.

If you are interested in fasting - check out the fasting mimicking diet - it's a vegan high fat eating regime - you still get to 'eat' but your body behaves as though fasting.  Valter Longo is the creator http://gero.usc.edu/faculty/longo/

And to make it doable - you can purchase the 5 day eating programme ready prepared in a box - I'm really not meaning to push his product, but it's the best fasting solution I've come across.  https://prolonfmd.com/

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1 hour ago, Pereise1 said:

Can't say I am, although I'm aware that I always feel hot. Strangely, if it's cold enough to lower my internal body temperature, it takes forever for my body to warm up again, although it's still less annoying than the heat so it's still a welcome change. The Lateral Hypothalamus regulates body temperature so it's not surprising there would be some related problem. Haven't really looked into ways of lowering this unfortunately.

I'm wondering whether the temperature increases are also responsible for the continuation of the fight against the autoimmune system. 

Manipulation of Core Body and Skin Temperature Improves Vigilance and Maintenance of Wakefulness in Narcolepsy  2008 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2225580/ has suggestions for monitoring and regulating. 

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@Pereise1 Here is my overall theory into why it works (minus the anti-inflammatory and glucose regulation stuff) and what I do: 

 

 

@Jacky I'll check it out, but I am hesitant. 

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@Pereise1That's a lot of interesting information right there, glad I joined the discussion since I've been figuring a lot of this stuff out for myself the past few years. 

To answer: after two unsuccesful trials with xyrem I have been faring quite well without medication. I generally don't eat a lot during the day, at least no heavy meals, and drink a lot of water, but that gets released quite fast, which would be explained by the vasopressin-part. 

As I already mentioned: I'm a fulltime artist, so I have a studio where I get to make my own hours, which makes coping a little easier, although keeping productivity up is still a hassle. I also work on large murals, which means I might be very active for a week or two (on my feet, and pushing through sleep attacks) and then recovering in my studio for the next week or two. 

My wakefulness seems very much tied to periods in which my main wakeful hours shift every week or two. I have tried xyrem for a while, but found its effects on my general mood quite bad. Did two trials of about three months each, slowly building up, but both times ended up with bouts of severe black mood, which I normally don't have. I also quite disliked the idea of being tied to this expensive drug for the rest of my days, and worried about being blacked out during the night. 

During the past two years a shift occurred in which general symptoms and severity of especially the hallucinations/hypnagogic state, lessened. At the same time my water/hydration management got out of whack, which stopped me from getting enough exercise. For the first time in my life I nearly fainted during exercise, which was a red flag. Also my heart seems to have trouble pumping enough blood, which could relate to dehydration yet again. Especially severe conditions like exercise or going on a rollercoaster made me feel very bad and light headed. While general wakefulness increased and cataplexy is quite manageable, my body does feel quite distressed all the time. Lots of aches and small things I never used to have: shaking muscles, especially after carrying stuff, a lot less general energy and trouble relaxing. As I also already stated I see quite a pattern in the cycles of dehydration, bodily stress, histamine release and breathing: each are very indicative of a sleep-attack onset, which (if not suppressed) occur just about every 2 hours. The attacks have shortened somewhat during the last two years. Oh, and I tend to do one test per year on general health/vitamins, which (even when heavily supplemented) always show very low vitamjn D and suboptimal B12.

I keep a dated journal with experiments to improve wakefulness and productivity and also write down dreams and hypnagogic experiences in my sketchbooks. So there's a lot of stuff I'm leaving out here, but this is a general impression of the current state. 

Edit: I would be quite interested to know if you have solved your mold issue, and how. The last studio I had, and especially the one I have now did have some issues with mold that had to be resolved before moving in. Never thought about that. Could I be more susceptible to this by way of the low vitamin D/lowered state of immune response? Also: how would one best compensate for the absent AVP? I have tried upping my water intake to levels where I go to the bathroom more (now I go about two or sometimes three times every day, even when drinking up to 3,5/4 litres) but it's unreasonable to be chugging even more water I think. Also I just don't feel when I'm dehydrated: there's no real thirst, just as there is (almost) no sense of smell. I'm 6'8, so 4 litres is about the optimal I can go for during a day. I also tried drinking water with salt in it, which does seem to help with the tingling hands and feet. 

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14 hours ago, Nocturne said:

low vitamin D

How much do you supplement vit D? I currently take 4000IU, but I believe you can go up to double that.

14 hours ago, Nocturne said:

lowered state of immune response

Have you tried Aswaganda? This was recommended to me by Natdoc and I like its effect. You can find it as a tincture in natural health food stores and it is added to a glass of water for easy consumption. In the evening, I like to consume a bowl of probiotic yoghurt mixed with some whole grains for fibre, plus a little fruit like a banana, plus powdered prebiotic inulin (ground jerusalem artichoke). That should help with your immune system and sleep.

14 hours ago, Nocturne said:

drinking up to 3,5/4 litres

You should likely watch the level of all your electrolytes - sodium, potassium, calcium, and magnesium.

Always consult your doctor on such matters.

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Is it really true that the forum is closing??  Any suggestions/desire for setting something else up to keep this going???????

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Shall we all move to reddit then?

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On 6/20/2017 at 6:54 PM, Nocturne said:

@Pereise1That's a lot of interesting information right there, glad I joined the discussion since I've been figuring a lot of this stuff out for myself the past few years. 

To answer: after two unsuccesful trials with xyrem I have been faring quite well without medication. I generally don't eat a lot during the day, at least no heavy meals, and drink a lot of water, but that gets released quite fast, which would be explained by the vasopressin-part. 

As I already mentioned: I'm a fulltime artist, so I have a studio where I get to make my own hours, which makes coping a little easier, although keeping productivity up is still a hassle. I also work on large murals, which means I might be very active for a week or two (on my feet, and pushing through sleep attacks) and then recovering in my studio for the next week or two. 

My wakefulness seems very much tied to periods in which my main wakeful hours shift every week or two. I have tried xyrem for a while, but found its effects on my general mood quite bad. Did two trials of about three months each, slowly building up, but both times ended up with bouts of severe black mood, which I normally don't have. I also quite disliked the idea of being tied to this expensive drug for the rest of my days, and worried about being blacked out during the night. 

During the past two years a shift occurred in which general symptoms and severity of especially the hallucinations/hypnagogic state, lessened. At the same time my water/hydration management got out of whack, which stopped me from getting enough exercise. For the first time in my life I nearly fainted during exercise, which was a red flag. Also my heart seems to have trouble pumping enough blood, which could relate to dehydration yet again. Especially severe conditions like exercise or going on a rollercoaster made me feel very bad and light headed. While general wakefulness increased and cataplexy is quite manageable, my body does feel quite distressed all the time. Lots of aches and small things I never used to have: shaking muscles, especially after carrying stuff, a lot less general energy and trouble relaxing. As I also already stated I see quite a pattern in the cycles of dehydration, bodily stress, histamine release and breathing: each are very indicative of a sleep-attack onset, which (if not suppressed) occur just about every 2 hours. The attacks have shortened somewhat during the last two years. Oh, and I tend to do one test per year on general health/vitamins, which (even when heavily supplemented) always show very low vitamjn D and suboptimal B12.

I keep a dated journal with experiments to improve wakefulness and productivity and also write down dreams and hypnagogic experiences in my sketchbooks. So there's a lot of stuff I'm leaving out here, but this is a general impression of the current state. 

Edit: I would be quite interested to know if you have solved your mold issue, and how. The last studio I had, and especially the one I have now did have some issues with mold that had to be resolved before moving in. Never thought about that. Could I be more susceptible to this by way of the low vitamin D/lowered state of immune response? Also: how would one best compensate for the absent AVP? I have tried upping my water intake to levels where I go to the bathroom more (now I go about two or sometimes three times every day, even when drinking up to 3,5/4 litres) but it's unreasonable to be chugging even more water I think. Also I just don't feel when I'm dehydrated: there's no real thirst, just as there is (almost) no sense of smell. I'm 6'8, so 4 litres is about the optimal I can go for during a day. I also tried drinking water with salt in it, which does seem to help with the tingling hands and feet. 

I haven't resolved the mold issue, I still live in a house with mold problems and I still have the same issues with excessive memory loss, brain fog, photosensitivity, constant dehydration and constant trips to the restroom whenever I try to re-hydrate myself. As for the AVP issues, I have seen Desmopressin, a safer synthetic version of AVP, being sold on a number of credible online pharmacies. Of course, it's a hormone so I'd read up well on it before deciding to try it but it seems to be the best option. Aside from that, Licorice increases aldosterone, also involved in hydration. For vasopressin, it seems Forskolin has similar effects (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1193004/).

It can be a huge rollercoaster sometimes, despite everything, ups and downs seem to be normal for me now. Here's hoping you can find a solution for the hydration issues.

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I haven't heard of anything either as far as the forum closing, no announcements, and no emails. I'm personally not a fan of reddit's format as it pushes down quality conversations irregardless of the popularity of it. It's a nice place to vent, but their Narcolepsy subreddit doesn't seem to be particularly open to scientific discussion or alternative treatment options for those of us who don't feel 100% with current Rx options, which is pretty much everyone.

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There is a lot of work and research that has gone into this thread. Please copy and paste it somewhere onto something for your future reference just in case the forum does shut down.

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Proboards let you create and manage a free forum (has pop up ads though!), or RareConnect.org have a narcolepsy group that we could join??

Fingers crossed that the email saying this forum is closing is a hoax.

 

Edited by Jacky

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