Blocking Inflammation From PUFA Reverses Brain Aging

[Blossom]

Maybe pau d'arco or haidut's new product would be worth looking into. Pau d'arco worked nicely for me as a mucolytic when I was experiencing some bronchial congestion last year.

 

[ecstatichamster]

I have not tried extra B12. I do use methods to increase CO2, such as breathing with mouth shut, tenting blanket over face at night, and B7 increasing CO2. I do not think my problem is dominantly a CO2 issue as this seems to come on in a seasonal way and has responded to inhalers and leukotriene inhibitor more than anything.

you may not think so, but I think so. I have never seen a cough like you describe that wasn't fixed with higher CO2. Seasonal and inhalers and whatnot doesn't mean anything...it STILL is most likely low CO2.

Just because you are doing those things doesn't mean they are effective. Buteyko method involves the control pause (CP) which is a measurement of progress and a feedback loop.

I've worked with a lot of coughers and CO2 raising is almost ALWAYS the way to fix the cough.

CP under 15 involves coughing quite often. You don't need to raise it all that much to stop the coughing. But just doing things without measuring your results and without a feedback loop doesn't accomplish the goal.

 

[Peata]

It's that seasonal thing I get every year, end of Sept - Spring. Haven't needed an inhaler, singulair, advair, etc. for months now. No issues at all. So I don't think my CO2 elevated on its own to fix the problem half the year every year, though I could be wrong of course. I'm not trying to be obstinate about it. Petting a cat can set it off, for example any time of year.

 

[Philomath]

This study is important on several levels. First, it shows that it is possible to fully reverse brain aging. Second, it suggests that one of the main mechanisms for brain aging is inflammation induced by the primary metabolites of PUFA - the leukotrienes. I talked about them in my first show with Danny Roddy. So, how can PUFA be good for us if its metabolites cause inflammation and brain aging, and bloking their effect or inhibiting their synthesis reverses brain aging?!?! Show this to your doctor the next time he tries to tell you about "essential" fatty acids.
Finally, the study suggests that there are drugs that can block some of the negative effects of already stored PUFA. Scroll to the end for more on that.

https://www.newscientist.com/article/dn ... AL-twitter

"...A drug called montelukast (Singulair), regularly prescribed for asthma and allergic rhinitis, blocks these receptors, so Aigner and his colleagues tried it on young and old rats. The team used oral doses equivalent to those taken by people with asthma. The older animals were 20 months old – roughly equivalent to between 65 and 75 in human years. The younger rats were 4 months old – about 17 in human years. The animals were fed the drug daily for six weeks, while another set of young and old rats were left untreated. There were 20 young and 14 old rats in total....By the end of their six-week drug regime, though, old animals performed as well as their younger companions. “We’ve restored learning and memory 100 per cent, to a level comparable with youth,” says Aigner. He presented his findings last week at the Society for Neuroscience meeting in Chicago."

The drug used to reverse brain aging is called montelukast and it acts as a leukotriene antagonist. I guess in Peat-world you can also call it a partial PUFA antagonist, with aspirin being another.

Montelukast - Wikipedia

Another related drug that has the same effect is called zafirlukast. The second drug acts by inhibiting the enzyme 5-lipoxygenase (5-LO), which prevents leukotrienes from even getting synthesized. So, montelukast is to zafirlukast what cyproheptadine is to fenclonine, so to speak. According to the FDA database, both montelukast and zafirlukast have nearly identical effects. Why am I bringing this up? Because another very potent 5-LO inhibitor is good ole' minocycline.
https://en.wikipedia.org/wiki/Arachidon ... inhibitors

And since this would not be a haidut post without an honorable mention of cyproheptadine, this study shows that cyproheptadine is also a leukotriene antagonist, albeit weaker than montelukast:
Leukotriene cysLT1 (LTD4) receptor antagonism of H1-antihistamines: an in vitro study. - PubMed - NCBI

So there you have it - restricting PUFA intake, or taking minocycline reverses brain aging. This is really not that surprising, minocycline has been shown in animal models to inhibit pretty much every neurodegenerative condition (MS, ALS, AD, PD, etc). Guess what they all have in common? Inflammation.

Btw, this study raises the interesting possibility of using minocycline (or other tetracyclines) or cyproheptadine to block some of the effects of already ingested PUFA. Taking aspirin as well should block the remaining.

"We analysed the effects of a 6-week oral montelukast (10 mg kg−1 body weight) treatment of young (4-months old) and old (20-months old) rats on learning and memory."
Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug : Nature Communications

 

[haidut]

"We analysed the effects of a 6-week oral montelukast (10 mg kg−1 body weight) treatment of young (4-months old) and old (20-months old) rats on learning and memory."
Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug : Nature Communications

Just wanted to add that ketotifen may be able to do the same at lower doses. It is also a leukotriene antagonist, it is anticholinergic, and human doses are in the 1mg-2mg range.

 

[Philomath]

Just wanted to add that ketotifen may be able to do the same at lower doses. It is also a leukotriene antagonist, it is anticholinergic, and human doses are in the 1mg-2mg range.

"Ketotifen has a chemical structure similar to some first-generation antihistamines, such as cyproheptadine and azatidene."
Ketotifen in the management of chronic urticaria: resurrection of an old drug

 

[haidut]

"Ketotifen has a chemical structure similar to some first-generation antihistamines, such as cyproheptadine and azatidene."
Ketotifen in the management of chronic urticaria: resurrection of an old drug

Ketotifen was developed as a cypro derivative. In fact, it is the same molecule with an extra ketone, hence the "keto" in the name. I don't know how well it will match the anti-serotonin properties of cypro but it is worth asking Peat about it. There are studies showing it has anti-serotonin properties, but they are indirect so not much about its serotonin receptor profile is known.

 

[Philomath]

I asked. Here was what he thought about Ketotifin:
"I haven’t used ketotifen, but I know a doctor who prescribes it occasionally. Its effects seem to be very similar to cyproheptadine’s; the presence of the sulfur, thiophene group, makes me suspect that it’s more likely to be allergenic than cyproheptadine. I don’t know whether there was a good reason for designing the structure."
I'll bet that's why it was never approved as an asthma drug here in the US.

 

[freedom]

I'm confused. Doesn't eating linoleic produce some DGLA which blocks the conversion of AA to leukotriene? If not why not just eat evening primrose oil?

Evening primrose oil (EPO) is extremely high in linoleic acid (LA) (70–74%) and γ-linolenic acid (GLA) (8–10%), which may contribute to the proper functioning of human tissues because they are precursors of anti-inflammatory eicosanoids. EPO supplementation results in an increase in plasma levels of γ-linolenic acid and its metabolite dihomo-γ-linolenic acid (DGLA). This compound is oxidized by lipoxygenase (15-LOX) to 15-hydroxyeicosatrienoic acid (15-HETrE) or, under the influence of cyclooxygenase (COX), DGLA is metabolized to series 1 prostaglandins. These compounds have anti-inflammatory and anti-proliferative properties. Furthermore, 15-HETrE blocks the conversion of arachidonic acid (AA) to leukotriene A4 (LTA4) by direct inhibition of 5-LOX:
Evening Primrose (Oenothera biennis) Biological Activity Dependent on Chemical Composition

 

[Momado965]

So aspirin, taurine, cypro, vitamin E gama, minocyline, vitamin c are all good substances for brain diabetes.

 

[Lizb]

Signez la pétition

This appeared on a Buteyko Facebook page today

 

[Momado965]

Telmisartan is an interesting drug since endurance athletes use it as a doping agent.
https://en.wikipedia.org/wiki/Telmisart ... _of_action

The *sartan drugs seem to be able to dramatically increase mitochondrial biogenesis, and reverse aging in some animal models. The related drug losartan has been to shown to reverse mitochondrial aging in rats.
Switch in Cell's 'Power Plant' Declines with Age, Rejuvenated by Drug: anti-aging blood pressure drug losartan

Btw, taurine has the same angiotensin II blocking effects as all the *sartan drugs an unsurprisingly taurine has also been found to reverse mitochondrial aging.

By mitochondrial again you mean the ability to oxidise glucose am I right? Also taurine in the sense should be similar to glycine in that effect. Can taurine be used alone and whats the dose?

 

[Mauritio]

So nobody's worrying about aspirins effect on leukotriene?
That's what travis said once about taking aspirin:

I am saying that the indicated function of cyclooxygenase inhibitors—i.e. to inhibit cyclooxygenase— invariably has the effect of of increasing substrate availability of arachidonic and eicosapentaenoic acids for 5-lipoxygenase, thereby increasing leukotriene concentrations and the consequences of such.

So basically you get less less prostaglandins but more leukotrienes, sounds pretty bad if you read the OP :
The explanation for aspirin-induced asthma was then postulated as simply being caused by shunting of arachidonic acid from the generation of prostaglandins to the biosynthesis of leukotrienes.' ―Szczeklik

 

[inthedark]

I know this is an older post, however I’d like to point out that Montelukast is now associated with a high incidence of very adverse mental/emotional side effects including hallucinations, nightmares, worsened or new anxiety and depression and suicidal thoughts and actions. It also potentially causes bad withdrawl symptoms upon cessation. The FDA was recently compelled to add a black box warning to this medication indicating the risks of these side effects. In addition I emailed Ray Peat to see if he knew anything about the medication, and did mention the study originally posted here. He told me that “there are effective alternatives that are less risky”.

I was recently prescribed this drug and initially excited to try it as it seems effective for asthma and seasonal allergies. But upon further research I’m not impressed and will be trying to get a prescription for Ketotifen or Cromoglycate instead.

What Do We Know About Montelukast and Mental Health? | Psychreg

There’s a Facebook group for people who have suffered bad side effects or have had such happen with their children: Montelukast (Singulair) Side Effects Support and Discussion Group Public Group | Facebook

While blocking the effects of Leukotrines is a great idea, it seems clear that this drug is potentially very dangerous. I wonder if it has to do with the claim that it blocks the effects of Leukotrines rather than stops the production of them?

 

[revenant]

What about St. John's wort?

"Some chemicals found in trace amounts in food, and some dietary supplements, also have been shown to inhibit 5-LOX, such as baicalein,[10] caffeic acid,[10] curcumin,[10] hyperforin[4][5][6] and St John's wort."

Antileukotriene - Wikipedia

 

[inthedark]

What about St. John's wort?

"Some chemicals found in trace amounts in food, and some dietary supplements, also have been shown to inhibit 5-LOX, such as baicalein,[10] caffeic acid,[10] curcumin,[10] hyperforin[4][5][6] and St John's wort."

Antileukotriene - Wikipedia

St. John’s wort is apparently serotonergic, which would make it frowned upon here. However it’s also apparently somewhat dopaminergic so maybe the jury is still out.

 

[inthedark]

So nobody's worrying about aspirins effect on leukotriene?
That's what travis said once about taking aspirin:



So basically you get less less prostaglandins but more leukotrienes, sounds pretty bad if you read the OP :
The explanation for aspirin-induced asthma was then postulated as simply being caused by shunting of arachidonic acid from the generation of prostaglandins to the biosynthesis of leukotrienes.' ―Szczeklik

This is very interesting. I used to get aspirin (and ibuprofen) induced asthma but no longer do, even though I use aspirin very frequently and sometimes in very large doses, and am still prone to exercise and allergen induced asthma. I wonder if this is because I’ve greatly reduced PUFA in my diet in the last few years, so perhaps there’s less Leukotrines produced.

 

[Mauritio]

This is very interesting. I used to get aspirin (and ibuprofen) induced asthma but no longer do, even though I use aspirin very frequently and sometimes in very large doses, and am still prone to exercise and allergen induced asthma. I wonder if this is because I’ve greatly reduced PUFA in my diet in the last few years, so perhaps there’s less Leukotrines produced.

Yeah probably, but I still find it curious that such a major peaty drug like aspirin has such big side effects yet I have never come across this or how significant these effects are . Neither on this forum nor at a post from peat or danny roddy .

 

[Amazoniac]

- Synthetically-tailored and nature-derived dual COX-2/5-LOX inhibitors: Structural aspects and SAR

@DaveFoster

 

[aliml]

Repurposing the asthma medication montelukast for other medical conditions

Repurposing montelukast for Alzheimer's, enlarged prostate and other age related medical conditions

montelukast-repurposed.org

I am a American living in Ghana, 75 years old and retired from the US Department of Veterans Affairs, where I worked in accounting and finance. In early 2015, I started experiencing extreme mental fatigue and had difficulty concentrating on various tasks. My doctor thought it was possible early stage Alzheimer (my mother was diagnosed with Alzheimer in her early 70's) even though my memory and problem solving abilities were not affected.

In February 2016, after reading about Dr Ludwig Aigner's research in Austria on this drug as a treatment for Alzheimer, I started taking montelukast 10 mg twice a day. Within a week, my extreme mental fatigue disappeared and I was completely back to normal. I am now taking 10 mg three times a day. I have had no bad side effects and I also sleep much more soundly.

An additional benefit was that the enlarged prostate problem I had been experiencing disappeared after about a month. Montelukast worked, whereas the prostate drugs I was taking before didn't work. This showed me that montelukast in multiple doses throughout the day can be used to treat many age related chronic inflammatory conditions. One 10 mg tablet per day as prescribed for asthma won't be effective.