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Ibuprofen vs montelukast (Singulair)
Larrytherunner
Posted: Wednesday, July 4, 2018 6:56 AM
Joined: 2/26/2016
Posts: 108


In early 2015, I began feeling a tremendous mental fatigue every day, and it was especially bad when focusing on solving a problem. I also had occasional confusion. Sometimes when walking or taking a taxi, I could not remember where I was going or why.

In 2015, after reading about some research on the NSAID Ibuprofin, I started taking it 3 times a day (I don't remember the dosage) for about 3 months. I quit taking it because I could not see any improvement. and because there are some serious risks with this drug long term. 

After reading about Dr. Aigner's research using montelukast in animal research, I started taking 10 mg once a day (recommended dosage for prevention of asthma attacks). Within a few days, I felt my mental fatigue go away for about half a day. After switching to 10 mg twice a day, it went away completely. I later started taking 20 mg twice a day, and I have been taking it more than two years now, and I am completely back to normal.

Anti-inflammatory drugs, if they work, work right away and you can feel the improvement. For me, Ibuprofen did not work, and montelukast did and it also much safer for long term use. It was that simple.

Some results from the montelukast clinical trial for Alzheimer's should be available by the end of 2018 or beginning of 2019.


Birdies
Posted: Wednesday, July 4, 2018 9:57 AM
Joined: 7/3/2018
Posts: 11


Hi Larry, I’m sure you’ve read about Dr. Praticòs work with Zyleuton (Zyflo):

 http://www.philly.com/philly/health/an-asthma-drug-shows-promise-against-alzheimers-temple-university-research-20180608.html?__vfz=medium%3Dsharebar

I’ve been following your posts and see that you’ve had positive results with montelukast(Singulair).  I’m hoping to get my Mom on Zyflo (will need Dr to prescribe off label), in the meantime we’ve started her on a 5 LOX Inhibitor.  


Lane Simonian
Posted: Wednesday, July 4, 2018 3:53 PM
Joined: 12/12/2011
Posts: 4286


Nitro-oxidative stress is probably the primary trigger for Alzheimer's disease with inflammation being a secondary contributor.

Anti-inflammatory effects of the two test agents [Montelukast and L-carnitine] may be attributed partly to their anti-oxidant effects as oxidative stress triggers inflammatory cascade. 


Results. The results demonstrated pronounced oxidative stress in the institutionalized elderly group, which also had a lower antioxidant status compared to noninstitutionalized subjects. High levels of proinflammatory cytokines were also observed in the institutionalized elderly. Furthermore, the raised levels of inflammatory markers were correlated with increased oxidative stress, and both were associated with low cognitive performance. However, based on multiple linear regression analysis, oxidative stress appears to be the main factor responsible for the cognitive decline. Conclusions. The findings suggest that individuals with lower antioxidant status are more vulnerable to oxidative stress, which is associated with cognitive function, leading to reduced life quality and expectancy.

Protein kinase C is the enzyme that initially trigger nitro-oxidative stress and inflammation in Alzheimer's disease.  Without its initial activation there is no Alzheimer's disease.  Or to put it another way controlling oxidation and inflammation is the key to preventing and treating Alzheimer's disease.

Malinow’s team found that when mice are missing the PKC alpha gene, neurons functioned normally, even when amyloid beta was present. Then, when they restored PKC alpha, amyloid beta once again impaired neuronal function. In other words, amyloid beta doesn’t inhibit brain function unless PKC alpha is active.

Dozens of other factors besides amyloid beta contribute to oxidation, nitration, and inflammation in Alzheimer's disease.  Moreover, protein kinase C activation can also contribute to memory and learning as well as destroying them, so it is better to concentrate instead on finding anti-inflammatory and anti-oxidant compounds.

NSAID's like ibuprofen only partially fit this bill.

Most non-steroidal anti-inflammatory drugs were moderately (indomethacin, diclofenac, naproxen, tolmetin) or only weakly (sulindac, ibuprofen, aurothioglucose, flurbiprofen, sulphasalazine, salicylate, penicillamine disulphide) effective in preventing tyrosine nitration and alpha 1-antiproteinase inactivation by peroxynitrite, but 5-aminosalicylate and penicillamine were much more effective, as was the antibiotic tetracycline (but not ampicillin).

Tyrosine nitration (mediated by peroxynitrite) inhibits or prevents the regeneration of neurons and limits blood flow and the transport of glucose in the brain (which can lead to delusions).   Peroxynitrite damage to DNA causes inflammation and the death of neurons.

It makes sense to combine Montelukast (which is a better anti-inflammatory) with L-carnitine (which is a better anti-oxidant) in the treatment of Alzheimer's disease.

These deleterious effects are mostly due to oxidative and inflammatory pathways [this study is for lung damage but also applies to brain damage]...Regarding inflammatory progression, several mediators may arise from the COX-II cascade involving release of biologically active prostaglandins (PG`s), or may be synthesized through the action of LOX [lipoxygenase], involving leukotrienes (LT`s) which are the second main family of arachidonic acid derivatives, which also have a major role in the inflammatory process...On the other side, investigation of anti-inflammatory potential of ML and LC in the current investigation revealed true anti-inflammatory ability of both agents represented by significant reductions of COX-II and LOX levels in sera of ML or LC-pretreated rats compared with control CP [cyclophosphamide] rats...Opposite to results of oxidative parameters, ML showed more significant anti-inflammatory potential compared with LC.

Find the right combination of anti-oxidant and anti-inflammatory compounds and you at least delay the onset of Alzheimer's disease, stop its early progression, and slow its later progression.

Lane Simonian
Posted: Wednesday, July 4, 2018 5:00 PM
Joined: 12/12/2011
Posts: 4286


L-carnitine in meat is an antioxidant, but other compounds in some meats such as nitrites and nitrates can act as oxidants.  Moreover, charring meat also has oxidative effects.  

The antioxidants contained in a healthy diet may reduce or eliminate the need for supplementation.  But in some cases, supplementation with additional herbs, spices, and vitamins may be helpful.

Nitro-oxidative stress is involved in other forms of dementia, so what helps for Alzheimer's disease may help for other conditions.

Viruses, bacteria, and fungal infections can either directly or indirectly increase oxidation, nitration, and inflammation in the brain.  In the case of the recent herpes virus study, oxidation and inflammation activate specific herpes viruses which can in turn cause more oxidation and inflammation.



Lane Simonian
Posted: Wednesday, July 4, 2018 5:05 PM
Joined: 12/12/2011
Posts: 4286


The main problem in Alzheimer's research is that mice are designed to have only one factor that leads to oxidative stress (amyloid).  They are not exposed to environmental toxins, given various medications, fed lots of sugar, carbohydrates, and salt, or given cigarettes.  So they gave anti-amyloid compounds to mice and they  improved, but as every trial seems to prove, if you remove amyloid in human beings you don't successfully treat the disease.
Lane Simonian
Posted: Wednesday, July 4, 2018 5:41 PM
Joined: 12/12/2011
Posts: 4286


Naproxen and acetaminophen can scavenge peroxynitrite but they can also increase peroxynitrite levels by increasing the release of intracellular calcium.

These data suggest a revision of the original ADAPT hypothesis that NSAIDs reduce AD risk, thus: NSAIDs have an adverse effect in later stages of AD pathogenesis, while asymptomatic individuals treated with conventional NSAIDs like naproxen experience reduced AD incidence, but only after 2 – 3 years. Thus, treatment effects differ at various stages of disease. This hypothesis is consistent with data from both trials and epidemiological studies.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149804/

https://www.omicsonline.org/open-access/the-role-of-acetaminophen-in-the-development-of-dementia-2155-6121.1000172.php?aid=25634



 


dolor
Posted: Wednesday, July 4, 2018 5:46 PM
Joined: 11/9/2017
Posts: 104


Lane, right, it's a waste on so many levels.
Lane Simonian
Posted: Wednesday, July 4, 2018 6:01 PM
Joined: 12/12/2011
Posts: 4286


Thanks, dolor.  Another contradiction, tomatoes contain lycopene which is an antioxidant.

https://www.ncbi.nlm.nih.gov/pubmed/20491642

Cooking tomatoes may increase pro-inflammatory compounds, however.

The contradictions really use to get to me, but not so much anymore.  The same compound can have different effects on different parts of the body, or can trigger certain pathways that are beneficial and others that are harmful, or can be safe at one dose and not at another, or can be safe for one person but not for another, or can be harmful at one stage of life but not at another.  Often one substance contains multiple compounds which complicates things even more.  

After fourteen years of studying Alzheimer's disease, I am still not completely at ease regarding the triggers, pathways, and potential treatments for the disease, but I am less befuddled and frustrated than I was before.  


Larrytherunner
Posted: Thursday, July 5, 2018 7:23 AM
Joined: 2/26/2016
Posts: 108


Dolor. Thanks for your interest. Even though monteukast is a very safe drug for long term use, the problem is getting a doctor to prescribe it. You can get a prescription for three months and then take 10 mg twice a day, or 20 mg twice a day for a couple of weeks. This is just to see if it shows a benefit. If it shows a benefit, then continue. 

As far as the type of dementia, I think that any dementia due to aging would show positive results due to a reduction in inflammation.

Good luck.


Larrytherunner
Posted: Thursday, July 5, 2018 7:26 AM
Joined: 2/26/2016
Posts: 108


Birdies. Thanks for informing me. I read another article earlier this week about Dr Pratico's work with Zyleuton. There are three drugs available in the US that inhibit leukotrienes - montelukast (Singulair), zafirlukast (Accolate), and zilenton (Zyflo). Montelukast and zafirlukast block inflammation causing leukotrienes from entering cells. Zilenton works differently. It interferes with the body's ability to make leukotrienes, and it has been found to have some serious side effects in some people. Therefore there is no need to consider using zilenton since montelukast and zafirlukast are both very safe for long term use. I have been using montelukast for over two years with no problems.

Dr. Aigner did animal research in 2015 and showed that rats with signs of dementia which were treated with montelukast were returned to normal. Dr. Pratico showed that mice with dementia treated with zilenton were returned to normal and that tau that was damaged in the brains of the mice began functioning normally again. 

More importantly a clinical trial for the treatment of Alzheimer's using montelukast is going on now in Canada. We should see some results by the end of 2018 or the beginning of 2019.


Larrytherunner
Posted: Thursday, July 5, 2018 11:28 AM
Joined: 2/26/2016
Posts: 108


Lane, Lane, Lane. Why are you stepping on my post? I first saw this post on Malinow about two years ago and you have kept posting it over and over. You seem to have a whole library of posts you keep sending out over and over. These are confusing posts with a lot of unsupported conclusions.

You are interfering with me telling my story. I am trying to give some practical info on a possible drug treatment for Alzheimer's and also about an ongoing clinical trial. 

What you are doing is confusing people. Your thinking is just not clear because you jump to conclusions without any clear proof. It is very unscientific..

Lane, I have a degree in mathematics and consider myself a pretty smart guy. I took a lot of chemistry and biology in college. I don't claim to be a scientist, but I am educated enough to detect your scientific sounding b s. Exactly what are your qualifications, Lane. 

If you want to comment on my post, please limit it to a few sentences. I don't need an incomprehensible scientific lecture, and I don't appreciate you taking over my post. Thanks.


Birdies
Posted: Thursday, July 5, 2018 12:48 PM
Joined: 7/3/2018
Posts: 11


Larry, thanks so much for taking the time to share your experiences.  And also, for thoughtful responses.  
I’m curious as to what level of memory impairment you had before starting Monteleukast (Singulair)?  You mentioned brain fog/fatigue, but were you actually having trouble finding words?  Forgetting where you were?  Did you have any problems with spatial relations?  Getting dressed?  
I will not be offended if you don’t want to answer or think I’m prying!

Thank you!


dolor
Posted: Thursday, July 5, 2018 1:16 PM
Joined: 11/9/2017
Posts: 104


Oops, Larry, it was really my fault. I jumped in with a dozen questions, sorry!

Next time, I'll attack Lane with questions on his own thread.

Apologies again.


Larrytherunner
Posted: Thursday, July 5, 2018 2:25 PM
Joined: 2/26/2016
Posts: 108


Hi Birdies. I am really not a grouchy old man. The only person that irritates me on this site is Lane, who is our resident pretend scientist. He (or she - not sure) irritates a lot of other people also.

I was diagnosed in early 2015 in Ghana with early stage age related dementia. I was experiencing extreme mental fatigue and occasional confusion, but I appeared normal to everyone. I started taking montelukast in early 2016 and I was back to normal, so I am lucky not to have spent much time with dementia. I am also fortunate that I live in a country where I don't need to have a prescription to buy the drug. 

There is a Dr Rozin in Lawrenceville, GA, who did a study of patients that he treated with montelukast, and it appeared that patients from all stages benefited from the treatment. Over 90 per cent of the patients benefited in some way. 

He prescribed 80 mg a day. I only take 20 mg twice a day, so I think 40 mg a day may be more reasonable. Montelukast has a very good safety record with long term use. Here is the web address of the study and also his website address.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5420184/

http://drrozin.com/

Thanks and good luck.


Larrytherunner
Posted: Thursday, July 5, 2018 2:37 PM
Joined: 2/26/2016
Posts: 108


Dolor. It is not your fault. I thought Lane and I had called a truce, but here we are again. Feel free to post me any time. And Lane has many of his own posts so you can post him any time also. Thanks
Lane Simonian
Posted: Thursday, July 5, 2018 2:42 PM
Joined: 12/12/2011
Posts: 4286


The questions dolor asked were both relevant and important.  

Providing the study on Montelukast and L-carnitine showed the potential value of using anti-inflammatories and anti-oxidants in tandem (although the study was for lung injuries and not Alzheimer's disease). 

The other major area covered was the limitations of non-steroidal anti-inflammatory drugs and their sometimes damaging side effects.

My background is in environmental history, especially in Latin American environmental history.  That includes an understanding of the effects of pollutants and other toxins on the environment and on human health, which now includes Alzheimer's disease.

I have taken a number of biology courses in areas such as ecology, conservation, and evolution and also a course which covered biochemistry.  I started studying Alzheimer's disease fourteen years ago when my aunt and cousin were in the late stages of the disease and my mother was in the early stages of the disease.  I began using aromatherapy three years later when my mother was in the later stages of Alzheimer's disease.  With aromatherapy, she recognized her home again, could recognize objects, could remember her name, could remember phrases, had a better sense of time, and was more alert and aware.

I take the criticisms as they come even the very biting criticisms.  What I know may some day be of value to my harshest critics.



Lane Simonian
Posted: Thursday, July 5, 2018 6:13 PM
Joined: 12/12/2011
Posts: 4286


I will go back to the truce.  On another site I promised not to write anymore about Alzheimer's disease until there is a breakthrough.  While I am not counting on it, I hope that Montelukast will be a breakthrough.

I have never claimed to be a scientist; only someone who has devoted many years to trying to understand Alzheimer's disease.  Sometimes I repeat critical findings, sometimes I don't explain myself clearly, sometimes I devote too much time to complicated subjects, sometimes I make mistakes, sometimes I veer off into tangents.  I have tried my best to understand Alzheimer's disease and to explain the science as clearly and as well as I can.


Birdies
Posted: Thursday, July 5, 2018 11:18 PM
Joined: 7/3/2018
Posts: 11


Thanks for all the information Larry.  I’m hopeful that this may help my mom.  As I said before, she’s on 5 Lox Inhibitor now (6 days).  Will see if there’s any benefit with this and then try and get a script for Singulair.
Birdies
Posted: Sunday, July 8, 2018 12:01 PM
Joined: 7/3/2018
Posts: 11


Hi Larry, when you started Singulair did you have any nightmares or other neuropsychiatric events (depression, aggression)? 

Also; have you encountered any other AD or dementia patients on this site (or otherwise), that have benefitted from Singulair like yourself?

Thanks!


Birdies
Posted: Sunday, July 8, 2018 3:42 PM
Joined: 7/3/2018
Posts: 11


No problem.

I asked Larry about the “nightmares - etc”, because they are one of the adverse effects of Singulair.  I think mainly in children.  Just google it.

I better clarify with Larry what i meant!


Birdies
Posted: Sunday, July 8, 2018 3:47 PM
Joined: 7/3/2018
Posts: 11


Hi Larry,

This is to clarify my last question:

Did you have any adverse effects like, nightmares-insomnia-etc when you started taking Singulair?

Thanks again!


Lxy
Posted: Monday, July 9, 2018 12:33 AM
Joined: 1/20/2018
Posts: 5


Larrytherunner wrote:

Dolor. Thanks for your interest. Even though monteukast is a very safe drug for long term use, the problem is getting a doctor to prescribe it. You can get a prescription for three months and then take 10 mg twice a day, or 20 mg twice a day for a couple of weeks. This is just to see if it shows a benefit. If it shows a benefit, then continue. 

As far as the type of dementia, I think that any dementia due to aging would show positive results due to a reduction in inflammation.

Good luck.

 

Is there any workaround for patients in the USA to get access to Montelukast if a doctor won't prescribe it for Alzheimer's since it is designated as an asthma medication?

I don't know if my LO's neurologist would be willing to prescribe the repurposing of Montelukast in this manner. 

Thanks.

 


Larrytherunner
Posted: Monday, July 9, 2018 9:34 AM
Joined: 2/26/2016
Posts: 108


The chance that your neurologist will prescribe montelukast (Singulair) for Alzheimer's is slim to none. Neurologists have a very, very limited number of drugs that they can prescribe for Alzheimer's and dementia that are generally accepted by the medical establishment. They have a lot of very sick patients, and they are not going to stray from what is considered medically accepted, regardless of how safe or promising the drug is.

 

If you don't have a relative or personal friend who is a medical doctor, then I suggest you go see a family physician, GP, etc, who is not part of your plan and does not have access to your medical records. Tell him or her that you have taken montelukast before for asthma and want to start back. The standard dosage for asthma attack prevention is 10 mg once a day. Get about a 3 month supply or what ever you can get.

 

Try out the drug for about 2 weeks taking a minimum of one 10 mg tablet twice a day, or a maximum of two 10 mg tablets twice a day. Anti-inflammatory drugs work very quickly. If the patient shows improvement, then continue. If not, he or she can stop. Sorry, this is the only solution I can come up with, unless you want to leave the states. Good luck.


markus8174
Posted: Tuesday, July 10, 2018 7:48 AM
Joined: 1/25/2018
Posts: 90


Well Larry, I've taken the plunge. My DW's AD has taken a drastic turn in the last month. I suspect the Namenda and Aricept have hit the wall and can no longer compensate for her reduced mental capacity. I had to order the Montelukast from an out of country pharmacy at an exorbitant mark-up in that out doctor will only offer 10mg once daily. I now have enough to move to 10mg twice daily, and then to 10mg in morning and 20mg in evening for about 5 weeks. If I start seeing improvement in the next couple of weeks I'll have to continue paying very exorbitant prices for this med. It makes me crazy that a safe, tested med may have some benefit, but for fear of litigation or unwanted heat from health care network managers, I cannot get Montelukast for the cash price of $15.00 for 60 10mg tabs (without using insurance via "Goodrx"). Instead I have to pay $160. for the same med from some sketchy pharmacy in some backwater country outside or the scrutiny of the US health care machine. My DW has stated many times-"Risk-I don't care about risk, If I have a chance of keeping my mind a little longer I want to try it". Wish us luck. Thanks for your insights.
Birdies
Posted: Tuesday, July 10, 2018 10:07 AM
Joined: 7/3/2018
Posts: 11


Marcus,

Will you post how the Montleukast is going with your DW?

I would like to get my Mom on it too.


Larrytherunner
Posted: Tuesday, July 10, 2018 12:13 PM
Joined: 2/26/2016
Posts: 108


Markus, I glad that you have found a way to get montelukast for your wife. I am sorry to hear that you have to pay such an outrageous price. I hope the overseas pharmacy will come through quickly. Here is hoping the US government doesn't intercept the package. The government seems to be working extra hard to protect big pharma monopolies in the US. 

I still think the easiest way is to go to a family physician, GP, etc and say that you have taken this medication before for asthma, and he\she will write the prescription on the spot. Of course you may only be able to get a 10 mg per day prescription, so you have to go to multiple physicians and pay for multiple visits, so there is a big cost there too. But once you get the prescriptions, renewing is easy. Good luck to you and your wife.


markus8174
Posted: Tuesday, July 10, 2018 9:49 PM
Joined: 1/25/2018
Posts: 90


I'll update how thing are going in a couple of weeks. I considered seeing a GP and trying to wheedle a Rx. for myself to give to my wife, but that only gets me to 20mg/day. My goal is, if I see significant improvement I will discuss increasing the current Rx. dose with our PCP. If she is still resistant to increasing the dose despite evidence of it's effectiveness and tolerance, I'll consider seeing another doc on the side. It makes me a little nuts that I worked as an RN with most of the docs in the area for 30 years and still can't think of one that would be willing to consider 20-40 mg per day. We did have a doc that I'm sure would be willing to try it, but he is out of practice. I can't just give him a call at his home begging for a prescription. On top of everything else, our cat, and my main support system, has developed cancer. We are trying chemo, but the cancer is progressing very quickly. If chemo doesn't work my cat is going to be gone in a week or two. This kind of emotional strain isn't going to make evaluating my DW's response very clear. It may be a few weeks after the upped dose of Montelukast and over the grief of losing our kitty before I can be sure if it is doing any good. If anyone out there can, please pray for my wife, my cat, and me. I'm beginning to feel a little like Job.
markus8174
Posted: Wednesday, July 11, 2018 8:00 AM
Joined: 1/25/2018
Posts: 90


My kitty has Lymphoma-blood cancer. Removing it wouldn't be very therapeutic. I am luck to have a skilled animal oncologist in the area. He says there is a small chance of complete remission, but a good chance of improvement and another 6 months to a year of quality life.  Not great news but it gives us a chance to get used to the idea of losing our little buddy. Only 2 problems-1) he will die in the middle of the winter when it is impossible to plant him in the "pet cemetery" we have used in our yard, and 2) $$$$. Chemotherapy for kitties is cheaper than for peoples, but it ain't cheap!  SORRY LARRY, I didn't mean to hijack your  thread with kitty talk.
Larrytherunner
Posted: Thursday, July 12, 2018 6:00 AM
Joined: 2/26/2016
Posts: 108


Marcus, I know you are going through a lot of stress. Hang in there, and keep us posted. Take care.
Birdies
Posted: Thursday, July 12, 2018 9:34 PM
Joined: 7/3/2018
Posts: 11


Marcus, we co-share a cat with my mom and dad... and said cat is a wonderboy, who provides much comfort, joy and peace to all of us during this really difficult time with my mom.  Hang in there... because that’s the only option.
 
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