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J147 - A new Alzheimers-reversing drug based on curcumin extract

alzheimers memory

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#91 88LS

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Posted 19 August 2015 - 03:26 PM

Going to try or have tried? I'm very interested in ordering some, but not yet sure if it's worth it as there aren't allot of experience reports on this substance yet. Wondering how it compares to the likes of Cerebro and NSI.



#92 elfanjo

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Posted 13 November 2015 - 08:29 AM

http://m.medicalxpre...anti-aging.html

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#93 Logic

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Posted 13 November 2015 - 10:57 AM

 

 

"Initially, the impetus was to test this drug in a novel animal model that was more similar to 99 percent of Alzheimer's cases," says Antonio Currais, the lead author and a member of Professor David Schubert's Cellular Neurobiology Laboratory at Salk. "We did not predict we'd see this sort of anti-aging effect, but J147 made old mice look like they were young, based upon a number of physiological parameters."

 

14-experimental.jpg

 

The old mice that received J147 performed better on memory and other tests for cognition and also displayed more robust motor movements. The mice treated with J147 also had fewer pathological signs of Alzheimer's in their brains. Importantly, because of the large amount of data collected on the three groups of mice, it was possible to demonstrate that many aspects of gene expression and metabolism in the old mice fed J147 were very similar to those of the young animals. These included markers for increased energy metabolism, reduced brain inflammation and reduced levels of oxidized fatty acids in the brain.

Another notable effect was that J147 prevented the leakage of blood from the microvessels in the brains of old mice. "Damaged blood vessels are a common feature of aging in general, and in Alzheimer's, it is frequently much worse," says Currais.


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#94 elfanjo

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Posted 13 November 2015 - 11:00 AM

Thxs :)

#95 Benjy

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Posted 20 November 2015 - 06:28 AM

Any new updates @sk_scientific 

 

Love to hear how it's going now



#96 maxwatt

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Posted 20 November 2015 - 02:16 PM

Any word on the mechnism(s) of a action?  What I recall having gleaned from press accounts is that J147 increases BDNF in the brain, possibly via increasing irisin levels.

 

Things that increase irisin levels:  exercise, berberine, dihydromyricetin.....

 



#97 tunt01

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Posted 20 November 2015 - 06:01 PM

Any word on the mechnism(s) of a action?  What I recall having gleaned from press accounts is that J147 increases BDNF in the brain, possibly via increasing irisin levels.

 

 

I think the MOA is basically the same as how Bexarotene works.  It increases ABCA1 transporter expression in HDL, such that HDL can better scavenge abeta aggregates for clearance.

 

Alzheimer's seems to be is primarily a disease of poor cholesterol handling.  The mechanism of action seems consistent in those who have APOE4, which is deficient in cholesterol handling and whose carriers typically have lower HDL.  Bexarotene was seen increasing HDL 15% in studies.

 

I think Curcumin and Telmisartan have similar properties in their effect on AT1 receptors in that they are ang-II blockers.  Ang-II is upstream and suppresses ABCA1 expression

 

If I'm not 100% clear, please forgive me, as I am still grasping the biochemical pathways of this situation.  But I think the same mechanisms involved in reverse cholesterol transport (which prevent damage to the arterial lining) are in play here.  It's also why Alzheimer's correlates so well with arterial health.

 

My first thought after seeing the study was:  "OK.  But what was the ultimate mortality of these mice and how many of them died from lung cancer?"  As we know Telmisartan upregulates some cancer risk.  Statements like "mice that look younger" and "appear to have an anti-aging effect", sounds like well worded half-truths to me.  I fully believe J-147 had anti-alzheimer's benefits, but I'd like to see mortality/toxicity data.

 

I'd personally be wary of taking anything like this on a long-term basis.  Think the safest thing with so many unknowns is intermittent, short regimen dosing of a drug like J-147.  It's impossible to know what the long-term implications of taking such a drug on a continuous basis.  I also would be careful on Bexarotene, which has been known to cause the liver to spew out abnormal levels of Trigs.  I think we know a lot more about long-term risks of telmisartan (pharmaceutical) and curcumin (dietary supplement) and that is what I would look at for long-term, constant dosing regimens.

 

 

EDIT:  Note this tweet which seems to concur with what I've written here.  Mechanism of action = Abeta clearance.


Edited by prophets, 20 November 2015 - 06:23 PM.

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#98 tunt01

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Posted 20 November 2015 - 06:12 PM

Incidentally, does anyone know what the half-life of J-147 is?  That would be good to know.



#99 maxwatt

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Posted 20 November 2015 - 08:08 PM

It is very easy to show life-extension and anti-aging effects in genetically fucked-up mice, which these were.


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#100 malbecman

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Posted 20 November 2015 - 10:07 PM

 That said, my mother-in-law with advanced dementia does remind me of the mouse on the left.


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#101 maxwatt

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Posted 21 November 2015 - 03:36 AM

 That said, my mother-in-law with advanced dementia does remind me of the mouse on the left.

 

Give her some dihydromyricetin; it's the nearest thing t J147 I've found in that it increases irisin levels resulting in an increase in BDNF in the brain.  It also inhibits COMT, resulting in higher dopamine levels.which should cheer her up.  This in addition to it's better known properties as a sobriety pill. 


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#102 uz8797

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Posted 21 November 2015 - 10:05 PM

A user on r/nootropics recently did a test on many products from teamtlr. I believe that all of teamtlr's proprietary extracts tested were all found to be the same inactive compound. The normal noopet and piracetam tested was legit however. But sadly there is a high chance that what you got sent is not j147z so any experiences you have with this compound should be taken with a dose of scepticism.

 

https://www.reddit.c...esting_results/

 

Hello,

 

I found that post, that match what you said...



#103 uz8797

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Posted 21 November 2015 - 11:52 PM

After reading a long post about TLR here (where, obviously some people are taking drugs there  :-D ), i couldn't really come to a clear opinion about the trust i can have about the company. 

But i would have delete my previous comment if i could (being irrelevant as redundant).



#104 sk_scientific

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Posted 23 November 2015 - 01:24 AM

I dropped the semax due to its dopaminergic action interfering with medications that I am currently taking.  

 

J147 has shown itself to mildly and subtly enhance working memory and recall in my assay.  I've not gone habitual, chronic, regular dosing long term but sporadically and acutely over several months.  I can detect the difference in my cognition 48 hours after cessation, that is, my recall is enhanced for 48 hours and then I start having the frequent "tip-of-the-tongue effect" all over again.  This is only an account of acute effects, I cannot speak on long term memory rescue.  I still struggle with some amount of recall problems.  I just had a blood panel done to look for various issues.  I await a conversation with my primary care provider to speak at length.  On a 10 hour fast, my blood sugar was high, my cholesterol was high, and my vitamin D was low, according to the preliminary information.

 

I am not saying that any of this has anything to do with J147, however.  I have been taking EPA/DHA tablets along with plant-sourced phosphatidyl serine.  I also did a fair amount of drinking with buddies the night prior to the blood draw, ate duck fat fries with truffle aioli, cheese and a pretzel.  Although I fasted overnight until the blood work, I slept with a gut full of beer, fatty foods, and took fatty acid tablets that night around 9 p.m..  I am quite certain that my dietary choices and partying the evening before almost certainly impacted the baseline plasma values.  I stopped taking j147 a couple of weeks prior to the blood panel because I didn't want to have to submit details of my endeavors to an individual who is keeping traceable logs if the metabolites of J147 threw up any false positives in other areas.

 

Anyhow, I found that an oral dose of J147 at 50 mgs to be ideal for me.  I did not try any other routes of administration such as intranasal, intravenous or sublingual.  My understanding is that the bioavailability by oral route is somewhere around 50 percent, perhaps even less, but I do not have strong pharmacokinetic data to support this. It's hearsay from a trusted source, but could easily be incorrect.

 

Bottom line: I believe that J147 works as long as I'm taking it with regularity and I'm unable to comment on long-term cognitive rescue in the absence of chronic administration nor any manner of safety.  The LD50 appears to be quite high but  I only naively assume that the safety of the substance is relative to that of curcumin.

 

In any case, I can say that it does work.  Whether or not it's a cure, is another issue entirely.

 

As of this month, the Salk Institute released a red-herring on its webpage citing J147's ostensible anti-aging properties, but in so far as I can tell, there are no empirical data to support the assertion which are readily available.  Provided that the statements are accurate, supporting data withheld, this suggests to me that J147 is intended to be a long term treatment, unlike NSI-189.

 

Anyone else that may have personal experience with J147 to share with the group would be strongly advised to make their contributions now. 


Edited by sk_scientific, 23 November 2015 - 01:32 AM.

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#105 resveratrol_guy

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Posted 23 November 2015 - 12:10 PM

 I can detect the difference in my cognition 48 hours after cessation, that is, my recall is enhanced for 48 hours and then I start having the frequent "tip-of-the-tongue effect" all over again.  

 

 

This is the first precious data point by which we might compare J147 with Longvida. 400 mg of the latter will provide 5 hours, more or less, of enhanced recall. That jives with the pharmacokinetics and my own extensive experience. You're using roughly an order of magnitude less J147 than a standard dose of Longvida, and obtaining another order of magnitude expansion in effect. Which is all to say that J147 sounds like it's 100X as potent as the best lipidated curcumin on the market. That's impressive, although it's rather implausible, considering that most analogs (e.g. racetams, benzos, etc.) don't have such massive effect variances. I wonder whether something fundamentally different is going on between these 2 supplements, as in, maybe J147 should not be considered as a curcumin analog. More data would be great.
 


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#106 sk_scientific

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Posted 23 November 2015 - 02:21 PM

Yes, I thought briefly on similar, resveratrol_guy, that is whether we should think of J147 as a prodrug or not.  I'm not arguing with your claim regarding the duration of action of lipidated curcumin.  However, given the molecular difference, maybe J147 has a much longer half life.  Or perhaps there are tertiary products of J147's drug action that continue on well after it has been metabolized and excreted.  For example, perhaps its preventing of oxidation of fatty acids, and their subsequent absorption into brain tissue lends to enhanced cognition for duration exceeding the drug action.  Who knows?  I just noticed that I'm sharper when I take J147, and it seems to wear off a couple days past cessation.  Mind you, I haven't stayed on it for months on end, as I had NSI-189, but in the case of NSI-189, I didn't really begin to notice how significant the impact to my affective stability was until many months later (meaning that the acute perceivable effects were not the benefit of the drug, and that my brain took an extended duration of time to apparently consolidate and make use of the structural changes provoked by NSI-189).  Though the drug action of NSI-189 is entirely different from J147, I only mean to suggest that there could be longer term benefits than what is perceived in my acute trials, and perhaps more is at play here. 

 

I'm not sure that we should compare J147 with racetams, and certainly not with benzodiazepines.  I think that we're used to traditionally considering brain drugs in terms of their relationship to neurotransmitters such as in the cases of SSRI's or Amphetamines, J147 on the other hand seems to be very different.


Edited by sk_scientific, 23 November 2015 - 02:22 PM.

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#107 malbecman

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Posted 23 November 2015 - 05:39 PM

 I would think that with those 3 fluorines on there that J147 would have much better bioavailability as well as a longer half life than curcumin (not to mention a better ability to cross the BB barrier).   That is probably why they put those

in there as they designed the molecule.    I'm a chemist and used to study metabolism, fwiw.


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#108 maxwatt

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Posted 23 November 2015 - 05:48 PM

 

Any word on the mechnism(s) of a action?  What I recall having gleaned from press accounts is that J147 increases BDNF in the brain, possibly via increasing irisin levels.

 

 

I think the MOA is basically the same as how Bexarotene works.  It increases ABCA1 transporter expression in HDL, such that HDL can better scavenge abeta aggregates for clearance.

......(snip)

My first thought after seeing the study was:  "OK.  But what was the ultimate mortality of these mice and how many of them died from lung cancer?"  As we know Telmisartan upregulates some cancer risk.  Statements like "mice that look younger" and "appear to have an anti-aging effect", sounds like well worded half-truths to me.  I fully believe J-147 had anti-alzheimer's benefits, but I'd like to see mortality/toxicity data.......

 

 

WRT telmisartan, below from te FDA website.  One study found a modest increase in lung cancer risk from ARBs, ther studies have shown an anti-cancer effect from telmisartan in the case of breast and colon cancers.  In response to the one meta-analysis showing the increase in lung-cancer risk, the FDA conducted their own, moreextensive analysis and found no increase in risk. 

 

Safety Announcement

[06-02-2011] The U.S. Food and Drug Administration (FDA) has completed a review of the potential risk of cancer associated with the class of medications known as angiotensin receptor blockers (ARBs). FDA has concluded that treatment with an ARB medication does not increase a patient’s risk of developing cancer. A list of medications containing an ARB is available here.

 

Facts about Angiotensin Receptor Blockers (ARBs)

  • ARBs are widely used to treat patients with high blood pressure.  
  • Brand names include Atacand, Avapro, Benicar, Cozaar, Diovan, Micardis, and Teveten, as well as the combination product brand names included in Table 1 below.
 

In July 2010, FDA communicated its intent to conduct a safety review of ARBs after a published meta-analysis of 5 randomized clinical trials reported a small but statistically significant increase in risk of cancer in patients taking an ARB compared to patients not taking an ARB.1

To further evaluate the reported link between use of ARBs and cancer, FDA conducted a trial-level meta-analysis of clinical trials in which patients had been randomized to an ARB treatment or a non-ARB treatment. This analysis included 31 trials and approximately 156,000 patients, far more than the approximately 62,000 in the published analysis. FDA’s more comprehensive meta-analysis did not show an increased risk of cancer in the patients taking an ARB medication.

Based on our review and analysis of all currently available data regarding this potential safety signal, FDA has concluded that treatment with an ARB medication does not increase the risk of cancer.


 



#109 maxwatt

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Posted 23 November 2015 - 06:03 PM

This from pubmed

 

 

 
Alzheimers Res Ther. 2013 May 14;5(3):25. doi: 10.1186/alzrt179. eCollection 2013.
The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice.
Abstract
INTRODUCTION:

Despite years of research, there are no disease-modifying drugs for Alzheimer's disease (AD), a fatal, age-related neurodegenerative disorder. Screening for potential therapeutics in rodent models of AD has generally relied on testing compounds before pathology is present, thereby modeling disease prevention rather than disease modification. Furthermore, this approach to screening does not reflect the clinical presentation of AD patients which could explain the failure to translate compounds identified as beneficial in animal models to disease modifying compounds in clinical trials. Clearly a better approach to pre-clinical drug screening for AD is required.

METHODS:

To more accurately reflect the clinical setting, we used an alternative screening strategy involving the treatment of AD mice at a stage in the disease when pathology is already advanced. Aged (20-month-old) transgenic AD mice (APP/swePS1ΔE9) were fed an exceptionally potent, orally active, memory enhancing and neurotrophic molecule called J147. Cognitive behavioral assays, histology, ELISA and Western blotting were used to assay the effect of J147 on memory, amyloid metabolism and neuroprotective pathways. J147 was also investigated in a scopolamine-induced model of memory impairment in C57Bl/6J mice and compared to donepezil. Details on the pharmacology and safety of J147 are also included.

RESULTS:

Data presented here demonstrate that J147 has the ability to rescue cognitive deficits when administered at a late stage in the disease. The ability of J147 to improve memory in aged AD mice is correlated with its induction of the neurotrophic factors NGF (nerve growth factor) and BDNF (brain derived neurotrophic factor) as well as several BDNF-responsive proteins which are important for learning and memory. The comparison between J147 and donepezil in the scopolamine model showed that while both compounds were comparable at rescuing short term memory, J147 was superior at rescuing spatial memory and a combination of the two worked best for contextual and cued memory.

CONCLUSION:

J147 is an exciting new compound that is extremely potent, safe in animal studies and orally active. J147 is a potential AD therapeutic due to its ability to provide immediate cognition benefits, and it also has the potential to halt and perhaps reverse disease progression in symptomatic animals as demonstrated in these studies.

PMID:   23673233   [PubMed]    PMCID:   PMC3706879     Free PMC Article

Nothing about ABCA1. The conclusion in the Salk Institute paper :The ability of J147 to improve memory in aged AD mice is correlated with its induction of the neurotrophic factors NGF (nerve growth factor) and BDNF (brain derived neurotrophic factor) as well as several BDNF-responsive proteins which are important for learning and memory"

 



#110 tunt01

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Posted 23 November 2015 - 06:13 PM

 

 

My first thought after seeing the study was:  "OK.  But what was the ultimate mortality of these mice and how many of them died from lung cancer?"  As we know Telmisartan upregulates some cancer risk.  Statements like "mice that look younger" and "appear to have an anti-aging effect", sounds like well worded half-truths to me.  I fully believe J-147 had anti-alzheimer's benefits, but I'd like to see mortality/toxicity data.......

 

 

WRT telmisartan, below from te FDA website.  One study found a modest increase in lung cancer risk from ARBs, ther studies have shown an anti-cancer effect from telmisartan in the case of breast and colon cancers.  In response to the one meta-analysis showing the increase in lung-cancer risk, the FDA conducted their own, moreextensive analysis and found no increase in risk. 

 

 

 

 

 

I specifically cited lung cancer for this reason.  One of the highest concentration of angiotensin receptors in the body can be found in the lungs.  ACE inhibitors also have been found to contribute to higher lung cancer risk.

 

 

 

 

 

 

 

Safety Announcement

[06-02-2011] The U.S. Food and Drug Administration (FDA) has completed a review of the potential risk of cancer associated with the class of medications known as angiotensin receptor blockers (ARBs). FDA has concluded that treatment with an ARB medication does not increase a patient’s risk of developing cancer. A list of medications containing an ARB is available here.

 

Facts about Angiotensin Receptor Blockers (ARBs)

  • ARBs are widely used to treat patients with high blood pressure.  
  • Brand names include Atacand, Avapro, Benicar, Cozaar, Diovan, Micardis, and Teveten, as well as the combination product brand names included in Table 1 below.
 

In July 2010, FDA communicated its intent to conduct a safety review of ARBs after a published meta-analysis of 5 randomized clinical trials reported a small but statistically significant increase in risk of cancer in patients taking an ARB compared to patients not taking an ARB.1

To further evaluate the reported link between use of ARBs and cancer, FDA conducted a trial-level meta-analysis of clinical trials in which patients had been randomized to an ARB treatment or a non-ARB treatment. This analysis included 31 trials and approximately 156,000 patients, far more than the approximately 62,000 in the published analysis. FDA’s more comprehensive meta-analysis did not show an increased risk of cancer in the patients taking an ARB medication.

Based on our review and analysis of all currently available data regarding this potential safety signal, FDA has concluded that treatment with an ARB medication does not increase the risk of cancer.

 

 

This is a blanketed statement from the FDA about all ARBs and all forms of cancer.  Telmisartan has a longer half-life (~24 hrs IIRC), which is substantially longer than other ARBs.  This latter part is the issue that bothers me the most about it.  If Telmisartan were a 3-4 hr half-life, I might be popping it like it were candy.

 

I don't think this makes Telmisartan a bad choice for an intervention or even incredibly risky.  I just think there is a likely risk here, that is probably still a calculated attractive risk/reward ratio.  But that risk/reward trade-off also probably depends on the individual.  I have a family member who is an ex-smoker of 30 years . If I had a similar background, I would not take such a drug, without seriously investigating the matter further.  You and I both live in a major metropolitan city.  If I were to spend all day in cab traffic sucking down exhaust fumes, my first move in the morning would not be to swallow a pile of of Telmisartan pills.

 

When engaging in a long-term intervention that changes the metabolism of an individual over the course of their lifespan (30+ years), there is a lot we don't know about drugs like this and it's very hard to know with certitude.  For a healthy/normal individual, I just think 'do no harm' is the first step towards better health, then adding in slight tweaks where appropriate (i.e. less protein in diet, higher dietary fiber).


Edited by prophets, 23 November 2015 - 06:34 PM.

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#111 tunt01

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Posted 23 November 2015 - 06:43 PM

Re: Internal dispute at FDA over Telmisartan - Lung Cancer Risk.



#112 tunt01

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Posted 24 November 2015 - 09:05 PM

 

Nothing about ABCA1. The conclusion in the Salk Institute paper :The ability of J147 to improve memory in aged AD mice is correlated with its induction of the neurotrophic factors NGF (nerve growth factor) and BDNF (brain derived neurotrophic factor) as well as several BDNF-responsive proteins which are important for learning and memory"

PMID:   23673233   [PubMed]    PMCID:   PMC3706879     Free PMC Article

 

 

1.  I would be very surprised if J-147 did not induce higher levels of HDL and increased expression of ABCA1, as is found in curcumin.

 

2.  Just because NGF and BDNF are upregulated, doesn't mean the mechanism of J-147 is to stimulate peptide hormone production.  They appear to be measuring an outcome variable, not delineating a mechanism of action.  As you say, "it is correlated"  and that does not mean causative.

 

It's very plausible that the improved cerebrovascular architecture from J-147 (and curcumin) is via cholesterol handling and that induces higher levels of NGF/BDNF.  Alzheimer's is a disease of cholesterol handling and reverse cholesterol transport is an important part of that process in maintaining the integrity of a vascular system and keeping the brain healthy and "clean".

 

EDIT:  I will try to read the paper over the holiday, as I have been buried.  It looks like a metabolics assay screening process and comparison, which is kind of nice but also doesn't necessarily delineate causation (as far as I can tell).

 

 


Edited by prophets, 24 November 2015 - 09:06 PM.


#113 maxwatt

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Posted 25 November 2015 - 06:23 PM

I appreciate your looking into this.

 

 

 

Nothing about ABCA1. The conclusion in the Salk Institute paper :The ability of J147 to improve memory in aged AD mice is correlated with its induction of the neurotrophic factors NGF (nerve growth factor) and BDNF (brain derived neurotrophic factor) as well as several BDNF-responsive proteins which are important for learning and memory"

PMID:   23673233   [PubMed]    PMCID:   PMC3706879     Free PMC Article

 

 

1.  I would be very surprised if J-147 did not induce higher levels of HDL and increased expression of ABCA1, as is found in curcumin.

 

2.  Just because NGF and BDNF are upregulated, doesn't mean the mechanism of J-147 is to stimulate peptide hormone production.  They appear to be measuring an outcome variable, not delineating a mechanism of action.  As you say, "it is correlated"  and that does not mean causative.

 

It's very plausible that the improved cerebrovascular architecture from J-147 (and curcumin) is via cholesterol handling and that induces higher levels of NGF/BDNF.  Alzheimer's is a disease of cholesterol handling and reverse cholesterol transport is an important part of that process in maintaining the integrity of a vascular system and keeping the brain healthy and "clean".

 

EDIT:  I will try to read the paper over the holiday, as I have been buried.  It looks like a metabolics assay screening process and comparison, which is kind of nice but also doesn't necessarily delineate causation (as far as I can tell).

 

 



#114 megatron

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Posted 25 November 2015 - 08:53 PM

Yes, I thought briefly on similar, resveratrol_guy, that is whether we should think of J147 as a prodrug or not.  I'm not arguing with your claim regarding the duration of action of lipidated curcumin.  However, given the molecular difference, maybe J147 has a much longer half life.  Or perhaps there are tertiary products of J147's drug action that continue on well after it has been metabolized and excreted.  For example, perhaps its preventing of oxidation of fatty acids, and their subsequent absorption into brain tissue lends to enhanced cognition for duration exceeding the drug action.  Who knows?  I just noticed that I'm sharper when I take J147, and it seems to wear off a couple days past cessation.  Mind you, I haven't stayed on it for months on end, as I had NSI-189, but in the case of NSI-189, I didn't really begin to notice how significant the impact to my affective stability was until many months later (meaning that the acute perceivable effects were not the benefit of the drug, and that my brain took an extended duration of time to apparently consolidate and make use of the structural changes provoked by NSI-189).  Though the drug action of NSI-189 is entirely different from J147, I only mean to suggest that there could be longer term benefits than what is perceived in my acute trials, and perhaps more is at play here. 

 

I'm not sure that we should compare J147 with racetams, and certainly not with benzodiazepines.  I think that we're used to traditionally considering brain drugs in terms of their relationship to neurotransmitters such as in the cases of SSRI's or Amphetamines, J147 on the other hand seems to be very different.

 

Have you done any objective testing, like the Cambridge tests or dual n-back?


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#115 sk_scientific

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Posted 25 November 2015 - 09:04 PM

I've been blind tested by colleagues.  I only have personal subjective information to offer at this time, though I'm keen to their "tells".



#116 resveratrol_guy

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Posted 30 November 2015 - 03:01 AM

I've been blind tested by colleagues.  I only have personal subjective information to offer at this time, though I'm keen to their "tells".

 

So apart from the question of before-vs-months-after brain game scores, I think there's something else to learn here, which is the width of this cognitive enhancement window which you suggested was on the order of days. It would be interesting to a few repeats of daily scores for, say, 5 days, several times over, starting just before you pop the pill. Obviously your colleagues' blind data is going to be cleaner with regards to placebo, but given enough tests, we might see a sort of "enhancement hump" that coincides with peak drug effect. So you could play the same memory game 5 times on each session, or whatever would be required for cleaner statistics.

 

And yeah, I rather suspect that your long effect window has to do with downstream metabolites as opposed to J147 itself. (Presumably there's also a superlong window of epigenetic activation/deactivation, but I don't think that's what we're looking at here.) After all, lipidated curcumin is quite fat soluble, and yet we only see a matter of hours of enhancement in healthy subjects (according to Verdure Sciences, if you need to find the study).



#117 maxwatt

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Posted 01 December 2015 - 12:03 PM

There are more than a few papers finding no significant effect of ARBs on lung cancer, some that even show a protective effect!!!

I surmise this rests on the statistical techniques used, and the standards for 'statistical significance' are inadequate.  Or maybe it is analogous to quantum phenomena that change state when one tries to measure them.

 

Whatever the effect, it seems so small as to be irrelevant.  But back to J147

 

 

 

 

My first thought after seeing the study was:  "OK.  But what was the ultimate mortality of these mice and how many of them died from lung cancer?"  As we know Telmisartan upregulates some cancer risk.  Statements like "mice that look younger" and "appear to have an anti-aging effect", sounds like well worded half-truths to me.  I fully believe J-147 had anti-alzheimer's benefits, but I'd like to see mortality/toxicity data.......

 

 

WRT telmisartan, below from te FDA website.  One study found a modest increase in lung cancer risk from ARBs, ther studies have shown an anti-cancer effect from telmisartan in the case of breast and colon cancers.  In response to the one meta-analysis showing the increase in lung-cancer risk, the FDA conducted their own, moreextensive analysis and found no increase in risk. 

 

 

 

 

 

I specifically cited lung cancer for this reason.  One of the highest concentration of angiotensin receptors in the body can be found in the lungs.  ACE inhibitors also have been found to contribute to higher lung cancer risk.

 

 

 

 

 

 

 

Safety Announcement

[06-02-2011] The U.S. Food and Drug Administration (FDA) has completed a review of the potential risk of cancer associated with the class of medications known as angiotensin receptor blockers (ARBs). FDA has concluded that treatment with an ARB medication does not increase a patient’s risk of developing cancer. A list of medications containing an ARB is available here.

 

Facts about Angiotensin Receptor Blockers (ARBs)

  • ARBs are widely used to treat patients with high blood pressure.  
  • Brand names include Atacand, Avapro, Benicar, Cozaar, Diovan, Micardis, and Teveten, as well as the combination product brand names included in Table 1 below.
 

In July 2010, FDA communicated its intent to conduct a safety review of ARBs after a published meta-analysis of 5 randomized clinical trials reported a small but statistically significant increase in risk of cancer in patients taking an ARB compared to patients not taking an ARB.1

To further evaluate the reported link between use of ARBs and cancer, FDA conducted a trial-level meta-analysis of clinical trials in which patients had been randomized to an ARB treatment or a non-ARB treatment. This analysis included 31 trials and approximately 156,000 patients, far more than the approximately 62,000 in the published analysis. FDA’s more comprehensive meta-analysis did not show an increased risk of cancer in the patients taking an ARB medication.

Based on our review and analysis of all currently available data regarding this potential safety signal, FDA has concluded that treatment with an ARB medication does not increase the risk of cancer.

 

 

This is a blanketed statement from the FDA about all ARBs and all forms of cancer.  Telmisartan has a longer half-life (~24 hrs IIRC), which is substantially longer than other ARBs.  This latter part is the issue that bothers me the most about it.  If Telmisartan were a 3-4 hr half-life, I might be popping it like it were candy.

 

I don't think this makes Telmisartan a bad choice for an intervention or even incredibly risky.  I just think there is a likely risk here, that is probably still a calculated attractive risk/reward ratio.  But that risk/reward trade-off also probably depends on the individual.  I have a family member who is an ex-smoker of 30 years . If I had a similar background, I would not take such a drug, without seriously investigating the matter further.  You and I both live in a major metropolitan city.  If I were to spend all day in cab traffic sucking down exhaust fumes, my first move in the morning would not be to swallow a pile of of Telmisartan pills.

 

When engaging in a long-term intervention that changes the metabolism of an individual over the course of their lifespan (30+ years), there is a lot we don't know about drugs like this and it's very hard to know with certitude.  For a healthy/normal individual, I just think 'do no harm' is the first step towards better health, then adding in slight tweaks where appropriate (i.e. less protein in diet, higher dietary fiber).

 

Telmisartan exerts anti-tumor effects by activating peroxisome proliferator-activated receptor-γ in human lung adenocarcinoma A549 cells.

Li J, Chen L, Yu P, Liu B, Zhu J, Yang Y.

Molecules. 2014 Mar 5;19(3):2862-76. doi: 10.3390/molecules19032862.

PMID:  24603556  

Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals.

ARB Trialists Collaboration.

J Hypertens. 2011 Apr;29(4):623-35. doi: 10.1097/HJH.0b013e328344a7de. Review.


PMID:  21358417    -- ... found no significant increase [vs controls]

 

Lancet Oncol. 2010 Jul;11(7):627-36. doi: 10.1016/S1470-2045(10)70106-6. Epub 2010 Jun 11.
Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials.
....
FINDINGS:

Telmisartan was the study drug in 30,014 (85.7%) patients who received ARBs as part of the trials with new cancer data. Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7.2%vs 6.0%, risk ratio [RR] 1.08, 95% CI 1.01-1.15; p=0.016). When analysis was limited to trials where cancer was a prespecified endpoint, the RR was 1.11 (95% CI 1.04-1.18, p=0.001). Among specific solid organ cancers examined, only new lung-cancer occurrence was significantly higher in patients randomly assigned to receive ARBs than in those assigned to receive control (0.9%vs 0.7%, RR 1.25, 1.05-1.49; p=0.01). No statistically significant difference in cancer deaths was observed (1.8%vs 1.6%, RR 1.07, 0.97-1.18; p=0.183).

INTERPRETATION:

This meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis. Given the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug. These findings warrant further investigation.

PMID: 20542468

 

J Hypertens. 2013 Aug;31(8):1669-75. doi: 10.1097/HJH.0b013e3283621ea3.
Angiotensin receptor blockers: are they related to lung cancer?
Abstract
INTRODUCTION:

Angiotensin receptor blockers (ARBs) are commonly used antihypertensive medication with several other additional proven benefits. Recent controversy on association of lung cancer and other solid malignancy with the use of ARBs is concerning, although the follow-up studies have shown no such association.

METHODS:

We used data from the Department of Veterans Affairs electronic medical record system and registries to conduct a retrospective cohort study that compared first-time ARB users with nonusers in 1:15 ratio, after balancing for many baseline differences using inverse probability of treatment weights. We conducted time-to-event survival analyses on the weighted cohort.

RESULTS:

Of the 1 229 902 patients in the analytic cohort, 346 (0.44%) of the 78 075 treated individuals had a newly incident lung cancer and 6577 (0.57%) of 1 151 826 nontreated individuals were diagnosed with lung cancer. On double robust regression, the weighted hazard ratio was 0.74 (0.67-0.83, P < 0.0001), suggesting a lung cancer reduction effect with ARB use. There was no difference in rates by ARB subtype.

CONCLUSION:

In this large nationwide cohort of United States Veterans, we found no evidence to support any concern of increased risk of lung cancer among new users of ARBs compared with nonusers. Our findings were consistent with a protective effect of ARBs

PMID: 23822929

 

Murky indeed. 


 



#118 RobbieG

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Posted 19 January 2016 - 08:49 PM

 I would think that with those 3 fluorines on there that J147 would have much better bioavailability as well as a longer half life than curcumin (not to mention a better ability to cross the BB barrier).   That is probably why they put those

in there as they designed the molecule.    I'm a chemist and used to study metabolism, fwiw.

 

Curious, given your background as a chemist, how difficult would J147 be to make?  They include their formula instructions on a couple of the papers I saw.  If you need the instructions I can track them down and send them to you.  Thanks, - Rob 



#119 Fafner55

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Posted 20 January 2016 - 12:30 AM

I purchased 3 gm of J147 from teamtlr  It appears light brownish orange, has a spice-like smell reminiscent of maraschino cherries and is slightly bitter to the taste.  I divided it into 50 mg doses.  My daily log follows.

 

 

2015-12-05  Took the first dose without food.  While J147 is purported to be a potent drug, a blogger report indicates that its bioavailability when taken orally is about 50%.  To give it the best chance of being effective, I have decided to take it in the morning without food.

2015-12-09  Today is the 5th day of taking J147.  The only difference that might be traceable to J147 is that a chronically inflamed bump of skin on my right wrist appears smaller and less red than usual.  This apparent reduction in inflammation is not entirely surprising since curcumin is known to be anti-inflammatory through multiple pathways.  I have had this inflamed bump of skin on my wrist of years.

  1. http://examine.com/supplements/curcumin/

  2. http://www.lifeextension.com/magazine/2012/8/safely-manage-joint-inflammation/page-01

  3. http://www.ncbi.nlm.nih.gov/pubmed/12676044

  4. http://

  5. http://

2015-12-17   I have taken J147 daily for nearly two weeks now.  There appears to be a general decrease in inflammation in skin tissues, as noted above.  Other than that, I am not aware of other benefits.

Note that suppression of inflammation (specifically blocking NF-kappaB) has been shown to reverse some symptoms of aging, and has been strongly correlated with the extreme aged.

  1. “Reversal of aging by NFκB blockade” (2008) https://www.researchgate.net/publication/5594780_Reversal_of_aging_by_NFkB_blockade

  2. “Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians” (2015) http://www.ebiomedicine.com/article/S2352-3964(15)30081-5/fulltext

2015-12-19   The inflamed bump of skin on my wrist continues to recede.

2015-12-28   I have been taking J147 daily without side effects or significant benefits.  There are no improvements to my skin (such as decreased crepiness) other than the continued regression of the bump on my right wrist.  On 12/26 a skateboarding accident resulting in the separation of my right acromioclavicular joint, scrapes to my right arm and torso and a deep bruise to my right hand.  All are healing without complications.

2015-12-29  I noticed this yesterday but waited until today to confirm the observation.  My 12/26 accident has caused extensive swelling in my right shoulder, arm and hand, to the extent that i can barely make a fist.  Within 15 minutes of ingesting J147, swelling in my hand started going down, and within an hour I could make a fist without difficulty.

2015-12-31  Each day my ability to make a fist followed taking J147.  To eliminate the possibility that reduced swelling was a time of day occurrence (since I took it each day in the morning after a hot shower and after I began moving around) I took J147 again about 5 PM and got the same fist making result.

2016-01-08  I have not missed a day taking J147 since my last report.  Other than reduced swelling, I have not noticed any changes.

2016-01-18  I continue to take J147 without apparent benefit other than the reduced inflammation and swelling previously noted.

 

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#120 jddavies

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Posted 08 March 2016 - 05:56 AM

Powerful curcumin supplements: Longvida or BCM-95

 

 

The newest one is the J147 https://www.tocris.c...p?ItemId=399926


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