142 replies to this topic

[JASOG888]

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.

  

The appearance makes me wary to order any of this from your source. Is this what everyone else posting here is buying?

[recon]

This is a large bump.

I am planning to get some J147, probably from teamtlr.

I’m wondering if anyone else have tried this. Should this be taken with food or other curcumin supplements?

[Daniel Cooper]

 

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.

 

 

 

 

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.

 

 

 

@prophets

 

If you were APOE4 positive, what would you do?  Take turmeric extract chronically?  Take one of the more powerful derivatives like Longvida, BCM-95, or J147 chronically or intermittently?  Something else?

[recon]

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.

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.

@prophets

If you were APOE4 positive, what would you do? Take turmeric extract chronically? Take one of the more powerful derivatives like Longvida, BCM-95, or J147 chronically or intermittently? Something else?

Not him but I’d guess for Longvida. None others, IIRC, have documented studies proving entry into the brain.

[cannabidiol]

 

 

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.

 

 

 

 

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.

 

 

 

@prophets

 

If you were APOE4 positive, what would you do?  Take turmeric extract chronically?  Take one of the more powerful derivatives like Longvida, BCM-95, or J147 chronically or intermittently?  Something else?

 

If I had inherited this gene from one, or even both parents I would keep perspective. Evidence that dietary, and lifestyle modification are the true deciding factors of whether or not this disease will progress within you is mounting. That is not to say that these genes do not increase your odds. For you, it is even more important to improve your diet, and keep that blood pressure down. Dietary measures of reducing LDL are of great importance because high LDL is your greatest risk. Drug interventions to lower LDL have side effects including memory loss, and muscle loss of around 40% at target doses. That would be a bummer, and would reduce your mortality 20-30% at best. 

Refer to the conclusion of "Apolipoprotein E ϵ4 Allele, Elevated Midlife Total Cholesterol Level, and High Midlife Systolic Blood Pressure Are Independent Risk Factors for Late-Life Alzheimer Disease" : "The risk for Alzheimer disease from treatable factors—elevated total cholesterol level and blood pressure—appears to be greater than that from the apoE ϵ4 allele."

Please respond with any additional fears or questions because this is a complicated topic with new and hopeful emerging scientific data which has broadened the scope of understanding regarding prevention of AZ. 

I am not against curcumin, and the new derivatives looked interesting last I checked. Safety data should be considered before attempting a new treatment though. I personally take turmeric with 10% black pepper orally several times per day, which I am satisfied is safe and effective. It would be wonderful to see, say, ten years down the line, that some of these curcuminoids can be shown effective, and safe for general use. When that happens I will probably use these compounds as directed, or as I see fit from careful analysis of the medical data.

 

[albedo]

In case you have overlooked this:

 

Goldberg J, Currais A, Prior M, et al. The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging Cell. 2018;

http://onlinelibrary...acel.12715/full

 

Aging is a major driving force underlying dementia, such as that caused by Alzheimer's disease (AD). While the idea of targeting aging as a therapeutic strategy is not new, it remains unclear how closely aging and age-associated diseases are coupled at the molecular level. Here, we discover a novel molecular link between aging and dementia through the identification of the molecular target for the AD drug candidate J147. J147 was developed using a series of phenotypic screening assays mimicking disease toxicities associated with the aging brain. We have previously demonstrated the therapeutic efficacy of J147 in several mouse models of AD. Here, we identify the mitochondrial α-F₁-ATP synthase (ATP5A) as a target for J147. By targeting ATP synthase, J147 causes an increase in intracellular calcium leading to sustained calcium/calmodulin-dependent protein kinase kinase β (CAMKK2)-dependent activation of the AMPK/mTOR pathway, a canonical longevity mechanism. Accordingly, modulation of mitochondrial processes by J147 prevents age-associated drift of the hippocampal transcriptome and plasma metabolome in mice and extends lifespan in drosophila. Our results link aging and age-associated dementia through ATP synthase, a molecular drug target that can potentially be exploited for the suppression of both. These findings demonstrate that novel screens for new AD drug candidates identify compounds that act on established aging pathways, suggesting an unexpectedly close molecular relationship between the two.

[ceridwen]

What would you do if you already had symptoms? I already have subjective cognitive decline and my LDL is 219mg/dl, HDL37,LDL159.I am an APOE4 carrier and have an APP and a PSEN2 mutation.When I joined before all of this kicked in I just wanted to live longer. Have been trying to reverse this since I was 54 I am now 58 and am still very sick. Currently trying to lower Homocysteine and blood sugar. I can't remember where I leave anything

[albedo]

@ceridwen, maybe supplementing curcumin from which I understand J417 is derived, is not a bad idea. I would try as much as I can to monitor and lower inflammation (CRP, ferritin, fibrinogen, ...). Also, considering the cardiovascular, I would do an in depth panel of lipids, including next to LDL (include the particles size, pattern A good, pattern B bad), HDL, Apo B, Apo A-I, ratio ApoB/Apo A-I, LP(a), TG's, ...... From your other posts I think you are already looking rightly at dietary interventions as cholesterol metabolism responds well, e.g. see what I just posted on the APOE genotype. The best study I ever found on diet x cholesterol interaction is posted here. I am pretty sure there is a strong connection between Alzheimer and cardiovascular diseases risks. Get good guidance.

Edited by albedo, 11 January 2018 - 05:44 PM.

[Turnbuckle]

What would you do if you already had symptoms? I already have subjective cognitive decline and my LDL is 219mg/dl, HDL37,LDL159.I am an APOE4 carrier and have an APP and a PSEN2 mutation.When I joined before all of this kicked in I just wanted to live longer. Have been trying to reverse this since I was 54 I am now 58 and am still very sick. Currently trying to lower Homocysteine and blood sugar. I can't remember where I leave anything

 

Aβ plaques are the initiators of the disease, which also involve tau as a secondary aspect. I'd suggest you try the following combination to dissolve these Aβ plaques and render the dissolved portion non-toxic. All items are available from Amazon in the US, but HEPPS may be a bit more difficult to get in the UK--

 

Alzheimer's protocol — experimental

Once a day for several months—

 

HEPPS [aka, EPPS] — 1g (1/4 level teaspoon)

Taurine — 8g (2 level teaspoons)

Oleuropein — 200 mg

Vitamin C — 2g

 

 

References—

 

Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis.

Aβ is upstream of tau in AD pathogenesis and triggers the conversion of tau from a normal to a toxic state, but there is also evidence that toxic tau enhances Aβ toxicity via a feedback loop. Because soluble toxic aggregates of both Aβ and tau can self-propagate and spread throughout the brain by prionlike mechanisms, successful therapeutic intervention for AD would benefit from detecting these species before plaques, tangles, and cognitive impairment become evident and from interfering with the destructive biochemical pathways that they initiate.

https://www.ncbi.nlm...pubmed/24493463

 

EPPS reduces Aβ-aggregate-induced memory deficits in mice

Previously, we reported a series of small ionic molecules that could accelerate the formation of Aβ aggregates in vitro. Unexpectedly, in addition to the compounds facilitating Aβ aggregation, we identified six small molecules that inhibited the formation of Aβ oligomers and fibrils13. In the current study, we tested whether these molecules could affect AD-like cognitive impairments of rodents. For this purpose, we induced memory deficits in 8.5-week-old Imprinting Control Region (ICR) mice (male, n=9–10 per group) by injecting Aβ42 aggregates (Fig. 1a,b) into the intracerebroventricular region14. This Aβ-infusion model allowed us to control the onset of abnormal Aβ deposition before or after the administration of our compounds. Among the six orally administered molecules, only 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic acid (EPPS) ameliorated AD-like phenotypes in our mouse model.

https://www.nature.com/articles/ncomms9997

 

Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer's disease

We orally administered taurine via drinking water to adult APP/PS1 transgenic mouse model for 6 weeks. Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice.

https://www.nature.com/articles/srep07467

 

Noncovalent Interaction Between Amyloid-β-Peptide (1-40) and Oleuropein Studied by Electrospray Ionization Mass Spectrometry

The successful detection of the noncovalent complex between Aβ and OE [Oleuropein] could be invaluable in a series of studies focused on screening the ability of several bioactive phytochemicals in terms of complexating Aβ and Aβox and “locking” them in a non-toxic conformation, thus acting as potential anti-amyloidogenic agents. This may offer an ideal protective alternative against Aβ toxicity.

http://www.sciencedirect.com/science/article/pii/S104403050501024X?via%3Dihub

 

Preventive and therapeutic potential of ascorbic acid in neurodegenerative diseases.

Ascorbic acid acts mainly by decreasing oxidative stress and reducing the formation of protein aggregates, which may contribute to the reduction of cognitive and/or motor impairments observed in neurodegenerative processes.

https://www.ncbi.nlm.nih.gov/pubmed/28980404

Edited by Turnbuckle, 11 January 2018 - 07:43 PM.

[tunt01]

Turnbuckle has great suggestions.  In addition to homocysteine, you have to fix your lipids.  Get HDL to above 50 if you are a female, above 40 if you are a male.  Get your LDL-c down, if possible.

 

Maybe intermittent fasting as a dietary intervention.

[recon]

I’m planning to finally ordered some J147 from teamtlr in light of the recent news about J147.

Anyone have any idea on the consumption dosaging? How much constitutes what? What’s the density, I suppose?
Someone should make it encapsulated or scooped.

[Jochen]

this looks like another compound to keep on my radar to treat my dad. Will research a bit. Definitely keen to hear any experience people have.

[VitD_1]

I’m planning to finally ordered some J147 from teamtlr in light of the recent news about J147.

Anyone have any idea on the consumption dosaging? How much constitutes what? What’s the density, I suppose?
Someone should make it encapsulated or scooped.

Did you end up taking the J147? If so, did you notice any effect? 

[recon]

I’m planning to finally ordered some J147 from teamtlr in light of the recent news about J147.

Anyone have any idea on the consumption dosaging? How much constitutes what? What’s the density, I suppose?
Someone should make it encapsulated or scooped.

Did you end up taking the J147? If so, did you notice any effect?

Unfortunately, I did not purchase J147. I placed the order but was not able to pay. The methods of payment did not work for me. The only two that might were crypto and credit card, but I do not know how to use crypto and I do not like sending my credit card details via email.

This is unfortunate. I hope to maybe buy a reloadable gift card to use instead.

[recon]

I have had a friend to purchase the J147.
I’ll be consuming it too.

How should I dosage it? I wonder if I can just use a 00 Vcaps.
I’m planning to take it with my other curcumin products.

[recon]

So since there’s no further input, I’m just buying some 00 Vcaps from NOW and manually encapsulating the J147 and take it with dinner along with other curcumin products.

[tunt01]

So since there’s no further input, I’m just buying some 00 Vcaps from NOW and manually encapsulating the J147 and take it with dinner along with other curcumin products.

 

How's it going, out of curiosity?

[recon]

So since there’s no further input, I’m just buying some 00 Vcaps from NOW and manually encapsulating the J147 and take it with dinner along with other curcumin products.

How's it going, out of curiosity?

The capsules are still on the way. They are not included as Prime shipping.

I’d expect that there will be no visible effect after taking though. I’d think that it works passively over time, probably in a couple of months. Rather than improving cognition, I’m thinking it’d prevent the decline thereof.

I’m planning to take it with meals, and with all other curcumin and turmeric supplements. Do you think this is a good idea?
I read a post above that stated that he ate them on an empty stomach to increase absorption but would it? I’d guess that having fat would improve absorption of lipid-soluble molecules and that taking other things at the same time that would overwhelm the glucuronidation process will spare more of the others.

[tunt01]

J147 was administered with food in Prior 2013 study.  CAD-31 seems to have been 'by gavage' and 'by food'.  I would assume with food is the proper approach.

 

There is one line in the CAD-31 study that says gavage with corn oil showed excellent pharmacokinetics.  I would actually think mixing with olive oil might be the best move.  Then have it in the AM on an empty stomach, skip breakfast and have lunch/dinner.

 

 

Additional file 1: Table S1 shows that CAD-31 has good bioavailability in rats and excellent distribution to the brain when administered by gavage in corn oil

 

 

If the compound mimics exercise, then I think having it without the food also has merits.  It should improve fat burning OXPHOS.

 

Prior, M., Dargusch, R., Ehren, J., Chiruta, C., & Schubert, D. (2013). The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice. Alzheimer's Research & Therapy, 5(3), 25. doi:10.1186/alzrt179

 

Daugherty, D., Goldberg, J., Fischer, W., Dargusch, R., Maher, P., & Schubert, D. (2017). A novel Alzheimer’s disease drug candidate targeting inflammation and fatty acid metabolism. Alzheimer's Research & Therapy, 9(1). doi:10.1186/s13195-017-0277-3

[recon]

J147 was administered with food in Prior 2013 study. CAD-31 seems to have been 'by gavage' and 'by food'. I would assume with food is the proper approach.

There is one line in the CAD-31 study that says gavage with corn oil showed excellent pharmacokinetics. I would actually think mixing with olive oil might be the best move. Then have it in the AM on an empty stomach, skip breakfast and have lunch/dinner.

Additional file 1: Table S1 shows that CAD-31 has good bioavailability in rats and excellent distribution to the brain when administered by gavage in corn oil

If the compound mimics exercise, then I think having it without the food also has merits. It should improve fat burning OXPHOS.
Prior, M., Dargusch, R., Ehren, J., Chiruta, C., & Schubert, D. (2013). The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice. Alzheimer's Research & Therapy, 5(3), 25. doi:10.1186/alzrt179
Daugherty, D., Goldberg, J., Fischer, W., Dargusch, R., Maher, P., & Schubert, D. (2017). A novel Alzheimer’s disease drug candidate targeting inflammation and fatty acid metabolism. Alzheimer's Research & Therapy, 9(1). doi:10.1186/s13195-017-0277-3

Wouldn’t mixing with olive oil and then eating with a meal be a better choice? I don’t think the oil mixture is sufficient compared to that along with a fatty meal or meal taken along with fish oils.

[tunt01]

I don't know enough about glucocordination to know any better.  I was thinking of rotating like 1 day of longvida curcumin and then 1 day of J147 in olive oil in the AM on a fast.  Part of my interest is based on this study in pre-diabetics of curcumin.

 

CAD-31 half-life is about 4 hrs, max plasma and brain is 8 hrs.  J147 maybe has similar pharmacokinetics, IDK.  I wonder why they moved from J147 to CAD-31.

 

The thought on an empty stomach is also partly informed by the fact that J147 and CAD-31 stimulate fat burning metabolism, ketogenesis and increase AMPK.  Seems to have features of an exercise mimetic.

[Thealchemist26]

Is anyone currently using this?

[timedilation]

Is there any reason to be concerned about the 3 fluorine atoms in J147?  Is it possible they could break off and cause problems when the body starts to metabolize the molecule?