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J-147 and Fisetin for Treatment Resistant Depression and Aging in General

j-147 j147 fisetin aging depression energy fatigue bipolar antiaging sports

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#121 biggyrat

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Posted 12 September 2020 - 01:12 AM

The only info I’ve found for solubility mentions it’s highly soluble in DMSO and insoluble in water. You’ll have to use tequila or a higher proof alcohol to test it out.

Edit: sciencebio’s website notes it is soluble in ethanol so most high proof alcohols should work.

Thank you much! 



#122 aribadabar

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Posted 12 September 2020 - 02:22 AM

What is the best way to store J-147 powder: room temperature, refrigerator, freezer?

 

Provided it is properly packaged, everything lasts longer/stays fresher at lower temps so RT<fridge<freezer.



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#123 p75213

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Posted 13 September 2020 - 04:46 AM

j147 at a dose of 10mg/kg, reversed cognitive impairment in aged alzheimer's disease mice (https://www.ncbi.nlm...les/PMC3706879/). Is the HED 46mg for a 70kg human?

 

On another note it would be nice to know the results from the phase 1 trials - https://www.clinical...udy/NCT03838185.



#124 APBT

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Posted 23 September 2020 - 01:05 PM

Has anyone else purchased and trialed J-147?  What is your user experience? 



#125 Daniel Cooper

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Posted 23 September 2020 - 06:39 PM

j147 at a dose of 10mg/kg, reversed cognitive impairment in aged alzheimer's disease mice (https://www.ncbi.nlm...les/PMC3706879/). Is the HED 46mg for a 70kg human?

 

On another note it would be nice to know the results from the phase 1 trials - https://www.clinical...udy/NCT03838185.

 

(10mg/kg)/12.3 (mouse to human) x 70kg = 57mg 

 

Call it 60mg.  The precision involved in these HEDs swamp out that 3mg. 


Edited by Daniel Cooper, 23 September 2020 - 06:39 PM.


#126 p75213

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Posted 24 September 2020 - 07:11 PM

I was using equation 1 from this paper - http://europepmc.org...cle/PMC/4804402 (HED (mg / kg = Animal NOAEL mg/kg) × (Weightanimal [kg]/Weighthuman [kg])(1–0.67) Eq. (1)).

Equation 2 is: HED (mg / kg) = Animal does (mg / kg) × (Animal Km / Human Km) Eq. (2)

When is it appropriate to use one formula over another? Maybe take the average of the two?

#127 Daniel Cooper

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Posted 24 September 2020 - 07:37 PM

You could easily split the difference, but I think we'd be fooling ourselves if we think these HED conversion schemes are highly accurate.  They hopefully get you in the ballpark, but there can be an enormous difference between how different species metabolize and eliminate different compounds.  These schemes which are usually based around mass, volume, and surface area which do not take detailed differences in metabolism into consideration at all.  Take for instance the differences in the way humans and cats metabolize acetaminophen, which is absolutely not reflected if you simply convert from human to feline using HED schemes (pro tip - don't give your cat Tylenol).

 

Bottom line, I think you could use your HED or my HED and not see a whole lot of difference in effect.  

 

 

 

 


Edited by Daniel Cooper, 24 September 2020 - 07:38 PM.


#128 bladedmind

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Posted 12 March 2021 - 07:37 PM

I’m 71 with type-2 diabetes moderately controlled by metformin and a lower carb diet.  My fasting blood glucose has been100.  My hgb1ac crept up to 5.8, so I recently undertook corrective measures. I went back to intermittent fasting (dinner at 6, breakfast at 10), lowered carbs a bit and raised good fats, and strived once again to implement what Dr. Dale Bredesen calls a keto-adapted diet for APOE 4/4s like me.  It does not aim for full ketosis, but rather keto-adaptation, to be in mild ketosis (BHB between 1.0 and 5.0 mmol/L) at least once a day, your body switching between glucose and ketones.   The older, Alzheimer’s-prone brain becomes insulin resistant and works better if it can access both ketones and some glucose, the story goes. 

 

In the last six months I’ve consistently been taking ND cordyceps 10:1 extract.  Also, months ago I obtained Aasraw J147 and dabbled with 20-40 mg/day, not feeling any mood or energy changes, and set it aside.   In the last two months I’ve added ND rhodiola, 3% salidroside with good mood and energy results. 

 

I dreaded attempting to reach ketosis again.  I had tried it 20 years ago for six months, and felt only exhaustion and anxiety.   Since then I’ve made a one-month try and a two-month try with the same result.   Past attempts at the milder Bredesen diet did not feel good. 

 

Two weeks ago I resumed J147 40 mg/day and began a keto-adapted diet pattern.  I continued cordyceps and rhodiola (I keep mentioning this because it confounds causation of the outcome).  The results are remarkable.   Fasting bg is 70.  Two-hour post-prandial is 100 – and 5 hours out is down to 70.   I awake in mild ketosis and feel great.   Using the ketone meter I’ve learned to sense the ketosis state – sometimes I am in it for a bit between meals.   First time ever I’ve  felt great in ketosis.   Good mood, good energy, mental clarity, and the physical stamina of 35 years ago.

 

It turns out that rhodiola and cordyceps can normalize blood sugar regulation (can provide references on request).   But I’m here to talk about J147 and ketosis. 
 

 

https://en.wikipedia.org/wiki/J147

 

Enhanced neurogenic activity over J147 in human neural precursor cells has its derivative called CAD-31. CAD-31 is enhancing the use of free fatty acids for energy production by shifting of the metabolic profile of fatty acids toward the production of ketone bodies, a potent source of energy in the brain when glucose levels are low.

 

 

https://journals.plo...al.pone.0027865

 

J147 is also neuroprotective against glucose starvation

 

 

I have no biochemistry training and hope to hear comments on the phenomena of eased and comfortable ketosis associated with J147 intake. 

 

Also, in today’s research came across:

Sub-Acute Treatment of Curcumin Derivative J147 Ameliorates Depression-Like Behavior Through 5-HT1A-Mediated cAMP Signaling

This 2020 article is a followup to a 2018 article by the same team. 


Edited by bladedmind, 12 March 2021 - 07:39 PM.

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#129 bladedmind

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Posted 14 March 2021 - 08:07 PM

Also,

A novel curcumin derivative for the treatment of diabetic neuropathy
 

Abstract.  Neuropathy is a common complication of long-term diabetes. Proposed mechanisms of neuronal damage caused by diabetes that are downstream of hyperglycemia and/or loss of insulin signaling include ischemic hypoxia, inflammation and loss of neurotrophic support. The curcumin derivative J147 is a potent neurogenic and neuroprotective drug candidate initially developed for the treatment of neurodegenerative conditions associated with aging that impacts many pathways implicated in the pathogenesis of diabetic neuropathy….

Chronic oral treatment with J147 protected the sciatic nerve from progressive diabetes-induced slowing of large myelinated fiber conduction velocity while single doses of J147 rapidly and transiently reversed established touch-evoked allodynia. ….

The diverse biological and therapeutic effects of J147 suggest it as an alternative to the polypharmaceutical approaches required to treat the multiple pathogenic mechanisms that contribute to diabetic neuropathy.

 



#130 graatch

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Posted 05 December 2021 - 12:13 PM

This looks like the most active J147 thread.

 

Those few of us who have used it, may I ask if you noticed any initial side effects? I received some of this from science.bio a little while ago. The first time I took it I seemed to react kind of strangely ... I remember getting flushed and hot. I was probably in a biological state of some stress at the time that I took it, as I'd missed some sleep. It was weird and uncomfortable enough for me to put the stuff away until I got a chance to talk about it with others. And now I am trying to do so. I took, by the way, 10 milligrams.


Edited by graatch, 05 December 2021 - 12:13 PM.


#131 The Capybara

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Posted 07 December 2021 - 06:24 AM

This looks like the most active J147 thread.

 

Those few of us who have used it, may I ask if you noticed any initial side effects? I received some of this from science.bio a little while ago. The first time I took it I seemed to react kind of strangely ... I remember getting flushed and hot. I was probably in a biological state of some stress at the time that I took it, as I'd missed some sleep. It was weird and uncomfortable enough for me to put the stuff away until I got a chance to talk about it with others. And now I am trying to do so. I took, by the way, 10 milligrams.

 

 

Now that's interesting !!!

 

It seems that most people don't appear to feel effects from J-147.

I had (and continue to have) profound effects, and I've been on it years at this point.

I think that I was the first person to try this compound, and because I couldn't find anyone else I had to calibrate my own dose.

I now suspect that personal dosages are all over the place. Perhaps the reason that many others haven't seen any effects from taking J-147 is because they aren't taking enough to feel it. They haven't found their optimal dose.

One also can't dismiss the possibility that not feeling the effects does not mean that there's no health benefits.

I tend to believe that both are true.

 

When I was calibrating my personal dose, I began by calculating the Human Equivalent Dose (see other's posts just above).

I then cut that dose in 1/4 and began there.

My HED was about 40mg, and so I began at 10mg. I'd double the dose every few days.

When I got to 40mg I felt great after about four days at that dose (see the very start of this thread).

I then doubled that dose to 80mg to see how that dosage played out.

I soon felt hot, and was heat intolerant going outside. I felt unwell overall, which lasted a few hours.

Propranolol helped a good amount..

Because of this, I backed off to 40mg and stayed there for a few years, extremely happy with the effects.

It changed my life.

 

What you're feeling "Graatch" sounds like too high a dose for you.

I wouldn't give up, and I'd take these side effects as a likely positive response to J-147, but at too high a dose.

Do keep me posted on your experiment if you decide to go on.


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#132 Daniel Cooper

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Posted 14 December 2021 - 03:43 PM

Where are you getting your J147 Capybara?

 

I sourced mine from Reach Genius in Sweden and never felt anything one way or the other. However, apparently their J147 has been called into question by some. I thought they were out of business but I see the website is still up.

 

 



#133 APBT

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Posted 19 December 2021 - 02:40 PM

Where are you getting your J147 Capybara?

 

I sourced mine from Reach Genius in Sweden and never felt anything one way or the other. However, apparently their J147 has been called into question by some. I thought they were out of business but I see the website is still up.

 

From the last paragraph of his original post:  "I order my J-147 from aas19@aasraw.com."



#134 ThaNiteHawK

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Posted 20 April 2023 - 08:45 PM

Hi,
Are there more people now that can report back on this substance?
Does somebody know a supplier with good prices that ships from Europe?

#135 ThaNiteHawK

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Posted 19 June 2023 - 01:29 AM

Nobody active here anymore?

 

I just wanted to order it but then I read this:

https://www.ncbi.nlm...les/PMC8649847/

 

According to this research paper it inhibits melanogenesis which should brighten the skin.

That sounds not good. Also I assume this will will lead to even more grey hair. :-/


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#136 The Capybara

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Posted 19 June 2023 - 04:51 AM

Ha! Pretty interesting paper.
I live in Arizona, still take J147 (for nearly 10 years I suppose). I still tan normally.
I have to guess that taking the compound at reasonable amounts never reaches the blood concentrations needed to noticeably suppress melanogenesis.
Interesting paper though.
Ha! Pretty interesting paper.
I live in Arizona, still take J147 (for nearly 10 years I suppose). I still tan normally.
I have to guess that taking the compound at reasonable amounts never reaches the blood concentrations needed to noticeably suppress melanogenesis.
Interesting paper though.

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#137 The Capybara

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Posted 19 June 2023 - 04:57 AM

I do have more information on the compound.
Are people still following this thread?
If so, there’s some data on why it’s very active in some, and seems to do nothing in others. That phenomenon has been observed in animal models, including C. elegans. In the case of the unresponsive flatworm, it was changed to responsive totally by accident. That’s how science often works.

For the record, I still buy my J147 from the same source. If it’s not broke……

Edited by The Capybara, 19 June 2023 - 05:02 AM.






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