4029 replies to this topic

[rikelme]

@streamlover Thanks for you updated protocol!

 

Do you mind clarifying this step?

- before opening, rotate bottle upside down to right side up for 15-20 secs.

 

 

[streamlover]

This is just my interpretation of accomplishing the same thing as "shaking" the container described in this paper. (Down where they're discussing their "Super saturated hydrogen generating apparatus".) I assumed their purpose is to move the trapped H2 through the water rapidly to force more into solution. When I shake these bottles, it doesn't seem to accomplish much bubbling through the water. Also the rods clank against the bottom of the bottle and I thought I could have some breaks eventually. By just rotating them about 180 a few times, it seems to get the bubbles moving up and down the bottle. Whether this actually helps much...haven't done any comparative testing. Could probably just skip this and not lose much efficiency.

[resveratrol_guy]

Hi folks, I think we need more people to analyze the salsalate study in this thread. It basically shut down hippocampal atrophy in mice, but does it matter for humans? Please post any replies over there.

[lostfalco]

Hi folks, I think we need more people to analyze the salsalate study in this thread. It basically shut down hippocampal atrophy in mice, but does it matter for humans? Please post any replies over there.

Thanks, resveratrol_guy...I'll check it out. 

 

Have you guys discussed or tested intranasal insulin on that Alzheimer's thread?  

 

As you know, it's shown some promising effects in humans already and is currently being tested long term in the SNIFF trial. https://clinicaltria...how/NCT01767909

 

Insulin receptors are very prevalent in the hippocampus where i-insulin acts a growth factor and enhances learning and memory while inhibiting the phosphorylation of tau. 

 

http://www.ncbi.nlm....pubmed/22205300

 

Mol Neurobiol. 2012 Aug;46(1):4-10. doi: 10.1007/s12035-011-8229-6. Epub 2011 Dec 29.

Brain insulin signaling and Alzheimer's disease: current evidence and future directions.

Schiöth HB1, Craft S, Brooks SJ, Frey WH 2nd, Benedict C.

Author information

Abstract

Insulin receptors in the brain are found in high densities in the hippocampus, a region that is fundamentally involved in the acquisition, consolidation, and recollection of new information. Using the intranasal method, which effectively bypasses the blood-brain barrier to deliver and target insulin directly from the nose to the brain, a series of experiments involving healthy humans has shown that increased central nervous system (CNS) insulin action enhances learning and memory processes associated with the hippocampus. Since Alzheimer's disease (AD) is linked to CNS insulin resistance, decreased expression of insulin and insulin receptor genes and attenuated permeation of blood-borne insulin across the blood-brain barrier, impaired brain insulin signaling could partially account for the cognitive deficits associated with this disease. Considering that insulin mitigates hippocampal synapse vulnerability to amyloid beta and inhibits the phosphorylation of tau, pharmacological strategies bolstering brain insulin signaling, such as intranasal insulin, could have significant therapeutic potential to deter AD pathogenesis.

 

Edited by lostfalco, 14 August 2016 - 07:13 PM.

[Amorphous]

[/quote]

4 months of materials to be learned in 1 hour? Amazing....in your lostfalco.com.... I mean the method works, but it doesn't seem like it works that well for me........Maybe I am not doing it
Hey Amorphous, this is a good question.

As I mentioned in the blog post, the semester's worth of material was for 13 to 15 year old biology students, "Using The 20/10 Method, 13 to 15 year old biology students were able to score just as well on standardized tests as their peers…" http://www.lostfalco...e-2010-method/

While it optimizes long term memory formation, it's still going to take numerous 20/10 study sessions to learn upper division college level content.

For example, I always use it after lectures to help me retain the information. Right after the lecture I take a 10 minute break, then study the lecture content again for 20 minutes, 10 min break, study again for 20 minutes.

I do this after each lecture and then I also study this way for the midterms.

So, I am using The 20/10 Method over and over again to retain material.

There is just A LOT more material in a difficult college course than a middle school biology course.

[/quote]

Lossfalco, thanks for your clarification. In this case, I think I've been doing it correctly. Actually I find it difficult to find time and motivation to do more than 2 sessions in a day. I usually reserve this method for very difficult to learn and condensed materials. Using mnemonic, method of loci, and Major system ( or PAO and/or variation) are among the choice I have for easy to grasp materials and hopefully I can remember stuffs in 1-2 settings. It is amazing to see some people can apply the techniques so efficiently to the level of the "superbrain competition" in China.
What do you think of tDCS as a role in learning? Does it really lower IQ?
At one time I was really obsessed with efficient learning and I tried all the methods in sleep learning techniques, even incorporating with neurophone/Echofone. I failed miserably with nothing but disturbed sleep. I think sleep learning is just a fancy idea and I don't think it works for me.

Edited by Amorphous, 14 August 2016 - 09:42 PM.

[resveratrol_guy]

Thanks, resveratrol_guy...I'll check it out. 

 

Have you guys discussed or tested intranasal insulin on that Alzheimer's thread? 

No, I don't believe we've discussed i-insulin in that thread. You might want to link back to here.

I just read the metastudy you posted above. It sounds like individuals with at least one copy of APOE4 would not benefit from 20 IU/d, and oddly enough those without any copies of this gene would not benefit from 40 IU/d (even though 20 was therapeutic to memory in that case). The author speculates that APOE4 carriers might require even lower doses to see an effect. And surely there are confounding factors unrelated to APOE4, which is all to say that it might take months for a person to properly calibrate.

It would be interesting to know the outcome of lifelong administration in rats. Maybe i-insulin is a one-time boost that's too dangerous to continue beyond a few months. Or perhaps it's best administered daily for life, or maybe for a month at a time several months apart. Unfortunately, chronic intranasal administration is very diffult to do in an animal study (although it was done in one particular NGF study). So in reality, the only way to learn the answer to these questions might be to follow longterm users and see how their health evolves.

I would hedge my bets with honokiol, which has shown activity against brain cancer, but I'm watching i-insulin with interest.

 

[lostfalco]

It would be interesting to know the outcome of lifelong administration in rats.

This isn't lifelong administration (it was 6 weeks)...but here is the most recent rodent study on i-insulin for Alzheimer's. Definitely worth checking out.

"Intranasal insulin alleviates cognitive deficits and amyloid pathology in young adult APPswe/PS1dE9 mice."

http://www.lostfalco...d-enhances-hip/

 

Have you read through all of the human studies yet? http://www.lostfalco...ain-injury-etc/

 

 

 

Edited by lostfalco, 15 August 2016 - 03:47 AM.

[bossmanglb]

http://bja.oxfordjou...9.full.pdf html

 

 

This paper caused a rather radical updating of my understanding of insulin. 

 

It doesn't address issues of the brain per se. But its exposition of the underappreciated inhibitory effects of insulin was enlightening and, I think, a valuable insight. 

 

Moreover, it lead me to wonder to what extent we truly understand the full scope of how insulin works in the brain. 

 

[bossmanglb]

LostFalco, I'm also curious to know you find IN insulin to be a potentiator for other nootropics or stimulants?

[resveratrol_guy]

 

It would be interesting to know the outcome of lifelong administration in rats.

This isn't lifelong administration (it was 6 weeks)...but here is the most recent rodent study on i-insulin for Alzheimer's. Definitely worth checking out.

"Intranasal insulin alleviates cognitive deficits and amyloid pathology in young adult APPswe/PS1dE9 mice."

http://www.lostfalco...d-enhances-hip/

 

Have you read through all of the human studies yet? http://www.lostfalco...ain-injury-etc/

 

 

That rodent study is astonishing! I mean, I get that insulin should enhance metabolic function in neurons like any cell type, due to immediately enhanced glucose uptake, but it's so weird that it should cause neurogenesis and reduce inflammation in the brain when it would happily upregulate inflammation anywhere else. (Geez, maybe it's upstream of NGF...)

Also, I really like the way you pre-extracted the highlights. It saves so much time and tedium going through all the minutiae, many of which would only matter to someone attempting to reproduce the experiment. Multiply that by your audience of millions of lurkers over the next century, and you've already saved hundreds of lives worth of wasted time!

I have to admit that it's a little unnerving to contemplate snorting the most reviled substance in the ketogenic theory of metabolic management. But then, I wouldn't have believed in hormesis, either, until I read that the oldest human ever was a light smoker. And none of your human studies indicate any effect on systemic glucose level.

I do wonder whether years of sleep apnea may have induced some degree of T3D independently of good metabolic health otherwise, with my fasting glucose happily in the 70s. After considering the vastly different effects of insulin on either side of the BBB, I wonder whether T2D and T3D can actually evolve way out of sync.

"Insulin treatment results in fewer areas of impaired brain glucose use (indicated by yellow)" -- You might want to clarify. In the PET scans on top, yellow is a midrange color. In the PET deltas on the bottom, it's a peak color.

It's interesting how i-insulin actually reduces olfactory sensitivity in normosmic individuals, but enhances olfactory memory in MCI/AD patients; these observations are not contradictory, but exemplify the nuances at work here.

"This effect was moderated by APOE status (p < 0.05), reflecting improvement for APOE-ε4 carriers (p < 0.02), and worsening for non-carriers (p < 0.02). Higher insulin resistance at baseline predicted greater improvement with the 40 IU dose" -- These statements seem to vary significantly across the studies, and sometimes indicate the opposite both in terms of APOE4 status and effective dose. Maybe this is just the result of small sample size, or the difference between long and short acting insulin (regular human vs. insulin aspart vs. insulin detemir), but suffice to say that calibration might take months to get right, and would ideally involve memory game scores.

"Intranasal insulin modulates intrinsic reward and prefrontal circuitry of the human brain in lean women." -- You posted this twice.

 

Anyways, great stuff!

 

bossmanglb, I think you're right: Insulin is a jeckyll-and-hyde hormone which depends heavily on dosing regimen and route of administration.


 

Edited by resveratrol_guy, 15 August 2016 - 04:14 PM.

[lostfalco]

LostFalco, I'm also curious to know you find IN insulin to be a potentiator for other nootropics or stimulants?

Hey bossmanglb...yep.

 

It pairs quite well with armodafinil (I haven't tried it with modafinil yet).

 

It pairs extremely well with caffeine and ephedrine. My theory (which is only a theory) was that ephedrine/caffeine would increase blood glucose while intranasal insulin would increase uptake of that glucose by neurons. Whether that's what actually happened or not...it subjectively worked brilliantly.  

 

This should, of course, be considered high risk. I just wanted to test the idea. See the study below for more info.

 

I have links to all of these here if anyone wants to try them.

http://www.lostfalco...harmaceuticals/

http://www.lostfalco.com/supplements/

 

 

https://www.ncbi.nlm...pubmed/15060505

 

Clin Pharmacol Ther. 2004 Apr;75(4):259-73.

Enhanced stimulant and metabolic effects of combined ephedrine and caffeine.

Haller CA¹, Jacob P 3rd, Benowitz NL.

Author information

Abstract

OBJECTIVE:

Herbal weight loss and athletic performance-enhancing supplements that contain ephedrine and caffeine have been associated with serious adverse health events. We sought to determine whether ephedrine and caffeine have clinically significant pharmacologic interactions that explain these toxicities.

METHODS:

Sixteen healthy adults ingested 25 mg ephedrine, 200 mg caffeine, or both drugs in a randomized, double-blind, placebo-controlled crossover study. Plasma and urine samples were collected over a 24-hour period and analyzed by liquid chromatography-tandem mass spectrometry for ephedrine and caffeine concentrations. Heart rate, blood pressure, and subjective responses were recorded. Serum hormonal and metabolic markers were serially measured during a 3-hour fasting period.

RESULTS:

Ephedrine plus caffeine increased systolic blood pressure (peak difference, 11.7 +/- 9.4 mm Hg; compared with placebo, P =.0005) and heart rate (peak difference, 5.9 +/- 8.8 beats/min; compared with placebo, P =.001) and raised fasting glucose, insulin, free fatty acid, and lactate concentrations. Ephedrine alone increased heart rate and glucose and insulin concentrations but did not affect systolic blood pressure. Caffeine increased systolic blood pressure and plasma free fatty acid and urinary epinephrine concentrations but did not increase heart rate. Compared with ephedrine, caffeine produced more subjective stimulant effects. Clinically significant pharmacokinetic interactions between ephedrine and caffeine were not observed. Women taking oral contraceptives had prolonged caffeine elimination (mean elimination half-life, 9.7 hours versus 5.0 hours in men; P =.05), but sex differences in pharmacodynamic responses were not seen.

CONCLUSIONS:

The individual effects of ephedrine and caffeine were modest, but the drugs in combination produced significant cardiovascular, metabolic, and hormonal responses. These enhanced effects appear to be a result of pharmacodynamic rather than pharmacokinetic interactions.

 

Edited by lostfalco, 16 August 2016 - 05:49 PM.

[lostfalco]

That rodent study is astonishing! I mean, I get that insulin should enhance metabolic function in neurons like any cell type, due to immediately enhanced glucose uptake, but it's so weird that it should cause neurogenesis and reduce inflammation in the brain when it would happily upregulate inflammation anywhere else. (Geez, maybe it's upstream of NGF...)

"Insulin treatment results in fewer areas of impaired brain glucose use (indicated by yellow)" -- You might want to clarify. In the PET scans on top, yellow is a midrange color. In the PET deltas on the bottom, it's a peak color.

It's interesting how i-insulin actually reduces olfactory sensitivity in normosmic individuals, but enhances olfactory memory in MCI/AD patients; these observations are not contradictory, but exemplify the nuances at work here.

"This effect was moderated by APOE status (p < 0.05), reflecting improvement for APOE-ε4 carriers (p < 0.02), and worsening for non-carriers (p < 0.02). Higher insulin resistance at baseline predicted greater improvement with the 40 IU dose" -- These statements seem to vary significantly across the studies, and sometimes indicate the opposite both in terms of APOE4 status and effective dose. Maybe this is just the result of small sample size, or the difference between long and short acting insulin (regular human vs. insulin aspart vs. insulin detemir), but suffice to say that calibration might take months to get right, and would ideally involve memory game scores.

"Intranasal insulin modulates intrinsic reward and prefrontal circuitry of the human brain in lean women." -- You posted this twice.

 

Anyways, great stuff!

 

I know! It's pretty crazy. This is why it's received major funding as a treatment for Alzheimer's. 

 

Yeah, the APOE studies have shown mixed results...sometimes positive sometimes not. That's why they're still testing it to look for various dosing regimens based on genotype. 

 

Thanks for the heads up on the blog post. I'll make the proper corrections. 

 

[lostfalco]

Alright, quick request from everyone.

 

I'm working on a huge blog post to end all blog posts on intranasal insulin and I need your help. 

 

I was wondering if you guys would be so kind as to ask me EVERY major question you have about it so that I can make sure to cover every major issue in the post. 

 

I can't guarantee that I'll answer all of them...but I'll try!

 

So, if there is anything that you have questions about, ask away!

[resveratrol_guy]

1. Should we take regular human insulin, insulin aspart, or insulin detemir?

2. It's doubtful that a few months' intervention with i-insulin could deter AD for more than a few months; after all, it's easier to destroy brain tissue than to remediate  it. For this reason, it's likely that some people will want to continue it longterm, in the hopes of indefinitely forestalling the disease. What risk mitigation strategies would be warranted in this case? For example, should we be looking out for nascent T3D evidenced by the need for increasing doses, or brain tumors evolving near the insufflation site, which might first manifest as phantosmia?

3. Elevated systemic insulin is connected with a wide range of cancers and reduced lifespan. Is there any evidence, human or otherwise, for or against this association between i-insulin and the brain?

4. What steps can we take to thwart the risk of brain cancer without interfering with i-insulin's benefits? (It's great that modified polio virus, and to some extent honokiol, has been used against glioblastoma rather successfully of late, but brain cancer is hardly a trivial consideration even though it's rare even in hyperinsulinemic individuals.)
 

P.S. As has been discussed in the honokiol thread, it seems to foster neurite outgrowth despite suppressing brain cancer. I wonder if we would actually obtain better safety and a stronger effect by snorting i-insulin suffused with honokiol.

Edited by resveratrol_guy, 17 August 2016 - 05:44 PM.

[lostfalco]

1. Should we take regular human insulin, insulin aspart, or insulin detemir?

2. It's doubtful that a few months' intervention with i-insulin could deter AD for more than a few months; after all, it's easier to destroy brain tissue than to remediate  it. For this reason, it's likely that some people will want to continue it longterm, in the hopes of indefinitely forestalling the disease. What risk mitigation strategies would be warranted in this case? For example, should we be looking out for nascent T3D evidenced by the need for increasing doses, or brain tumors evolving near the insufflation site, which might first manifest as phantosmia?

3. Elevated systemic insulin is connected with a wide range of cancers and reduced lifespan. Is there any evidence, human or otherwise, for or against this association between i-insulin and the brain?

4. What steps can we take to thwart the risk of brain cancer without interfering with i-insulin's benefits? (It's great that modified polio virus, and to some extent honokiol, has been used against glioblastoma rather successfully of late, but brain cancer is hardly a trivial consideration even though it's rare even in hyperinsulinemic individuals.)
 

P.S. As has been discussed in the honokiol thread, it seems to foster neurite outgrowth despite suppressing brain cancer. I wonder if we would actually obtain better safety and a stronger effect by snorting i-insulin suffused with honokiol.

Awesome list! Thanks, rg. 

[Groundhog Day]

 

Thanks, resveratrol_guy...I'll check it out. 

 

Have you guys discussed or tested intranasal insulin on that Alzheimer's thread? 

No, I don't believe we've discussed i-insulin in that thread. You might want to link back to here.

I just read the metastudy you posted above. It sounds like individuals with at least one copy of APOE4 would not benefit from 20 IU/d, and oddly enough those without any copies of this gene would not benefit from 40 IU/d (even though 20 was therapeutic to memory in that case). The author speculates that APOE4 carriers might require even lower doses to see an effect. And surely there are confounding factors unrelated to APOE4, which is all to say that it might take months for a person to properly calibrate.

It would be interesting to know the outcome of lifelong administration in rats. Maybe i-insulin is a one-time boost that's too dangerous to continue beyond a few months. Or perhaps it's best administered daily for life, or maybe for a month at a time several months apart. Unfortunately, chronic intranasal administration is very diffult to do in an animal study (although it was done in one particular NGF study). So in reality, the only way to learn the answer to these questions might be to follow longterm users and see how their health evolves.

I would hedge my bets with honokiol, which has shown activity against brain cancer, but I'm watching i-insulin with interest.

 

 

 

 

 

I have at least 1 APOE4 if I am comprehending this correctly:

 

https://www.23andme....rs/techreport/#

 

rs7412 CC

rs429358 ?

 

I noted definite benefit from 10 iu/d. I only did it for 3 weeks and regained substantial insulin sensitivity after 15 years of insulin resistance.

[resveratrol_guy]

 

 

No, I don't believe we've discussed i-insulin in that thread. You might want to link back to here.

I just read the metastudy you posted above. It sounds like individuals with at least one copy of APOE4 would not benefit from 20 IU/d, and oddly enough those without any copies of this gene would not benefit from 40 IU/d (even though 20 was therapeutic to memory in that case). The author speculates that APOE4 carriers might require even lower doses to see an effect. And surely there are confounding factors unrelated to APOE4, which is all to say that it might take months for a person to properly calibrate.

It would be interesting to know the outcome of lifelong administration in rats. Maybe i-insulin is a one-time boost that's too dangerous to continue beyond a few months. Or perhaps it's best administered daily for life, or maybe for a month at a time several months apart. Unfortunately, chronic intranasal administration is very diffult to do in an animal study (although it was done in one particular NGF study). So in reality, the only way to learn the answer to these questions might be to follow longterm users and see how their health evolves.

I would hedge my bets with honokiol, which has shown activity against brain cancer, but I'm watching i-insulin with interest.

 

 

 

 

 

I have at least 1 APOE4 if I am comprehending this correctly:

 

https://www.23andme....rs/techreport/#

 

rs7412 CC

rs429358 ?

 

I noted definite benefit from 10 iu/d. I only did it for 3 weeks and regained substantial insulin sensitivity after 15 years of insulin resistance.

 

How do you know that your insulin resistance decreased?

 

I find it strange that your report only produced results for one of the SNPs in question. But yes it looks like you have at least one copy. If you look at Table 3, though, it's actually impressive that 32% of women and 48% of men with 2 copies still don't have AD by 85. (These numbers only apply to Caucasians according to the supporting studies, but considering that APOE4 causes similar disease in mice, the conclusion is likely valid for humans generally.) So if you do in fact have another copy, it doesn't sound like something to panic about. Just do everything you can to be as deep into that 40% as possible. Hopefully by the time you would need to worry, you'll take a trip to Thailand and get a CRISPR done.(There's no reason, except for excessive regulation, that you shouldn't at least have the choice today.)  For now, if you have trouble maintaining a ketogenic diet (which is associated with having APOE4), look into a vegetable juice diet. At least, you found the right forum to hang out in!
 

Edited by resveratrol_guy, 17 August 2016 - 08:16 PM.

[Groundhog Day]

 

 

 

No, I don't believe we've discussed i-insulin in that thread. You might want to link back to here.

I just read the metastudy you posted above. It sounds like individuals with at least one copy of APOE4 would not benefit from 20 IU/d, and oddly enough those without any copies of this gene would not benefit from 40 IU/d (even though 20 was therapeutic to memory in that case). The author speculates that APOE4 carriers might require even lower doses to see an effect. And surely there are confounding factors unrelated to APOE4, which is all to say that it might take months for a person to properly calibrate.

It would be interesting to know the outcome of lifelong administration in rats. Maybe i-insulin is a one-time boost that's too dangerous to continue beyond a few months. Or perhaps it's best administered daily for life, or maybe for a month at a time several months apart. Unfortunately, chronic intranasal administration is very diffult to do in an animal study (although it was done in one particular NGF study). So in reality, the only way to learn the answer to these questions might be to follow longterm users and see how their health evolves.

I would hedge my bets with honokiol, which has shown activity against brain cancer, but I'm watching i-insulin with interest.

 

 

 

 

 

I have at least 1 APOE4 if I am comprehending this correctly:

 

https://www.23andme....rs/techreport/#

 

rs7412 CC

rs429358 ?

 

I noted definite benefit from 10 iu/d. I only did it for 3 weeks and regained substantial insulin sensitivity after 15 years of insulin resistance.

 

How do you know that your insulin resistance decreased?

 

I find it strange that your report only produced results for one of the SNPs in question. But yes it looks like you have at least one copy. If you look at Table 3, though, it's actually impressive that 32% of women and 48% of men with 2 copies still don't have AD by 85. (These numbers only apply to Caucasians according to the supporting studies, but considering that APOE4 causes similar disease in mice, the conclusion is likely valid for humans generally.) So if you do in fact have another copy, it doesn't sound like something to panic about. Just do everything you can to be as deep into that 40% as possible. Hopefully by the time you would need to worry, you'll take a trip to Thailand and get a CRISPR done.(There's no reason, except for excessive regulation, that you shouldn't at least have the choice today.)  For now, if you have trouble maintaining a ketogenic diet (which is associated with having APOE4), look into a vegetable juice diet. At least, you found the right forum to hang out in!
 

 

 

 

I have been diagnosed with:

pre-diabetes/impaired glucose tolerance
hyperinsulinema

While I haven’t been retested lately, (I’m not anxious to dump another 70g of sugar on my liver again) my symptoms greatly improved after i-insulin and I’ve tried everything under the sun.

The symptoms of insulin resistance are vast and can vary a lot based on the individual, but my IR is/was predominantly characterized by:

*Brain fog.... problems focusing and thinking, so if I went 4-5 hours without eating, I felt like I had a lobotomy and I couldn’t remember how to drive home. Really strong and impairing.

*Absurd hunger.... when it first started (15 years ago in HS after I frequently skipped meals and ate excessive candy) I had to eat every 2 hours or I felt cold, sick and brain dead. I quickly figured out to cut sugar and jack protein up....things improved slightly but still was quite bad.

About a week into insulin, I noticed my full signals coming back to life. So I would be toward the end of a meal, and I would be like, "oh god, I actually feel full". Before it felt like I could eat forever, especially carbs, and I would still have this hollow, unsatisfied feeling or signaling in my brain. For the first time in 15 years, I ate a meal, felt full and content, and then focused my mind on something else. And I could write significantly more, but I don't want to bore you... I just know after that many years that my relationship to food changed back for the better.

 

I'm only on break right now because I have very temperamental, chronic insomnia and many supplements will stimulate me and kill any chance to fall asleep. i-insulin did this at higher doses and after 3 week consistent use, but I am pretty determined to do 6-8 weeks of 10 iu/d. My sleep just has to be steady before I start it up again.

 

Interesting note about the ketogenic diet and APOE4- I tried several times to get into ketosis last year and it was absolute hell because it sent me from little sleep to no sleep. I was attempting to do it for several reasons, but my body just wouldn't produce ketones.. likely my liver producing too much sugar from the protein I consumed.

 

 

[resveratrol_guy]

It sounds like your ketogenic saga was less than successful, so maybe it's time to look into a juice diet (maybe with eggs). (I completely agree that drowning yourself in sugar all day is an unsatisfying way to live, but at least fruits and veggies actually have a flavor, unlike giant blobs of coconut oil.) I realize, furthermore, that it's counterintuitive to consume so much sugar in an attempt to lower fasting glucose, but there's some evidence that it does just that. I would also recommend looking into melatonin.

It's interesting that your response to i-insulin took about a week to manifest, although it does indeed sound like improved sensitivity. Could plaque disaggregation occur that quickly? If not, and if this is purely an insulin signalling phenomenon, then why didn't you see the full benefit within hours? I'm at a loss as to whether disaggregation and neurogenesis are primarily responsible for its effects, or merely receptor resensistization. This is not a trivial question, of course, as the answer relates to whether or not this constitutes a strategy for longerm cognitive health, rather than a brief boost.

I'm sorry that you've had trouble remembering how to drive home. Can you provide more detail as to how, if at all, i-insulin has affected your memory? Does it prevent you from descending into brain fog for more hours, in the absence of food? Or is it something else?

[Groundhog Day]

It sounds like your ketogenic saga was less than successful, so maybe it's time to look into a juice diet (maybe with eggs). (I completely agree that drowning yourself in sugar all day is an unsatisfying way to live, but at least fruits and veggies actually have a flavor, unlike giant blobs of coconut oil.) I realize, furthermore, that it's counterintuitive to consume so much sugar in an attempt to lower fasting glucose, but there's some evidence that it does just that. I would also recommend looking into melatonin.

It's interesting that your response to i-insulin took about a week to manifest, although it does indeed sound like improved sensitivity. Could plaque disaggregation occur that quickly? If not, and if this is purely an insulin signalling phenomenon, then why didn't you see the full benefit within hours? I'm at a loss as to whether disaggregation and neurogenesis are primarily responsible for its effects, or merely receptor resensistization. This is not a trivial question, of course, as the answer relates to whether or not this constitutes a strategy for longerm cognitive health, rather than a brief boost.

I'm sorry that you've had trouble remembering how to drive home. Can you provide more detail as to how, if at all, i-insulin has affected your memory? Does it prevent you from descending into brain fog for more hours, in the absence of food? Or is it something else?

 

You're referencing a juice diet in what context? I've experimented with lots of different diets but I'm unfamiliar with juice diets association with anything other than fad dieting. 

 

Melatonin for sleep? I've done extensive experimenting with various doses of melatonin and a majority of the time it does nothing, if not make my sleep more shallow.

 

I'm not sure what impact i-insulin has had on my memory. I think I am forming new memories better, though, as before so much of my life was in grind mode..... just survive. Being chronically sleep deprived, starving to death and thinking about food,  my focus and clarity didn't really exist too often. Now, with some of that alleviated, I think my memory might start sharpening back up.

 

Where I really noticed i-insulin helping me cognitively, has been with verbal articulation. This was apparent while I was on it... I should say. Explaining things more effectively in conversations, using more words... speaking better.

[Groundhog Day]

 

Does it prevent you from descending into brain fog for more hours, in the absence of food?

 

 

Yes, that's exactly what it does.

[resveratrol_guy]

As you can imagine, there is no financial incentive to study the impact of imbibing several liters of vegetable and fruit extracts everyday. What we do know is that the Kame study showed a larger protection against Alzheimer's than any other monotherapy. There is also this interesting video which followed a small group of subjects with a large number of simultaneous diseases through 4 weeks of juice dieting (as in, no solid food) and tracked their HbA1c and other basic parameters, all of which seem to have improved. It's one thing when someone goes on YouTube and posts a video saying substance X has changed their life. It's quite another when you can actually see them looking better week after week. Some people call it a "juice fast", which is a misnomer because in its usual form it imposes no restriction on caloric intake. (But CR probably occurs anyway; after all, how much brocolli juice do you really want to drink?!)

Part of the reason for the diet's success, apart from the countless phytochemicals involved, is simply carbosis. Carbosis would appear to be second only to ketosis for the sake of maintaining metabolic health (based on Jean Calment vs. other supercentenarians, which I admit is a weak statistic), which is ironic, considering the dangers of eating a SAD diet rich in sugar. But the difference may disappear entirely when one accounts for said phytochemicals; obviously, the particular selection of fruits and vegetables is important, but secondary to the benefits of carbosis itself. SAD is dangerous because it combines sugar with methionine in the relative absence of phytochemicals and in the presence of industrial chemicals (not that all phytochemicals are good and all industrial chemicals are bad, but that's certainly a reasonable approximation).

As you can see in the videos, anyone attempting a juice diet is pretty much guaranteed to hate life for the first week or two. It helps to keep extremely busy with work while your gut microbiome and hormonal networks adjust and stop craving SAD garbage. (Some higher end probiotics, like the ones requiring refrigeration, would probably help. Or maybe a teaspoon of unsweetened Greek yoghurt per day for the first 2 weeks, e.g. Faye full fat.) Having shifted among a ketogenic diet, a supercentenarian diet, and a juice diet supplemented with raw eggs and olive oil, I'm convinced at this point that the last one is most effective for me. You might want to look into it.

As to melatonin, you might try a combination of quick release 3 mg with delayed release 1 mg, or thereabouts. Otherwise I guess it just doesn't work for you.

Verbal articulation? How odd. I thought that had more to do with the right hemisphere than the hippocampus. My verbal articulation, and in particular deciding how I need to express myself, is fairly retarded. My math skills are excellent, despite having brain damage on the left side and none on the right. Go figure. Anyway at risk of placeboing myself, I really hope to achieve the same effect.
 

Your affirmation that it keeps away the brain fog for extended periods of time sounds like modafinal, even though I wouldn't expect them to operate in the same manner. Very, very cool.

[lostfalco]

Weird. I just came across some research indicating that the thyroid hormone, T2, is an allosteric modulator of cytochrome C oxidase. Really interesting.

 

"COX subunit Va, which localizes to the matrix (Fig. 1), was shown to bind the thyroid hormone T2. Upon binding, the allosteric ATP inhibition is released, allowing a high turnover even at high ATP/ADP ratios [24]."  http://www.ncbi.nlm....les/PMC3229836/

 

http://www.ncbi.nlm..../pubmed/8013649

 

FEBS Lett. 1994 Jun 13;346(2-3):295-8.

Interaction of diiodothyronines with isolated cytochrome c oxidase.

Goglia F1, Lanni A, Barth J, Kadenbach B.

Author information

Abstract

Diiodothyronines (3,3'-T2 and 3,5-T2) stimulate the activity of isolated cytochrome c oxidase (COX) from bovine heart mitochondria. Maximal stimulation of activity (about 50%) is obtained with 3,3'-T2 at pH 6.4 and with 3,5-T2 at pH 7.4. In contrast, 3,5,3'-triiodothyronine (T3) exhibited no or little stimulation of COX activity. Binding of the hormones to COX leads to conformational changes as shown by modified visible spectra of the oxidized enzyme. It is suggested that 'short-term' effects of thyroid hormones on mitochondrial respiration are at least partly due to the allosteric interaction of diiodothyronines with the COX complex.

 

Edited by lostfalco, 21 August 2016 - 08:42 PM.

[resveratrol_guy]

Alright, quick request from everyone.

 

I'm working on a huge blog post to end all blog posts on intranasal insulin and I need your help. 

 

I was wondering if you guys would be so kind as to ask me EVERY major question you have about it so that I can make sure to cover every major issue in the post. 

 

I can't guarantee that I'll answer all of them...but I'll try!

 

So, if there is anything that you have questions about, ask away!

 

Sorry to come back to this, but I have one more question, regarding the mechanical process by which to create the spray solution. Your photo here is a bit confusing, but it sounds from the notes as though it's actually a photo of 2 different bottle types, as opposed to 2 projections of the same type. It also sounds as though you suggest removing the top at the base of the neck, as opposed to the collar of the pump mechanism. Finally, I don't know if you want to mention anything about it, but using plain old garage pliers might be a bad idea, as one could deposit metal powder or whatever gunk the pliers have accumulated on the neck; this is too close for comfort for insufflation purposes, and not everyone has your level of attention to detail.

 

I've already told lots of friends about this page you've set up. Thanks for the continuing public service.

Edited by resveratrol_guy, 22 August 2016 - 06:47 PM.

[lostfalco]

Sorry to come back to this, but I have one more question, regarding the mechanical process by which to create the spray solution. Your photo here is a bit confusing, but it sounds from the notes as though it's actually a photo of 2 different bottle types, as opposed to 2 projections of the same type. It also sounds as though you suggest removing the top at the base of the neck, as opposed to the collar of the pump mechanism. Finally, I don't know if you want to mention anything about it, but using plain old garage pliers might be a bad idea, as one could deposit metal powder or whatever gunk the pliers have accumulated on the neck; this is too close for comfort for insufflation purposes, and not everyone has your level of attention to detail.

 

I've already told lots of friends about this page you've set up. Thanks for the continuing public service.

 

Thanks for telling people about my page, rg!

 

Have you purchased a vial of i-insulin yet? The way the cap fits on to the bottle makes it extremely unlikely that the pliers would cause shards to get mixed in. You're right though, I'll mention that people should be careful since it never hurts to be overly cautious with one's brain. I should really just make a video. ha

[bossmanglb]

In re potentiation and our concern for brain energetics and metabolic/ATP optimization: 

 

I'm wondering if IN insulin would increase creatine uptake to the brain, permitting supraphysiological levels with sufficient supplementation and time. 

Can't say for certain if this would be beneficial in normal/high-functioning individuals. But perhaps. 

 

 

 

Edited by bossmanglb, 23 August 2016 - 05:42 AM.

[MindExplorer]

Questions related to i-insulin:

 

1. What are your thoughts on meta-cresol?
2. Did that longitudinal study ever finish?
3. Did it use human insulin that was preserved with meta-cresol like Novolin-R?

[lostfalco]

Questions related to i-insulin:

 

1. What are your thoughts on meta-cresol?
2. Did that longitudinal study ever finish?
3. Did it use human insulin that was preserved with meta-cresol like Novolin-R?

1. I messaged Dr. Suzanne Craft to get her thoughts on meta-cresol in intransal insulin. She is Professor of Gerontology and Geriatric Medicine at Wake Forest and is one of the leading researchers on intranasal insulin as a treatment for Alzheimer's. She's actually spearheading the SNIFF trial. https://www.nia.nih....etfulness-sniff

 

Here's her faculty page. http://www.wakehealt...aft-Suzanne.htm

 

Anyway, here was her response when I asked her about the risk of meta-cresol in i-insulin (quoted with permission).

 

"You are correct that meta-cresol is frequently used as a preservative for insulin and that animal studies have raised questions about its safety in large doses or after prolonged exposure. As with most preservatives, there is a balance that has to be achieved between the possible negative effects of the preservative and the possible negative effects of contaminated or “spoiled” insulin, particularly when one is targeting the brain, which is susceptible to bacterial infections. Several companies are working on developing meta-cresol-free insulin formulations and hopefully they will be available soon to test for the purpose of treating neurodegenerative disease, but currently they are not widely available and they are expensive relative to regular insulin. Regarding the specific risk for Alzheimer’s patients, as it is a fatal disease with no current effective treatments, I believe most scientists would agree that the potential benefit of the insulin outweighs the risks of the meta-cresol since those risks have not been definitively documented in humans at the doses used in current insulin formulations."

 

2. SNIFF is scheduled to finish in 2017.

 

3. Almost certainly yes...but I say 'almost' because the results haven't been published yet. Virtually every available insulin has metacresol in it. 

 

4. I've been in discussions with Paul at Ceretropic and with the owner of irc.bio about providing a metacresol free insulin formulation and they were both interested in looking into it. If people want to message them to show there is demand...I wouldn't complain. =)

Ceretropic: https://www.reddit.c...terYouAreSoDumb

irc.bio: https://irc.bio/contact-us/

Edited by lostfalco, 23 August 2016 - 02:49 PM.

[resveratrol_guy]

Thanks for telling people about my page, rg!

 

Have you purchased a vial of i-insulin yet? The way the cap fits on to the bottle makes it extremely unlikely that the pliers would cause shards to get mixed in. You're right though, I'll mention that people should be careful since it never hurts to be overly cautious with one's brain. I should really just make a video. ha

 

I haven't purchased it yet. But it's in my pipeline, for sure at this point.

 

I wasn't so worried about shards as metallic dust that would tend to aggregate on the neck, and spread from there to other parts of the pump due to handling. The problem is easily averted with proper warnings. Yeah, a video would be ideal.

 

+1 for metacresol-free (but not preservative-free) insulin. (It makes you wonder what the replacement would be, though. Maybe i-insulin doesn't work but metacresol hormesis enhances brain power!)
 

[lostfalco]

In re potentiation and our concern for brain energetics and metabolic/ATP optimization: 

 

I'm wondering if IN insulin would increase creatine uptake to the brain, permitting supraphysiological levels with sufficient supplementation and time. 

Can't say for certain if this would be beneficial in normal/high-functioning individuals. But perhaps. 

Interesting question, bossmanglb. I'm not totally sure about creatine uptake but it does increase phosphocreatine in human brains. 

 

"In a double-blind, placebo-controlled, within-subject comparison, 15 healthy men (BMI 22.2 ± 0.37 kg/m(2)) aged 22-28 years were intranasally administered insulin (40 IU) or placebo after an overnight fast. Cerebral energy metabolism was assessed by (31)P magnetic resonance spectroscopy. At 100 min after spray administration, participants consumed ad libitum from a test buffet. Our data show that intranasal insulin increases brain energy (i.e., adenosine triphosphate and phosphocreatine levels). Cerebral energy content correlates inversely with subsequent calorie intake in the control condition." http://www.ncbi.nlm....pubmed/22586589

Edited by lostfalco, 23 August 2016 - 09:17 PM.