4029 replies to this topic

[magta39]

Lostfalco, how are you timing pyruvate and butyrate as far as your studying sessions?  It seems to help me by taking them 2 or 3 hours after studying/learning, helping to consolidate everything into my long term memory for the next day...your thoughts?

[lostfalco]

Lostfalco, how are you timing pyruvate and butyrate as far as your studying sessions?  It seems to help me by taking them 2 or 3 hours after studying/learning, helping to consolidate everything into my long term memory for the next day...your thoughts?

Hey magta, the timing is a bit complex but yes, HDACi seems to enhance consolidation and should be administered after the learning event. I think each of us will probably have to experiment with different timings in order to find what works best in our individual cases. =) 

 

rodent study, ip injection of sodium butyrate

 

http://www.ncbi.nlm....les/PMC2695069/

 

"Again, mice were subject to habituation, 3 min of training, followed immediately by an injection of vehicle or NaBut."

 

"Mice treated with NaBut (NaBut, DI = 39.4 ± 7.6%; n = 9; t = 2.49, P < 0.01) showed significantly better memory for the familiar object than vehicle controls (vehicle, DI = 16.0 ± 5.5%; n = 8; Fig. 3A)."

 

 

http://www.ncbi.nlm....les/PMC3111848/

 

"Despite the consistent enhancements of long-term memory by loss of HDAC3 function, short-term memory for the object recognition task was unaffected. A major difference between these forms of memory is that, in general, transcription is essential for the formation of long-term memory, but not short-term memory. We and others have found that HDAC inhibition by sodium butyrate, TSA, or SAHA have no effect on short-term memory (Yeh et al., 2004; Levenson et al., 2004; Korzus et al., 2004; Vecsey et al., 2007; Stefanko et al., 2009). Therefore, HDAC3 inhibition is likely enhancing memory through increased gene expression."

 

 

Neurobiol Learn Mem. 2011 Jul;96(1):27-34. doi: 10.1016/j.nlm.2011.04.002. Epub 2011 Apr 16.

HDAC3 and the molecular brake pad hypothesis.

McQuown SC1, Wood MA.

Author information

Abstract

Successful transcription of specific genes required for long-term memory processes involves the orchestrated effort of not only transcription factors, but also very specific enzymatic protein complexes that modify chromatin structure. Chromatin modification has been identified as a pivotal molecular mechanism underlying certain forms of synaptic plasticity and memory. The best-studied form of chromatin modification in the learning and memory field is histone acetylation, which is regulated by histone acetyltransferases and histone deacetylases (HDACs). HDAC inhibitors have been shown to strongly enhance long-term memory processes, and recent work has aimed to identify contributions of individual HDACs. In this review, we focus on HDAC3 and discuss its recently defined role as a negative regulator of long-term memory formation. HDAC3 is part of a corepressor complex and has direct interactions with Class II HDACs that may be important for its molecular and behavioral consequences. And last, we propose the "molecular brake pad" hypothesis of HDAC function. The HDACs and associated corepressor complexes may function in neurons, in part, as "molecular brake pads." HDACs are localized to promoters of active genes and act as a persistent clamp that requires strong activity-dependent signaling to temporarily release these complexes (or brake pads) to activate gene expression required for long-term memory formation. Thus, HDAC inhibition removes the "molecular brake pads" constraining the processes necessary for long-term memory and results in strong, persistent memory formation.

[magta39]

 

Lostfalco, how are you timing pyruvate and butyrate as far as your studying sessions?  It seems to help me by taking them 2 or 3 hours after studying/learning, helping to consolidate everything into my long term memory for the next day...your thoughts?

Hey magta, the timing is a bit complex but yes, HDACi seems to enhance consolidation and should be administered after the learning event. I think each of us will probably have to experiment with different timings in order to find what works best in our individual cases. =) 

 

rodent study, ip injection of sodium butyrate

 

http://www.ncbi.nlm....les/PMC2695069/

 

"Again, mice were subject to habituation, 3 min of training, followed immediately by an injection of vehicle or NaBut."

 

"Mice treated with NaBut (NaBut, DI = 39.4 ± 7.6%; n = 9; t = 2.49, P < 0.01) showed significantly better memory for the familiar object than vehicle controls (vehicle, DI = 16.0 ± 5.5%; n = 8; Fig. 3A)."

 

 

http://www.ncbi.nlm....les/PMC3111848/

 

"Despite the consistent enhancements of long-term memory by loss of HDAC3 function, short-term memory for the object recognition task was unaffected. A major difference between these forms of memory is that, in general, transcription is essential for the formation of long-term memory, but not short-term memory. We and others have found that HDAC inhibition by sodium butyrate, TSA, or SAHA have no effect on short-term memory (Yeh et al., 2004; Levenson et al., 2004; Korzus et al., 2004; Vecsey et al., 2007; Stefanko et al., 2009). Therefore, HDAC3 inhibition is likely enhancing memory through increased gene expression."

 

 

Neurobiol Learn Mem. 2011 Jul;96(1):27-34. doi: 10.1016/j.nlm.2011.04.002. Epub 2011 Apr 16.

HDAC3 and the molecular brake pad hypothesis.

McQuown SC1, Wood MA.

Author information

Abstract

Successful transcription of specific genes required for long-term memory processes involves the orchestrated effort of not only transcription factors, but also very specific enzymatic protein complexes that modify chromatin structure. Chromatin modification has been identified as a pivotal molecular mechanism underlying certain forms of synaptic plasticity and memory. The best-studied form of chromatin modification in the learning and memory field is histone acetylation, which is regulated by histone acetyltransferases and histone deacetylases (HDACs). HDAC inhibitors have been shown to strongly enhance long-term memory processes, and recent work has aimed to identify contributions of individual HDACs. In this review, we focus on HDAC3 and discuss its recently defined role as a negative regulator of long-term memory formation. HDAC3 is part of a corepressor complex and has direct interactions with Class II HDACs that may be important for its molecular and behavioral consequences. And last, we propose the "molecular brake pad" hypothesis of HDAC function. The HDACs and associated corepressor complexes may function in neurons, in part, as "molecular brake pads." HDACs are localized to promoters of active genes and act as a persistent clamp that requires strong activity-dependent signaling to temporarily release these complexes (or brake pads) to activate gene expression required for long-term memory formation. Thus, HDAC inhibition removes the "molecular brake pads" constraining the processes necessary for long-term memory and results in strong, persistent memory formation.

 

 

Thanks for these research citations Lostfalco...I will play with the timing a bit....the reason for the 2 or 3 hour delay is because that's when my pyruvate shipment arrived!

 

[lostfalco]

Recent article on molecular hydrogen. =)

 

http://www.ncbi.nlm....les/PMC4610055/

 

Med Gas Res. 2015 Oct 19;5:12. doi: 10.1186/s13618-015-0035-1. eCollection 2015.

Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles.

Ichihara M1, Sobue S1, Ito M2, Ito M3, Hirayama M4, Ohno K2.

Author information

Abstract

Therapeutic effects of molecular hydrogen for a wide range of disease models and human diseases have been investigated since 2007. A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. About three-quarters of the articles show the effects in mice and rats. The number of clinical trials is increasing every year. In most diseases, the effect of hydrogen has been reported with hydrogen water or hydrogen gas, which was followed by confirmation of the effect with hydrogen-rich saline. Hydrogen water is mostly given ad libitum. Hydrogen gas of less than 4 % is given by inhalation. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases. Specific extinctions of hydroxyl radical and peroxynitrite were initially presented, but the radical-scavenging effect of hydrogen cannot be held solely accountable for its drastic effects. We and others have shown that the effects can be mediated by modulating activities and expressions of various molecules such as Lyn, ERK, p38, JNK, ASK1, Akt, GTP-Rac1, iNOS, Nox1, NF-κB p65, IκBα, STAT3, NFATc1, c-Fos, and ghrelin. Master regulator(s) that drive these modifications, however, remain to be elucidated and are currently being extensively investigated.

 

 

 

 

[lostfalco]

Molecular hydrogen water increases ghrelin (rodent study) which affects learning, memory, and recovery from brain injury. 

 

http://www.ncbi.nlm....les/PMC4443295/

 

"Ghrelin exhibits dense receptor expression in the hippocampus [188], where it has been found to forms of learning and memory performance in rodents. For example, ghrelin administration has been shown to promote long term potentiation in the hippocampus, increase spine density of neurons in the hippocampal CA1 region, and enhance performance in several types of hippocampal-dependent learning and memory tasks [188,248]. Additionally, ghrelin has been shown to increase survival and reduce cell death of hippocampal neurons following ischemia/reperfusion injury [249]. Finally, it was recently shown that ghrelin cells receive direct synaptic input from the suprachiasmatic nucleus and the lateral geniculate nucleus, suggesting that ghrelin is implicated in mediating circadian and visual cues for the hypothalamic arousal system [250]"

 

 

http://www.ncbi.nlm....les/PMC4070541/

 

Sci Rep. 2013 Nov 20;3:3273. doi: 10.1038/srep03273.

Oral 'hydrogen water' induces neuroprotective ghrelin secretion in mice.

Matsumoto A1, Yamafuji M, Tachibana T, Nakabeppu Y, Noda M, Nakaya H.

Author information

Abstract

The therapeutic potential of molecular hydrogen (H₂) is emerging in a number of human diseases and in their animal models, including in particular Parkinson's disease (PD). H₂ supplementation of drinking water has been shown to exert disease-modifying effects in PD patients and neuroprotective effects in experimental PD model mice. However, H₂ supplementation does not result in detectable changes in striatal H₂ levels, indicating an indirect effect. Here we show that H₂ supplementation increases gastric expression of mRNA encoding ghrelin, a growth hormone secretagogue, and ghrelin secretion, which are antagonized by the β1-adrenoceptor blocker, atenolol. Strikingly, the neuroprotective effect of H₂ water was abolished by either administration of the ghrelin receptor-antagonist, D-Lys(3) GHRP-6, or atenolol. Thus, the neuroprotective effect of H₂ in PD is mediated by enhanced production of ghrelin. Our findings point to potential, novel strategies for ameliorating pathophysiology in which a protective effect of H₂ supplementation has been demonstrated.

 

 

 

 

Edited by lostfalco, 01 December 2015 - 12:22 AM.

[lostfalco]

http://www.ncbi.nlm....les/PMC3890894/

 

Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):E149-58. doi: 10.1073/pnas.1313798111. Epub 2013 Dec 23.

Ghrelin triggers the synaptic incorporation of AMPA receptors in the hippocampus.

Ribeiro LF1, Catarino T, Santos SD, Benoist M, van Leeuwen JF, Esteban JA, Carvalho AL.

Author information

Abstract

Ghrelin is a peptide mainly produced by the stomach and released into circulation, affecting energy balance and growth hormone release. These effects are guided largely by the expression of the ghrelin receptor growth hormone secretagogue type 1a (GHS-R1a) in the hypothalamus and pituitary. However, GHS-R1a is expressed in other brain regions, including the hippocampus, where its activation enhances memory retention. Herein we explore the molecular mechanism underlying the action of ghrelin on hippocampal-dependent memory. Our data show that GHS-R1a is localized in the vicinity of hippocampal excitatory synapses, and that its activation increases delivery of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic-type receptors (AMPARs) to synapses, producing functional modifications at excitatory synapses. Moreover, GHS-R1a activation enhances two different paradigms of long-term potentiation in the hippocampus, activates the phosphatidylinositol 3-kinase, and increases GluA1 AMPAR subunit and stargazin phosphorylation. We propose that GHS-R1a activation in the hippocampus enhances excitatory synaptic transmission and synaptic plasticity by regulating AMPAR trafficking. Our study provides insights into mechanisms that may mediate the cognition-enhancing effect of ghrelin, and suggests a possible link between the regulation of energy metabolism and learning.

 

[magta39]

Turmeric increases gut production of Hydrogen.

Effect of dietary turmeric on breath hydrogen.

Shimouchi A¹, Nose K, Takaoka M, Hayashi H, Kondo T.

Author information

Abstract

Turmeric is widely used in Indian cuisine. The main constituents of turmeric are curcumin and its analogues, which are well-known antioxidant compounds. In the present study, we hypothesized that turmeric in curry might increase bowel motility and activate hydrogen-producing bacterial flora in the colon, thereby increasing the concentration of breath hydrogen. Eight healthy subjects fasted for 12 h and ingested curry and rice with or without turmeric (turmeric knockout curry). Breath-hydrogen concentrations were analyzed every 15 min for 6 h by gas chromatography with a semiconductor detector. Curry with turmeric significantly increased the area under the curve of breath hydrogen and shortened small-bowel transit time, compared with curry not containing turmeric. These results suggested that dietary turmeric activated bowel motility and carbohydrate colonic fermentation.

PMID: 19034660 [PubMed - indexed for MEDLINE]

[lostfalco]

 

Turmeric increases gut production of Hydrogen.

 

Nice find, magta! Yeah, our microbiome is a major source of molecular hydrogen as well. Lactulose has also been shown to significantly increase H2. 

 

http://www.ncbi.nlm....pubmed/23954468

 

Free Radic Biol Med. 2013 Dec;65:731-41. doi: 10.1016/j.freeradbiomed.2013.08.004. Epub 2013 Aug 13.

Lactulose ameliorates cerebral ischemia-reperfusion injury in rats by inducing hydrogen by activating Nrf2 expression.

Zhai X1, Chen X, Shi J, Shi D, Ye Z, Liu W, Li M, Wang Q, Kang Z, Bi H, Sun X.

Author information

Abstract

Molecular hydrogen has been proven effective in ameliorating cerebral ischemia/reperfusion (I/R) injury by selectively neutralizing reactive oxygen species. Lactulose can produce a considerable amount of hydrogen through fermentation by the bacteria in the gastrointestinal tract. To determine the neuroprotective effects of lactulose against cerebral I/R injury in rats and explore the probable mechanisms, we carried out this study. The stroke model was produced in Sprague-Dawley rats through middle cerebral artery occlusion. Intragastric administration of lactulose substantially increased breath hydrogen concentration. Behavioral and histopathological verifications matched biochemical findings. Behaviorally, rats in the lactuloseadministration group won higher neurological scores and showed shorter escape latency time in the Morris test. Morphologically, 2,3,5-triphenyltetrazolium chloride showed smaller infarction volume; Nissl staining manifested relatively clear and intact neurons and TUNEL staining showed fewer apoptotic neurons. Biochemically, lactulose decreased brain malondialdehyde content, caspase-3 activity, and 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine concentration and increased superoxide dismutase activity. The effects of lactulose were superior to those of edaravone. Lactulose orally administered activated the expression of NF-E2-related factor 2 (Nrf2) in the brain as verified by RT-PCR and Western blot. The antibiotics suppressed the neuroprotective effects of lactulose by reducing hydrogen production. Our study for the first time demonstrates a novel therapeutic effect of lactulose on cerebral ischemia/reperfusion injury and the probable underlying mechanisms. Lactulose intragastrically administered possessed neuroprotective effects on cerebral I/R injury in rats, which could be attributed to hydrogen production by the fermentation of lactulose through intestinal bacteria and Nrf2 activation.

 

Edited by lostfalco, 02 December 2015 - 03:14 AM.

[panel]

Hello guys 

 

I want to try TULIP since I read about. It's been few months, but the day of my trial is closer and closer ;-)

After visting Philipines seeing people so happy I am very curios what is the reason for this....Is it only culture os simply so much sun.

 

I am thinking about buying one or few strond LED halogens  and I wonder what is the recommended light source haracteristics:

1. Wich light temperature sgoult I target for? warm/cold or mabye some other light temperature? (https://en.wikipedia...lor_temperature)

2. What abount of lumens should I target for?

3. Is it possible buy halogents that will emmit to much light?

4. What would be your choose for today and why?

 

 

Edited by panel, 02 December 2015 - 07:16 PM.

[lostfalco]

Hello guys 

 

I want to try TULIP since I read about. It's been few months, but the day of my trial is closer and closer ;-)

After visting Philipines seeing people so happy I am very curios what is the reason for this....Is it only culture os simply so much sun.

 

I am thinking about buying one or few strond LED halogens  and I wonder what is the recommended light source haracteristics:

1. Wich light temperature sgoult I target for? warm/cold or mabye some other light temperature? (https://en.wikipedia...lor_temperature)

2. What abount of lumens should I target for?

3. Is it possible buy halogents that will emmit to much light?

4. What would be your choose for today and why?

Hi panel, if you want to read about using halogen lamps I'd recommend checking out Scott Robert's site here. http://heelspurs.com/led.html

 

For TULIP I use 850nm LED arrays like this one. http://www.amazon.co.../dp/B00QNC2ICM/

[Noottropics7]

Hi Lostfalco,

 

I have followed this thread for a long time, and I am very grateful for your amazing contribution to our journey to better ourselves.  I want to start Tulip, just Tulip, for cognitive purposes, so I was wondering what is the current regimen of Tulip that you use.  Basically, I want to do a minimalist regimen of Tulip that would still be effective.  So what doses of LLT would you currently recommend and what supportive supplements would you suggest?  That is, supplements that accentuate LLT's effect and that do not potentially have too many detrimental side effects.  Thanks in advance for your suggestions.

[lostfalco]

Hey Noottropics7, thanks for your kind words. I'm glad you've found some interesting things on the thread. =)

 

If you've never tried LLLT before, the first thing I would recommend is to just start out with LLLT alone. I would start out lasering your whole brain at 30 seconds to 1 minute per spot and gradually increase from there until you find your own sweet spot. Use the 96 and/or 48 LEDs for this (I like to use both). 

 

Once you get settled there (which might take a few weeks) then I would look into adding PQQ or some other enhancer of mitochondrial biogenesis. Tinker with this for a while to find what works for you and only then move on to adding CoQ10 (and possibly shilajit). 

 

Anyway, that should keep you busy for a while. =) There are MANY more things to try but I think an incremental approach will allow you to best customize your regimen to your own unique physiology. 

 

Keep us updated!

 

 

 

 

 

 

 

[lostfalco]

http://www.ncbi.nlm....les/PMC4168688/

 

Front Syst Neurosci. 2014 Sep 19;8:164. doi: 10.3389/fnsys.2014.00164. eCollection 2014.

Circadian gating of neuronal functionality: a basis for iterative metaplasticity.

Iyer R1, Wang TA2, Gillette MU3.

Author information

Abstract

Brain plasticity, the ability of the nervous system to encode experience, is a modulatory process leading to long-lasting structural and functional changes. Salient experiences induce plastic changes in neurons of the hippocampus, the basis of memory formation and recall. In the suprachiasmatic nucleus (SCN), the central circadian (~24-h) clock, experience with light at night induces changes in neuronal state, leading to circadian plasticity. The SCN's endogenous ~24-h time-generator comprises a dynamic series of functional states, which gate plastic responses. This restricts light-induced alteration in SCN state-dynamics and outputs to the nighttime. Endogenously generated circadian oscillators coordinate the cyclic states of excitability and intracellular signaling molecules that prime SCN receptivity to plasticity signals, generating nightly windows of susceptibility. We propose that this constitutes a paradigm of ~24-h iterative metaplasticity, the repeated, patterned occurrence of susceptibility to induction of neuronal plasticity. We detail effectors permissive for the cyclic susceptibility to plasticity. We consider similarities of intracellular and membrane mechanisms underlying plasticity in SCN circadian plasticity and in hippocampal long-term potentiation (LTP). The emerging prominence of the hippocampal circadian clock points to iterative metaplasticity in that tissue as well. Exploring these links holds great promise for understanding circadian shaping of synaptic plasticity, learning, and memory.

 

 

http://www.ncbi.nlm....les/PMC4105720/

 

Learn Mem. 2014 Jul 17;21(8):417-23. doi: 10.1101/lm.035451.114. Print 2014 Aug.

Genetic disruption of the core circadian clock impairs hippocampus-dependent memory.

Wardlaw SM1, Phan TX1, Saraf A1, Chen X1, Storm DR2.

Author information

Abstract

Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1-/- mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippocampus. Bmal1-/- mice exhibit impaired contextual fear and spatial memory. Furthermore, LTP in hippocampal slices from Bmal1-/- mice is also significantly decreased relative to that from wild-type mice. Activation of Erk1,2 MAP kinase (MAPK) during training for contextual fear memory and diurnal oscillation of MAPK activity and cAMP in the hippocampus is also lost in Bmal1-/- mice, suggesting that the memory defects are due to reduction of the memory consolidation pathway in the hippocampus. We conclude that critical signaling events in the hippocampus required for memory depend on BMAL1.

 

Edited by lostfalco, 06 December 2015 - 09:12 PM.

[Noottropics7]

Hey Noottropics7, thanks for your kind words. I'm glad you've found some interesting things on the thread. =)

 

If you've never tried LLLT before, the first thing I would recommend is to just start out with LLLT alone. I would start out lasering your whole brain at 30 seconds to 1 minute per spot and gradually increase from there until you find your own sweet spot. Use the 96 and/or 48 LEDs for this (I like to use both). 

 

Once you get settled there (which might take a few weeks) then I would look into adding PQQ or some other enhancer of mitochondrial biogenesis. Tinker with this for a while to find what works for you and only then move on to adding CoQ10 (and possibly shilajit). 

 

Anyway, that should keep you busy for a while. =) There are MANY more things to try but I think an incremental approach will allow you to best customize your regimen to your own unique physiology. 

 

Keep us updated!

 

Hi Lostfalco, thank you very much for your suggestions.  I will try it as you say and will report back on how it works for me.  Thank you again for taking the time to answer me. 

[lostfalco]

 

Hi Lostfalco, thank you very much for your suggestions.  I will try it as you say and will report back on how it works for me.  Thank you again for taking the time to answer me. 

 

You are very welcome. =)

[lostfalco]

Molecular hydrogen increases ghrelin increases growth hormone. I use this (sorry it's so expensive!) http://www.amazon.co.../dp/B00FBSST8G/

Another option might be MK-677 (see study below). http://www.ceretropi...k-677-solution/

Nyles7 is selling MK-677 on ebay as well. I've ordered from him in the past and he seems legit. http://www.ebay.com/...1-/181499559038     

 

http://www.ncbi.nlm....pubmed/23590874

 

Prog Neuropsychopharmacol Biol Psychiatry. 2013 Aug 1;45:11-20. doi: 10.1016/j.pnpbp.2013.04.005. Epub 2013 Apr 13.

Cognitive improvement by acute growth hormone is mediated by NMDA and AMPA receptors and MEK pathway.

Ramis M1, Sarubbo F, Sola J, Aparicio S, Garau C, Miralles A, Esteban S.

Author information

Abstract

It has been reported that Growth hormone (GH) has an immediate effect enhancing excitatory postsynaptic potentials mediated by AMPA and NMDA receptors in hippocampal area CA1. As GH plays a role in adult memory processing, this work aims to study the acute effects of GH on working memory tasks in rodents and the possible involvement of NMDA and AMPA receptors and also the MEK/ERK signalling pathway. To evaluate memory processes, two different tests were used, the spatial working memory 8-arm radial maze, and the novel object recognition as a form of non-spatial working memory test. Acute GH treatment (1mg/kg i.p., 1h) improved spatial learning in the radial maze respect to the control group either in young rats (reduction of 46% in the performance trial time and 61% in the number of errors), old rats (reduction of 38% in trial time and 48% in the number of errors), and adult mice (reduction of 32% in the performance time and 34% in the number of errors). GH treatment also increased the time spent exploring the novel object respect to the familiar object compared to the control group in young rats (from 63% to 79%), old rats (from 53% to 70%), and adult mice (from 61 to 68%). The improving effects of GH on working memory tests were blocked by the NMDA antagonist MK801 dizocilpine (0.025 mg/kg i.p.) injected 10 min before the administration of GH, in both young and old rats. In addition, the AMPA antagonist DNQX (1mg/kg i.p.) injected 10 min before the administration of GH to young rats, blocked the positive effect of GH. Moreover, in mice, the MEK inhibitor SL 327 (20mg/kg i.p.) injected 30 min before the administration of GH, blocked the positive effect of GH on radial maze and the novel object recognition. In conclusion, GH improved working memory processes through both glutamatergic receptors NMDA and AMPA and it required the activation of extracellular MEK/ERK signalling pathway. These effects could be related to the enhancement of excitatory synaptic transmission in the hippocampus reported by GH.

 

 

http://www.ncbi.nlm..../pubmed/9349662

 

Neuroendocrinology. 1997 Oct;66(4):278-86.

Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man.

Copinschi G1, Leproult R, Van Onderbergen A, Caufriez A, Cole KY, Schilling LM, Mendel CM, De Lepeleire I, Bolognese JA, Van Cauter E.

Author information

Abstract

Previous studies have indicated the existence of common mechanisms regulating sleep and somatotropic activity. In the present study, we investigated the effects of prolonged treatment with a novel, orally active, growth hormone secretagogue (MK-677) on sleep quality in healthy young and older adults. Eight young subjects (18-30 years) followed a double-blind, placebo-controlled, three-period crossover design. Each subject participated in three 7-day treatment periods (with bedtime drug administration), presented in random (Latin square) order, and separated by at least 14 days. Doses were 5 and 25 mg MK-677 and matching placebo. Six older subjects, ages 65-71 years, each participated in two 14-day treatment periods (with bedtime drug administration) separated by a 14-day washout. Doses were 2 and 25 mg MK-677 during the first and second periods, respectively. Baseline sleep and hormonal data were obtained on the 2 days preceding the beginning of the first 14-day treatment period. In young subjects, high-dose MK-677 treatment resulted in an approximately 50% increase in the duration of stage IV and in a more than 20% increase in REM sleep as compared to placebo (p < 0.05). The frequency of deviations from normal sleep decreased from 42% under placebo to 8% under high-dose MK-677 (p < 0.03). In older adults, treatment with MK-677 was associated with a nearly 50% increase in REM sleep (p < 0.05) and a decrease in REM latency (p < 0.02). The frequency of deviations from normal sleep also decreased (p < 0.02). The present findings suggest that MK-677 may simultaneously improve sleep quality and correct the relative hyposomatotropism of senescence.

 

http://www.ncbi.nlm..../pubmed/8954023

 

J Clin Endocrinol Metab. 1996 Dec;81(12):4249-57.

Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects.

Chapman IM1, Bach MA, Van Cauter E, Farmer M, Krupa D, Taylor AM, Schilling LM, Cole KY, Skiles EH, Pezzoli SS, Hartman ML, Veldhuis JD, Gormley GJ, Thorner MO.

Author information

Abstract

Aging is associated with declining activity of the GH axis, possibly contributing to adverse body composition changes and increased incidence of cardiovascular disease. The stimulatory effects on the GH-insulin-like growth factor I (IGF-I) axis of orally administered MK-677, a GH-releasing peptide mimetic, were investigated. Thirty-two healthy subjects (15 women and 17 men, aged 64-81 yr) were enrolled in a randomized, double blind, placebo-controlled trial. They received placebo or 2, 10, or 25 mg MK-677, orally, once daily for 2 separate study periods of 14 and 28 days. At baseline and on day 14 of each study period, blood was collected every 20 min for 24 h to measure GH, PRL, and cortisol. Attributes of pulsatile GH release were assessed by 3 independent algorithms. MK-677 administration for 2 weeks increased GH concentrations in a dose-dependent manner, with 25 mg/day increasing mean 24-h GH concentration 97 +/- 23% (mean +/- SE; P < 0.05 vs. baseline). This increase was due to an enhancement of preexisting pulsatile GH secretion. GH pulse height and interpulse nadir concentrations increased significantly without significant changes in the number of pulses. With 25 mg/day MK-677 treatment, mean serum IGF-I concentrations increased into the normal range for young adults (141 +/- 21 microgram/L at baseline, 219 +/- 21 micrograms/L at 2 weeks, and 265 +/- 29 micrograms/L at 4 weeks; P < 0.05). MK-677 produced significant increases in fasting glucose (5.4 +/- 0.3 to 6.8 +/- 0.4 mmol/L at 4 weeks; P < 0.01 vs. baseline) and IGF-binding protein-3. Circulating cortisol concentrations did not change, and PRL concentrations increased 23%, but remained within the normal range. Once daily treatment of older people with oral MK-677 for up to 4 weeks enhanced pulsatile GH release, significantly increased serum GH and IGF-I concentrations, and, at a dose of 25 mg/day, restored serum IGF-I concentrations to those of young adults.

 

 

Edited by lostfalco, 08 December 2015 - 05:02 AM.

[lostfalco]

https://www.ncbi.nlm...pubmed/23629538

 

Nat Rev Endocrinol. 2013 Jun;9(6):357-65. doi: 10.1038/nrendo.2013.78. Epub 2013 Apr 30.

Growth hormone and cognitive function.

Nyberg F1, Hallberg M.

Author information

Abstract

Emerging data indicate that growth hormone (GH) therapy could have a role in improving cognitive function. GH replacement therapy in experimental animals and human patients counteracts the dysfunction of many behaviours related to the central nervous system (CNS). Various behaviours, such as cognitive behaviours related to learning and memory, are known to be induced by GH; the hormone might interact with specific receptors located in areas of the CNS that are associated with the functional anatomy of these behaviours. GH is believed to affect excitatory circuits involved in synaptic plasticity, which alters cognitive capacity. GH also has a protective effect on the CNS, as indicated by its beneficial effects in patients with spinal cord injury. Data collected from animal models indicates that GH might also stimulate neurogenesis. This Review discusses the mechanisms underlying the interactions between GH and the CNS, and the data emerging from animal and human studies on the relationship between GH and cognitive function. In this article, particular emphasis is given to the role of GH as a treatment for patients with cognitive impairment resulting from deficiency of the hormone.

 

Edited by lostfalco, 08 December 2015 - 05:01 AM.

[Jochen]

Hey Falco (and fellow longecitiers), what do you think of the latest fab in Jack Cruse's world: https://thequantlet.com/ ?

 

It does contain a lot of red flags for me (quantum something anyone?) and I just want to hear your honest opinion about the topic.

 

it has LLT and cold exposure thrown into a gadget mix

 

Edited by Jochen, 08 December 2015 - 09:08 AM.

[lostfalco]

Hey Falco (and fellow longecitiers), what do you think of the latest fab in Jack Cruse's world: https://thequantlet.com/ ?

 

It does contain a lot of red flags for me (quantum something anyone?) and I just want to hear your honest opinion about the topic.

 

it has LLT and cold exposure thrown into a gadget mix

Hey, what's up Jochen? It's been a while. Hope you're doing well!

 

So, the quantlet looks interesting but I would say I'm fairly skeptical while remaining open to the ideas behind the device. I actually have the core control glove http://www.avacore.c...roduct/rtx-pro/    and I don't really recommend it for the cost. I've messed around with it over the years (I've had it for over two years) and have never really noticed anything...just my personal anecdote. If the quantlet is able to make it more effective by combining it with LLLT then I'm all ears but I would really need to see some hard data...especially with Dr. Kruse involved. Sadly, Kruse mixes so many outright lies and exaggerations with good information that you have to triple check all of his statements with quantifiable studies. Here is just one example...make sure you read the comments too. http://freetheanimal...cking-liar.html

 

Kruse also has no understanding of correlation vs. causation. (See Kruse's Factor X as quoted by Richard Nikoley, "Factor X: An asteroid hit the planet way back when, but it did so on a southern trajectory, spewing all the dust and ash southward, which, once everything evened out, still left a bit in the arctic region of the north and probably everything died except for those who could survive the cold.")

 

Of course, the fact that Kruse is untrustworthy doesn't automatically make his ideas false...that would be an ad hominem fallacy. However, it does mean that he must really back up anything he says with some serious evidence before I will believe him. 

 

On the plus side, James Carroll is involved and he is a legitimate LLLT scientist who has worked closely with Dr. Hamblin over the years and is the founder of Thor Lasers. http://www.thorlaser.com   This definitely adds some credibility to the venture but it looks as though he only worked on the LLLT module. 

 

Anyway, I'm obviously a big fan of LLLT/Photobiomodulation and I also think there is something to Cold Thermogenesis/Core Cooling techniques so I'll keep an eye on this device but I'm not holding my breath. =)

Edited by lostfalco, 08 December 2015 - 05:11 PM.

[mettmett]

Hey guys,

 

I just finished part I of my II part series on mitochondria.

 

You might find it interesting:  http://remedyrising.com/mitochondria-atp/

 

Also Lostfalco, that's a good find on the mk-677.

 

I was weary of using it at first because I thought it had a "Growth Hormone Bleed" effect, which would go against the natural pulsatile nature GH has and result in things like acromegaly...

 

...but apparently this might not be the case : http://www.ncbi.nlm....s01491-0357.pdf

 

Looks like I have another item on my Wish List

 

[resveratrol_guy]

...and the drug best targetted to treat acromegaly is pegvisomant, which hammers down IGF1, and with it, cancer risk. So I really wouldn't mess with GH unless I had exhausted all other options for neurological enhancement. But if you have a way to know how much you can safely get away with, go for it.

 

My other 2 cents, as to cold exposure, is that phosphotau development is stimulated by low body temperature. (See my post here on 7/27/2015 for context.) I always figured that hot implies high entropy, and cold implies more order, so cold must be superior for fundamental thermodynamic reasons. So much for logic; I'll stick to cooking my scalp with LLLT.

 

[BigPapaChakra]

...and the drug best targetted to treat acromegaly is pegvisomant, which hammers down IGF1, and with it, cancer risk. So I really wouldn't mess with GH unless I had exhausted all other options for neurological enhancement. But if you have a way to know how much you can safely get away with, go for it.

 

My other 2 cents, as to cold exposure, is that phosphotau development is stimulated by low body temperature. (See my post here on 7/27/2015 for context.) I always figured that hot implies high entropy, and cold implies more order, so cold must be superior for fundamental thermodynamic reasons. So much for logic; I'll stick to cooking my scalp with LLLT.

I wouldn't necessarily say that is so, it's not as simple as that: Modern Trends in BioThermoKinetics 3, 50-61, 1994. What is (Schrödinger's) Negentropy?

 

I think Dr. Ray Peat has a much more mechanistically 'truthful' view, though it is put in his best words in his books Generative Energy and Mind and Tissue (which contains tons of Soviet neurophysiology, parapsychology, sociology, gerontology, etc. research - very fascinating book); many individuals haven't really read the research of people such as Dr. Mae Wan Ho, Dr. Gilbert Ling, Prof. Gerald Pollack, geophysicist V.I. Vernadsky, etc. and thus Dr. Peat's ideas seem wacky at first glance, unfortunately. I will post a quote of his below, from an article of his, though as I said, some of his ideas on entropy in organisms are more fully developed in his books. The below will be long-winded, so everyone, skip ahead if one wishes. I apologize for the length, I couldn't really decide what would be a good portion to take out.

 

"The brain, like the other organs, stops growing when the food supply is used up. But an experimenter (Zamenhof) opened the egg shells at the stage of development when the brain normally stops growing, and added glucose, and found that the brain continued growing, producing chickens with bigger brains. The "genes" of a chicken, as part of a system, have something to do with the development of that system, but the environment existing in and around the organism is able to guide and support the way the system develops. The size, complexity, and intelligence of the brain represents a very large part of the "information" contained in the organism, and Zamenhof's experiment showed that the ability to realize this potential, to create this complexity, comes from the support of the environment, and that the "genetic nature of the chicken" didn't constitute a limit to the development of its brain. 

 

I am going to argue that Alzheimer's disease is analogous to the situation confronted by the developing chicken embryo or the rat or human fetus, when the environment is unable to meet the needs of the highly energetic, demanding and sensitive brain cells, and the brain cells begin to die, instead of developing into a more complex state, passing beyond various barriers and limitations. There are two stereotypes that are in conflict with this view: (1) That the structure of the brain is determined at an early point in life, sometimes explicitly stated as the age of 12 or 16, and (2) that the structure of the brain goes into an "entropic" deterioration during the process of aging. My position is that the brain cells are in a vital developmental process at all times, and that the same things that injure the brain of a fetus also injure the brain of an aging person. 

 

If novelty is really appearing during development, then it is hard to maintain that "entropy increases" during the development of an individual. Isn't a child a richer organization than a fertilized egg? Isn't an adult more individualized or realized than an infant? Seen from the inside, our known world gets richer with experience. Learning is certainly anti-entropic. Where does the idea of "increasing entropy with living" come from? Many things contribute, including a doctrine of genetic determinism, the old Platonic idea of the imperfection of the concrete, the unreality of the existent, and the medieval idea of the "corruption of the body." These philosophies still motivate some people in aging research. The astrophysicist, N. A. Kozyrev, showed that the idea of an "entropic cosmos" derived simply from the assumptions of 19th century deism, "God set the clockwork universe in motion, and left it to run down." Early in this century, Raymond Pearl argued that the "rate of living" governed the life-span, so that "fast living" meant a short life. He based his argument on cantaloupe seeds: the faster they grew, the sooner they died. This was because he didn't give them anything but water, so they had to live on their stored energy; if they grew quickly, obviously they ran out of stored energy sooner. I have never heard that described as a stupid idea, but I think politeness is sometimes carried too far. In the clock analogy, or the seed analogy, the available energy is used up. 

The clock with its wound-up spring and the seed in a dish of water may be considered as closed systems, and we can understand their fate. But if it is foolish to argue from a confined seed to free-living organisms, then it is just as foolish to argue from a clock to a cosmos. Unfortunately, these inferences about closed systems are often applied to real situations that aren't energetically closed.

 

The "rate of living" theory of aging picked up the idea of aging as a natural physical property of time, and gave it expression in mathematical form, arguing (Hershey, "Entropy, basal metabolism and life expectancy," Gerontologia 7, 245-250, 1963) that "the total lifetime entropy production" could be calculated, to give insight into "life expectancy and evolutional development." Unfortunately, the equation Hershey used assumed that the flow of heat out of the body into the surroundings is reversible. This suggests an image of Dr. Frankenstein vivifying his monster with lightning, putting the heat back into the body. If heat is to be "put back into the body," it is necessary to make sure that it is appropriate for the structure as it exists. 

 

Actually, it is just the directed flow of energy which generates the structures. If any biological argument can be made from the idea of entropy, it is that it would be extremely difficult to regenerate food, by putting heat into a person. In a few situations, it is possible to show that living structures can directly absorb heat from their environment (causing the temperature to fall)--"negative heat production"--but the exact meaning of this isn't clear. (B. C. Abbott, et al., "The positive and negative heat production associated with a nerve impulse," Proc. R. Soc. B 148, 149, 1958; R. D. Keynes and J. M. Ritchie, "The initial heat production of amphibian myelinated nerve fibres," Proc. Physiol. Soc., June 1970, page 29P-30P: "It is now clear that in both crustacean...and mammalian (Howarth, et al., 1968) non-myelinated fibres there is an initial production of heat during (or soon after) the action potential, 80% of which is rapidly reabsorbed.") A. I. Zotin ("Aging and rejuvenation from the standpoint of the thermodynamics of irreversible processes," Priroda, No. 9, 49-55, 1970), citing the theory of Prigogine-Wiame, argued that the aging process involves both a decrease in entropy and a decrease in the rate of heat production. 

 

Regeneration involves a production of entropy, as when an egg is formed. (The temperature fluctuation at the time of ovulation might make a contribution to the construction of the entropic egg.) The argument that aging of the animal (like aging of the cosmos) is governed by "the tendency of entropy to increase" has led people to say that rejuvenation would be like unscrambling an egg. Zotin's argument is interesting, because he says that an egg is a "scrambled animal." This view is very much like Warburg's and Szent-Gyorgyi's theory of cancer, that it is like a reversion to a simpler state of life. To sketch out what I have argued in different contexts, water is the part of the living substance that we can most meaningfully discuss in terms of entropy. In fact, much of the concept of entropy has derived from the study of water, as it changed state in steam engines, etc. Cancer cells, like egg cells, have a higher water content than the differentiated, functioning cells of an adult, and the water is less rigidly ordered by the cellular molecules. This different, more mobile state of the water, can be measured by the NMR (nuclear magnetic resonance) machines which are used for MRI (magnetic resonance imaging)."

Edited by BigPapaChakra, 09 December 2015 - 02:49 AM.

[BigPapaChakra]

Also, in regards to CT, there is this - from the guy who Joe Cohen on his blog called a "Kruse Guru": http://tanyewwei.com...g/ct-hormetic/ 

 

In other words, everything Ruben and Jack have said about cold and the quantlet seems to have no merit. It's NOT to say that the quantlet won't work, but cold is not going to, via "gravitational lensing" or anything such as that, allow tissues to absorb more photons and allow them to distribute them more efficiently. In terms of exercise, the mitigation of hyperthermia obviously makes sense, and thus the quantlet as applied to athletics seems superior to other products. I could imagine a future where EMTs, trauma surgeons, etc. use similar technologies to cause temporary hypometabolism in certain tissues while using red and/or infrared photons to impact blood aggregtion and what not. 

 

I found some devices on amazon, ebay, and alibaba from China that combine intranasal and vascular irradiation, sans cold, for much cheaper than the Quantlet. May experiment with them in the near future. Here is one (and it is a more expensive one, yet I believe still less expensive than the quantlet): http://www.amazon.co...ords=wrist LLLT

 

Here is another one: http://www.ebay.com/...&chn=ps&lpid=82

Edited by BigPapaChakra, 09 December 2015 - 03:00 AM.

[mettmett]

...and the drug best targetted to treat acromegaly is pegvisomant, which hammers down IGF1, and with it, cancer risk. So I really wouldn't mess with GH unless I had exhausted all other options for neurological enhancement. But if you have a way to know how much you can safely get away with, go for it.

That's the thing, mk-677 doesn't cause acromegaly. It normalizes GH levels(which includes IGF).

IGF isn't the enemy. It's only bad when it reaches supraphysiological levels. Mk-677 isn't the same as having a pituitary tumor as the medication you listed is prescribed for..

The study I posted suggests that mk acts similar to ghrp-6 which has a much shorter half life, but you have to pin it.

This study:One-year intranasal application of growth hormone releasing peptide-2 improves body weight and hypoglycemia in a severely emaciated anorexia nervosa patient, Izumi Haruta, Journal of Cachexia, Sarcopenia and Muscle (2015)

Used ghrp-2 for a year and only saw beneficial effects. Ghrp2 is similar to ghrp6 which acts similarly to mk-677.

As it stands, I don't see harm in RESPONSIBLY using these. They are tested for by WADA though if that applies to you.

https://www.wada-ama...prohibited-list

Edited by mettmett, 09 December 2015 - 04:43 AM.

[lostfalco]

haha TOTALLY off topic...but check out our boy Gwern! This is pretty freaking cool.

 

http://www.wired.com...tralian-genius/

 

"The first evidence pointing to Wright appeared in mid-November, when an anonymous source close to Wright began leaking documents to Gwern Branwen, a pseudonymous, independent security researcher and dark web analyst. Branwen provided those documents to WIRED, and they immediately led to several direct, publicly visible connections between Nakamoto and Wright."

 

 

[mettmett]

Here is another one: http://www.ebay.com/...&chn=ps&lpid=82

 

That's a great find BigPapa - By the way, do you like it when I call you that? ;P

 

It's a way better price than what VieLight has to offer.   

 

Have you happened to find anything similar to the Vielight Nuero?

[mettmett]

 

Molecular hydrogen water increases ghrelin (rodent study) which affects learning, memory, and recovery from brain injury. 

 

http://www.ncbi.nlm....les/PMC4443295/

 

"Ghrelin exhibits dense receptor expression in the hippocampus [188], where it has been found to forms of learning and memory performance in rodents. For example, ghrelin administration has been shown to promote long term potentiation in the hippocampus...

 

http://www.ncbi.nlm....les/PMC4070541/

 

Sci Rep. 2013 Nov 20;3:3273. doi: 10.1038/srep03273.

Oral 'hydrogen water' induces neuroprotective ghrelin secretion in mice.

Matsumoto A1, Yamafuji M, Tachibana T, Nakabeppu Y, Noda M, Nakaya H.

Author information

 

 

Also, anyone who wants to improve ghrelin the "natural way," could considering drinking Oolong Tea.

 

http://www.sciencedi...02194981500054X

 

In rats: "Teaghrelins are unique acylated flavonoid tetraglycosides found in Chin-shin oolong tea, and have been demonstrated to be responsible for the hunger induction just as the endogenous hunger hormone, ghrelin [21] and [22]. Similar to ghrelin, teaghrelins are able to induce hunger sensation of rats as well as stimulate growth hormone secretion of rat primary anterior pituitary cells [21]."

 

"...Our results suggest that Compounds 5, 6, 9, and 10 as well as teaghrelins are adequate ligands of the ghrelin receptor, and possess potential to be developed into oral ghrelin analogues. Moreover, it is reasonable to anticipate that different types of ghrelin analogues may be present in the rich sources of natural compounds from diverse herbal medicines. Indeed, emoghrelin found in Heshouwu (an adaptogen also known as fo-ti)was recently demonstrated to be a promising agonist of the ghrelin receptor [33]. It is expected that more candidate compounds for ghrelin analogues should be continually identified from natural sources."

Edited by mettmett, 09 December 2015 - 11:14 PM.

[lostfalco]

Hey guys,

 

I just finished part I of my II part series on mitochondria.

 

You might find it interesting:  http://remedyrising.com/mitochondria-atp/

 

Also Lostfalco, that's a good find on the mk-677.

 

I was weary of using it at first because I thought it had a "Growth Hormone Bleed" effect, which would go against the natural pulsatile nature GH has and result in things like acromegaly...

 

...but apparently this might not be the case : http://www.ncbi.nlm....s01491-0357.pdf

 

Looks like I have another item on my Wish List

What's up mettmett? Nice article man. I'm a big fan of mitochondria myself. =)

 

Yeah, MK-677 is very interesting. Not only does it maintain the pulsatile GH but it also doesn't raise cortisol. Regarding learning and memory, growth hormone causes instant working memory improvements in young and old rodents through enhanced NMDA and AMPA activity. http://www.ncbi.nlm....pubmed/23590874   Could mix very well with an ampakine (obligatory excitotoxicity warning). 

[lostfalco]

...and the drug best targetted to treat acromegaly is pegvisomant, which hammers down IGF1, and with it, cancer risk. So I really wouldn't mess with GH unless I had exhausted all other options for neurological enhancement. But if you have a way to know how much you can safely get away with, go for it.

 

My other 2 cents, as to cold exposure, is that phosphotau development is stimulated by low body temperature. (See my post here on 7/27/2015 for context.) I always figured that hot implies high entropy, and cold implies more order, so cold must be superior for fundamental thermodynamic reasons. So much for logic; I'll stick to cooking my scalp with LLLT.

Hey resveratrol_guy, I totally understand if you want to keep IGF1 low. However, people with acromegaly usually have pituitary tumors (or tumors elsewhere) that result in extremely elevated growth hormone levels...sometimes 10 times higher than normal. We are not going to get anywhere close to that with MK-677. 

 

The study you linked on cold exposure discussed anesthesia induced hypothermia for long periods of time (at least 60 minutes in vivo). Very different than cold thermogenesis. 

 

"Anesthesia induced a progressive and drastic drop in temperature reaching ∼26°C after 60 minutes of anesthesia." 

 

"All general anesthetics induce hypothermia through the deregulation of both non- shivering and shivering thermogenesis regulation." 

 

"This hypothermia directly results in an in vivo increase of AD-related tau phospho-epitopes..."

 

http://www.nature.co...icles/srep00480

 

Do you have a study showing that cold thermogenesis causes tau hyperphosphorylation?

 

I'm with you about logic...that's why we do experiments! I've been surprised more times than I can count. 

 

LLLT (at the power density and wavelength we currently use) has a very minimal heating effect and current evidence indicates that this is not a major contributor to its effects. So, hopefully your scalp will remain uncooked. =)

 

Edited by lostfalco, 10 December 2015 - 04:33 AM.

[lostfalco]

Also, in regards to CT, there is this - from the guy who Joe Cohen on his blog called a "Kruse Guru": http://tanyewwei.com...g/ct-hormetic/ 

 

 

Really enjoyed this link, Papa. Thanks, man. Nice to see some sanity applied to Kruse's ideas...and the author is a Nick Lane fan! Win and win.