4019 replies to this topic

[lostfalco]

Myth: Substance X MUST cross the blood brain barrier to affect the brain. 

Myth Debunked: Substance X affects a peripheral system that directly affects a central system. Read on for details!

 

Let's put this nootropic community myth to rest once and for all, shall we! =) (btw, I know that many of you already know that this is a myth)

 

Question: Can supplements/drugs that DO NOT cross the blood brain barrier affect learning and memory in the central nervous system?

 

Answer: Yes, yes, a million times yes. =)

 

How? Peripheral epinephrine (which does not easily cross the BBB) affects the vagus nerve; the vagus nerve causes the amygdala to release norepinephrine into the central nervous system. 

 

http://www.ncbi.nlm....les/PMC3384987/

 

"...epinephrine does not gain access to the CNS due to the restrictive properties of the blood-brain barrier (BBB)."

 

"The results from Experiment 1 demonstrated that increasing neural transmission along ascending vagal fibers following learning produces a significant and long lasting improvement in memory for emotional experiences."

 

"The results from Experiment 2 demonstrated that epinephrine increases firing discharge along afferent fibers of the vagus nerve and this change persisted for up to one hour post-injection. The epinephrine-induced increase in vagal firing was accompanied by significant elevations in extracellular concentrations of norepinephrine in the basolateral amygdala that remained high for up to 120 min post-injection."

 

"Findings emerging from the final study reveal that systemic epinephrine injection and VNS induce similar patterns of neuronal activation within brain regions associated with memory."

 

"In conclusion, the collective findings demonstrate an integral role of epinephrine and the vagus nerve in influencing central noradrenergic systems ascribed a role in processing memory for emotionally arousing experiences."

 

More Random Quotes from the Study: (just to hammer the nails in this coffin)

 

"Our findings indicate that treatments that raise circulating levels of epinephrine in the periphery or increase discharge along ascending fibers of the vagus nerve produce similar changes in the expression of Fos proteins in noradrenergic neurons in the NTS, LC, VLM, and their areas of termination."

 

"The results show that central noradrenergic nuclei represent a primary target of peripheral systems that are engaged by exposure to emotionally arousing events."

 

"In turn, activation of noradrenergic release in each of the limbic circuits identified in this study constitutes areas wherein the beneficial effects of heightened levels of arousal in the periphery influence the effective storage of events into memory."

 

"Significant increases in cerebral blood flow after acute left vagal stimulation was noted bilaterally in the hippocampus, amygdala, orbitofrontal gyri, cingulate, thalami, hypothalami, and the anterior insula."

 

"...changes observed after vagal stimulation in a fMRI study of patients with intractable depression involved increased blood oxygenation level in bilateral orbitofrontal and parieto-occipital cortex, left temporal cortex, amygdala, and the hypothalamus."

 

"...VNS-induced activation was detected in bilateral thalamus, insular cortices, postcentral gyri and inferomedial occipital gyri, left basal ganglia, and right posterior superior temporal gyrus."

 

"...experiments suggest that epinephrine's actions on memory and in potentiating norepinephrine output in the amygdala may be mediated by the initial activation of peripheral vagal fibers that project to the brain."

 

"The projection of vagal afferents to the NTS is important in understanding how vagal activation may affect distinct neuronal circuits to regulate norepinephrine release in the amygdala."

 

"For instance, ascending fibers of the vagus synapse on the A2 norepineprhine-containing neurons in the NTS (Sumal et al., 1983) that course through the brainstem to innervate and release norepinephrine in the amygdala."

 

"A2 neurons in the NTS also project directly to locus coeruleus neurons (LC; Van Bockstaele et al., 1999) that provide the major source of noradrenergic innervation to the basolateral amygdala."

 

"...electrical stimulation of ascending vagal fibers or epinephrine injection alone, produces significant and long lasting increases in amygdala norepinephrine levels that are attenuated by inactivating the site of termination of vagal axons in the brainstem, the NTS."

 

"Thus, vagal activation in response to epinephrine secretion may represent one mechanism by which emotionally arousing events facilitate memory processing by initiating norepinephrine release in the amygdala."

 

"...peripheral levels of epinephrine affect vagal nerve discharge and the subsequent potentiation of norepinephrine release in the basolateral amygdala."

 

"Findings emerging from this collection of studies establish the importance of ascending fibers of the vagus nerve as an essential pathway for conveying the peripheral consequences of physiological arousal on brain systems that encode new information into memory storage."

 

"Findings from this series of studies reveal an integral relationship between the arousal related hormone epinephrine and ascending fibers of the vagus nerve in influencing memory processing through interactions with central noradrenergic systems."

 

 

 

Edited by lostfalco, 31 August 2015 - 03:40 AM.

[BieraK]

 

Is Kordon really okay for human consumption? What is the best source available for human consumption? Pharmaceutical grade seems hard to get and need to invest in a huge quantity (20gm) which is not ideal for trying out. What's the best way to mix it is another question. Anyone has any suggestion? I know those are very low level questions about MB, but at this stage as a beginner, I am still trying to figure this out.

I would not use Kordon's. Unknown risk of contaminants. 

 

I've purcahsed MB from bluebrainboost and Nyles7 on ebay. Both seem legit to me. 

 

https://www.bluebrai...-blue-solution/

 

http://www.ebay.com/...=item27d8ca900e

 

Low dose MB in the scientific literature ranges from 0.5 to 4 mg/kg. So, if you weigh 70kg, then 35mg to 280mg. 

 

"But systemic low-doses (0.5–4 mg/kg) of methylene blue that stimulate mitochondrial respiration in vivo are safe and effective in both animals and humans."

http://www.ncbi.nlm....les/PMC4428125/

 

This human study used 260mg. http://www.ncbi.nlm....les/PMC4467026/

 

I'm currently testing bluebrainboost's droppers at 10 to 30mg/day. I'll try a 260mg dose of powder soon. 

 

Hello Falco, I think that 260 mg is a high dose, If you take that dose you could enter in the zone of the risk, that is loosing the benefits the of low dose MB, even due to the hormetic dose response of MB, loose the cognitive benefits and obtain the contrary, a possible detrimental effect on cognition.

For those who wish to combine LLLT with MB, this is an Important thing:

Please do not take MB and then use LLLT (LED or Lasers) with Red Light (600-700 nm), Methylene Blue is safe with infra-red light, but with Red Light the MB reacts and produce singlet oxygen (a Free Radical), that singlet oxygen can produce DNA Damage.

I don't know exactly how is the specific combination of LOW dose MB with Red light, because I have not found any study about that combination, however there are studies about MB (in a high doses) with Lasers of red light, in relation a procedure called chromoendoscopy, the lasers/light used with that procedure apparently are very high in relation to the J/cm2... 

Then I insist, perhaps Low Dose MB with Red Light is relatively safe, but MB in a High dose with Red Light isn't safe at all, and as there is no studies about Low Dose MB combined with Red light is better to stay in the safe side and do not take MB with LLLT devices or Lasers of Red Light, of course if you use the LLLT Red light first, and then you take MB I think that there is no problem.

That is for the users of Red Light devices, for the users of Infra-red devices like 850 nm or 808 nm, there is no problem, MB does not react with that range of light.

Apart from this, I can say that Methylene Blue looks like a great substance, I've looked into various studies recently and there are very interesting things with the  substance, for example recently I looked into a study talking about AMPK and SIRT1 activation by methylene blue :O

Another study talking about Nrf2 induction and mitochondrial biogenesis. There are many studies done by or with the participacion of Dr. Gonzalez-Lima talking about the cognitive benefits of Methylene Blue, I will put the links and the abstracts later .

Edited by BieraK, 31 August 2015 - 06:59 AM.

[lostfalco]

Hello Falco, I think that 260 mg is a high dose, If you take that dose you could enter in the zone of the risk, that is loosing the benefits the of low dose MB, even due to the hormetic dose response of MB, loose the cognitive benefits and obtain the contrary, a possible detrimental effect on cognition.

 

 

Hey BieraK, thanks for your concern. =)

 

260mg is actually considered "low dose" in the scientific literature. The study I am imitating is actually a human study run by Dr. Gonzalez-Lima himself. Here's an extended quote on the dosing given to 42 women:

 

"The 260 mg methylene blue dose corresponds to the 4 mg/kg dose shown to be effective in previously published preclinical studies of object recognition memory and fear extinction (22, 24, 29). Methylene blue and placebo were administered using a schedule divided into three 86.66 mg capsules. One capsule was administered immediately following the completion of extinction training. The participants were instructed to take the second capsule before going to bed that night (6-10 hours later), and to take the last capsule after waking up (another 6-10 hours later). The divided dosing schedule was intended to reduce possible urinary tract irritation sometimes associated with methylene blue excretion through the urine. Participants were instructed to take the capsules with a large glass of water, in order to further minimize the chance of urinary tract irritation and to reduce the intensity of urine discoloration. Since the average half-life for urinary excretion of methylene blue is 6.6 hours (39), our administration procedure served to maintain methylene blue in the circulation throughout the entire memory consolidation period following extinction training."

 

http://www.ncbi.nlm....les/PMC4467026/

[BieraK]

Some things about my personal experimentation:
IDRA-21 is a decent nootropic, very good when combined with coluracetam and/or PRL-8-53.
Sunifiram to my is the most potent and fantastic nootropic, however have somes risks due to PKCa activation, is regrettable the absence of more studies about the safety of this nootropic, unlike IDRA-21 this stimulates the release of acetylcholine, that's why for now I think that IDRA-21 with Coluracetam It is a good combination to replace the sunifiram effect's in a remotely manner.

About MB with LLLT, well according to my experience, the LLLT and MB does not produce a redudant effect, and the effects of the combination are different if you use the LLLT first and then MB or if you use MB before the LLLT application, I have not been able to reach an accurate and precise conclusion on this because LLLT alone not always produce the same effects to me, some days I notice a more powerful enhancement and other days I notice a less potent effect compared to the previous application :/, some days I notice immediate energy and other days I notice the sleep effect of the LLLT. Another thing that has not allowed me to reach an accurate and concise conclusion is the combination of other variables in the equation that Is C60 :P.

I hope that other people can compare the effects of the combination of Low Dose MB with LLLT (Infra-red, near read), and with this we can finally reach to a conclusion about the effects.

For example I remember very well one day: c60 in my body, then MB low dose, and then LLLT, before applying the laser had much sleep, had slept only three hours the day before, and the hour was 7:00 PM, after the LED application I received a ton of energy and excelent mood I could continue smoothly awake until 4:00 am (Of course that was not healthy).

Other interesting application was a time when I first used the combination of MB with LLLT, I dosed with Lase in my leg, then I taked like 1 mg of MB after that I noticed a strong analgesic effect, I was able to feel sensations in the area of my leg where I applied the laser, however the sensation of pain was downgraded, and the sensations of touch was different, was like having an injection of anesthesia :s

I was able of reproduce that effect with my mother and with a girlfriend, in my case I tried to repeat the experiment, I was able of repeat the effects in two more ocasions, however after that I have not been able to repeat the effects :/ I think that the dose of MB applied before the LLLT and the time of application could be the key.

In relation of LLLT combined with other substances:
First Forskolin+LLLT, first time I received a notorious sleep effect a slight and transient headache in some areas of my head due to vassodilation, then I slept wonderfully for three hours.

The second time I received the sleep effect of LLLT and then a good stimulatory effect, a decent amount of energy, no headache this time.
Third time the same to the second, sleep effect and then a stiomulatory effect with no headache.

Sildenafil+LLLT only one ocassion, I can't say much of this, this made me sleepy and tired and can't remember if after this came a stimulatory effect.

Why is important to my the sleeping and tired effect of LLLT? Because If I apply LLLT alone with no other supplement I just no receive that effect, I need to apply LLLT 200 seconds per spot to feel a instant energy effect but without feeling the tired and sleepy effect, If I apply LLLT just for 60 seconds I do not feel much... I do not use a Laser I use the 850 nm Illuminator.

[BieraK]

 

Hello Falco, I think that 260 mg is a high dose, If you take that dose you could enter in the zone of the risk, that is loosing the benefits the of low dose MB, even due to the hormetic dose response of MB, loose the cognitive benefits and obtain the contrary, a possible detrimental effect on cognition.

 

 

Hey BieraK, thanks for your concern. =)

 

260mg is actually considered "low dose" in the scientific literature. The study I am imitating is actually a human study run by Dr. Gonzalez-Lima himself. Here's an extended quote on the dosing given to 42 women:

 

"The 260 mg methylene blue dose corresponds to the 4 mg/kg dose shown to be effective in previously published preclinical studies of object recognition memory and fear extinction (22, 24, 29). Methylene blue and placebo were administered using a schedule divided into three 86.66 mg capsules. One capsule was administered immediately following the completion of extinction training. The participants were instructed to take the second capsule before going to bed that night (6-10 hours later), and to take the last capsule after waking up (another 6-10 hours later). The divided dosing schedule was intended to reduce possible urinary tract irritation sometimes associated with methylene blue excretion through the urine. Participants were instructed to take the capsules with a large glass of water, in order to further minimize the chance of urinary tract irritation and to reduce the intensity of urine discoloration. Since the average half-life for urinary excretion of methylene blue is 6.6 hours (39), our administration procedure served to maintain methylene blue in the circulation throughout the entire memory consolidation period following extinction training."

 

http://www.ncbi.nlm....les/PMC4467026/

 

 

Yes is a low dose, but only if the 260 mg is divided in tree different doses separated by time.
A 260 mg dose to my understant It is still in the range of 0.5 to 4 mg, however that dose is in the upper high end of the range, If you look to other studies of Dr Gonzalez-Lima, doses of 1 mg/kg in rat are used, for a human of 70 kg that equals to a 11 mg dose. I think that is better to use a dose similar to the dose of the Alzheimer disease trial.
for example look a this 2012 study

Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue

Julio C. Rojas,a Aleksandra K. Bruchey,a and F. Gonzalez-Limaa,*

 

 

In contrast, MB at low (1-4 mg/kg) and intermediate (10 mg/kg) doses did not result in any non-specific behavioral effects. Remarkably the 4 mg/kg dose was the most reliable at enhancing memory after single administration, significantly improving both long-term behavioral habituation and object memory recognition (Riha et al., 2005). An equivalent MB dose has been given to humans chronically without side effects (Naylor et al., 1986).

Reference: http://www.ncbi.nlm....les/PMC3265679/

 

- 4 mg/kg rat dose is a 0,64 mg/kg human dose, for a 70 kg human that equals to 30 mg.

 

-10 mg/kg rat dose is a 1,62 mg/kg human dose, for a 70 kg human that is a 113, 4 mg.

 
A 30 mg dose tree times a day is a good dose looks perfect according to that study. If you look some posts in the c60 forum, Turnbuckle reported a bad experience of taking 100 mg of MB, that experience is reported in the profile ot Turnbuckle, he talks about reversing the effects of the 100 mg with 500 mg of Niacin: Point number 11 http://www.longecity...69-turnbuckle/ 

However, you have the reason 260 mg of MB corresponds to 4 x 70 kg, and the low dose MB correspond to the range between 0,5 - 4 mg/kg for a human, so 260 mg is still considered low dose of methylene. The problem is that considering the 2012 study, 260 mg look like more a intermediate dose than a low dose.

After all a 260 mg for a 70 kg human isn't a dangeours or a harm dose, but does not look optimal, of course if the 260 mg is divided in tree different doses that is better.
 

 

Edited by BieraK, 31 August 2015 - 08:16 AM.

[BieraK]

Finally I wan't to share this, I hope not to distort the current theme of the post:

 

 

Methylene blue upregulates Nrf2/ARE genes and prevents tau-related neurotoxicity.

Stack C1, Jainuddin S1, Elipenahli C1, Gerges M1, Starkova N1, Starkov AA1, Jové M2, Portero-Otin M2, Launay N3, Pujol A4, Kaidery NA5, Thomas B5,Tampellini D6, Beal MF1, Dumont M7.

Author information

 

Abstract

Methylene blue (MB, methylthioninium chloride) is a phenothiazine that crosses the blood brain barrier and acts as a redox cycler. Among its beneficial properties are its abilities to act as an antioxidant, to reduce tau protein aggregation and to improve energy metabolism. These actions are of particular interest for the treatment of neurodegenerative diseases with tau protein aggregates known as tauopathies. The present study examined the effects of MB in the P301S mouse model of tauopathy. Both 4 mg/kg MB (low dose) and 40 mg/kg MB (high dose) were administered in the diet ad libitum from 1 to 10 months of age. We assessed behavior, tau pathology, oxidative damage, inflammation and numbers of mitochondria. MB improved the behavioral abnormalities and reduced tau pathology, inflammation and oxidative damage in the P301S mice. These beneficial effects were associated with increased expression of genes regulated by NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE), which play an important role in antioxidant defenses, preventing protein aggregation, and reducing inflammation. The activation of Nrf2/ARE genes is neuroprotective in other transgenic mouse models of neurodegenerative diseases and it appears to be an important mediator of the neuroprotective effects of MB in P301S mice. Moreover, we used Nrf2 knock out fibroblasts to show that the upregulation of Nrf2/ARE genes by MB is Nrf2 dependent and not due to secondary effects of the compound. These findings provide further evidence that MB has important neuroprotective effects that may be beneficial in the treatment of human neurodegenerative diseases with tau pathology..

 

We found that MB improved behavioral abnormalities, reduced tau pathology, reduced oxidative stress and inflammation and increased mitochondrial biogenesis in P301S mice, and that these neuroprotective effects were associated with increased expression of NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) activated genes.

 

MB has been shown to increase mitochondrial function (11,13,24). Mitochondrial biogenesis was assessed by measuring mitochondrial DNA (mtDNA) copy number, which correlates with numbers of mitochondria (25). There was a significant increase in mtDNA copy number in the P301S mice fed the MB low dose diet when compared with P301S mice fed a control diet, indicating improved mitochondrial biogenesis in these mice (Fig. 6A). The levels of activity superoxide dismutase (SOD), a key enzyme involved in cellular antioxidant defense and controlled by the Nrf2 transcription factor, were also assessed. P301S mice fed the MB low dose diet showed a significant increase in SOD activity when compared with P301S mice fed a control diet

 

We observed improvements in behavior and tau-related pathology that were associated with decreased phospho-tau accumulation, increased expression of antioxidant defenses, decreased inflammation and increased mitochondrial biogenesis. Therefore, these data provide further evidence that compounds such as MB, which increase expression of Nrf2/ARE-dependent genes, may be effective for the treatment of tauopathies and related neurodegenerative diseases.

That's what I say that this compound looks great :D, they used two doses 4 mg/kg and 40 mg/kg in mouse

4 mg/kg in mice is a 0,3243 mg/kg dose for a human, so for a 70 kg person that is just 22 mg :O
40 mg/kg in mice is a 3,2432 mg/kg dose for a human, so for a 70 kg person that is 227

In the study the found better results with the called low dose, that is 4 mg/kg.

Edited by BieraK, 31 August 2015 - 08:34 AM.

[BieraK]

And this is the last Methylene blue related post of the night (Here is 5:36 AM)
http://www.ncbi.nlm....pubmed/24486702
 

SIRT1 activation by methylene blue, a repurposed drug, leads to AMPK-mediated inhibition of steatosis and steatohepatitis.

Shin SY1, Kim TH1, Wu H1, Choi YH2, Kim SG3.

Author information

 

Abstract

Sirtuins maintain energy balance. Particularly, sirtuin 1 (SIRT1) activation mimics calorie restriction and nutrient utilization. However, no medications are available for the up-regulation of SIRT1. Methylene blue (MB) had been in clinical trials for the treatment of neurological diseases. This study investigated the effect of MB on sirtuin expression in association with the treatment of steatosis and steatohepatitis, and explored the underlying basis. The effects of MB on mitochondrial function, molecular markers, pharmacokinetics, and histopathology were assessed using hepatocyte and/or mouse models. Immunoblotting, PCR and reporter assays were done for molecular experiments. After oral administration, MB was well distributed in the liver. MB treatment increased NAD(+)/NADH ratio in hepatocytes. Of the major forms, MB treatment up-regulated SIRT1, and thereby decreased PGC-1α acetylation. Consistently, hepatic mitochondrial DNA contents and oxygen consumption rates were enhanced. MB treatment also notably activated AMPK, CPT-1 and PPARα: the AMPK activation relied on SIRT1. Activation of LXRα and the induction of SREBP-1c and its target genes by T0901317 were diminished by MB. In addition, MB treatment antagonized the ability of palmitate to acetylate PGC-1α, and increase SERBP-1c, FAS, and ACC levels. In mice fed on a high-fat diet for 8 weeks, MB treatment inhibited excessive hepatic fat accumulation and steatohepatitis. The ability of MB to activate SIRT1 promotes mitochondrial biogenesis and oxygen consumption and activates AMPK, contributing to anti-lipogenesis in the liver. Our results provide new information on the potential use of MB for the treatment of steatosis and steatohepatitis.

Too much for today, I will go for some Methylene Blue :D

 

Edited by BieraK, 31 August 2015 - 08:31 AM.

[Bluecheer]

I would just like to say how much I appreciate this post. 

 

my only criticism is its so hard sometimes to sith through all the information, I love condensed information. 

 

Thanks Falco!

[lostfalco]

No problem, Bluecheer. I'm glad you've found something of value in this crazy labyrinth of a thread!

 

And I want to thank everyone who has contributed. This certainly isn't a one man show and this thread wouldn't be what it is without all of you guys. So...thanks!

 

I totally agree with you about condensed information. I'm currently taking a web design class and I plan on setting up a site that distills and organizes all of the disparate parts of this albatross so that it's much more accessible to everyone. Just give me a semester or so. =)   

[Bluecheer]

Yeah of course, there is quite a bit of information that is useful!

Wow, that actually sounds like such a nice thing to do. I know there is a lot of people out there that would after getting the information that they need simply have no interest in sharing it with others... let alone doing something like organizing it! 

I guess that's why I prefer Longecity to most forums, the community seems like a more sophisticated emphatic sort. But maybe I am being a little delusional. 

Also, I note on your first post you mention Pregnenolone being a miracle for you. Is this infact something in which for it to be most effective it would need to be injected? 

I'm also curious as to your opinion on the "Braverman test" to determine levels of neurotransmitters in the brain? After listing to a specific podcast with a guest on from tim ferriss, I noted that he specified it is a more valid way to test then blood test... Your thoughts on the test?  

Regards,

Bluecheer.

Edited by Bluecheer, 02 September 2015 - 09:03 AM.

[lostfalco]

No worries...I kinda enjoy simplifying and organizing everything. 

 

I've gained a lot from Longecity so it's cool to (try to) give back a little. =)

 

Pregnenolone? absorbs pretty well orally where it's turned into PregS. See my post here. http://www.longecity...-83#entry741089

 

Braverman? very skeptical

 

 

http://www.ncbi.nlm....icles/PMC23857/

 

"Oral Ingestion of P Results in Increases in Steroid and IGF-1/GH Levels in Serum. 

Data obtained in two healthy male subjects during the first 8 hr after ingestion of 175 mg of P (Fig. ​

(Fig.2)2) are consistent with the idea that oral P could be a precursor of glucocorticoids, mineralocorticoids, and sex steroids produced, as depicted in Fig. ​Fig.2.2. PS showed the greatest relative postingestion increase of any of the steroids (Figs. ​(Figs.22 and ​and3),3), increasing more than P. PS levels remained elevated at 24 hr, at which time P values had returned to control levels or below. Orally ingested P probably largely is converted to PS in the intestine, which is rich in steroid-conjugating enzyme activity, the PS being absorbed rapidly into the blood (17). Various tissues, blood cells (18), and blood lipoprotein complexes (19, 20) may take up PS and use it either as such or, after uptake convert it to P by widely occurring, tissue-specific, steroid sulfate-splitting enzymes (21–23). A small amount of P enters the blood stream. The prolonged elevation of serum PS by comparison with P is attributable to the fact that the latter is cleared approximately three times more quickly than PS (24). Elevations over control values were noted after ingestion of P in both subjects at all or most of the time intervals up to 8 hr in contents of P, PS, DHEA, total estrogens, 17α-OH PROG, and PROG."

 

 

[Lucas N]

Hey lostfalco, excellent news that you are planning to make a website, very glad to hear it =)

 

I never tried IDRA-21 or Ephedrine with Caffeine. There are some other concerns about the Ephedrine caution other than the cardiovascular? It's safe to consume like you do (aournd 25mg per day?) And did you experimented any side effect when you are on IDRA-21? 

 

Thanks man.

[crusader]

why is it that we are doing 2 days on 1 day off when there is irrefutable research that has proven that doing LLLT daily for 7 days had the most benefit? only when the patient did LLLT daily for 14 days did the patient regress back to baseline; LLLT daily for 7 days had much more benefit then doing it daily for 1 day and even 3 days daily. Whose idea was it to tell people to dose it with just 2 days in a row with 1 day off?  from what I have skimmed through in this read is that LLLT has an accumulative effect, so doing it only 2 days in a row seems to be really preventing yourself from reaping all of the benefits.

 

so wouldn't it be better to do LLLT daily for 7 days with 2-3 days off?

 

If the researchers are wrong about this please refer me to another study which refutes it properly.

 

 

 

 

 

 

[Bluecheer]

Mmmh.. Its claiming a lot, but I'm definitely intrigued. Is there a particular brand you would recommend LostFalco?

[lostfalco]

Hey crusader, thanks for checking out the thread!

 

I'm short on time so I must be brief. Please don't take my brevity as rudeness...it's not meant that way. =)

 

...there is irrefutable research that has proven that....

 

 

The study or studies you are referencing refer to experiments in cell or animal models. Therefore, please defend this proposition: "results in cell/animal studies constitute 'irrefutable proof' of what will happen in healthy human trials." 

 

Second, please provide a link to the study you are referring to. I am aware of a couple that deal with the issue you are talking about and I want to make sure that I'm talking about the exact same study as you are. Thanks!

Edited by lostfalco, 06 September 2015 - 10:59 PM.

[lostfalco]

Mmmh.. Its claiming a lot, but I'm definitely intrigued. Is there a particular brand you would recommend LostFalco?

Hey Bluecheer...my claim is simply that it's an interesting idea for experimentation. Nothing more. =)

 

I don't have a particular brand I can say stands out above the others...I'm currently testing out SmartPowders pregnenolone bulk powder. Trying to cut some costs. https://smartpowders...enolone-powder/

Edited by lostfalco, 07 September 2015 - 07:19 AM.

[lostfalco]

Holy shite!!! Full text pdf at the bottom of this post. Read it! (if you have time...and want to have your mind blown =))

 

"At the intracellular level, discoveries now reveal the existence of 'mitochondrial synapses' establishing mitochondrial networks, with defined chromatin-modifying mitochondrial output signals capable of orchestrating gene expression across the genome. These discoveries raise the possibility that in addition to their role as powerhouses and neuromodulators, mitochondria behave as intracellular signal-processing networks."

 

http://www.ncbi.nlm....pubmed/26187720

 

Trends Neurosci. 2015 Aug;38(8):468-74. doi: 10.1016/j.tins.2015.06.001. Epub 2015 Jul 15.

Mitochondrial synapses: intracellular communication and signal integration.

Picard M1.Author information

• 1Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia and the University of Pennsylvania, PA 19104, USA. Electronic address: mp3484@columbia.edu.

Abstract

Communication is a central theme in biology. Consequently, specialized structures have evolved to permit rapid communication among cells, tissues, organs, and physiological systems, thus enhancing the overall function and adaptation of the organism. A prime example is the neuronal synapse. In the brain, synaptic communication establishes neuronal networks with the capacity to integrate, process, and store information, giving rise to complex output signals capable of orchestrating functions across the organism. At the intracellular level, discoveries now reveal the existence of 'mitochondrial synapses' establishing mitochondrial networks, with defined chromatin-modifying mitochondrial output signals capable of orchestrating gene expression across the genome. These discoveries raise the possibility that in addition to their role as powerhouses and neuromodulators, mitochondria behave as intracellular signal-processing networks.

 

 

Highlights

•Signal processing by brain neurons arises from synaptic connections.

•Mitochondrial networks transmit information analogous to brain neuronal networks.

•Information is exchanged between mitochondria via ‘mitochondrial synapses’.
•Chromatin-remodeling mitochondrial signals impact nuclear gene expression.
•Mitochondria are neuromodulators, impacting presynaptic neurotransmitter release.

 

 1-s2.0-S0166223615001307-main.pdf   1.45MB   22 downloads

 

Edited by lostfalco, 07 September 2015 - 01:50 AM.

[88LS]

So what does this mean LF - we've got to upgrade our mitos to the max, and then some?

[Bluecheer]

 

Mmmh.. Its claiming a lot, but I'm definitely intrigued. Is there a particular brand you would recommend LostFalco?

Hey Bluecheer...my claim is simply that it's an interesting idea for experimentation. Nothing more. =)

 

I don't have a particular brand I can say stands out above the others...I'm currently testing out SmartPowders pregnenolone bulk powder. Trying to cut some costs. https://smartpowders...enolone-powder/

 

Hey sorry i was in a rush and mis read something you posted in the previous post you linked to about Pregnenolone, My bad!   



I must ask you about any experience or thoughts on Ergoloids?  i.e Hydergine? Or something similar.. ive been tempted to try it for quite some time but as with all supplements online theres a ridiculous skew of hate and love for the product so i am interested in your opinon?

 

[mettmett]

I used hydergine in the past and I loved it. Unfortunately I no longer have an affordable source.

[ceridwen]

It pulled me back from my 1st bout of Alzheimers? in my 20s! Then I thought it was unobtainable and I got the serious memory losses again. I was eating way too much sugar but there might be a genetic problem there as well. I got 30 years of healthy life in between so the effects of Hydergeine lasted quite a long time. The only side effects I had was nausea I had to take it with food but that was minor compared to what I had been going through. Highly recommended. Don't know why it isn't more popular.
I have found it doesn't work with this second more serious bout of illness suggesting a window at the very beginning of the disease where treatment with Hydergine can be effective. Sigh

[Matty72]

I've been motivated to try LLLT by this thread and I've also done a fair bit of reading as well, one thing that  I came across somewhere as a throwaway line was that LLLT works when there is a single frequency of light involved.

 

I've purchased a mixed 120 LED device that is pretty much half infrared at 850nm and half red at 660nm, I'm just wondering if I'm better served using both frequencies at the same time or whether the view is that I should only use one of the frequencies. I haven't found anything about using the 2 frequencies concurrently.

 

Whilst I'm primarily using it to enhance brain function I also want to use it on my liver and right kidney which have been chronically inflamed since an ill judged self administered mercury detox protocol where I dropped a high dose of cilantro onto the top of my head which resulted in a very rapid mobilisation that overwhelmed the 2 unfortunate organs in question. Anyway I'm just wondering about the inverted U response curve in relation to non brain application, presumably it still exists but at the same time I'm assuming that I can be far more relaxed in terms of duration of treatment, I've applied light at both frequencies to both organs for 10 minutes does this seem reasonable, could I go for longer?

 

Also as an afterthought I picked up a cheap intranasal device, meant for hayfever, that emits light at 630nm, once again does the response curve come into play when applying in this way, which I guess is really more about having the light absorbed by the blood as it passes through. Could you overdo this and lose the benefits or could I sit there for hours on end with this thing hanging out of my nostrils?

 

I've just received an ICES-PEMF so I'm using both to deal with some problems that stem from brain inflammation and underperfusion, so it will make it difficult to know which is responsible for any benefits but you know what it's like when you have health problems the most important thing is to resolve it, so I feel like I want to give the issue both barrels.

 

Thanks in advance for any answers and thanks to Lostfalco and everybody else that has contributed.

 

 

[Adaptogen]

Also as an afterthought I picked up a cheap intranasal device, meant for hayfever, that emits light at 630nm, once again does the response curve come into play when applying in this way, which I guess is really more about having the light absorbed by the blood as it passes through. Could you overdo this and lose the benefits or could I sit there for hours on end with this thing hanging out of my nostrils?

 

i bought a knock-off Bionase device, and i too am wondering how much is too much. i've been combining it with other lllt.

 

can't really say if the intranasal device has helped my allergies, as they were surprisingly not that bad before i started using it, but i do seem to have less flare-ups of allergic rhinitis than i'm accustomed to.

Edited by Adaptogen, 19 September 2015 - 08:03 AM.

[Santino]

Hello lostfalco,

 

how are you and how was your experience with the ICES device?

 

I received an ICES device today and I am little sceptic that this works. I know there are lots of studies but as a scientist I also know that studies often are either influenced by publication bias + it´s all about the money ;-)

 

However, I find Dr. Dennis to be trustworthy and he say that the ICES does "something".

 

Please let me know what it could do for you so far.

 

I also tried out tadalafil, Vardenafil and Sildenafil.

 

But for unknown reasons I got intolerant to Tadalafil and Vardenafil. I have various autoimmune diseases. Maybe it has to do with the substances influecing cytokines?!

 

best regards,

 

Santino

[lostfalco]

how are you and how was your experience with the ICES device?

 

I received an ICES device today and I am little sceptic that this works. I know there are lots of studies but as a scientist I also know that studies often are either influenced by publication bias + it´s all about the money ;-)

 

However, I find Dr. Dennis to be trustworthy and he say that the ICES does "something".

 

Please let me know what it could do for you so far.

 

I also tried out tadalafil, Vardenafil and Sildenafil.

 

But for unknown reasons I got intolerant to Tadalafil and Vardenafil. I have various autoimmune diseases. Maybe it has to do with the substances influecing cytokines?!

 

best regards,

 

Santino

Hey, what's up Santino? I'm doing great. I haven't had great results with ICES so far. Nothing bad...but nothing great either. 

 

Sorry to hear about the intolerance to PDE5i's. I'm not sure what the mechanism would be there. I've been on them for a number of months now and they still work great for me. I'm currently taking tadalafil. 

[lostfalco]

I've purchased a mixed 120 LED device that is pretty much half infrared at 850nm and half red at 660nm, I'm just wondering if I'm better served using both frequencies at the same time or whether the view is that I should only use one of the frequencies. I haven't found anything about using the 2 frequencies concurrently.

 

Anyway I'm just wondering about the inverted U response curve in relation to non brain application, presumably it still exists but at the same time I'm assuming that I can be far more relaxed in terms of duration of treatment, I've applied light at both frequencies to both organs for 10 minutes does this seem reasonable, could I go for longer?

 

Also as an afterthought I picked up a cheap intranasal device, meant for hayfever, that emits light at 630nm, once again does the response curve come into play when applying in this way, which I guess is really more about having the light absorbed by the blood as it passes through. Could you overdo this and lose the benefits or could I sit there for hours on end with this thing hanging out of my nostrils?

 

I've just received an ICES-PEMF so I'm using both to deal with some problems that stem from brain inflammation and underperfusion, so it will make it difficult to know which is responsible for any benefits but you know what it's like when you have health problems the most important thing is to resolve it, so I feel like I want to give the issue both barrels.

 

Thanks in advance for any answers and thanks to Lostfalco and everybody else that has contributed.

Hey Matty, no problem. I'm glad you've found something useful in the thread. =) 

 

It is somewhat of an open question whether single wavelengths or multiple wavelengths might be better. I think each experiment is worth a try. The MIT study from page one of this thread discussed two TBI patients who mixed 870nm and 633nm wavelengths with good effects. 850nm and 660nm are both worth a try individually and together imo.

 

I haven't experimented extensively with non-brain LLLT applications...but from what I've read in the scientific literature the mechanism is the same and so the inverted U definitely still applies. 

 

Intranasal: it's always possible to overdo something but it would take quite a bit of intranasal LLLT to get to that point. The blood that you are irradiating is going to be constantly flowing through and will therefore be different from moment to moment. 

 

I hope ICES works well for you! I'm still looking for a protocol with it that works for me. 

 

[Santino]

Yes, I once was active in a german platform and there were many men who took it for years on a daily basis for erectile dysfunction. So they seem quite safe.

 

Too bad that you did not notice anything from ICES. I never found someone who is not involved in selling PEMF or ICES who had really convincing benefits from it yet.

 

I will try it out during the next week and hope to get benefit. At least for orthopedic injuries. I won´t use it on m brain. I did it once but it seemed to trigger exactly hat I wanted to treat: brain fog. Got pretty severe afterwards.

 

How long did you experiment with it and did you use the device for 3-4 weeks for one "problem" everyday for many hours or did you just test things out here and there for a few minutes or a few hours without using it on one issue for 3-4 weeks everyday?

 

I spoke to Dr. Dennis and he told me to use it continuously for 3-4 weeks on one thing I want to treat. I am doing that right now. Used it everyday and night so far. Maybe just 2 hours each day without. So far I do not notice any benefit.

 

 

Ordered this device here as well:

 

http://www.ebay.de/i...6da918fa8d&cp=1

 

 

216 LED, 30 W CCTV device for LLLT.

 

What do you think about it? I recently saw an interview with Dr. Hamblin where he said that the upper limit should be 100mW per cm^2 when doing LLLT.

Do you know how I should use this device? Sit 75cm away from it?! How many minutes should one use it on the brain? I thought 10 minutes.

 

Have a nice day/evening!

Edited by Santino, 27 September 2015 - 07:07 PM.

[lostfalco]

How long did you experiment with it and did you use the device for 3-4 weeks for one "problem" everyday for many hours or did you just test things out here and there for a few minutes or a few hours without using it on one issue for 3-4 weeks everyday?

 

Ordered this device here as well:

 

http://www.ebay.de/i...6da918fa8d&cp=1

 

216 LED, 30 W CCTV device for LLLT.

 

What do you think about it? I recently saw an interview with Dr. Hamblin where he said that the upper limit should be 100mW per cm^2 when doing LLLT.

Do you know how I should use this device? Sit 75cm away from it?! How many minutes should one use it on the brain? I thought 10 minutes.

 

Have a nice day/evening!

I've tested ICES dozens of times now. Tried different settings, locations, lengths of time, etc. Never daily for 3 or 4 weeks though. I'll have to test that one of these days when I have more time.

 

Your LLLT device looks good. For transcranial LLLT you'll want to take the glass off and press the LEDs against your skin and past your hair for maximal skull penetration. Very little of the light makes it through bone and you can enhance this by pressing the LEDs into your skin as far as is comfortable. I would start with 30 seconds to 1 minute to begin with and gradually work your way up from there. Eventually, 10 minutes per spot is certainly a reasonable amount. I've lasered for 20 to 30 minutes per spot without issue.  

 

100mW per cm^2 is a VERY conservative upper limit. Did Hamblin say that in his interview with Joe from selfhacked? Do you have a time mark by any chance? 

 

Have a good evening too!

[Santino]

Yes, he did say that in the interview with Joe. Look at 08:40 for about 20 sec. 

 

My device will arrive this week. I am a bit afraid to use it on my head, because I am bipolar II with very rapid cycling. I have many diseases (Alopecia Areata, Vitiligo, chronic eosinophilic proctitis, IGA-Nephritis, very severe food intolerances and bipolar II ultra rapid cycling).

 

My bipolar disorder is very difficult to control. If I keep my circadian rhythms and avoid food triggers it evens out on a slightly depressive level. Any antidepressive agent (even yoga and meditation if I do it daily or too often) kicks me into hypomanic symptoms. First I get euphoric, then this switches into anxiety/irritability/agitation and the I have very fast cycling between depression and this hypomanic state for 1-5 days until it evens out again.

 

So if LLLT has an strong antidepressive effect, it may kick me into this cycling.

 

On the other hand, I know that it increases BDNF, so the antidepressive action might be different from any other methods I tried so far. I know that bipolar people are lacking BDNF as well as major depressive people. But long term bipolar patient have increased BDNF compared to normal and in the study I read they said this was not due to medication.

 

It would be important to see the ratio BDNF/proBDNF they concluded.

 

 

So in your eyes, the upper limit is much higher? How do you know that? It would be great to get some more insight into that before I try anything. If I try it, I definitively start with 30 sec. max.

 

By the way, the hair won´t be a problem because I have no hair anymore ;-)

 

I am just checking out to use ICES everyday for 3-4 weeks and can report back to you if you like!

[Bateau]

It is somewhat of an open question whether single wavelengths or multiple wavelengths might be better. I think each experiment is worth a try. The MIT study from page one of this thread discussed two TBI patients who mixed 870nm and 633nm wavelengths with good effects. 850nm and 660nm are both worth a try individually and together imo.

 

Have you ever seen a study were LLLT effects were actually successful solely using light <800nm?

 

I remember hearing that the range for effective LLLT is 800nm to 2 microns, meaning 660 would be useless.