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Chemically induced LTP?

ciltep pde4 forskolin ltp

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#1921 maxwatt

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Posted 22 September 2013 - 11:22 AM

One question for the group: I believe artichoke extract is used as a PDE-4 inhibitor. Luteolin is an extremely effective PDE-4 inhibitor, and in theory could stand in for Artichoke extract. Would this be acceptable? Has anyone used it? Less would be needed, probably less expensive. /How much does ALCAR add to the effect?

@acrunchyfrog: L-carnitine and ALCAR hove overlapping effects, do not know if it would work here, but I believe much more would be needed, possibly prohibitive in a capsule.

#1922 Godof Smallthings

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Posted 22 September 2013 - 12:37 PM

Either LPA or ALCAR made me feel positively awesome yesterday.

Woke up, took my daily bacopa on an empty stomach with a glass of water. 45 min later, had a few pieces of buttered toast with a capsule Max DHA. No noticeable effects from that (not that I expected any).

Went out for lunch. Brought 300 mg ALCAR, 500 mg Artichoke, 1000mg salmon oil, 500 mg LPA, and 1000 mg bioflavonoid vit C. Took the pills right after lunch.

Roadtrip into the mountains, stopped at a cafe, waded in a mountain stream in clear sunshine, had a cup of latte and a small piece of cake. Went to a huge almost deserted agri/horticultural fairground area (to give my son some space to practice his bicycle skills) and walked around in the tropical afternoon sun for a good 1.5 hours. Started to feel a little tired. Then found that one of the pills I had brought for lunch was still in my pocket. Took it, and some 30 min later I experienced a surge of energy. It was a white coloured capsule so it must have been either the ALCAR or the LPA. Either way, I had immense energy and positive mood for a good two hours following, while the rest of the family were completely drained of energy. Got home and cooked up a storm. Thing is, I am usually dead tired and quite grumpy in the evening, especially before dinner. Not yesterday. So it's pretty significant.

Which one do you think it was? The ALCAR or the LPA? I guess I need to try to replicate the experiment...

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#1923 raincheck

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Posted 22 September 2013 - 08:57 PM

One question for the group: I believe artichoke extract is used as a PDE-4 inhibitor. Luteolin is an extremely effective PDE-4 inhibitor, and in theory could stand in for Artichoke extract. Would this be acceptable? Has anyone used it? Less would be needed, probably less expensive. /How much does ALCAR add to the effect?

@acrunchyfrog: L-carnitine and ALCAR hove overlapping effects, do not know if it would work here, but I believe much more would be needed, possibly prohibitive in a capsule.


It's been discussed in this thread but it doesn't pan out

#1924 stephen_b

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Posted 22 September 2013 - 11:38 PM

One question for the group: I believe artichoke extract is used as a PDE-4 inhibitor. Luteolin is an extremely effective PDE-4 inhibitor, and in theory could stand in for Artichoke extract. Would this be acceptable? Has anyone used it? Less would be needed, probably less expensive. /How much does ALCAR add to the effect?

@acrunchyfrog: L-carnitine and ALCAR hove overlapping effects, do not know if it would work here, but I believe much more would be needed, possibly prohibitive in a capsule.


It's been discussed in this thread but it doesn't pan out


Here is the post mentioning luteolin.
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#1925 magta39

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Posted 23 September 2013 - 01:43 AM

Does magnesium l threonate have an acute effect on the brain and you notice it immediately, or does its effects slowly build up over time? Also, has anyone tried a Forskolin+Artichoke+ALCAR+PQQ stack?

#1926 Amby

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Posted 23 September 2013 - 11:59 AM

I also "stack" ciltep with Yerba maté and Green tea as my only stimulants.


First up a newbie warning if what I'm saying is rubbish, but as a Yerba mate drinker myself (pre-CILTEP stack... waiting for Paypal funds to clear) I saw chung pao's post and then read this: http://www.matefacto...-nutrition.html which mentions Theobromine and Theophylline as components of Yerba mate:

Theobromine
cAMP-inhibitor IC50= 0.06 mg/mL, cAMP-phosphodiesterase-inhibitor, diuretic 300 to 600 mg/day, stimulant, myorelaxant
Theophylline
cAMP-inhibitor IC50= 0.06 mg/mL, cAMP-phosphodiesterase-inhibitor, diuretic, choleretic, stimulant, vasodilator, myorelaxant 100 μM

As a cAMP inhibitor would these in fact point to avoiding yerba mate while on the stack to maximise impact and just sticking with normal coffee for caffeine impact?

#1927 chung_pao

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Posted 23 September 2013 - 12:13 PM

I also "stack" ciltep with Yerba maté and Green tea as my only stimulants.


First up a newbie warning if what I'm saying is rubbish, but as a Yerba mate drinker myself (pre-CILTEP stack... waiting for Paypal funds to clear) I saw chung pao's post and then read this: http://www.matefacto...-nutrition.html which mentions Theobromine and Theophylline as components of Yerba mate:

Theobromine
cAMP-inhibitor IC50= 0.06 mg/mL, cAMP-phosphodiesterase-inhibitor, diuretic 300 to 600 mg/day, stimulant, myorelaxant
Theophylline
cAMP-inhibitor IC50= 0.06 mg/mL, cAMP-phosphodiesterase-inhibitor, diuretic, choleretic, stimulant, vasodilator, myorelaxant 100 μM

As a cAMP inhibitor would these in fact point to avoiding yerba mate while on the stack to maximise impact and just sticking with normal coffee for caffeine impact?


How can Theobromine and Theophylline simultaneously be cAMP-inhibitors and PDE-inhibitors?
Asking out of curiosity. Please elaborate.

#1928 noema

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Posted 23 September 2013 - 05:20 PM

My friend created a "combined" form of the supplement. I'd prefer not to link to it directly because I want to respect the rules etc but he charges 34.99 for a 30 day supply. More expensive than buying the ingredients and splitting the capsules yourself but hey, its wildly convenient and the quality is there. I'd expect his version to grow in supply as the demand for this interesting combination of supplements increases within the nootropic community.

#1929 xsiv1

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Posted 23 September 2013 - 05:32 PM

I knew it'd only be a matter of time. I'm sure others will follow suit with added ingredients. No harm, no foul. I do find it a bit of a pain to be breaking up certain capsules to get the desired dose but it just means that I need a good little while "alone" and without my wife and little ones around to prepare and have it last me a while.

#1930 chung_pao

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Posted 23 September 2013 - 06:39 PM

Title: Can Repetition needed for learning Motor Skills be decreased using PDE-5 inhibitors?
(or manipulating the NO/cGMP pathway in other ways)

In case anyone is interested in learning motor skills; actual movement patterns: (musical instruments, strength, fighting, online gaming)
PDE-5 inhibition might be worth looking into.

First off, some basics on the Cerebellum:
*In addition to its direct role in motor control, the cerebellum also is necessary for several types of motor learning.
*The cerebellum (Latin for little brain) is a region of the brain that plays an important role in motor control.
*"These findings suggest that specific circuitry in the cerebellum may be dedicated to specific motor control parameters such as force amplitude and force rate."
*"These results are consistent with theoretical proposals that motor learning takes place in the cerebellum through changes in the strength of transmission of parallel fiber synapses on Purkinje cells caused by the climbing fiber input."
Posted Image

Relevant results after searching Pubmed.com for "PDE5 + motor neurons/cerebellum".

Phosphodiesterase inhibitors are neuroprotective to cultured spinal motor neurons.

Furthermore, semiquantitative analysis of the immunostaining intensity revealed that PDE5 was more abundant in motor neurons than in nonmotor neurons. In addition, the results of this study raise the possibility that PDE5 inhibitors might be used as a treatment for amyotrophic lateral sclerosis (a neurodegenerative disease of motor neurons).


A case in point is differential expression of cGMP PDEs in neuronal cells. For example, we have recently found that PDE5 is expressed in all Purkinje neurons. (i.e. the cerebellum)


Sildenafil induces cGMP accumulation through phosphodiesterase-5 (PDE5) inhibition. The results demonstrate a protective effect of sildenafil in the cerebellum.

These results demonstrate that cGMP is a specific and allosteric activator of PDE5, and suggest that in cells containing PDE5, such as cerebellar Purkinje cells, intracellular cGMP concentrations may be regulated autonomously through effects of cGMP on PDE5.


Still, recent immunohistochemical and reverse transcriptase-polymerase chain reaction analysis have demonstrated the presence of anti-PDE5 antibodies and PDE5 transcripts in rat cerebellum, kidney, pancreas, aortic smooth muscle cells, heart, placenta, skeletal muscle, and, to a much lesser extent, in other regions of the brain, liver and lungs.

This is the first in vivo functional study showing that, in cortex, PDE1, -2, and -5/9 degrade cGMP, with PDE9 probably playing a major role; in hippocampus, PDE5/9 and PDE1 are mainly involved and seem almost equally active, but PDE2 and -3 also contribute; in cerebellum, PDE5/9 are the main cGMP hydrolyzing enzymes, but also PDE1 and -4 significantly operate.


I'm currently looking into the practical applications of this.
What first made me interested in this was that I was very jittery, peripherally (i.e. in neurons regulating movement), as opposed to centrally (racing mind, thinking in words), after high dosing Artichoke, Forskolin with high doses of Theobromine (some studies indicate it's a PDE-5 inhibitor).
I was not talkative or concentrated, just very inclined to move around.

Myself, I'm applying this to strength training, in the hope that strong PDE-5 inhibition will increase progression in Neural performance and learning of movement patterns. I'm also suddenly very inclined to take up some form of fighting or musical instrument.

Also, before everyone starts mentioning the potential for involuntary boners with PDE-5 inhibitors, it's not necessarily a side-effect of tinkering with this mechanism.
If you avoid being sexually stimulated during the activity, it won't be a problem.

My proposed stack for learing Motor skills so far:
Theobromine, Forskolin, Artichoke.
There are many studies showing interactions synergistic between cAMP and cGMP, which makes me inclined to include Forskolin.

Anyone else interested? If so, please help by adding potentially synergistic agents or mechanisms. (cGMP- and NO-inducers, PDE-5 inhibitors, etc.)

Edited by chung_pao, 23 September 2013 - 06:40 PM.

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#1931 Amby

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Posted 23 September 2013 - 08:25 PM

How can Theobromine and Theophylline simultaneously be cAMP-inhibitors and PDE-inhibitors?
Asking out of curiosity. Please elaborate.


Hi Chung pao, sorry as I flagged I'm still very new to nootropics so I wasn't sure myself, which prompted the question.

I really appreciate your experimentations and am looking forward to taking my first step on this journey.

PS Loved you PDE-5 posting. Very interesting.

My proposed stack for learing Motor skills so far:
Theobromine, Forskolin, Artichoke.
There are many studies showing interactions synergistic between cAMP and cGMP, which makes me inclined to include Forskolin.


Is there a specific brand of Theobromine you find works well?

#1932 xsiv1

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Posted 24 September 2013 - 02:05 AM

Uh yeah, I don't think I'd ever try Theobromine in conjunction with this stack personally. The risks aren't worth it for someone like me physiologically-speaking.

#1933 raincheck

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Posted 24 September 2013 - 03:23 AM

Uh yeah, I don't think I'd ever try Theobromine in conjunction with this stack personally. The risks aren't worth it for someone like me physiologically-speaking.


Are the risks you mention overdose, or withdrawals or can you specify?

#1934 raincheck

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Posted 24 September 2013 - 03:28 AM

My friend created a "combined" form of the supplement. I'd prefer not to link to it directly because I want to respect the rules etc but he charges 34.99 for a 30 day supply. More expensive than buying the ingredients and splitting the capsules yourself but hey, its wildly convenient and the quality is there. I'd expect his version to grow in supply as the demand for this interesting combination of supplements increases within the nootropic community.

There are contract manufacturers who will source it and cap it, minimum order is usually 50,000 capsules. They'll bottle and label it to meed FDA regs, and even do label artwork for additional fee.
Do we have a general consensus what the content should be? I can price it with no commitment if people are curious.


Towards the end of the year, we should poll for a group buy and save ourselves some money and time.

#1935 xsiv1

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Posted 24 September 2013 - 12:53 PM

Uh yeah, I don't think I'd ever try Theobromine in conjunction with this stack personally. The risks aren't worth it for someone like me physiologically-speaking.


Are the risks you mention overdose, or withdrawals or can you specify?


Nah, none of the above. I was speaking about myself personally since I drink 2-3 cups of coffee each day, and use other workout supplements. Theobromine is said to have a diuretic effect (which could be good for some I suppose given that they're electrolyte/ mineral balances are kept optimal) and also raise heart rate which, for me, isn't a good thing since I'm already using enough things that 'assist' in fat-burning. For others it may work well and without deleterious effect but I'd still, at the very least, look at it's Wiki page to see if it's something you want to add. Chung Pao, I'm thinking is at least 20 years younger than me, so that would make a difference as well with regards to the disparity of effect it may have between his use of Theobromine and mine.

#1936 maxwatt

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Posted 24 September 2013 - 01:14 PM

My friend created a "combined" form of the supplement. I'd prefer not to link to it directly because I want to respect the rules etc but he charges 34.99 for a 30 day supply. More expensive than buying the ingredients and splitting the capsules yourself but hey, its wildly convenient and the quality is there. I'd expect his version to grow in supply as the demand for this interesting combination of supplements increases within the nootropic community.

There are contract manufacturers who will source it and cap it, minimum order is usually 50,000 capsules. They'll bottle and label it to meed FDA regs, and even do label artwork for additional fee.
Do we have a general consensus what the content should be? I can price it with no commitment if people are curious.


Towards the end of the year, we should poll for a group buy and save ourselves some money and time.

If only two ingredients, I see little benefit from combining into a single pill. Forskolin all comes from India, and most if not all artichoke extract from Italy.

As for Luteolin, if you used Lutimax to test it, test again. The current Lutimax formulation contains several other things, and the amount of luteolin actually in it is not specified. They can do that as its part of a 'proprietary blend'.

#1937 raincheck

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Posted 24 September 2013 - 03:19 PM

Maxwatt, we've yet to finalize the ingredients which is why I suggested we wait towards the end of the year at the latest. Currently there are many different variations people are using.

#1938 Amby

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Posted 24 September 2013 - 09:22 PM

Uh yeah, I don't think I'd ever try Theobromine in conjunction with this stack personally. The risks aren't worth it for someone like me physiologically-speaking.


Are the risks you mention overdose, or withdrawals or can you specify?


Nah, none of the above. I was speaking about myself personally since I drink 2-3 cups of coffee each day, and use other workout supplements. Theobromine is said to have a diuretic effect (which could be good for some I suppose given that they're electrolyte/ mineral balances are kept optimal) and also raise heart rate which, for me, isn't a good thing since I'm already using enough things that 'assist' in fat-burning. For others it may work well and without deleterious effect but I'd still, at the very least, look at it's Wiki page to see if it's something you want to add. Chung Pao, I'm thinking is at least 20 years younger than me, so that would make a difference as well with regards to the disparity of effect it may have between his use of Theobromine and mine.


I'll probably give it a miss then as like yourself xsiv I'm in my very early 40's, workout a lot, take all the good supplements associated with working out (protein, creatine, PAGG/AGG and a good swag of vitamins and minerals to make up for being on the slow carb diet.)

On other news I've ordered my stack at last! NOW artcihoke extract, better body sports C-bolic, ALCAR, L-Phenylalanine and Panax Ginseng. Being in Australia it should take 2 weeks to get here though, but looking forward to it.

#1939 bossmanglb

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Posted 25 September 2013 - 01:04 AM

Has anyone experienced fat loss or positive body recomposition as a result of forskolin supplementation?

#1940 Sholrak

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Posted 25 September 2013 - 01:23 AM

I have noticed much better coordination and a little and subjective physical improvement.

I wanted to ask, you mates do the ciltep every day? I think this is a stack/noot to be taken 2-4 times a week at max. It has improved everything a lot, and it looks like staying long term (obviously if it's LONG TERM potentiation) with me. Sometimes I find it too strong. Sometimes undesirable/anxyogenic but definitely worth and subtle after all.

#1941 magta39

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Posted 25 September 2013 - 01:35 AM

Personally, for me, forskolin works best every other day. The other components of the stack I take pretty much every day.

#1942 formergenius

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Posted 25 September 2013 - 12:45 PM

Hello.
I'm considering trying the CILTEP stack, however I'd like to know how this would effect Dynorphins. I know it has to do with cAMP and CREB, which would affect Dynorphin, however I'm having trouble connecting the dots myself. Does anybody know if adding the CILTEP stack would increase/decrease Dynorphin production, and how this is mediated? I don't want to disrupt this thread, so if you can, please reply here. Thanks.

#1943 lostfalco

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Posted 26 September 2013 - 03:30 PM

Hey guys, I was just messaging with Jesse Lawler over at the Smart Drugs Smarts podcast http://smartdrugsmarts.com/ and he told me that none other than Abelard Lindsay himself was going to be the featured guest in the next week or two (either episode #21 or #22). Very cool. Props to you Abelard for CILTEP and I can't wait to hear your interview!

-Posted with Jesse's permission.

Edited by lostfalco, 26 September 2013 - 03:31 PM.


#1944 abelard lindsay

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Posted 27 September 2013 - 01:50 AM

Hey guys, I was just messaging with Jesse Lawler over at the Smart Drugs Smarts podcast http://smartdrugsmarts.com/ and he told me that none other than Abelard Lindsay himself was going to be the featured guest in the next week or two (either episode #21 or #22). Very cool. Props to you Abelard for CILTEP and I can't wait to hear your interview!

-Posted with Jesse's permission.


I'm still trying to figure out what to make of this whole CILTEP phenomenon but it just kind of keeps growing on its own momentum. Maybe at some point it will inspire a SENS like effort around cognitive enhancement. I wouldn't mind being a part of that. Anyway, I'm sure you'll enjoy the interview.

#1945 lostfalco

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Posted 27 September 2013 - 02:10 AM

Hey guys, I was just messaging with Jesse Lawler over at the Smart Drugs Smarts podcast http://smartdrugsmarts.com/ and he told me that none other than Abelard Lindsay himself was going to be the featured guest in the next week or two (either episode #21 or #22). Very cool. Props to you Abelard for CILTEP and I can't wait to hear your interview!

-Posted with Jesse's permission.


I'm still trying to figure out what to make of this whole CILTEP phenomenon but it just kind of keeps growing on its own momentum. Maybe at some point it will inspire a SENS like effort around cognitive enhancement. I wouldn't mind being a part of that. Anyway, I'm sure you'll enjoy the interview.

I wouldn't mind either. Let's make it happen man.

#1946 swen

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Posted 27 September 2013 - 05:42 AM

Awesome man! I think you did an awesome thing with sharing CILTEP the way like you did :)

#1947 Babychris

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Posted 27 September 2013 - 08:29 PM

That's funny in my sweat country (Lebanon), Grandmas used to give to their child every morning and more before an exam, a meal with a lot of artichoke coupled with Zaatar (it's thyme mixed with some stuff including a CAMP increaser) it was known to give the strenght of the Lion and to allievate to a certain extent stresS.

#1948 abelard lindsay

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Posted 27 September 2013 - 10:42 PM

That's funny in my sweat country (Lebanon), Grandmas used to give to their child every morning and more before an exam, a meal with a lot of artichoke coupled with Zaatar (it's thyme mixed with some stuff including a CAMP increaser) it was known to give the strenght of the Lion and to allievate to a certain extent stresS.

Is this what you're talking about?

http://www.food.com/...ng-sauce-486975

#1949 Babychris

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Posted 29 September 2013 - 10:40 AM

Haha you're awesome ! That's very close to what's my loving mom used to eat in the war times, but not exactly. This version is more of a jew recipe,
In our Christian valley we don't put mayonnaise nor we put mustard (I'm not sure for this one though) anyway it's still the same idea. It's maybe why Lebanese and Sefarade people are so intelligent (I'm joking of course)

anecdotically most people drink with this, some strong lebanese coffee (which is in fact turkish) : We have the "original" CILTEP stack here haha.

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#1950 chung_pao

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Posted 29 September 2013 - 06:25 PM

I advice everyone who take this stack regularly to keep an extra eye on their mineral intakes - Make sure you're getting 100% of your RDI.

I had been noticing symptoms of mild Metabolic Acidosis (low blood pH): weaker joints and increased inflammation, among other things. I also noticed that CILTEP was losing effect, and making me tired instead of alert.

This was reversed upon supplementation with Calcium, Magnesium and Sodium Bicarbonate, and some dietary changes.
(More greens. Chlorophyll = Magnesium)

There are a few studies implicating blood-pH in the activity of cAMP/AC.

Bicarbonate-regulated soluble adenylyl cyclase.
"sAC is directly stimulated by bicarbonate ion..."
http://www.ncbi.nlm....pubmed/11875252

"These alterations are associated with a decrease in the content and function of Gs alpha, suggesting a role of Gs in the renal adaptation to phosphate depletion and acidosis."
http://www.ncbi.nlm..../pubmed/2113772

"Incubation of rat hepatocytes with 10 nM glucagon at pH 7.4 caused an immediate increase in cAMP concentrations (8-fold), and this rise was almost 50% lower at acidic extracellular pH (6.9). Whatever the experimental model, calcium appeared to be required for maximal stimulation of cAMP production by glucagon. "
http://www.ncbi.nlm..../pubmed/2829979

"Acidosis inhibited lipolysis and cyclic AMP accumulation due to NA non-competetively. Maximal lipolysis (3 muM NA) was inhibited by 25% at pH 7.0 and by 61% at pH 6.6 Cyclic AMP accumulation 5 min after 3 muM NA was inhibited by 57% at pH 7.0 and by 83% at pH 6.6. Since NA-induced lipolysis is a cyclic AMP-mediated process it is suggested that at least part of the antilipolytic effect of acidosis is due to inhibition of cyclic AMP formation."
http://www.ncbi.nlm....gov/pubmed/3944

"Adenylate cyclase activity was depressed at pH 6.8 and 6.0. These data suggest that the inotropic effect of isoproterenol is diminished in the acidotic muscle. This may be due to the decreased activation of cAMP production, which in turn most likely results from depressed adenylate cyclase activity."
http://www.ncbi.nlm..../pubmed/2827507

"In addition to the diminished effects of isoproterenol, acidic myocytes had smaller responses to extracellular forskolin and internally applied adenosine 3',5'-cyclic monophosphate, compared with control."
http://www.ncbi.nlm....523439


Point being: If CILTEP isn't working, or causing fatigue, you might be deficient in certain minerals, or have a slightly acidic pH.
Even if CILTEP is working, and you take it regularly, pay attention to your mineral intake. Ensure 100% of RDI, at least.
CILTEP, at least when used with caffeine, can increase mineral losses due to diuresis, and production of acidic products of metabolism.

Simplification: CILTEP (= Increased Diuresus = Increased mineral losses) = Lower blood pH = Suppressed response to CILTEP, unless minerals are replenished/pH restored.

*I've also noticed that ciltep might be more likely to cause fatigue in a state of mineral-deficiency/acidosis.

If anyone is more versed in acid-base/kidney physiology, please correct me. Just making a stab in the dark.





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