Creatine Blunts Serotonergic Effects Of Methylene Blue And Caffeine

Waremu

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Anyone have a mechanistic theory on this? How are MB's serotonin raising effects altered by creatine's metabolic pathway?

Creatine helps recycle ATP, among many other things. Dr. Chris Masterjohn (who actually agrees on many of the same things Dr. Peat teaches) did a good podcast piece on Creatine. I highly recommend listening to it. In it he explains many of the biochemical mechanistic pathways. I'm on creatine and have noticed many of the same benefits as well. Here is the link:

https://chrismasterjohnphd.com/2017...e-than-a-performance-enhancer/?_sf_s=creatine
 

Pulstar

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Thanks, but are there actual studies on a subject?

To be honest, that link looks like another popular health site, which claims that the lack of serotonin leads to depression and aggression (which is not true according to RP). There are linked articles to the main article, in which they are promoting serotonin as something very beneficial, and that's what directly contradicts Ray's views. Have you read Ray's articles regarding coffee and serotonin?

Here's few quotes:

Serotonin excess causes several of the features of depression, such as learned helplessness and reduced metabolic rate, while coffee stimulates the uptake (inactivation or storage) of serotonin, increases metabolic energy, and tends to improve mood. In animal studies, it reverses the state of helplessness or despair, often more effectively than so-called antidepressants.
From <Caffeine: A vitamin-like nutrient, or adaptogen. Questions about tea and coffee, cancer and other degenerative diseases, and the hormones.>

Carbon dioxide, high altitude, thyroid, progesterone, caffeine, aspirin, and decreased tryptophan consumption protect against excessive serotonin release. When sodium intake is restricted, there is a sharp increase in serotonin secretion. This accounts for some of the antiinflammatory and diuretic effects of increased sodium consumption--increasing sodium lowers both serotonin and adrenalin.
From <Tryptophan, serotonin, and aging>
 

Owen B

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When I was experimenting with creatine last summer i developed an URTI. Not too much fun.

But I'm almost sure i saw a reference somewhere when i was researching the stuff that it's use mimics the effects of prolonged, endurance style exercise. That is, it pulls fluids away from the intestinal walls and allows bacterial permeability.

I'm pretty certain that's how I got the infection.

I liked it's psychological effect but in light of all this other stuff I think it's too risky.
 

Zpol

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Per Nathan Hatch creatine raises the level of phosphate in the body because of the way it is metabolized.
"CREATINE is often used as a body-building, athletic supplement, but creatine raises levels of phosphate in the body and supplementing it can dramatically alter the balance between calcium/phosphorus"
... he doesn't expand on this further on his blog though.
I have his book, I'm hoping he goes into it more. Until I understand fully I am staying away from it.
If anyone on this thread could help explain this claim, do share please!
 

Amazoniac

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I wasn't aware of coffee having serotonergic effects. On an empty stomach it can give obvious issues but along with a meal highish in proteins it may not be optimal for most.
Thanks for sharing though, Amazoniac has made posts on creatine. I don't remember if they would fit here.
Missed this. Here's another one:
Ask Dr. Andro: The Pharmacokinetics of Creatine (Part I/II) - How Is Creatine Absorbed into the Bloodstream? - SuppVersity: Nutrition and Exercise Science for Everyone*

*Jen, Rose, Lamb, Tata, Steve, Jeff, Kate all made their appearance elsewhere on issues with bicarbonate supplementation.
 

Wagner83

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ddjd

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@Waynish @Amarsh213 @vulture @Arrade @General Orange @BrightStar @Diokine

A little update guys. I've found that DHEA in a small dose of about 10mg (as peat recommends) does the exact same thing as the creatine as in it also completely stops the stress reaction to coffee. I'm using a swanson 25mg dhea product and letting 1/3 of a capsules powder just dissolve in my mouth for better absorption.

I'm wondering exactly what mechanism is having this positive effect, like the creatine. Is it the increase in DHT?? I think creatine potently increases DHT also?
 

Zpol

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@Amazoniac @Zpol @hotte @Owen B @Waremu you may also find the update above about DHEA also working interesting
Thanks for the update. I did buy some creatine but haven't touched it due to fact it indirectly increases phosphate and due to the L-arginine component (too much arginine=viral flare ups). Also, the more I research creatine, it appears many (not all) of the purported benefits are the same as with glycine alone. I already consume lot of L-arginine and methonine via meat so theoretically I would just need to add glycine to equal the creatine trifecta.
But that doesn't exactly address the hormonal aspect as far as I know. So I've been thinking of adding Pregnenalone in the form of Pansterone; it has DHEA in the mix so good to know your positive experience.
 
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I read that DHEA can acutely increase noradrenaline and dopamine production. - link
We have found the following: 1) DHEA, DHEAS, and ALLO increased acutely (peak effect between 10–30 min) and dose-dependently (EC50 in the nanomolar range) catecholamine levels (norepinephrine and dopamine). 2) It appears that the acute effect of these steroids involved actin depolymerization/actin filament disassembly, a fast-response cellular system regulating trafficking of catecholamine vesicles. Specifically, 10−6m phallacidin, an actin filament stabilizer, completely prevented steroid-induced catecholamine secretion.

3) DHEAS and ALLO, but not DHEA, also affected catecholamine synthesis. Indeed, DHEAS and ALLO increased catecholamine levels at 24 h, an effect blocked by l-2-methyl-3-(-4hydroxyphenyl)alanine and 3-(hydrazinomethyl)phenol hydrochloride, inhibitors of tyrosine hydroxylase and l-aromatic amino acid decarboxylase, respectively, suggesting that this effect involved catecholamine synthesis.

"Creatine...has been shown to increase DA synthesis in the substantia nigra of mice by protecting against striata DA depletion (Klivenyi. 2003) and / or by enhancing the tyrosine hydroxylase activity and thus increasing the production of dopamine from its precursor tyrosine (Matthews. 1999)."

It seems Creatine and DHEA can both increase dopamine production via enhanced tyrosine-dopamine biosynthesis.
So then hypothetically, when high amounts of caffeine is used and resulting in depleted dopamine, or one has low dopamine stores, the DHEA can be used to replenish them with similar effect of creatine.
One having low dopamine stores is then more sensitive to low dosage of caffeine, but also one with low DHEA-S or sulfur / sulfyration. Then be sure to get more sunlight or cholesterol and sulfur from foods.
 
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Another interesting view I have found is this DHEA - Serotonin relation I stumbled upon, more relating to the Methylene Blue part:

"DHEA administration causes a significant increase in serotonin levels (R) and there are findings showing the interactions between serotonin, BDNF, and DHEA (R). BDNF is a mediator of the DHEA activity in the brain tissue (R). BDNF promotes the survival and differentiation of serotonin neurons (R). On these bases several lines of evidence suggest that BDNF might be an important agent of therapeutic recovery from depression, and it might also provide protection against stress-induced neuronal damage (R) (R)."
 
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Funny thing, the MB should protect against the depletion of dopamine from high caffeine not?

Methylene blue protects dopaminergic neurons against MPTP-induced neurotoxicity by upregulating brain-derived neurotrophic factor. - link
Our results indicate that pretreatment with MB significantly attenuated MPTP-induced loss of dopaminergic neurons, glial cell activation, and depletion of dopamine.
 
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As for the adrenaline inhibiting part of DHEA I found this:

"DHEA-S inhibits the norepinephrine release induced by activators of [Ca2+]i and Na+. DHEA also suppresses K+-induced norepinephrine secretion but without influencing the [Ca2+]i rise [15]. This inhibitory effect of DHEA/S is dose dependent and occurs at physiologically relevant concentrations. (R)

DHEA can antagonize physiological functions of endogenous glucocorticoid inducing a dose-related up-regulation of GRβ (R)."
 
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edit double post..
and then it continues:

"DHEA/S, by increasing BDNF leads to a priming of GR signalling (R). This is largely how antidepressants really work – through increases in serotonin, which increases BDNF, which ultimately leads to a re-establishment of cortisol sensitivity.

This means that DHEA/S helps restore cortisol sensitivity.

Overall, it’s the Cortisol/DHEA ratio (Or cortisol/DHEA-S – see next section) rather than the absolute values of either are what matter. Shifting the balance too far in either direction could be a problem." - source

edit
Nice! :smug: if just hit my 1kilobyte post lol :borg:
 
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ddjd

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This means that DHEA/S helps restore cortisol sensitivity.
This would make more sense. I wonder then in that case whether the loose stools from caffeine and methylene blue is just caused by high Cortisol. Have you ever heard of high Cortisol causing loose stools? They also both cause me insomnia which would also support the idea of them raising cortisol. Thanks for finding this, I think you're on the money with regards to DHEA restoring cortisol sensitivity.

Regarding dhea raising Serotonin, my experience is the opposite and there's been a few studies on the forum attainatt to that. I'll try and dig them out.
 

Arrade

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Doesn't coffee increase DHT though by increasing the 5AR enzyme activity
 

Elephanto

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Doesn't coffee increase DHT though by increasing the 5AR enzyme activity
The Chlorogenic Acid in coffee has a 5-AR inhibiting effect at doses that can easily be obtained with 1-2 cups of coffee (apparently dark roasts have less CA too). Not sure what the net effect is when considering the opposing effect of caffeine. We also see an association in males between coffee consumption and higher T and SHBG, perhaps from a reduced conversion into DHT.

the high and medium dose of chlorogenic acid could significantly reduce prostate index and levels of acid phosphatase, prostatic acid phosphatase and typeⅡ5-alpha-reductase (P<0.05 or P<0.01).
mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice.
Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice. - PubMed - NCBI
 

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