Fermented cacao sludge: epigenetic/microRNA active polyphenols and tetrahydro-β-carbolines

[Alchemica]

So I've fermented cacao, that was good according to taste testers. I had some of the alcohol free yeasted sludge from the bottom of the fermentation yesterday... it's a good healer.
 

Watch out ayahuasca... we have a new healer in town. This ones been yeasting for a bit now...

 

Fermented cacao solids, sans the alcohol part
 

For me it's a friendlier intelligence to work with. More heart-centred, less crazily spirited but intelligent and healing.

Tastes a hell of a lot better too.
 

Save some of the next batches for roasting
.

Mmm active flavonols, phenolic acids, funky alkaloids... I bring you brewed cacao SLUDGE!

 

Got through half that, seems sufficient. It's maybe more an integration tool, not a vision ally, returning to heart, balancing energies, settling disturbances. Definitely a nice stabilising heart-resonance, definitely healing, cognitively clear with good emotional attunement.
 

I'd guess the spirited alkaloid constituents would carry into the ethanolic portion so that dimension wasn't overly prevalent, this remnant sludge is like the grounding, healing heart energy counterbalance. The two would be nice together. Given me good balanced healing with just this. Kind of the bit I need to work with at the moment, the yeasted polyphenol rich portion. Good relief from my issues from that, see how long it lasts.
 

If you brewed a strong cacao sludge you could get a dense alkaloid rich solution with minimal alcohol, too. Then roast. I'll play with that at some stage.

 

The other part of the traditional preparation involves roasting... why might that be important?
 

First the fermentation would increase both interesting bioactive/GABAergic polyphenols, including the parent serotonergic/opioid-active flavonols, and NMDA sperimidine alkaloids but also tetrahydro-β-carbolines (maybe even TIQs from the PEAs) and decent quantities of their precursor tryptamines! On roasting, Maillard-type reactions would occur and the remaining tryptamines form more tetrahydro-β-carbolines, possibly also undergoing decarboxylation to better levels of better actives...

Tetrahydro-β-carbolines
 

We have previously reported that several foods and fermented alcoholic beverages contain appreciable amounts of two of those THβCs found in chocolates, THCA and MTCA, reaching up to several mg/kg (Herraiz et al., 1993, Herraiz, 1996-2000). Interestingly, the concentration of THCA and MTCA in chocolate and cocoa is comparable to that of alcoholic beverages such as wine, beer, and liquor, which contain a relatively high amount of those compounds.
 

The origin of these tetrahydro-β-carbolines is a reaction involving L-tryptophan and aldehydes that are present or otherwise released during the processing of foods and beverages. Its chemical formation depends on the amount of precursors, storage time, pH, temperature, and processing conditions (Herraiz and Ough, 1993; Herraiz, 1996).

 

The same reaction is likely to occur in chocolates that suffer a fermentation from cacao beans and heating processes. Then, it is expected that serotonin, L-tryptophan, and tryptamine afford the corresponding THβCs (6OHMTHβC, MTCA, and MTHβC) through a Pictet-Spengler condensation with acetaldehyde
 

The biological significance of tetrahydro-β-carbolines and β-carbolines is related to their potential pharmacological actions on the nervous system, playing a role as neuromodulators via effects on monoamine oxidase (MAO), biogenic amine (serotonin) uptake/release, and benzodiazepine receptor binding. Then, these compounds exogenously supplied, or hypothetically produced in vivo, might become bioactive, exhibiting behavioral and/or toxicological implications. In this regard, it is very likely that part of the β-carbolines found in the human tissues and fluids have a dietary origin.

Tetrahydro-beta-carbolines, potential neuroactive alkaloids, in chocolate and cocoa.

http://sci-hub.bz/10.1021/jf000508l

 

microRNA

 

One level cacao sludges likely work at is the epigenetic, particularly microRNA, level: on the short, non-coding regulatory RNAs. Their main, although not unique, function, consists in regulating the translation and/or degradation of so-called target messenger RNAs

 

Numerous studies have shown microRNAs to regulate fundamental processes, including muscle, cardiac, neural, and lymphocyte development, or the regulation of both the innate and adaptative immune responses. microRNAs are changed in a number of pathologies, such as metabolic, autoimmune, cardiovascular, mental and neuro-inflammatory diseases or cancers.

 

Strong anti-inflammatory/immunomodulating/protective/restorative effects of polyphenols found in cacao extracts have been noted with reduced levels of pro-inflammatory enzymes such as NF-kB, 5-Lipoxigenase (5-LOX), prostaglandin E2 (PGE2), reactive oxygen species (ROS), nitric oxide (NO), and TNF. They also likely get in at (IGF)-1/AKT/rapamycin (mTOR) pathway, by reducing the expression of IGF1 and Insulin receptor (INSR) genes, reduce the levels of Ribosomal protein S6 kinase beta-1 (p70S6K), activation of pro-survival PI3K/AKT pathway. and act at the ERK1/2-mTOR pathway. The break down flavonol polyphenols are also epigenetically active, modulating PKC, reducing pro-inflammatory cytokines, reduced apoptosis, reduction of vascular endothelial growth factor (VEGF) expression, and attenuated oxidative stress markers.

 

There is strong regulation of microRNAs related to the mind and things like NF-kB, AKT, and MAP kinase pathways
 

We really don't know how deep this goes!

Promiscuous Effects of Some Phenolic Natural Products on Inflammation at Least in Part Arise from Their Ability to Modulate the Expression of Global Regulators, Namely microRNAs.

Edited August 4, 2017 by Alchemica

[ThunderIdeal]

Promiscuous effects!

[Alchemica]

Yeah, makes up for all the healthy wild promiscuity I never got to have I just had the unhealing drug sort

This brew sludge could be rich in B vitamins, too!
 

Things as simple as even basic B group vitamins at higher than RDI doses shouldn't be neglected as mood therapeutics...
 

Thiamine inhibited the upregulation of GSK-3β induced by stress, and reduced stress-induced behavioural changes in anxiety and exploration. Coincident, thiamine improved learning and extinction of contextual fear, and the acquisition of the step-down avoidance task. Our data indicate that thiamine has antidepressant/anti-stress effects that are associated with reduced GSK-3β expression and conditioning of adverse memories. Thus thiamine may modulate GSK-3β functions in a manner that is dependent on whether the contextual conditioning is adaptive or maladaptive.
 

The mood stabiliser lithium inhibits glycogen synthase kinase-3, maybe high thiamine supplementation may be protective against bipolar etc?
 

I feel more stable with higher dose B-groups on board in my diet, subtle but part of better health, particularly if you've fallen down to alcohol.

It's also the neuroprotective, antidepressant part rich in phenolic acids:

The Neuroprotective Effects of Phenolic Acids: Molecular Mechanism of Action

Not only is cacao brew spiritual but also way more likely to be healthy for you than plain neurotoxic and hepatotoxic alcohol brews: The flavonols are neuroprotective, cardioprotective, likely hepatoprotective and really healing healthy, so too the phenolic acids.

Edited August 3, 2017 by Alchemica

[Alchemica]

Not only can this fermentation change from the main cacao catechins being NO/5-HT1A/opioid mediated effects to something else but also change how it acts on GABAARs. similarly to tea processing
 

I coupled a bit of L-theanine with my cacao sludge today to try and get my stress scores down a bit.
 

The same changes occurring in cacao brews happen in teas when they are formed. This process changes the polyphenols and the way they modulate GABAA receptors. Some of these compounds are also ligands for the GABAA receptor benzodiazepine site. the higher catechins like EGCG being PAMS at some sites. EGCG reversed the effects of GABAA receptor negative modulators and picrotoxin and methyl beta-carboline-3-carboxylate, EGCG and chlordiazepoxide fully generalised in substitution studies. The phenolic acids are also GABAergic, potentially at different GABAA subtypes. [see Flavonoid modulation of GABAA receptors: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087128/]

Healthy properties of green and white teas: an update.
 

Polyphenols are the most relevant family of phytochemicals in terms of beneficial effects on human health. Within them, flavonoids constitute a very extensive group and are distributed in a great variety of vegetables. They have a common basic structure of (C6-C3-C6) diphenylpropane, which usually forms an oxygenated heterocycle. Flavonoids are usually bound to sugars (glycosides) and for that reason they tend to be water-soluble. Green and white tea are especially rich in flavonoids, specifically catechins. In this line, the consumption of green tea is considered the main source of catechins in the diet. The content in phenolic acids (gallic acid, benzoic acid, cinnamic acid, chlorogenic acid, caffeic acid), gallic esters of glucose (gallic tannins), quercetin and proanthocyanidols is also highlighted. Total polyphenols range between 10.60-25.95 g/100 g in white tea and between 13.7-24.7 g/100 g in green tea.

The most abundant catechins in green and white tea are (-) epigallocatechin gallate (EGCG), representing approximately the 59% of the total catechins; (-) epigallocatechin (EGC), whichaccounts for the 19%, (-) epicatechin gallate (ECG) in a proportion close to the 13% and (-) epicatechin (EC), around the 6% of the total. According to Hilal and Engelhardt and Carloni et al. catechin content in tea ranges from 9.89 to 17.00 g/100 g in green tea, from 7.94 to 16.56 g/100 g in white tea and from 0.74 to 10.00 g/100 g in black tea. Catechins content is consistent with the fermentation degree, since black, white and green teas are fully, slightly and non-fermented, respectively.10 Levels from 2.76 to 9.34g/100 g for catechins in white tea have also been reported. Regarding EGCG, the amounts change between 4.40-9.60 g/100 g in green tea and between 5.23-9.49 g/100 g in white tea. Cabrera et al. observed that the content of EGCG in green tea leaves was higher than 80 mg/g, whereas in black tea it did not exceed 30mg/g. Wu and Wei reported that one cup of green tea (2.5 g tea leaves/200 mL water) may contain 90 mg of EGCG and Johnson et al. estimated that the daily intake of 3-5 cups of green tea (720- 1200 mL) could provide up to 250 mg of catechins.
 

Polyphenols and L-theanine for stress:
 

Although green tea contains caffeine, its consumption produces a noticeable relaxation effect, which is attributed to the presence of catechins, L-theanine or both compounds. Furase et al. indicated that EGCG has sedative and hypnotic effects at the brain level, by acting partially at the level of GABA receptors moderating the response to the acute stress. In addition, a positive effect against anxiety in mice has been observed. The sedative effect is enhanced by the presence of L-theanine. This amino acid is considered as a neuroprotective agent that reduces psychological and physiological stress. However, the consumption of green tea does not induce sleep due to the caffeine content, which produces the opposite effect, stimulating the central nervous system and promoting wakefulness. Effects attributed to L-theanine also include promoting the secretion and functions of certain neurotransmitters in the central nervous system. For all these reasons, the consumption of green tea may be advisable in certain diseases associated with stress and anxiety.
 

http://sci-hub.bz/10.1039/c7fo00611j

[etherealdrifter]

Howl, your thread has been(as usual) great reading to follow

On a side note- it's really so pharma but i've seen a chocolatier in a Belgium shop where you can insufflate pure cocaos in a contraption that force feeds the stuff up the nasal passage ala yopo style.

i even saw it in an episode of the 'two hairy bikers'.

respect

[Alchemica]

I've had a couple of sessions with this. It's potent heart medicine...

 

It is definitely strong but gentle heart medicine, it's an effect that builds for days after use, a slow resonance that grows, restores, in a healing way. I needed to have an energetic upgrade, two sessions with the yeasted cacao product tuned me deeper to the heart. Definitely feel the new actives are far more potent and efficacious than raw cacao as the plant offers directly. If you do DIY beer brewing, do a substitution with some cacao. Don't need to be fancy about how you do it, just add the resonance of the plant in good quantity! Use a bit of vitamin C to prevent oxidation of the polyphenols!
 

If anyone needs an initial R&D recipe, the one in the other thread works fine for a healing brew. The spirited aspect (methylxanthines, some of the flavonols/polyphenols, tetrahydro-β-carbolines, other biogenic amines including spermidine-like alkaloids) seemingly carries into the alcohol brew, the heart healing resonance seems to be retained to a large degree in the solids. If you can, don't decant off the solids from the brew when you bottle, keep them in the brew, just gently redisperse before a session!
 

I'll optimise this using greater doses of cacao and getting the alcohol percentage down, even though a bit is useful for preserving the product. Soon I'll move to kombucha cacao as it's likely the resonance that is more suitable for my healing work.
 

I find this interesting. How much of our mind dysfunction is immune-dysfunction? I find cacao enriching my diet restores my mind, maybe the immune system plays a role:
 

"The ability of cocoa to interact with the immune system in vitro and in vivo has been described. In the latter context, a cocoa-enriched diet in healthy rats was able to modify the immune system's functionality. This fact could be observed in the composition and functionality of lymphoid tissues, such as the thymus, spleen, and lymph nodes. Consequently, immune effector mechanisms, such as antibody synthesis, were modified. A cocoa-enriched diet in young rats was able to attenuate the serum levels of immunoglobulin (Ig) G, IgM, and IgA and also the intestinal IgM and IgA secretion. Moreover, in immunized rats, the intake of cocoa decreased specific IgG1, IgG2a, IgG2c, and IgM concentrations in serum. This immune-regulator potential was then tested in disease models in which antibodies play a pathogenic role. A cocoa-enriched diet was able to partially prevent the synthesis of autoantibodies in a model of autoimmune arthritis in rats and was also able to protect against IgE and T helper 2-related antibody synthesis in two rat models of allergy. Likewise, a cocoa-enriched diet prevented an oral sensitization process in young rats."

https://www.ncbi.nlm.nih.gov/pubmed/28702458

[Anodyne]

 

Quote

These effects were only produced by a 10% cocoa diet whereas a 4% cocoa dose was insufficient to influence the phenotype of mesenteric lymph nodes

 

Quote

Results showed that the 10% cocoa-enriched diet, but not the 4% dose, was able to decrease serum immunoglobulin (Ig) G, IgM, and IgA concentrations ... Moreover, it was observed that the minimum dose to achieve such an effect was 5% cocoa in the diet

 

I dunno, 10% of your diet is a LOT of cocoa. I understand why researchers use megadoses of things (to see quicker & more obvious effects), but these don't always scale down neatly in a nice dose-dependent manner - some drug effects only occur at high doses, because certain receptors or transporters or enzymes become overloaded. I would want to see more studies using a range of doses before I got excited about this.

 

Best of luck with the kombucha, yesterday I found a forgotten bottle of chilli-cacao kombucha at the back of my fridge, hot damn that is tasty stuff! All of those converted amines make for great umami flavour - it is like a natural flavour-enhancer!

[Alchemica]

10% is viable at my rate of consumption They had me at 'dose-dependent improvements in cognition' in another study so I'm loaded on it... knocks my appetite way down, too... But if we can? go an oral rodent -> human dose equivalent, ie divide by ~12 we get something more achievable. I say it's possible

Edited August 6, 2017 by Alchemica

[Alchemica]

Found out the hard way rate of cacao fermentation STRONGLY ∝ to cacao concentration. Damnit! Now have cacao sludge going nuclear on me and overflowing. Be careful...

Like it seems you actually want to use a raw cacao that's maybe even gritty and planty and not overly fine, not the better tasting chocolate grade... first batch was fine using 200g/4L of the slightly more gritty raw organic product, this smoother chocolatey cacao isn't a good brewing one at 500g in the brew...