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The Marshall Protocol Study Site > PROF. MARSHALL'S PERSPECTIVE > Prof. Marshall's Perspective > Chlorogenic Acid in Coffee is powerful Immune modulator


Chlorogenic Acid in Coffee is powerful Immune modulator
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Dmitry
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 Posted: Sat Nov 7th, 2020 23:43

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For one thing Chlorogenic Acid appears to be yet another antibiotic:

Synergistic Effect of Chlorogenic Acid and Caffeic Acid with Fosfomycin on Growth Inhibition of a Resistant Listeria monocytogenes Strain
https://pubs.acs.org/doi/10.1021/acsomega.0c00352

Chlorogenic acid and caffeic acid are phenolic acids, which are secondary metabolites of plants like blueberry(44−46) among others. Studies have shown that chlorogenic acid and caffeic acid have antimicrobial and antioxidant effects.(47,48) Chlorogenic acid gained substantial attention due to its various biological and pharmacological effects, e.g., anti-diabetics, anti-obesity, anti-oxidation, anti-inflammation, anti-hypertension, antimicrobial activities, and metabolism regulation. It was suggested that chlorogenic acid had bactericidal effects against some pathogens through various mechanisms.(49) It has been shown that the treatment of chlorogenic acid at the concentrations of 2MIC or 4MIC could induce cell constituents’ release, reduce intracellular ATP concentration, and reduce the intracellular pH.(45) Furthermore, chlorogenic acid could limit oxidation of polyunsaturated lipids and delayed the growth of L. monocytogenes.(44) Besides L. monocytogenes, chlorogenic acid also had growth inhibitory effects on other bacteria, such as Salmonella enteritidis and Staphylococcus aureus.(46,48) Similarly, caffeic acid was also shown to have inhibitory effects on L. monocytogenes, S. aureus, Escherichia coli, and Bacillus cereus.(45,50−52) The compound can increase membrane permeability, resulting in the release of cell contents and access of hydrophobic antibiotics.(45,53)

Last edited on Sat Nov 7th, 2020 23:45 by Dmitry



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 Posted: Sun Nov 8th, 2020 11:30

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So, what does THIS mean ? Are all/most of those with verified Th1 or Th17 conditions BETTER off avoiding coffee altogether ? ? ?

Please also see my post of 25 Oct 2020 - & implications for (100%) cocoa powder, . . . . & olive oil ?


All the best to all contributors & readers,
SB :)

PS: Dmitry, your picture looks ominous; would not want to come across you on a dark night in St Petersburg - & as things are, . . . . probably never shall ! ;)
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Last edited on Sun Nov 8th, 2020 15:43 by SuperBiome



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 Posted: Sun Nov 8th, 2020 13:24

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SuperBiome wrote:
So, what does THIS mean ? Are all/most of those with verified Th1 or Th17 conditions BETTER off avoiding coffee altogether ? ? ?

Please also see my post of 25 Oct 2020 - & implications for (100%) cocoa powder, . . . . & olive oil ?


Well maybe it helps to intercept(in blood?) some of the bugs which later contribute to chronic microbiome otherwise..

Population do not seem to regress that much and too fast on caffeine comparing the quality of life on and off this substance (esp. compared to other "life enhancement" drugs) - coffee seems to cover up at least mild CFS for the majority of its consumers for decades without much of expected rapid regression - for ex my mom is a coffee drinker for like 40 years already and her CFS is at stable level for the last decades.

As for olive oil I've noticed that similar to coffee, it also contains polyphenols(phenolic-class antibiotics)...

http://www.thegreekoliveestate.com/healthy-evoo/
Research has found that Virgin Olive Oils have a Natural Polyphenol level that can range from anywhere between 50 – 5000 mg/kg (using NMR Spectroscopy). On Average, EVOOs (the highest quality Olive Oil) range between 100-250 mg/kg polyphenols.

Total Polyphenol Intake Is Inversely Associated with a Pro/Anti-Inflammatory Biomarker Ratio in European Adolescents of the HELENA Study
https://academic.oup.com/jn/article/150/6/1610/5813248

...

In any case people can not release their possession towards coffee and/or chocolate anyway so maybe we should start looking on some of its substances from a bright side. ;)



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 Posted: Sun Nov 8th, 2020 16:03

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Thanks Dmitry,

I'm interpreting that as not really much to worry about in the main ( - altho' there may be exceptions in individual cases) - for coffee ( - 100% cocoa powder ?) & even olive oil.

A few years ago, I came across early research which seem to show quite clearly that a 10-15ml daily dose of a high quality olive oil was beneficial to overall health, and at reducing the risk of neurological conditions like Alzheimer's and dementia. However, important questions might include 'for whom' ? Everyone ? Seems like a 'harmless' thing to trial, . . . given the length of time humans have been using it ?

Frankly, I'm having some 'fun' considering the gut microbiome, increasing FIBRE from natural foods, to support mine, and observing what the effects are. The gut microbiome determines which drugs we can metabolise, says Prof Martin Blaser, author of Missing Microbes.

Wishing all a PENSIVE Remembrance Day - may our tendencies to cause others, & this planet harm diminish faster & faster - THAT seems more important than ever now !

SB :)


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 Posted: Mon Nov 9th, 2020 17:33

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A few years ago, I came across early research which seem to show quite clearly that a 10-15ml daily dose of a high quality olive oil was beneficial to overall health, and at reducing the risk of neurological conditions like Alzheimer's and dementia. However, important questions might include 'for whom' ? Everyone ? Seems like a 'harmless' thing to trial, . . . given the length of time humans have been using it ?


So even 10..15ml of olive oil are being able to modulate immune response. Interesting...

I'm interpreting that as not really much to worry about in the main ( - altho' there may be exceptions in individual cases) - for coffee ( - 100% cocoa powder ?) & even olive oil.

Usually all anti inflammatory substances are highly addictive. :(

Last edited on Mon Nov 9th, 2020 17:52 by Dmitry



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 Posted: Mon Nov 16th, 2020 17:36

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Effects of decaffeination process on the phenolic content and antioxidant capacity of brewed coffees
https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.24.1_supplement.921.14
...This study suggests that some decaf methods may not alter phenolic content and antioxidant capacity...

Evaluating the effect of decaffeination on nutritional and antioxidant status of different coffee brands
https://www.researchgate.net/publication/330410913_Evaluating_the_effect_of_decaffeination_on_nutritional_and_antioxidant_status_of_different_coffee_brands

Total phenolic contents (TPC)

Phenolics and polyphenolic compounds constitute the main class of natural antioxidants present in plants and may contribute directly to antioxidative action (Awika et al., 2003) therefore it is necessary to calculate total phenolic content.

TPC was determined following a modified Follin–Ciocalteu method and results were expressed as gallic acid equivalents.

Total phenolic contents in Table 11 revealed:

* T3(caffeinated ground coffee) ---> 1720(mg/100g)
* T0(instant coffee) ----------------> 1711(mg/100g)
* T2(decaffeinated coffee beans) --> 1490(mg/100g)

Last edited on Mon Nov 16th, 2020 17:42 by Dmitry



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 Posted: Tue Nov 17th, 2020 19:28

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Am now wondering if there is any known connection/association between these 'polyphenols' ( - which, are molecules with multiple carbon or 'phenly/phenolic' rings ?) and short & medium chain fatty acids (SCFAs . . . & MCFAs) ? ? ?

One common MCFA is said to be butyric acid, which I surmise is a 'linear type' molecule, with four carbon atoms. These MCFAs are said to be important to health, and by-products of a healthy (gut) microbiome.

Any clarifications to these comments invited from those with greater insights into biochemistry, microbiome, nutrition and health !

SB :)
Somehow, . . . . hanging in there & coping, thru' continuing 'choppy waters' to life ! ! !



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 Posted: Mon Mar 15th, 2021 17:44

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Coffee extracts suppress tryptophan breakdown in mitogen-stimulated peripheral blood mononuclear cells
https://pubmed.ncbi.nlm.nih.gov/25738401/

Results: Filtered extracts of coffee and decaffeinated coffee both suppressed tryptophan breakdown and neopterin formation in mitogen-stimulated PBMCs efficiently and in a dose-dependent manner. Of 4 coffee compounds tested individually, only gallic acid and less strong also caffeic acid had a consistent suppressive influence but also affected cell viability, whereas pure caffeine and chlorogenic acid exerted no relevant effect in the PBMC assay.

Regular consumption of black tea increases circulating kynurenine concentrations: A randomized controlled trial
https://pubmed.ncbi.nlm.nih.gov/26673554/

Results: Regular consumption of tea over 6 months, compared to control, did not significantly alter neopterin (p = 0.13) or tryptophan (p = 0.85) concentrations, but did result in significantly higher kynurenine (p = 0.016) and KYN/TRP (p = 0.012). Relative to the control group, in the tea group kynurenine and KYN/TRP increased during the treatment period by 0.28 μmol/L (95% CI: - 0.04, 0.60) and 3.2 μmol/mmol (95% CI: - 1.6, 8.0), respectively at 3 months, and by 0.48 μmol/L (95% CI: 0.16, 0.80) and 7.5 μmol/mmol (95% CI: 2.5, 12.5), respectively at 6 months.

Conclusions: Increased circulation of kynurenine and KYN/TRP following regular black tea consumption may indicate enhanced tryptophan breakdown, possibly due to immune activation-induced tryptophan degrading enzyme indoleamine 2,3-dioxygenase.

General significance: The influence of black tea consumption on biomarkers of immune system activation could relate to its general health benefits. Data suggests that the net effect strongly depends on the individual immune state, being stimulatory in healthy individuals, while acting more immune dampening in situations with an inflammatory background.

The kynurenine system and immunoregulation
https://pubmed.ncbi.nlm.nih.gov/21744051/

There is developing interest in the role of the kynurenines in the immune function. A considerable amount of evidence has accumulated as concerns interactions between the kynurenine pathway, cytokines and the nervous system. Indoleamine 2,3-dioxygenase (IDO) occupies a key position connecting the immune system and the kynurenine pathway. There are evidences of the immunosuppressive effect of IDO. Following the interferon (IFN)-mediated activation of antigen presenting cells, the induction of IDO and the kynurenine system exerts a counter-regulating effect, maintaining the homeostasis. Inhibition of T cell functions, activation of the regulatory T cells, and the inhibition of Natural Killer cells are among the important factors in the immunosuppressive effects of IDO and kynurenines. There is a close connection between cytokines (IFN-α, IFN-γ, TNF-α, TGF-β, IL-4 and IL-23) and the kynurenine system, and an imbalance in the TH1/TH2 cytokine profile may possibly lead to neurologic or psychiatric disorders.

As the tryptophan metabolic pathway is activated by pro-inflammatory stimuli, the anti-inflammatory effect of kynurenic acid provides a further feedback mechanism in modulating the immune responses.

Last edited on Mon Mar 15th, 2021 17:57 by Dmitry



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 Posted: Mon May 17th, 2021 17:02

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Metabolomic response to coffee consumption: application to a three‐stage clinical trial

https://onlinelibrary.wiley.com/doi/full/10.1111/joim.12737

A total of 115 metabolites were significantly associated with coffee intake (P < 0.05 and Q < 0.05). Eighty‐two were of known identity and mapped to one of 33 predefined biological pathways. We observed a significant enrichment of metabolite members of five pathways (P < 0.05): (i) xanthine metabolism: includes caffeine metabolites, (ii) benzoate metabolism: reflects polyphenol metabolite products of gut microbiota metabolism, (iii) steroid: novel but may reflect phytosterol content of coffee, (iv) fatty acid metabolism (acylcholine): novel link to coffee and (v) endocannabinoid: novel link to coffee.

there is some steroid, i have not heard of, in coffee

We observed a significant enrichment of coffee‐metabolite associations mapping to the steroid pathway (Fig. 3) and which we hypothesize to be attributable to at least one phytosterol present in coffee: campesterol

Last edited on Mon May 17th, 2021 17:09 by wrotek



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 Posted: Mon May 17th, 2021 18:18

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yeah

Sterols of coffee
https://www.sciencedirect.com/science/article/abs/pii/S003194220089946X

The sterols of the bean of the coffee tree (Coffea arabica L.) have been identified as cycloartenol, 24-methylenecyloartanol, cycloeucalenol, obtusifoliol, citrostadienol, 24-methylenelophenol, stigmasterol, sitosterol, campesterol, stigmastanol, and campestanol. No trace of the previously reported lanosterol, dihydrolanostero, or coffeasterol could be detected in either the beans or in the commercial coffee oil. Trace amounts of cholesterol and cholestanol were also indicated. Combined gas chromatography-mass spectrometry has tentatively identified 4α,24R-dimethyl-5α-cholest-8-en-3β-ol, 4α-24R-dimethyl-5α-cholest-7-en-3β-ol, and 4α-methyl-5α-stigmast-7-en-3β-ol.

Phytosterols Suppress Phagocytosis and Inhibit Inflammatory Mediators via ERK Pathway on LPS-Triggered Inflammatory Responses in RAW264.7 Macrophages and the Correlation with Their Structure
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915509/

Phytosterols, found in many commonly consumed foods, exhibit a broad range of physiological activities including anti-inflammatory effects. In this study, the anti-inflammatory effects of ergosterol, β-sitosterol, stigmasterol, campesterol, and ergosterol acetate were investigated in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Results showed that all phytosterol compounds alleviated the inflammatory reaction in LPS-induced macrophage models; cell phagocytosis, nitric oxide (NO) production, release of tumor necrosis factor-α (TNF-α), and expression and activity of pro-inflammatory mediator cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and phosphorylated extracellular signal-regulated protein kinase (p-ERK) were all inhibited. The anti-inflammatory activity of β-sitosterol was higher than stigmasterol and campesterol, which suggests that phytosterols without a double bond on C-22 and with ethyl on C-24 were more effective. However, inconsistent results were observed upon comparison of ergosterol and ergosterol acetate (hydroxy or ester group on C-3), which suggest that additional research is still needed to ascertain the contribution of structure to their anti-inflammatory effects.



| btw, it is also presented in many fruits, vegetables, etc:

https://en.wikipedia.org/wiki/Campesterol

Many vegetables, fruits, nuts,[1] and seeds contain campesterol, but in low concentrations. Banana, pomegranate, pepper, coffee, grapefruit, cucumber, onion, oat, potato, and lemon grass (citronella) are few examples of common sources containing campesterol at roughly 1–7 mg/100 g of the edible portion. In contrast, canola and corn oils contain as much as 16–100 mg/100 g. Levels are variable and are influenced by geography and growing environment. In addition, different strains have different levels of plant sterols. A number of new genetic strains are currently being engineered with the goal of producing varieties high in campesterol and other plant sterols.[2] It is also found in dandelion coffee.

| Few mgs could be a lot since immune system could be highly sensitive to even micrograms.

...

[citrus] fruits also contain limonoids:

https://www.frontiersin.org/articles/10.3389/fchem.2020.00073/full
The anti-inflammatory effects of all limonoids were evaluated in lipopolysaccharide (LPS)-treated RAW 264.7 cell lines. Compounds 5, 7–11, and 13 were found to inhibit LPS-induced nitric oxide (NO) production. Moreover, dictamlimonol D (5), fraxinellone (11), and dasylactone A (13) were found to reduce the LPS-induced expressions of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), inducible nitric oxide synthase (iNOS), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and cyclooxygenase-2 (COX-2) at the protein levels in a dose-dependent manner.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273274/
Citrus limonoids (CLs) are a group of highly oxygenated terpenoid secondary metabolites found mostly in the seeds, fruits and peel tissues of citrus fruits such as lemons, limes, oranges, pumellos, grapefruits, bergamots, and mandarins.

Last edited on Mon May 17th, 2021 21:28 by Dmitry



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 Posted: Fri May 21st, 2021 13:50

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Adenosine Receptor Signaling Modulates Permeability of the Blood–Brain Barrier



https://www.jneurosci.org/content/31/37/13272

in vivo. A1 and A2A AR activation facilitated the entry of intravenously administered macromolecules, including large dextrans and antibodies to β-amyloid

Last edited on Fri May 21st, 2021 13:51 by wrotek



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 Posted: Sun May 23rd, 2021 14:03

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Chlorogenic Acid Decreases Intestinal Permeability and Increases Expression of Intestinal Tight Junction Proteins in Weaned Rats Challenged with LPS(endotoxin)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041575/

Chlorogenic acid, a natural phenolic acid present in fruits and plants, provides beneficial effects for human health. The objectives of this study were to investigate whether chlorogenic acid (CHA) could improve the intestinal barrier integrity for weaned rats with lipopolysaccharide (LPS) challenge. Thirty-two weaned male Sprague Dawley rats (21±1 d of age; 62.26±2.73 g) were selected and randomly allotted to four treatments, including weaned rat control, LPS-challenged and chlorogenic acid (CHA) supplemented group (orally 20 mg/kg and 50 mg/kg body). Dietary supplementation with CHA decreased (P<0.05) the concentrations of urea and albumin in the serum, compared to the LPS-challenged group. The levels of IFN-γ and TNF-α were lower (P<0.05) in the jejunal and colon of weaned rats receiving CHA supplementation, in comparison with the control group. CHA supplementation increased (P<0.05) villus height and the ratio of villus height to crypt depth in the jejunal and ileal mucosae under condictions of LPS challenge. CHA supplementation decreased (P<0.05) intestinal permeability, which was indicated by the ratio of lactulose to mannitol and serum DAO activity, when compared to weaned rats with LPS challenge. Immunohistochemical analysis of tight junction proteins revealed that ZO-1 and occludin protein abundances in the jejunum and colon were increased (P<0.05) by CHA supplementation. Additionally, results of immunoblot analysis revealed that the amount of occludin in the colon was also increased (P<0.05) in CHA-supplemented rats. In conclusion, CHA decreases intestinal permeability and increases intestinal expression of tight junction proteins in weaned rats challenged with LPS.

Intestinal inflammation

To gain insight into the effect of CHA on inflammatory cytokines in the intestinal tissue of weaned rats, we determined the concentrations of IFN-γ, TNF-α and IL-10 in the jejunum and colon. CHA50 and CHA20 significantly reduced (P<0.05) the concentration of IFN-γ in the jejunum and colon, compared with weaned rats challenged with LPS (the LPS group) (Fig. 1A). Rats in the CHA 20 and 50 groups had a lower (P<0.05) concentration of TNF-α, compared to the LPS group (P<0.05). Only CHA 50 affected (P<0.05) the concentration of IL-10 I in the jejunum, compared to the LPS group (Fig. 1B).

Normalization of the increased translocation of endotoxin from gram negative enterobacteria (leaky gut) is accompanied by a remission of chronic fatigue syndrome
https://www.ncbi.nlm.nih.gov/pubmed/18063928

There is now evidence that chronic fatigue syndrome (CFS) is accompanied by an increased translocation of endotoxins from gram-negative enterobacteria through the gut wall, as demonstrated by increased prevalences and median values for serum IgM and IgA against the endotoxins of gram-negative enterobacteria. This condition can also be described as increased gut permeability or leaky gut and indicates intestinal mucosal dysfunction (IMD). Here we report a case of a 13 year old girl with CFS who showed very high values for serum IgM against the LPS of some enterobacteria and signs of oxidative and nitrosative stress, activation of the inflammatory response system, and IgG3 subclass deficiency. Upon treatment with specific antioxidants and a "leaky gut diet", which both aim to treat increased gut permeability, and immunoglobins intravenously, the increased translocation of the LPS of gram negative enterobacteria normalized and this normalization was accompanied by a complete remission of the CFS symptoms.

The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression
https://pubmed.ncbi.nlm.nih.gov/18283240/

Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria
https://pubmed.ncbi.nlm.nih.gov/19112401/

Last edited on Sun May 23rd, 2021 14:08 by Dmitry



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 Posted: Sun May 30th, 2021 23:31

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Antioxidant and Antiradical Activity of Coffee
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665516/

The most antioxidant-rich beverages are [1]: coffee—200–550 mg/cup; tea—150–400 mg/cup; red wine—150–400 mg/glass. Intake of these drinks makes a significant contribution to the total amount of antioxidants consumed by people.

Green coffee beans contain large amounts of polyphenolic antioxidants, such as chlorogenic, caffeic, ferulic, and n-coumarinic acids. Coffee roasting significantly alters the composition of polyphenols due to Maillard reaction (chemical reaction between amino acids and sugars).

A cup of coffee which contains 10 g of roasted coffee beans may have 15 to 325 mg of chlorogenic acids. On average in America, one cup contains approximately 200 mg of chlorogenic acid. Antioxidant activity of ferulic and caffeic acids was studied both in vitro and in vivo. Ferulic acid presented in coffee has anti-inflammatory, anti-allergic, antibacterial, antiplatelet, and antiviral effect [34]. Pharmacological properties of ferulic acid are related to its high antioxidant activity, in particular, its ability to inhibit lipid peroxidation in biological membranes.

In one study, it has been shown that ferulic acid at a concentration of 10−3 mol/L in a perfusion solution reduces arrhythmia [40].

People consume coffee or tea every day, sometimes several times a day. Coffee is the main drink in Europe, America and Asia. In recent years, consumption of coffee has increased even in England, a prominently tea-drinking country. Coffee consumption is rising rapidly in China and Japan where a centuries-old tradition of tea consumption is strongest.



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 Posted: Sun May 30th, 2021 23:31

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Caffeine Stimulation of Cortisol Secretion Across the Waking Hours in Relation to Caffeine Intake Levels
https://www.researchgate.net/publication/7561673_Caffeine_Stimulation_of_Cortisol_Secretion_Across_the_Waking_Hours_in_Relation_to_Caffeine_Intake_Levels

Caffeine increases cortisol secretion in people at rest or undergoing mental stress. It is not known whether tolerance develops in this response with daily intake of caffeine in the diet. We therefore tested the cortisol response to caffeine challenge after controlled levels of caffeine intake. Men (N = 48) and women (N = 48) completed a double-blind, crossover trial conducted over 4 weeks. On each week, subjects abstained for 5 days from dietary caffeine and instead took capsules totaling 0 mg, 300 mg, and 600 mg/day in 3 divided doses. On day 6, they took capsules with either 0 mg or 250 mg at 9:00 AM, 1:00 PM, and 6:00 PM, and cortisol was sampled from saliva collected at 8 times from 7:30 AM to 7:00 PM. After 5 days of caffeine abstinence, caffeine challenge doses caused a robust increase in cortisol across the test day (p < .0001). In contrast, 5 days of caffeine intake at 300 mg/day and 600 mg/day abolished the cortisol response to the initial 9:00 AM caffeine dose, although cortisol levels were again elevated between 1:00 PM and 7:00 PM (p = .02 to .002) after the second caffeine dose taken at 1:00 PM. Cortisol levels declined to control levels during the evening sampling period. Cortisol responses to caffeine are reduced, but not eliminated, in healthy young men and women who consume caffeine on a daily basis.

Stress-like adrenocorticotropin responses to caffeine in young healthy men
https://pubmed.ncbi.nlm.nih.gov/8951977/

The effects of oral caffeine (3.3 mg/kg, equivalent to 2-3 cups of coffee) on plasma adrenocorticotropin (ACTH) and cortisol (CORT) were tested in 47 healthy young men at rest in a double-blind, placebo-controlled, crossover study. Following caffeine, ACTH was significantly elevated at all times from 30 min to 180 min, and CORT was elevated from 60 min to 120 min (Fs > or = 8.4, ps < 0.01). Peak increases relative to placebo were: ACTH, 33% (+5.2 pg/ml) and CORT, 30% (+2.7 micrograms/dl) at 60 min postcaffeine. The results suggest that caffeine can activate important components of the pituitary-adrenocortical response in humans during the resting state. Caffeine's known ability to increase CORT production appears at least partly due to an increase in ACTH release at the pituitary.
[..]
In relation to caffeine’s enhancement of HPAC function, there is evidence that caffeine can counteract the effect of drugs that normally suppress pituitary secretion. Chronic prednisolone administration suppresses corticosterone secretion in rats, and caffeine can increase the rate of recovery of the HPAC following discontinuation of the prednisolone (15). In humans, rises in ACTH and CORT following morning or evening coffee consumption may produce a false positive response to the dexamethasone suppression test. A single dose of 480 mg of caffeine produced a significant escape from dexamethasone suppression in 34% of one sample (29), suggesting that dietary caffeine intake should be examined as a possible confounding factor in diagnostic tests of HPAC axis function.
[..]
Caffeine’s pharmacological effects on the central nervous system are due to blockade of the adenosine receptor and to
interference with cyclic adenosine monophosphate (CAMP) phosphodiesterase (19,22,25). Each of these can result in increased availability of CAMP, which stimulates expression of the corticotropin releasing factor (CRF) gene (27). CRF secretion at the median eminence of the hypothalamus, in turn, stimulates ACTH release by the pituitary, resulting in increased CORT production by the adrenal cortex (22). Caffeine may, therefore increase CRF, ACTH, and CORT through CAMP accumulation in the median eminence or pituitary, as has been shown in rat (15,30).

Caffeine may also contribute indirectly to increased ACTH release through stimulation of epinephrine secretion (20) which can enhance CAMP production in relevant neuronal systems. In addition, caffeine blocks adenosine in the mesopontine reticular formation resulting in activation of this system (24) contributing to increased generalized arousal, and in turn, enhancing HPAC activity.

A third issue raised by the present results concerns caffeine’s effects on pituitary-adrenocortical function in relation to stress responses. It is noteworthy that CORT and ACTH are core components of the endocrine response to a variety of stressors (17) including mental stress (18). Threatening or aversive challenges increase CORT production in preference to nonaversive challenges (lOJ4). Studies of mental stress show that peak ACTH increases may range from 3.5 pg/ml during routine psychometric testing (18) to 4.8 pg/ml during mental arithmetic challenge (1) to 5.1 pg/ml during simulated public speaking (26) to 13 pg/ml during an actual oral examination in front of a committee (16). The maximum difference from placebo seen in the present study was 5.2 pg/ml, placing the changes we observed to caffeine alone well within the range reported to psychological stressors. In the same vein, epinephrine secretion, another important element in the endocrine response to stress, is increased by caffeine in resting
persons
(28). Therefore, caffeine alone may evoke both adrenocortical and adrenomedullary components of the fight flight response in persons at rest and in the absence of explicit challenge.

Mechanisms of Disease: the adrenocorticotropin receptor and disease
https://www.nature.com/articles/ncpendmet0165

The action of the peptide hormone adrenocorticotropin (ACTH) to stimulate glucocorticoid production by the adrenal gland is an essential physiologic process, yet is dependent on a single unique genetic component—the ACTH receptor or melanocortin 2 receptor. Genetic defects that cause abnormalities in this receptor or in a protein required for its expression at the cell surface result in a potentially fatal disease (familial glucocorticoid deficiency). Overexpression of this receptor or inability to desensitize it is found in adrenal adenomas or hyperplasia associated with glucocorticoid overproduction (Cushing syndrome). These disorders are uncommon, but there are considerable data to show that the hypothalamo–pituitary–adrenal axis is overactive, or in some circumstances underactive, in more common situations including depressive illness and septic shock. The origin of these latter disturbances is undoubtedly complex and multifactorial, but there is good evidence that a component of this phenomenon is an altered responsiveness of the ACTH receptor to ACTH. Understanding the basis of ACTH responsiveness might, therefore, contribute to the understanding of disorders such as these and perhaps enable the hypothalamo–pituitary–adrenal axis to be manipulated beneficially in these circumstances.

Last edited on Mon May 31st, 2021 00:34 by Dmitry



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 Posted: Fri Jun 4th, 2021 13:18

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In Vitro Antibacterial and Antibiofilm Activities of Chlorogenic Acid against Clinical Isolates of Stenotrophomonas maltophilia including the Trimethoprim/Sulfamethoxazole Resistant Strain
https://www.hindawi.com/journals/bmri/2013/392058/

The in vitro antibacterial and antibiofilm activity of chlorogenic acid against clinical isolates of Stenotrophomonas maltophilia was investigated through disk diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill and biofilm assays. A total of 9 clinical S. maltophilia isolates including one isolate resistant to trimethoprim/sulfamethoxazole (TMP/SMX) were tested. The inhibition zone sizes for the isolates ranged from 17 to 29 mm, while the MIC and MBC values ranged from 8 to 16 μg mL−1 and 16 to 32 μg mL−1. Chlorogenic acid appeared to be strongly bactericidal at 4x MIC, with a 2-log reduction in viable bacteria at 10 h. In vitro antibiofilm testing showed a 4-fold reduction in biofilm viability at 4x MIC compared to 1x MIC values ( A 490 nm) of chlorogenic acid. The data from this study support the notion that the chlorogenic acid has promising in vitro antibacterial and antibiofilm activities against S. maltophilia.

Antibacterial activity and action mode of chlorogenic acid against Salmonella Enteritidis, a foodborne pathogen in chilled fresh chicken
https://link.springer.com/article/10.1007/s11274-020-2799-2

The study evaluated the antibacterial activity of chlorogenic acid (CA) against Salmonella Enteritidis S1, a foodborne pathogen in chilled fresh chicken. Its minimum inhibitory concentration for S. Enteritidis S1 was 2 mM. 1 MIC CA treatment reduced the viable count of S. Enteritidis S1 by 3 log cfu/g in chilled fresh chicken. Scanning electron microscopy examination indicated that CA induced the cell envelope damage of S. Enteritidis S1. Following this, 1-N-Phenylnaphthylamine assay and LPS content analysis indicated that CA induced the permeability of outer membrane (OM). Confocal laser scanning microscopy examination further demonstrated that CA acted on the inner membrane (IM). To support this, the release of intracellular protein and ATP after CA treatment was also observed. CA also suppressed the activities of malate dehydrogenase and succinate dehydrogenase, two main metabolic enzymes in TCA cycle and electron transport chain. Thus, damage of intracelluar and outer membranes as well as disruption of cell metabolism resulted in cell death eventually. The finding suggested that CA has the potential to be developed as a preservative to control S. Enteritidis associated foodborne diseases.

Antibacterial Activity and Mechanism of Action of Chlorogenic Acid
https://www.researchgate.net/publication/221895198_Antibacterial_Activity_and_Mechanism_of_Action_of_Chlorogenic_Acid

In this study, the antibacterial activity and mechanism of action of chlorogenic acid against bacteria were assessed. The data from minimum inhibitory concentration (MIC) values showed that chlorogenic acid effectively inhibited the growth of all tested bacterial pathogens, and the MIC values were ranging from 20 to 80 μg/mL. An investigation into action mode of chlorogenic acid against the pathogen indicated that chlorogenic acid significantly increased the outer and plasma membrane permeability, resulting in the loss of the barrier function, even inducing slight leakage of nucleotide. The leakage of cytoplasmic contents was also observed by electron micrographs. These results supported our hypothesis that chlorogenic acid bound to the outer membrane, disrupted the membrane, exhausted the intracellular potential, and released cytoplasm macromolecules, which led to cell death.



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 Posted: Mon Jun 21st, 2021 11:47

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Caffeine downregulates inflammatory pathways involved in autoimmunity
https://www.biorxiv.org/content/10.1101/241539v1.full

Objectives

Caffeine is a widely consumed pharmacologically active product. In the present study, we focused on characterizing immunomodulatory effects of caffeine on peripheral blood mononuclear cells (PMBCs).

Methods

The effect of caffeine on gene expression profiles was initially evaluated using RNA sequencing data. Validation experiments were performed to confirm the results and examine dose-dependent effects of caffeine on PBMCs from healthy subjects. Gene expression levels were measured by real-time quantitative PCR, and cytokine production was determined using a multiplex cytokine assay.

Results

Caffeine at high doses showed a robust downregulatory effect of immune-related genes in PBMCs. Functional annotation analysis of downregulated genes revealed significant enrichment in cytokine activity and in genes related to several autoimmune diseases including lupus and rheumatoid arthritis. Dose-dependent validation experiments showed significant downregulation at the mRNA levels of key inflammatory genes including STAT1, TNF, and PPARG. TNF and PPARG were suppressed even with the lowest caffeine dose tested, which corresponds to the serum concentration of caffeine after administration of one cup of coffee.

Cytokine levels of IL-8, MIP-1β, IL-6, IFN-γ, GM-CSF, TNF, IL-2, IL-4, MCP-1, and IL-10 were decreased significantly with caffeine treatment.



Caffeine inhibits STAT1 signaling and downregulates inflammatory pathways involved in autoimmunity
https://pubmed.ncbi.nlm.nih.gov/29678503/

Caffeine is a widely consumed pharmacologically active product. We focused on characterizing immunomodulatory effects of caffeine on peripheral blood mononuclear cells. Caffeine at high doses showed a robust downregulatory effect on cytokine activity and genes related to several autoimmune diseases including lupus and rheumatoid arthritis. Dose-dependent validation experiments showed downregulation at the mRNA levels of key inflammation-related genes including STAT1, TNF, IFNG, and PPARG. TNF and PPARG were suppressed even with the lowest caffeine dose tested, which corresponds to the serum concentration of caffeine after administration of one cup of coffee. Cytokine levels of IL-8, MIP-1β, IL-6, IFN-γ, GM-CSF, TNF, IL-2, IL-4, MCP-1, and IL-10 were decreased significantly with caffeine treatment. Upstream regulator analysis suggests that caffeine inhibits STAT1 signaling, which was confirmed by showing reduced phosphorylated STAT1 after caffeine treatment. Further studies exploring disease-modulating potential of caffeine in autoimmune diseases and further exploring the mechanisms involved are warranted.
...
To understand the mechanism of the immunomodulating effects observed with caffeine, we performed bioinformatics analysis to identify upstream regulators of genes downregulated with caffeine treatment identified by RNA sequencing. We identified STAT1 as the most significant transcription factor regulating these genes and which is predicted to be inhibited by caffeine (z-score= -8.2, P= 1.22X10-32). This suggests a role for STAT1 signaling defect in mediating the effect of caffeine in PBMCs[..]
[..]
TNF, being an important inflammatory cytokine in many immune-mediated diseases, is target of several therapeutics [20]. Previous studies indicated that TNF is involved in the release of other inflammatory cytokines such as IL-1 and IL-6 [21]. We demonstrate suppression of TNF production both at the mRNA and protein levels with low to intermediate caffeine concentrations. Indeed, caffeine concentrations corresponding to serum levels after the consumption of one cup of coffee was associated with significant suppression of TNF production in PBMCs.
[..]
Cytokines are known to have a key role in autoimmune diseases, and several pro-inflammatory cytokines were reduced with caffeine treatment in our study. IL-6 and IL-10 which are both significantly elevated in the serum with increased disease activity in lupus patients can be downregulated with caffeine. IL-10 is produced in increased amounts by lupus PBMCs and IL-10 levels have been shown to correlate with disease activity in lupus patients [22].
[..]
Previous studies have demonstrated higher levels of IFNγ mRNA in peripheral blood T cells from patients with lupus compared to normal controls after CD28 costimulation [23]. Moreover, in lupus monocytes IFNγ signaling has been found to be more effective in inducing STAT1 phosphorylation compared with monocytes from healthy individuals [24]. It has been also reported that lupus patients have elevated STAT1 and IFNγ expression in PBMCs and that this elevation correlates with disease activity [23, 24]. Cytokines that signal through STATs are crucial in host defense and inflammation, and overactivation of STATs can induce immune pathologies [25]. Our data demonstrate significant down regulation of both STAT1 and IFNγ with caffeine. Further, we demonstrate that caffeine exerts its immunomodulatory effects, at least in part, through suppressing STAT1 phosphorylation.
[..]
Chemokines are crucial for regulating leukocyte recruitment to the inflamed tissue therefore play key roles in the development and progression of autoimmune diseases. In our study we showed that caffeine treatment significantly lowered chemokine levels such as MCP-1 and IL-8 released by PBMCs. Serum levels of MCP-1 (also known as CCL2) were found to be elevated significantly in patients with lupus [26-29], systemic sclerosis (SSc) [30, 31], or rheumatoid arthritis (RA) [32-34] compared to healthy controls. In SSc, higher serum levels of MCP-1 have also been reported in patients with pulmonary fibrosis [30, 31].
[..]
In summary, we demonstrate that caffeine, even with low concentrations, can suppress gene expression of pro-inflammatory genes and cytokines that play key roles in autoimmune diseases. Additional work to further characterize the mechanisms involved in the anti-inflammatory effects observed and whether caffeine supplementation might have beneficial effects in patients with autoimmune diseases are worthy of investigation.

STAT1 activation during monocyte to macrophage maturation: role of adhesion molecules
https://pubmed.ncbi.nlm.nih.gov/10383940/

Human monocytes isolated from peripheral blood of healthy donors show a time-dependent differentiation into macrophages upon in vitro cultivation, closely mimicking their in vivo migration and maturation into extravascular tissues. The mediator(s) of this maturation process has not been yet defined. We investigated the involvement of signal transducers and activators of transcription (STAT) factors in this phenomenon and reported the specific, time-dependent, activation of STAT1 protein starting at day 0/1 of cultivation and maximally expressed at day 5.
[..]
Taken together these results indicate that STAT1 plays a pivotal role in the differentiation/maturation process of monocytes as an early transcription factor initially activated by adherence and then able to modulate the expression of functional genes, such as ICAM-1 and FcgammaRI.

Last edited on Mon Jun 21st, 2021 15:07 by Dmitry



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 Posted: Sun Jun 27th, 2021 12:18

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Robin Quivers gets colon cancer, her previous "healthy" habits were - coffee enemas https://youtu.be/Qz06OHRTWog?t=2772 (quite a lot of them if i remember correctly), vegan diet.

full piece https://youtu.be/Qz06OHRTWog

Last edited on Sun Jun 27th, 2021 12:20 by wrotek



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 Posted: Thu Jul 1st, 2021 17:22

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I wonder what this means


Probing the binding selected metal ions and biologically active substances to the antimicrobial peptide LL-37 using DSC, ITC measurements and calculations
https://link.springer.com/article/10.1007/s10973-019-08310-9

Furthermore, the ITC method supported by theoretical calculations (peptide–ligand docking) were used to study the interactions between LL-37 and some divalent metal ions, namely Cu2+, Zn2+, and Ni2+ ions as well as acetylsalicylic acid, ascorbic acid, and caffeine molecules

This contribution initiates a series of efforts confined to the study of the interactions of LL-37 with the commonly used substances, i.e., acetylsalicylic acid (aspirin) and ascorbic acid (vitamin C) as well as caffeine presented in coffee, tea and also energy drinks.

In the case of tests with caffeine, the ligand turned out to be very unspecific system. During the process, the caffeine molecule approached in many areas of LL-37, for a distance of about 5 Å (Asp4, Phe6, Lys8 and Arg19, Arg23, Phe27) which proves the dynamics and high unspecificity of the possible process of interactions of LL-37 with caffeine.

Last edited on Thu Jul 1st, 2021 17:23 by wrotek



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 Posted: Wed Jul 14th, 2021 14:11

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wrotek wrote:
Association of coffee consumption with serum adiponectin, leptin, inflammation and metabolic markers in Japanese workers: a cross-sectional study

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347755/

https://en.wikipedia.org/wiki/Leptin

Leptin (from Greek λεπτός leptos, "thin") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate energy balance by inhibiting hunger

so that is why i want to eat so much after coffee

https://en.wikipedia.org/wiki/Adiponectin

Conclusion:

Coffee consumption was associated with high adiponectin and low leptin levels. We speculated that adipocytokines mainly explain the associations of coffee consumption with lipids and hs-CRP. Factors other than adipocytokines may explain the association between coffee consumption and liver function.



fascinating coffee effects are on human body, the complexity is...


https://www.hindawi.com/journals/ipid/2016/9415364/
The inflammatory cytokine response is linked to development of clinical manifestations of TB. For instance, higher levels of IFN-γ and IL-10 are associated with lower body weight and wasting in newly infected TB patients [8, 9]. Whilst a higher IFN-γ to IL-10 ratio is associated with protection and TB cure [10], a lower IFN-γ to IL-10 ratio is linked to TB relapse [6, 11]. Furthermore, increased plasma adiponectin levels are associated with severe TB characterised by extensive pulmonary lesions [12]. Although adiponectin promotes IL-10 release and impairs IFN-γ secretion in human macrophages [13], the magnitude of IFN-γ and IL-10 to adiponectin production as an indicator of inflammatory response and clinical manifestations in TB is largely unknown.


https://www.fivejourneys.com/how-to-increase-adiponectin-the-fat-burning-hormone/

Oil

Daily intake of fish or omega-3 increased adiponectin by a whopping 14-60%. This could also be achieved by eating other yummy monounsaturated fats like avocados, nuts, olives and olive oil.

Fiber

60-115% increase in adiponectin levels! It’s super important, can help stabilize blood sugar. Checking fiber levels of every meal and making sure that you are getting enough fiber. If not, supplemental fiber should be added.

Exercise

Yes, tried and true. This is always one we come back to. Exercise is vital to increasing our adiponectin levels. At least 30 minutes 3 times a week of moderate exercise can increase levels. I personally think that is a good start and that 4-5 days a week of moderate exercise is a better way to go.

Caffeine

As much as I don’t personally do well with caffeine, studies have shown that people with caffeine intake – either coffee or tea – have high levels of adiponectin. Consider white or green tea – it contains ECGC that has so many other benefits. If coffee is your caffeine of choice, please at least look for organic. Coffee is one of the highest pesticide-sprayed foods.

Cold
I have a love/hate relationship with cold. I use it, it works, love the effects, don’t always love the process. There is some evidence that sleeping in a cold environment – 66 F (19 C) increases adiponectin. Also, shivering has a transient increase in adiponectin.

Supplements

Curcumin – got to love your Curcumin, it’s just about good for everything, including raising your adiponectin levels.

Raspberry Ketones – this is found in Raspberry.

Cyanidin 3-glucoside – well that is a mouthful. Think Blueberries! This is the antioxidant found in blueberries that helps increase adiponectin levels.

There you have it – Eat good fat and fiber, exercise, a little caffeine, cold and a few supplements will get you in shape in no time!


:D

+++

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486142/
Adiponectin is the most abundant peptide secreted by adipocytes

https://eje.bioscientifica.com/view/journals/eje/160/6/965.xml
25(OH)D was inversely correlated with FPG, insulin, and HOMA index (P=0.003, P=0.005, P=0.003 respectively), and positively correlated with adiponectin and HDL-cholesterol (P=0.002 and P=0.005 respectively). After adjustment for BMI, the correlation of 25(OH)D persists for SBP and glucose (P=0.009 and P=0.015 respectively) but is at the limit of significance for WC (P=0.08), adiponectin (P=0.11), and HDL-cholesterol (P=0.052).

A low-fat high-carbohydrate diet reduces plasma total adiponectin concentrations compared to a moderate-fat diet with no impact on biomarkers of systemic inflammation in a randomized controlled feeding study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524794/

Last edited on Wed Jul 14th, 2021 16:07 by Dmitry



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 Posted: Wed Jul 21st, 2021 05:19

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Long-Term Coffee Consumption is Associated with Fecal Microbial Composition in Humans

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282261/



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