Eating More Plant Protein Associated With Lower Risk Of Death

Amazoniac

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Wagner83 said:
You (and many others) said that coffee lost its stimulant properties over time, do you know if the pro-digestion effects of coffee would disappear with regular use?


@haidut I know you love your pepsi so that could be interesting for you.
I guess Zeus sips: slurps, gargles, and concludes with a tongue snap followed by a satisfaction sigh.
Travis said:
Coca~Cola
I don't know why everyone's trying to play cool and pretend that nothing happened. He never inclines the fonts if not for an enthusiastic proclamation, which probably includes jumping from his chair. Not this time. Also, there was no other reason for irradiating the hyphen if not for artistic purposes.
 

Travis

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You (and many others) said that coffee lost its stimulant properties over time, do you know if the pro-digestion effects of coffee would disappear with regular use?
I think perhaps the routine use of coffee could downregulate the opiate receptors a bit, but I'm certain that they are still there. No matter how long a person drinks coffee, caffeoyl quinide should still block the μ‐receptors wherever they are found—regardless of their numbers. I don't think it's unreasonable to suppose that that a person could get habituated to caffeine, in the brain, yet still remain sensitive to the anti‐opiate both in the brain and periphery.
 

raypeatclips

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I think perhaps the routine use of coffee could downregulate the opiate receptors a bit, but I'm certain that they are still there. No matter how long a person drinks coffee, caffeoyl quinide should still block the μ‐receptors wherever they are found—regardless of their numbers. I don't think it's unreasonable to suppose that that a person could get habituated to caffeine, in the brain, yet still remain sensitive to the anti‐opiate both in the brain and periphery.

How long does the anti-opiate effects of the coffee last?
 

ratstrain

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There's a direct μ‐opioid antagonist in coffee similar in strength to naloxone,⁽¹⁾ yet you take a more indirect approach to arrive at the same receptor. Besides being highly circuitous and entirely unnecessary—in light of caffeoyl quinide's presence—it doesn't even concord with observations; and here's why:

Exhibit A: Brown, S. R. "Effect of coffee on distal colon function." Gut (1990)

In this two‐part study, Doctor Brown administered a questionnaire to some and a rectal probe + coffee to others. He had also examined the effects of decaffinated coffee in the same subjects:

'Twenty nine per cent (63% women) claimed that coffee induced a desire to defecate.' ―Brown

'Coffee has been shown to have profound effects on the gastrointestinal system;' ―Brown

'Intraluminal pressure in the rectum and distal sigmoid colon were recorded using a 5 lumen, flexible, manometric assembly (od 5 mm)...' ―Brown

View attachment 8466

'Both regular and decaffeinated coffee contain exorphines that can bind to opiate receptors. Opiate receptors, both in the brain and within the gut wall, mediate important effects on colonic motility; Sun and his colleages have shown that opiate receptors are necessary for the colonic response to food.' ―Brown

'A similar increase was seen after drinking decaffeinated coffee in all coffee responders tested. No increase in rectosigmoid motility was seen after a drink of hot water.' ―Brown

'In conclusion, our results confirm the common belief that coffee promotes the desire to defecate. This response, which can also be induced by decaffeinated coffee, is seen in about a third of the population...' ―Brown

Thus: the laxative agent in coffee could not be removed through the decaffination procedure, adding even more proof—as if it needed any more—that caffeoyl quinide is primarily responsible for these effects.

[1] Boublik, J. H. "Coffee contains potent opiate receptor binding activity." Nature (1983)

It can be multifactorial.

If like S R Brown et al. reported diarrhea after drinking coffee happens only in about one third of the population, a given opioidergic mechanism as the explanation of diarrhea would be far from systematic; this tends to indicate a modulatory rather than one-sided effect, which would be consistent with the findings of Simón Brailowsky et al. about theophylline. And for S R Brown et al., the exorphins would stimulate the transit by acting as agonists, like morphine. Caffeoyl quinide could also be modulatory, sometimes facilitating, sometimes inhibitory depending on the conditions, and it could act only peripherally, if it does at all in vivo. Otherwise, in case of a marked inhibitory effect, coffee would be rather uninteresting for consumers. Besides, does naloxone cause diarrhea in people who haven't taken opiates, likely not, unless endogenous opioids are already acting to calm down preceding inflammatory diarrhea, possibly (Pol O et al., 1994; Pol O et al., 1995). Also, naloxone can increase beta-endorphin (Naber D et al., 1981; Levin ER et al., 1981; Levin ER et al. 1984), can alleviate diarrhea (Dajani EZ et al., 1979; Ganes E et al., 1987) and can oppose normal transit (E. A. Sun et al., 1982; France Blanquet et al., 1982).

As for decaffeinated coffee, it still contains substances other than caffeoyl quinide that have the potential to cause diarrhea, by raising cyclic AMP - more so than caffeine - and by exerting a muscarinic effect.

What are the authors referring to with the part pasted below? Are they saying that the opiate receptors are needed for the bowel to move after eating? And do they mean “response” as in activation of the opiate receptors?

Sun and his colleages have shown that opiate receptors are necessary for the colonic response to food.' ―Brown

Yes, see the references at the end.
 

Travis

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It can be multifactorial.
And for S R Brown et al., the exorphins would stimulate the transit by acting as agonists, like morphine.
Now you appear to be just trying to distort reality. It's well known that opiates reliably slow intestinal time, and nerve transmission.

Daniel, H. "Effect of casein and β-casomorphins on gastrointestinal motility in rats." The Journal of nutrition (1990)
Morley, J. "
Effect of exorphins on gastrointestinal function, hormonal release, and appetite." Gastroenterology (1983)
Galligan, J. "
Centrally mediated inhibition of small intestinal transit and motility by morphine in the rat." It can be multifactorial.Journal of Pharmacology and Experimental Therapeutics (1983)

'The differences be tween the CAS and the WPS groups were partly (GER) or completely (GITT) abolished by pretreating the animals with the specific opiate-receptor antagonist naloxone. It is assumed that opioid peptides released from casein during digestion slowed gastrointestinal motility by direct interaction with gut opiate receptors.' ―Hannelore

'Hydrolyzed gluten prolonged intestinal transit time, and this effect was reversed by concomitant administration of naloxone.' ―Morley

'The effects of morphine treatment on small intestinal propulsion and contractile activity were investigated in unanesthetized rats. Intragastrically, s.c. and i.c.v. administered morphine produced dose-related decreases in the transit of a radioactive marker (⁵¹Cr) through the small intestine.' ―Galligan
As for decaffeinated coffee, it still contains substances other than caffeoyl quinide that have the potential to cause diarrhea, by raising cyclic AMP - more so than caffeine - and by exerting a muscarinic effect.
It sure does: Besides 4-caffeoyl-1,5-quinide, roasted coffee has an entire suite of very similar antiopiate lactones; it's not even the strongest one but 3,4-dicoumaroylquinide is. However! do to its much greater abundance, caffeoyl quinide represents the flagship of coffee's anti-opiate fleet.

coffee.png


I mean, you were thinking about thee other anti-opiates right? . . . you know, those things that have been consistently proven to increase intestinal motility.

It can be multifactorial. [...] Caffeoyl quinide could also be modulatory, sometimes facilitating, sometimes inhibitory depending on the conditions,

'Weaseling out of things is important to learn. It’s what separates us from the animals… except the weasel.' ―Simpson
...and it could act only peripherally,
Why would you assume that? It's well-known that its parent compound, 4-caffeoylquinic acid, is absorbed and has been detected in the plasma:

coffee.png


Now why exactly would you expect the lactone to be any different? It differs by only 4.5% by mass, is smaller, and is slightly less polar.

And not only has it's parent compound been proven to be absorbed, it's sulfated form has been as well:

'Within 1 h, some of the components in the coffee reached low nmol/L peak plasma concentrations while chlorogenic acid metabolites, including caffeic acid-3-O-sulfate and ferulic acid-4-O-sulfate, and sulfates of 3- and 4-caffeoylquinic acid lactones, had higher Cmax values. The short time to reach Cmax indicates absorption of these compounds in the small intestine.' ―Stalmach

Stalmach, A. "Metabolite profiling of hydroxycinnamate derivatives in plasma and urine following the ingestion of coffee by humans: identification of biomarkers of coffee consumption." Drug Metabolism and Disposition (2009)
Renouf, M. "Dose–response plasma appearance of coffee chlorogenic and phenolic acids in adults." Molecular nutrition & food research (2014)
...if it does at all in vivo.

But it does act in vivo: Remember that decaffinated coffee had been shown to increase intestinal motility? Why could a person imagine that an antiopiate with μ-receptor binding affinity similar to that of naloxone wouldn't act in vivo?
Also, naloxone can increase beta-endorphin (Naber D et al., 1981; Levin ER et al., 1981; Levin ER et al. 1984),
You know: Naber has more than one 1981 articles on this topic, making it impossible for me to find out the source for your statement. Could you post the full citation? with a quote?
 
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Travis

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How long does the anti-opiate effects of the coffee last?
I don't think they'd last very long in the digestive tract due to the high enzymatic activity in that location and also the high volume of diluting substances they'd encounter. But in the brain I think they can last for a few days, based on my experience with eating dairy products.

Just as Ray Peat often mentions that it might be a good idea to drink coffee while eating meat (for iron), it could be a good idea to drink coffee before eating cheese—to block the receptors. If a person decides to eat a meat + cheese combination, then perhaps a French-press' worth amount of coffee should be prepared (yum!).

From my experience: if a person doesn't like coffee this simply means they're drinking the wrong kind—the wrong origin, roast, grind, or brewing technique. Black coffee done right is the cat's meow.
(-.-)
 
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ratstrain

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I was referring to other compounds which are water-soluble melanoidins, not cinnamoylquinides.

Montoya GA et al. Modulation of 3',5'-cyclic AMP homeostasis in human platelets by coffee and individual coffee constituents. Br J Nutr. 2014 Nov 14;112(9):1427-37. doi: 10.1017/S0007114514002232. Epub 2014 Sep 23.

Teresa Röhrig et al. Identification of a Phosphodiesterase-Inhibiting Fraction from Roasted Coffee (Coffea arabica) through Activity-Guided Fractionation. J. Agric. Food Chem., 2017, 65 (19), pp 3792–3800.

Argirova MD et al. New biological properties of coffee melanoidins. Food Funct. 2013 Aug;4(8):1204-8. doi: 10.1039/c3fo60025d.

You know: Naber has more than one 1981 articles on this topic, making it impossible for me to find out the source for your statement. Could you post the full citation? with a quote?

Naber D et al. Naloxone effects on beta-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG in plasma of normal volunteers. Psychopharmacology (Berl). 1981;74(2):125-8.

Levin ER et al. Morphine and naloxone: effects on beta-endorphin immunoreactivity in canine plasma and secretions from rat pituitaries. Endocrinology. 1981 Jul;109(1):146-51.

Levin ER et al. Studies of naloxone-induced secretion of beta-endorphin immunoreactivity in dogs. Life Sci. 1984 Oct 8;35(15):1535-45.

Kenneth M. Hargreaves et al. Naloxone, fentanyl, and diazepam modify plasma beta-endorphin levels during surgery. Clin Pharmacol Ther. 1986 Aug;40(2):165-71.

Reker D et al. Naloxone, tardive dyskinesia, and endogenous beta-endorphin. Psychiatry Res. 1982 Dec;7(3):321-4.
 

Kartoffel

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From my experience: if a person doesn't like coffee this simply means they're drinking the wrong kind—the wrong origin, roast, grind, or brewing technique. Black coffee done right is the cat's meow. (-.-)

How are you preparing your coffee, Travis?

092716_BreakingBadCoffee.png
 
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Travis

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I was referring to other compounds which are water-soluble melanoidins, not cinnamoylquinides.

Montoya GA et al. Modulation of 3',5'-cyclic AMP homeostasis in human platelets by coffee and individual coffee constituents. Br J Nutr. 2014 Nov 14;112(9):1427-37. doi: 10.1017/S0007114514002232. Epub 2014 Sep 23.

Teresa Röhrig et al. Identification of a Phosphodiesterase-Inhibiting Fraction from Roasted Coffee (Coffea arabica) through Activity-Guided Fractionation. J. Agric. Food Chem., 2017, 65 (19), pp 3792–3800.

Argirova MD et al. New biological properties of coffee melanoidins. Food Funct. 2013 Aug;4(8):1204-8. doi: 10.1039/c3fo60025d.



Naber D et al. Naloxone effects on beta-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG in plasma of normal volunteers. Psychopharmacology (Berl). 1981;74(2):125-8.

Levin ER et al. Morphine and naloxone: effects on beta-endorphin immunoreactivity in canine plasma and secretions from rat pituitaries. Endocrinology. 1981 Jul;109(1):146-51.

Levin ER et al. Studies of naloxone-induced secretion of beta-endorphin immunoreactivity in dogs. Life Sci. 1984 Oct 8;35(15):1535-45.

Kenneth M. Hargreaves et al. Naloxone, fentanyl, and diazepam modify plasma beta-endorphin levels during surgery. Clin Pharmacol Ther. 1986 Aug;40(2):165-71.

Reker D et al. Naloxone, tardive dyskinesia, and endogenous beta-endorphin. Psychiatry Res. 1982 Dec;7(3):321-4.
naloxone.png


The β-endophin is very likely being displaced from the μ-receptor by naloxone, where it cannot do anything of importance with naloxone blocking its receptor.

Volavka, J. "Short-term hormonal effects of naloxone in man." Psychoneuroendocrinology (1980)

'As naloxone displaces endorphins and ACTH from the opiate receptor...' ―Volavka
 

Travis

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How are you preparing your coffee, Travis?
41gBSNXd2VL.jpg


These last longer than any drip maker constructed out of China plastic—as long as you don't break it. Perhaps the best part about them is the portability, allowing easy access to coffee wherever you go. But the same property which makes it convenient often results in massive coffee consumption, upwards of three liters per day.
 

ratstrain

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View attachment 8488

The β-endophin is very likely being displaced from the μ-receptor by naloxone, where it cannot do anything of importance with naloxone blocking its receptor.

Volavka, J. "Short-term hormonal effects of naloxone in man." Psychoneuroendocrinology (1980)

'As naloxone displaces endorphins and ACTH from the opiate receptor...' ―Volavka

Naloxone has a short duration of action though.

Also, it has a dose-dependant analgesic effect.

But it's not necessarily through this mechanism that it stops pain, diarrhea and transit.

After all, it also increases cyclic AMP, which is pro-diarrheal and increases beta-endorphin, it inhibits the stimulatory effect of opioid agonists on transit, and opioid agonists can cause pain.
 

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