Coffee Inhibits Cortisol Synthesis

Discussion in 'Scientific Studies' started by haidut, May 22, 2016.

  1. haidut

    haidut Member

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    I was really pleased to see that study for two reasons. First, it gives more credibility to Peat's statement that coffee/caffeine do NOT boost cortisol, contrary to what many people claim and would like to believe. This matches well the few animal studies I have posted showing caffeine and coffee to reverse insulin insensitivity and obesity. Second, the study was published by a few fellow Bulgarians, albeit working at a Swiss university. :):
    As I have mentioned on the Danny Roddy shows and on many threads in this forum, cortisol synthesis depends on the enzyme 11β-HSD1 and it converts the inactive cortisone into the active cortisol. Big Pharma is in hot pursuit of an effective and selective 11β-HSD1 inhibitor as a treatment of obesity, diabetes, Cushing syndrome, depression, mania, and a few other serious conditions. The study below investigated the 11β-HSD1 inhibiting effects of compounds in espresso coffee. It found caffeine to be neutral in regards to 11β-HSD1 and an unknown compound in coffee to be a strong inhibitor. The unknown inhibitor of 11β-HSD1 in coffee seems to be very water soluble but given that there are several thousand such compounds present in coffee it would take some time and effort before it is isolated. For the record, cocoa powder was not an effective 11β-HSD1 inhibitor.

    http://www.sciencedirect.com/science/article/pii/S0014579306007538

    "...To test our hypothesis that coffee beverage contains compounds with anti-diabetic effects due to decreased local glucocorticoid reactivation, we prepared a coffee extract with a composition similar to that of an Italian Espresso and tested its effect on 11β-HSD1-dependent conversion of cortisone to cortisol. The presence of coffee extract at a final concentration of 1% almost completely inhibited the 11β-HSD1-dependent oxoreduction of cortisone in cell lysates (Fig. 1). Upon incubation with various concentrations of coffee extract, a dose-dependent inhibition curve with an IC50 of approximately 0.25% was observed in cell lysates and of 0.7% in intact cells. Coffee extract similarly inhibited 11β-HSD1 activity in fully differentiated mouse 3T3-L1 adipocytes and in mouse C2C12 myotubes (not shown), two metabolically relevant endogenous cell models [24]. Inhibition of 11β-HSD1 was 7–10-fold more efficient than that of 11β-HSD2 and 17β-HSD1 (not shown), indicating that coffee preferentially inhibits glucocorticoid reactivation. Comparable results were obtained with five different commercially available coffee brands, while extracts from cocoa powder, which is also a rich source of polyphenolic compounds, did not inhibit 11β-HSD1."

    "...Next, we measured the effect of extracts from decaffeinated coffee on 11β-HSD1 activity and obtained an inhibition comparable to that of normal coffee extract. Moreover, 2 mM of pure caffeine did not affect 11β-HSD1 activity. We also found no inhibitory effect with 200 μM of caffeic acid, chlorogenic acid or trigonelline, three well-known biologically active substances present in coffee beverage (not shown)."

    "...We performed experiments to obtain initial information on the stability and polarity of the inhibitory compound. Boiling of the aqueous coffee extract for 30 min did not affect its effect, demonstrating that the inhibitor is thermo-stable (Fig. 2.). The inhibitory effect of the extract was abolished, however, upon charcoal treatment. To further assess the solubility of the inhibitor, the aqueous coffee extract was mixed with an equal volume of the organic solvents n-hexane, dichloromethane, or ethyl acetate, followed by separation of the two phases and determination of the presence of the inhibitory substance in both phases ( Fig. 3). An equal partition was obtained with water/ethyl acetate, whereas highly hydrophobic solvents such as n-hexane extracted only small amounts of the inhibitor. These observations and the fact that it is solubilized from coffee beans with water suggest that the inhibitor is a fairly polar compound."
     
  2. zooma

    zooma Member

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    Maybe more importantly, it supports what Ray has said many times; coffee is much more than caffeine.

    I haven't read the study yet, but if this is true, couldn't this be a huge breakthrough? Your talk with Danny on weight loss concisely sums it up; inhibit stress, and you will lose weight. Sucrose seems to be a good inhibitor of adrenaline, so coffee with lots of sugar essentially inhibits stress?
     
  3. cats

    cats Member

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    What happens to the cortisone if it is not being converted into cortisol? Does it have any effects of its own?
     
  4. lvysaur

    lvysaur Member

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    There's also some compound in it that makes you poop, it's great
     
  5. OP
    haidut

    haidut Member

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    Yep, coffee + sugar would be a great way to lower stress and lose weight. Older studies in the 1920s showed weight loss from 10+ sweetened coffees a day.
     
  6. OP
    haidut

    haidut Member

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    It does have glucocorticoid effects, but it is about 10-times weaker than cortisol. It is also much more easily excreted in urine and that is another reason it is preferable to cortisol.
    Cortisone - Wikipedia, the free encyclopedia
     
  7. DaveFoster

    DaveFoster Member

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    So, you're saying that caffeine does not contain this inhibitor of 11-beta-HSD1.

    Does this mean that caffeine will raise both ACTH and cause cortisol to remain elevated, but coffee may not have this effect, or rather that this effect will be somewhat blunted in comparison?
     
  8. milk_lover

    milk_lover Member

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    Interesting find, thanks haidut!

    I wonder what in coffee is responsible for inhibiting that enzyme. Could it be magnesium or niacin or B1? I think you've mentioned those substances in your other recent post about aspirin lowering cortisol. Anyways, this makes me fall in love with coffee even more. Similar to tea having its own cortisol lowering agent (theanine), it seems coffee got also its own. This explains why I love Starbucks cold-brew coffee with a lot of sucrose syrup pumps :)
     
  9. OP
    haidut

    haidut Member

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    What the study says is that caffeine is neutral - neither raises nor lowers cortisol, while coffee contains a compound that lowers cortisol synthesis. Some other studies have found that caffeine raises ACTH, but this will happen with any substance that improves metabolism without enough nutrients. Thyroid does the same.
     
  10. OP
    haidut

    haidut Member

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    I think niacin could very well be that agent. In animal and human studies it was found that niacin made them sleepy and the dose was low enough so the benzodiazepine effects of niacinamide are probably not involved. Lowering cortisol tends to make people sleepy so if niacin causing sleepiness could very well be from lowered cortisol. I am going to write to the fellow countrymen who wrote the study and ask what they think this magic compound is.
     
  11. DaveFoster

    DaveFoster Member

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    Thanks for the reply. By nutrients, I'd assume you mean sucrose (or any form of glucose).

    Do you know of any time-delay between this effect or any experiences with timing? I know Peat says to take coffee "with a meal," but I'm not sure that simultaneous ingestion of sucrose and coffee in the morning will blunt the response if you haven't suppressed the nocturnal stress hormones.
     
  12. tyw

    tyw Member

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    Good study :) As usual, I will highlight the areas where I see common pitfalls for people. In this case, the phenomena of coffee without adequate nutrition.

    I think I was listening to yourself in one of the Generative Energy podcast episodes, whereby I somehow got the impression that Coffee without adequate nutrition was a combo for higher cortisol.

    It would make sense that any transient metabolic increase from coffee and/or isolated caffeine would demand more resources to be mobilised. And if there aren't any sufficient resources around, then there needs to be extra pressure to mobilise these resources, and/or extra synthesis.

    eg: you are ketogenic and glycogen depleted and are drinking coffee in the morning (which is an overnight-fasted state) --> Cortisol goes up in an attempt to mobilise whatever glycogen and fat (and maybe even protein from lean tissue) from peripheral tissues, with the hope of getting glycogenesis in the liver.

    In that sense, a lack of resources likely trumps any cortisol inhibitory effects of compounds in coffee.

    As for amount of carbohydrate that is required to prevent this, my gut sense is that anything which adequately replenishes or equalises liver glycogen content would work. This could be as low as 25g of sugar, but more likely at least 50g.

    As for @DaveFoster's quote:

    Do you know of any time-delay between this effect or any experiences with timing? I know Peat says to take coffee "with a meal," but I'm not sure that simultaneous ingestion of sucrose and coffee in the morning will blunt the response if you haven't suppressed the nocturnal stress hormones.​

    At least in terms of caffeine, the pharmacokinetics are much quicker (starting with buccal absorption) than sugar.

    ie: The effect of caffeine at least are much quicker than the effects of sucrose (though don't know about the other compounds in coffee).

    The best bet IMO to reduce the nocturnal stress response is still going to be bright light. Artificial light may work, but sunlight probably best.

    Still take some carbohydrate with the coffee, since the carbohydrate should hit the bloodstream relatively quickly, and provide some added buffer (still need to wait to hit small intestine, but first thing in the morning, that should happen within 30 mins).

    .....
     
  13. OP
    haidut

    haidut Member

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    Sugar is absorbed almost immediately in the stomach, and it also has anti-stress effects even without ingestion, which suggests that there are sugar "receptors" in the mouth sensing its presence and alerting the brain so that it can stop pumping out CRH and ACTH. So, if it's just coffee/caffeine + sugar you are consuming then the sugar should be able to act first. Caffeine takes about 15min to reach maximum blood concentrations, which again is a good thing.
     
  14. cats

    cats Member

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    Yes... I definitely notice a strong sensation when there's sugar in my mouth. You might even say it's pleasant...

    Sorry, couldn't resist. Seriously, though, this could probably be explained as a "Pavlovian" response to the taste of sugar.
     
  15. docall18

    docall18 Member

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    I am sure that coffee/caffeine is fine for the people who are in good health. However most people, esp on this forum, do have health issues and taking caffeine has a negative impact.

    In general people with poor health should steer clear of caffeine. No one has a deficiency of caffeine/coffee.

    People here should focus on common deficiencies, such as magnesium. This is a major cause of high cortisol.
     
  16. tyw

    tyw Member

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    I think this statement needs to be qualified. There are very very real nervous system effects of carbohydrate simply being in the mouth. eg: this study with significantly increased cycling times with "carbohydrate rinsing" --
    https://www.researchgate.net/profil...erformance/links/55d2e18708aec1b0429efd25.pdf

    Again, this likely has to do with some sort of sensing involving multiple systems, including the nervous system. For an extreme example, if you put rats through a gastric bypass surgery, you see the Sweet Taste Receptors get horribly blunted -- Transformation of postingestive glucose responses after deletion of sweet taste receptor subunits or gastric bypass surgery | Endocrinology and Metabolism

    The same happens in humans with gastric bypass surgery, or other similar surgeries like severing of the vagus nerve.


    Whether or not a particular human has this sort of robust response depends on a couple of factors, ranging from existing state of health, to factors beyond our immediate control:
    - We see genetic variance -- Association between Common Variation in Genes Encoding Sweet Taste Signaling Components and Human Sucrose Perception
    - As well as early cultural environment effects -- Genetic and Environmental Determinants of Bitter Perception and Sweet Preferences

    I cannot say with 100% certainty that "sugar will have it's effect before caffeine". People should experiment with this and see how they respond ;)

    ....
     
  17. Tarmander

    Tarmander Member

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    I am one of those that most would say has compromised health. I studied peat for about a year before I made the coffee plunge.

    If you do have poor health, caffeine and coffee can still be a great health asset. I started drinking coffee last November. I made sure my work load was lower then usual and did not take on any new projects.

    The first week was hellish, the second week almost as bad, and at about a month I got into a routine that did not feel like it was taking away from my ability to function. Now I drink coffee everyday, a lot of it, and it's fantastic. But it can be rocky to start. You can add all the sugar you want, it's still tough if your health is not great.
     
  18. OP
    haidut

    haidut Member

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    I concur, but after checking other sources I see that "time to onset of action" for caffeine is 1 hour (so my 15min estimate was too aggressive). I think we can all agree that if the person has not responded to the sugar ingestion within 1 hour then there is a serious problem and they probably would not be drinking coffee anyways :): So, for all intents and purposes, the organism should have reacted to the sugar before or together with caffeine. But whether coffee will generate a stress response is dependent on more than that - i.e. liver health, kidney health, and HPA status, etc. So yes, experiment is the ultimate arbiter.
     
  19. zooma

    zooma Member

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    The study says that decaf produced a similar inhibitory effect, so this could be useful for people who don't want to use caffeine. It may be useful anyway, because you can use a much larger dose.
     
  20. kaybb

    kaybb Member

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    I was worried about the cortisol thing and taking caffeine because a small amount sent me on a bad high...even 1 can of caffeinated pop. I started at about 20-30mg of caffeine and upped it slow. But what took away my stress response/jitters/heart pounding etc., was using taurine/theanine everyday with it. (thanks @hadiut for suggestion) I can do up to 600mf. now if I need to.
     
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