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Caffeine Increases Pregnenolone & Progesterone In The Brain

Discussion in 'Scientific Studies' started by haidut, Apr 9, 2014.

  1. haidut

    haidut Member

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    As a follow up on my other posts, caffeine is really shaping up to be another Peatarian panacea. At doses achievable in humans with supplementation, caffeine seems to increase the levels of all important steroids in the brain, and in fact this may be the mechanism behind its stimulant effects.

    http://www.ncbi.nlm.nih.gov/pubmed/10837842

    "...A single intraperitoneal injection of caffeine induced dose- and time-dependent increases in the concentrations of pregnenolone, progesterone, and 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) in the cerebral cortex."

    The effective HUMAN dosage seems to be in the range of 3.6mg-14.3mg per kg of body weight.

    "...The increases were significant at a caffeine dose of 25 mg/kg and greatest (+188, +388, and +71%, respectively) at a dose of 100 mg/kg in rats killed 30 min after caffeine administration."

    Finally, the researchers think that raising the levels of these neurosteroids may be behind caffeine's cognitive effects.

    "...These results suggest that neuroactive steroids may modulate the stimulant and anxiogenic effects of caffeine."

    Boy, am I glad to have my caffeine pills:):
     
  2. jyb

    jyb Member

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    I've seen you mention that caffeine pills are handy in practice, as opposed to making coffee throughout the day. But I don't really understand why. If you get some instant coffee, you can make some very strong coffee with just one teaspoon or two, and a bit of hot tap water - you don't need to have all day access to an expresso machine. Or just make some very strong coffee and store in thermos for sipping during the day. Like that, you get some minerals which you don't get from caffeine pills.
     
  3. OP
    haidut

    haidut Member

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    I certainly drink a lot of coffee on the weekends when I am at home. However, when I am at work or on the road there is no substitute for the convenience of the pills. Also, it allows me to control the dosage more accurately if I am experimenting with something. With coffee, you never quite know how much caffeine you are ingesting. As you can see a lot of these studies mention specific dosages, and even mention a maximum or minimum dosage. With brewed coffee or espresso I would not be able to approximate well and test the studies on myself.
    I am not a pill maniac:) I just use whatever gets the job done as quickly as possible since I am typically quite busy and sometimes don't even have the time to get coffee. Sounds crazy, but such is modern life, at least for me.
     
  4. OP
    haidut

    haidut Member

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    Just wanted to post a quote from the study on the specific increases for the steroids:

    "...The injection of caffeine (25 to 100 mg/kg IP) resulted in dose-dependent increases in the cerebral cortical concentrations of pregnenolone, progesterone, and allopregnanolone that were apparent after 30 min (Fig. 1). The effects of caffeine on the cortical concentrations of these three steroids were already significant (72, 90, and 47%, respectively) at the dose of 25 mg/kg, with the greatest observed effects (188, 388, and 71%, respectively) apparent at the dose of 100 mg/kg."

    So, at the highest dose, which translates to about 1,200mg of caffeine for a human (single/bolus dose), levels of pregnenolone almost tripled, levels of progesterone almost quadrupled, and allopregnanolone almost doubled.
    I find it interesting that many of the studies I found on caffeine, including the one extending maximal lifespan by 52%, noticed the biggest effect at a human dosage of about 1,200mg per day. Some studies used it as a split dosage (life extension study) and others like this one used a bolus dose. I wonder if there is a reason behind this convergence of effects around the dosage of 1,200mg. If I find something I will post it here.
     
  5. Vinero

    Vinero Member

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    I wonder how in the world anyone would be able to tolerate that, 1200 mcg. It would be extremely unpleasant I suppose.
    Maybe if you build it up and take it with a lot of sedative-like substances like Niacinamide, Progesterone, or GABA drugs, then you can tolerate higher dosages better.
     
  6. OP
    haidut

    haidut Member

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    I have taken 800mg at once, with 1,500mg of niacinamide and it made me sleepy actually. I would not do that on a regular basis, but in the study above even at the low dosage of about 300mg for a human there were still significant increases in all steroids. Taking 300mg should not be a problem for most people even without taking niacinamide.
     
  7. Peata

    Peata Member

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    Another reason to try to increase my caffeine, besides liver health.
     
  8. superhuman

    superhuman Member

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    I love it

    I find i can tolerate bigger more infrequent dosages then smaller more frequent. Strange i know

    Also remember if you opt to take 200mg or more in a dose take it right after a good meal if not it will stimulate metabolism and release alot of FFA wich can be harmfull if you dont have enough sugar to burn.

    In terms of the caffeine study haidut.

    Did they mention anything in terms of eating around the dosages or in terms for humans ?

    If you take that high dosages when fasted or on more empty i guess it would make you really awfull and sleepy since i have done that myself.

    Taken 400mg on empty stomach after waking up and felt reeeeeeeeaaaallly sleepy and just could not give a **** about anything. Like sleepy and lethargic as ****
     
  9. OP
    haidut

    haidut Member

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    I don't think they fed the rats anything prior to giving caffeine, or at least they did not time it to occur after a meal. Given the large increases in pregnenolone and progesterone it is not surprising that some people get sleepy. I think Peat said that 600mg+ is a huge dose and likely to cause increase in cortisol in pretty much anybody. It happen in the rats from the study as well.

    "...The plasma concentrations of THDOC and DHEA were not significantly affected by caffeine, whereas that of corticosterone, the major adrenal corticosteroid in the rat, was increased by caffeine in a dose-dependent manner. The effect of caffeine on the plasma concentration of corticosterone was significant (96%) at the dose of 25 mg/kg and greatest (304%) at the dose of 100 mg/kg."

    "...Caffeine induces a stresslike response of the hypothalamic-pituitary-adrenal (HPA) axis in rats. Thus through a stimulatory action on the release of corticotropin-releasing factor (CRF), caffeine elicits marked increases in the plasma concentrations of corticosterone and adrenocorticotropic hormone (ACTH) (31). Moreover, caffeine induces behavioral and neurochemical effects in rats that are similar to those triggered by CRF or stressful stimuli (4,9,36). The HPA axis plays an important role in determining the peripheral and central concentrations of neuroactive steroids either under stressful conditions or after administration of anxiogenic drugs (4). Thus the observations that caffeine induces both neurotransmitter release (10,33) and anxiety-like behavior associated with increases in the plasma and brain concentrations of neuroactive steroids suggest that the HPA axis might mediate such actions of caffeine. This conclusion is also consistent with our present data showing that caffeine failed to increase the concentrations of neuroactive steroids in either the brain or plasma of Adx-Orx rats, and that this drug elicited a marked increase in the plasma concentration of corticosterone in control rats. However, the possibility that the adrenalectomy-induced removal of catecholamines as well as at other agents produced by the adrenal cortex might influence the synthesis of neurosteroids in the brain cannot be ruled out."

    So, I think the morale of the story is that caffeine will increase cortisol unless you provide enough fuel. The same is true of thyroid hormone. However, the cortisol boosting effect can be stopped by taking about the same dosage of theanine at the same time. Since theanine is also a GABA agonist, you may end up getting even more sedated but very energetic. Kind of similar to the feeling Peat says you should get from thyroid - "energized but feeling like napping in the afternoon".
     
  10. superhuman

    superhuman Member

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    Cool.
    I dont have theanine available tho :p

    Im gonna aim for 1200mg caffeine a day for sure in the coming days but i dont have the caffeine powder now so i need to get it from coffee.

    I feel like 3 dosages of 400mg caffeine from coffee would be best for me instead of say 200mg caffeine at 6 intervals, feel like the caffeine tend to overlap things and i get a little trouble.

    In terms of getting sleeping problems or trouble getting to sleep if i drink to close to bed or have 2 frequent feedings of coffee close to bed i get a bit wired or head is racing.

    I think 120-140 gram coffee from filter coffee is the same as 1200mg caffeine content. So that will be like 2 liters coffee a day :D
     
  11. superhuman

    superhuman Member

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    haidut: in terms of the "negative" effects people can get from caffeine like i mention sleepy or fatigued. Or anxity or other bad things. Why do you think that is? and what to do about it?

    So that one can get to that 1200mg amount as a goal etc.

    Also do you feel there i any difference in terms of frequency of the caffeine dosage, in terms of caffeine halftime or effect time etc.
     
  12. OP
    haidut

    haidut Member

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    My original post explains why caffeine makes some people jittery - cortisol and activating the HPA axis. It's all in the study. I don't know why it makes some people fatigued, but it has been shown to increase lactic acid so that may be it.
     
  13. Peata

    Peata Member

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    I hope that a smaller amount than 1,200 mg. can still improve on things, because i'd rather not go that high.
     
  14. superhuman

    superhuman Member

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    Thanx haidut
     
  15. OP
    haidut

    haidut Member

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    Also, for those people taking high doses - I saw a study that shows caffeine in doses of 600mg+ per single dose impairs ammonia clearance and also may cause kidney damage. The ammonia clearance study was in humans so I think it is legit. The kidney damage was in rats so more questionable but may be this is why Ray says 600mg in single dose will cause a stress response. A better approach may be 400mg three times a day for those who want to reach 1,200mg. I personally feel best at 800mg daily and do not get jittery.
     
  16. 4peatssake

    4peatssake Member

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    Yeah, first time I took 200 mg, about 20 minutes later I dragged myself to bed. :lol:
    Can't remember if it was on an empty stomach or not but it was midday and I was done for.
    But I'm working now to support the body to reach that level and then up to 400 mg. ;)
     
  17. superhuman

    superhuman Member

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    im going for 900-1200mg the next days and see how it effects me.

    What i esp LOVE about coffee is that it makes me feel so clean on the inside. Bowels and everything gets so smooth
     
  18. Peata

    Peata Member

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    I"m having caffe latte in the mornings and caffeine pills later.
     
  19. lindsay

    lindsay Member

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    why would you take caffeine pills when you could just drink a strong coffee?? Or eat chocolate covered coffee beans :) I drink about 8 oz. of espresso once or twice per day - when the sun is out, I find I don't need as much. 8 oz. of espresso has about 500 mg of caffeine. And, I've actually found that adding salt to coffee with cream and sugar is quite tasty!
     
  20. Peata

    Peata Member

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    Mainly because I can know exactly how much caffeine I get from the pills. With the coffee I'm using, I think it's 65 mg. per t (instant) but I'm not sure. I just want to be sure for now.

    lindsay, what sort of benefits have you seen from increased coffee/caffeine? Do you feel it helped you raise or retain progesterone or can you tell?
     
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