Caffeine Has Same Effects On Metabolism As Dinitrophenol

Discussion in 'Scientific Studies' started by haidut, Aug 16, 2013.

  1. haidut

    haidut Member

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    Hi all,

    As you many of you probably know, back in the 1930s there was a very popular drug for weight loss called dinitrophenol. It works by uncoupling mitochondria (just like aspirin does in high doses), which makes them release energy as heat instead of ATP. Due to several high profile fatal hyperthermia accidents, dinitrophenol is banned in many countries and is viewed as toxic. Ray Peat has spoken favorable of it and compared it to caffeine.
    I found a study that compares the effect of the two drugs and it looks like they have almost identical effects on oxygen consumption and metabolism:
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698477/

    "...This work explored the effects on mitochondrial biosynthesis of caffeine and DNP in human rhabdomyosarcoma cells, a model organism for metabolic observation. We show that treatment of muscle cells with caffeine or DNP will induce the PGC-1α mRNA and protein in a dose- and time-sensitive manner. We also demonstrate that caffeine or DNP increases mitochondrial content as well as enhances oxidative and total metabolism. These are the first observations that directly compare caffeine with DNP and demonstrate the effects of both treatments on glycolytic and oxidative metabolism in skeletal muscle cells."

    Also from the study - caffeine increased Ogygen Consumption Rate (OCR) by 900%, however the lower dose caffeine increased metabolism more than the higher one:
    "...Cells treated with caffeine at 250 or 500 μM significantly increased total metabolism; however, caffeine at 250 μM increased metabolic rate to a greater extent than caffeine at 500 μM"

    So, the question is how much caffeine does one need to take to get to 250μM concentration? This study offers a hint:
    http://interactive.snm.org/docs/Caffein ... eptors.pdf

    "...Half-maximal displacement was achieved at a plasma caffeine concentration of 67μM, which corresponds to 450mg in a 70-kg subject or approximately 4.5 cups of coffee"

    So, if 450mg achieve 67μM, then (assuming linear dose-dependency) you need about 1680mg caffeine to achieve the concentration from the first study, shown to increase metabolism. Needless to say, I would not take nearly as much caffeine at once but in divided doses it is very doable. I am currently taking 400mg x3 a day for a total of 1200mg.

    Interestingly enough, this dosage 1200mg-1400mg is very close to the dosage shown to increase lifespan by 52% in the study I posted couple of weeks ago...
     
  2. superhuman

    superhuman Member

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    Thats very cool.

    I know RP says 12+cups of strong coffee a day is recommended for hypothyroid people because it can be used as thyroid.
    He says 1 cup strong coffee every hour is enough so you dont need big hits everytime.

    Would be cool to know the timespan of the 1600 of caffeine. Was it in one shot or divided throughout the day?
     
  3. jyb

    jyb Member

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    If one tries to use caffeine throughout the day to use for its thyroid like action, how would it differ from aspirin? On that note, I think that RP said that caffeine combines with aspirin for a stronger thyroid like effect.

    In the morning I'm taking 1-2 tabs of aspirin (which is a lot, but the milk I drink is rich in K2). I get a boost from it, but I'm not sure how it compares to caffeine - it's more subtle. If I had a poor nights sleep, aspirin and caffeine at breakfast will usually make my brain function perfectly for the morning, but in the afternoon the effect of sleep can be felt.
     
  4. superhuman

    superhuman Member

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    Yes RP says aspirin combined with caffeine has almost the same effect as T3. Im a litle sceptical about the aspirin because of the nosebleeding with higher dosages then 325mg, and i dont like supplementing with more stuff
     
  5. jyb

    jyb Member

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    You won't nosebleed if you're taking K2. This is how I determine if milk is good quality: if I nosebleed, I know it's low in K2. If the milk is quality, I can megadose on aspirin without ever nosebleeding.
     
  6. superhuman

    superhuman Member

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    Thats cool, does this apply to skim milk or full fat milk? how much milk are we talking about?
     
  7. superhuman

    superhuman Member

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  8. charlie

    charlie The Law & Order Admin

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    nwo2012 is a member here and he uses dinitrophenol.
     
  9. superhuman

    superhuman Member

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    why does he use it?
     
  10. charlie

    charlie The Law & Order Admin

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    I didn't ask him.
     
  11. superhuman

    superhuman Member

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    i sent him a message
     
  12. OP
    haidut

    haidut Member

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    The study on life extension used nematodes (worms) and hinted that the 1200mg-1400mg is in divided doses since it says the human equivalent to the nematode treatment would be 100mg-200mg every 4 hours. Bioavailability of caffeine is essentially 100% but half-half varies according to the person. Here are some more studies on that:
    http://www.ncbi.nlm.nih.gov/pubmed/6832208

    "...The rapid absorption resulted in essentially complete bioavailability of the oral caffeine, F(%) = 108.3 +/- 3.6%. The caffeine plasma half-lives varied from 2.7 to 9.9 h, indicating substantial inter-subject variability in its elimination."

    And one more:
    http://www.ncbi.nlm.nih.gov/pubmed/11839447

    So, personally I'd stick to the 200mg pills every 4 hours. Higher dosage makes me a bit uneasy.
     
  13. superhuman

    superhuman Member

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    Thanx a ton when do you take your last 200mg pill or 200mg of caffeine? do you suffer from any sleep problems taking it close to bed? and any tricks to avoid that
     
  14. Padmaaa

    Padmaaa Member

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    Can coffee increase adrenalin and cortisol for those who already have high adrenalin and cortisol?
     
  15. OP
    haidut

    haidut Member

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  16. OP
    haidut

    haidut Member

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    Yes, if you dont drnik it enough sugar it will raise adrenalin. I take every 200mg pill with a glass of orange juice, which provides about 30g of sugar. For me thats enough to block the adrenalin effect.
     
  17. superhuman

    superhuman Member

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    i seem to just cant handle caffeine yet. Cant fall asleep no matter how much or litle coffee i drink or when during the day i drink it
     
  18. messtafarian

    messtafarian Member

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    Boy I wish coffee worked like a weight loss pill, lol.
     
  19. superhuman

    superhuman Member

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    Hehe i cant seem to tolerate coffee so im gonna switch over to aspirin and increase the dosage there. Hopefully it will have the same effect :)
     
  20. jyb

    jyb Member

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    I think I was prone to this coffee problem with sleep, but I don't think it's a problem anymore. I mean, I can take about 5 cups of coffee (I stop mid afternoon just in case) without particular problem. As a precaution, I don't take a double shot at once - I prefer to spread out the caffeine throughout the morning or afternoon. As usual, I never ever drink coffee without some milk and sugar, and avoid drinking it if I feel hungry. I also take aspirin for breakfast at the same time as my first coffee cup, as RP mentioned both can combine.

    It's possible that I could take twice that without side effects, but I think that coca cola on empty stomach a few hours before bed isn't good for my sleep.
     
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