Caffeine Reverses Stress, Insulin Resistance, Hypertension

haidut

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I think should clarify some misconceptions about caffeine. Many people are experiencing a stress response to caffeine, and the more studies I see and the more I experiment with friends/family the more I get convinced that the stress response is:

1. Temporary (last no more than 4 days as shown by studies and experiment)
2. It is mostly due to liver issues (caffeine metabolism is used as a clinical test for liver disease)

For a long time I was confused about caffeine myself. Ray would say great things about it, but then many studies will show that acute (for 1-2 days) administration of caffeine actually impaired insulin sensitivity and even made people temporarily diabetic. However, long-term studies unequivocally point to caffeine being strongly protective about any form of diabetes.
I think this study finally confirms Ray's opinion and combined several other studies showing that while caffeine may indeed trigger a stress response when administered for 1-2 days, in the course of just 2 weeks it actually lowered stress hormones, and ever reversed diabetes. Personally, I think that the beneficial effects are due to the fact that caffeine, like no other substance known to man, reverses liver dysfunction in just 2 weeks but in the initial period of 1-4 days flushed a lot of fat from the liver into the bloodstream. There could be other things at play but this is probably the main mechanism.
So, couple of other important things about the study. First, high sucrose diet did NOT make the animals fat as opposed to high fat diet. So, this is actually a study where high sugar (sucrose) diet really was high sucrose only and not high sucrose plus other crap. So, of anybody doubts that sugar will not make them fat this should alleviate some of those doubts. Second, caffeine reduced fat/weight in the high fat diet group, which once again points to the connection between liver dysfunction and weight gain. I am saying this b/c caffeine in the doses administered, though high, was not enough to increase thermogenesis to the point of burning all that excess fat in just 2 weeks. Keep in mind that the animals kept eating the fattening diet for those 2 weeks so something else in addition to the direct effects of caffeine must be at play here. I think it is much more likely that caffeine helped through its effects on liver function, which is still amazing in terms of doing so in just 2 weeks (confirmed by other studies). Last, the caffeine dose used was on the high end for most people - i.e. 1,200mg - 1,500mg per day for a human.
Since acute caffeine intake is known to increase lactate, for people experiencing this I would suggest taking a decent dose of thiamine (vitamin B1) about an hour before caffeine and then repeat this dose before every other caffeine dose during the day. Ray has said 300mg every 4 hours is fine, but some people may need more than that to balance the increase in lactic acid.

http://www.ncbi.nlm.nih.gov/pubmed/21733336

"...Recently, the benefits of caffeine withdrawal have been questioned, since a number of epidemiological studies showed no association between long-term coffee consumption, type 2 diabetes risk
(5,6) and high blood pressure (7–10), which confirms that acute and chronic caffeine intakes have opposite effects."

"...The HF diet caused a significant increase in weight gain per-d compared with control animals, whereas the HSu diet did not (control ¼ 1·53 (SEM0·26) g/d; HF ¼ 4·32 (SEM 0·45) g/d; HSu: 2·66 (SEM 0·25) g/d). Caffeine intake did not significantly modify weight gain either in control or in HSu animals (Caff ¼ 1·14 (SEM 0·16) g/d; HSuCaff ¼ 2·51 (SEM 0·29) g/d). In contrast, caffeine administration significantly reduced weight gain to 2·39 (SEM 0·36) g/d in HF animals (Fig. 3(a))."

"...The HSu and HF diets significantly increased plasma catecholamines by 211·9 and 124·1 %, respectively, from a control value of 50·03 (SEM 6·91). Chronic caffeine intake did not modify plasma catecholamines in control animals; however, when administered together with the HSu and HF diets, caffeine prevented the increase in circulating catecholamines, suggesting that the metabolic and haemodynamic effects of chronic caffeine intake are mediated by a decrease in sympathetic activation."

Some other studies by the same group showing the opposite effects of caffeine when administered short and long term. Keep in mind that the positive effects of caffeine were observed in just 15 days in the studies by this group, and that caffeine fully reversed whatever metabolic dysfunction there was, EVEN in aged rats.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776116/
"...Aged rats exhibited diminished insulin sensitivity accompanied by hyperinsulinemia and normoglycemia, increased visceral and total fat, decreased TAC and plasma catecholamines, and also decreased skeletal muscle Glut4 and AMPK protein expression. Chronic caffeine intake restored insulin sensitivity and regularized circulating insulin and NEFA in both aging models. Caffeine neither modified skeletal muscle AMPK expression nor activity in aged rats; however, it decreased visceral and total fat in 12 M rats and it restored skeletal muscle Glut4 expression to control values in 24 M rats. We concluded that chronic caffeine intake reverses aging-induced insulin resistance in rats by decreasing NEFA production and also by increasing Glut4 expression in skeletal muscle."

http://www.ncbi.nlm.nih.gov/pubmed/25661425
"...Acute caffeine decreased insulin sensitivity in a concentration dependent manner (Emax=55.54±5.37%, IC50=11.61nM), an effect that was mediated by A1 and A2B adenosine receptors. Additionally, acute caffeine administration significantly decreased Glut4, but not AMPK expression, in skeletal muscle. We found that A1, but not A2B agonists increased glucose uptake in skeletal muscle. SNP partially reversed DPCPX and MRS1754 induced-insulin resistance. Our results suggest that insulin resistance induced by acute caffeine administration is mediated by A1 and A2B adenosine receptors. Both Glut4 and NO seem to be downstream effectors involved in insulin resistance induced by acute caffeine."
 

NathanK

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Im still in the "I really dont understand caffeine camp". Ive attempted high dose caffeine with and without stress hormone inducing substances like theanine, niacinamide, ashwagandha, etc. From what Ive found is many times it makes my feet cold and at higher doses over a week Ive noticed increased weight. I can probably handle about 600mg max/day, but my body can only handle that for a few days tops before it catches up with my like a beast.

I theorize that at a certain threshhold cortisol kicks into the fat retention protection. A line easily crossed. This has even happened to me in the past on short lived ECA stacks, which are designed for weight loss of all things.

I dont know, but ive tried to do caffeine right for a long time and getting to the point where I think I should cease anything that increases any stress hormones at all. I dont think Im as unhealthy as a lot of people too-- though I readily admit my body runs chronically on stress hormones than having a well functioning metabolism.

One thing thats bounced around my head too about the fatty liver - caffeine tolerance connection that youve mentioned-- wouldnt that mean that teenagers would have the highest tolerance of caffeine or even alcohol due to less damage as a whole? I just dont see, or have experienced, what you have. Id appreciate any clarification
 

Tarmander

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Yeah I have a really tough time reconciling some of these caffeine posts, and my personal experience. Like I remember back in college, and growing up, I used to drink Caffeine all the time. I remember when I finally quit I actually really enjoyed better sleep and a more even energy level. Without the caffeine rushes I noticed that I never got tired like I did when I would crash on Caffeine. It is tough to argue with science and these studies...but there have to be studies out there detailing some of the pitfalls of caffeine...right?
 

ravster02

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Your personal experience doesn't add anything because what you did back then involving caffeine wasn't idea and to be blunt, stupid.

If you're taking caffeine, even in small doses like 10mg, you need to take it alongside taurine, magnesium and sugar (there's probably 1-2 other supps you could/should be taking too).
 

Tarmander

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ravster02 said:
post 98549 Your personal experience doesn't add anything because what you did back then involving caffeine wasn't idea and to be blunt, stupid.


Dude what's your problem?
 
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haidut

haidut

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NathanK said:
post 98527 Im still in the "I really dont understand caffeine camp". Ive attempted high dose caffeine with and without stress hormone inducing substances like theanine, niacinamide, ashwagandha, etc. From what Ive found is many times it makes my feet cold and at higher doses over a week Ive noticed increased weight. I can probably handle about 600mg max/day, but my body can only handle that for a few days tops before it catches up with my like a beast.

I theorize that at a certain threshhold cortisol kicks into the fat retention protection. A line easily crossed. This has even happened to me in the past on short lived ECA stacks, which are designed for weight loss of all things.

I dont know, but ive tried to do caffeine right for a long time and getting to the point where I think I should cease anything that increases any stress hormones at all. I dont think Im as unhealthy as a lot of people too-- though I readily admit my body runs chronically on stress hormones than having a well functioning metabolism.

One thing thats bounced around my head too about the fatty liver - caffeine tolerance connection that youve mentioned-- wouldnt that mean that teenagers would have the highest tolerance of caffeine or even alcohol due to less damage as a whole? I just dont see, or have experienced, what you have. Id appreciate any clarification

I hear you, I still think one can overdo caffeine but it seems that the length of intake and adaptation play a big role. Here is something on cortisol from one of the studies above.
"...The effect of chronic caffeine intake on cortisol levels in 3-, 12-, and 24-month-old rats is depicted in Fig. 3a. Aging increases cortisol levels in 12 M and 24 M rats in comparison with 3 M rats (cortisol 3 M = 4.077 ± 0.14 ng/ml; 12 M = 6.62 ± 0.71 ng/ml; 24 M = 6.48 ± 1.01vng/ml), but chronic caffeine intake did not significantly alter cortisol levels (Fig. 3a)."

So, higher cortisol is probably due to the aging process in general - i.e. low metabolism, like Ray has mentioned so may times. Chronic caffeine intake does not seem to have an effect on that, which matched other human studies - i.e. high cortisol people (depression, PTSD) have a boost in cortisol in short term caffeine use, but cortisol goes back to their baseline levels with chronic caffeine use.
There are ways to mitigate that effects of course, and some other posts below talk about that. DHEA in doses of about 5mg will lower directly cortisol production, and taurine / magnesium / theanine will do the same to control caffeine jitters.
As far as young people and caffeine - they can handle large quantities without crashing. The crash effect happens with aging - i.e. most people I know start getting crashes after 30 years of age and with short term larger doses of caffeine.
 
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haidut

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Berk_Peat said:
post 98686 How long did it take you to get rid of fatty liver using caffeine?

I was taking both caffeine and vitamin K2. That was more than a year ago, and I was taking 400mg caffeine and 15mg - 30mg K2 (MK-4). Within a week I was able to pound 1,000mg+ daily and that "tolerance" never disappeared afterwards. Within 2 weeks I was able to skip meals without getting stress reaction symptoms, which means glycogen storage improved a lot. I am assuming the "tolerance" to caffeine the studies talk about is simply improved liver function and ability to metabolize caffeine quickly.
 
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narouz

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haidut said:
post 98687
Berk_Peat said:
post 98686 How long did it take you to get rid of fatty liver using caffeine?

I was taking both caffeine and vitamin K2. That was more than a year ago, and I was taking 400mg caffeine and 15mg - 30mg K2 (MK-4). Within a week I was able to pound 1,000mg+ daily and that "tolerance" never disappeared afterwards. Within 2 weeks I was able to skip meals without getting stress reaction symptoms, which means glycogen storage improved a lot. I am assuming the "tolerance" to caffeine the studies talk about is simply improved liver function and ability to metabolize caffeine quickly.

haidut-
Okay, so in your experience you used caffeine + k2.
Since then you (and others--Such for example)
have kicked around other "co-factors" or "synergists" or whatever for liver therapy.
Off the top of my head:
-b1
-b6 (or 5P5) I think Such likes this
-glycine
-famotidine
-methylene blue
-milk thistle maybe

(leaving aside niacinamide and aspirin for now,
operating under your theory that they may be unhelpful until liver healing happens...)

Would you like to add or subtract from the list?
Do you think they might all be used well together?
Or maybe not?
 
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andrewdcjr

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How do you take your caffeine to get 400 mg to 1000 mg +? Coffee or other supplementation?
 

RPDiciple

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andrewdcjr said:
post 98692 How do you take your caffeine to get 400 mg to 1000 mg +? Coffee or other supplementation?

he has already answered that in many threads. Do some searching before you ask
 
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SQu

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Thank you for this ,haidut. A really central issue. I've been planning to revisit caffeine. Seems worth trying again from another angle.
 
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Such_Saturation has mentioned this before and it does somewhat match my experience: the more euphoric one feels after a caffeine dose, the more stress hormones one will experience soon after a.k.a the crash.

If you take caffeine and feel a sense of euphoria and soon after notice cold feet and cold (and sweaty) hands, you're running on stress hormones.
 

NathanK

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I wouldn't consider myself "old" at 38, but I am older with stress issues. Just to paint a picture, I'm muscular and what most would think in good shape and health with the exception of an excess of visceral fat. Ive loved drinking coffee for many years and the caffeine in a few cups a day has little effect on me. Theres a definite line for me though esp when it comes to pure caffeine supplements.

I think there could be a slower increased tolerance method for high dose caffeine. I think that it's also a viable option to go cold turkey on stress inducing substances as well to see how it effects you (easier said than done in my case because I rely on adrenaline to "run").

The eye opening way some studies go full blown high caffeine and the quick tolerance adaption and positive results that Haidut's experienced is what I find remarkable. I personally have done the high dose K2 as well as all of the substances mentioned above (and more) to further help my liver along as well as ameliorate the "blown curcuits" response with varying results (i have labs this week so those will be telling how far Ive come in the past 6 months). My experiences could be unique to me or my testing methods may need more discipline. I do make very concerted efforts though.

Ultimately everyone's body and situation is different and there are few "one size fits all" approaches, but different testing approaches are required to find that sweet spot of effectiveness.

Here's my personal master list of things that I use or have used in the past to help lower stress responses (feel free to add or comment):

The Rockstars (In order of effectiveness and duration for me):
Cyproheptadine (my favorite magic pill thus far)
Taurine
Food! (esp salt, sugar, protein)
Ashwagandha (potentially adversely effects serotonin)

The other options that are said to help with varying personal results:
Niacinamide
Magnesium
Gelatin
DHEA
B6
Zinc
Theanine (no noticeable effect)
GABA (waste of money)
Progesterone (I've only tried Haidut's Stress Non and liked it)
Clonadine and Xanax I haven't used before or know the sides, but imagine could help.

On a side note from above, I also noticed increased lactate at times with higher doses. I just used baking soda in water and that worked. B1 sounds like a good alternative option as well.
 

andrewdcjr

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Right but according to Haidut's first post these stress hormones should subside after 1-4 days of adaptation to a higher caffeine intake if I'm reading the post right, but according to Nathan this wasn't the case for him.
 

Peata

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I tried higher doses in the winter and did not adapt at that time, but I feel my metabolism was not as good as it is now, plus I probably didn't have enough sugar with each caffeine dose.
 
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haidut

haidut

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narouz said:
post 98690
haidut said:
post 98687
Berk_Peat said:
post 98686 How long did it take you to get rid of fatty liver using caffeine?

I was taking both caffeine and vitamin K2. That was more than a year ago, and I was taking 400mg caffeine and 15mg - 30mg K2 (MK-4). Within a week I was able to pound 1,000mg+ daily and that "tolerance" never disappeared afterwards. Within 2 weeks I was able to skip meals without getting stress reaction symptoms, which means glycogen storage improved a lot. I am assuming the "tolerance" to caffeine the studies talk about is simply improved liver function and ability to metabolize caffeine quickly.

haidut-
Okay, so in your experience you used caffeine + k2.
Since then you (and others--Such for example)
have kicked around other "co-factors" or "synergists" or whatever for liver therapy.
Off the top of my head:
-b1
-b6 (or 5P5) I think Such likes this
-glycine
-famotidine
-methylene blue
-milk thistle maybe

(leaving aside niacinamide and aspirin for now,
operating under your theory that they may be unhelpful until liver healing happens...)

Would you like to add or subtract from the list?
Do you think they might all be used well together?
Or maybe not?

I used K2 and caffeine specifically for liver health. The other things you list are also beneficial but for liver health the most helpful would be the following, ranked in order of importance:

Caffeine, K2
Aspirin, glycine, MB
Taurine
Vitamin E
Theanine
Thiamine
BCAA
Pyridoxine
Biotin

Obviously, these can be used in tandem. Vitamin B1 is probably a good adjunct to caffeine as it helps control the lactate response some people get from it.
 
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haidut

haidut

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I think the overall message of the studies on caffeine is this - if one can't handle a decent dose of caffeine (200mg - 400mg), taken with food if necessary, without getting a stress response then glycogen stores are poor. Ability to store glycogen is largely determined by liver function, and liver function is a good approximator of overall health. Poor liver function means high estrogen, poor PUFA detoxification, poor conversion of T4 into T3, etc. Most people over 30 have some form of NAFLD - i.e. fatty liver. I posted a study long time ago showing that as little as 2mg/kg human dose taken for 2 weeks restored proper liver fat metabolism and got the liver lean again. Here is that study.
http://www.ncbi.nlm.nih.gov/pubmed/23929677

So, maybe the "adaptation" the studies above found was simply this - improved liver function and ability to store glycogen. Btw, thyroid hormone also triggers a stress response in people with poor liver function. So, the effect of caffeine is not to somehow innately cause a stress reaction but simply to push a poorly functioning organism beyond its ability to handle energetic demands. As liver function improves (and how long it takes is unique to each person), so does the ability to handle caffeine.
 

narouz

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haidut said:
I used K2 and caffeine specifically for liver health. The other things you list are also beneficial but for liver health the most helpful would be the following, ranked in order of importance:

Caffeine, K2
Aspirin, glycine, MB
Taurine
Vitamin E
Theanine
Thiamine
BCAA
Pyridoxine
Biotin

Obviously, these can be used in tandem. Vitamin B1 is probably a good adjunct to caffeine as it helps control the lactate response some people get from it.

Great, haidut.
Thanks!

(With the BCAA in this liver therapy context...about how much per day roughly?)
 
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haidut

haidut

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narouz said:
post 98912
haidut said:
I used K2 and caffeine specifically for liver health. The other things you list are also beneficial but for liver health the most helpful would be the following, ranked in order of importance:

Caffeine, K2
Aspirin, glycine, MB
Taurine
Vitamin E
Theanine
Thiamine
BCAA
Pyridoxine
Biotin

Obviously, these can be used in tandem. Vitamin B1 is probably a good adjunct to caffeine as it helps control the lactate response some people get from it.

Great, haidut.
Thanks!

(With the BCAA in this liver therapy context...about how much per day roughly?)

I'd say 6g - 9g daily based on animal studies. But if you are doing a liver "protocol" the substances towards the top are much better than BCAA. Glycine and taurine are much more liver protective and regenerative than BCAA.
 
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