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."
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."