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Dietary Caffeine. Most widely consumed drug in the world. 87% of individuals consume caffeine.Average intake 193mg/day for adults or 340ml of brewed coffee/day. Children: Soft drink consumption has increased by 48% from 1977 to 1998.. Frary CD. J. Am Diet Assoc. 2005 Jan;105(1):110-3. . . Caffeine.
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3. Dietary Caffeine Most widely consumed drug in the world.
87% of individuals consume caffeine.
Average intake 193mg/day for adults or 340ml of brewed coffee/day.
Children: Soft drink consumption has increased by 48% from 1977 to 1998.
Soft drinks comprise 10% of caloric intake in children
Soft drinks comprise 10% of caloric intake in children
4. Caffeine Once ingested, caffeine has a half-life of 3-5hr in humans. This is dependent on the individual, as well as their diet, duration and level of exposure to caffeine.
It is removed from the circulation by the p450 system in the liver. In this graph, we show caffeine concentration on the x-axis expressed on a log scale and the percent effect on the y –axis.
In the lower end of the range, we see the amount of caffeine ingested from a single cup of coffee, while the second line indicates toxic levels of caffeine. To reach toxic levels of caffeine, one would have to consume the equivalent of 75 cups of coffee.
As you can see from the graph, coffee effects a number of biochemical systems in the body. However, at concentrations found in the diet, they mediate the majority of their effects by the non-selective antagonism of adenosine receptors.
Adenosine is a metabolite of tissues that utilize ATP, so it is produced all over the body.
We have 4 subclasses of adenosine receptors, A1,A2a, A2b, A3 – differentially expressed in tissues. For example, adipose tissue primarily expresses A1 while the majority of receptors in muscle are A2.
75 cups of coffee a day tp reach toxic levels.
Similar structure to adenosine – ring stuructureOnce ingested, caffeine has a half-life of 3-5hr in humans. This is dependent on the individual, as well as their diet, duration and level of exposure to caffeine.
It is removed from the circulation by the p450 system in the liver. In this graph, we show caffeine concentration on the x-axis expressed on a log scale and the percent effect on the y –axis.
In the lower end of the range, we see the amount of caffeine ingested from a single cup of coffee, while the second line indicates toxic levels of caffeine. To reach toxic levels of caffeine, one would have to consume the equivalent of 75 cups of coffee.
As you can see from the graph, coffee effects a number of biochemical systems in the body. However, at concentrations found in the diet, they mediate the majority of their effects by the non-selective antagonism of adenosine receptors.
Adenosine is a metabolite of tissues that utilize ATP, so it is produced all over the body.
We have 4 subclasses of adenosine receptors, A1,A2a, A2b, A3 – differentially expressed in tissues. For example, adipose tissue primarily expresses A1 while the majority of receptors in muscle are A2.
75 cups of coffee a day tp reach toxic levels.
Similar structure to adenosine – ring sturucture
5. The differential expression of adenosine receptors helps to explain caffeine’s diverse effects in the body. Since it is so non-selective, it is a difficult drug to study.
In the liver, caffeine increases net hepatic glucose uptake, but also increases its lacate output.
In the kidneys, caffiene is a directic, situlating mild fliud loss
In the gut, caffeine slightly increases gut motility
In the heart, caffeine use slightly increases heart rate. It also has mild effects on blood pressure, increasing BP by 5-10 millimeter of mercury for the naïve user.
In adipose tissue, it stimulates lipolysis.
In the brain, caffeine crosses the blood brain barrier, altering mood.
Whole body basis, the combined effect is an increase in thermogenesis. Consuption of 5mg/kg body weight to a individual who does not regularly consume caffeine resuilts in an increased energy expenditure of ~100 calories.
Caffeine consumption is also know to decrease food consumption and have profound effects on carbodyhrate management.
The differential expression of adenosine receptors helps to explain caffeine’s diverse effects in the body. Since it is so non-selective, it is a difficult drug to study.
In the liver, caffeine increases net hepatic glucose uptake, but also increases its lacate output.
In the kidneys, caffiene is a directic, situlating mild fliud loss
In the gut, caffeine slightly increases gut motility
In the heart, caffeine use slightly increases heart rate. It also has mild effects on blood pressure, increasing BP by 5-10 millimeter of mercury for the naïve user.
In adipose tissue, it stimulates lipolysis.
In the brain, caffeine crosses the blood brain barrier, altering mood.
Whole body basis, the combined effect is an increase in thermogenesis. Consuption of 5mg/kg body weight to a individual who does not regularly consume caffeine resuilts in an increased energy expenditure of ~100 calories.
Caffeine consumption is also know to decrease food consumption and have profound effects on carbodyhrate management.
6. I’ve put together this summary slide of some of the recent findings from our laboratory…showing serum insulin concentrations during a 75 g OGTT in male subjects: either lean, obese or individuals with type 2 diabetes.
In all cases subjects ingested 5 mg of caffeine/kg body weight and 1 hour later consumed a 75 g oral glucose load
In both the lean and obese subjects caffeine resulted in a significantly elevated serum insulin response throughout the OGTT….this caffeine effect is especially dramatic in obese subjects as serum insulin is not even close to baseline levels at 2 hours post glucose load.
In type 2 diabetic subjects we also saw an increased insulin response with caffeine which was still present 3 hours post-glucose load. Again, blood glucose was also significantly elevated with caffeine ingestion, indicating an acute caffeine-induced insulin resistance in these subjects.
We think these findings may have important implications for those already experiencing insulin resistance, such as in obesity, type 2 diabetes and in pregnancy.
Such an impairment may be of particular concern in pregnancy, both with and without gestational diabetes mellitus, since an increase in insulin resistance and/or impairment in maternal glucose tolerance may negatively impact on fetal/neonatal outcome.
I’ve put together this summary slide of some of the recent findings from our laboratory…showing serum insulin concentrations during a 75 g OGTT in male subjects: either lean, obese or individuals with type 2 diabetes.
In all cases subjects ingested 5 mg of caffeine/kg body weight and 1 hour later consumed a 75 g oral glucose load
In both the lean and obese subjects caffeine resulted in a significantly elevated serum insulin response throughout the OGTT….this caffeine effect is especially dramatic in obese subjects as serum insulin is not even close to baseline levels at 2 hours post glucose load.
In type 2 diabetic subjects we also saw an increased insulin response with caffeine which was still present 3 hours post-glucose load. Again, blood glucose was also significantly elevated with caffeine ingestion, indicating an acute caffeine-induced insulin resistance in these subjects.
We think these findings may have important implications for those already experiencing insulin resistance, such as in obesity, type 2 diabetes and in pregnancy.
Such an impairment may be of particular concern in pregnancy, both with and without gestational diabetes mellitus, since an increase in insulin resistance and/or impairment in maternal glucose tolerance may negatively impact on fetal/neonatal outcome.
7. I’ve put together this summary slide of some of the recent findings from our laboratory…showing serum insulin concentrations during a 75 g OGTT in male subjects: either lean, obese or individuals with type 2 diabetes.
In all cases subjects ingested 5 mg of caffeine/kg body weight and 1 hour later consumed a 75 g oral glucose load
In both the lean and obese subjects caffeine resulted in a significantly elevated serum insulin response throughout the OGTT….this caffeine effect is especially dramatic in obese subjects as serum insulin is not even close to baseline levels at 2 hours post glucose load.
In type 2 diabetic subjects we also saw an increased insulin response with caffeine which was still present 3 hours post-glucose load. Again, blood glucose was also significantly elevated with caffeine ingestion, indicating an acute caffeine-induced insulin resistance in these subjects.
We think these findings may have important implications for those already experiencing insulin resistance, such as in obesity, type 2 diabetes and in pregnancy.
Such an impairment may be of particular concern in pregnancy, both with and without gestational diabetes mellitus, since an increase in insulin resistance and/or impairment in maternal glucose tolerance may negatively impact on fetal/neonatal outcome.
I’ve put together this summary slide of some of the recent findings from our laboratory…showing serum insulin concentrations during a 75 g OGTT in male subjects: either lean, obese or individuals with type 2 diabetes.
In all cases subjects ingested 5 mg of caffeine/kg body weight and 1 hour later consumed a 75 g oral glucose load
In both the lean and obese subjects caffeine resulted in a significantly elevated serum insulin response throughout the OGTT….this caffeine effect is especially dramatic in obese subjects as serum insulin is not even close to baseline levels at 2 hours post glucose load.
In type 2 diabetic subjects we also saw an increased insulin response with caffeine which was still present 3 hours post-glucose load. Again, blood glucose was also significantly elevated with caffeine ingestion, indicating an acute caffeine-induced insulin resistance in these subjects.
We think these findings may have important implications for those already experiencing insulin resistance, such as in obesity, type 2 diabetes and in pregnancy.
Such an impairment may be of particular concern in pregnancy, both with and without gestational diabetes mellitus, since an increase in insulin resistance and/or impairment in maternal glucose tolerance may negatively impact on fetal/neonatal outcome.
8. I’ve put together this summary slide of some of the recent findings from our laboratory…showing serum insulin concentrations during a 75 g OGTT in male subjects: either lean, obese or individuals with type 2 diabetes.
In all cases subjects ingested 5 mg of caffeine/kg body weight and 1 hour later consumed a 75 g oral glucose load
In both the lean and obese subjects caffeine resulted in a significantly elevated serum insulin response throughout the OGTT….this caffeine effect is especially dramatic in obese subjects as serum insulin is not even close to baseline levels at 2 hours post glucose load.
In type 2 diabetic subjects we also saw an increased insulin response with caffeine which was still present 3 hours post-glucose load. Again, blood glucose was also significantly elevated with caffeine ingestion, indicating an acute caffeine-induced insulin resistance in these subjects.
We think these findings may have important implications for those already experiencing insulin resistance, such as in obesity, type 2 diabetes and in pregnancy.
Such an impairment may be of particular concern in pregnancy, both with and without gestational diabetes mellitus, since an increase in insulin resistance and/or impairment in maternal glucose tolerance may negatively impact on fetal/neonatal outcome.
I’ve put together this summary slide of some of the recent findings from our laboratory…showing serum insulin concentrations during a 75 g OGTT in male subjects: either lean, obese or individuals with type 2 diabetes.
In all cases subjects ingested 5 mg of caffeine/kg body weight and 1 hour later consumed a 75 g oral glucose load
In both the lean and obese subjects caffeine resulted in a significantly elevated serum insulin response throughout the OGTT….this caffeine effect is especially dramatic in obese subjects as serum insulin is not even close to baseline levels at 2 hours post glucose load.
In type 2 diabetic subjects we also saw an increased insulin response with caffeine which was still present 3 hours post-glucose load. Again, blood glucose was also significantly elevated with caffeine ingestion, indicating an acute caffeine-induced insulin resistance in these subjects.
We think these findings may have important implications for those already experiencing insulin resistance, such as in obesity, type 2 diabetes and in pregnancy.
Such an impairment may be of particular concern in pregnancy, both with and without gestational diabetes mellitus, since an increase in insulin resistance and/or impairment in maternal glucose tolerance may negatively impact on fetal/neonatal outcome.
10. Weight Loss & Thermogenesis Does caffeine/coffee ingestion alter body composition?
100kcal/day – 10lbs/year?
Prospective Study: 58,157 & 12yr follow-up. Caffeine intake (2-4 y), weight, food frequency.
Caffeine & Weight- Men:
-0.43 kg, Women -0.41 kg
Obesity is a risk factor towards the development of metabolic diseases including type 2 diabetes, CVD, cancer, brain among others.
Ingestion of 600mg of caffeine results in increased energy expenditure of approx 100kcal?
Confounders: Age, sex, smoking, BMI, E Intake, activity, etc.Obesity is a risk factor towards the development of metabolic diseases including type 2 diabetes, CVD, cancer, brain among others.
Ingestion of 600mg of caffeine results in increased energy expenditure of approx 100kcal?
Confounders: Age, sex, smoking, BMI, E Intake, activity, etc.
11. Dietary Supplements 15.2% dietary weight loss supplement (21% ?, 10%?)
~74% caffeine or other stimulant, Average intake = 600mg + diet. Expenditure = 100kcal/d*
Greatest use, women 18-34 years – 17%, 11% in the past year
Average intake is 3 times that of dietary source – does not include sources of other dietary caffeine
Often done without supervision of phyician or other health care
Habituation?
suffer insomnia, anxiety, palpitations, depression and stomach problems Greatest use, women 18-34 years – 17%, 11% in the past year
Average intake is 3 times that of dietary source – does not include sources of other dietary caffeine
Often done without supervision of phyician or other health care
Habituation?
suffer insomnia, anxiety, palpitations, depression and stomach problems
12. Caffeine + Weight Loss Is there an additive effect?
90 obese subjects (76 female/14male), BMI = ~35, Age = 36yr.
1000kcal/day diet for 24wk with i) placebo ii) caffeine (600mg/d).
No difference in weight loss over 24wk. Next question – what about caffeine as a adjunct to weight loss? Is the addition of caffeine to a weight loss program more effective than each intervention alone?
Next question – what about caffeine as a adjunct to weight loss? Is the addition of caffeine to a weight loss program more effective than each intervention alone?
13. No long term effects on BP, HR, Plasma Renin, catecholamines.
Begin 12–24 h after sudden cessation of caffeine consumption, PEAK after 20–48 h.
Reversible.May include Headaches, Irritability, Anxiety, Dizziness, Impaired Concentration.
Biological responses are proportional to the number of receptors being occupied – altered caffeine responsiveness deveops
Increase in adenosine receptor populations in various tissues
Lipolytic reductions
Effects on long term weight maintainene are not known. No long term effects on BP, HR, Plasma Renin, catecholamines.
Begin 12–24 h after sudden cessation of caffeine consumption, PEAK after 20–48 h.
Reversible.May include Headaches, Irritability, Anxiety, Dizziness, Impaired Concentration.
Biological responses are proportional to the number of receptors being occupied – altered caffeine responsiveness deveops
Increase in adenosine receptor populations in various tissues
Lipolytic reductions
Effects on long term weight maintainene are not known.
14. http://www.muscletech.comhttp://www.muscletech.com
17. Coffee Coffee represents the major source of caffeine in the diet
54% of adults drink coffee daily
25% of adults drink coffee occasionally
Among regular coffee drinkers, average intake is 3.1 cups/day
Overall population:4.4 kg/year, 1.9cups/day men, 1.4 cups per day women
18. Coffee Nutrients
19. Controversy
23. This effect of DIFEQ is consistent with previous studies examining chlorogenic acids showing that they inhibit liver glucose-6-phosphatase (G-6-Pase), the enzyme that catalyzes the terminal reaction of glycogenolysis and gluconeogenesis (18–21). This effect of DIFEQ is consistent with previous studies examining chlorogenic acids showing that they inhibit liver glucose-6-phosphatase (G-6-Pase), the enzyme that catalyzes the terminal reaction of glycogenolysis and gluconeogenesis (18–21).
24. Whole Body Glucose Disposal
27. Antioxidants
28. Antioxidants Coffee contains natural antimicrobial agents against enterobacteria, and, therefore, could be used in foods as a natural preservative to control their growth.
The rationale for probiotics is that the body contains a miniature ecology of microbes, collectively known as the gut flora. The number of bacterial types can be thrown out of balance by a wide range of circumstances including the use of antibiotics or other drugs, excess alcohol, stress, disease, exposure to toxic substances, or even the use of antibacterial soap.
The gutflora is very complex. It has been estimated that up to 1000 bacterial species may be present in the GI tract of a healthy person, consisting of 100.000.000.000.000 cells, or 1014. Bacteria in the GI tract are not equally distributed. The stomach is not a favourable environment to bacteria because of the low pH of 2. Therefore it harbours a small number of bacteria (approx. 103 cfu = colony forming units per gram). Bacteria in the stomach are acid tolerant, like Lactobacilli, Streptococci and some yeasts.
The small intestine can be divided in 3 parts: duodenum, jejunum and ileum. Duodenum is still unfavourable to bacteria. Bile and pancreatic juice are added. Downstream the small intestine becomes more and more favourable and the amount of bacteria rises (up to 108 cfu per gram). Besides Lactobacilli and Streptococci; Enterobacteria, Bifidobacteria, Bacteroides and Fusobacteria can be found. The amount of oxygen declines and more strictly anaerobes (bacteria not tolerating the presence of oxygen) are present. The large intestine is strictly anaerobic. The highest bacterial
Coffee contains natural antimicrobial agents against enterobacteria, and, therefore, could be used in foods as a natural preservative to control their growth.
The rationale for probiotics is that the body contains a miniature ecology of microbes, collectively known as the gut flora. The number of bacterial types can be thrown out of balance by a wide range of circumstances including the use of antibiotics or other drugs, excess alcohol, stress, disease, exposure to toxic substances, or even the use of antibacterial soap.
The gutflora is very complex. It has been estimated that up to 1000 bacterial species may be present in the GI tract of a healthy person, consisting of 100.000.000.000.000 cells, or 1014.Bacteria in the GI tract are not equally distributed. The stomach is not a favourable environment to bacteria because of the low pH of 2. Therefore it harbours a small number of bacteria (approx. 103 cfu = colony forming units per gram). Bacteria in the stomach are acid tolerant, like Lactobacilli, Streptococci and some yeasts.
The small intestine can be divided in 3 parts: duodenum, jejunum and ileum. Duodenum is still unfavourable to bacteria. Bile and pancreatic juice are added. Downstream the small intestine becomes more and more favourable and the amount of bacteria rises (up to 108 cfu per gram). Besides Lactobacilli and Streptococci; Enterobacteria, Bifidobacteria, Bacteroides and Fusobacteria can be found. The amount of oxygen declines and more strictly anaerobes (bacteria not tolerating the presence of oxygen) are present. The large intestine is strictly anaerobic. The highest bacterial
29. Coffee contains natural antimicrobial agents against enterobacteria, and, therefore, could be used in foods as a natural preservative to control their growth.
The rationale for probiotics is that the body contains a miniature ecology of microbes, collectively known as the gut flora. The number of bacterial types can be thrown out of balance by a wide range of circumstances including the use of antibiotics or other drugs, excess alcohol, stress, disease, exposure to toxic substances, or even the use of antibacterial soap.
The gutflora is very complex. It has been estimated that up to 1000 bacterial species may be present in the GI tract of a healthy person, consisting of 100.000.000.000.000 cells, or 1014. Bacteria in the GI tract are not equally distributed. The stomach is not a favourable environment to bacteria because of the low pH of 2. Therefore it harbours a small number of bacteria (approx. 103 cfu = colony forming units per gram). Bacteria in the stomach are acid tolerant, like Lactobacilli, Streptococci and some yeasts.
The small intestine can be divided in 3 parts: duodenum, jejunum and ileum. Duodenum is still unfavourable to bacteria. Bile and pancreatic juice are added. Downstream the small intestine becomes more and more favourable and the amount of bacteria rises (up to 108 cfu per gram). Besides Lactobacilli and Streptococci; Enterobacteria, Bifidobacteria, Bacteroides and Fusobacteria can be found. The amount of oxygen declines and more strictly anaerobes (bacteria not tolerating the presence of oxygen) are present. The large intestine is strictly anaerobic. The highest bacterial
Coffee contains natural antimicrobial agents against enterobacteria, and, therefore, could be used in foods as a natural preservative to control their growth.
The rationale for probiotics is that the body contains a miniature ecology of microbes, collectively known as the gut flora. The number of bacterial types can be thrown out of balance by a wide range of circumstances including the use of antibiotics or other drugs, excess alcohol, stress, disease, exposure to toxic substances, or even the use of antibacterial soap.
The gutflora is very complex. It has been estimated that up to 1000 bacterial species may be present in the GI tract of a healthy person, consisting of 100.000.000.000.000 cells, or 1014.Bacteria in the GI tract are not equally distributed. The stomach is not a favourable environment to bacteria because of the low pH of 2. Therefore it harbours a small number of bacteria (approx. 103 cfu = colony forming units per gram). Bacteria in the stomach are acid tolerant, like Lactobacilli, Streptococci and some yeasts.
The small intestine can be divided in 3 parts: duodenum, jejunum and ileum. Duodenum is still unfavourable to bacteria. Bile and pancreatic juice are added. Downstream the small intestine becomes more and more favourable and the amount of bacteria rises (up to 108 cfu per gram). Besides Lactobacilli and Streptococci; Enterobacteria, Bifidobacteria, Bacteroides and Fusobacteria can be found. The amount of oxygen declines and more strictly anaerobes (bacteria not tolerating the presence of oxygen) are present. The large intestine is strictly anaerobic. The highest bacterial
30. Gut Peptides Gut expresses peptide hormones in endocrine cells.
Released after meal ingestion and stimulate insulin secretion.
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) CGA's putative impact on glucose absorption may reflect the ability of this compound to inhibit glucose-6-phosphate translocase 1, now known to play a role in intestinal glucose transport. Delayed glucose absorption may itself protect beta cells by limiting postprandial hyperglycemia -- though, owing to countervailing effects of caffeine on plasma glucose, and a paucity of relevant research studies, it is still unclear whether coffee ingestion blunts the postprandial rise in plasma glucose. More generally, diets high in "lente carbohydrate", or administration of nutraceuticals/pharmaceuticals which slow the absorption of dietary carbohydrate, should help preserve efficient beta cell function by boosting GLP-1 production, as well as by blunting the glucotoxic impact of postprandial hyperglycemia on beta cell function.
Glucose-dependent insulinotropic polypeptide secretion decreased throughout the experimental period (P < 0.005), and glucagon-like peptide 1 secretion increased 0-120 min postprandially (P < 0.01) after decaffeinated coffee consumption compared with the control. Glucose and insulin profiles were consistent with the known metabolic effects of caffeine. However, the gastrointestinal hormone profiles were consistent with delayed intestinal glucose absorption. CGA's putative impact on glucose absorption may reflect the ability of this compound to inhibit glucose-6-phosphate translocase 1, now known to play a role in intestinal glucose transport. Delayed glucose absorption may itself protect beta cells by limiting postprandial hyperglycemia -- though, owing to countervailing effects of caffeine on plasma glucose, and a paucity of relevant research studies, it is still unclear whether coffee ingestion blunts the postprandial rise in plasma glucose. More generally, diets high in "lente carbohydrate", or administration of nutraceuticals/pharmaceuticals which slow the absorption of dietary carbohydrate, should help preserve efficient beta cell function by boosting GLP-1 production, as well as by blunting the glucotoxic impact of postprandial hyperglycemia on beta cell function.
Glucose-dependent insulinotropic polypeptide secretion decreased throughout the experimental period (P < 0.005), and glucagon-like peptide 1 secretion increased 0-120 min postprandially (P < 0.01) after decaffeinated coffee consumption compared with the control. Glucose and insulin profiles were consistent with the known metabolic effects of caffeine. However, the gastrointestinal hormone profiles were consistent with delayed intestinal glucose absorption.
31. Specifically, coffee consumption has been shown to reduce the risk of diabetes by 20-50% depending on the population studied and the amount of coffee consumed. In men, risk reductions of 1.00, 0.98, 0.93, 0.71, 0.46 were noted with the consumption of 0, 1, 3-4, 5, and 6 cups of coffee respectively (95% Figure 2. – Effects of coffee consumption on serum ALT levels. All decrements in ALT were significant to p<0.001. Values in brackets beside ALT values represent estimated caffeine consumed in mg/day. Adapted from Ruhl et al. Gastroenterology, 128:24-32, 2005.
CI, 0.26 to 0.82; P= 0.007 for trend) (manuscript attached in appendix)(47). Much like the ALT-coffee results, these protective effects occurred in a dose-responsive manner. Such findings are dramatic and of interest as insulin resistance is hallmark to NASH. Specifically, coffee consumption has been shown to reduce the risk of diabetes by 20-50% depending on the population studied and the amount of coffee consumed. In men, risk reductions of 1.00, 0.98, 0.93, 0.71, 0.46 were noted with the consumption of 0, 1, 3-4, 5, and 6 cups of coffee respectively (95% Figure 2. – Effects of coffee consumption on serum ALT levels. All decrements in ALT were significant to p<0.001. Values in brackets beside ALT values represent estimated caffeine consumed in mg/day. Adapted from Ruhl et al. Gastroenterology, 128:24-32, 2005.
CI, 0.26 to 0.82; P= 0.007 for trend) (manuscript attached in appendix)(47). Much like the ALT-coffee results, these protective effects occurred in a dose-responsive manner. Such findings are dramatic and of interest as insulin resistance is hallmark to NASH.
32. Hepatic Glucose Management
33. Net Hepatic Glucose Fractional Extraction
35. Dr. Terry Graham, University of Guelph
Dr. David Wasserman, Vanderbilt University
Dr. Adriana Farah, University of Rio de Janeiro
Elizabeth Sellars, University of Arkansas
Shearer Laboratory, University of Calgary
National Coffee Association
