#acl 3891E,3887E,3813E:read,write Default Itt írjon a(z) Coffee_drinking-ról/ről '''Physiological Effects of Drinking Coffee in Higher Amounts''' <> == Coffee – Background and Introduction == ----- As the world evolves, one thing remains certain and that’s the average person’s love and dependency of coffee. With this drink being the beverage of choice each day for more than 107 million people drinking it daily and over 400 million cups of coffee consumed each year (Editors of Publications International, Ltd 2008). When it comes to coffee, you’ll see it in the hands of students, doctors, teachers, moms, dads –– unmistakably we can see almost everyone drinking coffee in their day to day lives. It’s no surprise the world’s scientists and researchers are always discovering more and more about this specific stimulant. Coffee is a complex mixture of chemicals containing significant amounts of chlorogenic acid and caffeine. It is a unique blend of carbohydrates, lipids, nitrogenous compounds, vitamins, minerals, alkaloids, and phenolic compounds [[ (Higdon, Frei 2007) ]]. Research suggests that coffee consumption may help prevent several chronic diseases, such as type 2 diabetes mellitus, liver disease, and Parkinson’s disease. However, when coffee is consumed in high doses, it is correlated with an increase in cardiovascular disease risk factors, including blood pressure and plasma homocysteine. Consuming 3-4 cups of coffee a day is considered to be moderate amounts of caffeine. Such doses are not particularly associated with health risks, however, it is known that children, the elderly, and adults with hypertension are more vulnerable to the side effects of caffeine. Coffee contains several micronutrients such as magnesium, potassium, niacin, and vitamin E, which are known to contribute to beneficiary health effects. The effect of coffee is dependent on many factors and not all case studies are going to have the same results due to the high amount of limiting factors. This includes health and underlying medical conditions, age, gender, diet, lifestyle (including smoking and alcohol intake), and whether the subject is a habitual or low/non-user of coffee. == Coffee’s Main Component: Caffeine == ----- It can be presumed that 1 cup of coffee consists of 100mg of caffeine, please note its structure in Figure 1.1. When it comes to caffeine, it is almost completely absorbed in the stomach and small intestines. After that process is completed, it is then distributed to all tissues, including the brain. Primary metabolism of caffeine occurs in the liver via cytochrome P450 enzyme which converts caffeine into paraxanthine and methylxanthine and various other compounds. Caffeine is a purine alkaloid that exerts most of its biological effects via the antagonism of A1 and A2 subtypes of the adenosine receptor. These receptors are expressed in the basal ganglia, mainly involved and dealing with the motor control. Adenosine is an endogenous neuromodulator which functions as a general inhibitor of neuronal activity (Higdon, Frei 2007). Caffeine’s psychostimulant properties are due to its ability to interact with various neurotransmissions in the brain, thus promoting behavioral functions such as attention, mood, and arousal (Fisone, Usiello 2003). Caffeine stimulates arousal by blocking the A1 receptor-mediated inhibition of cholinergic neurons involved in the regulation of cortical activity. The ability of caffeine to stimulate cortical activity enhances vigilance and information processing. Evidence has also been provided to show that caffeine delays fatigue during exercise, which is due to its production of biphasic stimulation of locomotor activity. {{attachment:caffeine1.jpg}} ==== Figure 1.1: Molecular structure of Caffeine ==== === Other Physiological Effects of Caffeine === ---- Caffeine and theophylline both act as competitive inhibitors of cyclic nucleotide phosphodiesterase isoenzymes. Their affinity for phosphodiesterase, however, is low, and thus results in high concentrations of caffeine being required to produce significant effects. Caffeine is also known to mobilize calcium ions from intracellular stores, an effect mediated by the activation of ryanodine-sensitive channels. Caffeine inhibits benzodiazepine binding to GABA receptors. Caffeine increases extracellular dopamine in the striatum, resulting in increased locomotion. === Cafestol and Kahweol === ---- These diterpenes may be extracted from ground coffee during brewing. High levels may be encountered in unfiltered coffee, whereas filtered/instant coffee only contains around 0.5 mg of diterpenes per cup. Studies show that around 70% of diterpenes are absorbed intestinally. Consumption of cafestol and kahweol in coffee has been found to result in persistent increases in cholesterol ester transfer protein (CETP) activity, which may contribute to an increase in low-density lipoprotein cholesterol. CETP transfers cholesteryl esters from HDL to the apolipoprotein B-containing lipoproteins, LDL and VLDL. Cafestol mainly elevates serum cholesterol and triacylglycerols, whilst kahweol has little additional effect. Both cafestol and kahweol elevate liver alanine aminotransferase level. This indicates that lipid metabolism and liver function may be affected by coffee diterpenes (Urgert, Katan 1995). To better understand the chemical structures and makeup of Kahweol and Cafestol, reference Figure 1.2. {{attachment:Kahweol + cafestol1.jpg}} ==== Figure 1.2: Molecular structures of Kahweol and Cafestol ==== === Chlorogenic Acid === ---- Chlorogenic acids are a family of esters formed between quinic and trans-cinnamic acids, which are an important group of dietary phenols. The chlorogenic acid content of a cup of coffee has been reported to range from 70-350 mg, providing around 35-75mg of caffeic acid. There is 33% of chlorogenic acid and 95% of caffeic acid that is absorbed intestinally. Thus around 2/3rd of ingested chlorogenic acid reaches the colon where it is broken down by colonic microflora. It is likely hydrolyzed to caffeic acid and quinic acid (Higdon, Frei 2007). Both chlorogenic and caffeic acid are known for their antioxidant, anti-inflammatory, and inhibitory effects. Certain studies have shown how caffeic acid inhibits the rupture and hemolysis of erythrocytes (Onhishni, Toda 1993). == Effects of Caffeine on the Body == ----- ||||||'''Table 1.1 Summarizing the impacts of caffeine on bodily functions'''|| ||'''OUTCOME'''||'''IMPACT OF CAFFEINE'''|| ||'''Cognitive effects''''||More effective in withdrawn and fatigued individuals|| ||'''Cardiovascular function'''||Dose dependent effects on blood pressure and heart rate, can be harmful|| ||'''Vascular system'''||Causes vasoconstriction and can increase risk of myocardial ischemia|| ||'''Reproductive effects'''||High caffeine can increase the risk of a miscarriage|| ||'''Birth weight'''||Can result in lower birth weight|| ||'''Sleep'''||Disturbed sleep pattern|| ||'''Anxiety'''||Effects on CNS result in anxiety-like symptoms|| ||'''Physical Performance'''||Increased tolerance and fatigue resistance|| === Table 1.1: Summarizing the impacts of Caffeine on bodily functions === === Coronary Heart Disease === ---- Some case studies proved that high coffee intakes are associated with increased risk of coronary heart disease or myocardial infarction. However, some other studies have concluded that there is absolutely no correlation between the two. Eight case-control studies found that coronary heart disease risk was 40-60% higher in those who consumed 5 or more cups of coffee daily, compared to those who did not drink coffee (Higdon, Frei 2007). One case study found a J-shaped relationship between coffee intake levels and the risk of developing acute coronary syndrome. The odds of being diagnosed were three times higher in people who drank 600 ml of coffee daily, when compared to those who did not drink coffee. Another case study proved that people who suffered from coronary artery disease and also drank 10 cups of coffee daily, had a significant increase in the risk of sudden cardiac arrest. As previously mentioned, cafestol and kahweol are responsible for increasing the body’s overall serum and LDL cholesterol levels. These are some of the primary cardiovascular disease risk factors. Another important coronary risk factor is elevated plasma total homocysteine concentration levels. Controlled clinical trials have confirmed the homocysteine-raising effects of relatively high intakes of coffee. The results of the trial suggest that caffeine and chlorogenic acid contribute to this effect. In a certain case study, abstention from coffee consumption for 6 weeks resulted in an 11% decrease in plasma homocysteine levels (Higdon, Frei 2007). With each 2-3 cups of coffee a day, it has been found to increase systolic and diastolic blood pressure, which will result in possible hypertension. This is also another recognized risk factor for CHD and stroke. To understand the effects of coffee on the body more clearly and thoroughly, refer to Table 1.1. === Effect on Digestion === ---- In a study that Roth and Ivy conducted about coffee and peptic ulceration, they concluded that when consuming large quantities of coffee, there's a predisposition of certain prone individuals to peptic ulceration, and coffee was the cause of exacerbating pre-existing ulcers. In the study, prolonged stimulation of caffeine was administered in beeswax. The development of gastric ulcers in cats and guinea pigs was provoked. Each patient that exhibited active duodenal ulcers responded to oral caffeine with a greater and more prolonged secretion of gastric acid (Wagner, SM, et al. 1978). When it comes to black coffee, it has almost no buffering capacity, and while the maximum stimulation of caffeine ends up producing only half or less of the acid output, which maximal stimulation with pentagastrin can end up provoking. The acid that's secreted in the end will be largely unbuffered (unless creamers, milk, or any food is taken with coffee). Coffee, as well as decaffeinated coffee, are much stronger stimulators of acid secretion than caffeine is on its own. This information leads to the conclusion that there’s a potent gastric acid stimulant in coffee, which is not just caffeine and that coffee is more than just simply flavorful caffeine (Wagner, SM, et al. 1978). Many have mentioned coffee being a cause of dyspeptic symptoms, whereas there being no actual connection found between coffee and dyspepsia. Heartburn obviously being the most frequently reported symptom time and time again after drinking coffee. Coffee can stimulate gastrin release and gastric acid secretion, but there are numerous studies on the effect on lower esophageal sphincter pressure yield that end up conflicting these claims. Caffeine within coffee can come with positive impacts as well, as seen in Figure 1.3. Cancer is already something near impossible to tackle still to this day, but with more and more research conducted daily, waves have been made (such as coffee being able to help reduce the risk). Coffee is responsible for inducing cholecystokinin release and contracting the gallbladder, which seems to be the explanation of why patients that have symptomatic gallstones often avoid drinking coffee. This drink can also increase rectosigmoid motor activity within 4 minutes after ingestion in some people. With coffee, it also stimulates the contraction of the and the motor activity in the colon (Boekema, PJ, et al. 1999). === Effect on Gastrointestinal Tract === ---- The gastrointestinal tract (also known as the GI tract) is an organ system that takes food into the body and digests it to both extract and absorb energy and nutrients. When it comes to the digestive system, your colon acts as a muscle, and since caffeine is responsible for stimulating the muscles, the caffeine intake the body goes through can stimulate peristalsis (which is in control of the rhythmic contractions of the GI tract. Phosphodiesterases (also known as PDEs) are a supersized group of enzymes that regulate intracellular signaling through metabolic inactivation. The signaling that goes through metabolic inactivation involves the cyclic adenosine monophosphate (cAMP) and also cyclic guanosine monophosphate (cGMP). Phosphodiesterases are known to normally catalyze the breakdown of tissue cyclic nucleotides, in which the effect of caffeine can be looked at for the increases in cyclic nucleotide contractions. When it comes to the relaxation of the lower esophageal sphincter, stimulating the gastric acid secretion, as well as stimulating the intestinal secretion, they have each been known to occur with an increased cyclic adenosine monophosphate (cAMP) concentrations in the relevant tissues (Wagner, SM, et al. 1978). {{attachment:IMG_2283.jpg}} ==== Figure 1.3: The reduced risk of liver cancer based on drinking coffee ==== === Effect on Mood and Cognitive Performance === ---- Caffeine has an overall effect of increasing alertness and wakefulness. It can inhibit the binding of both adenosine and benzodiazepine receptor ligands to brain membranes. These neurotransmitters usually slow down brain activity, however, if this is inhibited the effect is lessened. Caffeine also affects other neurotransmitters, such as, noradrenaline, dopamine, serotonin, acetylcholine, glutamate, and gamma‐aminobutyric acid (Fredholm et al. 1999). Caffeine has been shown to increase short term memory (Ritchie K, 2007) and reaction time (Kamimori GH, 2015). A positive mood and less feeling tired were also found. Some of the symptoms of caffeine intake within the CNS resemble an anxiety attack, for example: agitation, headaches, irritability, and occasional muscle twitches, also known as coffee nerves (Ritchie JM, 1970). Insomnia is also a side effect. Withdrawal symptoms can also be seen, such as irritability, nervousness, lethargy, and restlessness (Goldstein A, 1969). One case study compared the cognitive effects in habitual and non-users to test increased tolerance. It was found that habitual users showed greater cognitive and mood effects. This was not predicted since theoretically tolerance would build with increased consumption thus decreasing cognitive and mood effects (Childs & de Wit 2006). === Effect on Physical Performance === ---- The International Olympic Committee, until 2004, had restricted coffee consumption to about 5 cups a day, as it was believed that caffeine was an ergogenic compound, resulting in enhanced performance, thus giving an advantage to the athlete. One mechanism in which caffeine can impact physical performance is due to increased fatty acid oxidation, which would spare glycogen and prolong the duration of the exercise. (Nehlig & Debry 1994; Paluska 2003). Caffeine has also been found to increase plasma free fatty acids thus increasing insulin resistance (Norager et al. 2005). Muscle contractions can also be enhanced via changes to sodium, calcium and potassium concentrations (Magkos & Kavouras 2005), and increased tolerance to fatigue via the production of plasma catecholamines and inhibition of adenosine receptors (Nehlig & Debry 1994). To better understand this part of caffeine's effect on physical performance, reference Figure 1.4. {{attachment:IMG_2290.jpg}} ==== Figure 1.4: Effect of Physical performance ==== === Effect on Reproduction, Pregnancy, and Infancy === ---- Caffeine is readily absorbed by the mother’s GI tract, and then passed across the placenta to the fetus. The exposure in the fetus is prolonged due to the increased ½ life in the fetus. This is due to the fact that there are no enzymes to oxidize the methylated xanthines (James and Paull 1985). Caffeine increases the level of cAMP in the fetus which interferes with cell growth and development (Karen 2000). It may also block adenosine receptors which maintains the availability of tissue oxygen, blockage could lead to hypoxia. In a study it was found that two cups of coffee increased the level of epinephrine in the mother and decreased placenta blood flow (Fortier et al. 1993). The risk of spontaneous abortions can also be increased. In one study it was found that pregnancy loss increased by 8% for every 2 additional cups of coffee per day (Chen LW, et al,2016). Various studies showed a correlation between coffee consumption and low birth weight (Hoyt AT et al 2014). === Vascular System Effects === ---- Caffeine can improve endothelial cell function at rest due to increased intracellular calcium concentrations, which stimulates endothelial nitric oxide synthase, thus stimulating the endothelial cells to produce nitric oxide. The nitric oxide then diffuses into vascular smooth muscle, below the endothelial cells, causing vasodilation (Sumpio BE et al 2002). Caffeine can also bind directly to the vascular smooth muscle cell receptors and cause vasoconstriction (Echeverri D, et al 2010). Consuming caffeine immediately before or during exercise can increase the risk of myocardial ischemia (Namdar M et al 2009). It reduces myocardial blood flow. This reduction is due to caffeine’s ability to block adenosine receptors that modulate coronary vasomotor tone. This vasoconstrictive effect is more pronounced in non-habitual drinkers. When caffeine blocks adenosine receptors, it reduces the ability of the coronary arteries to improve their flow commensurate with the increased myocardial demand of exercise, which could result in supply-demand ischemia (Higgins JP, et al 2013). === Effects on Thermogenesis & energy intake === ---- Caffeine increases catecholamines through the sympathetic nervous system and adenosine and also increases cyclic adenosine monophosphate through phosphor-diesterase which all have a net effect of increasing energy expenditure, lipolysis, satiety, and decreasing hunger. This can be seen with reference to Figure 1.5. {{attachment:Diagram.jpg}} ==== Figure 1.5: Effects on thermogenesis and energy intake ==== == References == ----- * Boekema.; PJ. et al. (1999): Coffee and Gastrointestinal Function: Facts and Fiction. A Review. Coffee and Gastrointestinal Function: Facts and Fiction. A Review. 230: (25) 9 * Brazier JL.; Ritter J.; Berland M.; Khenfer D.; Faucon G. (1983): Pharmacokinetics of caffeine during and after pregnancy. Dev Pharmacol Ther. 6: 315–22 * Chen LW.; Wu Y.; Neelakantan N.; Chong MF.; Pan A.; van Dam RM. (2016): Maternal caffeine intake during pregnancy and risk of pregnancy loss: a categorical and dose-response meta-analysis of prospective studies. Public Health Nutr. 19: 1233–44 * Childs E.; De Wit H. (2006): Subjective, behavioral, and physiological effects of acute caffeine in light, nondependent caffeine users. Psychopharmacology 185: 514–23 * Echeverri D.; Montes FR.; Cabrera M.; Galan A.; Prieto A. (2010): Caffeine’s vascular mechanisms of action. Int J Vasc Med. * Fisone.; G. et al. (2004): Caffeine as a Psychomotor Stimulant: Mechanism of Action. Cellular and Molecular Life Sciences (CMLS) 61: (7-8) 857–872 * Fredholm BB.; Battig K.; Holman J. et al. (1999): Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacological Reviews 51: 83–133 * Goldstein A.; Kaizer 5. (1969): Psychotropic effects of caffeine in man, III: a questionnaire survey of coffee drinkers and its effects in a group of housewives. Clin Pharmacol Ther 10: 477-488 * Higdon, J. V.; Balz F. (2006): Coffee and Health: A Review of Recent Human Research. Critical Reviews in Food Science and Nutrition 46: (2) 101-123 * Higgins JP, Babu KM. (2013): Caffeine reduces myocardial blood flow during exercise. Am J Med. * Hoyt AT.; Browne M.; Richardson S.; Romitti P.; Druschel C. (2014): National Birth Defects Prevention Study. Maternal caffeine consumption and small for gestational age births: results from a population-based case-control study. Matern Child Health J (18) 1540–51 * Kamimori GH.; McLellan TM.; Tate CM.; Voss DM.; Niro P.; Lieberman HR. (2015): Caffeine improves reaction time, vigilance, and logical reasoning during extended periods with restricted opportunities for sleep. Psychopharmacology (Berl) * Magkos F.; Kavouras SA. (2005): Caffeine use in sports, pharmacokinetics in man, and cellular mechanisms of action. Critical Reviews in Food Science and Nutrition 45: 535–62 * Namdar M.; Schepis T.; Koepfli P.; Gaemperli O.; Siegrist PT.; Grathwohl R. et al. (2009): Caffeine impairs myocardial blood flow response to physical exercise in patients with coronary artery disease as well as in age-matched controls. PLoS One. * Nehlig A.; Debry G. (1994): Caffeine and sports activity: a review. International Journal of Sports Medicine 15: 215–23. * Norager CB.; Jensen MB.; Madsen MR. et al. (2005): Caffeine improves endurance in 75‐yr‐old citizens: a randomized, double‐blind, placebo‐controlled, crossover study. Journal of Applied Physiology 99: 2302–6 * Paluska SA. (2003): Caffeine and exercise. Current Sports Medicine Reports 2: 213–19. * Ritchie JM. (1970): Central nervous system stimulants, II: the xanthines, in The Pharmacological Basis of Therapeutics, 4th ed. Edited by Goodman LS. Gilman A. New York, Macmillan Publishing Co. 358-370 * Ritchie K.; Carriere I.; de Mendonca A.; Portet F.; Dartigues JF.; Rouaud O. et al. (2007): The neuroprotective effects of caffeine: a prospective population study. The Three-City Study. Neurology. * Sato.; Yuki. et al. (2011): In Vitro and in Vivo Antioxidant Properties of Chlorogenic Acid and Caffeic Acid. ScienceDirect. 403: (1-2) 136–138 * Sumpio BE.; Riley JT.; Dardik A. (2002) Cells in focus: endothelial cell. Int J Biochem Cell Biology. * Urgert.; R. et al. (1995): Effects of Cafestol and Kahweol from Coffee Grounds on Serum Lipids and Serum Liver Enzymes in Humans. The American Journal of Clinical Nutrition. 61: (1) 149–154 * Wagner.; SM. et al. (1978): Coffee and Gastrointestinal Tract. Gastro Journals - Editorials. 75: (3) 529–530 == Other References == ----- * Editors of Publications International, Ltd. "Coffee Facts" HowStuffWorks, HowStuffWorks, 29 May 2008, recipes.howstuffworks.com/coffee-facts.htm. == Figures == ----- * Figure 1.1: Molecular structure of Caffeine Drawn by Lisa Bonaci * Figure 1.2: Molecular structures of Kahweol and Cafestol Drawn by Lisa Bonaci * Table 1.1: Summarizing the impacts of Caffeine on bodily functions Drawn by Niamh Cox * Figure 1.3: The reduced risk of liver cancer based on drinking coffee drawn by Kathrina Boleratzky * Figure 1.4: Effect of Physical performance Drawn by Kathrina Boleratzky * Figure 1.5: Effects on thermogenesis and energy intake Drawn by Lisa Bonaci