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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. 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 which 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.

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).

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

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.

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. 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).

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. Which 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).

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

References

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Other References

• Editors of Publications International, Ltd. "Coffee Facts" HowStuffWorks, HowStuffWorks, 29 May 2008, recipes.howstuffworks.com/coffee-facts.htm.