1.CAFFEINE Very high doses are used, often in

1.CAFFEINE PLASMA CONCENTRATION AMONG TEAAnd COFFEE USERSEach day, billions of people rely on caffeine for a wake-up boost.

In fact, this natural stimulant is one of the most commonly used ingredients in the world. Caffeine is often talked about for its negative effects on sleep and anxiety. However, studies also report that it has various health benefits.Caffeine is a natural stimulant most commonly found in tea, coffee and cacao plants. It works by stimulating the brain and central nervous system, helping you to stay alert and preventing the onset of tiredness.

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Coffee was reportedly discovered many years later by an Ethiopian shepherd who noticed the extra energy it gave his goats.Nowadays, 80% of the world’s population consumes a caffeinated product each day, and this number goes up to 90% for adults (1).1.1.

Structure of Caffeine Caffeine, nitrogenous organic compound of the alkaloid group, substances that have marked physiological effects. Caffeine is chemically related to the adenine and guanine bases of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) (4). Caffeine has another names such as 1,3,7-Trimethylxanthine, Coffeinum Purrum, Coffeinum N, Caffedrine, Dexitac and Vivarin. Caffeine has molecular formula C8H10N4O2  and molecular Weight 94.194 g/mol.(5) Figure (1): Structure of caffeine 1.

2.Sources of caffeineCaffeine is an alkaloid occurring naturally in some 60 plant species, of which cocoa beans, kola nuts, tea leaves and coffee beans are the most well-known. Other natural sources of caffeine include yerba maté, guarana berries, guayusa, and the yaupon holly. Caffeine is added to many popular soft drinks, and is also a component of a number of pharmacological preparations and over-the-counter medicines including analgesics, diet-aids, and cold/flu remedies (6).1.

3.Caffeine uses and benefits Caffeine is most commonly used to improve mental alertness, but it has many other uses. Caffeine is used by mouth or rectally in combination with painkillers (such as aspirin and acetaminophen) and a chemical called ergotamine for treating migraineheadaches. It is also used with painkillers for simple headaches and preventing and treating headaches after epidural anesthesia.Some people use caffeine for asthma, gallbladder disease, attention deficit-hyperactivity disorder (ADHD), shortness of breath in newborns, and low blood pressure. Caffeine is also used for weight loss and type 2 diabetes. Very high doses are used, often in combination with ephedrine, as an alternative to illegal stimulants(7).

1.3.1.Caffeine and cardiovascular disease The majority of prospective cohort studies looking at coffee/caffeine consumption did not find any adverse effect of coffee/caffeine consumption on cardiovascular function. There was no association between caffeine consumption and arrhythmias , atrial fibrillation  and cardiac variability showing that there is no need to abstain from caffeine in those populations.  Moderate coffee consumption is inversely associated with risk of heart failure.1.

3.2.Caffeine and Blood pressure Caffeine has a slight, transient hypertensive effect. At low doses. It is useful in person with hypotension(6).1.4.

Mechanism of caffeine actionOnce consumed, caffeine is quickly absorbed from the gut into the bloodstream. From there, it travels to the liver and is broken down into compounds that can affect the function of various organs. That being said, caffeine’s main effect is on the brain. It functions by blocking the effects of adenosine, which is a neurotransmitter that relaxes the brain and makes you feel tired(2).Normally, adenosine levels build up over the day, making you increasingly more tired and causing you to want to go to sleep.

Caffeine helps you stay awake by connecting to adenosine receptors in the brain without activating them. This blocks the effects of adenosine, leading to reduced tiredness.It may also increase blood adrenaline levels and increase brain activity of the neurotransmitters dopamine and norepinephrine(3).This combination further stimulates the brain and promotes a state of arousal, alertness and focus. Because it affects your brain, caffeine is often referred to as a psychoactive drug.

Additionally, caffeine tends to exert its effects quickly(1).Figure (2): Mechanism of action of caffeine1.5.Caffeine metabolismOnce ingested, caffeine is rapidly absorbed from the gastrointestinal tract into the bloodstream and becomes metabolized in the liver . Bonati and others found that caffeine is extensively metabolized by the liver (99%) to form 3 major metabolites 3,7-dimethylxanthine, 1,7-dimethylxanthine(paraxanthine), and 1,3-dimethylxanthine(theophylline) showing that 70 to 100 mg of caffeine exhibit a linear pharmacokinetics(1). Figure(3): Caffeine metabolism  1.6.Side effects of caffeine  Caffeine is possibly unsafe when taken by mouth for a long time or in fairly high doses.

Caffeine can cause insomnia, nervousness and restlessness, stomach irritation, nausea and vomiting, increased heart rate and respiration, and other side effects. Caffeine can make sleep disorders in patients with acquired immunodeficiency syndrome (AIDS) worse. Larger doses might cause headache, anxiety, agitation, chest pain, and ringing in the ears.Caffeine is likely unsafe when taken by mouth in very high doses as it can cause irregular heartbeats and even death.

1.6.1.Pregnancy and breast-feeding Caffeine is possibly safe in pregnant or breast-feeding women when used daily amounts of less than 200 mg. Consuming larger amounts during pregnancy or when breast-feeding is possibly unsafe. When consumed in larger amounts during pregnancy, caffeine might increase the chance of miscarriage and other problems. Also, caffeine can pass into breast milk, so nursing mothers should closely monitor caffeine intake to make sure it is on the low side.

High intake of caffeine by nursing mothers can cause sleep disturbances, irritability, and increased bowel activity in breast-fed infants. 1.6.2.

Anxiety disordersCaffeine might make these conditions worse. Use with care.1.6.

3.Bleeding disordersThere is concern that caffeine might aggravate bleeding disorders. Use caffeine with care if you have a bleeding disorder.1.6.

4Heart conditionsCaffeine can cause irregular heartbeat in sensitive people. Use caffeine with caution.1.6.

5.Diabetes: Some research suggests that caffeine may affect the way the body uses sugar and might worsen diabetes. However, the effect of caffeinated beverages and supplements has not been studied. If you have diabetes, use caffeine with caution. 1.6.6.Diarrhea Caffeine, especially when taken in large amounts, can worsen diarrhea.

 1.6.7.Epilepsy People with epilepsy should avoid using caffeine in high doses. Low doses of caffeine should be used cautiously. 1.

6.7.Glaucoma Caffeine increases the pressure inside the eye. The increase occurs within 30 minutes and lasts for at least 90 minutes after drinking caffeinated beverages. 1.6.8High blood pressure Consuming caffeine might increase blood pressure in people with high blood pressure.

However, this effect might be less in people who use caffeine regularly. 1.6.9.Weak bones (osteoporosis) Caffeine can increase the amount of calcium that is flushed out in the urine. If you have osteoporosis or low bone density, caffeine should be limited to less than 300 mg per day(7).  Reverences 1. ABA American Beverage Assoc.

Available from: http://www.ameribev.org/all-about-beverage-products/index.aspx. Accessed 2008 Nov 15. 2.

 The role of adenosine in the regulation of sleep.Huang ZL, Urade Y, HayaishiO.Curr Top Med Chem. 2011; 11(8):1047-57 3. J Neurochem. 2008 May;105(4):1067-79. Epub 2007 Dec 18. 4.

 Mitchell, Diane C.; Knight, Carol A.; Hockenberry, Jon; Teplansky, Robyn; Hartman, Terryl J. (1 January 2014). “Beverage caffeine intakes in the U.S”.

 Food and Chemical Toxicology. 63: 136–142. doi:10.

1016/j.fct.2013.10.042 5. Nathanson JA: Caffeine and related methylxanthines: possible naturally occurring pesticides. Science. 1984 Oct 12;226(4671):184-7.

. 6. Fredholm B.B. et al. (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev, 51:83-133.

 7. Davis, J. K. and Green, J. M. Caffeine and anaerobic performance: ergogenic value and mechanisms of action. Sports Med 2009;39(10):813-832. View abstract.

 8. 2001 by the National Academy of Sciences. All rights reserved.Bookshelf ID: NBK223808