Effects of alcohol and caffeine on blood coagulation

Introduction

An energy drink is a type of beverage containing stimulant drugs chiefly caffeine, which is marketed as proving mental and physical stimulation they may or may not be carbonated and may also contain sugar or otherwise sweeteners, herbal extracts and amino acids. They are subsets of layers of energy products which includes bars and gels. There are many bonds and varieties of energy drinks such as tea, coffee and other naturally caffeinated beverages like four loko used to contain caffeine and other stimulants however such drinks were banned in the united state in 2010, (United States Food and Drug Administration,2010).

Energy drinks are also popular as drinks mixed –red bull and vodka is a popular combination in US, a product called “four loko ” mixed beer with caffeine while kahlua is a coffee flavoured alcoholic beverage (Roberto, 2014). Some energy drinks have no caffeine but instead use the stimulant Taurine which is equivalent of caffeine.

Coagulation (clotting) is the process by which blood changes from liquid to gel and it potentially result in haemostasis, the cessation of blood loss from a damaged vessel followed by repair. The mechanism of coagulation involves activation, adhesion and aggregation of platelets along with deposition and maturation of fibrin. Disorders of coagulation are disease state which can result in bleeding (haemorrhage or bruising) or obstructive clotting (thrombosis) (David,Negel, Michael and Denise, 2009).

Coagulation factors are proteins in the blood that are essential for coagulation, clotting factor circulates in the blood as inert protein until the coagulation cascade initiate their conversion into participants into blood clotting. The clotting factor interact with one another as well as other enzymes in the blood, notably fibrin and thrombin form blood clot. The liver produce clotting factor such as i (firinogen)  ii (prothrombin) proaccelerin), factor vii (thromboplastin) factor ix (plasma thromboplastin) and factor x (stuart power factor).

Deficiencies of specific clotting factors cause coagulation disorder such as haemophilia (excessive bleeding) and thrombophilia (excessive clot formation) coagulation factors are named according to a system of roman numerals which relates to their order of discovery rather than their order of activation. Each coagulation factor also has one or more synonymy which may be used.

Factor most common synonymy

1. Fibrinogen
2. Prothrombin
3. Tissue thromboplastin
4. Calcium ions
5. Proaccelerin/ labile factor
6. Proconvertin /cothromboplastin
7. Anti-haemophilic factor (AHF)
8. Christmas factor
9. Staurt power factor
10. Plasma thromboplastin antecedent
11. Hageman factor
12. Fibrin stabilizing factor

(Baker, Pallister and Silverston, 2001).

Energy drinks are beverages that contain stimulant drugs which are marketed as providing mental and physical stimulant (FDA, 2010)

History of energy drink

Energy drinks were an active subset of the early soft drink industry for instance coca-cola’s name was derive from it two active ingredient both known stimulant: coca leaves and kola nuts (a source of caffeine). In UK Lucozadeenergy drink was originally introduced in 1929 as a hospital drink replenishing lost energy.

In 1985 jolt cola was introduced in the United State its marketing strategy centred on drinks caffeine content billing it as a means to promote wakefulness. (Official Sold, 2011). On August 14 2012 the word Energy drinks was listed for the first in Merriam Webster’s collegiate dictionary (Italien and Leane, 2012).

Alcohol

This is a class of chemical compound, alcohol is any organic compound in which the hydroxyl functional group (-OH) is bound to a saturated carbon atom, the term primary alcohol (ethanol). The predominant alcohol in alcoholic beverage is most referred as alcohol. IUPAC(1997).

Alcohol is produced by fermentation of yeast, sugar and starches; it is a central nervous system depressant that is rapidly absorbed from the stomach and small intestine into the blood stream. Alcohol beverages are drinks which contain substantial amount of psychoactive drug ethanol (informally called alcohol) as one of the most widely use recreational drugs in the world (National Institute on Drug Abuse,2013).

Alcohol is a depressant which means it slows it slows down body’s responds in all many kinds of ways just enough can make a person sociable, too much and it will make a person hangover the next day and may not remember what one got up to and way too much alcohol in a single session could put a person in a coma or lead to death.

Effect alcohol can cause

Reduced feeling of anxiety and inhibitions making you feel sociable. Some exaggerations of whatever mood you are in when you start drinking causing a wide range of physical health problems either as a result of binge drinking or from drinking most days of the week over recommended levels, the problem caused by drinking includes cancers, heart problems, high blood pressure, stroke, liver diseases, and falls and accidents (National Institute on Drug Abuse,2013).

Caffeine

Caffeine is a substance is found in certain plants, it can also be man- made and added to foods. It is a central nervous system stimulant and a diuretic (substance that helps get rid of body fluids). It is a central nervous system (CNS) stimulant of the methylxanthine class of psychoactive drugs; it is world’s most widely consumed psychoactive drugs. it is legal and unregulated in nearly all the parts of the world, it is a bitter, white crystalline purine, a methylxanthine alkaloid and thus closely related chemically to adenine and guanine contained in deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) it is found in the seeds, nuts or leaves of a number of plants native to south America and East Asia, the most well know source of caffeine is the seed (commonly incorrectly referred to as “beans”) of the Arabia coffee plant. Beverages containing caffeine are ingested to relieve or prevent drowsiness and to increase one’s energy level, caffeine is extracted from plant part containing it for making beverages by sleeping it in water, a process called infusion. The beverages are very popular in the North America, 90% of adults consume caffeine daily (Lovett, 2005).

Function

Caffeine is absorbed and passes quickly into the brain, it does not collect in the blood stream or get in the body, it leaves the body in the urine many hours after it has been consumed. There is no nutritional need for caffeine. It can be avoided in the diet.

Caffeine stimulates or excites the brain and nervous system, it will not reduce the effect of alcohol although many people still believe a cup of coffee will help a person “sober up”.  Caffeine can be use for short term relief and drowsiness.

Food sources

Caffeine is widely consumed, it is found naturally in leaves, seed and fruits to more than to plants including:

• Tea leaves
• Kola nuts
• Coffee
• Cocoa beans

It is also found in the processed foods :

• Coffee
• Tea
• Chocolate
• Most cola
• Candies, energy drinks, snacks, gum.

Composition of energy drinks

Energy drinks generally contain methylananthine (including caffeine) B-vitamins carbonated water and high fructose corn syrup (for nor diet version) other commonly used ingredients are Yerba mate, guaranainsitol, tourinemaltodextrin (Barry, 2013) Energy drinks contain about three times the amount of caffeine us cola (Salamon, 2011) twelve ounces of coca cola classic contains 35mg of caffeine where as a monster Energy drinks contains 120mg of caffeine (Heckman, Melanie, Weil, Jorge, Mejia and Elvira, 2010).

Energy drinks increment and what they do

Caffeine is the most widely used drug on the planet and was been used for centuries for its stimulating effects. Caffeine is bitter crystalline xanthine alkaloid (O’Connor, 2012) caffeine is found in varying quantity in the seeds leaves and fruits of some plant where it acts as natural pesticide that paralyses and kill certain insects feeding on plants.

It is most times consumed by humans in intensions extracted from the seed of the coffee plant and leaves of the tea bush as well as various foods and drinks containing produce derived from cola nut in humans, caffeine acts as a central nervous system stimulant temporally coding off drowsiness and restoring alertness (Loveth, 2005) consumption of 100mg-1500mg per day us associated with a condition known as caffeinism (Nehlig, Daval and Derby, 1998) caffeinism usually combines caffeine depending with a wide range of  unpleasant physical and mental conditions including nervousness irritability, restlessness, insomnia, headache and heart palpitation after caffeine use because is psychoactive drug it is often regulated in the United StatesFood and Drug Administration (FDA) restricts beverages to contain less that 0.02% caffeine.

Yerba mate

Yerba mate contains poly phenols which may benefit the immune system (Scarlbert, Augustine and Willianson, 2000) it relives allergies reduce the risk of diabetes and cause hypoglycemiain mice (Brenmer, Paul Heinrich and Michael, 2010).

Taurine or 2- amino ethanesulfonic acid

Taurine or 2- aminoethane sulfonic and is an organic acid widely distributed in animals tissue. It is a major constituent for bile and can be found in the large intestine and accounts for up to 0.1% of total human body weight (Hxytable, 1992) taurine has mainly fundamental biological roles such as conjugation of bile acids, antioxidant, osmo-regulation or calcium signalling.

Taurine occurs naturally in food especially in sea food and meat. The mean daily intake of omnivore diets was determined to be around 58gm (range from 9-372mg) and to be low or negligible from stick vega diet (Bouck, Enooghe,Remacle and Reusen, 2006)

Guarana

Guarana is a climbing plant in the maple family, sapidance native to the Amazon basin and especially common in Brazil. Guarana feature large leaves and cluster or flowers, and it is best known for its fruit which is about the size of coffee bean. As a dietary supplement Guarana is an effective stimulant (Johannes and Laura, 2010). Guarana is used in sweetened or carbonated soft drinks and energy shots an ingredient of herbal tea or contained in capsules, generally, South American obtain most of its caffeine from Guarana (Weinbery and Beaker, 2001) Guarana extract reduce aggregation of rabbit platelets by up to 3.7% below control values and decreased platelets thromboxane formation from archidonic acids value by 78% below control values (ByLowski, D’Amilo and Chamoie, 1991).

Acai berry fruit

Acai berry fruit commonly known as super food because of it oxidant qualities is a small round, black-purple drupe about similar appearance to a grape, but smaller with less pulp and produced in branched panicles or 500 to 900 fruits (Marcason, 2009)

Physiological and psychological effect of energy drink

Energy drink produce due to its caffeine and sugar content and are little or in evidence that the wide variety of other ingredients have any effect (Meire, 2013). However a variety or physiological and psychological effect have been attributed to energy drink and their ingredients two students reported significant improvements in mental and cognitive performance as well as increased subject alertness (Howard, Ma, and Marcdinki, 2010). Excessive consumption of energy drink may induce mild to moderate euphoria primarily caused by stimulant properties of caffeine and many also induce agitation anxiety, irritability and insomnia (Alford, Cox and Wescolt, 2001). During repeated cycling test in young healthy adults and energy drink significantly increased upper body muscle endurance (Forbes, Cancow, Little and Magnus, 2007) consumption of two or more drinks in a single energy will not lead to excessive caffeine intake, but consumption or two or more drinks in a single day can (Loeb and heather 2009) other stimulants such as ginseng are often added to energy drinks and may enhance the effect of caffeine and ingredients such as guarana themselves contain caffeine.

Adverse effects associated with caffeine consumption in amounts greater than that 400mg include nervousness irritability, sleeplessness increased urination abnormal health rhythms (arrhythmia) and dyspepsia. Consumption also has been known to cause pupil dilation when taken with certain antidepressant or SSRIS (Winston, 2005) most main stream energy drinks do not provide electrolytes and have a higher likelihood of an energy “Crash and burn” effect caffeine in energy drink can cause the excretion of water from body to dilate high concentration of sugar entering the blood stream, landing to dehydration. If the body is dehydrated by 1% performance is decrease by up to 10%.

Energy drink and the world economy

Market research from euro monitor calculated the global energy drink market was worth US$ 3.8 billion in 1999 and the value grew to US$ 27.5 billion in 2013 (Roberto, 2014) in 2000 the US energy drink market was worth US$ 3500 million and data from the package facts company show that the industry grew by 60% between 2008 and 2012 in the US-by 2012 total sales were over U$$ 12.5 billion. Red bull and monster were the two best selling brand in 2012 accounting for nearly 80% of US energy drink sales and the energy shot market is worth over US$ 1 billion in 2014 (Roberto, 2014).

History of coagulation factor

A first clue as to the actual complexity in the system of coagulation was the discovery of proaccelerin (Initially and later called factor V) by Paul Owen (1905-1990) in 1947, he also postulated its function to be the generation of accelerin (factor VI) which later turned out to be activated form of factor VI is not now in active use (Glangrande, 2003) factor VIII (also known as serum prothrombin conversion accelerator proconvertion precipitated by barium sulphate) was discovered in young female patient in 1949 and 1951 by different groups, factor VIII turned out to be deficient in clinically recognized but etiologically elusive haemophilia. As of was identities in the 1950 and in alternatively called anti-haemophilic globulin due to its capacity to correct haemophilia (Glangrande, 2003) factor IX was discovered in 1952 in a young patient with haemophilia B named Stephen Christmas. Hageman factor, now known as factor XII was identified in 1955 in an asymptomatic patient with a prolonged bleeding time named or John Hageman, factor X or start power factor followed in 1956. Thrombokinas/thromboplastin (factor iii) is released by damaged tissue reacting with prothrombin (II) which together with calcium (IV) forms thrombin which coverts fibrinogen into fibrin (I) (Glangrande, 2003).

Cascade of coagulation

The   coagulation of secondary haemostatic has two pathways which lead to fibrin formation. These are the contact activation pathway and the tissue factors. It is now known that the primary pathways for the initiation of blood coagulation are the tissue factor pathway. The pathways are a series of reactions in which zymogens (inactive enzyme precursor) of a serine protease and its glycoprotein co-factor are activated to become active components that theycatalyze the next reaction in the cascade, ultimately resulting in cross linked fibrin.

Coagulation factors are generally indicated by Roman numerals with a lower case appended to indicate an active form (Pallister and Watson, 2010). The Coagulation factors are generally seinne protease (enzymes) which act by cleaving downstream protein there are some exceptions for example, fviii and Fv are glycoprotein’s and factor xiii is a transglutaminase, Coagulation factors circulate as inactive zymogens. The Coagulation cascade is classically divided into three pathways of factor x thrombin and fibrin (Hoffbrand, 2002).

Contact activation pathway (intrinsic)

The contact activation pathway begins with formation of the primary complex on collagen by high molecular weight kinmogen (HMWK). Prekallikrein and fxiia (Hageman factor) prekallikrein is converts to kallikerein and fxii becomes fxiia, fxiia converts fxi into fxiii factor xia activate fix. Which with its co-factor fviiia form the tenase complex, which activates fx to fxa the minor role that the contact activation pathways has in initiating clot formation can be illustrated by the fact that patients with severe deficiencies of fxii high molecular weight kininogen and prekallikrein do not have bleeding disorder instead contact activation systems seems to be more involved in inflammation (Pallister and Watson, 2010).

Tissue factor pathway (extrinsic)

The main role of the tissue factor pathway is to generate “Thrombin burst” a process by which thrombin. The most important constituent of the coagulation cascade in terms of its feedback activation roles, it released very rapidly fviia circulates in a higher amount than any other activated coagulation factor the process includes the following step(Pallister and Watson, 2010)following damage to the blood vessel. Fvii leaves the circulation and comes into contact with tissue factor (TF) expressed on tissue factor bearing cells (stromal fibroblastic and leukocyte) forming an activated complex (TF-fviia) TF-fviia  activates fix and fx. Fvii is itself activated by thrombin, fxiafxii and fxa.

The activation of fx (to form fxa) by TF-fviia is almost immediately inhibited by tissue factor pathway inhibitor (TFPI). thrombin then activates other components to the coagulation cascade including fv and fvii (which activates fxi) and activate and research fviii from being bound to VWF.  Fviiia is the co-factor of fix and together they form the “terase” complex which activities fx and so the cycle continues (“Tenase”) is a contraction of  “ten” and the suffix “ase” used for the enzymes.

The final common pathway

The division of coagulation into two pathways is mainly artificial. It originates from laboratory tests in which clotting time were by thromboplastin (a mix of tissue factor and phospholipids) in fact thrombin is present from the very beginning already when platelets are making the plug, thrombin has a large array of functions not only the conversion of fibrinogen to fibrin the building block of a homeostatic plug. In addition it is the most important platelet activation and on top of that it activates factor viii and v and their inhibitors protein (in the presence of thrombomodulon) and it activates factor xiii, which forms covalent bonds that crosslink the fibrin polymers that form activated monomers (Pallister and Watson, 2010) following activation by the contact factor or tissue factor pathways. The coagulation cascade fviii and fix to form the tenase complex and it is down regulated by the anticoagulant pathways (Pallister and Watson, 2010).

Physiology of coagulation

Coagulation beings almost instantly after any injury to the blood to the space under the endothelium initiates two process changes in platelets, and the exposure of subendothilia tissue factor to plasma factor vii which intimately leads to fibrin formation. Platelets immediately form a plug at the site of injury this is called primary haemostatic. Secondary haemostats occurs simultaneously additional coagulation cascade to form fibrin stand or factors or clotting factors beyond factor vii, respond in a complex cascade to form fibrin strands which strengthen the platelets plug (Furie and Furie, 2005).

Prothrombin time

Prothrombin time (PT) is a blood test that measures how long it takes blood to clot. A Prothrombin time test can be used to check for bleeding problem. PT is also used to check whether medicine to prevent blood clots is working.

A PT Test may also be called an INR test (International normalized ratio) stand for a way of standardizing the results or Prothromoin time test no matter the testing method.Blood clotting factors are needed for blood to clot (coagulation) Prothrombin or factor II is one of the clotting factors made by the liver vitamin K is needed to make Prothrombin and other clotting factors Prothrombin time is an important test because it checks to see if five different clotting factor (factor I, II, VII, and X) are present the Prothrombin time is made longer by

• Blood thinning medicine such as war farine
• Low level of blood clotting factor
• A change in the activity or any of the clotting factors
• Other substance called inhibitors that affects the clotting factor
• The absence of any of the clotting factor
• An increase in the use of clotting factor

An abnormal Prothrombin time is often called by liver disease or injury or by treatment with blood thinners. Another blood clotting test, called partial thromboplastin time (PTT) might be used if you take another type of blood thinning medicine called heparin. This test measures other clotting factor partial thromboplastin time and Prothrombin  time are often done at the same time and form bleeding problems or the chances for too much bleeding in surgery (Pagna, 2010).

Why is a prothrombin time test performed

When you get a cut and your blood vessel is ruptured blood platelets collects at the site of the wound creating a temporary plug to stop bleeding in order to create a strong blood clot a series of 12 plasma proteins or coagulation “factors” act together to create a substance called fibrin that seals the wound. If the body does not create a certain coagulation factor or does do incorrectly it can be due to a bleeding disorder known as haemophilia symptoms of a bleeding disorder includes

• Easy bruising
• Bleeding that won’t stop even after applying pressure to the wound
• Blood in urine
• Swollen or painful joint
• Nose bleeds

The Prothrombin time was developed by Dr Armand Quick and colleagues in 1985 (Quick, Stanley, Brown and Bancroft, 1985). Also called the “P and P” or prothrombin and preconventin” method. It aided in the identification of anticoagulant dicumarol and warafin and was used subsequently as a measure of activity or warafin when used therapeutically (Campbell, Smith, Roberts & Link, 2010).

What are the associated risk with prothrombin time test

There are very few risk association with having blood drawn from a PT test. However because the test is often performed on patients who having bleeding disorders they are at a slightly risk for excessive bleeding and hematoma (blood that accumulates under the skin).Sight pain or soreness may be felt at the site where blood was drawn and also a slight risk of injection where blood was punctured from (Chereneckyand  Berger, 2008).

What affects the test

Reason you may not be able to have the test or why the result may not be helpful includes

• Taking medicine that can affect the action of blood thinners (such as warafin and vitamin K. these include antibiotics aspirin birth control pill hormone therapy and vitamin K supplement.
• Drinking of alcohol.
• Taking some herbal product or natural remedies.

(Pagnaand Pagna, 2010)

Effect of caffeine

Caffeine is likely safe for most adult when use appropriately. Caffeine is possibly unsafe when taken by mouth for a long time or fairly high doses. Caffeine can cause insomnia nervousness and restlessness stomach irritation nausea and vomiting.

Bleeding disorder

There is concern that caffeine might aggravate bleeding disorder use caffeine with are if you have bleeding disorder. Bronthropulmonary dysplasia in premature infants for both prevention and treatment it may improve. Weight gain during therapy and remove incidence or cerebral palsy as well as reduced language and cognitive delay on the other hand subtle long form side effects as possible (Henderson and Paoli, 2010).

Effect of alcohol (short term effect)

The short term effect of alcohol ethanol consumption range from a decrease in anxiety and motor skills at lower doses to unconscious anterograde amnesia and central nervous system depression at higher doses cell membrane are highly permeable to alcohol so once alcohol is in the blood stream it can diffuse into nearly every cell in the body.

The concentration of alcohol in blood is via blood alcohol content (BAC) the amount and circumstance of consumption play a large part in determining the extent of intoxication for example, eating a heavy meal before alcohol intake cause alcohol to absorb more slowly, Hydration also plays a role especially in determining  the extent of hangover after excessive drinking unconsciousness can occur and extreme levels of consumption can lead to alcohol poisoning and death ( a  concentration in the blood stream of 0.40% will kill half of those affected)(Alcohol Awareness Page Carleton College Wellness Centre Blood Alcohol Concentration, 2013).

Alcohol may also cause death indirectly by asphyxiation from vomit Alcohol can greatly exacerbate sleep problems during abstinence residual disruption is sleep regularity and sleep patterns are dreamer predictor of relapse(Fegie and Scalls, 2007).The following lists are the common effect on the body depending on the blood alcohol concentration (BAC). However tolerance varies considerably between individual as those individuals respond to a given dosage the effect of alcohol varies or differs between people Hence BAC percentage are just estimated use for illustrative purpose. Euphoria (BAC 0.3% to 0.12%).

• Overall improvement in the mode and positive euphoria
• Increased sociability
• Decreased anxiety

Long term effect

Health effect associated with alcohol intake in large amounts include an increased risk of alcoholism malnutrition, chronic pancreatic alcohol, liver disease and cancer in addition damage to the central nervous system and peripheral nervous system can occur from chronic alcohol abuse. (Muller, Koch, Von Specht, Voilke, Munch and  Koch,1995).The long term of alcohol is capable of damaging nearly every organ and system in the body. (Caan, Woody,Bellerocheand Jackie, 2002)

Effect of alcohol on caffeine

According to DSST (Dantes Subject Standardized Test) formerly known as credit by examination alcohol provides a reduction in performance and caffeine has a significant improvement in performance (Mackay.Triplay and Scholey,2012).

When alcohol and caffeine are consumed Jointly the effect produced by caffeine are affected but the alcohol effect remains the same for example when additional caffeine is added the drug effect produced by alcohol is not reduced. However the jitteriness and alertness given by caffeine is decreased when additional alcohol is consumed. Alcohol consumption alone reduced both inhibitory and activational antagonized aspect of behavioural control but has no effect on the inhibitory behavioural control (Marczinski, 2003).

References

Alford, C., Cox, H.andWescolt, R.(2001).The effect of Red Bull Energy Drink on Human Performance and Mood.Amino Acids21 (2);  139-50.

Barry, M. (2013).New Aisle Energy Drink side Step Some Rules. The                    New York Times. 17(2) 130 – 179

Bouckenooghe, T., Remacle, C. andReusens, B. (2006). Is Taurine a functional Nutrient? Current option in clinicalNutrition and metabolic care9 (6): 728-33.

Bremmer, Paul, Heinrich and Michael (2010).Natural Products as Targeted Modulator of the NuclearFactor – KB pathway.Journal of Pharmacy and Pharmacology 54 (4): 453-472.

Bylowski,S.P., Damico, E.A. andChamoie, D.A. (1991).An Aqueous Extract of Guarana (Pawloniacupana) Decrease thromboxane synthesis Braz. J.  Med Boil Res. 24(4):421-4

Campbell,H.A., Smith,W.K., Robert,W.L. and Link,K.P. (2010).Studies on the     Hemorrhagic Sweet Clover Disease 11. The Bioasis or Hemorrhagic Concentrates By Following TheProthombic level in Plasma of Rebate Blood” 11 (6): 32

Fornes, S.C.,Candolo, D.G. little, J. P. Magnus, C. andChilibeck, P.D. (2007): Effect of Red Bull Drink on Repeated Wingate Cycle Performance and Bench-press Muscle Endurance.InternationalJournal of Sport Nutrition and Exercise metabolism 17(5): 433-44.

Feige, B.,Scalls, S., Hornyak, M.,Aann, H. andRermann, D. (2007). Caffeine summary of clinical use. 13 (47): 270 – 41

Furie,B.C. andFurie, B. (2005).Thrombus Formation in Invivo. J. Clninvest,11(12): 3355-62.

Glangrande, P. L. (2003).Siu characters in search of an Author. The History of the Nomeclature of Coagulating factors.BRJ.Haemotol, 14(5): 703-12.

Hernecky, K. andBerger,B.T. (2008). Laboratory Tests and Diagnosis Procedure          (5^thed.). St. Louis: Sounders. 12 (11): 326 – 41

Herderson, Y., Smart,D.J. and De Poaoli, A.G. (2010). Prophylactic MethylanxthineFor Prevention of Disease In Pattern Infant. 17 (2): 410 – 12.

Hoffbrand, A. V. (2002). Essential Haematology Oxford: Backwell    Science pp. 243-245.

Howard, M.A. andMarczingki, C.A.(2011). Acute Effect of a glucoseEnergy Drink on Behavioural Control.Experimental and clinical psychopharmiacolgy15(16):553-61

Hyxtable, R.J. (1992). Physiological Actions of Taurine.Physiol Rev 72 (1):101-163

IUPAC, Compendium of Chemical Technology, 2^nded (The Gold Book”)   (1997): Online Corrected Version (2006)

Johannes, L. (2010). Can a Caffeine Packed Plant Give a Boost? The Wall Street JournalP.D3.

Lovett, R. (2005). Coffee, The Demon Drink? New scientist 2:5-18

Maller, D., Koch, R.D., Von Speeht,H., Volker, W., Munch, E., Koch,V.

Marcason, W. (2009). What is AcaiBery and Their Health Benefits? Journal of America Dietetic Association 109 (11): 1968-1910.

Nehlig, A.,Davai, J. L. andDebry, G. (1988).Caffeine and The Central Nervous System Mechanism Of Action, Biochemical Metabolic and psychostimulant. Effect Brain Res Rev. 17(2):139-70.

Pallister, C. J.and Watson, M.S. (2010).Haematologyscion publishing  pp. 334-336

Quick,A.J.,Stantley-Broon, M. andBremcroft,F.W. (1935).A Study of The Coagulation Defect Hemophilia and in Jaundice Am J Med science.

Roberto, F. (2014): The American Energy Drink Raze in Two Highly Caffeinated Charts Quarter.

United States Food and Drug Administration (2010). List OfManufacturers of Caffeinated Alcohol Beverages”.pp11-3.

Weinberg, B. A. andBeaker, B. K. ( 2001). The World Of Caffeine Th Science And Culture Of The World Most Popular Drug. New York:Routledgepp.230.

Winston, A. P. (2005).Neuropsychiatric Effect of Caffeine Advances.Psychiatric Treatment 11 (6): 32.