WHAT ARE THE DANGERS OF CAFFEINE
Death by Caffeine
DEATH BY CAFFEINE CHECK>>>>>>>
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CAFFEINE Side Effects & Safety
Caffeine is LIKELY SAFE
for most adults when used appropriately. 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.
Large doses may be UNSAFE and can cause irregular heartbeats and even death.
Anxiety disorders: Caffeine might make these conditions worse. Use with care.
Bipolar disorder: Too much caffeine might make this condition worse. In one case, a 36-year-old man with controlled bipolar disorder was hospitalized with symptoms of mania after drinking several cans of an energy drink containing caffeine, taurine, inositol, and other ingredients (Red Bull Energy Drink) over a period of 4 days. Use caffeine with care and in low amounts if you have bipolar disorder.
Bleeding disorders: There is concern that caffeine might aggravate bleeding disorders. Use caffeine with care if you have a bleeding disorder.
Heart conditions: Caffeine can cause irregular heartbeat in sensitive people. Use caffeine with caution.
Diabetes: Some research suggests that caffeine may affect the way the body uses sugar and might worsen diabetes. But the effect of caffeinated beverages and herbs has not been studied. If you have diabetes, use caffeine with caution.
Diarrhea: Caffeine, especially when taken in large amounts, can worsen diarrhea.
Irritable bowel syndrome (IBS): Caffeine, especially when taken in large amounts, can worsen diarrhea and might worsen symptoms of IBS.
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.
High 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.
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 (approximately 2-3 cups of coffee). It’s also a good idea to get extra calcium to make up for the amount that may be lost in the urine. Older women with an inherited disorder that affects the way vitamin D is used should use caffeine with caution. Vitamin D works with calcium to build bones.
Large doses may be UNSAFE and can cause irregular heartbeats and even death.
Special Precautions & Warnings:
Pregnancy and breast-feeding: Caffeine is POSSIBLY SAFE in pregnant or breast-feeding women in daily amounts of less than 200 mg. This is about the amount in 1-2 cups of coffee. Consuming larger amounts during pregnancy might increase the chance of miscarriage and other problems. Caffeine passes into breast milk, so nursing mothers should closely monitor caffeine intake to make sure it is on the low side. Caffeine in large amounts is POSSIBLY UNSAFE during breast-feeding. Caffeine can cause sleep disturbances, irritability, and increased bowel activity in breast-fed infants.Anxiety disorders: Caffeine might make these conditions worse. Use with care.
Bipolar disorder: Too much caffeine might make this condition worse. In one case, a 36-year-old man with controlled bipolar disorder was hospitalized with symptoms of mania after drinking several cans of an energy drink containing caffeine, taurine, inositol, and other ingredients (Red Bull Energy Drink) over a period of 4 days. Use caffeine with care and in low amounts if you have bipolar disorder.
Bleeding disorders: There is concern that caffeine might aggravate bleeding disorders. Use caffeine with care if you have a bleeding disorder.
Heart conditions: Caffeine can cause irregular heartbeat in sensitive people. Use caffeine with caution.
Diabetes: Some research suggests that caffeine may affect the way the body uses sugar and might worsen diabetes. But the effect of caffeinated beverages and herbs has not been studied. If you have diabetes, use caffeine with caution.
Diarrhea: Caffeine, especially when taken in large amounts, can worsen diarrhea.
Irritable bowel syndrome (IBS): Caffeine, especially when taken in large amounts, can worsen diarrhea and might worsen symptoms of IBS.
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.
High 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.
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 (approximately 2-3 cups of coffee). It’s also a good idea to get extra calcium to make up for the amount that may be lost in the urine. Older women with an inherited disorder that affects the way vitamin D is used should use caffeine with caution. Vitamin D works with calcium to build bones.
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About HERBALIFE Product
Heart Palpitations:
Palpitations may be from caffeine sensitivity. The tea does have caffeine in it so you could either stop using the tea or eventually you will get used to caffeine and the palpations should recede. The shake mix does not contain any caffeine.
In the nineties it was found that Ephedra caused increased heart rate and Herbalife discontinued using Ephedra in any of its products.
About HERBALIFE Product
Heart Palpitations:
Palpitations may be from caffeine sensitivity. The tea does have caffeine in it so you could either stop using the tea or eventually you will get used to caffeine and the palpations should recede. The shake mix does not contain any caffeine.
In the nineties it was found that Ephedra caused increased heart rate and Herbalife discontinued using Ephedra in any of its products.
FOR MORE DETIAL http://herbalife-sideeffects.blogspot.in
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Caffeine: Energy or Addiction
How many times have I tried to give up caffeine? Too many to count I’m afraid. You know the drill, well at least maybe you do.
I get this notion in my head that I don’t need caffeine and that I can save a lot of money if I quit consuming lattes and energy drinks. So I quit could turkey, endure the three day headache, fight the extreme fatigue, and then finally I’m free! OK, well until a few days later a friend asks me out for a coffee and I digress and rationalize.
I think “If I only have one a week then I can keep myself from depending on it”. However, I start drinking that hot soothing beverage and something strange comes over me, some type of euphoria really. The aroma, the taste, my sinuses clear, my head feels lighter, and I’m ready to conquer the world….yeah!
Once a week turns into twice a week, then every other day, then wouldn’t you know it, I’m hooked again.
I know I’m not alone and there has been much research as to whether caffeine really gives the feeling of energy or if it just satisfies physical and psychological withdraw symptoms. Studies have shown that just consuming 100 milligrams of caffeine a day is enough to cause dependence.
So when we have our daily dose, we aren’t actually increasing our alertness or energy, but instead just easing withdrawal symptoms which gives us the illusion of such positive feelings.
The good news is we are all hopeless addicts and there never has been a larger support group worldwide consisting of well over a billion members strong. In fact over 90% of adults in the US consume caffeine daily.
My struggle continues, but there are way worse things to be addicted to, so drink up energy fiends!
Caffeine Allergy: Top 20 Symptoms
Way back in yesteryear (2005), we published a post entitled “Yes, You Can Be Allergic to Caffeine” .Since then this post has received over 190 comments from mostly those who have experienced some type of adverse reaction to caffeine.
I have painstakingly sifted through all those comments and have derived the top 20 caffeine allergic reactions in order from most common to least common. Note that this is entirely anecdotal evidence so don’t take it as gospel, but rather consider these caffeine allergy symptoms as possible since they were reported by a number of people.
Also, there is a fine line between caffeine sensitivity and allergy, but overall we’re dealing with the body not being able to correctly process the caffeine molecule so whether you want to call that sensitivity or allergy it’s up to you. In most cases these symptoms were reported after only having a little to moderate amount of caffeine.
Most Common Allergic Reactions to Caffeine
- Skin problems such as hives, eczema, rashes, acne, severe itching.
- Headaches/ migraines.
- Anxiety and panic attacks.
- Can’t focus or concentrate
- Tongue, glands, or throat swelling.
- Heart racing/ palpitations.
- Angry, irritable, bad mood.
- Fatigue.
- Dizziness.
- Extreme jitters.
- Chest Pain.
- Depression.
- Numbness in face, hands, or feet.
- Muscle pain.
- Shortness of breath/ tightness of chest.
- Delusions/ hallucinations.
- Flu/ cold like symptoms.
- Vision problems.
- Cold sweats.
- Eyes swollen shut.
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Caffeine
From Wikipedia, the free encyclopedia
This article is about the stimulant drug. For other uses, see Caffeine (disambiguation).
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| Systematic (IUPAC) name | |||
| 1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione |
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| Clinical data | |||
| AHFS/Drugs.com | monograph | ||
| Pregnancy cat. | B?(AU) C(US) | ||
| Legal status | Unscheduled (AU) GSL (UK) OTC (US) | ||
| Routes | Oral, insufflation, enema | ||
| Pharmacokinetic data | |||
| Bioavailability | 99% | ||
| Protein binding | 17% to 36% | ||
| Metabolism | demethylation by CYP1A2 | ||
| Half-life | 5 hours | ||
| Excretion | urine (100%) | ||
| Identifiers | |||
| CAS number | 58-08-2 | ||
| ATC code | N06BC01 | ||
| PubChem | CID 2519 | ||
| DrugBank | DB00201 | ||
| ChemSpider | 2424  |
||
| UNII | 3G6A5W338E |
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| KEGG | D00528 |
||
| ChEBI | CHEBI:27732 |
||
| ChEMBL | CHEMBL113 |
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| Chemical data | |||
| Formula | C8H10N4O2 | ||
| Mol. mass | 194.19 g/mol | ||
| SMILES | eMolecules & PubChem | ||
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In humans, caffeine acts as a central nervous system stimulant, temporarily warding off drowsiness and restoring alertness. It is the world's most widely consumed psychoactive drug, but, unlike many other psychoactive substances, it is both legal and unregulated in nearly all parts of the world. Beverages containing caffeine, such as coffee, tea, soft drinks, and energy drinks, enjoy great popularity; in North America, 90% of adults consume caffeine daily.[5]
Caffeine is toxic at sufficiently high doses. Ordinary consumption can have low health risks, even when carried on for years – there may be a modest protective effect against some diseases, including certain types of cancer. Caffeine can have both positive and negative effects on anxiety disorders.[citation needed] Some people experience sleep disruption if they consume caffeine, especially during the evening hours, but others show little disturbance and the effect of caffeine on sleep is highly variable.
Evidence of a risk to pregnancy is equivocal, but some authorities have concluded that prudent advice is for pregnant women to limit consumption to the equivalent of two cups of coffee per day or less.[6] Caffeine has diuretic properties when administered to people who are not used to it, but regular users develop a tolerance to this effect, and studies have generally failed to support the common notion that ordinary consumption contributes significantly to dehydration. With heavy use, strong tolerance develops rapidly and caffeine can produce clinically significant physical and mental dependence.
Contents |
Health effects
Stimulant effects
Caffeine is a central nervous system and metabolic stimulant,[7] and is used both recreationally and medically to reduce physical fatigue and to restore alertness when drowsiness occurs. It produces increased wakefulness, faster and clearer flow of thought, increased focus, and better general body coordination.[8] The amount of caffeine needed to produce effects varies from person to person, depending on body size and degree of tolerance. Effects begin less than an hour after consumption, and a moderate dose usually wears off in about five hours.[8]Caffeine has a number of effects on sleep, but does not affect all people in the same way. It improves performance during sleep deprivation but may lead to subsequent insomnia.[9] In shift workers it leads to fewer mistakes caused by tiredness.[10] In athletics, moderate doses of caffeine can improve sprint,[11] endurance,[12] and team sports performance,[13] but the improvements are usually not very large. High doses of caffeine, however, can impair athletic performance by interfering with coordination.[14] Evidence shows that, contrary to common advice, caffeine may be helpful at high altitude.[15]
Physical effects
Consumption of large amounts of caffeine – usually more than 250 mg per day – can lead to a condition known as caffeinism. Caffeinism usually combines caffeine dependency with a wide range of unpleasant physical and mental conditions including nervousness, irritability, restlessness, insomnia, headaches, and heart palpitations after caffeine use.[16]Coffee consumption is associated with a lower overall risk of cancer.[17] This is primarily due to a decrease in the risks of hepatocellular and endometrial cancer, but it may also have a modest effect on colorectal cancer.[18] There does not appear to be a significant protective effect against other types of cancers, and heavy coffee consumption may increase the risk of bladder cancer.[18] On the other hand, caffeine has been shown to inhibit cellular DNA repair mechanisms.,[2] but only at extreme high concentrations (which would be lethal in humans).[19] There is little or no evidence that caffeine consumption increases the risk of cardiovascular disease, and it may somewhat reduce the risk of type 2 diabetes.[20] Drinking four or more cups of coffee per day does not affect the risk of hypertension compared to drinking little or no coffee. However those who drink 1–3 cups per day may be at a slightly increased risk.[21] Caffeine increases intraocular pressure in those with glaucoma but does not appear to affect normal individuals.[22] It may protect people from liver cirrhosis.[23] There is no evidence that coffee stunts a child's growth.[24] Caffeine may increase the effectiveness of some medications including ones used to treat headaches.[25]
Caffeine consumption during pregnancy does not appear to increase the risk of congenital malformations, miscarriage or growth retardation even when consumed in moderate to high amounts.[26] However as the data supporting this conclusion is of poor quality some suggest limiting caffeine consumption during pregnancy.[27][28] For example the UK Food Standards Agency has recommended that pregnant women should limit their caffeine intake, out of prudence, to less than 200 mg of caffeine a day – the equivalent of two cups of instant coffee, or one and a half to two cups of fresh coffee.[29] Although the evidence that caffeine may be harmful during pregnancy is equivocal, there is clear evidence that the hormonal changes associated with pregnancy slow the metabolic clearance of caffeine from the system, causing a given dose to have longer-lasting effects (as long as 15 hours in the third trimester).[30]
On the positive side, caffeine is the primary treatment of the breathing disorders apnea of prematurity[31] and may also be effective in preventing bronchopulmonary dysplasia in premature infants.[32] The only short-term risk associated with caffeine citrate treatment is a temporary reduction in weight gain during the therapy,[33] and longer term studies (18 to 21 months) have shown lasting benefits of treatment of premature infants with caffeine.[34] However, the possibility of subtle long-term developmental problems cannot be ruled out fully.[35]
When doses of caffeine equivalent to 2–3 cups of coffee are administered to people who have not consumed caffeine during prior days, they produce a stimulation in urinary output.[36] Because of this diuretic effect, some authorities have recommended that athletes or airline passengers avoid caffeine in order to reduce the risk of dehydration.[36] Most people who consume caffeine, however, ingest it daily. Regular users of caffeine have been shown to develop a strong tolerance to the diuretic effect,[36] and studies have generally failed to support the notion that ordinary consumption of caffeinated beverages contributes significantly to dehydration, even in athletes.[37][38][39]
Psychological
The US National Institutes of Health states "too much caffeine can make you restless, anxious, and irritable. It may also keep you from sleeping well and cause headaches, abnormal heart rhythms, or other problems. If you stop using caffeine, you could get withdrawal symptoms. Some people are more sensitive to the effects of caffeine than others. They should limit their use of caffeine. So should pregnant and nursing women."[40]Four caffeine-induced disorders are recognized by the American Psychiatric Association (APA) including: caffeine intoxication, caffeine-induced sleep disorder, caffeine-induced anxiety disorder and caffeine-related disorder not otherwise specified (NOS).[41] The DSM-IV defines caffeine-induced sleep disorder, as an individual who regularly ingests high doses of caffeine sufficient to induce a significant disturbance in his or her sleep, sufficiently severe to warrant clinical attention.[41] As of 2010 the effect of caffeine on people with ADHD is not known.[42] Some studies have however found a modest protective against Alzheimer disease, but the evidence is inconclusive.[43][44][45]
Caffeine can have both negative[46] and positive[citation needed] effects on anxiety disorders. A number of clinical studies have shown a positive association between caffeine and anxiogenic effects and/or panic disorder.[47][48][49] For some people, anxiety can be very much reduced by coming off caffeine.[50] Anxiety sufferers can have high caffeine sensitivity.[51][52][53][54][55]
At high doses, typically greater than 300 mg, it can both cause and worsen anxiety[56] and rarely trigger mania and psychosis. In moderate doses caffeine may reduce symptoms of depression and lower suicide risk.[42] In moderate doses caffeine typically does not affect learning or memory.[57] It does however improve cognitive function in people who are fatigued, due to its effect on alertness.
Caffeine intoxication
Extreme overdose can result in death.[61][62] The median lethal dose (LD50) given orally, is 192 milligrams per kilogram in rats. The LD50 of caffeine in humans is dependent on individual sensitivity, but is estimated to be about 150 to 200 milligrams per kilogram of body mass or roughly 80 to 100 cups of coffee for an average adult.[4] Though achieving lethal dose with caffeine would be exceptionally difficult with regular coffee, there have been reported deaths from overdosing on caffeine pills, with serious symptoms of overdose requiring hospitalization occurring from as little as 2 grams of caffeine. An exception to this would be taking a drug such as fluvoxamine or levofloxacin, which blocks the liver enzyme responsible for the metabolism of caffeine, thus increasing the central effects and blood concentrations of caffeine five-fold.[60][61][62][63] Death typically occurs due to ventricular fibrillation caused by effects of caffeine on the cardiovascular system.
Treatment of severe caffeine intoxication is generally supportive, providing treatment of the immediate symptoms, but if the patient has very high serum levels of caffeine then peritoneal dialysis, hemodialysis, or hemofiltration may be required.[58]
Addiction and tolerance
Main article: Caffeine addiction
With repetitive use, physical dependence or addiction are likely to occur. Also, the stimulatory effects of caffeine are substantially reduced over time, a phenomenon known as a tolerance.
Tolerance develops quickly to some (but not all) effects of caffeine,
especially among heavy coffee and energy drink consumers.[64] Some coffee drinkers develop tolerance to its sleep-disrupting effects, but others apparently do not.[30]Withdrawal
Withdrawal symptoms – including headache, irritability, inability to concentrate, drowsiness, insomnia, and pain in the stomach, upper body, and joints – may appear within 12 to 24 hours after discontinuation of caffeine intake, peak at roughly 48 hours, and usually last from 2 to 9 days.[65] In prolonged caffeine drinkers, symptoms such as increased depression and anxiety, nausea, vomiting, physical pains and intense desire for caffeine containing beverages are also reported. Peer knowledge, support and interaction may aid withdrawal.[66]In other animals
See also: Effect of psychoactive drugs on animals
While safe in humans, caffeine is considerably toxic to various animals, such as dogs and birds.[67][68]The increased toxicity of caffeine in some animals is at least partly due to a poorer ability to metabolize the compound.[69]
Caffeine also has a pronounced effect on mollusks, various insects, and spiders.[70]
Sources and consumption
| Product | Serving size | Caffeine per serving (mg) | Caffeine (mg/L) |
|---|---|---|---|
| Caffeine tablet (regular-strength) | 1 tablet | 100 | — |
| Caffeine tablet (extra-strength) | 1 tablet | 200 | — |
| Excedrin tablet | 1 tablet | 65 | — |
| Foosh Energy Mints | 1 mint | 100.0 | — |
| Buzz Bites Chocolate Energy Chews | 1 chew | 100.0 | — |
| Hershey's Special Dark (45% cacao content) | 1 bar (43 g/1.5 oz) | 31 | — |
| Hershey's Milk Chocolate (11% cacao content) | 1 bar (43 g/1.5 oz) | 10 | — |
| Percolated coffee | 207 mL (7.0 US fl oz) | 80–135 | 386–652 |
| Drip coffee | 207 mL (7.0 US fl oz) | 115–175 | 555–845 |
| Coffee, decaffeinated | 207 mL (7.0 US fl oz) | 5–15 | 24–72 |
| Coffee, espresso | 44–60 mL (1.5–2.0 US fl oz) | 100 | 1,691–2,254 |
| Tea – black, green, and other types, – steeped for 3 min. | 177 millilitres (6.0 US fl oz) | 22–74[74][75] | 124–416 |
| Guayakí yerba mate (loose leaf) | 6 g (200 US fl oz) | 85[76] | approx. 358 |
| Coca-Cola Classic | 355 mL (12.0 US fl oz) | 34 | 96 |
| Mountain Dew | 355 mL (12.0 US fl oz) | 54 | 154 |
| Guaraná Antarctica | 350 mL (12 US fl oz) | 30 | 100 |
| Jolt Cola | 695 mL (23.5 US fl oz) | 280 | 403 |
| Red Bull | 250 mL (8.5 US fl oz) | 80 | 320 |
Caffeine is found in many plant species, where it acts as a natural pesticide, with high caffeine levels being observed in seedlings still developing foliage but lacking mechanical protection;[78] caffeine paralyzes and kills certain insects feeding on the plant.[79] High caffeine levels have also been found in the surrounding soil of coffee bean seedlings. Therefore, caffeine is understood to have a natural function as both a natural pesticide and an inhibitor of seed germination of other nearby coffee seedlings, thus giving it a better chance of survival.[80]
Common sources of caffeine are coffee, tea, soft drinks and energy drinks, and (to a lesser extent) chocolate derived from cocoa beans.[81] Less commonly used sources of caffeine include the yerba maté, guarana and ilex guayusa plants,[82] which are sometimes used in the preparation of teas and energy drinks. Two of caffeine's alternative names, mateine and guaranine, are derived from the names of these plants.[83]
The disparity in experience and effects between the various natural caffeine sources could be because plant sources of caffeine also contain widely varying mixtures of other xanthine alkaloids, including the cardiac stimulants theophylline and theobromine, and other substances such as polyphenols that can form insoluble complexes with caffeine.[84]
One of the world's primary sources of caffeine is the coffee "bean" (which is the seed of the coffee plant), from which coffee is brewed. Caffeine content in coffee varies widely depending on the type of coffee bean and the method of preparation used;[85] even beans within a given bush can show variations in concentration. In general, one serving of coffee ranges from 80–100 milligrams, for a single shot (30 milliliters) of arabica-variety espresso, to approximately 100–125 milligrams for a cup (120 milliliters) of drip coffee.[86][87] Arabica coffee typically contains half the caffeine of the robusta variety.[85]
In general, dark-roast coffee has very slightly less caffeine than lighter roasts because the roasting process reduces a small amount of the bean's caffeine content.[86][87]
Tea contains more caffeine than coffee by dry weight. A typical serving, however, contains much less, since tea is normally brewed much weaker. Also contributing to caffeine content are growing conditions, processing techniques, and other variables. Thus, certain types of tea may contain somewhat more caffeine than other teas.[88]
Tea contains small amounts of theobromine and slightly higher levels of theophylline than coffee. Preparation and many other factors have a significant impact on tea, and color is a very poor indicator of caffeine content. Teas like the pale Japanese green tea, gyokuro, for example, contain far more caffeine than much darker teas like lapsang souchong, which has very little.[88]
Chocolate derived from cocoa beans contains a small amount of caffeine. The weak stimulant effect of chocolate may be due to a combination of theobromine and theophylline, as well as caffeine.[90] A typical 28-gram serving of a milk chocolate bar has about as much caffeine as a cup of decaffeinated coffee, although some dark chocolate currently in production contains as much as 160 mg per 100 g.[72]
Various manufacturers market caffeine tablets, claiming that using caffeine of pharmaceutical quality improves mental alertness. These effects have been borne out by research that shows caffeine use (whether in tablet form or not) results in decreased fatigue and increased attentiveness.[8]
These tablets are commonly used by students studying for their exams and by people who work or drive for long hours.[91] One U.S. company is also marketing dissolving caffeine strips as an alternative to energy drinks.[92] Another unusual intake route is SpazzStick, a caffeinated lip balm.[93]
Chemical properties and biosynthesis
The two amide groups of caffeine exist predominately as zwitterionic resonance structures where the nitrogen and carbon atoms are double bonded to each other so that both of these nitrogen atoms are essentially planar (in sp2 orbital hybridization). The fused ring system therefore contains a total of ten pi electrons and hence according to Hückel's rule is aromatic.[citation needed]
Caffeine is synthesized in plants from the purine nucleotides AMP, GMP, and IMP. These in turn are transformed into xanthosine and then theobromine, the latter being the penultimate precursor of caffeine.[99]
Being readily available as a byproduct of decaffeination, caffeine is not usually synthesized chemically.[100] If desired, it may be synthesized from dimethylurea and malonic acid.[95][96][101]
Pure anhydrous caffeine is a white colorless powder with a melting point of 227–228 °C. Caffeine is moderately soluble in water at room temperature (2 g/100 mL), but very soluble in boiling water (66 g/100 mL).[102] It is also moderately soluble in ethanol (1.5 g/100 mL).[102] It is weakly basic (pKa = ~0.6) requiring strong acid to protonate it.[3]
Pharmacology
Inside the body caffeine acts through several mechanisms, but its most important effect is to counteract a substance called adenosine that naturally circulates at high levels throughout the body, and especially in the nervous system. In the brain, adenosine plays a generally protective role, part of which is to reduce neural activity levels – for example, there is some evidence that adenosine helps to induce torpor in animals that seasonally hibernate.[103]Mechanism of action
Because caffeine is both water-soluble and lipid-soluble, it readily crosses the blood–brain barrier that separates the bloodstream from the interior of the brain. Once in the brain, the principal mode of action is as a nonselective antagonist of adenosine receptors (in other words, an agent that reduces the effects of adenosine). The caffeine molecule is structurally similar to adenosine, and is capable of binding to adenosine receptors on the surface of cells without activating them, thereby acting as a competitive inhibitor.[104]
Adenosine is found in every part of the body, because it plays a role in the fundamental adenosine triphosphate (ATP) related energy producing mechanism and is also needed for RNA synthesis, but it has additional functions in the brain. The evidence indicates that brain adenosine acts to protect the brain by suppressing neural activity and by increasing blood flow via receptors located on vascular smooth muscle.[105] Brain adenosine levels are increased by various types of metabolic stress, including lack of oxygen and interruption of blood flow. There is evidence that adenosine functions as a synaptically released neurotransmitter in some parts of the brain; however, stress-related adenosine increases appear to be produced mainly by extracellular metabolism of ATP. Unlike most neurotransmitters, adenosine does not seem to be packaged into vesicles that are released in a voltage-controlled manner, but the possibility of such a mechanism has not been ruled out fully.[105]
Several classes of adenosine receptors have been described, with different anatomical distributions. A1 receptors are widely distributed, and act to inhibit calcium uptake. A2A receptors are heavily concentrated in the basal ganglia, an area that plays a critical role in behavior control, but can be found in other parts of the brain as well, in lower densities. There is evidence that A 2A receptors interact with the dopamine system, which is involved in reward and arousal. (A2A receptors can also be found on arterial walls and blood cell membranes.)[106]
Beyond its general neuroprotective effects, there are reasons to believe that adenosine may be more specifically involved in control of the sleep-wake cycle. Robert McCarley and his colleagues have argued that accumulation of adenosine may be a primary cause of the sensation of sleepiness that follows prolonged mental activity, and that the effects may be mediated both by inhibition of wake-promoting neurons via A1 receptors, and activation of sleep-promoting neurons via indirect effects on A2A receptors.[106] More recent studies have provided additional evidence for the importance of A2A, but not A1, receptors.[107]
Caffeine, like other xanthines, also acts as a phosphodiesterase inhibitor.[108] A number of potential mechanisms have been proposed for the athletic performance-enhancing effects of caffeine.[109] In the classic, or metabolic theory, caffeine may increase fat utilization and decrease glycogen utilization. Caffeine mobilizes free fatty acids from fat and/or intramuscular triglycerides by increasing circulating epinephrine levels. The increased availability of free fatty acids increases fat oxidation and spares muscle glycogen, thereby enhancing endurance performance. In the nervous system, caffeine may reduce the perception of effort by lowering the neuron activation threshold, making it easier to recruit the muscles for exercise.[110]
Caffeine metabolites
Metabolites of caffeine also contribute to caffeine's effects. Paraxanthine is responsible for an increase in the lipolysis process, which releases glycerol and fatty acids into the blood to be used as a source of fuel by the muscles. Theobromine is a vasodilator that increases the amount of oxygen and nutrient flow to the brain and muscles. Theophylline acts as a smooth muscle relaxant that chiefly affects bronchioles and acts as a chronotrope and inotrope that increases heart rate and force of contraction.[111]Metabolism
The biological half-life of caffeine – the time required for the body to eliminate one-half of the total amount of caffeine – varies widely among individuals according to such factors as age, liver function, pregnancy, some concurrent medications, and the level of enzymes in the liver needed for caffeine metabolism. It can also be significantly altered by drugs or hormonal states. In healthy adults, caffeine's half-life has been measured with a range of results. Some measures get 4.9 hours,[117] and others are at around 6 hours.[118] Heavy cigarette smokers show a decrease in half-life of 30–50%, oral contraceptives can double it, and pregnancy can raise it even more, to as much as 15 hours during the last trimester. In newborn infants the half-life can be 80 hours or more; however it drops very rapidly with age, possibly to less than the adult value by the age of 6 months.[30] The antidepressant fluvoxamine (Luvox) reduces the clearance of caffeine by more than 90%, and prolongs its elimination half-life more than tenfold; from 4.9 hours to 56 hours.[117]
Caffeine is metabolized in the liver by the cytochrome P450 oxidase enzyme system (to be specific, the 1A2 isozyme) into three metabolic dimethylxanthines,[119] each of which has its own effects on the body:
- Paraxanthine (84%): Increases lipolysis, leading to elevated glycerol and free fatty acid levels in the blood plasma.
- Theobromine (12%): Dilates blood vessels and increases urine volume. Theobromine is also the principal alkaloid in the cocoa bean, and therefore chocolate.
- Theophylline (4%): Relaxes smooth muscles of the bronchi, and is used to treat asthma. The therapeutic dose of theophylline, however, is many times greater than the levels attained from caffeine metabolism.[citation needed]
Some quinolone antibiotics exert an inhibitory effect on the cytochrome P-450 enzyme CYP1A2, thereby reducing clearance of caffeine and thus increasing blood levels.[121]
A 2011 analysis published by PLoS Genetics reviewed five studies covering more than 47,000 subjects of European descent. Researchers determined that habitual caffeine intake is associated with variations in two genes that regulate how quickly the body processes caffeine. Subjects who had a high-intake mutation of either gene on both chromosomes consumed 40 mg more caffeine per day (equivalent to a can of cola) than people who did not.[122]
Detection in biological fluids
Caffeine can be quantified in blood, plasma, or serum to monitor therapy in neonates, confirm a diagnosis of poisoning, or facilitate a medicolegal death investigation. Plasma caffeine levels are usually in the range of 2–10 mg/L in coffee drinkers, 12–36 mg/L in neonates receiving treatment for apnea, and 40–400 mg/L in victims of acute overdosage. Urinary caffeine concentration is frequently measured in competitive sports programs, for which a level in excess of 15 mg/L is usually considered to represent abuse.[123]Decaffeination
Main article: Decaffeination
Extraction of caffeine from coffee, to produce decaffeinated coffee
and caffeine, is an important industrial process and can be performed
using a number of different solvents. Benzene, chloroform, trichloroethylene, and dichloromethane
have all been used over the years but for reasons of safety,
environmental impact, cost, and flavor, they have been superseded by the
following main methods:- Water extraction: Coffee beans are soaked in water. The water, which contains many other compounds in addition to caffeine and contributes to the flavor of coffee, is then passed through activated charcoal, which removes the caffeine. The water can then be put back with the beans and evaporated dry, leaving decaffeinated coffee with its original flavor. Coffee manufacturers recover the caffeine and resell it for use in soft drinks and over-the-counter caffeine tablets.[124]
- Supercritical carbon dioxide extraction: Supercritical carbon dioxide is an excellent nonpolar solvent for caffeine, and is safer than the organic solvents that are otherwise used. The extraction process is simple: CO2 is forced through the green coffee beans at temperatures above 31.1 °C and pressures above 73 atm. Under these conditions, CO2 is in a "supercritical" state: It has gaslike properties that allow it to penetrate deep into the beans but also liquid-like properties that dissolve 97–99% of the caffeine. The caffeine-laden CO2 is then sprayed with high pressure water to remove the caffeine. The caffeine can then be isolated by charcoal adsorption (as above) or by distillation, recrystallization, or reverse osmosis.[124]
- Extraction by organic solvents: Certain organic solvents such as ethyl acetate present much less health and environmental hazard than chlorinated and aromatic organic solvents used formerly. Another method is to use triglyceride oils obtained from spent coffee grounds.[124]
History
Main articles: History of chocolate, History of coffee, History of tea, and History of yerba mate
Caffeine was first isolated from coffee in 1820 by the German chemist Friedlieb Ferdinand Runge, and then independently in 1821 by French chemists Pierre Robiquet, Pierre Pelletier, and Joseph Caventou. Pelletier coined the word "cafeine" from the French word for coffee (café), and this term became the English word "caffeine".According to Chinese legend, the Chinese emperor Shennong, reputed to have reigned in about 3000 BCE, accidentally discovered tea when he noted that when certain leaves fell into boiling water, a fragrant and restorative drink resulted.[126] Shennong is also mentioned in Lu Yu's Cha Jing, a famous early work on the subject of tea.[127]
The history of coffee has been recorded as far back as the ninth century. During that time, coffee beans were available only in their place of origin, Ethiopia. Legends trace the discovery of coffee either to a Sufi dervish named Omar, or to a goatherder named Kaldi, who observed goats become elated and sleepless at night after grazing on coffee shrubs and, upon trying the berries the goats had been eating, experienced the same vitality.[128] The earliest literary mention of coffee may be a reference to Bunchum in the works of the 9th-century Persian physician al-Razi.[128]:11 The first reliable record of the use of coffee outside Ethiopia comes from Aden, in 1451.[128]:16 The appreciation of coffee as a beverage in Europe dates from the 17th century. The first coffee house in Venice opened some time in the late 1640s.[128]:127 In Britain, the first coffee house was opened in Oxford in 1650.[128]:41 They soon became popular throughout Western Europe, and played a significant role in social relations in the 17th and 18th centuries.[129]
Use of the kola nut, like the coffee berry and tea leaf, appears to have ancient origins. It is chewed in many West African cultures, individually or in a social setting, to restore vitality and ease hunger pangs. In 1911, kola became the focus of one of the earliest documented health scares, when the US government seized 40 barrels and 20 kegs of Coca-Cola syrup in Chattanooga, Tennessee, alleging the caffeine in its drink was "injurious to health".[130] Although the judge ruled in favor of Coca-Cola, two bills were introduced to the U.S. House of Representatives in 1912 to amend the Pure Food and Drug Act, adding caffeine to the list of "habit-forming" and "deleterious" substances, which must be listed on a product's label.[131][unreliable source?]
The earliest evidence of cocoa bean use comes from residue found in an ancient Mayan pot dated to 600 BCE. In the New World, chocolate was consumed in a bitter and spicy drink called xocolatl, often seasoned with vanilla, chile pepper, and achiote. Xocolatl was believed to fight fatigue, a belief probably attributable to the theobromine and caffeine content. Chocolate was an important luxury good throughout pre-Columbian Mesoamerica, and cocoa beans were often used as currency.[citation needed]
Xocolatl was introduced to Europe by the Spaniards, and became a popular beverage by 1700. The Spaniards also introduced the cacao tree into the West Indies and the Philippines. It was used in alchemical processes, where it was known as "black bean".[citation needed]
The leaves and stems of the yaupon holly (Ilex vomitoria) were used by Native Americans to brew a tea called asi or the "black drink".[132] Archaeologists have found evidence of this use stretch back far into antiquity,[133] possibly dating to Late Archaic times.[132]
Discovery
Pelletier's article on caffeine was the first to use the term in print (in the French form Caféine).[136] It corroborates Berzelius's account:
German chemist Hermann Emil Fischer (1852–1919) first synthesized caffeine from raw materials in 1895 and two years later, he also derived the structural formula of the compound.[citation needed]Caffeine, noun (feminine). Crystallizable substance discovered in coffee in 1821 by Mr. Robiquet. During the same period – while they were searching for quinine in coffee because coffee is considered by several doctors to be a medicine that reduces fevers and because coffee belongs to the same family as the cinchona [quinine] tree – on their part, Mssrs. Pelletier and Caventou obtained caffeine; but because their research had a different goal and because their research had not been finished, they left priority on this subject to Mr. Robiquet. We do not know why Mr. Robiquet has not published the analysis of coffee which he read to the Pharmacy Society. Its publication would have allowed us to make caffeine better known and give us accurate ideas of coffee's composition ...
Robiquet was one of the first to isolate and describe the properties of pure caffeine[137] while Pelletier was the first to perform an elemental analysis.[138]
Berzelius later acknowledged Runge's priority in the extraction of caffeine, stating:[139] "However, at this point, it should not remain unmentioned that Runge (in his Phytochemical Discoveries, 1820, pages 146–147) specified the same method and described caffeine under the name Caffeebase a year earlier than Robiquet, to whom the discovery of this substance is usually attributed, having made the first oral announcement about it at a meeting of the Pharmacy Society in Paris. According to Runge, he did this at the behest of Johann Wolfgang von Goethe."[140] In 1827, M. Oudry isolated "theine" from tea,[141] but it was later proved by Mulder[142] and by Carl Jobst[143] that theine was the same as caffeine.[140] The structure of caffeine was elucidated near the end of the 19th century by Hermann Emil Fischer, who was also the first to achieve its total synthesis. This was part of the work for which Fischer was awarded the Nobel Prize in 1902.[144]
Legality
Today, caffeine is legal and available in many forms in all jurisdictions[citation needed].Historically, coffee and thus caffeine was illegal for some classes in Mecca in parts of the 16th century,[145] in the Ottoman empire,[146] Charles II of England tried to ban it in 1676,[147][148] Frederic II of Prussia banned it in 1777,[149][150] and coffee was banned in Sweden in the years 1756–1769, 1794–1796, 1799–1802, and 1817–1823. The bans on coffee have often had religious, economic, or political reasons rather than being based on concerns for the well-being of the population.
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