Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a psychoactive stimulant drug and a mild diuretic.Caffeine was discovered by a German chemist, Friedrich Ferdinand Runge, in 1819. He coined the term "kaffein", a chemical compound in coffee, which in English became caffeine. Caffeine is also called guaranine when found in guarana, mateine when found in mate, and theine when found in tea; all of these names are synonyms for the same chemical compound.
Caffeine as a Psychoactive Stimulant Drug and a Mild Diuretic
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a psychoactive stimulant drug and a mild diuretic.
Caffeine was discovered by a German chemist, Friedrich Ferdinand Runge, in 1819. He coined the term "kaffein", a chemical compound in coffee, which in English became caffeine. Caffeine is also called guaranine when found in guarana, mateine when found in mate, and theine when found in tea; all of these names are synonyms for the same chemical compound.
In general, each of the following contains approximately 200 milligrams of caffeine:
• One 200 milligram caffeine pill
• 3 x espresso shots (30 mL, or 1 fl. oz each)
• 355 mL (12 fl. oz) cup of regular coffee
• 680 g (1.5 lb) of milk chocolate
• 540 mL (18 fl. oz) of black tea
• 710 mL (24 fl. oz) of Red Bull energy drink
• 1.2 L (40 fl. oz) of Mountain Dew
• 2 L (68 fl. oz) of Coca-Cola
• 2.4 L (80 fl. oz) of green tea
• 12 L (400 fl. oz) of decaffeinated coffee
Caffeine extraction 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have all been used over the years but for reasons of safety, environmental impact, cost and flavor, they have been superseded by the following main methods:
1. Water excreation
2. Suprecritical carbon dioxide extraction
3. Extraction by organic solvents
2. PHARMACOLOGY OF CAFFIENE
Caffeine is a central nervous system and metabolic stimulant,4 and is used both recreationally and medically to reduce physical fatigue and restore mental alertness when unusual weakness or drowsiness occurs. Caffeine stimulates the central nervous system first at the higher levels, resulting in increased alertness and wakefulness, faster and clearer flow of thought, increased focus, and better general body coordination, and later at the spinal cord level at higher doses.5 complex chemistry, and acts through several mechanisms as described below.
2.1. MECHANISM OF ACTION:
Caffeine's principal mode of action is as an antagonist of adenosine receptors in the brain.
Adenosine release mechanisms in the brain are complex.6 There is evidence that adenosine functions as a synaptically released neurotransmitter in some cases, but stress-related adenosine increases appear to be produced mainly by extracellular metabolism of ATP. It is not likely that adenosine is the primary neurotransmitter for any group of neurons, but rather that it is released together with other transmitters by a number of neuron types. 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. More recent studies have provided additional evidence for the importance of A2A, but not A1, receptors.7
Some of the secondary effects of caffeine are probably caused by actions unrelated to adenosine. Caffeine is known to be a competitive inhibitor of the enzyme cAMP-phosphodiesterase (cAMP-PDE), which converts cyclic AMP (cAMP) in cells to its noncyclic form, thus allowing cAMP to build up in cells. Cyclic AMP participates in activation of Protein Kinase A (PKA) to begin the phosphorylation of specific enzymes used in glucose synthesis.
2.2. METABOLISM & HALF LIFE
Caffeine is metabolized in the liver into three primary metabolites: paraxanthine (84%), theobromine (12%), and theophylline (4%).Caffeine from coffee or other beverages is absorbed by the stomach and small intestine within 45 minutes of ingestion and then distributed throughout all tissues of the body8. It is eliminated by first-order kinetics.9 Caffeine can also be ingested rectally, evidenced by the formulation of suppositories of ergotamine tartrate and caffeine (for the relief of migraine)10 and chlorobutanol and caffeine (for the treatment of hyperemesis).11
The 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. In healthy adults, caffeine's half-life is approximately 3–4 hours. In women taking oral contraceptives this is increased to 5–10 hours, 12 and in pregnant women the half-life is roughly 9–11 hours.13 Caffeine can accumulate in individuals with severe liver disease, increasing its half-life up to 96 hours.14 In infants and young children, the half-life may be longer than in adults; half-life in a newborn baby may be as long as 30 hours. Other factors such as smoking can shorten caffeine's half-life.15
Caffeine is metabolized in the liver by the cytochrome P450 oxidase enzyme system (specifically, the 1A2 isozyme) into three metabolic dimethylxanthines, which each have their own effects on the body:
• Paraxanthine (84%): Has the effect of increasing 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 cocoa, 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. Each of these metabolites is further metabolized and then excreted in the urine.
• In large amounts, and especially over extended periods of time, caffeine can lead to a condition known as caffeinism.16 , 17
• Caffeinism usually combines caffeine dependency with a wide range of unpleasant physical and mental conditions including nervousness, irritability, anxiety, tremulousness, muscle twitching (hyperreflexia), insomnia, headaches, respiratory alkalosis, and heart palpitations.18, 19
• Furthermore, because caffeine increases the production of stomach acid, high usage over time can lead to peptic ulcers, erosive esophagitis, and gastroesophageal reflux disease.20
• There are four caffeine-induced psychiatric disorders recognized by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition: caffeine intoxication, caffeine-induced anxiety disorder, caffeine-induced sleep disorder, and caffeine-related disorder not otherwise specified (NOS).
2.3.1. Caffeine intoxication 22-28
An acute overdose of caffeine, usually in excess of about 300 milligrams, dependent on body weight and level of caffeine tolerance, can result in a state of central nervous system over-stimulation called caffeine intoxication, colloquially "caffeine jitters". The symptoms of caffeine intoxication are not unlike overdoses of other stimulants. It may include restlessness, nervousness, excitement, insomnia, flushing of the face, increased urination, gastrointestinal disturbance, muscle twitching, a rambling flow of thought and speech, irritability, irregular or rapid heart beat, and psychomotor agitation.22 In cases of much larger overdoses mania, depression, lapses in judgment, disorientation, disinhibition, delusions, hallucinations and psychosis may occur, and rhabdomyolysis (breakdown of skeletal muscle tissue) can be provoked.
In cases of extreme overdose, death can result. The median lethal dose (LD50) given orally, is 192 milligrams per kilogram in rats. The LD50 of caffeine in humans is dependent on weight and individual sensitivity and estimated to be about 150 to 200 milligrams per kilogram of body mass, roughly 80 to 100 cups of coffee for an average adult taken within a limited time frame that is dependent on half-life. 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. Death typically occurs due to ventricular fibrillation brought about 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.
2.3.2 Anxiety and sleep disorders 29-31
Two infrequently diagnosed caffeine-induced disorders that are recognized by the American Psychiatric Association (APA) are caffeine-induced sleep disorder and caffeine-induced anxiety disorder, which can result from long-term excessive caffeine intake.
In the case of caffeine-induced sleep disorder, an individual regularly ingests high doses of caffeine sufficient to induce a significant disturbance in his or her sleep, sufficiently severe to warrant clinical attention.
In some individuals, the large amounts of caffeine can induce anxiety severe enough to necessitate clinical attention. This caffeine-induced anxiety disorder can take many forms, from generalized anxiety to panic attacks, obsessive-compulsive symptoms, or even phobic symptoms.
Because this condition can mimic organic mental disorders, such as panic disorder, generalized anxiety disorder, bipolar disorder, or even schizophrenia, a number of medical professionals believe caffeine-intoxicated people are routinely misdiagnosed and unnecessarily medicated when the treatment for caffeine-induced psychosis would simply be to stop further caffeine intake. A study in the British Journal of Addiction concluded that caffeinism, although infrequently diagnosed, may afflict as many as one person in ten of the population.
3. EFFECT ON POPULATION
Global consumption of caffiene has been estimated at 120,000 tonnes per annum,making it one of the most popular psychoactive substances.This number equates to one serving of acaffiene beverage for every person, per day.
Caffeine: What the World Drinks
Here is a list of caffeine consumption worldwide.
sweden, Denmark and Norway — all around 400mg of caffeine per person per day! Those guys must be wired.
South American countries such as Argentina and Brazil get most of their caffeine from Maté.
The Brits are big tea drinkers .
The US Just 168mg of caffeine per person per day (mostly coffee).
Country Caffeine from coffee mg per day Caffeine from tea
mg per day Caffeine from maté
mg per day Caffeine from cocoa
mg per day Caffeine from all these sources
mg per day
Algeria 79 5 0 1 85
Angola 4 - 0 0 4
Argentina 1 52 5 100
Australia Australia 29 0 0 232
Austria 276 8 0 16 300
Brazi l26 1 10 4 40
Canada 180 18 0 12 210
China 2 14 0 0 16
Columbia 126 0 0 9 136
Denmark 35 15 0 21 390
Egypt 5 53 0 1 58
Finland 322 6 0 1 329
France 215 8 0 16 239
Germany 292 9 0 12 313
Guatemala 23 2 0 2 27
Honduras 160 - 0 2 162
Hungary 138 Japan 3 0 9 150
India 1 26 0 0 27
Ireland 81 127 0 5 213
Italy 198 3 0 8 210
Ivory Coast 6 1 0 13 20
Japan 119 44 0 5 169
Kenya 8 42 0 0 50
Kuwait 49 112 0 13 173
Malaysia 49 27 0 4 81
Netherlands 369 38 0 6 414
Nicaragua 219 - 0 1 221
Nigeria 1 2 0 1 4
Norway 8 8 0 13 400
Paraguay 51 1 101 3 156
Poland 100 33 0 8 141
Russian Fed 26 40 0 7 72
Saudi Arabia 14 13 0 2 28
South Africa 15 23 0 1 40
Sweden 388 12 0 7 407
Switzerland 275 11 0 1 288
Syria 35 Syria35 67 5 2 108
3Tanzania Tanzan3ia 4 0 0 7
UnitedArab Emirates 74 0 5 167
United Kingdom 92 96 0 14 202
United States 87 12 0 12 168
Venezuela 135 0 0 4 139
4.1. Association between caffeine intake and risk of Parkinson’s disease among fast and slow metabolizers
The study is carried with an objective of the relationship between caffeine intake and risk of PD in both fast and slow caffeine metabolizers. Genotyping of the CYP1A2 variant was carried out using the allelic discrimination method.As result Out of 1000 participants who were initially screened, 886 consisting of 418 PD and 468 race, sex and age matched controls were included. No evidence existed to suggest any association between CYP1A2 and the onset of PD (P=0.08).So by this conclusion is, the association between caffeine intake and risk of PD was similarly observed in both fast and slow caffeine metabolizers, supporting experimental evidence in animal models that both caffeine and its major metabolite, paraxanthine, are neuroprotective.
4.2 Effects on the heart
Caffeine binds to receptors on the surface of heart muscle cells which leads to an increase in the level of cAMP inside the cells (by blocking the enzyme that degrades cAMP), mimicking the effects of epinephrine (which binds to receptors on the cell that activate cAMP production). cAMP acts as a "second messenger," and activates a large number of protein kinase A (PKA; cAMP-dependent protein kinase). This has the overall effect of increasing the rate of glycolysis and increases the amount of ATP available for muscle contraction and relaxation. According to one study, caffeine in the form of coffee, significantly reduces the risk of heart disease in epidemiological studies. However, the protective effect was found only in participants who were not severely hypertensive (i.e. patients that are not suffering from a very high blood pressure). Furthermore, no significan protective effect was found in participants aged less than 65 years or in cerebrovascular disease. The mortality for those aged equal or more than 65 years.
4.3. Association between caffeine & risk of rheumatoid arthritis
The study carried out on an association between consumption of coffee or decaffeinated coffee and the risk of rheumatoid arthritis (RA), although data are sparse and somewhat inconsistent. Furthermore, existing studies measured dietary exposures and potential confounders only at baseline and did not consider possible changes in diet or lifestyle over the followup period. We studied whether coffee, decaffeinated coffee, total coffee, tea, or overall caffeine consumption was associated with the risk of RA, using the Nurses' Health Study, a longitudinal cohort study of 121,701 women. Result shows that not find a significant association between decaffeinated coffee consumption of >/=4 cups/day (compared with no decaffeinated coffee consumption) and subsequent risk of incident RA, in either an adjusted multivariate model (relative risk [RR] 1.1, 95% confidence interval [95% CI] 0.5-2.2) or a multivariate model using only baseline reports of decaffeinated coffee consumption (RR 1.0, 95% CI 0.6-1.7). Similarly, there was no relationship between cumulative caffeinated coffee consumption and RA risk (RR 1.1, 95% CI 0.8-1.6 for >/=4 cups per day versus none) or between tea consumption and RA risk (RR 1.1, 95% CI 0.7-1.8 for >3 cups/day versus none). Total coffee and total caffeine consumption were also not associated with the risk of RA.Means little evidence of an association between coffee, decaffeinated coffee, or tea consumption and the risk of RA among women.
5.1. EFFECT ON MEMORY & LEARNING
• An array of studies found that caffeine could have nootropic effects, inducing certain changes in memory and learning. However, the tests performed contradict one another and the results have proven inconsistent and inconclusive.
• Researchers have found that long-term consumption of low dose caffeine slowed hippocampus-dependent learning and impaired long-term memory in mice. Caffeine consumption for 4 weeks also significantly reduced hippocampal neurogenesis compared to controls during the experiment. The conclusion was that long-term consumption of caffeine could inhibit hippocampus-dependent learning and memory partially through inhibition of hippocampal neurogenesis. In another study, caffeine was added to rat neurons in vitro. The dendritic spines (a part of the brain cell used in forming connections between neurons) taken from the hippocampus (a part of the brain associated with memory) grew by 33% and new spines formed. After an hour or two, however, these cells returned to their original shape.
• Another study showed that subjects—after receiving 100 milligrams of caffeine—had increased activity in brain regions located in the frontal lobe, where a part of the working memory network is located, and the anterior cingulate cortex, a part of the brain that controls attention. The caffeinated subjects also performed better on the memory tasks.
• However, a different study showed that caffeine could impair short term memory and increase the likelihood of the tip of the tongue phenomenon. The study allowed the researchers to suggest that caffeine could aid short-term memory when the information to be recalled is related to the current train of thought, but also to hypothesize that caffeine hinders short-term memory when the train of thought is unrelated. In essence, caffeine consumption increases mental performance related to focused thought while it may decrease broad-range thinking abilities.
5.2.EFFECTS ON CHILDREN
Scientific studies contradict the common belief that caffeine consumption causes stunted growth in children. Children also can experience the same effects from caffeine as adults. Most energy drinks (containing extremely high amounts of caffeine) have been banned in many schools throughout the world.
5.3 CAFFIENE INTAKE DURING PREGNANCY
Despite its widespread use and the conventional that it is a safe substance, study suggested that pregnant women who consume 200 milligrams or more of caffeine per day have about twice the miscarriage risk as women who consume none. However, another 2008 study found no correlation between miscarriage and caffeine consumption. The UK Food Standards Agency has recommended that pregnant women should limit their caffeine intake to less than 200 mg of caffeine a day – the equivalent of two mugs of coffee. The recommendation was based on findings of increased levels of miscarriage in women who consume more caffeine than this. The FSA noted that the design of the studies made it impossible to be certain that the differences were due to caffeine per se, instead of other lifestyle differences possibly associated with high levels of caffeine consumption, but judged the advice to be prudent.
we concluded that an intake of 200 milligrams or more per day, representing two or more cups, "significantly increases the risk of miscarriage".
5.4 EPILEPSY IN NEW BORN
A research has found that if women drink too much coffee during pregnancy can increase the risk of their babies developing epileptic seizures or fits. Studies have found that caffeine may be linked to the development of epileptic discharges in cells from newborn mammals that have been briefly starved of oxygen.
A research team from the Institut National De La Santé in France examined cells from the hippocampus, a part of the brain that is thought to control memory.They subjected the cells to the same level of caffeine found in several cups of coffee, and starved them of oxygen for three to four minutes. They found that the cells all fired at the same time - a phenomenon seen during epileptic seizures. Nothing happened if caffeine was not added to the preparation, or if oxygen was present.
The researchers believe that the caffeine molecules bind to receptors in the cells, blocking the action of a chemical called adenosine which plays an important role in handling stress. During stressful episodes such as oxygen starvation, adenosine protects the nerve circuits from uncontrolled activity.
5.5 Caffeine intake and fecundability
Fecundability has been defined as the ability to achieve a recognized pregnancy. Several studies on caffeine and fecundability have been conducted but have been inconclusive. This may be explained partly by lack of stratification by smoking. Furthermore, few researchers have tried to separate the effect of caffeine from different sources (coffee, tea, cola, and chocolate). Clearly, the relationship between caffeine and fecundability needs further research, given the high prevalence of caffeine intake among women of childbearing age. We examined the independent and combined effects of smoking and caffeine intake from different sources on the probability of conception. From 1992 to 1995, a total of 430 couples were recruited after a nationwide mailing of a personal letter to 52,255 trade union members who were 20 to 35 years old, lived with a partner, and had no previous reproductive experience. At enrollment and in six cycles of follow-up, both partners filled out a questionnaire on different factors including smoking habits and their intake of coffee, tea, chocolate, cola beverages, and chocolate bars. In all, 1596 cycles and 423 couples were included in the analyses. The cycle-specific association between caffeine intake and fecundability was analyzed in a logistic regression model with the outcome at each cycle (pregnant or not pregnant) in a Cox discrete model calculating the fecundability odds-ratio (FR). Compared to nonsmoking women with caffeine intake less than 300 mg/d, nonsmoking women who consumed 300 to 700 mg/d caffeine had a FR of 0.88 [95% confidence interval (CI) 0.60-1.31], whereas women with a higher caffeine intake had a FR = 0.63 (95% CI 0.25-1.60) after adjusting for female body mass index and alcohol intake, diseases of the female reproductive organs, semen quality, and duration of menstrual cycle. No dose-response relationship was found among smokers. Among males, the same decline in point estimates of the FR was present. Smoking women whose only source of caffeine was coffee (>300 mg/d) had a reduced fecundability odds-ratio (FR = 0.34; 95% CI 0.12-0.98). An interaction between caffeine and smoking is biologically plausible, and the lack of effect among smokers may be due to faster metabolism of caffeine. Our findings suggest that especially nonsmoking women who wish to achieve a pregnancy might benefit from a reduced caffeine intake.
PIP: The independent and combined effects of smoking and caffeine intake from different sources on fecundability were assessed in a national survey of 423 Danish couples. Couples were recruited to the study in 1992-95 through a mailing to 52,255 female trade union members seeking women who were 20-35 years old, lived with a partner, had no previous pregnancies, and intended to discontinue contraception in order to become pregnant. A total of 1596 cycles were included in the 6-month study and the cycle-specific association between caffeine intake and fecundability was analyzed in a logistic regression model with the outcome (pregnant, not pregnant) in a Cox discrete model. Compared with nonsmoking women with a caffeine intake less than 300 mg/day, nonsmoking women who consumed 300-700 mg/day of caffeine had a fecundability odds ratio (FR) of 0.88 (95% confidence interval (CI), 0.60-1.31), while those with a higher consumption had an FR of 0.63 (95% CI, 0.25-1.60), after adjustments for body mass index, alcohol intake, diseases of the female reproductive organs, semen quality, and duration of the menstrual cycle. No such dose-response relationship was detected among smokers. The same decline in point estimates of the FR was present was males. Smoking women whose only source of caffeine was coffee (over 300 mg/day) had a reduced FR (0.34; 95% CI, 0.12-0.98). The lack of adverse effect among smokers may be due to faster metabolism and clearance of caffeine. Overall, these findings indicate that nonsmoking women who wish to achieve pregnancy should consider reducing their caffeine intake.
5.6 caffeine & teratogenicity
Caffeine is a methylated xanthine that acts as a mild central nervous system stimulant. It is present in many beverages, including coffee, tea, and colas, as well as chocolate. Caffeine constitutes 1-2% of roasted coffee beans, 3.5% of fresh tea leaves, and approximately 2% of mate leaves Many over-the-counter medications, such as cold and allergy tablets, headache medicines, diuretics, and stimulants also contain caffeine, although they lead to relatively minimal intake. In epidemiological studies, it is assumed that one cup of coffee contains < or =100 mg of caffeine, and soft drinks, such as colas, contain 10-50 mg of caffeine per 12-ounce serving. The per-capita consumption of caffeine from all sources is estimated to be about 3-7 mg/kg per day, or approximately 200 mg/day. Consumption of caffeinated beverages during pregnancy is quite common and is estimated to be approximately 144 mg/day, or 2.4 mg/kg for a 60-kg human . However, pregnant women appear to consume slightly less than do other adults, approximately 1 mg/kg per day . This decrease may be interrelated with taste aversion . The medical literature contains many varied references that appear to indicate that human adverse reproductive/developmental effects are produced by caffeine. If caffeine indeed causes such effects, the reproductive consequences could be very serious because caffeine-containing foods and beverages are consumed by most of the human populations of the world, and consumption in the United States is estimated to be 4.5-kg/person/year . Therefore, the medical literature dealing with developmental and reproductive risks of caffeine was reviewed, and the biological plausibility of the epidemiological and animal findings, as well as the methods and conclusions of previous investigators, were evaluated. The epidemiological studies describe exposures of women to caffeine during pregnancy, as well as the occurrence of congenital malformations, fetal growth retardation, small-for-date babies, effects, and maternal fertility problems that presumably resulted from the miscarriages (spontaneous abortions), behavioral caffeine consumption. A few epidemiological studies were concerned with the genetic effects of preconception exposures to caffeine. Animal studies, conducted mostly in pregnant rats and mice, were designed to produce malformations. The objectives of the present review are to summarize the findings from the various clinical and animals studies, objectively discuss the merits and/or faults inherent in the studies and establish a global reproductive risk assessment for caffeine consumption in humans during pregnancy. It should be noted that evaluation of the developmental risks of caffeine based solely on epidemiological studies is difficult because the findings are inconsistent. Even more important, is the fact that caffeine users are subject to multiple confounding factors that make analyses difficult and prevent investigators from reaching definitive conclusions. For example, the caffeine content of foods and beverages can vary considerably, which can interfere with obtaining valid interpretations from many human studies. Isolated epidemiological studies dealing with the risk of abortion, without evaluating other developmental and reproductive effects, are the most difficult to interpret, because they present special problems that are sometimes ignored in epidemiological studies. The results of animal studies are probably most helpful in solving some of the dilemmas created by the epidemiological studies. Proven human teratogens have an identifiable syndrome. The malformations described in the animal studies at very high doses fit the description of vascular disruptive types of malformations.
5.7. Caffeine effect on delayed conception
The authors examined the effects of caffeine consumption on waiting time to conception in the Reproductive Health Study, a retrospective study of 1,430 non-contracepting, parous women interviewed between July 1989 and June 1990 at Fishkill, New York, and Burlington, Vermont. Information was obtained on 2,501 pregnancies since 1980. Women's reported consumption of caffeinated beverages during the first month of pregnancy was used to estimate daily caffeine intake, which was categorized as none, 1-150, 151-300, and > or = 301 mg. Information on delayed conception was analyzed as a dichotomous variable (< or = 12 months delay vs. > 12 months delay), and the per cycle probability of conception (fecundability) was estimated using waiting time to conception as a continuous variable. Odds ratios of delayed conception and fecundability ratios adjusted for age, parity, smoking, last contraceptive used, infertility history, and race, were estimated by logistic regression and Cox proportional hazard models, respectively. Women who did not smoke and who consumed no caffeine were used as a reference group. The adjusted odds ratio of delayed conception for more than one year was not increased among women who consumed < or = 300 mg of caffeine daily. However, the odds ratio (OR) was 2.65 (95% confidence interval (CI) 1.38-5.07) among nonsmokers who consumed > or = 301 mg of caffeine daily. Although smoking per se was associated with a significant increased risk of delayed conception (OR = 1.77, 95% CI 1.33-2.37), no effect of high caffeine consumption was observed among women who smoked. Fecundability was reduced among nonsmokers who consumed
more than 300 mg caffeine daily (fecundability ratio = 0.74, 95% CI 0.59-0.92). Smoking reduced the fecundability ratio, but the authors observed no effect of caffeine consumption on fecundability among women who smoked. Other studies provide biologic plausibility for these findings. The authors conclude that high levels of caffeine consumption may result in delayed conception among women who do not smoke cigarettes.
Caffeine is widely consumed throughout the world in behaviorally active doses. Most of the data suggest that caffeine, in the doses that are commonly consumed, acts primarily by blocking adenosine A1 and A2A receptors.
Caffeine has important effects on alertness, and there is no doubt that caffeine is widely consumed by subjects who need to stay awake. Caffeine also has some poorly investigated analgesic actions that contribute to its use. In some contexts there are performance-enhancing actions.
So,Over all we can say that caffeine is beneficial in low doses which is used as neuroprotective, CNS stimulant.It doesn’t worse parkinsonism as well as no harmful effect on rheumatoid arthritis. It also give protective effect on heart.
Risk associated with use of caffeine are epilepsy in new borns, fecundability & delayed conception.It also produces teratogenic syndromes.