Risk of Caffeine Drug

By: Pharma Tips | Views: 1938 | Date: 27-May-2011


•    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.


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.


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".


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.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.

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.

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.

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