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4 March 2007; 5 November 2008
Last Updated: 27 September 2011 |
Caffeine
Facts, Amounts, Clinical Studies and Resources |
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Information about caffeine abounds on the Web, but a great deal of it is equivocal or contradictory.
Media interpretation regarding the significance of latest clinical studies at times appears hyperbolic or otherwise skewed,
making it difficult to appreciate the real significance of the reported study. Reviews of the literature, depending on the
objectives of the source, often focus on matters of causation (e.g., coffee does not cause pancreatic cancer),
as opposed to the idiosyncratic variables that must be considered in one's choice to use this stimulant, whether in food,
beverage or medicament. This page presents in-depth information from selected sources on the pharmacology, benefits and risks of
caffeine; caffeine content lists for foods, beverages and medicaments; clinical references and key resources for further enquiry. |
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Idiosyncratica...
People differ greatly in their sensitivity to caffeine. When analyzing caffeine’s effects on an individual, many factors
must be weighed:
- The amount ingested
- Frequency of consumption
- Individual metabolism
- Individual sensitivity
Caffeine is the world's favorite psychoactive substance. Only petroleum exceeds coffee as a globally traded commodity, and commerce and history of the United States are
closely linked to tea consumption. Soft drinks now rank as the most popular beverage in the United States, and most contain caffeine. Beverage trade groups estimate the
annual per capita soft drink consumption at 56 gallons. Research and worldwide beverage history confirm the safety of moderate caffeine consumption in healthy individuals.
The universal appeal of caffeine is related to its psychostimulant properties. In a healthy person, caffeine promotes cognitive arousal and fights fatigue. These same activating
properties can produce symptomatic distress in a small subset of the population. Susceptibility to this symptomatic distress is broadly determined by 3 factors — the dose consumed,
individual vulnerability to caffeine, and preexisting medical or psychiatric conditions (mood disorders in particular) that are aggravated by mild psychostimulant use. [...]
The literature suggests that the following effects on behavior of adult humans may occur when individuals consume moderate
amounts of caffeine.
- Caffeine increases alertness and reduces fatigue. This may be especially important in low arousal situations
(e.g. working at night).
- Caffeine improves performance on vigilance tasks and simple tasks that require sustained response.
Again, these effects are often clearest when alertness is reduced, although there is evidence that benefits may still occur when the
person is unimpaired.
- Effects on more complex tasks are difficult to assess and probably involve interactions between the caffeine
and other variables which increase alertness (e.g. personality and time of day).
- In contrast to the effects of caffeine consumption, withdrawal of caffeine has few effects on performance. There is often an increase in negative mood following withdrawal
of caffeine, but such effects may largely reflect the expectancies of the volunteers and the failure to conduct "blind" studies.
- Regular caffeine usage appears to be beneficial, with higher users having better mental functioning.
- Most people are very good at controlling their caffeine consumption to maximise the above positive effects. For example, the pattern of consumption over the
day shows that caffeine is often consumed to increase alertness. Indeed, many people do not consume much caffeine later in the day
since it is important not to be alert when one goes to sleep.
In contrast to effects found from normal caffeine intake, there are
reports that have demonstrated negative effects when very large amounts are given or sensitive groups (e.g. patients with anxiety
disorders) were studied. In this context caffeine has been shown to increase anxiety and impair sleep. There is also some evidence
that fine motor control may be impaired as a function of the increase in anxiety. Overall, the global picture that emerges depends on
whether one focuses on effects that are likely to be present when caffeine is consumed in moderation by the majority of the population
or on the effects found in extreme conditions. The evidence clearly shows that levels of caffeine consumed by most people
have largely positive effects on behavior. Excessive consumption can lead to problems, especially in sensitive individuals.
Many epidemiological studies have addressed the effects of coffee on cardiovascular disease. Most case-control studies suggest an increased risk in high
coffee consumers, whereas cohort studies indicate no clear association with cardiovascular risk. Several aspects could be considered to explain and/or
reconcile these inconsistencies. Selection bias and recall bias may explain a positive association supported by case-control studies. An inadequate adjustment
for many confounding factors (i.e., smoking, poor diet, sedentary lifestyle, etc.) could also affect the relationship between coffee consumption and cardiovascular
risk. Moreover, coffee contains several biologically active substances that may have either beneficial or harmful effects on the cardiovascular system. The
development of complete/partial tolerance to some caffeine effects in habitual drinkers adds to the complexity of coffee effects. Variation in cup size and
methods of coffee preparation may also explain some conflicting results. As it is not reasonable to conduct randomized controlled trials, it is recommended
that coffee consumption be moderate in healthy people and limited in individuals at high risk.
Caffeine is probably the most frequently ingested pharmacologically active substance in the world. It is found in common beverages (coffee, tea, soft drinks),
in products containing cocoa or chocolate, and in medications. Because of its wide consumption at different levels by most segments of the population, the public
and the scientific community have expressed interest in the potential for caffeine to produce adverse effects on human health. The possibility that caffeine
ingestion adversely affects human health was investigated based on reviews of (primarily) published human studies obtained through a comprehensive literature
search. Based on the data reviewed, it is concluded that for the healthy adult population, moderate daily caffeine intake at a dose level up to 400 mg day-1
(equivalent to 6 mg kg-1 body weight day-1 in a 65-kg person) is not associated with adverse effects such as general toxicity, cardiovascular effects, effects
on bone status and calcium balance (with consumption of adequate calcium), changes in adult behaviour, increased incidence of cancer and effects on male fertility.
The data also show that reproductive-aged women and children are 'at risk' subgroups who may require specific advice on moderating their caffeine intake. Based
on available evidence, it is suggested that reproductive-aged women should consume </=300 mg caffeine per day (equivalent to 4.6 mg kg-1 bw day-1 for a
65-kg person) while children should consume </=2.5 mg kg-1 bw day-1.
[...] Although not all of these side effects may occur, they may be more likely to
occur if caffeine is taken in large doses or more often than recommended. If
they do occur, they may need medical attention.
Check with your doctor as soon as possible if any of the following side
effects occur:
- More common
- Diarrhea; dizziness; fast heartbeat; hyperglycemia,
including blurred vision, drowsiness, dry mouth, flushed dry skin, fruit-like
breath odor, increased urination, ketones in urine, loss of appetite, nausea,
stomachache, tiredness, troubled breathing, unusual thirst, or vomiting (in
newborn babies); hypoglycemia, including anxious feeling, blurred vision,
cold sweats, confusion, cool pale skin, drowsiness, excessive hunger, fast
heartbeat, nausea, nervousness, restless sleep, shakiness, or unusual tiredness
or weakness (in newborn babies); irritability, nervousness, or severe
jitters (in newborn babies); nausea (severe) ; tremors;
trouble in sleeping ; vomiting
- Rare
- Abdominal or stomach bloating; dehydration ; diarrhea
(bloody); unusual tiredness or weakness
- Symptoms of overdose
- Abdominal or stomach pain; agitation, anxiety, excitement, or
restlessness; confusion or delirium; convulsions (seizures)—in acute
overdose ; dehydration; faster breathing rate; fast or
irregular heartbeat; fever; frequent urination;
headache; increased sensitivity to touch or pain ;
irritability; muscle trembling or twitching; nausea and vomiting,
sometimes with blood; overextending the body with head and heels bent
backward and body bowed forward; painful, swollen abdomen or vomiting (in
newborn babies); ringing or other sounds in ears; seeing flashes of
“zig-zag” lights; trouble in sleeping; whole-body tremors (in
newborn babies)
Other side effects may occur that usually do not need medical attention.
These side effects may go away during treatment as your body adjusts to the
medicine. However, check with your doctor if any of the following side effects
continue or are bothersome:
- More common
- Nausea (mild); nervousness or jitters (mild)
After you stop using this medicine, your body may need time to adjust. The
length of time this takes depends on the amount of medicine you were using and
how long you used it. During this time, check with your doctor if you notice any
of the following side effects:
- More common
- Anxiety; dizziness; headache; irritability; muscle
tension; nausea; nervousness; stuffy nose; unusual
tiredness
Other side effects not listed above may also occur in some patients. If you
notice any other effects, check with your doctor.
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Genetically Mediated Responses...
[...]
In doses typically contained in coffee, tea, energy drinks, foods, and pharmaceutical formulations,6 caffeine acts as an
adenosine receptor antagonist. Adenosinergic mechanisms appear to be critically involved in wake–sleep processes in
humans. Consistent with the "adenosine hypothesis" of sleep, caffeine prolongs sleep latency, decreases the deep
stages of non-rapid-eye movement (nonREM) sleep, reduces sleep efficiency, and alters the waking and sleep electroencephalogram
(EEG) in frequencies, which reliably reflect sleep need. These changes in sleep and the sleep EEG are
reminiscent of patients with primary insomnia (i.e., insomnia not related to another sleep, medical, or psychiatric disorder),
and caffeine intake was proposed to produce a model of insomnia in healthy volunteers. Unsatisfactory sleep quality
can indeed be a reason for some people to voluntarily reduce or abstain from caffeine consumption. Nevertheless, the
first scientific examinations of caffeine in humans have already revealed that the effects on sleep are highly variable
among individuals. The pharmacokinetic and/or pharmacodynamic mechanisms underlying these differences are
unknown and a matter of an ongoing debate.
Both the anxiogenic and stimulant properties of caffeine contribute to individual differences in the subjective response
to the drug. More specifically, a c.1083T4C polymorphism in the adenosine A2A receptor gene (ADORA2A)
modulates individual differences in symptoms of anxiety after caffeine. In addition, the perceived stimulation after
caffeine depends on the level of arousal at the time of drug intake. We found that optimal performance on a psychomotor
vigilance task was more impaired after one night without sleep in self-rated caffeine-sensitive individuals when
compared with caffeine-insensitive individuals. Moreover, the improvement in performance by caffeine was inversely
related to the impairment by sleep debt. [...]
TORONTO, March 7 - People with a gene variant that causes slow metabolism of caffeine have a sharply elevated risk of a
non-fatal heart attack if they drink large amounts of coffee, according to researchers here.
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Action Points
Explain to interested patients that the relationship between coffee drinking and heart attack has been confusing and
this study shows that a certain genetic make-up may increase the risk.
Caution that there is no commercially available test that can distinguish between the two genotypes studied.
[A commercial test is now available.]
Advise, however, that one implication of the study is that a single cup of coffee a day -- 250 mL -- is safe no matter
what genotype is involved. | |
In a large case-control study, only people who were slow to metabolize caffeine had an increased risk of non-fatal myocardial
infarction when they drank large amounts of coffee, found Ahmed El-Sohemy, Ph.D., a professor of nutritional sciences at the
University of Toronto here.
The finding begins to clarify the muddy picture of the coffee-heart risk interaction, Dr. El-Sohemy and colleagues at Harvard
and the University of Costa Rica reported in the March 8 issue of the Journal of the American Medical Association.
"It reveals for the first time that we need to take into account not just how much caffeine you take in but how much stays
in your system," Dr. El-Sohemy said in an interview.
Caffeine is "the most widely consumed stimulant in the world" and has been implicated in the development of such cardiovascular
diseases as acute MI, the authors noted.
But coffee contains a range of other chemicals and is associated with other lifestyle factors that cloud the link between
consumed caffeine and unwanted cardiovascular outcomes, the researchers wrote.
They noted also that 95% of consumed caffeine is metabolized in the liver by cytochrome P450 1A2 (CYP1A2), which varies
greatly in terms of activity among individuals. Specifically, a substitution - dubbed CYP1A2*1F -- in the CYP1A2 gene
decreases its activity, and carriers of the allele, whether homo- or heterozygous, are called "slow" metabolizers of caffeine.
By contrast, carriers of another variant -- CYP1A2*1A -- are called "fast" metabolizers of the stimulant, Dr. El-Sohemy and
colleagues noted.
In that context, between 1994 and 2004, he and colleagues enrolled 2,014 people in Costa Rica who had survived a first MI
and matched them for age, sex, and area of residence. They were genotyped to see which CYP1A2 allele they carried and a
food frequency questionnaire was used to assess how much caffeinated coffee they drank.
A cup of coffee was defined as 250 mL. Most of the coffee drunk in Costa Rica is filtered, rather than espresso or other
varieties of the drink.
Analysis of the study population showed that 55% of cases, or 1,114, and 54% of controls, or 1,082, carried the "slow"
allele. Using people who drank less than a cup of coffee a day as a reference group (with an odds ratio of 1.00), the
researchers found:
- Overall, only drinking more than four cups of coffee a day increased the risk of MI -- by 40%, with a 95% confidence
interval between 1.05 and 1.87. Other levels of intake were not significantly associated with increased risk.
- But for those carrying the "slow" allele, drinking two to three cups a day increased the risk by 36% (OR: 1.36) and
drinking four or more increased it by 64% (OR: 1.64). (The 95% confidence intervals were 1.01 to 1.83 and 1.14 to 2.34,
respectively.)
- Meanwhile, for those with the "fast" allele, there was no significant increase in risk even at or above the four-cup-a-day
level, compared with those who drank less than a cup a day.
In other words, the researchers argue, "coffee consumption increases the risk of MI only among individuals with a slow metabolizer
genotype."
The researchers also looked at the effects of cigarette smoking, which is associated with coffee drinking and also induces
CYP1A2 activity. The effect of CYP1A2 genotype on the risk of MI was similar among smokers and nonsmokers.
Earlier studies have hinted that the risk of MI associated with caffeine is greater in younger people, Dr. El-Sohemy and
colleagues noted. To look at that issue, they examined risk among participants above and below the median age of 59 and found
a significant gene/coffee interaction only among those younger than 59.
A similar pattern was found when they looked at participants younger than 50. There were 448 cases and 478 controls.
For carriers of the "slow" allele, the odds ratios of MI associated with consuming less than one, one, two to three, or
four or more cups of coffee per day were 1.00, 2.12, 2.43, and 4.07. The latter two were significant, with 95% confidence
intervals ranging from 1.89 to 8.74 and 1.22 to 4.82, respectively.
By contrast, fast metabolizers had corresponding odds ratios of 1.00, 0.39, 0.35 and 0.81, with 95% confidence intervals
of 0.15 to 0.97, 0.17 to 0.76, and 0.32 to 2.05, respectively.
Dr. El-Sohemy said he and his colleagues can't explain yet why drinking coffee might have an apparent protective effect
in young fast metabolizers. "We do know that coffee contains a number of different compounds, including anti-oxidants," he
said, adding it might be that because the caffeine is removed relatively quickly beneficial compounds are "unmasked."
He said the finding has no immediate clinical application, since there is no commercially available test for the different
CYP1A2 genes. But he added one conclusion that could be drawn from the study is that a single cup of coffee a day has no
adverse effect -- no matter what the genotype. |
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Harvard Women's Health Watch
[...] STAYING ALERT WITH COFFEE
Many of us like to drink a cup or two of coffee in the morning to get going, and perhaps take another
cup in the afternoon. But research suggests that you’ll stay more alert, particularly if you’re fighting
sleep deprivation, if you spread your coffee consumption over the course of the day. For instance, if
you usually drink 16 ounces in the morning, try taking a 2–3 ounce serving every hour or so. [...]
CARDIOVASCULAR EFFECTS ARE MODEST
Coffee has several cardiovascular effects.
Constricted arteries.
The caffeine in a cup of coffee can constrict
arteries that lie in areas away from the heart and lungs, such as the brain. This is one reason drinking a
cup of coffee sometimes relieves a throbbing headache caused by dilated blood vessels in the brain. It’s
also why caffeine is added to several over-the-counter analgesics. Increased heart rate. In some people,
coffee can slightly speed the heart rate. Increased blood pressure. A cup of coffee temporarily boosts blood
pressure, in much the same way as an activity such as climbing stairs does. But a coffee habit doesn’t cause
chronic high blood pressure. And several studies have found that blood pressure changes tend to occur only
in people who don’t usually drink coffee.
Irregular heartbeat.
The American Heart Association says that caffeine
(which is also found in tea, some soft drinks, and chocolate) may cause an occasional irregular heartbeat.
If you think coffee affects you this way, slowly cut back on the amount you drink each day, and talk to your clinician.
Increased cholesterol levels.
The coffee oils kahweol and cafestol can increase levels
of total and LDL (bad) cholesterol. Paper filters trap these compounds, so they’re not found in most cups of coffee in
America, and are a problem only for those who drink espresso, pressed, boiled, or other unfiltered coffee.
Homocysteine.
Several studies have linked coffee consumption to increased levels
of homocysteine, a substance in the blood that may increase the risk for heart disease. A Dutch study found that while
caffeine alone (the amount in 4 cups of strong coffee) raised homocysteine levels by 5%, getting that
amount in coffee more than doubled the effect. This suggests that compounds other than caffeine are
involved. But high homocysteine levels are also associated with some nutritional deficiencies (such as low
folate). In one study, coffee had no effect on homocysteine levels in people who ate a healthy diet.
Heart disease. The American Heart Association has concluded that moderate coffee use (which it defines
as 1–2 cups per day) is not harmful. And large, long-term studies (including Harvard’s Nurses’ Health
Study) have found that drinking even as many as 5–6 cups of coffee a day doesn’t increase the risk for
heart disease.
FOR WOMEN ONLY
Many women, particularly those of childbearing age, wonder whether coffee and other caffeine-containing
foods and drinks are safe for them. Fortunately, there’s plenty of scientific evidence about the effects of
coffee and caffeinated beverages on women’s health.
Fertility.
There’s no credible evidence that caffeine lowers a woman’s fertility.
Pregnancy. Although the evidence is somewhat mixed, low caffeine consumption (1–2 cups per day)
appears to be safe during pregnancy. Most of the studies that have linked caffeine to miscarriage, birth
defects, or low birth weight have either not taken into account other factors, or involved higher levels of
caffeine or coffee consumption (more than 300 mg of caffeine, or more than 3 cups of coffee, per day). A
2003 Danish study published in the British Medical Journal found that pregnant women who drank 4 or
more cups of coffee per day were at increased risk of stillbirth. Most authorities, including the FDA, the
March of Dimes, and the American College of Obstetricians and Gynecologists, agree that pregnant
women should limit their consumption of caffeine to the equivalent of no more than 1–2 cups of coffee
(about 100–200 mg of caffeine) per day.
Breast health.
Some women believe that abstaining from coffee and caffeinated
beverages alleviates the symptoms of fibrocystic breast disease (a condition of benign lumps in the breast). The
available research does not support this association.
Cancer.
Over the years, some flawed studies have linked caffeine and coffee to
several cancers, including cancers of the breast and ovaries as well as the pancreas and bladder. More thorough investigations
carried out during the 1990s have found no connection between coffee and cancer. The American Cancer
Society has concluded that caffeine is not a risk factor for cancer.
Osteoporosis.
Although caffeine can increase urinary excretion of calcium, the jury
is still out on whether it’s a factor in osteoporosis. Some studies, including Harvard’s Nurses’ Health Study, suggest
that drinking 4 cups or more per day can contribute to bone loss and hip fracture. On the other hand, one
study of lifetime coffee drinking (amounting to 2 cups per day) found no evidence of bone loss in women
who also drank at least 1 cup of milk per day. Until we know more, it’s best to avoid heavy coffee
consumption. Women who regularly drink coffee and caffeinated beverages should also be sure they get
adequate calcium (1,000–1,200 mg per day) from food and supplements [...]
POSSIBLE BENEFITS
Most studies investigating the health effects of coffee or caffeine consumption have focused on possible
harms. But some large investigations have identified several potential benefits from coffee drinking.
Diabetes. The risk for type 2 diabetes is lower among regular coffee drinkers than among those who
don’t drink coffee. In two studies, Harvard researchers found that women who drank 6 cups or more per
day reduced their risk for type 2 diabetes by 30% (Annals of Internal Medicine, Jan. 6, 2004). This
result is particularly significant because the studies tracked a total of 125,000 men and women for a
dozen years or more. Similarly, Finnish scientists following nearly 15,000 men and women, ages 35–64,
found that women who drank 3–4 cups per day had a 29% lower risk for diabetes, and drinking 10 or
more cups per day lowered the risk even further (Journal of the American Medical Association,
March 10, 2004). But no one is recommending that women drink 10 cups a day, or even more than 3 or 4
cups. Not enough is known about its other effects at high doses. We know that it may be harmful in some
circumstances, including pregnancy.
Gallstones.
A Harvard study found that women who drink 4 cups of
coffee per day have a reduced risk of developing gallstones. Coffee may alter the metabolism of bile acids,
which trigger the formation of the cholesterol crystals that become gallstones. Coffee also stimulates
gallbladder contractions, which may curb stone formation.
Colon cancer.
Several studies have found a reduced risk of colon
cancer in people who drink 4 or more cups of coffee per day, compared with those who rarely or never drink
coffee. In 2003, German researchers reported that they identified an antioxidant in coffee called methylpyridinium,
which boosts the activity of enzymes that may discourage the development of colon cancer. The compound is found in
both regular (caffeine-containing) and decaffeinated coffee.
Cognitive function.
Research involving older men and women participating in
the Rancho Bernardo Study found that lifetime coffee intake is associated with better performance by women (but not men) on
several cognitive tests. No relationship was found between cognitive function and decaffeinated coffee consumption.
Performance.
Caffeine has been shown to improve endurance performance in long-duration
physical activities such as running, cross-country skiing, and cycling. Studies suggest this effect occurs at doses of
2–9 mg of caffeine per 2.2 pounds of body weight. This is about the amount of caffeine found in 2–5 cups of coffee.
Liver disease.
Researchers at the National Institute of Diabetes and Digestive
and Kidney Diseases have found a strong association between coffee drinking and a reduced risk for liver damage in people at high
risk for liver disease. This includes heavy drinkers of alcohol, people with hepatitis B or C, and those with
iron overload disorders, such as hemochromatosis. The highest consumption, more than 2 cups of coffee per day, was correlated
with the greatest benefit.
Parkinson’s disease.
Several large studies have shown a reduced risk for Parkinson’s
disease in coffee drinkers. Although most of the data come from research in men, a 2001 Harvard School of Public Health
study found that women who consumed 1–3 cups of coffee per day had a 50% reduction in risk for Parkinson’s disease, with
no increased benefit at higher levels of intake. [...]
Those who view their morning coffee as a guilty pleasure can banish their misgivings. The latest research
discounts the notion that moderate coffee consumption — which we interpret to be about 2–4 cups per
day — causes significant or lasting harm. Indeed, some studies suggest that coffee and caffeine may offer
some real health benefits. |
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Health Canada extended the use of caffeine to non-cola soft drinks last year, even as it was being warned that children are already consuming too much of the stimulant, CBC News has learned.
Canada's blocking of IRN-BRU, the leading non-cola soft drink in Scotland, was "a long-standing trade irritant," according to the Department of Foreign Affairs and International Trade.
The drink contains caffeine, so it couldn't be sold in Canada, though the manufacturer had tried for years to get into the Canadian market.
"For decades, Canada was one of the few places in the world that insisted caffeine couldn't be added to those non-cola drinks," CBC senior investigative correspondent Diana Swain reported Monday on The National.
"But last year that rule was quietly dropped by Health Canada — not because caffeine was suddenly good for kids ... but because it was good for trade." [...]
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The amount of caffeine in tea and coffee can vary considerably and depends on the brand, the way that it is made, and the size of the cup or mug.
Effects of caffeine
The effects of any drug (including caffeine) vary from person to person. How caffeine affects a person depends on many things including their size, weight and health and also whether the person is used to
taking it, and the amount they have taken.
Regular caffeine users may have different experiences from people who consume caffeine products only occasionally.
There is no safe level of drug use.
Use of any drug always carries some risk—even medications can produce unwanted side effects. It is important to be careful when taking any type of drug.
Short-term effects
Caffeine takes 5–30 minutes to circulate in the body after it has been consumed. Its effects will continue as long as it is in the blood, which is usually around 12 hours. Some short-term effects of caffeine are:
- feeling more alert and active
- need to urinate more frequently
- rise in body temperature
- increased heart rate
- stimulation of the brain and nervous system.
This level of consumption usually does not cause any lasting damage. [...]
Use of caffeine can have a number of disturbing physical effects on some people, such as:
- anxiety
- irritability
- increased breathing and heart rates
- restlessness, excitability, dizziness
- headaches and lack of concentration
- gastrointestinal pains
- dehydration.
Children and young people who consume energy drinks containing caffeine may suffer from sleep problems, bed-wetting and anxiety.
Higher doses
Serious injury or death from caffeine overdose can occur, but it is extremely rare. A person would have to consume 5–10 grams of caffeine (or 80 cups of strong coffee, one after the other) to suffer an overdose.
Some effects of caffeine overdose include:
- involuntary shaking (tremors)
- nausea and vomiting
- irregular or rapid heart rate
- panic attack and confusion
- seizure.
In small children, caffeine poisoning can be seen with much smaller doses, such as up to 1 gram of caffeine (equal to around 12 energy drinks). [...] [Read More] |
Health Canada Review
The Issue
Caffeine in its natural and added forms is found in a growing list of products including coffee,
tea, cola beverages, new “energy” drinks, chocolate and even some medicines. The increasing presence of caffeine in our
lives raises the question of how much is too much for the average consumer. Health Canada’s recommendations on
caffeine intake for women of childbearing age and children were lowered in 2003 based on new research. For the
rest of the general population of healthy adults, the long-standing advice still applies of no more than 400 mg of
caffeine per day, the equivalent of about three 8-oz (237 ml) cups of brewed coffee.
Background
Caffeine is a natural ingredient found in the leaves, seeds or fruit of a number of plants, including coffee, tea, cocoa,
kola, guarana and yerba maté. It is also manufactured and used as a food additive in some carbonated drinks, and as an
ingredient in certain drug products, such as cold and headache remedies.
Canadian adults get an estimated 60% of their caffeine from coffee and about 30% from tea. The remaining 10% comes
from cola beverages, chocolate products and medicines.
For children aged one to five, about 55% comes from cola drinks, about 30% from tea, and about 14% from chocolate. The
rest comes from other sources, including medicines.
The Health Effects of Caffeine
It is difficult to link precise intake levels of caffeine to specific health effects because tolerance to caffeine differs
widely from person to person. For healthy adults, a small amount of caffeine may have positive effects, such
as increased alertness or ability to concentrate. However, some people are more sensitive to caffeine. For them, a small amount could cause
insomnia, headaches, irritability and nervousness.
There have been many studies over the years dealing with caffeine and human health. These studies have looked at the potential adverse effects
of caffeine in such areas as:
- general toxicity (e.g., muscle tremors, nausea, irritability)
- cardiovascular effects (e.g., heart rate, cholesterol, blood pressure)
- effects on calcium balance and bone health (e.g., bone density, risk of fractures)
- behavioural effects in both adults and children (e.g., anxiety, mood changes, attentiveness)
- potential links to cancer
- effects on reproduction (e.g., male and female fertility, birth weight)
Health Canada scientists recently reviewed these studies and found that:
- The general population of healthy adults is not at risk for potential adverse effects from caffeine if they limit their caffeine intake to
400 mg per day
- People who get an adequate daily amount of calcium have greater protection against the possible adverse effects
of caffeine on bone health. For most people, choosing foods according to Canada's Food Guide to Healthy Eating can
provide the calcium needed for good health.
- Compared to the general adult population, children are at increased risk for possible behavioural effects from
caffeine.
- Women of childbearing age are at increased risk of possible reproductive effects.
These conclusions prompted Health Canada to establish new recommendations on maximum daily caffeine intakes for
the groups that may be at higher risk.
Health Canada's New Recommendations
For children age 12 and under, Health Canada recommends a maximum daily caffeine intake of no more than 2.5
milligrams per kilogram of body weight. Based on average body weights of children, this means a daily caffeine
intake of no more than:
- 45 mg for children aged 4 - 6
- 62.5 mg for children aged 7 - 9
- 85 mg for children aged 10 - 12
Those recommended maximums are equivalent to about one to two 12-oz (355 ml) cans of cola a day. Health Canada has not developed definitive advice for adolescents 13 and older because of insufficient
data. Nonetheless, Health Canada suggests that daily caffeine intake for this age group be no more than 2.5 mg/kg body weight. This is because the maximum adult caffeine
dose may not be appropriate for light weight adolescents or for younger adolescents who are still growing.
The daily dose of 2.5 mg/kg body weight would not cause adverse health effects in the majority of adolescent caffeine consumers. This
is a conservative suggestion since older and heavier weight adolescents may be able to consume adult doses of caffeine without suffering adverse
effects.
For women of childbearing age, the recommendation is a maximum daily caffeine intake of no more than 300 mg, or a little over two 8-oz (237 ml)
cups of coffee.
For the rest of the general population of healthy adults, Health Canada advises a daily intake of no more than 400 mg. [...] [Read more] | |
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Pharmacologic Overview...
STIMULANTS: Methylxanthines/Xanthines ...
("minor" stimulants)
- PLANT SOURCES OF XANTHINES (ALKALOIDS)
- Coffee
- Coffea Arabica (Ethiopia originally)
- Coffea robusta (African Congo originally)
- Tea
- Camellia sinensis (China, India, Burma, Thailand, Laos & Vietnam)
- Chocolate
- Theobroma cacao (Amazon & Orinoco rivers)
- So.Amer. Holly
- Ilex guayusa (Amazon, Peru, Ecuador)
Achuar Jivaro tribesmen (xanthines act to repel insects)
- SPECIFIC ACTIVE INGREDIENTS & PLANT SOURCES
- Caffeine
– found in coffee, tea, colas, & So.Amer. holly
- Theophylline
– found in tea
- Theobromine
– found in chocolate (along with phenylethylamine & caffeine)
(caffeine > theophylline > theobromine)
- USERS OF XANTHINES
- Mean age of initial use:
of coffee = 19 years;
of tea = 22 years;
of colas = 14 years;
of choc?
- In USA > 85% of population consumes caffeine weekly > 98% of children/adolescents (5-18 yrs)
consume weekly 210-238 mg caffeine/person/day (all sources)(mostly coffee)
(Julien says 80-400 mg, = 3 to 5 5oz. "cups" of coffee/day)(vs. 444 mg caffeine/person/day in United Kingdom!)(mostly tea)[.]
[C]offee consumption was dropping & colas increasing – in early 1990’s (PS)
- In U.K. per capita consumption of chocolate is 16 lbs./year (vs. 12 lbs./year in USA).
[I]n U.K. around 20% of yearly chocolate is consumed at Xmas/NewYrs
- Worldwide 70mg caffeine/person/day (tea > coffee)[;] 80% of adult population consumes caffeine daily[.]
Summary: Xanthine use is worldwide & daily!
- GENERAL POSITIVE EFFECTS
- increased mental alertness
- wakefulness
- increased energy
- sense of well-being
[D]oes it have potential for toxicities? YES...
[D]oes it have potential for physical dependence? YES...
- PHARMACOKINETICS
- taken PO, rapidly absorbed from GI tract
- are alkaloids[,] so “should” ionize & get trapped in stomach[,] but
do not ionize easily in acidic environment; therefore remain in nonionized
form & readily pass out of stomach into bloodstream
- absorbed w/i 15-45 minutes, completely by 1½-2 hours
- peak plasma levels 2 hours after drinking, decrease thereafter
freely distributed to all body tissues
- crosses BBB easily & quickly crosses placental barrier easily & quickly[;]
90% metabolized by liver enzymes (CYP1A2), 10% excreted unchanged[,] mostly in urine[,] small amounts excreted
in feces, sweat, breast milk, etc.
- ½ life varies: 3½ to 5 hours (2½ - 7) in most adults
½ life increases in infants, pregnant women (3-10 hours), & elderly
½ life decreases in smokers (via liver enzyme induction)
- note: some TCAs & SSRIs, & grapefruit can inhibit CYP1A2 production
which then --- increases caffeine effects
e.g. Luvox/fluvoxamine (vs. Effexor/venlafaxine)
caffeine metabolized into 3 active (stimulant) metabolites:
theophylline & paraxanthine – active, acts like caffeine
theobromine – active, but does not act like caffeine
- PHARMACOLOGICAL EFFECTS OF CAFFEINE
(at low to medium doses)
- increased alertness, increased wakefulness
- increase in faster, clearer thinking
- increased mood, sense of well being, sociability
- decreased fatigue
- decreased sleep, increased restlessness, sensitivity to stimuli
- increased skeletal muscle activity (increased shaking, tremors --- decreased
fine motor control)
- increased respiratory drive & rate
- increased urine output (is a diuretic)
- increased HR, cardiac force, BP, dilation of coronary arteries (vs. cocaine)
- decreased smooth muscle activity (is a vasodilator in peripheral blood
blood vessels, but a vasoconstrictor of CNS blood vessels; opens
bronchi)
- increased basal metabolic rate
- TOXIC PHARMACOLOGICAL EFFECTS OF CAFFEINE
(at medium to high levels)
- usually seen at about 1 to 1.5 grams/day levels (= 12 cups coffee)
- increased agitation, anxiety (esp. in sensitive [Subjects])
- increased tremors, restlessness
- increased rapid, shallow breathing
- increased insomnia
- increased peripheral vasoconstriction (cold, sweaty hands)
- lethal dose = 10 grams caffeine/day (= 100 cups coffee)
(therefore, TI = 40)
- "caffeinism" – a clinical pattern seen with caffeine OD
anxiety, agitation, severe insomnia, labile mood swings (esp. irritability
to rage), tachycardia, HBP, cardiac arrhythmias, severe GI disturbances,
incl. diarrhea, gas, & cramping, and acid reflux, SOB, tinnitus, delerium
usually seen at > 500-1000 mg/day (= 5-10 cups coffee/day)
[...] Some investigators have hypothesized that caffeine is a vasoconstrictive substance. In the present study, systolic
and diastolic blood pressures were elevated after caffeine ingestion, suggesting vasoconstrictive effects of caffeine.
Caffeine should be an antagonist of the adenosine receptor. It is well known that adenosine induces vasodilation.
Therefore, antagonization of the adenosine receptor could induce vasoconstriction. However, although oral caffeine
ingestion did not change baseline FBF, FBF response to ACh was significantly increased in the caffeine group.
Hatano et al[1995] reported that caffeine promotes nitric oxide synthesis in the endothelium by the release of Ca2+ from the
endoplasmic reticulum through activation of the ryanodine-sensitive Ca2+ channel and the suppression of cyclic
guanosine monophosphate degradation in the isolated rat aorta, resulting in the caffeine-induced augmentation of
endothelium-dependent vasodilatation. In the present study, L-NMMA, a nitric oxide synthase inhibitor, completely abolished
the caffeine-induced augmentation of endothelium-dependent vasodilation. These findings suggest that caffeine
augments endogenous nitric oxide production by agonist stimulation. A balance of the vasodilatory effect of caffeine
as an endothelium-dependent vasodilator and the vasoconstrictive effect of caffeine as an adenosine receptor antagonist
may regulate vascular function.
In the present study, caffeine ingestion elevated systolic and diastolic blood pressures in the brachial artery. Our
results support those of previous studies showing that the acute administration of caffeine elevates peripheral blood
pressure. Karatzis et al[2005] demonstrated the augmentation of central blood pressure after the acute administration of
caffeine, but peripheral systolic blood pressure did not significantly change. It has been reported that various factors,
such as hypertension, exercise stress, and age, influence blood pressure response to caffeine. [...] |
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Neurological Effects...
Coffee and Caffeine Consumption
The 2 major coffee types are Arabica and Robusta. In a standard 150 mL cup, the content of caffeine ranges from 71-120
mg per cup for Arabica coffee and from 131-220 mg per cup for Robusta. Caffeine is present in a number of dietary sources
including tea, coffee, cocoa beverages, candy bars, and soft drinks. The caffeine content of these food items varies, ranging
from 71-220 mg/150 mL for coffee, 32-42 mg/150 mL for tea, 32-70 mg/330 mL for cola, and 4 mg/150 mL for cocoa. Average caffeine
consumption from all sources is approximately 76 mg/person/day but reaches 210-238 mg per person per day in the United States
and Canada and more than 400 mg per person per day in Sweden and Finland, where 80-100% of the caffeine intake is from coffee
alone. In the United Kingdom, the consumption of caffeine is similar to that in Sweden and Finland, but 72% is from tea.
The daily intake of caffeine from all sources in the United States is estimated at 3 mg/kg/person, with two thirds of it coming
from coffee consumed by subjects older than 10 years. If only caffeine consumers are evaluated, the daily caffeine consumption
is 2.4-4.0 mg/kg (170-300 mg) in individuals weighing 60-70 kg. In children, soft drinks represent 55%, chocolate foods and
beverages represent 35-40%, and tea represents 6-10% of the total caffeine intake.
Caffeine, or 1,3,7-trimethylxanthine, is related structurally to uric acid. It is metabolized by demethylation and oxidation.
The major human pathway results in paraxanthine (1,7-dimethylxanthine), leading to the principal urinary metabolites,
l-methylxanthine, 1-methyluric acid, and an acetylated uracil derivative. Minor degradation pathways involve the formation
and metabolism of theophylline and theobromine. No evidence exists to suggest that methylxanthines are converted to uric
acid or that their ingestion can exacerbate gout.
The rate of elimination of methylxanthines varies by individual due to both genetic and environmental factors, and 4-fold
differences are not uncommon. In most cases, metabolism obeys first-order elimination kinetics within the therapeutic range.
At higher concentrations, however, zero-order kinetics occur with the saturation of metabolic enzymes. This prolongs the
decline of caffeine concentrations.
The metabolism of methylxanthines also is influenced by the presence of other agents or specific diseases. For example, cigarette
smoking and oral contraceptives produce a small but appreciable increase in methylxanthine clearance. The half-life of theophylline
can be prolonged significantly in patients with hepatic cirrhosis, congestive heart failure, or acute pulmonary congestion; values
of more than 60 hours have been reported.
Caffeine has a half-life in plasma of 3-7 hours; this increases by about 2-fold in women during the later stages of pregnancy
or with long-term use of oral contraceptive steroids... [Read more] |
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Caffeine Withdrawal
Abstract
Rationale: Abrupt cessation of caffeine often results in
several withdrawal symptoms among habitual caffeine
consumers.
Objective: The objective of the study was to determine
whether caffeine withdrawal symptoms co-exist as clusters
in some individuals.
Materials and methods: Withdrawal symptoms and caffeine intake were assessed for men (n=126) and women (n=369), aged 20–29, using a caffeine habits questionnaire and
a semi-quantitative food frequency questionnaire, respectively.
Principal components factor analysis was used to identify common underlying factors among 14 well-described caffeine withdrawal symptoms. Odds ratios
(OR) and 95% confidence intervals (CI) were calculated to determine if the likelihood of reporting a withdrawal factor was associated with habitual caffeine consumption.
Results: The 14 withdrawal symptoms were grouped into three factors termed “fatigue and headache”, “dysphoric mood”, and “flu-like somatic”. The likelihood of reporting
the fatigue and headache and dysphoric mood factors increased with higher levels of habitual caffeine consumption. Compared to <100 mg/day of caffeine, the ORs (95% CI) of reporting
the fatigue and headache factor with a habitual intake of 100–200 mg/day and >200 mg/day were 1.97 (1.21, 3.21) and 4.44 (2.50, 7.86), respectively. The corresponding ORs (95% CI)
for the dysphoric mood factor were 1.55 (0.96, 2.52) and 3.34 (1.99, 5.60).
Conclusions: The 14 well-described caffeine withdrawal symptoms factor into three clusters, suggesting the existence of three distinct underlying mechanisms of caffeine withdrawal.
Increasing habitual caffeine consumption is associated with an increased likelihood of reporting the fatigue and headache and dysphoric mood symptoms, but not the flu-like
somatic symptoms.
[...]
Caffeine Withdrawal: A Daily Process
Caffeine is quickly and completely absorbed through the digestive tract. Blood levels peak in half an hour or so, and half of the caffeine in your body
is excreted within four to six hours. Withdrawal symptoms can start as soon as six hours after stopping use, though 12 to 24 hours is more common. Withdrawal
symptoms are very common on waking in the morning. Were you to stop ingesting caffeine, withdrawal symptoms probably would last at least a day or two; they
could go on for up to two weeks.
The most common withdrawal symptom is headache — about half of caffeine users get them. Fatigue, low energy, decreased alertness, irritability or depressed mood
are also common. Attention and motor performance get worse. About 10% of withdrawing caffeine users describe severe distress or find it very hard to function.
A friend of mine told me a family member would regularly play a trick on her, substituting decaf for caffeinated coffee without her knowing it. The trickster
was trying to prove that withdrawal symptoms were nothing more than expectations fulfilled. Controlled experiments have proven that theory wrong. Withdrawal
symptoms have their basis in pharmacology. The more caffeine you use, the worse the withdrawal symptoms. But the cure is quick — a drink of coffee or tea
can eliminate symptoms within an hour.
So what we experience as a performance enhancement is probably just a daily cycle of withdrawal and relief. That first cup tugs you back up to the starting
line rather than giving you a head start. [...] [Read more]
Sept. 30, 2004 -- Researchers are saying that caffeine withdrawal should now be classified as a psychiatric disorder.
A new study that analyzes some 170 years' worth of research concludes that caffeine withdrawal is very real -- producing enough
physical symptoms and a disruption in daily life to classify it as a psychiatric disorder. Researchers are suggesting that
caffeine withdrawal should be included in the next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM),
considered the bible of mental disorders.
"I don't think this means anyone should be worried," says study researcher Roland Griffiths, PhD,
professor of psychiatry and neuroscience at Johns Hopkins School of Medicine. "What it means is that
the phenomenon of caffeine withdrawal is real and that when people don't get their usual dose, they
can suffer a range of withdrawal symptoms."
His research, published in the October issue of Psychopharmacology, analyzes 66 previous studies on the
effects of caffeine withdrawal... Griffiths' analysis shows as little as one cup of coffee can cause an
addiction and withdrawal from caffeine produces any of five clusters of symptoms in some people:
- Headache, the most common symptom, which affects at least of 50% of people in caffeine withdrawal
- Fatigue or drowsiness
- "Unhappy" mood, depression, or irritability
- Difficulty concentrating
- Flu-like symptoms such as nausea, vomiting, muscle pain, and stiffness.
"Onset of these symptoms typically occurs within 12 to 24 hours of stopping caffeine and peaks one to two days after
stopping," Griffiths tells WebMD. "The duration is between two and nine days."
A new revelation in Griffith's analysis may be what upgrades caffeine withdrawal from its current "more study is needed"
status to "disorder" status: These withdrawal symptoms are severe enough in about one in eight people to interfere with
their ability to function on a day-to-day basis.
"The withdrawal symptoms can be mild or severe, but it's estimated that 13% of people develop symptoms so significant
that they can't do what they normally would do -- they can't work, they can't leave the house, they can't function," he says.
Abstract
Rationale: Although reports of caffeine withdrawal in the medical literature date back more than
170 years, the most rigorous experimental investigations of the phenomenon have been conducted only recently.
Objectives: The purpose of this paper is to provide a comprehensive review and analysis of the literature
regarding human caffeine withdrawal to empirically validate specific symptoms and signs, and to appraise
important features of the syndrome.
Methods: A literature search identified 57 experimental and 9 survey studies
on caffeine withdrawal that met inclusion criteria. The methodological features of each study were examined to
assess the validity of the effects.
Results: Of 49 symptom categories identified, the following 10 fulfilled
validity criteria: headache, fatigue, decreased energy/activeness, decreased alertness, drowsiness, decreased
contentedness, depressed mood, difficulty concentrating, irritability, and foggy/not clearheaded. In addition, flu-like
symptoms, nausea/vomiting, and muscle pain/stiffness were judged likely to represent valid symptom categories.
In experimental studies, the incidence of headache was 50% and the incidence of clinically significant distress or
functional impairment was 13%. Typically, onset of symptoms occurred 12–24 h after abstinence, with peak
intensity at 20–51 h, and for a duration of 2–9 days. In general, the incidence or severity of symptoms increased
with increases in daily dose; abstinence from doses as low as 100 mg/day produced symptoms. Research is reviewed
indicating that expectancies are not a prime determinant of caffeine withdrawal and that avoidance of withdrawal
symptoms plays a central role in habitual caffeine consumption.
Conclusions: The caffeine-withdrawal syndrome has been well characterized and there is sufficient empirical evidence to warrant inclusion of
caffeine withdrawal as a disorder in the DSM and revision of diagnostic criteria in the ICD. |
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Psychiatric Disorders
[...]
The 4 caffeine-induced psychiatric disorders include caffeine intoxication,
caffeine-induced anxiety disorder, caffeine-induced sleep disorder, and
caffeine-related disorder not otherwise specified (NOS).
- Diagnostic criteria for the 4 psychiatric disorders are described in the
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text
Revision (DSM-IV-TR).4
- DSM-IV-TR criteria for caffeine intoxication
- Recent consumption of caffeine, usually in excess of 250 mg (more than 2-3 cups of brewed coffee)
- Demonstration of 5 or more of the following signs during or shortly after caffeine use:
- Restlessness
- Nervousness
- Excitement
- Insomnia
- Flushed face
- Diuresis
- Gastrointestinal disturbance
- Muscle twitching
- Rambling flow of thought and speech
- Tachycardia or cardiac arrhythmia
- Periods of inexhaustibility
- Psychomotor agitation
- The above symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
- The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder, such as an anxiety disorder.
- DSM-IV-TR criteria for caffeine-induced anxiety disorder
- Prominent anxiety predominates in the clinical picture.
- There is evidence from the history, physical examination, or laboratory findings suggesting that the anxiety developed within 1 month of caffeine
intoxication or withdrawal or that medications containing caffeine are etiologically related to the disturbance.
- The disturbance is not better accounted for by an anxiety disorder that is not substance-induced.
- The disturbance does not occur exclusively during the course of a delirium.
- The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
- DSM-IV-TR criteria for caffeine-induced sleep disorder
- A prominent disturbance in sleep occurs that is sufficiently severe to warrant independent clinical attention.
- There is evidence from the history, physical examination, or laboratory findings that the sleep disturbance is the direct physiological consequence of caffeine consumption.
- The disturbance is not better accounted for by another mental disorder.
- The disturbance does not occur exclusively during the course of a delirium.
- The disturbance does not meet the criteria for breathing-related sleep disorder or narcolepsy.
- The sleep disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
- DSM-IV-TR criteria for caffeine-related disorder NOS
- This includes any caffeine disorder other than those previously listed.
- Symptoms of caffeine withdrawal that are not currently an officially
recognized diagnosis are present. [...]
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Sources of Caffeine...
Caffeine is found in the leaves, seeds and fruits of more than 63 plant species around the world1, and six caffeine-containing plants are
more widely used in the world than all other herbal materials put together: cacao, coffee,
guarana, kola, mate and tea2.
- http://www.eufic.org/gb/food/pag/food34/food343.htm
- http://chppm-www.apgea.army.mil/dhpw/Wellness/dietary/Caffeine.pdf
Caffeine (1, 3, 7-trimethylxanthine) [PDF] |
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What are the
sources of caffeine?
Caffeine is naturally found in certain leaves, seeds, and fruits of over 60 plants worldwide. The most common sources in our diet are coffee, tea leaves,
cocoa beans, cola, and energy drinks. Caffeine can also be produced synthetically and added to food, beverages, supplements, and medications.
Product labels are required to list caffeine in the ingredients but are not required to list the actual amounts of the substance. A low to moderate intake
is 130 to 300 mg of caffeine per day, while heavy caffeine consumption corresponds to more than 6,000 mg/day. It is estimated that the average daily
caffeine consumption among Americans is about 280 mg/day, while 20% to 30% consume more than 600 mg daily. The caffeine content in some common sources of
caffeine are listed [at right.]
There are many products that may contain caffeine without your awareness. Be
sure to read the label to see if caffeine is listed among the ingredients. |
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Caffeine Counts and More
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This is a partial list of countries ordered by annual per capita consumption of coffee, as of 2007 (latest complete data). Where no 2007 data are available, *2006 data are provided:
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