What is caffeine? How does caffeine work?

If your morning ritual consists of making a grab for a takeout tea or coffee to get your much-needed caffeine fix, you are not alone. Caffeine is used by the masses on a daily basis to increase wakefulness, alleviate fatigue, and improve concentration and focus.

Caffeine is the most commonly used drug in the world. Although the consumption of low to moderate doses of caffeine is generally safe and has many proven health benefits, caffeine is causing quite a stir as a potential source for certain health problems with continued use.

Contents of this article:

• What is caffeine?
• Where is caffeine found?
• What is caffeine used for?
• Caffeine content
• How does caffeine affect the body?
• How does caffeine work?
• Caffeine side effects
• Children and adolescents
• Caffeine tolerance
• What is caffeine dependence and withdrawal?
• Does caffeine have any health benefits?
• What are the risks of consuming caffeine?
• Caffeine allergy
• Caffeine overdose

You will also see introductions at the end of some sections to any recent developments that have been covered by my news stories. Also look out for links to information about related conditions.

Fast facts on caffeine

Here are some key points about caffeine. More detail and supporting information is in the main article.¹⁸

• At least 68 million Americans drink three cups of coffee every day.
• Some 30 million Americans drink five or more cups of coffee every day.
• Over 21 million Americans drink six or more cups of coffee every day.
• It is believed that some 3 out of 4 regular caffeine users are "addicted" to the substance.
• Consuming as little as 200 mg of caffeine a day can lead to addiction and altered chemistry in the brain.
• Around 5 grams of caffeine can be fatal. This is the equivalent of some 30-40 cups of regular coffee.
• Some 50% of people who quit using caffeine experience severe headaches that typically last between 2-9 days.
• The substance is derived from over 60 various types of plants around the world.
• Energy drinks with high volumes of caffeine: Red Bull is the most popular energy drink in the US with Monster a close second.
• Some 5% of adults consume 5-7 energy drinks every month. Over 2% of adults consume at least 10 energy drinks every month.

What is caffeine?

In the US, more than 90% of adults use caffeine regularly, with an average consumption of more than 200 mg of caffeine per day - more caffeine than in two 6 ounce cups of coffee or five 12 ounce cans of soft drinks.

More than 90% of adults in the US use caffeine regularly with an average consumption 200 mg or more per day.

Caffeine is a bitter, white crystalline xanthine alkaloid - a term used for substances produced as end products of nitrogen metabolism in some plants. 

The stimulant chemical is also known as coffeine, theine, mateine, guaranine, or methyltheobromine.¹⁴

Caffeine belongs to the family of heterocyclic compounds known as purines and is a member of a group of naturally occurring substances called methylxanthines. 

It has the systematic name 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione, also known as 1,3,7-trimethylxanthine, and 1,3,7-trimethyl-2,6-dioxopurine.

The chemical formula is C₈H₁₀N₄O₂. Caffeine has a molar mass of 194.19 grams (6.85 ounces). It is soluble in water and many organic solvents, has a melting point of 235-238 °C and it appears in pure form as white crystals. Caffeine can be prepared by extraction from natural sources or synthesis from uric acid.

Where is caffeine found?

Caffeine occurs naturally in the leaves, seeds or fruit of more than 60 plant species, including:

• Coffee beans - seed
• Tea leaves - leaves, bud
• Kola nuts - seed
• Cacao beans - seed
• Guarana - seed
• Yerba mate - leaf
• Yoco - bark.

Caffeine acts as a natural pesticide for the plants, and paralyzes and kills insects that attempt to feed on the plants. The German chemist Friedrich Ferdinand Runge first isolated the molecule in 1819.¹⁴

Man-made caffeine is sometimes added to foods, drinks, and medicines.³

What is caffeine used for?

The Food and Drug Administration (FDA) says that caffeine is both a drug and a food additive. Caffeine is used in both prescription and over-the-counter medicines to treat tiredness, drowsiness and to improve the effect of some pain relievers.³

Coffees, teas and chocolate can all contain caffeine.

When purified, caffeine is an intensely bitter white powder. It is added to enhance colas and other soft drinks so that they impart a pleasing bitter note. 

However, caffeine is also considered to be an addictive stimulant. 

In humans, caffeine stimulates the central nervous system, heart rate, and respiration, has psychotropic (mood-altering) properties and acts as a mild diuretic.¹³

Sources of caffeine include:

• Coffee and tea
• Chocolate
• Soda
• Sports beverages
• Energy drinks.

Caffeine belongs to the group of medicines called central nervous system (CNS) stimulants. In conventional foods, caffeine may help restore mental alertness when unusual tiredness, weakness or drowsiness occurs. Caffeine's use as an alertness aid should only be occasional. It is not intended to replace sleep and should not regularly be used for this purpose.¹²

Sources of caffeine in dietary supplements include:

• Capsules
• Tablets
• Powders
• Energy shots
• Energy drinks.

Caffeine is also used in combination with ergotamine, for the treatment of migraine and cluster headaches, or with certain pain relievers, such as aspirin and acetaminophen. Caffeine helps to increase the effectiveness of these medicines.¹²

Caffeine can also be used:

• To treat breathing problems in premature babies
• For postoperative infant apnea - breathing problems after surgery in young babies
• For psychiatric disorders requiring electroconvulsive or shock therapy (ECT).

Caffeine no longer only features in tea, coffee and chocolate. Caffeine is regularly added to gum, jelly beans, waffles, water and syrup to name a few.⁴

In response to the trend of "added caffeine" in a growing number of products, the FDA is investigating the safety of caffeine in foods and particularly its effects on children and adolescents.⁴

"Energy drinks" with caffeine are considered by some to be aggressively marketed, particularly to young people, with additional products appearing on the market, from "psyched up" oatmeal to "wired" waffles.

Caffeine is even being added to marshmallows, sunflower seeds and other snacks for its stimulant effect.⁴

Caffeine content

For healthy adults, the FDA has cited 400 milligrams of caffeine a day - about 4 or 5 cups of coffee a day - as an amount not associated with dangerous or negative side effects.

The FDA has not set an amount for children, but the American Academy of Pediatrics discourages the consumption of caffeine and other stimulants by children and adolescents.⁴

The amount of caffeine included in some common foods and beverages are:¹⁹

For healthy adults, about 4 or 5 cups of coffee a day is an amount not associated with dangerous or negative side effects.

• Coffee, brewed - 40 to 180 milligrams (mg) per cup
• Coffee, instant - 30 to 120 mg per cup
• Coffee, decaffeinated - 3 to 5 mg per cup
• Tea, brewed American - 20 to 90 mg per cup
• Tea, brewed imported - 25 to 110 mg per cup
• Tea, instant - 28 mg per cup
• Tea, canned iced - 22 to 36 mg per 12 ounces
• Caffeine-containing cola and other soft drinks - 36 to 90 mg per 12 ounces
• Cola and other soft drinks, decaffeinated - 0 mg per 12 ounces
• Cocoa - 4 mg per cup
• Chocolate, milk - 3 to 6 mg per ounce
• Chocolate, bittersweet - 25 mg per ounce.

How does caffeine affect the body?

Whether caffeine is consumed in food or as a medicine, it changes the way your brain and body work and changes how you behave and feel.

Caffeine is a central nervous system stimulant. The central nervous system includes the brain, spinal cord, and the other nerves in the body. Caffeine's main effect on the body is an increased temporary sense of wakefulness and alertness, but it can also cause issues such as:³

• Jitters and shakes
• Impeding sleep
• Fast heart beat
• Uneven heart rhythm
• High blood pressure
• Headaches
• Nervousness
• Dizziness
• Dehydration
• Dependency.

Once consumed, caffeine reaches peak level in the blood within one hour and remains there for four to six hours.

Caffeine increases the release of acid in your stomach, sometimes leading to an upset stomach or "heartburn." Caffeine is also a diuretic; causing the body to lose more water - it is considered neither beneficial for hydration nor thirst, although some studies dispute this.³

How does caffeine work?

Following oral consumption, caffeine is absorbed into the blood and body tissues with absorption virtually complete in around 45 minutes after ingestion. The peak plasma caffeine concentration is reached 15-120 minutes after ingestion.

Adenosine is a chemical that is present in all human cells. It readily combines with phosphate to form various chemical compounds, including adenosine monophosphate and adenosine triphosphate.

To a nerve cell, caffeine looks like adenosine. Caffeine uses all the receptors adenosine should bind to and as a result, instead of slowing down because of the adenosine level, the cells speedup.

In the brain, adenosine is an inhibitory neurotransmitter; it binds to adenosine receptors in the brain. This means adenosine can act as a central nervous system depressant.

In normal conditions, adenosine promotes sleep and suppresses arousal by slowing down nerve activity. Adenosine binding also causes blood vessels in the brain to dilate, to increase oxygen intake during sleep. When awake, the levels of adenosine in the brain rise each hour.

To a nerve cell, caffeine looks like adenosine. Caffeine binds to the adenosine receptors. 

However, in contrast to adenosine, it does not decrease the cell's activity. As caffeine utilizes all the receptors adenosine binds to, the cells can no longer sense adenosine. As a result, instead of slowing down because of the adenosine level, the cells speedup.

Caffeine blocks adenosine's ability to open up the brain's blood vessels, causing them to constrict - this is the reason caffeine is used in pain reliever medicine for headaches. If the headache is vascular, the caffeine closes down the blood vessels and gives relief.

With caffeine blocking adenosine, there is an increase in the firing of neurons in the brain. The pituitary gland observes the increased activity and perceives it as an emergency, so it releases hormones that tell the adrenal glands to produce adrenaline (epinephrine). Adrenaline is the "fight or flight" hormone and it has a number of effects on your body:

• Dilates pupils
• Opens breathing tubes
• Increases heartbeat
• Constricts surface blood vessels, increasing blood pressure
• Slows blood flow to stomach
• Releases sugar from the liver into the bloodstream for extra energy
• Tightens muscles.

Caffeine also increases levels of the neurotransmitter dopamine.¹⁴

Caffeine is quickly and completely removed from the brain. Its effects are short lived, and it tends not to affect concentration or higher brain functions negatively. However, continued exposure to caffeine leads to the development of a tolerance to it.

Smokers typically break down caffeine more quickly than non-smokers, while pregnancy tends to slow down the rate at which caffeine is broken down, particularly during the later stages. Elimination of caffeine from the body is accomplished mainly through metabolism in the liver, hence liver diseases might impact on the rate of caffeine elimination. This may also happen in individuals taking some medical treatments that are metabolized by the liver.

Caffeine side effects

Heavy daily caffeine use - more than 500 to 600 mg a day - may cause side effects such as:⁶

• Insomnia
• Nervousness
• Restlessness
• Irritability
• Stomach upset
• Diarrhea
• Dizziness
• Nausea
• Fast heartbeat
• Muscle tremors.

Most adults need seven to eight hours of sleep each night. Caffeine can interfere with the sleep cycle; it decreases the quantity of sleep and the temporal organization of slow and REM sleep. Sleep loss is cumulative, and even small nightly decreases can add up and disturb daytime alertness and performance.⁶

The negative effects linked to overconsumption are short lived once an individual returns to their regular pattern of consumption.

Some medicines and herbal supplements may interact with caffeine:⁶

• Some antibiotics: ciprofloxacin and norfloxacin - interfere with caffeine breakdown
• Theophylline: a bronchodilator - caffeine increases concentration of theophylline in blood
• Echinacea: herbal supplement - increases caffeine concentration in blood.

Children and adolescents

Physicians and policy makers are increasingly interested in caffeine intake among children and adolescents in the advent of increasing energy drink sales.²

The majority of caffeine intake among children and adolescents is due to soda and tea consumption. Energy drinks, which provide a potent source of caffeine, have increased in availability in the US in recent years. Specialty coffee drinks, and food products containing caffeine such as candy bars, potato chips, and gum have also dramatically increased and are often marketed toward children and adolescents²

Although the FDA deems caffeine a "safe" substance, its potential adverse effects on children and adolescents are largely unknown. The FDA does not currently regulate caffeine content in energy drinks unlike that of cola because energy drinks are marketed as and considered to be dietary supplements.²

Approximately 73% of children consume caffeine on a given day and this proportion has not changed over time. Percentage of consumers increased from 63% among children aged 2-5 to ∼75% among older age groups.²

Soda accounted for the majority of caffeine intake in 1999-2000 (62%), and tea was the second largest contributor to overall caffeine intake. Coffee accounted for only 10% of caffeine intake in 1999-2000 with an increase to nearly 24% in 2009-2010.

Energy drinks represent nearly 6% of caffeine intake in 2009-2010.²

Mean caffeine intake has not increased among children and adolescents in recent years. However, coffee and energy drinks represent a greater proportion of caffeine intake as soda intake has declined.

Case reports of caffeine toxicity and deaths among adolescents and adults reflect the potential dangers of excess caffeine or energy drink consumption.²

A study of seventh, eighth, and ninth-grade students in Ohio found that students took in an average of 53 mg of caffeine per day. Almost one in five students took in more than 100mg of caffeine each day.³

Caffeine tolerance

If individuals use caffeine on a daily basis, their bodies will no longer experience the "good effects" of feeling more awake and able to concentrate unless the dose is increased. This consequence is called "tolerance."³

When the adenosine receptors are blocked with caffeine molecules, dopamine (the feel good chemical) works more efficiently. The excess adenosine signals the adrenal glands to release adrenaline, which further perpetuates the feeling of alertness.

Over time, the brain adds more adenosine receptors to compensate for the caffeine, which causes a "tolerance" to build up to the caffeine molecule.

When a person misses or decides to quit their usual caffeine dose, the brain is then flooded with adenosine, and dopamine levels drop drastically causing the brain's chemistry to be out of balance.

The increased adenosine plus a drop in adrenaline levels leads to caffeine withdrawal symptoms.¹⁵

Some studies show that caffeine causes a physical dependence or addiction. If a person experiences withdrawal symptoms when they suddenly stop using caffeine then the person has a physical dependence on caffeine.³

Withdrawal symptoms can be unpleasant and include:¹⁵

• Severe headaches
• Sleepiness
• Lethargy
• Lack of concentration
• Constipation
• Muscle aches
• Temporary feelings of depression
• Flu-like symptoms
• Irritability
• Insomnia.

People often take more caffeine to make these symptoms "disappear," creating an ongoing cycle that is tough to break.³

What is caffeine dependence and withdrawal?

There has been much debate surrounding the question of whether caffeine is an addictive substance and whether the cessation of consumption will result in withdrawal-like symptoms.¹⁵

Caffeine does fit the definition of habituation, which in simple terms means to consume something in a regular pattern. Habituation and addiction are very different. In addition, a substance has to fulfill 4 out of 7 different criteria to be considered a drug of dependence, according to the American Psychiatric Association (APA).

In 2013, the APA added caffeine withdrawal to the list of recognized conditions in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Only a subset of the population of caffeine consumers suffers withdrawal symptoms. Symptoms begin about 12-24 hours after sudden cessation of caffeine consumption and reach a peak after 20-48 hours. A gradual reduction in consumption over a period of days does not result in these symptoms.

Research has shown that caffeine does not activate the pathways in the brain that are related to addiction and reward in opposition to "hard" drugs. Therefore, researchers conclude that caffeine is not an addictive substance.

Brain mapping technology indicates that caffeine is not linked to the brain circuit of dependence. This is supported by the fact that individuals do not develop a tolerance to the stimulant effects of caffeine. The American Psychological Association also does not recognize caffeine as being an addictive substance.

Does caffeine have any health benefits?

Studies have shown caffeine to have potential health benefits; some of these are discussed below.

Caffeine can improve physical performance during endurance exercise.

Weight loss

Caffeine may boost weight loss or prevent weight gain, although there is no conclusive evidence to determine long-term results. Possible theories of how caffeine might affect weight include:

• Appetite suppression: caffeine may reduce the desire to eat temporarily
• Calorie burning: caffeine may stimulate thermogenesis - one method your body uses to generate heat and energy from digesting food.

Alertness

The European Food Safety Authority (EFSA) concluded that a cause and effect relationship has been established between a 75 mg serving of caffeine and both increased attention and alertness.

Caffeine is said to be comparable to sleep when a break is needed from driving to recover alertness.

Caffeine does not make a drunken person sober or fit to drive - it does not get rid of the effects of alcohol.

Sports performance

Caffeine is known to have ergogenic benefits and can improve physical performance during endurance exercise.

The EFSA has recognized that a cause-and-effect relationship has been established for caffeine intake and increased endurance performance, endurance capacity (in both cases for 3 mg/kg body weight 1 hour before exercise), and reduction in perceived exertion (4 mg/kg body weight 1 hour before exercise).

The effects of caffeine on short-term high-intensity exercise remain inconclusive.

Caffeine mixed with carbohydrates replenishes muscle glycogen concentrations faster after exercise.

Caffeine also relieves post-workout muscle pain by up to 48%.

Brain function

Caffeine acts at brain level by antagonizing the A1 and A_2A adenosine receptors. When caffeine is absorbed in the form of coffee, certain other constituents of coffee, such as polyphenol antioxidants, act on various pathways and may play an additional protective role.

Cognitive decline

Several epidemiological studies suggest that a regular, lifelong, moderate consumption of caffeine may slow down physiological, age-related cognitive decline, especially in women and those over 80 years old. However, more studies are still needed to increase the statistical power for the detection of an association between caffeine and cognitive impairment.

Alzheimer's and Parkinson's disease

Caffeine decreases the risk for age-related cognitive decline in diseases such as Alzheimer's and Parkinson's.

Animal studies have shown that caffeine may be able to counteract a variety of pathologies related to Alzheimer's disease. A systematic review and meta-analysis found a trend toward a protective effect of lifelong caffeine consumption and the risk of developing Alzheimer's disease.

There is a wealth of epidemiological studies reporting an inverse association between coffee consumption and risk of Parkinson's disease. The relationship is dose-dependent and suggests a possible causal effect. According to animal studies, it is likely that caffeine in coffee is the main component responsible for the potential preventative effect of coffee in Parkinson's disease involving mainly its antagonism at A_2A adenosine receptors.

When caffeine is absorbed in coffee, the direct effects of caffeine on neuroprotection seem to be reinforced by the effects of some other coffee constituents that together seem to act on the brain vascular system, the blood-brain barrier and inflammation.

Memory

Research from Johns Hopkins University suggests that a dose of caffeine after a learning session may help to boost long-term memory. The team concluded that at least 200 mg of caffeine is required to observe enhancing effect of caffeine on memory consolidation.

Liver and colon

Caffeine may detox the liver and cleanse the colon when taken as a caffeine enema.

According to a study published in the journal Hepatology, researchers have discovered that increased caffeine intake may reduce the risk of non-alcoholic fatty liver disease.

Eyelid spasm

Caffeine may help protect people from an eye disorder known as blepharospasm, according to a study published in the Journal of Neurology, Neurosurgery and Psychiatry. The condition, caused by abnormal brain function, makes people blink incessantly and can leave them functionally blind.²⁰

Cataracts

Researchers from the University of Maryland School of Medicine in Baltimore, MD, found that caffeine may be effective in protecting the lens against damage that could lead to the formation of cataracts.

Skin cancer

A Rutgers study strengthens the theory that caffeine guards against certain skin cancers at molecular level by inhibiting a protein enzyme in the skin, known as ATR. Scientists believe that based on what they have learned studying mice, caffeine applied directly to the skin might help prevent damaging ultraviolet light from causing skin cancer.

In another study, researchers at Brigham and Women's Hospital, Harvard Medical School in Boston, MA, and Harvard School of Public Health, found drinking three cups of caffeinated coffee was linked to a 21% lower risk of developing basal cell carcinoma in women, and a 10% lower risk in men, compared to drinking less than one cup per month.

Suicide

The World Journal of Biological Psychiatry published a study that concludes with an association between caffeine consumption and a lower risk of suicide.²²

Fertility

Caffeine-consuming men showed an increase in semen volume, movement and significantly less sperm DNA fragmentation than non-caffeine-consuming men in a study.

Erectile dysfunction

A study by the University of Texas Medical School in Houston stated that the total caffeine intake equivalent to about 2-3 cups of coffee (250-375 mg/day) is associated with a significantly lower reportage of erectile dysfunction. Reduced risk was even observed among men consuming as little as 85 mg of caffeine daily.²³

Tinnitus

A prospective study published in The American Journal of Medicine followed a group of 65,085 nurses since 1991. Higher caffeine intake was associated with a lower risk of incident tinnitus in women.²⁴

Kidney stones

A study of 217,883 participants analyzed the association between caffeine intake and the risk of developing kidney stones in three large cohorts of US health professionals.²⁵

In all three cohorts, participants with higher intakes of caffeine had a reduced risk of developing kidney stones. Intake of caffeine from sources other than coffee was also associated with reduced risk of kidney stones.

Mouth and throat cancer

In a study of 968,432 men and women, participants who reported drinking more than 4 cups of coffee a day had a 49% lower risk of death from oral cancer compared with those who reported not drinking coffee at all or only an occasional cup.

Stroke

Data from Sweden, of 34,670 women without a history of cardiovascular disease in 1997, was examined finding women who drink more than one cup of coffee per day to have a 22 to 25% lower risk of stroke compared with women who drink less. They found that low or no coffee drinking was linked to an increased risk of stroke.

Type 2 diabetes

Analysis drawing data from three large studies, covering a 20-year period, found that the participants who increased their coffee intake by more than one cup a day (on average, an increase of 1.69 cups per day) over a 4-year period had an type 2 diabetes risk 11% lower over the subsequent 4 years, compared with people who did not change their intake.

In addition, people who lowered their daily consumption by more than one cup of coffee (on average, a decrease of two cups per day) showed a 17% higher risk for type 2 diabetes.

Further claimed health benefits of caffeine include:

• Decreased risk of endometrial cancer
• Reduced risk of prostate cancer
• Protection against head and neck cancer
• Helping to prevent the return of breast cancer.

What are the risks of consuming caffeine?

Before racing to the kitchen and brewing endless cups of tea and coffee to maximize on all the potential health benefits of caffeine, below are some of the potential risks of consuming caffeine.

While much of the research published does allude to the safety and even potential benefits of caffeine (in moderation), there are a handful of research studies that highlight the potential harmful effects of caffeine.

It is recommended that pregnant women consume less than 300 mg of caffeine a day.

Depression

There is no clear link between caffeine intake and depression. However, caffeine intake and depression may be linked indirectly among people who are particularly sensitive to the effects of caffeine or who have too much caffeine.⁸

Hypertension

Caffeine can cause a short but dramatic increase in your blood pressure. It is unclear what causes this spike in blood pressure. 

Some researchers believe that caffeine blocks a hormone that helps keep your arteries widened. Others think that caffeine causes your adrenal glands to release more adrenaline, causing blood pressure to increase.¹⁰

Caffeine has a stronger blood pressure increasing effect in men who are older than 70 or who are overweight.¹⁰

When people with high blood pressure were given 250mg of caffeine in a study (about two coffees), the data revealed that their blood pressure was elevated for about 2-3 hours.

Blood sugar

Caffeine impairs insulin action but does not necessarily affect blood sugar (glucose) levels in young, healthy adults. However, if you have type 2 diabetes, the impact of caffeine on insulin action may be associated with a small but detectable rise in blood sugar levels, particularly after meals. About 250 mg of caffeine - or the equivalent of 2 to 2 1/2 cups (473 to 591 milliliters) of plain, brewed coffee a day may cause this effect.¹¹

Pregnancy

Studies in humans have shown that caffeine may cause miscarriage or may slow the growth of a developing fetus when given in doses greater than 300 mg (an amount equal to around three cups of coffee) a day. In addition, use of large amounts of caffeine by the mother during pregnancy may cause problems with the heart rhythm of the fetus.¹³

Caffeine can cross the placenta and affect the baby's heart rate. While further research is needed, some studies suggest that drinking too much caffeine during pregnancy might be associated with an increased risk of miscarriage.

It is recommended that pregnant women consume less than 300 mg of caffeine a day. Studies in animals have shown that caffeine causes birth defects when given in very large doses (amounts equal to 12 to 24 cups of coffee a day) and problems with bone growth when given in smaller doses.¹³

Breast-feeding

Caffeine passes into breast milk in small amounts and may build up in the nursing baby. Studies have shown that babies may appear jittery and have trouble sleeping when their mothers drink large amounts of caffeine-containing beverages.¹³

Gout

Preliminary research suggests that an extra jolt or two of caffeine may trigger a gout attack in people with the painful and often disabling arthritic condition.

Drinking four servings of caffeinated beverages in 24 hours is associated with an 80% increased risk of recurrent gout attacks.

Incontinence

In a study from the University of Alabama evaluating data on 1,356 women who reported taking in 329 mg of caffeine a day - about three cups of coffee or more - 70% had a higher likelihood of having a bladder problem. Excess caffeine increases the likelihood of urinary incontinence in women.

Insomnia

Results from a study published in the Journal of Clinical Sleep Medicine showed that consuming caffeine 3 and even 6 hours before bedtime significantly disrupts sleep - even when consumed 6 hours before bedtime, it reduced objectively measured total sleep time by more than 1 hour.

Headaches

A population-based study published in Neurology found that dietary and medicinal caffeine consumption appears to be a modest risk factor for chronic daily headache onset, regardless of headache type.²⁷

Fertility

Caffeine reduces muscle activity in the fallopian tubes that carry eggs from a woman's ovaries to her womb. Caffeine stops the actions of specialized pacemaker cells in the wall of the tubes.

These cells coordinate tube contractions so that when they are inhibited, eggs cannot move down the tubes. The authors of the study say the findings provide an explanation as to why women with high caffeine consumption often take longer to conceive than women who do not consume caffeine. Caffeine can reduce a woman's chances of becoming pregnant by about 27%.

Menopause

A recent study published in The Journal of The North American Menopause Society showed that menopausal women who consumed caffeine had a greater degree of vasomotor symptoms.²⁸

Dangers of mixing alcohol and energy drinks

Energy drinks are beverages that typically contain caffeine, other plant-based stimulants, simple sugars and other additives. They are very popular among young people and are regularly consumed by 31% of 12- to 17-year-olds, and 34% of 18- to 24-year-olds.¹⁴

When alcoholic beverages are mixed with energy drinks, a popular practice among young people, the caffeine in these drinks can mask the depressant effects of alcohol.

Drinkers who consume alcohol mixed with energy drinks are three times more likely to binge drink (based on breath alcohol levels) than drinkers who do not report mixing alcohol with energy drinks. They are also twice as likely to report being taken advantage of sexually, taking advantage of someone else sexually, or riding with a driver who was under the influence of alcohol.

Death

Death by caffeine might sound unlikely, but it can and has happened.

The FDA knows of a 19-year-old college student who died after taking an overdose of caffeine tablets to stay awake. A caffeine tablet contains as much caffeine as one to three 5-ounce cups of coffee.³

A single teaspoon of pure caffeine is roughly equivalent to the amount in 25 cups of coffee. Pure caffeine is a powerful stimulant, and very small amounts may cause accidental overdose. Parents should be aware that these products might be attractive to young people.⁵

A Mayo Clinic partnered study found that men who drank more than four 8 fl oz cups of coffee had a 21% increase in all-cause mortality.

Studies suggest that moderate amounts of caffeine are not harmful. How much is moderate? One hundred to 200 mg (one to two 5-ounce cups of coffee) each day is the limit that some doctors suggest, but each person is different. How caffeine affects people varies with their size, their sex, and how sensitive they are to caffeine's effects. Experts agree that 600 mg (four to seven cups of coffee) of caffeine or more each day is too much.³

Caffeine allergy

Caffeine sensitivity is determined by the efficiency of the human body to process and metabolize caffeine. It is not the same as caffeine tolerance, which describes how the body responds to caffeine over time.¹⁷

Sensitivity has more to do with a person's unique genetic makeup, as this determines to what degree a given amount of caffeine will affect a person.

Caffeine is metabolized by the liver using the enzyme CYP1A2. The ability to produce this enzyme is regulated by the CYP1A2 gene. Slight changes in the DNA sequence of this gene determines how efficiently a person can metabolize caffeine and thus eliminate it from the body.

Some people genetically produce very little of this enzyme while others produce a large amount. The majority of humans are somewhere in the middle. 10% of the population are rapid caffeine metabolizers and not sensitive to caffeine.²

The third genetic link to caffeine sensitivity involves the type of adenosine receptors a person has in their brain. Those lacking the correct adenosine receptors in their brain are unresponsive to the awakening effects of caffeine because the caffeine molecule cannot properly bind to the receptors.³

The most recent research from The Harvard School of Public Health found six new genetic variants associated with the way people metabolize and form addiction to caffeine.

The 120,000-person study revealed:

• Two genes related to how caffeine is metabolized
• Two genes associated with how we feel rewarded from caffeine
• Two genes that regulate fat and sugar in the blood stream as a response to caffeine.

Based on the genetic data, people can be identified with three distinct levels of caffeine sensitivity, determining to what degree the effects of caffeine will be realized:

1. Hypersensitive to caffeine: react to very small amounts of caffeine. Even at amounts less than 100 mg
2. Normal sensitivity to caffeine: can usually have 200-400 mg of caffeine daily without any adverse reactions
3. Hyposensitive to caffeine: process caffeine so efficiently that these people report taking large doses (>500 mg) without much effect at all.

Some people could be normal but lean toward the hypersensitive or hyposensitive categories. Human genetics are complex and people are unique with many subtle genetic variations.

Caffeine overdose

Ingesting massive doses of caffeine all at once is particularly dangerous as the body does not have time to react accordingly. Overdose symptoms serve as a warning system from mild to severe and consist of:

Ingesting massive doses of caffeine all at once should be avoided as it can cause numerous health problems.

• Jitters, restlessness, and nervousness
• Increased heartbeat
• Nausea
• Anxiety
• Heart palpitations
• Insomnia
• Sweating
• Dizziness
• Vomiting
• Cardiac arrest.

If these symptoms are recognized, further caffeine intake should be stopped in order to avoid more serious and even life-threatening symptoms.

Caffeine intoxication is included in the DSM-5 physicians manual.

The official diagnosis can be made when any five of the following symptoms are present: restlessness, nervousness, excitement, insomnia, flushed face, diuresis, gastrointestinal disturbance, muscle twitching, rambling flow of thought and speech, tachycardia or cardiac arrhythmia, periods of inexhaustibility or psychomotor agitation.

There are mechanisms built into the human body to prevent excessive consumption and this includes caffeine overdose. Well before toxic level, a person would experience side effects to prevent them from consuming more - nausea and vomiting.

Before the 149 or so cans of caffeinated energy drink that it would take to kill an average adult male, vomiting would most certainly occur.

Since caffeine is consumed so widely, there are a lot of half-truths, hearsay, urban legends, media hype and even fiction often surrounding the substance.

References:

1.        Caffeine use disorder: A comprehensive review and research agenda, Steven E. Meredith, et al., Journal of caffeine research, doi: 10.1089/jcr.2013.0016, published online September 2013.

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