What is Caffeine?
For the average person, coffee or tea is their main source of caffeine. Coffea arabica and Coffea canephora (Robusta) are two types of plants that produce coffee beans. Meanwhile, the Camellia sinensis leaves are used for black, green, and white teas [3, 2].
Although coffee and tea both contain caffeine, they can have different effects on our health. This may be due to their different amounts of caffeine or other components. While coffee also contains diterpene alcohols that can raise cholesterol, tea contains polyphenols, which have many health benefits [4, 5].
Caffeine is consumed around the world for its beneficial effects on energy, physical and mental performance, alertness, and mood. Many people praise its ability to keep them awake and focused on their tasks. Additionally, most of its side effects tend to decrease with prolonged consumption .
How Does Caffeine Work?
Caffeine Inhibits Adenosine
Since caffeine’s structure is similar to adenosine, it can block adenosine receptors (mainly A1 and A2A). It increases the activation of the sympathetic (fight-or-flight) nervous system, which results in stimulatory effects .
Consumers may feel more energized and awake due to caffeine blocking A1 receptors. This also causes heart-pounding effects .
Caffeine Inhibits Phosphodiesterase
Caffeine binds to phosphodiesterase receptors and blocks phosphodiesterase activity. As less phosphodiesterase receptor molecules become available, cAMP cannot bind to the receptors and it accumulates in the cells. This produces effects such as vasodilation (widening of blood vessels), and fat oxidation (breakdown) [6, 8].
1) Improves Attention and Alertness
In a study of 36 participants, caffeine exhibited dose-dependent effects on alertness and attention. When people who usually do not drink caffeinated products consumed high doses of caffeine, they had a higher increase in brain function. Regular and tolerant users may still feel the same effects, but to a smaller extent .
Caffeine helps keep you alert and awake while driving. In one study, twelve young adults either had sufficient sleep (9 hours) or a lack-of-sleep (4 hours). 100 mg of caffeine improved both groups’ coordination, judgment, memory, and reaction time during a driving task .
2) Increases Strength and Endurance
Caffeine appears to help anaerobic exercises like sprinting or jumping. This effect may arise from its anti-fatigue effects and by improving endurance, physical strength, and power output .
In a study of 16 recreationally trained young men, caffeine improved upper and lower body muscle force. It improved smaller muscle strength by 6% and larger muscles by more than 13% .
It also positively affects the metabolic rate and increases oxygen uptake. When you can take in more oxygen, utilizing it at maximum exertion, you have better athletic performance .
In a study of 14 well-trained men, their power output significantly increased after caffeine ingestion, improving their sprint performance .
When caffeine delays fatigue, the body’s muscles can contract more forcefully. People may exercise longer and eventually increase their training volume or overall work. Aerobic exercise such as running, jogging, cardio workout, swimming, and biking can benefit the most from increased training volume .
In a study of 24 professional rugby players, an 800-mg dose of caffeine increased their testosterone by 21% during exercise, compared to 15% without caffeine. However, it also increased cortisol levels .
3) Prevents Weight Gain
Caffeine is a popular ingredient in over-the-counter fat burning supplements. It can increase energy usage and improve metabolic rate, which helps prevent weight gain .
In a study of ten lean and ten obese women, both groups produced more body heat, spent more energy, and had increased fat oxidation (breakdown) after coffee ingestion. Their increase in energy usage was short-lived compared to fat breakdown .
In a study of healthy and obese individuals, 4 different studies showed that caffeine increased free fatty acid (FFA) levels and fat breakdown .
By breaking down stored fat, caffeine shows benefits in weight loss management. In a study of 2,100 participants, the ones who drank 2 to 4 cups of caffeinated coffee a day were more successful at shedding weight than those who did not .
4) Can Improve Mood
For some people, 200 to 250 mg of caffeine may improve their mood for up to 3 hours .
5) May Protect Against Parkinson’s Disease
Caffeine is neuroprotective and can prevent nerve cell degeneration, which occurs in Parkinson’s .
In a study of 61 Parkinson’s patients, 100 mg of caffeine twice daily for 3 weeks reduced movement slowness (bradykinesia). However, it had no other effects on Parkinson’s symptoms .
In one study, out of 430 healthy subjects, those who consumed caffeinated coffee had a lower risk of developing Parkinson’s disease. It even reduced the risk in those genetically predisposed to develop the condition .
Additionally, in a study of 29,000 participants, both habitual coffee and tea drinkers had a lower risk for Parkinson’s .
6) May Enhance Memory
In a study of 95 healthy young adults, moderate doses of caffeine (200 mg) increased memory performance. Although the results were not significant, high to moderate caffeine users had increased memory recall compared to low users .
In another study, 140 young adults participated in two experiments. The participants that consumed caffeinated coffee in the morning had significantly better performances on a memory recall test in the early morning, but not in the late afternoon .
However, a review concluded that caffeine was inconsistent in its effects on memory. It was the most beneficial on improving memory during simple tasks, but not complex ones .
7) Reduces Dementia and Alzheimer’s Disease Risk
In a long-term study of 1,400 people, drinking 3 to 5 cups of coffee per day at midlife could decrease dementia or AD risk by about 65% during their elderly years .
In a review, coffee had a positive effect on brain function. Moderate caffeinated coffee consumption (around 4 cups) decreased the risk of dementia and Alzheimer’s later in life. However, caffeinated tea had no effect on dementia or Alzheimer’s risk .
In mice, caffeine suppressed amyloid beta production. Amyloid beta contributes to brain inflammation and the onset of Alzheimer’s disease. Thus, caffeine can protect and restore brain function .
8) Protects the Liver
Caffeine is associated with a lower risk of liver fibrosis (scar tissue in the liver). In a study of 306 patients with fatty liver disease, people who drank caffeinated coffee had less severe liver scarring than the ones who did not drink caffeinated coffee .
In a cross-sectional study of 910 veterans with chronic hepatitis C, a minimum of 100 mg of caffeine daily reduced the odds of liver tissue scarring .
Additionally, in a survey of 177 liver biopsy patients, caffeine consumption was associated with less severe liver tissue scarring. Two cups of coffee daily helped reduce the severity of tissue scarring .
A study of 274 cirrhosis cases and 458 healthy individuals found that caffeinated coffee prevented liver cirrhosis (chronic liver damage). However, intake from sources other than coffee (such as tea or energy drinks) did not show the same benefits .
9) May Lower Cancer Risk
Mouth and Throat Cancer
A 26-year cohort study examined almost 1 million men and women to look at the association between caffeine and oral/pharyngeal (mouth and throat) cancer .
There was an association between high caffeinated coffee intake and reduced risk of oral cancer. Those who consumed 4 to 6 cups of caffeinated coffee daily reduced their cancer risk by approximately 50% .
Colorectal cancer may be either proximal, distal, or rectal cancer. Proximal cancer affects the first and middle parts of the colon. Proximal tumors are associated with a higher death rate in colon cancer .
In a cohort study of 489,706 participants, there was an inverse association between caffeinated coffee and colon cancer risk. People who drank 4 to 5 cups of coffee daily had a lower risk of colon cancer and proximal tumors .
However, there was no link between caffeine and reduced rectal cancer risk in a different, 2 million person cohort study .
In a cohort study of more than 4 million subjects, caffeinated coffee drinkers had a lower risk of developing melanoma (skin cancer) than those who did not drink caffeine .
In rats with skin cancer, caffeinated tea consumption decreased the number of tumors and fat levels. Reducing fat levels in the skin can decrease tumor formation .
Liver cancer is normally secondary cancer that happens when cancer cells spread from other parts of the body. However, hepatitis, tissue scarring, and chronic liver damage may cause primary liver cancer .
A review of 4 cohorts and 5 case-control studies found a 43% decreased risk of liver cancer with the consumption of 2 cups of caffeinated coffee daily .
10) Protects the Skin
Caffeine has antioxidant properties that can help protect skin cells against UV radiation and skin aging due to sun exposure. Additionally, it is used in cosmetic products to prevent fat accumulation and cellulite formation .
In a study of 40 dermatitis patients, a topical cream containing 30% caffeine helped reduce redness, itchiness, scaling, and oozing .
11) Relieves Asthma
A review of 7 studies showed that caffeine could open airways and relieve bronchitis symptoms including wheezing, coughing, and breathlessness .
When airways open, this helps people with asthma breathe easier. The effect is similar to theophylline, a common asthma drug. Theophylline and caffeine are very similar in structure. However, caffeine’s effects are short-lived and last only up to 4 hours.
12) May Lower the Risk of Type 2 Diabetes
Consumption of caffeine may lower your risk of getting type 2 diabetes. In a prospective cohort study of nearly 90,000 healthy women, moderate caffeinated coffee consumption lowered the risk of type 2 diabetes in younger and middle-aged women .
Another review of 8 prospective studies also showed that drinking caffeinated coffee is associated with a reduced risk of type 2 diabetes .
13) May Prevent Erectile Dysfunction
A cohort study of 3,700 men showed that those who drank 2 to 3 cups of caffeinated coffee daily had a lower risk of erectile dysfunction. While healthy, overweight, and men with high blood pressure experienced these results, caffeine did not help diabetic men .
14) Reduces Kidney Stone Risk
In a 20-year cohort study of 217,883 healthy participants, high caffeine intake was associated with a reduced risk of kidney stones .
15) May Prevent Tinnitus
In a prospective study of 6,500 women, the women who consumed the most caffeine had the lowest reported incidence of tinnitus (ringing in the ears) .
16) Might Help Relieve Pain
There is a link between sleep deprivation and hyperalgesia (heightened sensitivity to pain) .
In mice, common painkillers (ibuprofen and morphine) had no noticeable effects on sleep-deprived mice. In contrast, caffeine relieved pain in sleep-deprived mice but not in normal mice .
17) May Prevent Gout
In a prospective study of 89,000 women, caffeinated coffee (but not tea) was associated with a lower risk of gout .
Some of the most common side effects are :
- Flushed face
- Increased urination
- Muscle twitching
- The rambling flow of thought and speech
However, most of caffeine’s side effects tend to decrease with prolonged consumption and tolerance.
Caffeine is a drug. Since its effects vary among individuals, people alter their needs according to their level of tolerance. For example, if you always drink a cup of coffee in the morning, going a day or two without that usual fix is tough both for the mind and body .
Caffeine withdrawal is a serious reaction. Symptoms include :
Those who take caffeine habitually, in any form, may build up the tolerance and several of its effects are dull for the same amount.
Drinking too much caffeine can worsen health issues.
2) Can Worsen Anxiety
The side effects of excessive caffeine intake include increased heart rate (tachycardia), restlessness, and anxiety. If you feel nervous and stressed, you should avoid it as well as sugar and other stimulants .
3) Can Contribute to Insomnia
It is a well-known fact that caffeine can help with wakefulness. While this is a benefit for some people, it’s a problem for others who have sleep-related problems. Caffeine might disrupt your body’s natural hormone levels and wake-and-sleep cycles that help promote restful sleep .
If you are suffering from insomnia, you should only have caffeinated drinks before noon or eliminate them altogether.
4) Reduces Insulin Sensitivity
In a study of 12 male participants, high doses of caffeine reduced their insulin responses .
In another study, high caffeinated coffee consumption decreased insulin sensitivity for over a period of 100 to 180 minutes. A greater release of neurotransmitters (catecholamines) and free fatty acids, high insulin secretion, or less insulin clearance in the liver could have caused this decrease in sensitivity .
However, for most healthy people, caffeine should not have any significant effect on blood sugar level. You can build a tolerance to the effects on fasting glucose levels after 5 days of caffeine intake .
5) Raises Blood Pressure
This effect depends on two factors: whether the user normally drinks caffeine and if they have a family history of hypertension (high blood pressure).
A meta-analysis of 16 studies showed that 410 mg of caffeine daily raised the risk for high blood pressure, even in healthy people. However, ingestion of caffeine through coffee only had a small effect on blood pressure .
New users may experience higher spikes in blood pressure, but the effects subside soon after (about 4 days). However, people with hypertension risk should consume it with caution .
6) Can Increase Cholesterol
Long-term consumption of caffeinated coffee may lead to alterations in the distribution of fat in the body and cause heart disease or your arteries to harden (atherosclerosis) .
7) Produces Tachycardia
Caffeine raises the blood level of adrenaline (the dosage depends on the person). This hormone can increase blood pressure, contractility of the heart, and heart rate (tachycardia). The effect is more pronounced in those who do not frequently consume it or in those who take high doses .
However, data for heart rate measurement are less consistent than other measurements, possibly due to the different ways you can measure heart rate and the instruments used .
8) May Cause Blood Clots
In mice, when it binds to A2a receptors, it may induce blood clotting .
In a study of 33 healthy subjects, a high dosage of caffeine increased blood platelet count and clotting, while exercise increased this effect even more. Fortunately, this response may be desensitized after prolonged usage .
9) Harms Eye Health (At High Doses)
In a cohort study of more than 120,000 healthy patients, the participants whose total caffeine consumption was more than 500 mg daily had a higher risk of getting glaucoma (elevated pressure in the eye) than those who consumed less than 125 mg daily .
In a different cohort study of 3,600 patients, habitual caffeinated coffee drinking was associated with higher eye pressure and glaucoma .
10) Increases Cortisol Levels
Cortisol, “the stress hormone,” helps control blood sugar levels, regulate metabolism, reduce inflammation, and assist with memory formulation. However, prolonged increases in cortisol are not good for your health .
In a study of 24 healthy athletes, an 800 mg dose of caffeine boosted their cortisol levels by 52% during and after exercise. However, lower doses did not have any effect on their cortisol levels .
Caffeine has conflicting effects on inflammation. It reduces inflammation in some people, while it increases inflammation in others.
In a study of 47 habitual coffee drinkers, drinking caffeinated coffee is associated with a decrease in inflammation markers (IL-18) .
However, in a study of blood cells from 8 healthy individuals, 165 mg of caffeine supplementation decreased inflammation markers (IL-6, IL-8, PGE2, PGA2, PGD2, etc.) in some blood samples while it increased them in others .
Additionally, caffeine increases inflammation in response to mental stress. In a study of 85 healthy subjects, habitual caffeinated coffee, but not tea, consumption was associated with increased blood vessel inflammation .
Metabolism and Excretion
The half-life of a drug means the amount of time for the concentration of the drug in the blood or body to reduce to 50% of its original levels. The average half-life of caffeine is 5 hours, but it can range from 2 – 9.5 hours and depends on the individual .
The human body readily absorbs caffeine, and it is 99% absorbed 45 minutes after ingestion. Peak levels in the blood occur between 15 – 120 minutes .
Smoking can quicken caffeine metabolism, while oral contraceptives can keep it in the body for a longer period of time (they may double caffeine’s half-life) .
It does not need to pass the stomach and intestines to get into the blood. Thus, caffeinated chewing gums have quicker absorption of caffeine, followed by capsules, coffee, soda, and chocolate [80, 81].
Caffeine metabolism occurs mainly in the liver. The main pathway is the formation of paraxanthine and its subsequent excretion into the urine in that form. It is also excreted in the urine in its normal form, or as different metabolism products (theophylline, uric acid, and uracil) [79, 82].
It can also be excreted through breast milk, but only in small amounts. 25 L of breast milk contains the same amount of caffeine as one cup of coffee .
There are various sources of caffeine; each has a different caffeine content depending on the product types and production methods .
- Caffeinated chewing gum (137 – 148/150 ml) 
- Energy drinks (51 – 95 mg/150 ml) 
- Coffee (40 – 180 mg/150 ml)
- Green tea (24 – 50 mg/150 ml)
- Guarana (24 mg/ 150 ml) 
- Yerba Mate (15 mg/150 ml) 
- Soda (12 – 24 mg/150 ml)
- Black tea (8 – 39 mg/150 ml) 
- White tea (8 -39 mg/150 ml) 
- Chocolate (5 – 193 mg/150 g)
- Topical cream (5 -45 mg/150 ml) [47, 48]
- Cocoa (2 – 7 mg/150 ml)
- Weight loss drugs/performance-enhancing pills (200 mg/pill)
Decaffeinated Coffee and Teas
There are various ways to produce decaffeinated beverages. Although many people think decaf coffee and tea is healthier, the process used to make it is far from natural.
The methods steam the coffee beans or tea leaves and add chemicals and solvents to the beans (including activated charcoal, carbon dioxide, ethyl acetate, and dichloromethane).
However, depending on the method, the decaffeinated coffee can still contain small amounts of caffeine .
Currently, researchers are developing genetically engineered coffee plants with reduced caffeine levels .
There is no single recommended dosage as it should tailor to individual differences, their genetic variability and their history with caffeine. An effective dose can range from 32 to 1,400 mg .
Medium doses (225 to 360 mg) were effective at improving physical performance, while 100 to 600 mg can help improve brain performance .
However, doses above 250 mg can cause symptoms that mimic anxiety. Additionally, prolonged use of at least 100 mg/day can cause tolerance and/or dependence .
Although there is no significant evidence that caffeine consumption can harm reproductive health or cause miscarriages, doctors still recommend pregnant women to refrain from drinking too much .
Overdose and Toxicity
Signs of Caffeine Overdose :
- Stomach pain
Cycling is defined as taking caffeine in intervals, instead of every day. For example, some people drink 2 cups of coffee on weekdays so that they could feel more energized at work. During weekends, they do not drink any coffee to ensure caffeine’s benefits without the need for more consumption.
Cycling may or may not be needed, depending on your own biology and response to caffeine consumption.
However, various studies have shown that habitual use does not have as many negative effects as stated. In a study (DB-RCT) of 40 endurance-trained athletes, the level of habitual caffeine consumption did not change its benefits. This means that there was no difference between drinking caffeine over a long vs. short period of time .
Theanine is an amino acid that promotes relaxation. When combined with caffeine, it may boost cognitive performance, alertness, and raise blood pressure and heart rate .
In a study of 44 young adults, a combination of 97 mg L-theanine with 40 mg of caffeine improved their focus during a demanding cognitive task .
2) ECA Stack
ECA stack stands for the mixture of ephedrine (75 to 150 mg), caffeine (150 mg), and aspirin (330 mg). Obese otherwise healthy subjects may take ECA for sustained weight loss. This method is potentially more effective if the person is dieting .
However, the FDA prohibited the sale of dietary supplements containing ephedrine in 2004. This is because ephedrine contributed to heart disease risk and deaths .
3) Methamphetamine (Meth)
In a study of 7 participants, fluvoxamine, an SSRI used to treat OCD and depression, inhibited CYP1A2, which is the main enzyme that breaks down caffeine. Taking Fluvoxamine and caffeine together may lead to caffeine staying in the body longer, possibly causing adverse effects .
Propranolol is a beta-blocker that can help treat heart disease, high blood pressure, and chest pain (angina). Anti-anxiety effects of beta-blockers can be reduced by high dosage of caffeine, as caffeine increases anxiety. Caffeine may interact with propranolol, increasing blood pressure .
Athletes normally use creatine to increase their exercise performance, including strength and endurance. However, caffeine consumption can reduce creatine’s effectiveness. In various studies, concurrent use of caffeine and creatine caused gut problems and dehydration .
Combining caffeine and alcohol is very common in the nightlife since many people add energy drinks to their alcoholic beverages to stay awake and be able to party all night long.
Both caffeine and alcohol block adenosine receptors. The receptors help mediate both their negative effects, such as sleepiness, lack of muscle coordination, and anxiety. So when you mix them, they block the A1 receptors and may prevent you from noticing the side effects .
Additionally, when caffeine blocks A2A receptors, it can contribute to the addictive effects of alcohol .
Limitations and Caveats
Although caffeine seems to have promising health benefits, most of the studies only showed associations between its consumption and health improvement (causal studies are lacking).
Additionally, since many studies used coffee as their source of caffeine, it is possible that other compounds contributed to its effects.
Users praised caffeine tablets and supplements for help with their weight loss. They also reported improvements in their mental stress, anxiety, alertness, and memory.
Other users also commented that they use caffeine to increase their energy and help with their exercise.
However, others complained that caffeine supplements made them more tired throughout the day or not being able to sleep well at night. Also, some people experience increased heart rate and anxiety right after drinking coffee.