Caffeine is the world’s most widely consumed psychoactive drug. It boosts physical and mental performance and may decrease the risk of type 2 diabetes, Parkinson’s disease, Alzheimer’s, and more. However, there are major drawbacks to consider. Read on to learn the caffeine benefits, side effects, and interactions.
What is Caffeine?
Caffeine is a plant compound and stimulant (methylxanthine). It has a similar structure to other plant compounds like theobromine, xanthine, and theophylline [1, 2].
For the average person, coffee or tea is the 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, polyphenols, or other components [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. Still, its prolonged use comes with certain drawbacks worth attention [1].
Snapshot
Proponents:
- Boosts physical and mental performance
- Relieves pain and headaches
- Protects the liver
- Helps prevent Parkinson’s and Alzheimer’s
- Helps prevent diabetes and kidney stones
- May support weight loss
Skeptics:
- Can cause tolerance and dependence
- Withdrawal can be extremely unpleasant
- May worsen anxiety and insomnia
- Increases blood pressure and heart rate
- May contribute to glaucoma at high doses
How Does it Work?
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 [6].
Consumers may feel more energized and awake due to caffeine blocking A1 receptors. This also causes heart-pounding effects [7].
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].
Caffeine Health Benefits
Effective:
1) Headache
Migraines
Caffeine is a part of different FDA-approved drugs for migraine headaches, along with acetaminophen, aspirin, sumatriptan, diclofenac, and others [9, 10, 11].
Other
Based on its proven efficacy, caffeine is also FDA-approved for simple (tension) headaches and the prevention of postoperative headaches [12, 13, 14].
Ironically, headache is one of the most common symptoms of caffeine withdrawal, which can be a limitation for its long-term use [15].
Likely Effective:
2) Attention and Alertness
Multiple clinical reviews have confirmed the potential of caffeine to increase mental alertness in low-to-moderate doses (40-300 mg). The effects were even more pronounced in non-regular users and during sleep deprivation [16, 17, 18].
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 [19].
A lack of sleep can cause delays in reaction times. In a study of 20 sleep-deprived participants, a total daily dose of 800 mg of caffeine helped improve reaction speed and accuracy [20].
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 [21].
However, some reviews have underlined the tolerance to its stimulant effects, abuse potential, and a potential toxicity that comes with higher doses [22, 23].
3) Physical Performance
A comprehensive clinical review summarized 21 meta-analyses on caffeine and physical performance. A large body of evidence suggests that “caffeine ingestion improves exercise performance in a broad range of exercise tasks.” It showed beneficial effects on [24]:
- Muscle endurance
- Muscle strength
- Aerobic endurance
- Anaerobic power
Caffeine particularly helps anaerobic exercises like sprinting or jumping. This effect may arise from its anti-fatigue effects and by improving endurance, physical strength, and power output [25].
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 [26].
Possibly Effective:
4) Parkinson’s Disease
Caffeine is neuroprotective and may prevent nerve cell degeneration, which occurs in Parkinson’s [27].
Additionally, by inhibiting adenosine receptors, it improves mobility and motor functions in Parkinson’s patients [28].
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 [29].
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 [30].
Additionally, in a study of 29,000 participants, both habitual coffee and tea drinkers had a lower risk for Parkinson’s [31].
5) Dementia and Alzheimer’s Disease
In a long-term study of 1,400 people, drinking 3 to 5 cups of coffee per day at midlife could decrease dementia or Alzheimer’s disease (AD) risk by about 65% during their elderly years [32].
In one review, coffee had a positive effect on brain function. Moderate caffeinated coffee consumption decreased the risk of dementia and AD later in life. However, caffeinated tea had no effects [32].
In mice, caffeine suppressed amyloid beta production. Amyloid beta contributes to brain inflammation and the onset of Alzheimer’s disease [33].
6) Liver Disease
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 [34].
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 [35].
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 [36].
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 [37].
7) Pain
According to a review of 20 studies with 7,238 participants, caffeine can slightly but significantly improve the effectiveness of acetaminophen, ibuprofen, and other painkillers [38].
8) Weight Loss
Many supplements are promoted to stimulate weight loss, but none of them has yet been supported by strong clinical evidence and approved by the health authorities. A healthy, calorie-controlled diet and increased physical activity remain the only proven strategies for weight control [39].
A combination of ephedrine and caffeine enhanced fat burning and weight loss and reduced blood lipids in five trials of over 500 participants [40, 41, 42, 43, 44].
That said, pure ephedrine and Ephedra-based products are banned by the FDA due to their high abuse potential and adverse effects on heart health [45, 46, 47].
Caffeine remained a popular ingredient in over-the-counter fat burning supplements. It may increase energy usage and improve metabolic rate, which helps prevent weight gain [48].
A meta-analysis published in 2019 included 13 clinical trials of 606 participants. The authors concluded that “caffeine intake might promote weight, BMI and body fat reduction” [49].
By breaking down stored fat, caffeine shows potential 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 [50].
9) 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 [51].
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 [52].
One review concluded that caffeine was inconsistent in its effects on memory. It was the most beneficial in improving memory during simple tasks, but not complex ones [53].
10) Asthma
According to a review of 7 clinical studies, caffeine can help open the airways and relieve bronchitis symptoms including wheezing, coughing, and breathlessness [54].
The effect is similar to theophylline, a common asthma drug. Theophylline and caffeine are very similar in structure, but caffeine’s effects are short-lived and last only up to 4 hours [55].
11) Cancer Prevention
Mouth and Throat Cancer
A 26-year observational 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 had up to 2 times lower cancer rates [56].
Colon Cancer
In an observational trial of 489,706 men, there was an inverse association between caffeinated coffee and colon cancer rates [57].
On the other hand, there was no link between caffeine and rectal cancer risk in a study of 120,000 nurses [58].
Skin Cancer
In a study of 450,000 subjects, caffeinated coffee drinkers had a lower risk of developing melanoma (skin cancer) than those who did not drink caffeine [59].
A meta-analysis of studies with non-melanoma skin cancer also found the protective effects of caffeine and coffee. Their regular intakes were associated with 14% and 18% lower cancer rates, respectively [60].
Liver Cancer
A review of 9 observational studies found 43% lower rates of liver cancer associated with the consumption of 2 cups of caffeinated coffee daily [61].
It’s worth mentioning that the above results come from observational studies. Additionally, other beneficial coffee ingredients may have contributed to the results. Well-designed clinical trials are needed to evaluate the potential anticancer effects of caffeine.
12) Type 2 Diabetes Prevention
In an observational study of nearly 90,000 healthy women, moderate caffeinated coffee consumption lowered the risk of type 2 diabetes in younger and middle-aged women [62].
Another review of 8 trials also showed that drinking caffeinated coffee is associated with a reduced risk of type 2 diabetes [63].
13) Kidney Stones
In a 20-year study of 217,883 healthy participants, high caffeine intake was associated with reduced rates of kidney stones [64].
Caffeine increases urinary excretion of calcium, which may cause kidney stone formation. At the same time, the higher intake of caffeine diluted urine and reduced kidney stone risk [64].
Insufficient Evidence:
No valid clinical evidence supports the use of caffeine for any of the conditions in this section. Below is a summary of up-to-date animal studies, cell-based research, or low-quality clinical trials which should spark further investigation. However, you shouldn’t interpret them as supportive of any health benefit.
14) Mood and Mental Health
In a large cohort study of 43,599 men and 164,825 women, people who consumed caffeinated coffee had a lower rate of suicide. This could be due to caffeine’s ability to increase dopamine [65].
However, higher amounts (600 mg) can increase tension and anxiety, which can negatively affect mood [66].
The effects of caffeine on depression are also conflicting: there are studies showing both increased and decreased rates associated with caffeine consumption [67, 68, 69, 70].
The explanation for conflicting results may lie in caffeine’s abuse potential and tolerance to both adverse and beneficial effects. Further research is warranted [22, 23].
15) Skin Protection
The protective effects against skin cancer likely stem from caffeine’s antioxidant properties that protect skin cells against UV radiation from sun exposure. Additionally, it is used in cosmetic products to prevent fat accumulation and cellulite formation [71].
In a study of 40 dermatitis patients, a topical cream containing 30% caffeine helped reduce redness, itchiness, scaling, and oozing [72].
More studies are needed to evaluate the skin-friendly effects of caffeine.
16) Erectile Dysfunction
An observational 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 benefits, caffeine did not help diabetic men [73].
17) Tinnitus
In a prospective study of 6,500 women, those who consumed the most caffeine had the lowest reported incidence of tinnitus (ringing in the ears) [74].
18) Gout
In a prospective study of 89,000 women, caffeinated coffee (but not tea) was associated with a lower risk of gout [75].
Controlled clinical trials are needed to evaluate the above benefits of caffeine found in observational studies.
Possibly Ineffective:
According to the available clinical evidence, caffeine supplementation may not help with:
Effects on Inflammation
In a study of 47 habitual coffee drinkers, drinking caffeinated coffee is associated with a decrease in inflammation markers (IL-18) [80].
Additionally, in another study of 1,390 healthy women and women with type 2 diabetes, those who drank caffeinated coffee had lower inflammatory marker (E-selectin and CRP) levels [81].
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 [82].
In a study of 33 athletes, caffeine supplementation caused higher levels of inflammatory cytokines (IL-6 and IL-10) after exercise. It enhanced the body’s inflammatory response to exercise [83].
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 [84].
Further clinical research should cast more light on the conflicting effects of caffeine on inflammation.
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.
Caffeine Side Effects
When used in adequate amounts, caffeine is likely safe for healthy individuals. Still, in sensitive people, it may cause some unpleasant side effects such as [85]:
- Restlessness
- Nervousness
- Dizziness
- Flushing
- Increased urination
- Diarrhea
- Vomiting
- Muscle twitching
- The rambling flow of thought and speech
However, most of caffeine’s side effects tend to decrease with prolonged consumption and tolerance.
1) Dependence
Caffeine is a psychostimulant 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 [86].
Caffeine Withdrawal
Caffeine withdrawal can be a serious reaction of the body to the lack of this stimulant, with symptoms such as [86]:
Caffeine Tolerance
Those who take caffeine habitually, in any form, may build up a tolerance to different health effects, both adverse and beneficial [87].
2) 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 [88].
In a large cohort study of secondary school children, there was a positive correlation between caffeine and anxiety. A high intake of caffeine worsened anxiety, stress, and depression symptoms [89].
3) 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 the body’s natural hormone levels and wake-and-sleep cycles that promote restful sleep [90].
If you are suffering from insomnia, you should only have caffeinated drinks before noon or eliminate them altogether.
4) Reduced Insulin Sensitivity
In a study of 12 male participants, high doses of caffeine reduced their insulin responses [91].
In another study, high caffeinated coffee consumption temporarily decreased insulin sensitivity. 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 [92].
However, for most healthy people, caffeine should not have any significant effect on blood sugar levels [92].
5) Increased 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, the ingestion of caffeine through coffee only had a small effect on blood pressure [93].
New users may experience higher spikes in blood pressure, but the effects subside soon after (about 4 days). Still, people with hypertension or those at risk should consume it with caution [94].
6) Increased Cholesterol
In a study of 30 adults, caffeine was associated with a significant increase in total blood cholesterol and LDL (bad) cholesterol [95].
Long-term consumption of caffeinated coffee may alter fat distribution in the body and contribute to atherosclerosis in some cases [95].
7) Tachycardia
Caffeine raises the blood level of adrenaline. 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 [94].
8) Blood Clotting
Caffeine blocks adenosine A2a receptors and causes blood vessels to constrict [96].
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 [97].
In mice, when it binds to A2a receptors, caffeine may induce blood clotting [98].
9) Glaucoma (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 higher glaucoma rates (elevated pressure in the eye) than those who consumed less than 125 mg daily [99].
In a different cohort study of 3,600 patients, habitual caffeinated coffee drinking was associated with higher eye pressure and glaucoma [100].
Caffeine Drug and Substance Interactions
1) SSRIs
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 impair caffeine elimination, possibly causing adverse effects [101].
2) Beta-Blockers
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 a high dosage of caffeine, as caffeine increases anxiety. Caffeine may interact with propranolol, increasing blood pressure [102].
3) Creatine
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 [103].
4) Alcohol
Combining caffeine and alcohol is very common in the nightlife since many people add energy drinks to their alcoholic beverages.
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 [104].
Additionally, when caffeine blocks A2A receptors, it can contribute to the addictive effects of alcohol [104].
