May 30, 2024

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NEJM authoritative review: the relationship of Coffee Caffeine and health

NEJM authoritative review: the relationship of Coffee Caffeine and health

NEJM authoritative review: the relationship of Coffee Caffeine and health.

Both coffee and tea are among the most popular beverages in the world. They contain a lot of caffeine, which makes caffeine the most widely consumed psychoactive substance.

People have always worried that coffee and caffeine may increase the risk of cancer and cardiovascular disease, but in recent years there has been evidence that coffee and caffeine are good for health.

On July 23, 2020, the New England Journal of Medicine (NEJM) published a review article: Coffee, Caffeine, and Health (the relationship between coffee, caffeine, and health), detailing the physiological and toxic effects of coffee and caffeine. The correlation with the risk of chronic diseases, and the precautions for pregnant women to drink coffee.

The review pointed out that a large amount of evidence suggests that drinking coffee does not increase the risk of cardiovascular disease and cancer, and drinking 3 to 5 cups of coffee a day is associated with a reduction in the risk of several chronic diseases.

NEJM authoritative review: the relationship of Coffee Caffeine and health

Metabolism, physiological effects and toxic effects

Absorption and metabolism

The activity of caffeine metabolizing enzymes is inherited to a certain extent. People whose caffeine metabolism is slower due to genetic factors tend to consume lower amounts of caffeine habitually than people who do not have this genetic characteristic. Caffeine can affect the effects of many drugs, and doctors should consider the possible interaction between caffeine and drugs when prescribing.

A key issue in the research of caffeine and coffee is that coffee also contains hundreds of other biologically active phytochemicals.

These compounds in coffee can reduce oxidative stress, improve the intestinal microbiota, and regulate glucose and fat metabolism, while the diterpene caffeol contained in unfiltered coffee can increase serum cholesterol levels.

Therefore, we should carefully interpret the results of studies on coffee and other dietary sources of caffeine, because its effects may not be caused by caffeine itself.

Cognitive function

An appropriate amount (40-300 mg) of caffeine reduces fatigue, improves wakefulness, and shortens reaction time (Figure 2). These effects of caffeine are seen in people who drink coffee non-habitually, as well as those who habitually drink coffee after they quit coffee temporarily.

Caffeine can also increase people’s alertness during long hours of work with low levels of excitement, such as working on assembly lines, driving long distances, and flying airplanes.

Although the above-mentioned mental benefits of caffeine are most obvious under sleep deprivation, caffeine cannot compensate for the decline in work performance after chronic sleep deprivation.

Effects on sleep, anxiety and withdrawal symptoms

Ingesting caffeine in the afternoon or evening will prolong sleep latency and reduce sleep quality. In addition, caffeine can induce anxiety, especially in high-dose intake (>200 mg each time or >400 mg daily) and in sensitive people (including patients with anxiety or bipolar disorder). The effects of caffeine on sleep and anxiety vary greatly from person to person.

These differences may reflect differences in caffeine metabolism and adenosine receptor gene mutations. People who consume caffeine and doctors should be aware of the possible side effects of caffeine, and should inform people who drink caffeine-containing beverages that if these side effects occur, they should reduce their caffeine intake or avoid taking them in the afternoon and evening. Into caffeine.

If you quit caffeine after habitual intake of caffeine, it may cause withdrawal symptoms, including headaches, fatigue, decreased brain sensitivity and moodiness, and in some cases flu-like symptoms. These symptoms usually peak 1 to 2 days after stopping caffeine intake, and last for 2 to 9 days. The withdrawal symptoms can be alleviated by gradually reducing the dose of caffeine.

Toxic effect

The side effects of very large amounts of caffeine include anxiety, restlessness, nervousness, irritability, insomnia, excitement, psychomotor agitation, and confusion in thinking and language. It is estimated that the consumption of ≥1.2 g of caffeine can produce toxic effects, and doses of 8.8 to 14 g of caffeine are considered fatal.

Caffeine poisoning is rare after drinking traditional sources of caffeine such as coffee and tea, because it takes a very large amount of caffeine in a short period of time (75-100 standard cups of coffee) to reach a lethal dose. Caffeine-related deaths are usually due to large doses of caffeine in pills or powdered or liquid supplements.

There are case reports that large amounts of energy drinks and small bottles of high-concentration energy drinks (especially when mixed with alcohol) are also associated with cardiovascular, psychological and neurological adverse events (including fatal events).

The caffeine in energy drinks and vials of high-strength energy drinks may have more adverse effects than other caffeinated beverages.

It is recommended that people who drink energy drinks carefully check the caffeine content and avoid large amounts of energy drinks (>200 mg caffeine per intake) or drink alcohol at the same time as drinking energy drinks.

Chronic disease risks

Methodological factors

Research on caffeine intake and health outcomes may have several potential limitations. First, the observed acute effects of caffeine may not reflect its long-term effects, because the body can develop tolerance to caffeine.

Second, epidemiological studies on caffeine intake and the risk of chronic diseases may have confounding factors such as smoking or other unhealthy lifestyles; early studies that did not fully consider this bias have produced misleading results.

Even in recent studies that have conducted a more comprehensive correction for potential confounding factors, residual confounding is still a worrying issue. Due to practical operation and cost considerations, long-term randomized trials are often not feasible.

Third, measurement errors will affect the evaluation of caffeine intake. However, the self-reported coffee frequency is usually highly accurate and reproducible.

Epidemiological studies on coffee intake usually do not record differences in the following aspects: cup size, coffee concentration, type of coffee beans, and the amount of sugar, milk, or cream added to the coffee, which leads to some classifications of exposure mistake.

Finally, in prospective studies on caffeine intake, coffee and tea have been the main sources of caffeine.

It is not clear whether these observations of caffeinated beverages also apply to other sources of caffeine.

Blood pressure, blood lipids and cardiovascular disease

A meta-analysis of longer-duration trials showed that consumption of pure coffee and therefore non-coffee or other beverages resulted in a small increase in systolic and diastolic blood pressure.

However, in trials on caffeinated coffee, blood pressure was not significantly affected, even in hypertensive patients.

The reason may be that other components in coffee (such as chlorogenic acid) counteract the blood pressure effect of caffeine. Similarly, in a prospective cohort study, coffee consumption was not associated with an increased risk of hypertension.

In unfiltered coffee (such as French press coffee, Turkish coffee or Scandinavian freshly brewed coffee), the cholesterol-raising compound caffeol has a high concentration; espresso espresso and moka pots are freshly brewed The coffee alcohol concentration in coffee is in the middle; while the coffee alcohol concentration in drip coffee, instant coffee and percolation coffee is negligible.

In randomized trials, large amounts of unfiltered coffee (median, 6 cups per day) increased LDL cholesterol levels by 17.8 mg/dL compared with filtered coffee, and the risk of major cardiovascular events is expected to increase by 11% .

In contrast, filtered coffee did not increase serum cholesterol levels. Therefore, restricting the consumption of unfiltered coffee and drinking espresso in moderation may help control serum cholesterol levels.

Human experiments and cohort studies have shown that caffeine intake is not related to atrial fibrillation. Studies have consistently shown that in the general population or people with a history of high blood pressure, diabetes or cardiovascular disease, compared with not drinking coffee, drinking up to 6 standard cups of caffeinated filter coffee per day is associated with coronary heart disease and stroke. The increased risk of vascular outcomes is not related. In fact, drinking coffee is associated with a lower risk of cardiovascular disease, and the risk of cardiovascular disease is lowest when drinking 3 to 5 cups of coffee a day. Observational results show that coffee drinking is negatively related to the risk of coronary heart disease, stroke, and death from cardiovascular causes.

Weight management, insulin resistance and type 2 diabetes

Metabolism studies suggest that caffeine can improve energy balance by reducing appetite and increasing the basal metabolic rate and thermogenesis caused by food.

In the cohort study, increased caffeine intake was associated with a slight decrease in long-term weight gain. Limited evidence from randomized trials also supports a small beneficial effect of caffeine on body fat. However, high-calorie caffeinated beverages (such as soft drinks, energy drinks, sweetened coffee or tea) may cause weight gain.

Drinking caffeinated coffee (4 to 5 cups a day) for up to 6 months did not affect insulin resistance. In addition, in the cohort study, there was a dose-response relationship between habitual coffee consumption and the risk of type 2 diabetes, and the relationship between caffeinated coffee and decaffeinated coffee and the risk of type 2 diabetes was similar.

In summary, these findings suggest that the adverse effects of caffeine on insulin sensitivity can be tolerated by the body, or that the aforementioned adverse effects are caused by the long-term beneficial effects of non-caffeine components on glucose metabolism (possibly in the liver). offset.

Cancer and liver disease

Many prospective cohort studies provide strong evidence that coffee consumption and caffeine intake are not associated with increased cancer incidence or cancer mortality. Coffee drinking is associated with a small reduction in the risk of melanoma, non-melanoma skin cancer, breast cancer, and prostate cancer.

Studies have found that coffee consumption is strongly negatively correlated with the risk of endometrial cancer and hepatocellular carcinoma.

For endometrial cancer, the above-mentioned association is similar when drinking caffeinated coffee and decaffeinated coffee, while for hepatocellular carcinoma, the above-mentioned association appears to be stronger when drinking caffeinated coffee.

Coffee is also associated with other aspects of liver health, including lower levels of enzymes that reflect liver damage, and a lower risk of liver fibrosis and cirrhosis. In addition, coffee polyphenols can improve the homeostasis of fat and reduce oxidative stress, and in this way prevent liver steatosis and fibrosis.

Stone disease

Drinking coffee is associated with a reduced risk of gallstones and gallbladder cancer, and compared with decaffeinated coffee, caffeinated coffee has a stronger association with the above risk reduction, suggesting that caffeine may have a protective effect. Drinking coffee can inhibit gallbladder fluid absorption, increase cholecystokinin secretion and stimulate gallbladder contraction, thereby preventing the formation of cholesterol stones.

Nervous system disease

Prospective cohort studies have shown that caffeine intake is strongly negatively correlated with the risk of Parkinson’s disease. Drinking decaffeinated coffee is not related to Parkinson’s disease, which suggests that the above-mentioned negative correlation comes from caffeine, not other components of coffee.

In several studies in the United States and Europe, coffee consumption and caffeine intake are also associated with a lower risk of depression and suicide, but these observations may not apply to people with high intakes (drinking ≥8 cups of coffee per day). Different studies on the relationship between coffee consumption and the risk of dementia or Alzheimer’s disease have inconsistent conclusions.

All-cause mortality

In global cohort studies and in cohort studies of Europeans, African Americans, and Asians, drinking 2 to 5 standard cups of coffee per day was associated with reduced mortality.

After adjusting for the confounding effects of smoking status, people who drink more than 5 cups of coffee a day have a lower or similar death risk than people who do not drink coffee.

The confounding effect of baseline health status may be a problem, but if the analysis population is limited to participants who have no chronic diseases at baseline and whose self-assessed health status is not bad, and after excluding the first few years of follow-up data, coffee consumption will be less The mortality rate is still relevant.

There is a similar association between consumption of caffeinated coffee and decaffeinated coffee and a reduced risk of all-cause mortality, and the negative correlation between coffee consumption and all-cause mortality does not differ depending on the rate of caffeine metabolism .

Pregnancy period

In prospective studies, higher caffeine intake was associated with a lower birth weight for babies and a higher risk of pregnancy loss for pregnant women. Caffeine easily passes through the placenta, and the slow metabolism of caffeine in pregnant women and fetuses leads to higher circulating caffeine concentrations.

Caffeine can increase the level of catecholamines in the blood of pregnant women and fetuses, causing uterine placental vasoconstriction and hypoxia. Studies have observed that both coffee and tea are associated with low birth weight and show a dose-response relationship with no obvious threshold.

Although the evidence regarding the adverse effects of caffeine on fetal health is not clear, it is prudent to limit caffeine intake during pregnancy to a maximum of 200 mg per day.


A lot of evidence suggests that drinking caffeinated coffee does not increase the risk of cardiovascular disease and cancer. In fact, drinking 3 to 5 standard cups of coffee a day is associated with a reduction in the risk of several chronic diseases. However, large amounts of caffeine intake can have various adverse effects.

It is recommended that non-pregnant and non-lactating adults limit their daily caffeine intake to no more than 400 mg, while pregnant and lactating women should use caffeine daily Intake is limited to no more than 200 mg.

Due to individual differences in caffeine metabolism and sensitivity, it may be appropriate to limit intake to a lower or slightly higher level in individual cases. Based on the available evidence, we have no reason to recommend caffeine or coffee to prevent diseases, but these evidences suggest that for adults who are not pregnant or breastfeeding, and have no special health conditions, drink coffee or tea in moderation Can be part of a healthy lifestyle.

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Important Note: The information provided is for informational purposes only and should not be considered as medical advice.