Editorials
Coffee Drinking and Risk of All-Cause Mortality and Cardiovascular Diseases
2019 年 83 巻 4 号 p. 711-712
詳細
2019 年 83 巻 4 号 p. 711-712
Coffee is one of the most commonly consumed beverages, both in Japan and worldwide. Because of its social and cultural importance, coffee has been studied for a long time. It is a rich source of compounds with antioxidant and anti-inflammatory properties, and studies have shown inverse associations between coffee consumption and chronic diseases, including all-cause death, cardiovascular diseases (CVDs), some types of cancer, liver fibrosis, diabetes, etc.1 All-cause death and CVDs, particularly, are of great concern, and these findings could provide assurance that coffee drinking is part of healthy lifestyle. However, because coffee contains caffeine, a stimulant that affects cardiovascular parameters, debate is still on-going whether drinking coffee is beneficial or harmful for human health.
Article p 757
Although a meta-analysis reported the possible protective effects of coffee drinking for CVD,1 historically coffee has not been considered part of a healthy diet because of its deleterious effects in the cardiovascular system (i.e., increase in low-density lipoprotein cholesterol,1 blood pressure2 and incident heart disease3). Coffee is a major source of caffeine, and caffeine has unfavorable effects on the human body.4 The enzyme, CYP1A2, mainly metabolizes caffeine and those who have a mutation in a specific part of the CYP1A2 gene (A to C substitution at position 734), have ‘‘slow’’ caffeine metabolism compared with those who do not (i.e., rapid metabolizer). Recent prospective studies have assessed whether the associations of coffee drinking with hypertension and myocardial infarction (MI) are different between slow and rapid metabolizers as defined by CYP1A2 genotype with adjustment for confounding factors. For carriers of the slow variant, the risk of incident hypertension was linearly elevated with coffee consumption.5 On the other hand, among rapid metabolizers, there were protective effects of coffee drinking on hypertension. Similarly for MI, deleterious effects of coffee drinking were observed in slow metabolizers, while among rapid metabolizers there was consuming 1–2 cups.6,7 The effects of coffee drinking, at least on MI, could be beneficial mainly among people with no mutation of CYP1A2.
Effects of coffee on mortality were summarized in meta-analyses of all-cause death as well as death from specific diseases, such as CVD or cancer. Overall, there was an inverse but non-linear association between coffee consumption and all-cause death, with the greatest benefit at 3–5 cups of coffee per day,1,3 and no significant effects for the highest amount of coffee drinking. Loftfield et al8 assessed possible modification of the effects of coffee by genetic caffeine metabolism, constructing a more comprehensive genetic score using data reported by a genome-wide association study.9 Interestingly, coffee drinking was consistently associated with decreased risk in all-cause death across any genetic caffeine metabolism category. This finding suggests that the protective effects of coffee intake are independent of caffeine metabolism for all-cause death and highlights the importance of the other components in coffee rather than solely caffeine in any relationship between coffee drinking and mortality.
In this issue of the Journal, Sado et al10 show that coffee drinking has a preventive effect on all-cause death and deaths from CVDs with adjustment for lifestyle and dietary factors in both men and women in the a 3-prefecture cohort in Japan. The frequency of coffee consumption was assessed by self-administered questionnaire and categorized into never, sometimes, 1–2 cups/day, 3–4 cups/day, and ≥5 cups/day. Both in men and women, the frequency of coffee consumption was linearly associated with a lower risk of all-cause death. Intriguingly, this study showed similar associations among smokers and non-smokers in both men and women, and suggested a consistent influence of coffee isolating smoking behavior. There were also risk reductions in deaths from cerebrovascular diseases in men and in deaths from heart disease in women, though some associations were non-linear and did not reach statistical significance. The high frequency of CYP1A2 mutation in Japanese people compared with Caucasians11 might affect these associations.
The underlying mechanisms of coffee’s effects are not fully understood, but some plausible explanations can be postulated (Figure). Coffee contains many components, including caffeine and antioxidants such as chlorogenic acid, diterpenes, trigonelline, etc.12 Studies have found that such antioxidants have many health-promoting influences by reducing inflammation,13 improving insulin resistance14 and endothelial function,13 and reducing arterial thrombus and plaque formation.13 On the other hand, there are deleterious effects of caffeine on the cardiovascular system stimulating the release of epinephrine, increasing blood pressure,3 decreasing insulin sensitivity,15 and blocking the adenosine receptors that reduce inflammation during MI.16,17 Further, the cholesterol contained in coffee beans increases the total and low-density lipoprotein cholesterol levels as well as that of triglycerides.1 Therefore, the balance of these mechanisms yields a health benefit. The effects of coffee intake were protective independent of caffeine metabolism for all-cause death, and, thus, coffee could likely yield benefits. For the onset of CVDs, especially MI, individual caffeine metabolism would tilt the balance. It should be noted that the associations found in epidemiological studies between coffee and death might be confounded by co-occurring lifestyle and dietary factors unless they are controlled in both the design and statistical analyses (e.g., shift towards benefit if coffee drinkers prefer a healthy lifestyle, and shift towards harm if coffee drinkers prefer an unhealthy lifestyle).
Possible mechanisms underlying the association between coffee and diseases. LDL, low-density lipoprotein.
In summary, coffee drinking seems to be protective for all-cause death as well as CVDs when mitigating the deleterious effects of caffeine. A better understanding of the health-related effects of coffee consumption could provide the evidence that coffee consumption could be part of a healthy diet. Further studies are needed to assess the details regarding high consumption, other outcomes and interactions with genetic factors in the Japanese population to provide further reassurance to coffee drinkers.
