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Caffeine consumption and mortality in chronic kidney disease: a nationally representative analysis - new study reports caffeine can reduce mortality in chronic kidney disease
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"In conclusion, this large observational study showed a significant inverse association between caffeine consumption and all-cause mortality among patients with CKD in the USA. If these results are to be confirmed by prospective studies, advising these patients to drink more caffeine may reduce their mortality. This would be a simple, clinically beneficial and inexpensive option in patients with CKD.....It is uncertain if caffeine consumption above a certain threshold may have deleterious health effects........During a median follow-up of 60 months (27 724 total person-years), 1283 (26%) participants died. In the unadjusted analysis (Figure 1), and also after multivariable analysis (Table 2), an inverse association between caffeine and all-cause mortality was observed among participants with CKD. Comparing with the first quartile (Q1) of caffeine consumption, the adjusted hazard ratio (HR) for all-cause mortality [reduced by 24-25%] was 0.74 (95% CI 0.60-0.91) for Q2, 0.75 (95% CI 0.61-0.92) for Q3 and 0.75 (95% CI 0.59-0.97) for Q4 (P = 0.02, for trend across quartiles)......CKD [defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (using the Chronic Kidney Disease Epidemiology Collaboration equation)and/or a urinary albumin:creatinine ratio >30 mg/g] (5696 subjects). We excluded participants with CKD Stage 5 and participants that were either on haemodialysis or peritoneal dialysis (107 subjects).
The possible protective effect of coffee might be conferred by the presence of caffeine and antioxidants [19]. Caffeine is a xanthine that increases intracellular calcium and stimulates the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide diffuses to the vascular smooth muscle cells and causes vasodilation [20]. Caffeine stimulates the cardiovascular system through the blockade of vascular adenosine receptors [21]......Considering the mean caffeine content per unit of caffeinated beverage (95 mg in 8 oz. of coffee, 48 mg in 8 oz. of tea and 30 mg in 12 oz. of cola), even small quantities of commonly consumed beverages may confer a protective effect regarding all-cause mortality in patients with CKD [23]. However, the mechanism that confers the protective effect of caffeine consumption is uncertain. It is possible that the same mechanism that justifies the inverse relationship between coffee consumption and mortality reported in the general population also exists with caffeine in patients with CKD [7].
Our study showed an inverse association between caffeine and all-cause mortality among participants with CKD. We did not detect a significant association between caffeine consumption and cardiovascular mortality or cancer mortality. There were no significant interactions between caffeine consumption quartiles and CKD stages or urinary albumin:creatinine ratio categories regarding all-cause mortality. Consequently, caffeine consumption appears to be safe through different stages of kidney disease.
Coffee consumption has multiple health-related effects. Coffee consumption has been shown to decrease uric acid levels and increase adiponectin and magnesium levels [14, 15]. An association between coffee consumption and increased eGFR has been detected [16]. However, the higher eGFR among coffee consumers does not appear to result from glomerular hyperfiltration [17]. The addition of a small amount of sugar to coffee does not seem to alter the effect on eGFR [18]."
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Caffeine Consumption May Extend Life Expectancy for People With Kidney Disease
A new study in Nephrology Dialysis Transplantation indicates that consuming more caffeine may help reduce the risk of death for people with chronic kidney disease.
An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the association between caffeine consumption and mortality for people with chronic kidney disease remains uncertain. The researchers hypothesized that caffeine consumption might be associated with lower mortality among participants with chronic kidney disease.
The possible protective effect of caffeine might be related with effects at vascular level as caffeine is known to promote the release of substances, such as nitric oxide, that improve the function of the vessel.
About 89 percent of the adult USA population consumes caffeine daily. Approximately 14 percent of adults in the United States have chronic kidney disease. Chronic kidney disease is associated with increased health care costs and a higher risk of death. The prevalence of the disease is expected to continue to increase worldwide.
The study involved data from 4,863 American people observed from 1999 to 2010. Compared with people who consumed a smaller amount of caffeine-containing beverages, caffeine consumers were more likely to be male, non-Hispanic white, have a higher education level and higher annual income, be current or former smokers, have higher alcohol consumption, and have fewer previous strokes.
The results of the analysis suggest an inverse association between caffeine consumption and all-cause mortality among participants with chronic kidney disease. Comparing with people that consumed less caffeine, patients that consumed higher levels of caffeine presented a nearly 25% reduction in the risk of death over a median follow-up of 60 months.
According to Miguel Bigotte Vieira, one of the study's lead authors, "Our study showed a protective effect of caffeine consumption among patients with chronic kidney disease. The reduction in mortality was present even after considering other important factors such as age, gender, race, smoking, other diseases, and diet. These results suggest that advising patients with kidney disease to drink more caffeine may reduce their mortality. This would represent a simple, clinically beneficial, and inexpensive option, though this benefit should ideally be confirmed in a randomized clinical trial." The author emphasized that this observational study cannot prove that caffeine reduces the risk of death in patients with chronic kidney disease, but only suggests the possibility of such a protective effect.
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Caffeine consumption and mortality in chronic kidney disease: a nationally representative analysis
Nephrology Dialysis Transplantation free
Published:
12 September 2018
https://academic.oup.com/ndt/advance-article/doi/10.1093/ndt/gfy234/5063554
ABSTRACT
Background
An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the association between caffeine consumption and mortality in patients with chronic kidney disease (CKD) remains uncertain.
Methods
We analysed 4863 non-institutionalized USA adults with CKD [defined by an estimated glomerular filtration rate (eGFR) of 15-60 mL/min/1.73 m2 and/or a urinary albumin:creatinine ratio >30 mg/g] in a nationwide study using the National Health and Nutrition Examination Survey (NHANES) 1999-2010. Caffeine consumption was evaluated by 24-h dietary recalls at baseline and all-cause, cardiovascular and cancer mortality were evaluated until 31 December 2011. We also performed an analysis of caffeine consumption according to its source (coffee, tea and soft drinks). Quartiles of caffeine consumption were <28.2 mg/day (Q1), 28.2-103.0 (Q2), 103.01-213.5 (Q3) and >213.5 (Q4).
Results
During a median follow-up of 60 months, 1283 participants died. Comparing with Q1 of caffeine consumption, the adjusted hazard ratio for all-cause mortality was 0.74 [95% confidence interval (CI) 0.60-0.91] for Q2, 0.74 (95% CI 0.62-0.89) for Q3 and 0.78 (95% CI 0.62-0.98) for Q4 (P = 0.02 for trend across quartiles). There were no significant interactions between caffeine consumption quartiles and CKD stages or urinary albumin:creatinine ratio categories regarding all-cause mortality.
Conclusions
We detected an inverse association between caffeine consumption and all-cause mortality among participants with CKD.
DISCUSSION
Our study showed an inverse association between caffeine and all-cause mortality among participants with CKD. We did not detect a significant association between caffeine consumption and cardiovascular mortality or cancer mortality. There were no significant interactions between caffeine consumption quartiles and CKD stages or urinary albumin:creatinine ratio categories regarding all-cause mortality. Consequently, caffeine consumption appears to be safe through different stages of kidney disease.
Coffee consumption has multiple health-related effects. Coffee consumption has been shown to decrease uric acid levels and increase adiponectin and magnesium levels [14, 15]. An association between coffee consumption and increased eGFR has been detected [16]. However, the higher eGFR among coffee consumers does not appear to result from glomerular hyperfiltration [17]. The addition of a small amount of sugar to coffee does not seem to alter the effect on eGFR [18].
The possible protective effect of coffee might be conferred by the presence of caffeine and antioxidants [19]. Caffeine is a xanthine that increases intracellular calcium and stimulates the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide diffuses to the vascular smooth muscle cells and causes vasodilation [20]. Caffeine stimulates the cardiovascular system through the blockade of vascular adenosine receptors [21].
An inverse relationship between coffee consumption and mortality has been observed in the general population and also in different racial/ethnic groups [7]. An analysis of the Multiethnic Cohort from 1993 to 2012, including 185 855 Native Hawaiians, African Americans, Japanese Americans, Latinos and whites 45-75 years of age at recruitment, detected an inverse association between coffee consumption and deaths due to heart disease, cancer, respiratory disease, stroke, diabetes and kidney disease in these ethnic groups, excluding Native Hawaiians [7]. An analysis of three large prospective cohorts detected a significant inverse association between coffee consumption and deaths attributed to cardiovascular disease, neurologic diseases and suicide. However, no significant association between coffee consumption and total cancer mortality was found [5]. Also, in a large prospective US cohort study there was a dose-dependent inverse association between coffee drinking and mortality from all causes, and specifically from heart disease, respiratory disease, stroke, injuries and accidents, diabetes and infections [22].
The possible protective effect of caffeine consumption in all-cause mortality was also detected when the analysis was performed according to caffeine consumption from soft drinks. This association was not expected in patients with CKD who consumed soft drinks. Sicker patients may avoid soft drinks with caffeine or the consumption of soft drinks may be associated with protective behaviours not evaluated in the current study (e.g. physical activity). The possible protective effect of caffeine consumption in all-cause mortality was not observed when the analysis was performed according to caffeine consumption from coffee or tea. We hypothesize that this may be due to a lack of statistical power.
Considering the mean caffeine content per unit of caffeinated beverage (95 mg in 8 oz. of coffee, 48 mg in 8 oz. of tea and 30 mg in 12 oz. of cola), even small quantities of commonly consumed beverages may confer a protective effect regarding all-cause mortality in patients with CKD [23]. However, the mechanism that confers the protective effect of caffeine consumption is uncertain. It is possible that the same mechanism that justifies the inverse relationship between coffee consumption and mortality reported in the general population also exists with caffeine in patients with CKD [7].
Regarding the strengths of our study, note that the NHANES includes a large number of patients who are non-institutionalized, and NHANES data were systematically collected and included hard outcome measures such as all-cause mortality. The presence of detailed information about the participants allowed for adjustment for the main biologically plausible confounders. As the database includes comprehensive information regarding CKD, NHANES survey data have previously been used to study this disease [24-33]. To our knowledge this is the first study to evaluate the effect of caffeine consumption on mortality in patients with CKD using a large database representative of the USA population.
Considering the limitations of our study, caffeine consumption was evaluated by 24-h dietary recalls. It cannot be excluded that data generated using this method may not represent the long-term dietary habits of the participants. We consider that the inclusion of data from non-consecutive recalls to estimate usual dietary intake distributions minimizes this risk. Although we have included additional information regarding diet in the studied population (such as consumption of carbohydrates, saturated fats or fibres) in the analyses, no adjustment was performed for additives present in caffeine-containing beverages. Nonetheless, other studies showed a significant association between coffee consumption and decreased risk of all-cause mortality even after adjustment for coffee additives, such as cream, milk, sugar or honey [8, 34]. Non-food sources of caffeine were not considered in our study. However, these sources correspond only to a small proportion of caffeine ingestion [35]. The absence of association between caffeine consumption and specific causes of mortality may be due to inaccurate classification of the cause of death. However, regardless of the subjacent mechanism, the reduction in all-cause mortality is clinically relevant. As in all observational studies, our analysis has an exploratory nature. Therefore it is possible that residual confounding exists due to unmeasured variables. It is also possible that the differences found are due to chance, or that caffeine consumers also perform other protective behaviours, contributing to a healthy user effect. Physical activity, which may correlate with caffeine consumption, was not included in our analysis [36].
Future research should focus on the benefits of other compounds present in caffeine-containing beverages and on the association between caffeine consumption and mortality in other world regions. It is uncertain if caffeine consumption above a certain threshold may have deleterious health effects. In conclusion, this large observational study showed a significant inverse association between caffeine consumption and all-cause mortality among patients with CKD in the USA. If these results are to be confirmed by prospective studies, advising these patients to drink more caffeine may reduce their mortality. This would be a simple, clinically beneficial and inexpensive option in patients with CKD.
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