Caffeine intake and the risk of kidney stones1,2,3
Pietro Manuel Ferraro,
Eric N Taylor, Giovanni Gambaro, and Gary C CurhanAuthor information Article notes Copyright and License information DisclaimerThis article has been cited by other articles in PMC. Go to:
Abstract
Background: Although caffeine intake may increase urine calcium excretion, caffeine-containing beverages have been associated with a lower risk of nephrolithiasis.
Objective: We sought to determine the association between caffeine intake and the risk of incident kidney stones in 3 large prospective cohorts.
Design: We prospectively analyzed the association between intake of caffeine and incidence of kidney stones in 3 large ongoing cohort studies, the Health Professionals Follow-Up Study (HPFS) and the Nurses’ Health Studies (NHS) I and II. Information on the consumption of caffeine and the incidence of kidney stones was collected by validated questionnaires.
Results: The analysis included 217,883 participants; over a median follow-up of >8 y, 4982 incident cases occurred. After multivariate adjustment for age, BMI, fluid intake, and other factors, participants in the highest quintile of caffeine intake had a 26% (95% CI: 12%, 38%) lower risk of developing stones in the HPFS cohort, a 29% lower risk (95% CI: 15%, 41%) in the NHS I cohort, and a 31% lower risk (95% CI: 18%, 42%) in the NHS II cohort (P-trend < 0.001 for all cohorts). The association remained significant in the subgroup of participants with a low or no intake of caffeinated coffee in the HPFS cohort. Among 6033 participants with 24-h urine data, the intake of caffeine was associated with higher urine volume, calcium, and potassium and with lower urine oxalate and supersaturation for calcium oxalate and uric acid.
Conclusion: Caffeine intake is independently associated with a lower risk of incident kidney stones.
Keywords: caffeine, kidney stones, nutrition, prospective study, coffeeGo to:
INTRODUCTION
Kidney stones are a common condition, with an estimated prevalence in the United States of 11% for men and 7% for women (1). Previous research highlighted the association between dietary habits and the risk of developing kidney stones; in particular, it was shown that increasing fluid intake would reduce the risk (2) and that the consumption of certain beverages such as coffee and tea may also further reduce the risk (3–5). However, whether the inverse association between such beverages and the risk of developing kidney stones is due to their caffeine content or to other properties of the beverages is not known; of note, an inverse association between the consumption of decaffeinated coffee and incident kidney stones was also reported (3–5). Caffeine intake has been shown to be associated with increased urinary calcium excretion (6) and, as such, could potentially increase the risk of developing kidney stones, although in our previous reports we consistently found an inverse association between consumption of caffeine-containing beverages, such as coffee and tea, and the risk of incident stones. The goal of this study was to analyze the association between caffeine intake and the risk of developing kidney stones in 3 large prospective cohorts. We also analyzed the cross-sectional association between intake of caffeine and 24-h urinary composition in a subgroup of participants with available data.
SUBJECTS AND METHODS
Study population
The Health Professionals Follow-Up Study (HPFS) started in 1986 with the enrollment of 51,529 male health professionals aged 40–75 y, who filled out a questionnaire on lifestyle and medical history. The Nurses’ Health Study (NHS) I started in 1976 with the enrollment of 121,700 female nurses aged 30–55 y, who completed a questionnaire on lifestyle and medical history. A second NHS cohort (NHS II) was enrolled in 1989, consisting of 116,430 female nurses aged 25–42 y. In all 3 cohorts, questionnaires have been sent every 2 y.
Participants with baseline self-reported history of kidney stones and/or cancer (except for nonmelanoma skin cancer) and those with missing baseline caffeine intakes were excluded from the analysis. Participants who developed cancer during the follow-up were censored. These studies were approved by the Partners Health Care institutional review board, which accepts return of the questionnaires as implied consent in these cohorts.
Assessment of caffeine intake and other nutrients
In 1980 (NHS I), 1986 (HPFS), and 1991 (NHS II), participants returned a food-frequency-questionnaire that asked about the average use of >130 foods, beverages, and supplements in the previous year; and dietary information was updated every 4 y. The validity and reliability of the self-reported food-frequency questionnaire were shown in subgroups of the main cohorts (7, 8). For the present analysis, we used data on intakes of calcium, phosphate, sodium, potassium, magnesium, total fructose, oxalate, phytate, total fluid, and vitamins B-6, C, and D. Except for oxalate, nutrient intakes were calculated from USDA data. The oxalate content of foods was measured by capillary electrophoresis as described elsewhere (9). The main contributors of caffeine were coffee (83%), tea (14%), and soda (2%). In our nutrient database, we assigned 95 mg caffeine per cup of caffeinated coffee.
Assessment of kidney stones
Participants who reported an incident kidney stone were asked to complete a supplementary questionnaire asking about the date of occurrence and symptoms such as pain or hematuria from the event. The self-reported diagnosis was shown to be valid in ∼95–98% of self-reported cases who completed the additional questionnaire in separate validation studies (10). Stone composition was analyzed in a subsample of the study population and found to be predominantly calcium oxalate (≥50%) in 86% of participants in the HPFS, 77% of participants in the NHS I, and 79% of participants in the NHS II cohort (10).
Assessment of urinary composition
Urine samples were obtained as part of a study to compare the urine composition of stone formers with non–stone formers as previously described (11). In brief, 24-h urine samples were collected in 2 cycles. In the first cycle, participants were ineligible if they were >70 y of age in the HPFS or >65 y in the NHS I or had a history of cancer or cardiovascular disease. In the second cycle, participants were ineligible if they were >75 y of age or had a history of cancer (other than nonmelanoma skin cancer). An additional third cycle was performed in NHS II non–stone formers, with the following exclusion criteria: age >55 y, non-Caucasian descent, and history of high blood pressure, coronary artery disease or cancer.
The 24-h urine collection procedure used the system provided by Mission Pharmacal (11) for the first 2 waves of collections. The third wave was performed by using the kit from the Litholink Corporation.
To remove participants with likely over- or undercollections, we excluded participants with 24-h urinary creatinine values in the top 1% or bottom 1% of the urinary creatinine distribution of non–stone formers in each cohort. If a participant submitted more than one 24-h urine collection, we used the first sample.
Other covariates
We used data obtained from the questionnaires about the following covariates: age, BMI, use of thiazides, use of calcium supplements, and intake of alcohol. BMI was derived from self-reported weight and height; these data were validated in 2 of the 3 cohorts (12).
Statistical analysis
Age-adjusted incidence rates of kidney stones were computed across quintiles of consumption of caffeine. The HRs and 95% CIs for developing kidney stones in each category of exposure compared with the lowest category were computed in each cohort by using Cox proportional hazards models adjusted for age (continuous), BMI (13 categories), use of thiazides (yes or no), use of calcium supplements (yes or no), intake of alcohol (7 categories), and intakes of dietary calcium, phosphate, sodium, potassium, magnesium, fructose, oxalate, phytate, total fluid, and total (food plus supplements) vitamins B-6, C, and D (all quintiles). Missing categories were used for participants with missing covariates. Exposure and covariates were updated every 4 y by using simple updating. Time at risk was 1980–2006 for NHS I, 1986–2006 for HPFS, and 1991–2007 for NHS II.
To assess trends across quintiles of consumption of caffeine and incidence of kidney stones, we evaluated intakes continuously by using the median value of each quintile. We also examined the possible nonlinear relation between caffeine intake and the risk of kidney stones nonparametrically with restricted cubic splines with 4 knots at the quintile cutoffs of the distribution and with the use of the population median as the referent value. Tests for nonlinearity used the likelihood ratio test, comparing the model with only the linear term with the model with the linear and the cubic spline terms. The previously described set of covariates was used for this analysis.
To determine the risk associated with caffeine intake independent of coffee intake, we also analyzed the association in a subgroup of the study population with low or no intake of caffeinated coffee (defined as <1 serving of caffeinated coffee/d).
To assess possible effect modification, the multivariate models were stratified by age (<50 or ≥50 y), BMI (in kg/m2; <25 or ≥25), use of calcium supplements (yes or no), and total fluid intake (<1 or ≥1 L/d). Significance for interaction terms was assessed by using the log-likelihood test.
We analyzed the association between intake of caffeine and 24-h urinary components by using linear regression models with each urinary component as the dependent variable and intake of caffeine in quintiles as the independent variable. We tested for linear trends by using the median intake for each quintile of caffeine intake. Models were adjusted for age, BMI, presence of diabetes, high blood pressure, gout, history of kidney stones, use of thiazides, 24-h urine volume, and all the other urinary components. Multivariate models with supersaturations as dependent variables were not adjusted for any of the other urinary components; log-linear regression models were used to derive percentage changes for supersaturation values. Each regression model was first conducted in cohort-specific subgroups and then merged with random-effects meta-analysis after checking for heterogeneity.
A P value <0.05 was considered significant. Analyses were performed with the use of SAS version 9.3 (SAS Institute).
RESULTS
Association between intake of caffeine and incident kidney stones
After exclusions, a total of 217,883 participants were included in the analysis, contributing 3,032,742 person-years of follow-up. Median follow-up times to an incident kidney stone were 8.3 y for HPFS, 14 y for NHS I, and 8.2 y for NHS II. The overall number of participants who developed a symptomatic incident kidney stone was 4982.
The baseline characteristics of participants by exposure status are shown for each cohort in Tables 1–3.. For higher intakes of caffeine, there was a trend toward a decreased intake of calcium and vitamin C and an increased intake of alcohol and total fluid in all the cohorts.
“Caffeine is good. Kidney stone bad.”