In this study, increased consumption of regular soft drinks was associated with prevalent hyperuricemia and CKD. Stratified analysis also suggested that the association between such sweetened beverages and kidney function was primarily among participants with elevated uric acid levels. However, in longitudinal analyses, these associations did not hold. These findings present new but conflicting evidence as to whether sugar-sweetened sodas, and potentially the HFCS used to sweeten them, are a dietary risk factor for development of hyperuricemia and CKD.
The results of this study complement a growing body of literature tying sugar-sweetened soda consumption to higher rates of chronic diseases such as obesity, hypertension, and diabetes.21–23
Our findings are consistent with previously published reports in which high sugar-sweetened soda consumption was associated with prevalent hyperuricemia and renal injury.4,19,20
Yet this study, to the best of our knowledge, is the first to examine whether sugar-sweetened soda consumption is associated with incident forms of these diseases. The results of these incidence analyses add an important note of caution to the literature on sugar-sweetened soda and HFCS. Although the cross-sectional analyses performed in this and other studies4,19
support a hypothesis that increased HFCS-sweetened soda consumption leads to higher uric acid levels that in turn induce renal damage, the longitudinal analyses do not support this theory.
Indeed, the associations shown in our cross-sectional analyses must be viewed in context of the lack of association in our longitudinal analyses, which arguably would provide stronger evidence for a causative role if they were sufficiently powered and free of bias. Post hoc power analyses showed that we had >80% power to detect a 6.5% higher incidence of hyperuricemia and a 3% higher incidence of CKD in participants who drank >1 soda per day compared with participants who drank <1 soda per day. Therefore, if the proposed causal link between sugar-sweetened soda consumption, hyperuricemia, and CKD that is suggested by ours and others’ cross-sectional analyses is real, we must explore the lack of association between soda consumption and incident disease in this cohort. We suggest four possible explanations.
First, the duration of sugar-sweetened soda exposure may be important. The mean follow-up in this cohort was approximately 9 years, and a longer exposure period may be needed to produce incident disease. This interpretation, admittedly, does not support a role for HFCS in the prevalence data, as the participants at visit 1 (1987–1989) would have likely had an even shorter exposure period to HFCS, which was only widely introduced in the early 1980s. Second, it is conceivable that enrollment in this study may have led to an improvement in general health behaviors that modified soda consumption over the course of the study period. Our sensitivity analysis of participants who reported high intake of soda at both visits 1 and 3, however, showed lower point estimates for the odds of developing new hyperuricemia or CKD. The third, and in our opinion most plausible, explanation is the role of survival bias in this type of analysis. Participants who had not yet developed hyperuricemia or CKD by the time of the initial ARIC visit, when mean age was 54.2 years, may have some unidentified protective factor making them less likely to develop either of these conditions in later years. If sugar-sweetened soda consumption truly elevated uric acid levels and/or reduced kidney function, it may be unlikely for this effect to first manifest after the age 50. Theoretically, a modern cohort of younger subjects with a longer duration of follow-up might yield different results from those presented here. Finally, as with all such observational studies, unmeasured confounding may have influenced the cross-sectional and/or longitudinal analyses.
This study has a number of limitations. Our exposure of interest is based on participants’ dietary recall, and measurement error is inevitable. However, when compared to values from the typical American diet, values for daily sodium, protein, and caloric intake reported by these participants () suggest underreporting across all exposure categories that should bias estimates toward the null if such misclassification is assumed to be nondifferential.24
Conversely, as sodium intake has previously been shown to be higher in individuals with heavy regular soda consumption,21
misclassification for this covariable may not be entirely random. Repeated-measures sensitivity analyses using dietary data from both visits 1 and 3 produced similar point estimates for our outcomes of interest, and multivariate models using a five-level category of exposure were consistent with our main models (Supplementary Table S2
). We did not have detailed information on participants’ medications and therefore were unable to adjust for use of drugs that could affect uric acid (for example, diuretics) or creatinine (for example, ACE inhibitors or ARBs) measurements. Similarly, we lacked data regarding heavy metal exposure that could also have affected uric acid and creatinine levels.
Like most epidemiologic studies of CKD, our definition of CKD is based on a limited number of isolated creatinine measurements that were not repeated within 3 months to confirm a chronic reduction in GFR.25
Nevertheless, the 3% prevalence and 8% incidence rates of CKD in this cohort are quite low when compared to national data (approximately 7% prevalence of eGFR<60 ml/min per 1.73 m2
among all US adults),26
particularly given the age of ARIC participants. The probable underdiagnosis of CKD in this cohort, if anything, biased our results again toward the null. Furthermore, sensitivity analyses using a more conservative definition of incident CKD and defining incident CKD by continuous changes in serum creatinine and eGFR produced similar results. Further, ancillary ARIC data on urinary albumin excretion from visit 4 found no association between increased soda consumption and either micro- or macro-albuminuria (Supplementary Table S3
). The prevalence and incidence rates of hyperuricemia in this study were slightly higher than the national average (18% prevalence rate for all US adults),4
but this is likely explained by the age of ARIC participants as our data concur with the prevalence of hyperuricemia published in a large middle-aged cohort in which the baseline prevalence approached 50%.5
Finally, our results strictly pertain to the intake of sugar-sweetened sodas in a generally healthy cohort; for these individuals, sugar-sweetened sodas were not associated with incident hyperuricemia and kidney disease. These findings do not justify unbridled consumption of sugar-sweetened sodas by individuals with and without CKD. Rather, our study is an important addition to the large and still-growing body of literature surrounding the potential health consequences of sugar-sweetened soda, which is based principally on observational studies such as this one.12–15
Our ‘negative’ study results—subject to the same potential sources of error (bias, chance, confounding) as others’ ‘positive’ study results— should be used to further inform, rather than end, the heated debate regarding this important public health issue. In addition, this study should not be interpreted as suggesting that uric acid does not have a role in the development of kidney injury and CKD, as shown in recent studies.5–8
This study is similar to the recently published study by Forman et al
. that found no association between fructose intake and the risk for incident hypertension over 14–20 years of follow-up27
despite substantial evidence that elevated uric acid levels increase the risk for developing hypertension.28–33
In fact, in both our cross-sectional and longitudinal studies, increased consumption of sugar-sweetened sodas in the presence of very elevated uric acid levels (≥9.0 mg/dl) did appear to influence development of kidney disease, although only 812 subjects had uric acid levels ≥9 mg/dl at the baseline visit, and only 64 (8%) drank more than one soda per day, so caution should be used when interpreting the results.
In this large biracial cohort, high consumption of sugar-sweetened sodas appeared to be associated with prevalent hyperuricemia and CKD. In stratified analysis, the association between soda and kidney function became more pronounced as uric acid levels increased. However, similar associations were not seen in longitudinal analyses of incident hyperuricemia and CKD. Therefore, our findings add to but in no way close the heated discussion over the potential dangers of sugar-sweetened soda.12,13,15–17,33,34