Consumption of sweetened soft drinks is associated with an increase in all-cause deaths, according to the largest pan-European study to date to investigate this association. The investigators assessed total consumption of soft drinks by examining the intake of sugar-sweetened and artificially sweetened beverages separately. The study, led by Amy Mullee, PhD, University College, Dublin, Ireland, was published online September 3 in JAMA Internal Medicine. "The striking observation in our study was that both sugar-sweetened and artificially sweetened soft drink consumption were positively related to risk of all-cause death," said senior author Neil Murphy, PhD, researcher at the International Agency for Research on Cancer (IARC), Lyon, France, in an interview with Medscape Medical News. Compared with those who consumed fewer than one glass per month, those who drank two or more glasses per day of artificially sweetened soft drinks had a 26% higher risk for all-cause mortality (P < .001); those who drank sugar-sweetened beverages had an 8% higher risk (P = .004). One specific association was a more than 50% increase in cardiovascular disease deaths linked with artificially sweetened drinks but not with sugar-sweetened ones — the latter observation was somewhat of a surprise, Murphy noted. "The results are supportive of public health campaigns aimed at limiting the consumption of soft drinks" and encourage healthier alternatives, say the researchers. "Where you can, stick with water and unsweetened tea or coffee, and keep soft drinks as a treat," noted Jeremy Pearson, associate medical director at the British Heart Foundation, in a statement. What Does This Add? More Evidence Gives Conclusions Greater Weight Studies investigating the association of soft drinks with health outcomes are accumulating, and Medscape Medical News asked Murphy about the value of having so many similar studies. He stressed the importance of conducting multiple high-quality epidemiologic studies of this nature. "Firm conclusions can never be drawn from one single study such as ours. Instead, it is better to assess a possible association by using results from multiple epidemiological studies, ideally in different populations and/or countries," he observed. "If consistent results are seen across such studies, this gives us greater confidence in the associations found." In their article, the authors note that previous studies of the relationship between soft drinks and mortality have shown inconsistent results. However, certain findings from the current study reflect those found in prior studies, including results of two large US-based studies published earlier this year. "Both studies found positive associations between artificially sweetened soft drinks and all-cause deaths similar to our finding. This consistency between studies is suggestive of a positive association between artificially sweetened soft drinks and mortality outcomes," he highlighted. For artificially sweetened soft drinks, explained Murphy, the current study is the third large one this year to observe a positive association with all-cause deaths, but he nevertheless stressed that further research is needed into the mechanisms that underlie this relationship. "Comprehensive" Data From 10 European Countries — EPIC The researchers investigated the consumption of total soft drinks and the resultant associations with total and cause-specific mortality among participants in the European Prospective Investigation Into Cancer and Nutrition (EPIC) study, a large multinational cohort. Total soft drinks referred to a combination of soft drinks, carbonated and isotonic drinks, and diluted syrups. Total soft drink consumption was subdivided into sugar-sweetened and artificially sweetened soft drink consumption for all countries except Italy, Spain, and Sweden, where types of soft drinks were not recorded. Participant data were drawn from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom). Related data were from the period 1992 – 2000. The final study cohort included 451,743 participants; 71.1% were women, and the mean age was 50.8 years. A total of 41,693 deaths occurred during the follow-up period of 16.4 years. Significantly higher all-cause mortality was found among participants who consumed two or more glasses of soft drinks per day in comparison with those who consumed less than one glass per month (hazard ratio [HR], 1.17; P < .001). "Overall, to our knowledge, this current study was the largest to date to investigate the associations between soft drink consumption and mortality outcomes as well as the first comprehensive European-based analysis," the researchers note. Only Artificially Sweetened Drinks Up Circulatory Disease Deaths With regard to specific causes of death, positive associations were observed between artificially sweetened soft drinks and circulatory disease mortality in those who consumed two or more glasses per day in comparison with those who consumed less than one glass per month (HR, 1.52; P < .001). For similar consumption of sugar-sweetened soft drinks, there was an increase in deaths from digestive diseases in comparison with persons who consumed one glass or less per month (HR, 1.59; P < .001). The lack of association between sugar-sweetened soft drinks and circulatory disease deaths, including ischemic heart disease, was unanticipated, remarked Murphy. "A recent large study in the US reported a positive association with cardiovascular disease deaths, and multiple studies have reported positive associations between sugar-sweetened soft drinks and the risk of developing cardiovascular disease," he noted. The lack of association in this study "may be a chance finding, as the totality of evidence from all available studies does suggest that higher intake of sugar-sweetened soft drinks is related to greater risks of cardiovascular disease outcomes," he remarked. Regarding the association between sugar-sweetened soft drink consumption and death from digestive diseases, the authors note, "Hyperglycemia resulting from consumption of sugar-sweetened soft drinks may alter gut-barrier function and increase the risk of enteric infection." No Link to Cancer, First to Parkinson Disease Of interest, a positive association was also found between Parkinson disease mortality and total soft drink consumption (HR, 1.59; P = .02). "This was the first study to find a positive association between soft drinks consumption and Parkinson's disease deaths," Murphy pointed out. "We have no prevailing hypothesis for the relationship we observed. It is possible that this result is spurious. Additional epidemiological and experimental studies are now required to investigate this association further." With regard to cancer, total soft drink consumption was only positively associated with colorectal cancer deaths (one or more glasses per day vs less than one glass per month) (HR, 1.25; P = .004), but not with any other cancer deaths. "The null result observed for total cancer mortality is consistent with previous studies that found little association between soft drink consumption and the risk of developing individual cancers," said Murphy. "It is possible that soft drink consumption, however, may contribute indirectly to cancer risk through weight gain and obesity, which are strong risk factors for multiple cancers," he cautioned. There were no notable differences between countries, and associations were similar among the 10 European countries. Reflecting on the findings, Murphy stressed that overall, the results do not mean that soft drinks cause early death, because other factors might lay behind the associations observed. "High soft drink consumption may be a marker of overall unhealthy diet. Also, in our study, high soft drinks consumers had higher BMI [body mass index] and were also more likely to be current tobacco smokers," he said. The researchers did adjust for BMI, smoking habits, and other risks, and the positive associations remained. "We saw similar associations in people smoking and nonsmoking and among lean and obese participants, which adds weight to the soft drink and mortality association not being strongly influenced by smoking habits and BMI," Murphy commented. "However, we cannot rule out the possibility that these factors were influencing our findings, and we cannot say the associations we observe are causal," he concluded. The EPIC study was funded by the European Commission and the International Agency for Research on Cancer. Disclosures of the authors' relevant financial relationships are included in the original article. JAMA Intern Med. Published online September 3, 2019. 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