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Advances in Nutrition recently published an umbrella review, a sweeping analysis that included 11 reports of 7 unique systematic reviews, evaluating the relationship between artificially-sweetened beverage (ASB) consumption and thirteen distinct health outcomes, including cardiovascular disease and diabetes. This more comprehensive review was undertaken in large part because of mixed findings with previously published systematic reviews; for example, some have found an increased risk of cancer with consumption, while others found no such risk.
The impact of ASBs on human health is a difficult one to untangle for several reasons. For one, the majority of studies are observational in nature, and reverse causality is difficult to rule out. As pointed out in the umbrella review, ASB consumers may have adopted these products after becoming ill or gaining weight, in an attempt to reduce sugar and calorie intake. Any association can also be complicated by a masking of the potential harm of ASBs following a reduction in sugar-sweetened beverages (SSBs). For example, switching from SSBs to ASBs may appear to reduce risk (assuming ASBs carry a lower risk than SSBs), but how does this compare to consuming neither? Randomized controlled trials (RCTs), which could help provide more solid conclusions, are typically industry-funded and short-term. This means they do not typically assess hard outcomes, such as heart attack incidence, but rely on biomarkers that may not be as predictive. Meta-analyses of existing RCTs were excluded from this analysis because there are so few; as shown in one of the tables, the longest among them was only 25 weeks, and assessed the effect of replacing SSBs with ASBs.
As a further complication, most studies do not distinguish between the individual ASBs (e.g., aspartame, acesulfame potassium, sucralose, etc.) but group them together, yet there is reason to think they are not identical. Additionally, ASBs are only one source of artificial sweetener consumption. In a large French cohort, ASBs represented only about ½ of total artificial sweetener use, so only assessing the type of beverage consumed may be missing the total influence of these products.
Nonetheless, this analysis attempted to both determine the nature of potential associations between ASBs and human health, and to grade the level of evidence behind these associations. Initial analysis suggested that 9 of the 13 conditions had positive and statistically significant associations. Subsequent statistical analysis concluded that 5 of these 9 conditions had a “highly suggestive” level of evidence, including obesity, type 2 diabetes, all-cause mortality, hypertension, and cardiovascular disease incidence. A “weak” level of certainty also linked ASB consumption to several cancers, cancer mortality, as well as kidney disease, stroke, cardiovascular mortality, and coronary artery disease. For the conditions with a “highly suggestive” level of evidence, there was a range of effect sizes, from a 13% increase for hypertension to a 128% increase for chronic kidney disease (comparing the lowest level of ASB intake to the highest).
Despite the limitations of this study, this should be a cause for concern. Both ASB consumption as well as artificial sweetener use in general are quite common. For example, among the more than 80,000 participants in the Women’s Health Initiative, just over 1/3 reported frequent to daily consumption of ASBs (which was associated with a 34% increase in kidney cancer). The prevalence data for artificial sweetener consumption that is not beverage-based is less readily available, but an estimate of at least 1/3 of the U.S. regularly having exposure is probably a good approximation. Given that marketing claims suggest ASBs are a part of a healthy lifestyle, it is unlikely that consumption will dramatically fall off.
Although many people switch to ASBs to reduce their risk of diabetes, obesity, etc., paradoxically this review and many observational studies suggest this behavior has the opposite effect. How is this occurring if the total calorie consumption is reduced (compared to typical SSB intake)? This is less clear, but there are several lines of evidence that point to possible mechanisms. Evidence published in Cell, for instance, found that non-nutritive sweeteners (including saccharin, sucralose, aspartame, and stevia) modified the stool and oral microbiome as well as the plasma metabolome within just 2 weeks, and both saccharin and sucralose impaired glycemic responses. In a separate study, young healthy volunteers had changes in their microbiome, including a decrease in Lactobacillus acidophilus and an increase in both the phylum Firmicutes and the species Blautia coccoides, all of which have been associated with impaired glycemic control, as was observed in this study. Within 10 weeks, those regularly consuming sucralose had dysbiosis as well as elevated insulin levels and a worsening in their response to oral glucose challenges.
It's also been suggested that ASBs are not as satisfying as SSBs, and therefore may drive more total calorie consumption, as it is clear that unsweetened beverages have a different effect on sweet taste preference than both ASBs and SSBs. In a 12-week clinical trial, healthy young adults who regularly consumed SSBs had a significant drop in their sugar preference when switching to water vs. ASBs. Both animal and human studies suggest that ASBs may not only stimulate greater caloric intake through this mechanism, but may also reduce resting metabolic rate, and elicit different responses in the brain (compared with sugar) that may explain differences in metabolism and intake (additional mechanisms reviewed here). Thus, it is clear that we should be extremely hesitant to recommend ASB consumption, even as a strategy to reduce SSB intake, given that it may be an independent risk factor for the most common chronic diseases, with many plausible mechanisms for harm.
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