In a recent article published in he European Journal of Clinical Nutrition, Researchers have expressed concern about the World Health Organization (WHO) guidelines for the use of non-sugar sweeteners (NSS) and have called for a re-evaluation.
Outlook: WHO guidelines on the use of sugar-free sweeteners: a need for reconsideration. Image credit: Towfiqu ahamed barbhuiya/Shutterstock
Based on a systematic review and meta-analysis (SRMA), the WHO Department of Nutrition and Food Safety recently published guidance on the use of NSS.
It explicitly mentions that randomized controlled trials (RCTs) and prospective cohort studies have demonstrated different effects of using NSS. The former showed a reduction in adiposity after NSS use, while the latter suggests an association with an increased risk of chronic diseases and adiposity.
According to the WHO recommendations in question, the use of NSS does not serve to control weight or reduce the risk of non-infectious diseases, while the latter is a conditional recommendation.
The authors’ first concern was that the WHO gave more importance to the results of observational studies than to RCTs, and their second concern was the methodologies applied in these observational studies. (called initial (or prevalent) analysis), which increases the risk of bias.
The WHO SRMA had results consistent with several other SRMAs showing that NSS reduced energy intake compared to equivalent calorie sources, which was beneficial for weight loss and body mass index (BMI) control. .
In contrast, prospective cohort studies included in the WHO SRMA suggest dangers associated with ASN consumption. They showed both positive and negative associations between NSS use and BMI, obesity, type 2 diabetes (T2D), cardiovascular diseases (CVD), and all-cause mortality. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach provides greater certainty to the evidence from RCTs due to its protection against bias.
Prospective cohort studies are less protected against bias and fail to establish a causal link between the intervention and the outcome; therefore, they start with low certainty in GRADE. Additionally, the NSS research community agreed that prospective cohort studies using routine analyzes to study the relationship of NSS with cardiometabolic outcomes were at high risk of bias due to three factors: clustering of behaviors, reverse causality and residual confusion.
The WHO SRMA recognized these limitations in prospective cohort studies. However, WHO guidelines consider these negative associations related to ASN consumption to be genuine. Thanks to advances in the analytical methodologies used in these studies, certain limitations posed by current analyzes have been overcome.
Examples include a sequential assessment to measure changes in exposure and a surrogate analysis that models NSS as a surrogate for caloric sugars. Overall, these robust analytical methods allow for a more precise assessment of the cardiometabolic benefits of NSS, while controlling for confounding factors and capturing caloric substitution as intended. Furthermore, studies using these methods have provided biologically plausible evidence that mirrors the results of NSS assays.
Recently, Lee et al. published an SRMA of 14 prospective cohort studies on NSS consumption that used sequential assessments and surrogate analyzes and adjusted for baseline adiposity while modeling NSS as surrogates for SSBs. This SRMA showed that higher NSS intake was associated with a reduction in body weight and waist circumference, but without adverse effects on T2DM. Furthermore, it demonstrated that replacing NSS beverages with sugar-sweetened beverages reduced weight, obesity risk, all-cause coronary heart disease, and cardiovascular disease mortality without showing adverse effects on type 2 diabetes.
In general, the WHO has completely ignored switch and substitution analyzes and RCT data, which are generally well recognized and accepted in nutrition research. The WHO SRMA cited only one study that used a meal replacement approach to show a 12% reduction in the risk of coronary heart disease with NSS drinks.
The rejection of RCT evidence and reliance on biased prospective cohort studies lacked biological reasoning and deviated from the WHO’s previous approach. At the same time, the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes recommended the use of NSS as a cardiometabolic risk reduction strategy. Recent research suggests that NSS use may not be the cause of harm but rather a response to increased disease risk. Therefore, there is an urgent need to reconsider the evidence base and WHO guidelines on the use of SNS.