Relative validity of habitual sugar and low/no-calorie sweetener consumption assessed by food frequency questionnaire, multiple 24-h dietary recalls and urinary biomarkers: an observational study within the SWEET project.

BACKGROUND: Studies investigating associations between sweeteners and health yield inconsistent results, possibly due to subjective self-report dietary assessment methods. OBJECTIVES: We compared the performance of a food frequency questionnaire (FFQ), multiple 24-h dietary recalls (24hRs), and urinary biomarkers to estimate intake of sugars and low/no-calorie sweeteners (LNCSs). METHODS: Participants (n = 848, age 54 ± 12 y) from a 2-y observational study completed 1 semiquantitative FFQ and ≥ 3 nonconsecutive 24hRs. Both methods assessed intake of sugars (mono- and disaccharides, sucrose, fructose, free and added sugars) and sweetened foods and beverages (sugary foods, fruit juice, and sugar or LNCS-containing beverages [sugar-sweetened beverages and low/no-calorie sweetened beverages (LNCSBs)]); 24hRs also included LNCS-containing foods and tabletop sweeteners (low/no-calorie sweetened foods [LNCSFs]). Urinary excretion of sugars (fructose+sucrose) and LNCSs (acesulfame K+sucralose+steviol glucuronide+cyclamate+saccharin) were simultaneously assessed using ultrapressure liquid chromatography coupled to tandem mass spectrometry in 288 participants with 3 annual 24-h urine samples. Methods were compared using, amongst others, validity coefficients (correlations corrected for measurement error). RESULTS: Median (interquartile range) FFQ intakes ranged from 0 (0-7) g/d for LNCSBs to 94 (73-117) g/d for mono- and disaccharides. LNCSB use was reported by 32% of participants. Median LNCSB+LNCSF intake using 24hRs was 1 (0-50) g/d and reported by 58%. Total sugar excretions were detected in 100% of samples [56 (37-85) mg/d] and LNCSs in 99% of urine samples [3 (1-10) mg/d]. Comparing FFQ against 24hRs showed VCs ranging from 0.38 (fruit juice) to 0.74 (LNCSB). VCs for comparing FFQ with urinary excretions were 0.25 to 0.29 for sugars and 0.39 for LNCSBs; for 24hR they amounted to 0.31-0.38 for sugars, 0.37 for LNCSBs, and 0.45 for LNCSFs. CONCLUSIONS: The validity of the FFQ against 24hRs for the assessment of sugars and LNCSBs ranged from moderate to good. Comparing self-reports and urine excretions showed moderate agreement but highlighted an important underestimation of LNCS exposure using self-reports.

Sugar and low/no-calorie-sweetened beverage consumption and associations with body weight and waist circumference changes in five European cohort studies: the SWEET project.

PURPOSE: Results of prospective studies investigating associations between low/no-calorie sweeteners (LNCS) and body weight-related outcomes are inconclusive. We conducted dose-response and theoretical replacement individual patient data meta-analyses using harmonised prospective data to evaluate associations between sugar-sweetened beverage (SSB) consumption, low/no-calorie sweetened beverage (LNCB) consumption, and changes in body weight and waist circumference. METHODS: Individual participant data were obtained from five European studies, i.e., Lifelines Cohort Study, NQplus study, Alpha Omega Cohort, Predimed-Plus study, and Feel4diabetes study, including 82,719 adults aged 18-89 with follow-up between 1 and 9 years. Consumption of SSB and LNCB was assessed using food-frequency questionnaires. Multiple regression analyses adjusting for major confounders and including substitution models were conducted to quantify associations in individual cohorts; random-effects meta-analyses were performed to pool individual estimates. RESULTS: Overall, pooled results showed weak adverse associations between SSB consumption and changes in body weight (+ 0.02 kg/y, 95%CI 0.00; 0.04) and waist circumference (+ 0.03 cm/y, 95%CI 0.01; 0.05). LNCB consumption was associated with higher weight gain (+ 0.06 kg/y, 95%CI 0.04; 0.08) but not with waist circumference. No clear associations were observed for any theoretical replacements, i.e., LNCB or water for SSB or water for LNCB. CONCLUSION: In conclusion, this analysis of five European studies found a weak positive association between SSB consumption and weight and waist change, whilst LNCB consumption was associated with weight change only. Theoretical substitutions did not show any clear association. Thus, the benefit of LNCBs as an alternative to SSBs remains unclear.

Development and validation of a UPLC-MS/MS method for the quantification of sugars and non-nutritive sweeteners in human urine.

High-intensity sweeteners ('sweeteners'), such as sucralose, saccharine, acesulfame, cyclamate and steviol, are replacing sugars in many food products, but biomarker-based data on their population-wide exposure, as well as analytical methods that can quantify urinary concentrations of sugars and sweeteners simultaneously, are lacking. Here, we developed and validated an ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method to quantify glucose, sucrose, fructose, sucralose, saccharine, acesulfame, cyclamate and steviol glucuronide in human urine. Urine samples were prepared by a simple dilution step containing the internal standards in water and methanol. Separation was achieved on a Shodex Asahipak NH2P-40 hydrophilic interaction liquid chromatography (HILIC) column using gradient elution. The analytes were detected using electrospray ionization in negative ion mode, and selective reaction monitoring was optimized using the [M-H]- ions. Calibration curves ranged between 34 and 19,230 ng/mL for glucose and fructose, and 1.8 to 1,026 ng/mL for sucrose and the sweeteners. The method has acceptable accuracy and precision, which depends on the application of appropriate internal standards. Storage of urine samples in lithium monophosphate gives the best overall analytical performance, and storage at room temperature without any preservatives should be avoided since this leads to reduced glucose and fructose concentrations. With the exception of fructose, all analytes were stable throughout 3 freeze-thaw cycles. The validated method was applied to human urine samples, demonstrating quantifiable concentrations of the analytes which were in the expected range. It is concluded that the method has acceptable performance to quantitatively determine dietary sugars and sweeteners in human urine.

Sugar-sweetened beverages, low/no-calorie beverages, fruit juice and non-alcoholic fatty liver disease defined by fatty liver index: the SWEET project.

BACKGROUND: Sweetened beverage intake may play a role in non-alcoholic fatty liver disease (NAFLD) development, but scientific evidence on their role is limited. This study examined associations between sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB) and fruit juice (FJ) intakes and NAFLD in four European studies. METHODS: Data for 42,024 participants of Lifelines Cohort, NQPlus, PREDIMED-Plus and Alpha Omega Cohort were cross-sectionally analysed. NAFLD was assessed using Fatty Liver Index (FLI) (≥60). Restricted cubic spline analyses were used to visualize dose-response associations in Lifelines Cohort. Cox proportional hazard regression analyses with robust variance were performed for associations in individual cohorts; data were pooled using random effects meta-analysis. Models were adjusted for demographic, lifestyle, and other dietary factors. RESULTS: Each additional serving of SSB per day was associated with a 7% higher FLI-defined NAFLD prevalence (95%CI 1.03-1.11). For LNCB, restricted cubic spline analysis showed a nonlinear association with FLI-defined NAFLD, with the association getting stronger when consuming ≤1 serving/day and levelling off at higher intake levels. Pooled Cox analysis showed that intake of >2 LNCB servings/week was positively associated with FLI-defined NAFLD (PR 1.38, 95% CI 1.15-1.61; reference: non-consumers). An inverse association was observed for FJ intake of ≤2 servings/week (PR 0.92, 95% CI: 0.88-0.97; reference: non-consumers), but not at higher intake levels. Theoretical replacement of SSB with FJ showed no significant association with FLI-defined NAFLD prevalence (PR 0.97, 95% CI 0.95-1.00), whereas an adverse association was observed when SSB was replaced with LNCB (PR 1.12, 95% CI 1.03-1.21). CONCLUSIONS: Pooling results of this study showed that SSB and LNCB were positively associated with FLI-defined NAFLD prevalence. Theoretical replacement of SSB with LNCB was associated with higher FLI-defined NAFLD prevalence. An inverse association was observed between moderate intake of FJ and FLI-defined NAFLD. Our results should be interpreted with caution as reverse causality cannot be ruled out.

Association of sweetened beverages consumption with all-cause mortality risk among Dutch adults: the Lifelines Cohort Study (the SWEET project).

PURPOSE: Examined associations between sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB), and fruit juice (FJ) consumption and all-cause mortality in Dutch adults. METHODS: Data of 118,707 adults participating (mean age = 45 years; 60% was women) the Lifelines Cohort Study were prospectively analyzed. Dietary intake was assessed using a validated food-frequency questionnaire. Participants' vital status was followed-up until February 2022 via the National Personal Records Database. Associations between beverages of interest and all-cause mortality risk were investigated using restricted cubic spline and Cox proportional hazard regression analyses, including substitution analyses. Models were adjusted for demographics, lifestyle, and other dietary factors. RESULTS: During follow-up (median = 9.8 years), a total of 2852 (2.4%) deaths were documented. Median (IQR) of SSB, LNCB, and FJ consumption were 0.1 (0.0-0.6), 0.1 (0.0-0.6), and 0.2 (0.0-0.6) serving/day, respectively. Dose-response analyses showed linear associations between SSB, LNCB, and FJ consumption and mortality risk. For each additional serving of SSB and LNCB, HRs of all-cause mortality risk were 1.09 (95% CI 1.03-1.16) and 1.06 (95% CI 1.00-1.11). Replacing SSB with LNCB showed a nonsignificant association with a lower mortality risk, particularly in women (HR 0.91, 95% CI 0.81-1.01). Finally, an inverse association between FJ and all-cause mortality was observed at moderate consumption with HR of 0.87 (95% CI 0.79-0.95) for > 0-2 servings/week and HR of 0.89 (95% CI 0.81-0.98) for > 2-< 7 servings/week when compared to no consumption. CONCLUSIONS: Our study showed adverse associations between SSB consumption and all-cause mortality. Replacing SSB with LNCB might be associated with lower mortality risk, particularly in women. Moderate intake of FJ was associated with lower all-cause mortality risk.

Dose-Response and Substitution Analyzes of Sweet Beverage Consumption and Body Weight in Dutch Adults: The Lifelines Cohort Study.

Background/Methods: Prospective studies investigating sweet beverages and body weight associations show inconsistent results. Within the SWEET project, we examined prospective dose-response associations of sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB), and fruit juice with body weight-related outcomes among 78,286 Dutch adults followed for ~4 years. Baseline intakes were assessed using a validated food-frequency questionnaire (FFQ) with 150 ml representing a standard serving. Outcome variables were body weight change, waist circumference change, overweight/obesity, and abdominal obesity. Associations were investigated by using linear and non-linear dose-response analysis, as well as substitution models while adjusting for multiple socio-demographic, lifestyle, health, and dietary variables. Results: Participants were 46 ± 13 (mean ± SD) years old and 60% were women. Adjusted dose-response analyzes indicated an association between SSB and LNCB, and both body weight (+0.02 kg/year; SE 0.01 and +0.06 kg/year; SE 0.01) and waist circumference changes (+0.04 cm/year; SE: 0.01 and +0.11 cm/year; SE: 0.01). Associations for overweight/obesity and abdominal obesity incidence were +3% (95%CI: 1.00-1.06) and +2% (95%CI: 0.99-1.06) for SSB and +8% (95%CI: 1.06-1.11) and +5% (95%CI: 1.03-1.07) for LNCB, respectively. Substitution of SSB with LNCB was associated with higher weight change (+0.04 kg/year), waist circumference change (+0.09 cm/year), overweight/obesity incidence (+6%), but not abdominal obesity incidence. For fruit juice, we observed beneficial associations for intake levels below ~1 serving/day with weight, waist circumference change, and overweight/obesity incidence, and no association with abdominal obesity. Subsequent substitution analyzes indicated a small beneficial association for the replacement of SSB with fruit juice on weight (-0.04 kg/year) and waist circumference (-0.04 cm/year), but not with other outcomes. Conclusions: Overall, our results suggest that habitual consumption of both SSB and LNCB may adversely affect weight-related outcomes. In contrast, fruit juice consumption <150 ml may be beneficial with respect to weight and waist circumference.