Results from meta-analyses (where possible) or individual studies for intake of nonnutritive sweeteners and long-term cardiometabolic health outcomes in randomized controlled trials and cohort studies
| Outcome: change or incidence | No. of studies* (participants) | Comparison | Estimate of NNS effect (95% CI) from meta-analysis or individual studies | Assoc. | Citation(s)* | Figure |
|---|---|---|---|---|---|---|
| Randomized controlled trials | ||||||
| BMI | 3 (242) | NNS v. control | MD −0.37 kg/m2 (−1.10 to 0.36), I2 9% | NS | (20), (36), (37) | 2 |
| Weight | 5 (791) | NNS v. control | SMD −0.17 (−0.54 to 0.21), I2 81% | NS | (19), (20), (34), (35), (38) | 2 |
| Percentage of fat mass | 1 (25) | NNS v. control | MD −1.01% (−3.01 to 0.99) | NS | (35) | – |
| Waist circumference | 3 (683) | NNS v. control | SMD −0.16 (−0.56 to 0.25), I2 83% | NS | (19), (20), (34) | S1‡ |
| Insulin resistance: HOMA-IR | 3 (99) | NNS v. control | SMD +0.10 (−0.57 to 0.76), I2 55% | NS | (20), (35), (37) | S3‡ |
| HbA1c | 1 (62) | NNS v. control | MD +0.07% (−0.00 to 0.14) | NS | (20) | – |
| Cohort studies | ||||||
| BMI | 2 (21 256) | Continuous correlation | WMC +0.05 (0.03 to 0.06), I2 0% | ↑ Gain | (14), (15) | 2 |
| 1 (3371) | Highest NNS intake quantile v. none | MD +0.77 kg/m2 (0.47 to 1.07) | ↑ Gain | (50) | – | |
| Weight | 4 (32 405) | Continuous correlation | WMC +0.06 (0.05 to 0.07), I2 46% | ↑ Gain | (21), (57) | 2 |
| Gestational weight gain | 1 (347) | Highest v. lowest NNS intake quantile | MD +2.5 kg (0.5 to 4.5) | ↑ Gain | (23) | – |
| Weight gain > 1 kg | 1 (7,194) | Highest v. lowest NNS intake quantile | OR 1.05 (0.93 to 1.19) | NS | (41) | – |
| Waist circumference | 1 (384) | Daily v. no NNS consumption | MD +2.27 cm (0.96 to 3.58) | ↑ Gain | (18) | – |
| Incident abdominal obesity | 1 (5011) | Highest v. lowest NNS intake quantile | HR 1.59 (1.23 to 2.07) | ↑ Gain | (60) | |
| Incident overweight/obesity | 3 (7917) | Highest v. lowest NNS intake quantile | OR 1.84 (1.28 to 2.66), I2 0% | ↑ Risk | (22), (50), (59) | S1‡ |
| Metabolic syndrome | 5 (27 914) | Highest v. lowest NNS intake quantile | RR 1.31 (1.23 to 1.40), I2 0% | ↑ Risk | (39), (47), (48), (54), (60) | S2‡ |
| Type 2 diabetes | 4 (221 363) | Per daily serving of NNS | RR 1.03 (1.01 to 1.05), I2 0% | ↑ Risk | (24), (42), (56) | S2‡ |
| 9 (400 571) | Highest v. lowest NNS intake quantile | RR 1.14 (1.05 to 1.25), I2 52% | ↑ Risk | (16), (24), (42), (49), (55), (56), (58), (60) | 2 | |
| Gestational diabetes | 1 (13 475) | Highest v. lowest NNS intake quantile | RR 0.87 (0.71 to 1.02) | NS | (44) | – |
| Impaired glucose tolerance | 1 (3728) | No v. any NNS consumption | HR 1.07 (0.91 to 1.26) | NS | (48) | – |
| Hypertension | 5 (232 630) | Highest v. lowest NNS intake quantile | HR 1.12 (1.08 to 1.13), I2 53% | ↑ Risk | (45), (48), (60) | S4‡ |
| Stroke | 2 (128 176) | Highest v. lowest NNS intake quantile | RR 1.14 (1.04 to 1.26), I2 0% | ↑ Risk | (40) | S4‡ |
| Cardiovascular events† | 2 (62 178) | Highest v. lowest NNS intake quantile | RR 1.32 (1.15 to 1.52), I2 0% | ↑ Risk | (17), (52) | S4‡ |
| Coronary heart disease | 2 (131 403) | Highest v. lowest NNS intake quantile | RR 0.98 (0.90 to 1.07), I2 0% | NS | (46), (51) | S4‡ |
| Chronic kidney disease | 1 (14 002) | Highest v. lowest NNS intake quantile | OR 0.80 (0.64 to 1.00) | NS | (43) | – |
Note: BMI = body mass index, CI = confidence interval, HbA1c = glycosylated hemoglobin, HOMA-IR = homeostatic model assessment for insulin resistance, HR = hazard ratio, MD = mean difference, NNS = nonnutrititve sweetener, NS = not significant, OR = odds ratio, RR = risk ratio, SMD = standardized mean difference, WMC = weighted mean group correlation (unitless).
↵* Number of studies does not always equal the number of citations, because some citations report results from multiple studies.
↵† Defined by the study authors as coronary heart disease, heart failure, myocardial infarction, coronary revascularization procedure, ischemic stroke, peripheral arterial disease and cardiovascular death; (17) or stroke, myocardial infarction and vascular death. (52)
↵‡ Appendix 1, available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.161390/-/DC1.