Table 3:
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.