Table 2:

Prospective cohort studies evaluating intake of nonnutritive sweetener and long-term cardiometabolic health

Study*CohortCountry, year of baseline NNS intakeNo. of participantsSexAge at baseline, mean ± SD, or range; yrBMI at baseline, mean ± SD, or % OW; kg/m2Follow-up, yrType or source of NNSExtreme NNS intake categories, servings†Measure of continuous NNS intakeOutcome
BMIWeightOverweight/obesityMetabolic syndromeType 2 diabetesHypertensionOtherQuality score‡
Lutsey et al. 200854ARICUSA, 19879154M, F54 ± 6–9AS sodaExtreme tertiles–•8
Bomback et al. 201043ARICUSA, 198714 002M, F54 ± 628 ± 59AS soda> 1/d v. < 1/d–CKD9
Palmer et al. 200855BWHSUSA, 200143 960F38 ± 1028 ± 74AS soda≥ 1/d v. < 1/mo–•6
Duffey et al. 201248CARDIAUSA, 19863728M, F25 ± 2625 ± 520ASBNone v. any–••IGT8
Haines et al. 200759EATUSA, 19982516M, F15 ± 211% OW5AS soda–serving/d•7
Lana et al. 2015§22ENRICASpain, 20082030M, F18–6026 ± 54AS soda≥ 1/d v. < 1/wk–•9
Fagherazzi et al. 201349EPIC-E3NFrance, 199366 118F53 ± 719% OW17ASB> 603 mL/wk v. never–•8
O’Connor et al. 201524EPIC-NorfolkUK, 199324 653M, F58 ± 926 ± 411ASB≥ 169 mL/d v. noneserving/d•8
Dhingra et al. 200747FOSUSA, 19921864M, F55 ± 1027 ± 54AS soda1/d v. < 1/wk–•9
Field et al. 201414GUTS IIUSA, 20047559M, F13 ± 220 ± 33AS soda–serving/d•6
Bernstein et al. 201240HPFSUSA, 198643 371M62 ± 1126 ± 322AS soda≥ 1/d v. noneserving/dStroke8
Bhupathiraju et al. 2013**42HPFSUSA, 198639 059M53 ± 1025 ± 522AS soda≥ 1/d v. < 1/moserving/d•7
Cohen et al. 201245HPFSUSA, 198637 360M40–7525 ± 322ASB≥ 1/d v. < 1/mo–•8
de Koning et al. 201246HPFSUSA, 198642 883M40–7526 ± 322ASB> 4/wk v. noneserving/dCHD8
Smith et al. 201521HPFSUSA, 198621 472M47 ± 625 ± 124AS soda–serving/d•6
Gearon et al. 2014§15MCCSAustralia, 199013 697M, F55 ± 926 ± 413AS soda–serving/wk•8
Nettleton et al. 200960MESAUSA, 20005011M, F62 ± 1128 ± 65AS soda≥ 1/d v. rare or never–•••Waist6
Fung et al. 200951NHS IUSA, 198088 520F34–5924 ± 224AS soda≥ 2/d v. < 1/mo–CHD8
Bernstein et al. 201240NHS IUSA, 198084 085F58 ± 1026 ± 528AS soda≥ 1/d v. noneserving/dStroke8
Bhupathiraju et al. 201342NHS IUSA, 198474 749F50 ± 725 ± 524AS soda≥ 1/d v. < 1/moserving/d•7
Cohen et al. 2012††45NHS IUSA, 198088 540F34–5923 ± 338ASB≥ 1/d v. < 1/mo–•8
Smith et al. 2015‡‡21NHS IUSA, 198648 449F49 ± 624 ± 124AS soda–serving/d•6
Pan et al. 2012§§56NHS IIUSA, 199182 902F36 ± 524 ± 518ASB≥ 4/d v. ≤ 1/wkserving/d•7
Chen et al. 200944NHS IIUSA, 199113 475F32 ± 323 ± 410ASB≥ 5/wk v. ≤ 3/moserving/dGDM8
Cohen et al. 2012††45NHS IIUSA, 199197 991F27–4223 ± 416ASB≥ 1/d v. < 1/mo–•8
Smith et al. 201521NHS IIUSA, 199148 071F38 ± 423 ± 216AS soda–serving/d•6
Gardener et al. 201252NOMASUSA, 19932564M, F69 ± 1028 ± 610AS soda≥ 1/d v. < 1/moserving/wkCVD7
Parker et al. 199757PHHPUSA, 1986465M, F47 ± 1427 ± 54Saccharin–log g/d•9
Fowler et al. 200850SAHSUSA, 19793371M, F44 ± 1127 ± 68ASB≥ 22/wk v. none–••7
Fowler et al. 2015¶¶18SALSAUSA, 1992384M, F70 ± 328 ± 59AS soda≥ 1/d v. none–Waist5
Sakurai et al. 201316–Japan, 20032037M46 ± 623 ± 37AS soda≥ 1/wk v. none–•8
Barrio-Lopez et al. 2013§39SUNSpain, 19998157M, F36 ± 1123 ± 36AS sodaExtreme quintiles–•7
Bes-Rastrollo et al. 2006§41SUNSpain, 19997194M, F37 ± 12–2AS sodaExtreme quintiles–Gain > 1 kg8
Renault et al. 201523TOPDenmark, 2009347F31 ± 434 ± 40.8AS soda≥ 1/d v. none–GWG7
Vyas et al. 201517WHIUSA, 199359 614F63 ± 759% OW9ASB≥ 2/d v. ≤ 3/mo–CVD6
Stinson et al. 201358WHIUSA, 199662 082F50–9–9–14ASB> 3/d v. < 3/mo–•6

  • Note: ARIC = Atherosclerosis Risk in Communities, AS soda = artificially sweetened soda (soft drinks), ASB = artificially sweetened beverages (including sodas and other beverages such as coffee or tea), BMI = body mass index, BWHS = Black Women’s Health Study, CARDIA = Coronary Artery Risk Development in Young Adults, CHD = coronary heart disease, CKD = chronic kidney disease, CVD = cardiovascular disease, E3N = Etude Epidemiologique aupres des femmes de la mutuelle generale de l’Education Nationale, EAT = Eating Among Teens, ENRICA = Study on Nutrition and Cardiovascular Risk in Spain, EPIC = European Prospective Investigation into Cancer and Nutrition, FOS = Framingham Offspring Study, F = female, GDM = gestational diabetes mellitus, GWG = gestational weight gain, GUTS II = Growing Up Today Study II, HPFS = Health Professionals Follow-Up Study, HOMA-IR = homeostatic model assessment for insulin resistance, IGT = impaired glucose tolerance, IQR = interquartile range, M = male, MCCS = Melbourne Collaborative Cohort Study, MESA = Multi-Ethnic Study of Atherosclerosis, NHS = Nurses’ Health Study, NOMAS = Northern Manhattan Study, NNS = nonnutritive sweetener, OW = overweight, PHHP = Pawtucket Heart Health Program, SAHS = San Antonio Heart Study, SALSA = San Antonio Longitudinal Study of Aging, SD = standard deviation, SUN = Seguimiento Universidad de Navarra, TOP = Treatment of Obese Pregnant Women, WHI = Women’s Health Initiative.

  • ↵* Sorted by cohort name. In some cases, different outcomes from a single cohort are reported in separate studies. Where multiple cohorts are reported in a single study, characteristics are reported per cohort rather than per study.

  • ↵† Unless otherwise specified.

  • ↵‡ Study quality was assessed using the Newcastle–Ottawa Scale;31 maximum score = 9. See Appendix 1, Table S5 for detailed quality assessment results.

  • ↵§ Unpublished data provided by study authors.

  • ↵ Excluded study InterAct 201353 reports overlapping data from the international EPIC study.

  • ↵** Excluded study de Koning et al. 201161 reports earlier type 2 diabetes data from this cohort.

  • ↵†† Excluded study Winkelmayer et al. 200562 reports earlier hypertension data from this cohort.

  • ↵‡‡ Excluded study Colditz et al. 199063 reports earlier weight data from this cohort.

  • ↵§§ Excluded study Schulze et al. 200464 reports earlier type 2 diabetes data from this cohort.

  • ↵¶¶ Body mass index data from this study were not reviewed because the SALSA cohort was recruited from the SAHS cohort, reported in Fowler et al. 2008.50