. 2017 Jul 17;189(28):E929–E939. doi: 10.1503/cmaj.161390

Table 2:

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

Study^*	Cohort	Country, year of baseline NNS intake	No. of participants	Sex	Age at baseline, mean ± SD, or range; yr	BMI at baseline, mean ± SD, or % OW; kg/m²	Follow-up, yr	Type or source of NNS	Extreme NNS intake categories, servings^†	Measure of continuous NNS intake	Outcome
Study^*	Cohort	Country, year of baseline NNS intake	No. of participants	Sex	Age at baseline, mean ± SD, or range; yr	BMI at baseline, mean ± SD, or % OW; kg/m²	Follow-up, yr	Type or source of NNS	Extreme NNS intake categories, servings^†	Measure of continuous NNS intake	BMI	Weight	Overweight/obesity	Metabolic syndrome	Type 2 diabetes	Hypertension	Other	Quality score^‡
Lutsey et al. 2008⁵⁴	ARIC	USA, 1987	9154	M, F	54 ± 6	–	9	AS soda	Extreme tertiles	–				•				8
Bomback et al. 2010⁴³	ARIC	USA, 1987	14 002	M, F	54 ± 6	28 ± 5	9	AS soda	> 1/d v. < 1/d	–							CKD	9
Palmer et al. 2008⁵⁵	BWHS	USA, 2001	43 960	F	38 ± 10	28 ± 7	4	AS soda	≥ 1/d v. < 1/mo	–					•			6
Duffey et al. 2012⁴⁸	CARDIA	USA, 1986	3728	M, F	25 ± 26	25 ± 5	20	ASB	None v. any	–				•		•	IGT	8
Haines et al. 2007⁵⁹	EAT	USA, 1998	2516	M, F	15 ± 2	11% OW	5	AS soda	–	serving/d			•					7
Lana et al. 2015^§²²	ENRICA	Spain, 2008	2030	M, F	18–60	26 ± 5	4	AS soda	≥ 1/d v. < 1/wk	–			•					9
Fagherazzi et al. 2013^¶⁴⁹	EPIC-E3N	France, 1993	66 118	F	53 ± 7	19% OW	17	ASB	> 603 mL/wk v. never	–					•			8
O’Connor et al. 2015^¶²⁴	EPIC-Norfolk	UK, 1993	24 653	M, F	58 ± 9	26 ± 4	11	ASB	≥ 169 mL/d v. none	serving/d					•			8
Dhingra et al. 2007⁴⁷	FOS	USA, 1992	1864	M, F	55 ± 10	27 ± 5	4	AS soda	1/d v. < 1/wk	–				•				9
Field et al. 2014¹⁴	GUTS II	USA, 2004	7559	M, F	13 ± 2	20 ± 3	3	AS soda	–	serving/d	•							6
Bernstein et al. 2012⁴⁰	HPFS	USA, 1986	43 371	M	62 ± 11	26 ± 3	22	AS soda	≥ 1/d v. none	serving/d							Stroke	8
Bhupathiraju et al. 2013^**⁴²	HPFS	USA, 1986	39 059	M	53 ± 10	25 ± 5	22	AS soda	≥ 1/d v. < 1/mo	serving/d					•			7
Cohen et al. 2012⁴⁵	HPFS	USA, 1986	37 360	M	40–75	25 ± 3	22	ASB	≥ 1/d v. < 1/mo	–						•		8
de Koning et al. 2012⁴⁶	HPFS	USA, 1986	42 883	M	40–75	26 ± 3	22	ASB	> 4/wk v. none	serving/d							CHD	8
Smith et al. 2015²¹	HPFS	USA, 1986	21 472	M	47 ± 6	25 ± 1	24	AS soda	–	serving/d		•						6
Gearon et al. 2014^§¹⁵	MCCS	Australia, 1990	13 697	M, F	55 ± 9	26 ± 4	13	AS soda	–	serving/wk	•							8
Nettleton et al. 2009⁶⁰	MESA	USA, 2000	5011	M, F	62 ± 11	28 ± 6	5	AS soda	≥ 1/d v. rare or never	–				•	•	•	Waist	6
Fung et al. 2009⁵¹	NHS I	USA, 1980	88 520	F	34–59	24 ± 2	24	AS soda	≥ 2/d v. < 1/mo	–							CHD	8
Bernstein et al. 2012⁴⁰	NHS I	USA, 1980	84 085	F	58 ± 10	26 ± 5	28	AS soda	≥ 1/d v. none	serving/d							Stroke	8
Bhupathiraju et al. 2013⁴²	NHS I	USA, 1984	74 749	F	50 ± 7	25 ± 5	24	AS soda	≥ 1/d v. < 1/mo	serving/d					•			7
Cohen et al. 2012^††⁴⁵	NHS I	USA, 1980	88 540	F	34–59	23 ± 3	38	ASB	≥ 1/d v. < 1/mo	–						•		8
Smith et al. 2015^‡‡²¹	NHS I	USA, 1986	48 449	F	49 ± 6	24 ± 1	24	AS soda	–	serving/d		•						6
Pan et al. 2012^§§⁵⁶	NHS II	USA, 1991	82 902	F	36 ± 5	24 ± 5	18	ASB	≥ 4/d v. ≤ 1/wk	serving/d					•			7
Chen et al. 2009⁴⁴	NHS II	USA, 1991	13 475	F	32 ± 3	23 ± 4	10	ASB	≥ 5/wk v. ≤ 3/mo	serving/d							GDM	8
Cohen et al. 2012^††⁴⁵	NHS II	USA, 1991	97 991	F	27–42	23 ± 4	16	ASB	≥ 1/d v. < 1/mo	–						•		8
Smith et al. 2015²¹	NHS II	USA, 1991	48 071	F	38 ± 4	23 ± 2	16	AS soda	–	serving/d		•						6
Gardener et al. 2012⁵²	NOMAS	USA, 1993	2564	M, F	69 ± 10	28 ± 6	10	AS soda	≥ 1/d v. < 1/mo	serving/wk							CVD	7
Parker et al. 1997⁵⁷	PHHP	USA, 1986	465	M, F	47 ± 14	27 ± 5	4	Saccharin	–	log g/d		•						9
Fowler et al. 2008⁵⁰	SAHS	USA, 1979	3371	M, F	44 ± 11	27 ± 6	8	ASB	≥ 22/wk v. none	–	•		•					7
Fowler et al. 2015^¶¶¹⁸	SALSA	USA, 1992	384	M, F	70 ± 3	28 ± 5	9	AS soda	≥ 1/d v. none	–							Waist	5
Sakurai et al. 2013¹⁶	–	Japan, 2003	2037	M	46 ± 6	23 ± 3	7	AS soda	≥ 1/wk v. none	–					•			8
Barrio-Lopez et al. 2013^§³⁹	SUN	Spain, 1999	8157	M, F	36 ± 11	23 ± 3	6	AS soda	Extreme quintiles	–				•				7
Bes-Rastrollo et al. 2006^§⁴¹	SUN	Spain, 1999	7194	M, F	37 ± 12	–	2	AS soda	Extreme quintiles	–							Gain > 1 kg	8
Renault et al. 2015²³	TOP	Denmark, 2009	347	F	31 ± 4	34 ± 4	0.8	AS soda	≥ 1/d v. none	–							GWG	7
Vyas et al. 2015¹⁷	WHI	USA, 1993	59 614	F	63 ± 7	59% OW	9	ASB	≥ 2/d v. ≤ 3/mo	–							CVD	6
Stinson et al. 2013⁵⁸	WHI	USA, 1996	62 082	F	50–9	–	9–14	ASB	> 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