

, SuJin Song2*
, Soo Kyoung Kim3, Jae Won Cho4, Jae Hyun Bae5,6, Shinje Moon7, Jeong Hyun Lim8, YeonHee Lee9, Ji-Yun Hwang10, YoonJu Song11
, Sang Soo Kim12
1Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
2Department of Food and Nutrition, Hannam University, Daejeon, Korea
3Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju, Korea
4Department of Dietetics, Samsung Medical Center, Seoul, Korea
5Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
6Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
7Department of Internal Medicine, Hanyang University Seoul Hospital, Seoul, Korea
8Department of Food Service and Nutrition Care, Seoul National University Hospital, Seoul, Korea
9Department of Food Service and Clinical Nutrition, Ajou University Hospital, Suwon, Korea
10Major of Foodservice Management and Nutrition, Sangmyung University, Seoul, Korea
11Department of Food Science and Nutrition, The Catholic University of Korea, Bucheon, Korea
12Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University Hospital and Pusan National University School of Medicine, Busan, Korea
Department of Food Science and Nutrition, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon 14662, Korea E-mail: yjsong@catholic.ac.kr
Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea E-mail: drsskim7@gmail.com Copyright © 2026 Korean Diabetes Association
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. ASBs may be used as a short-term substitution strategy for individuals with high SSBs consumption, particularly those at elevated cardiometabolic risk, as RCTs have demonstrated modest benefits in weight reduction and glycemic outcomes. (Strong Recommendation, Level of Evidence: Moderate)
2. ASBs are not recommended for initiating regular use in individuals with little or no prior SSBs or ASBs intake, nor for long-term reliance among those with high SSBs consumption, as evidence from prospective cohort studies indicates that high ASBs intake may be associated with increased risks of mortality, CVD, and T2DM, generally similar to those observed with SSBs. (Strong Recommendation, Level of Evidence: Moderate)
• Short-term RCTs show modest benefits in weight reduction when replacing SSBs with ASBs but have not demonstrated consistent improvements in glycemic control.
Substituting SSBs with ASBs reduces added sugar intake and may lower cardiometabolic risk.
• Concerns remain regarding the effects of ASBs on appetite regulation, gut microbiota, and glucose metabolism, particularly with prolonged use.
Long-term observational studies consistently show that both SSBs and ASBs are associated with increased risks of mortality, T2DM, and adverse cardiovascular outcomes, with broadly similar associations observed for ASBs.
• For short-term reduction of SSBs intake, ASBs offer a net benefit in populations at high metabolic risk.
• Regular use of ASBs is not recommended due to an uncertain long-term risk–benefit profiles; substitution should be transitional.
• ASBs may serve as a practical stepping stone for individuals seeking to reduce sugar intake but should not be viewed as a permanent solution.
• Public health messaging should reinforce the ultimate goal of shifting toward water or non-sweetened beverages.
• These recommendations apply across age groups, including children and adolescents, with a strong emphasis on reducing early exposure to sweetened beverages.
CONFLICTS OF INTEREST
Jae Hyun Bae has been a managing editor of the Diabetes & Me tabolism Journal since 2024. He was not involved in the review process of this article. Otherwise, there was no conflict of interest.
AUTHOR CONTRIBUTIONS
Conception or design: J.H.C., S.J.S., Y.J.S., S.S.K.
Acquisition, analysis, or interpretation of data: J.H.C., S.J.S., S.K.K., J.W.C., S.M., J.H.L., Y.H.L., J.Y.H., Y.J.S., S.S.K.
Drafting the work or revising: J.H.C., S.J.S., J.H.B., Y.J.S., S.S.K.
Final approval of the manuscript: all authors.
FUNDING
None
ACKNOWLEDGMENTS
The authors acknowledged that this was partially supported financially by the Korean Nutrition Society, including the literature search.
| Outcomes | Evidence source | Effect estimated (mean difference, 95% CI) | No. of participants (studies) | Quality of the evidence (GRADE)a | Comments |
|---|---|---|---|---|---|
|
Body weight, kg Follow-up: 3–76 weeks |
Updated MA of RCTs | −0.73 (−0.95 to −0.50) | 1,779 (12 studies) |
⊕⊕⊕⊖ Moderate |
Consistent, precise; downgraded for some RoB |
|
Body mass index, kg/m2 Follow-up: 4–76 weeks |
Updated MA of RCTs | −0.31 (−0.42 to −0.19) | 1,772 (12 studies) |
⊕⊕⊕⊖ Moderate |
Consistent, precise; downgraded for some RoB |
|
Body fat, % Follow-up: 12–76 weeks |
Updated MA of RCTs | −0.72 (−1.07 to −0.37) | 1,471 (7 studies) |
⊕⊕⊕⊖ Moderate |
Consistent, precise; downgraded for some RoB |
|
HbA1c, % Follow-up: 12 weeks |
Updated MA of RCTs | −0.20 (−0.39 to −0.01) | 536 (3 studies) |
⊕⊕⊖⊖ Low |
Few trials, imprecision |
|
Fasting glucose, mmol/L Follow-up: 8–52 weeks |
Updated MA of RCTs | −0.13 (−1.21 to −0.04) | 853 (7 studies) |
⊕⊕⊕⊖ Moderate |
Consistent but effect small |
|
HOMA-IR Follow-up: 12–26 weeks |
Updated MA of RCTs | −0.25 (−0.61 to 0.11) | 208 (3 studies) |
⊕⊖⊖⊖ Very low |
Imprecise, small samples |
|
LDL-C, mmol/L Follow-up: 8–52 weeks |
Updated MA of RCTs | 0.02 (−0.07 to 0.11) | 826 (6 studies) |
⊕⊕⊖⊖ Low |
No effect, some RoB |
|
HDL-C, mmol/L Follow-up: 8–52 weeks |
Updated MA of RCTs | 0.03 (−0.00 to 0.06) | 853 (7 studies) |
⊕⊕⊖⊖ Low |
No effect, imprecise |
|
Triglyceride, mmol/L Follow-up: 12–52 weeks |
Updated MA of RCTs | −0.09 (−0.18 to −0.00) | 792 (6 studies) |
⊕⊕⊖⊖ Low |
Small effect, imprecise |
|
Systolic blood pressure, mm Hg Follow-up: 8–52 weeks |
Updated MA of RCTs | −1.21 (−3.20 to 0.78) | 582 (6 studies) |
⊕⊕⊖⊖ Low |
Not significant, CI wide |
|
Diastolic blood pressure, mm Hg Follow-up: 8–52 weeks |
Updated MA of RCTs | −1.45 (−2.98 to 0.09) | 582 (6 studies) |
⊕⊕⊖⊖ Low |
Not significant, CI wide |
|
Question: In people replacing sugar-sweetened beverages with artificially sweetened beverages, what is the effect on body composition and metabolic outcomes? Population: Adults/adolescents/children Intervention/Exposure: Substitution SSBs with ASBs Comparator: Maintaining SSBs Study design: Updated meta-analyses of RCTs |
|||||
The basis for the assumed mean change is the average change from baseline in the control (SSBs) group across studies. The corresponding mean difference (and its 95% CI) reflects the estimated effect of replacing SSBs with ASBs, given the assumed mean change in the comparison group. Some trials had unclear allocation concealment or blinding, which may affect the certainty of evidence (downgraded one level for risk of bias). Visual inspection of the funnel plot did not suggest substantial publication bias.
ASB, artificially sweetened beverage; SSB, sugar-sweetened beverage; RCT, randomized controlled trial; CI, confidence interval; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; MA, meta-analysis; RoB, risk of bias; HbA1c, glycosylated hemoglobin; HOMA-IR, homeostatic model assessment of insulin resistance; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol.
a GRADE Working Group grades of evidence: High quality (Further research is very unlikely to change our confidence in the estimate of effect); Moderate quality (Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate); Low quality (Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate); Very low quality (We are very uncertain about the estimate).
| Outcomes | Evidence source | Effect estimated (risk ratio: lowest–highest) | No. of SR/MA | Quality of the evidence (GRADE)a | Comments | ||
|---|---|---|---|---|---|---|---|
| ASBs | SSBs | ASBs | SSBs | ||||
| Hypertension | Umbrella SR (NRS) | 1.08–1.14 | 1.10–1.27 | 4 |
⊕⊕⊖⊖ Low |
⊕⊕⊖⊖ Low |
Consistent, small effect; downgraded for RoB |
| Obesity | Umbrella SR (NRS) | 1.21 | 1.12 | 1 |
⊕⊕⊖⊖ Low |
⊕⊕⊖⊖ Low |
Few studies; consistent but downgraded for RoB |
| Metabolic syndrome | Umbrella SR (NRS) | 1.31–1.44 | 1.19–1.56 | 3 |
⊕⊕⊖⊖ Low |
⊕⊕⊖⊖ Low |
Few studies; consistent but downgraded for RoB |
| Type 2 diabetes mellitus | Umbrella SR (NRS) | 1.13–1.32 | 1.15–1.29 | 7 |
⊕⊕⊕⊖ Moderate |
⊕⊕⊕⊖ Moderate |
Consistent, upgraded due to evidence of dose-response relationship |
| Incidence of CVD | Umbrella SR (NRS) | 1.07–1.21 | 1.08–1.17 | 5 |
⊕⊕⊖⊖ Low |
⊕⊕⊖⊖ Low |
Consistent, small effect; downgraded for RoB |
| CVD mortality | Umbrella SR (NRS) | 1.04–1.26 | 1.08–1.31 | 7 |
⊕⊕⊕⊖ Moderate |
⊕⊕⊕⊖ Moderate |
Consistent, upgraded due to evidence of dose-response relationship |
| Cancer mortality | Umbrella SR (NRS) | 1.01–1.04 | 0.96–1.02 | 4 |
⊕⊖⊖⊖ Very low |
⊕⊖⊖⊖ Very low |
Effect close to null; downgraded for imprecision |
| All-cause mortality | Umbrella SR (NRS) | 1.04–1.15 | 1.03–1.14 | 8 |
⊕⊕⊕⊖ Moderate |
⊕⊕⊕⊖ Moderate |
Consistent, upgraded due to evidence of dose-response relationship |
|
Question: In the general population, what is the association between SSBs or ASBs consumption and health outcomes? Population: Adults/adolescents from cohort studies Intervention/Exposure: SSBs or ASBs consumption (highest vs. lowest, or per serving/day) Comparator: Lowest intake/non-consumers Study design: Systematic reviews of prospective cohort studies (NRS) |
|||||||
The basis for the estimated effect sizes (minimum and maximum risk ratios from the included systematic reviews) reflects the association between higher intake of SSBs or ASBs and various health outcomes, compared with lower intake or non-consumers, based on prospective cohort studies. All included systematic reviews/meta-analyses were derived from NRS, which start at a low level of certainty in the GRADE approach. Certainty of evidence was further downgraded for risk of bias (confounding, lack of protocol registration, incomplete adjustment), inconsistency (heterogeneity across studies), and imprecision (wide or borderline confidence intervals). For SSBs and type 2 diabetes mellitus incidence, the certainty was upgraded by one level due to consistent evidence of a dose-response relationship (per serving/day increase associated with higher risk). No upgrading was applied for ASBs outcomes due to lack of consistent dose-response evidence.
SSB, sugar-sweetened beverage; ASB, artificially sweetened beverage; NRS, non-randomized study; SR, systematic review; MA, meta-analysis; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; RoB, risk of bias; CVD, cardiovascular disease.
a GRADE Working Group grades of evidence: High quality (Further research is very unlikely to change our confidence in the estimate of effect); Moderate quality (Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate); Low quality (Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate); Very low quality (We are very uncertain about the estimate).
| Study | Study design | Protocol registration | Nationality | Duration, wk | Age group (mean age), yr | Mean BMI, kg/m2 | No. of participants (male:female) | Types of ASB | Beverage dosage, mL/day | |
|---|---|---|---|---|---|---|---|---|---|---|
| ASB | SSB | |||||||||
| Tordoff et al. (1990) [20] | Crossover RCT | NA | USA | 3 | Adults (25.6) | NA | 30 (21:9) | Aspartame | 1,135 | 1,135 |
| Reid et al. (2007) [21] | Parallel RCT | NA | UK | 4 | Adults (31.8) | 22.5 | 133 (0:133) | Aspartame | 1,000 | 1,000 |
| Reid et al. (2010) [22] | Parallel RCT | NA | UK | 4 | Adults (33.7) | 27.5 | 53 (0:53) | Aspartame | 1,000 | 1,000 |
| Reid et al. (2014) [23] | Parallel RCT | NCT01799096 | UK | 4 | Adults (35.0) | 32.7 | 41 (0:41) | Aspartame | 1,000 | 1,000 |
| Campos et al. (2015) [24] | Parallel RCT | NCT 01394380 | Switzerland | 12 | Adults (NA) | 30.7 | 27 (14:13) | NA | 1,300 | 1,300 |
| Engel et al. (2018) [25] | Parallel RCT | NCT00777647 | Denmark | 26 | Adults (38.6) | 32.1 | 45 (16:29) | Aspartame | 1,000 | 1,000 |
| Higgins et al. (2019) [26] | Parallel RCT | NCT02928653 | USA | 12 | Adults (27.3) | 29.6 | 154 (67:87) | Saccharin, aspartame, rebaudioside A, sucralose | 1,250–1,750 | 1,250–1,750 |
| Ebbeling et al. (2020) [27] | Parallel RCT | NCT01295671 | USA | 52 | Adults (27.0) | 26.0 | 203 (121:82) | NA | 355 | 355 |
| Mohan et al. (2023) [28] | RCT | NA | India | 12 | Adults (NA) | 28.3 | 152 (NA) | Sucralose | NA | NA |
| Kwok et al. (2024) [29] | Parallel RCT | NCT05264636 | Canada | 8 | Adults (31.3) | 22.6 | 59 (23:36) | Stevia | 473 | 473 |
| Mohan et al. (2024) [30] | Crossover RCT | ClinTrials Registry of India CTRI/2021/04/032686 | India | 12 | Adults (45.0) | 27.9 | 210 (84:126) | Sucralose | NA | NA |
| Ebbeling et al. (2006) [31] | Parallel RCT | NA | USA | 25 | Adolescent (15.9) | 25.3 | 103 (47:56) | NA | 1,400 | Usual (380 kcal/day at baseline) |
| Ebbeling et al. (2012) [32] | Parallel RCT | NCT00381160 | USA | 52 | Adolescent (15.3) | 30.3 | 224 (124:100) | NA | Home delivery of ASBs every 2 wk | Usual (324 kcal/day at baseline) |
| de Ruyter et al. (2012) [33] | Parallel RCT | NCT00893529 | Netherlands | 76 | Child (8.2) | 16.9 (z score=−0.03) | 641 (343:298) | Sucralose + acesulfame K | 250 | 250 |
| Study | Protocol registration | Search up | Duration, yr | Age group, yr | No. of databases searched | No. of studies included for analysis of each outcome | Included outcomes |
|---|---|---|---|---|---|---|---|
| Greenwood et al. (2014) [34] | NA | ~2013.06 | 6.9–24 | Healthy adults | 7 (Cochrane, MEDLINE, MEDLINE In-Process, Embase, CAB Abstracts, WoS, BIOSIS) | 6 | T2DM |
| Cheungpasitporn et al. (2015) [35] | NA | ~2015.01 | NA | Adults, adolescents | 3 (MEDLINE, Embase, Cochrane) | 8 | Hypertension |
| Imamura et al. (2015) [36] | NA | ~2014.02 | 3.4–21.1 | Healthy adults | 4 (PubMed, Embase, Ovid, Web of knowledge) | 21 | T2DM |
| Narian et al. (2016) [37] | NA | ~2015.07 | NA | Adults | 2 (MEDLINE, Embase) | 9 | CVD, All-cause mortality |
| Narian et al. (2017) [38] | NA | ~2015.07 | NA | Adults, adolescents, children | 2 (MEDLINE, Embase) | 12 | Metabolic Syndrome |
| Ruanpeng et al. (2017) [39] | NA | ~2015.05 | NA | Adults, adolescents | 3 (Embase, MEDLINE, Cochrane) | 13 | Obesity |
| Qin et al. (2020) [40] | NA | ~2019.09 | 6.8–19.7 | Healthy (18+) | 4 (PubMed, Embase, WoS, Open Grey) | 4–18 | All-cause mortality, T2DM, hypertension, obesity |
| Meng et al. (2021) [41] | NA | ~2020.6.20 | 5.5–34 | Healthy (18–79) | 3 (PubMed, Embase, and Ovid) | 8–17 | All-cause mortality, CVD, T2DM |
| Yin et al. (2021) [42] | PROSPERO CRD42019137454 | ~2019.12 | 9.8–28 | Healthy (35–75) | 2 (PubMed, Embase) | 4–10 | CVD mortality, CVD |
| Zhang et al. (2021) [43] | NA | ~2019.11.04 | NA | Adults, adolescents, children | 3 (PubMed, WoS, and Embase) | 4–16 | Metabolic syndrome |
| Zhang et al. (2021) [17] | NA | ~2020.03 | 5.9–31 | All adults (mean 42.8–74) | 7 (PubMed, Embase, WoS, Cochrane, ProQuest, ClinicalTrials.gov, International Clinical Trials Registry Platform) | 2–10 | All-cause mortality, CVD mortality, cancer mortality |
| Bhagavathula et al. (2022) [44] | NA | ~2021.07.31 | 3–28 (mean 12.2) | Healthy (mean 55.6) | 3 (PubMed, WoS, Embase) | 4–5 | CVD mortality |
| Li et al. (2022) [45] | PROSPERO CRD 42019140581 | ~2020.01.01 | NA | Healthy adults | 4 (PubMed, Embase, WoS, Cochrane) | 14 | All-cause mortality, CVD mortality, cancer mortality |
| Pan et al. (2022) [46] | PROSPERO CRD42020152223 | ~2020.09.21 | 11–22 | Healthy (47–74) | 5 (PubMed, Embase, WoS, Cochranme, PsycINFO) | 4–11 | All-cause mortality, CVD mortality, cancer mortality |
| Taneri et al. (2022) [47] | PROSPERO CRD42020151201 | ~2021.01.29 | 11.6–28 | Healthy adults | 5 (MEDLINE, Embase, WoS, Cochrane, Google Scholar) | 3–12 | All-cause mortality |
| Yang et al. (2022) [48] | PROSPERO CRD4202020068 | ~2021.02.09 | 6–34 | Healthy (20+) | 2 (Embase, Ovid) | 2–12 | CVD mortality, CVD |
| Li et al. (2023) [18] | PROSPERO CRD42022307003 | ~2022.12 | 4–38 | Healthy (18+) | 4 (PubMed, Embase, WoS, Cochrane) | 3–17 | All-cause mortality, T2DM, Hypertension |
| Bhandari et al. (2024) [49] | PROSPERO CRD42020214679 | ~2023.12 | 18.5–34 | Healthy (30–75) | 5 (MEDLINE, Embase, CINAHL, WoS, Scopus) | 2 | CVD mortality |
| Ding et al. (2024) [50] | NA | ~2023.03 | NA | T2DM (18+) | 4 (PubMed, Embase, WoS, Cochrane) | 1–3 | All-cause mortality |
| Zhao et al. (2024) [51] | PROSPERO CRD42021259128 | ~2021.02.02 | NA | Adults, adolescents, children | 3 (PubMed, Embase, and WoS) | 23 | Hypertension |
PubReader
ePub Link
Cite this Article
| Outcomes | Evidence source | Effect estimated (mean difference, 95% CI) | No. of participants (studies) | Quality of the evidence (GRADE) |
Comments |
|---|---|---|---|---|---|
| Body weight, kg Follow-up: 3–76 weeks |
Updated MA of RCTs | −0.73 (−0.95 to −0.50) | 1,779 (12 studies) | ⊕⊕⊕⊖ Moderate |
Consistent, precise; downgraded for some RoB |
| Body mass index, kg/m2 Follow-up: 4–76 weeks |
Updated MA of RCTs | −0.31 (−0.42 to −0.19) | 1,772 (12 studies) | ⊕⊕⊕⊖ Moderate |
Consistent, precise; downgraded for some RoB |
| Body fat, % Follow-up: 12–76 weeks |
Updated MA of RCTs | −0.72 (−1.07 to −0.37) | 1,471 (7 studies) | ⊕⊕⊕⊖ Moderate |
Consistent, precise; downgraded for some RoB |
| HbA1c, % Follow-up: 12 weeks |
Updated MA of RCTs | −0.20 (−0.39 to −0.01) | 536 (3 studies) | ⊕⊕⊖⊖ Low |
Few trials, imprecision |
| Fasting glucose, mmol/L Follow-up: 8–52 weeks |
Updated MA of RCTs | −0.13 (−1.21 to −0.04) | 853 (7 studies) | ⊕⊕⊕⊖ Moderate |
Consistent but effect small |
| HOMA-IR Follow-up: 12–26 weeks |
Updated MA of RCTs | −0.25 (−0.61 to 0.11) | 208 (3 studies) | ⊕⊖⊖⊖ Very low |
Imprecise, small samples |
| LDL-C, mmol/L Follow-up: 8–52 weeks |
Updated MA of RCTs | 0.02 (−0.07 to 0.11) | 826 (6 studies) | ⊕⊕⊖⊖ Low |
No effect, some RoB |
| HDL-C, mmol/L Follow-up: 8–52 weeks |
Updated MA of RCTs | 0.03 (−0.00 to 0.06) | 853 (7 studies) | ⊕⊕⊖⊖ Low |
No effect, imprecise |
| Triglyceride, mmol/L Follow-up: 12–52 weeks |
Updated MA of RCTs | −0.09 (−0.18 to −0.00) | 792 (6 studies) | ⊕⊕⊖⊖ Low |
Small effect, imprecise |
| Systolic blood pressure, mm Hg Follow-up: 8–52 weeks |
Updated MA of RCTs | −1.21 (−3.20 to 0.78) | 582 (6 studies) | ⊕⊕⊖⊖ Low |
Not significant, CI wide |
| Diastolic blood pressure, mm Hg Follow-up: 8–52 weeks |
Updated MA of RCTs | −1.45 (−2.98 to 0.09) | 582 (6 studies) | ⊕⊕⊖⊖ Low |
Not significant, CI wide |
| Question: In people replacing sugar-sweetened beverages with artificially sweetened beverages, what is the effect on body composition and metabolic outcomes? Population: Adults/adolescents/children Intervention/Exposure: Substitution SSBs with ASBs Comparator: Maintaining SSBs Study design: Updated meta-analyses of RCTs | |||||
| Outcomes | Evidence source | Effect estimated (risk ratio: lowest–highest) | No. of SR/MA | Quality of the evidence (GRADE) |
Comments | ||
|---|---|---|---|---|---|---|---|
| ASBs | SSBs | ASBs | SSBs | ||||
| Hypertension | Umbrella SR (NRS) | 1.08–1.14 | 1.10–1.27 | 4 | ⊕⊕⊖⊖ Low |
⊕⊕⊖⊖ Low |
Consistent, small effect; downgraded for RoB |
| Obesity | Umbrella SR (NRS) | 1.21 | 1.12 | 1 | ⊕⊕⊖⊖ Low |
⊕⊕⊖⊖ Low |
Few studies; consistent but downgraded for RoB |
| Metabolic syndrome | Umbrella SR (NRS) | 1.31–1.44 | 1.19–1.56 | 3 | ⊕⊕⊖⊖ Low |
⊕⊕⊖⊖ Low |
Few studies; consistent but downgraded for RoB |
| Type 2 diabetes mellitus | Umbrella SR (NRS) | 1.13–1.32 | 1.15–1.29 | 7 | ⊕⊕⊕⊖ Moderate |
⊕⊕⊕⊖ Moderate |
Consistent, upgraded due to evidence of dose-response relationship |
| Incidence of CVD | Umbrella SR (NRS) | 1.07–1.21 | 1.08–1.17 | 5 | ⊕⊕⊖⊖ Low |
⊕⊕⊖⊖ Low |
Consistent, small effect; downgraded for RoB |
| CVD mortality | Umbrella SR (NRS) | 1.04–1.26 | 1.08–1.31 | 7 | ⊕⊕⊕⊖ Moderate |
⊕⊕⊕⊖ Moderate |
Consistent, upgraded due to evidence of dose-response relationship |
| Cancer mortality | Umbrella SR (NRS) | 1.01–1.04 | 0.96–1.02 | 4 | ⊕⊖⊖⊖ Very low |
⊕⊖⊖⊖ Very low |
Effect close to null; downgraded for imprecision |
| All-cause mortality | Umbrella SR (NRS) | 1.04–1.15 | 1.03–1.14 | 8 | ⊕⊕⊕⊖ Moderate |
⊕⊕⊕⊖ Moderate |
Consistent, upgraded due to evidence of dose-response relationship |
| Question: In the general population, what is the association between SSBs or ASBs consumption and health outcomes? Population: Adults/adolescents from cohort studies Intervention/Exposure: SSBs or ASBs consumption (highest vs. lowest, or per serving/day) Comparator: Lowest intake/non-consumers Study design: Systematic reviews of prospective cohort studies (NRS) | |||||||
| Study | Study design | Protocol registration | Nationality | Duration, wk | Age group (mean age), yr | Mean BMI, kg/m2 | No. of participants (male:female) | Types of ASB | Beverage dosage, mL/day | |
|---|---|---|---|---|---|---|---|---|---|---|
| ASB | SSB | |||||||||
| Tordoff et al. (1990) [ |
Crossover RCT | NA | USA | 3 | Adults (25.6) | NA | 30 (21:9) | Aspartame | 1,135 | 1,135 |
| Reid et al. (2007) [ |
Parallel RCT | NA | UK | 4 | Adults (31.8) | 22.5 | 133 (0:133) | Aspartame | 1,000 | 1,000 |
| Reid et al. (2010) [ |
Parallel RCT | NA | UK | 4 | Adults (33.7) | 27.5 | 53 (0:53) | Aspartame | 1,000 | 1,000 |
| Reid et al. (2014) [ |
Parallel RCT | NCT01799096 | UK | 4 | Adults (35.0) | 32.7 | 41 (0:41) | Aspartame | 1,000 | 1,000 |
| Campos et al. (2015) [ |
Parallel RCT | NCT 01394380 | Switzerland | 12 | Adults (NA) | 30.7 | 27 (14:13) | NA | 1,300 | 1,300 |
| Engel et al. (2018) [ |
Parallel RCT | NCT00777647 | Denmark | 26 | Adults (38.6) | 32.1 | 45 (16:29) | Aspartame | 1,000 | 1,000 |
| Higgins et al. (2019) [ |
Parallel RCT | NCT02928653 | USA | 12 | Adults (27.3) | 29.6 | 154 (67:87) | Saccharin, aspartame, rebaudioside A, sucralose | 1,250–1,750 | 1,250–1,750 |
| Ebbeling et al. (2020) [ |
Parallel RCT | NCT01295671 | USA | 52 | Adults (27.0) | 26.0 | 203 (121:82) | NA | 355 | 355 |
| Mohan et al. (2023) [ |
RCT | NA | India | 12 | Adults (NA) | 28.3 | 152 (NA) | Sucralose | NA | NA |
| Kwok et al. (2024) [ |
Parallel RCT | NCT05264636 | Canada | 8 | Adults (31.3) | 22.6 | 59 (23:36) | Stevia | 473 | 473 |
| Mohan et al. (2024) [ |
Crossover RCT | ClinTrials Registry of India CTRI/2021/04/032686 | India | 12 | Adults (45.0) | 27.9 | 210 (84:126) | Sucralose | NA | NA |
| Ebbeling et al. (2006) [ |
Parallel RCT | NA | USA | 25 | Adolescent (15.9) | 25.3 | 103 (47:56) | NA | 1,400 | Usual (380 kcal/day at baseline) |
| Ebbeling et al. (2012) [ |
Parallel RCT | NCT00381160 | USA | 52 | Adolescent (15.3) | 30.3 | 224 (124:100) | NA | Home delivery of ASBs every 2 wk | Usual (324 kcal/day at baseline) |
| de Ruyter et al. (2012) [ |
Parallel RCT | NCT00893529 | Netherlands | 76 | Child (8.2) | 16.9 (z score=−0.03) | 641 (343:298) | Sucralose + acesulfame K | 250 | 250 |
| Study | Protocol registration | Search up | Duration, yr | Age group, yr | No. of databases searched | No. of studies included for analysis of each outcome | Included outcomes |
|---|---|---|---|---|---|---|---|
| Greenwood et al. (2014) [ |
NA | ~2013.06 | 6.9–24 | Healthy adults | 7 (Cochrane, MEDLINE, MEDLINE In-Process, Embase, CAB Abstracts, WoS, BIOSIS) | 6 | T2DM |
| Cheungpasitporn et al. (2015) [ |
NA | ~2015.01 | NA | Adults, adolescents | 3 (MEDLINE, Embase, Cochrane) | 8 | Hypertension |
| Imamura et al. (2015) [ |
NA | ~2014.02 | 3.4–21.1 | Healthy adults | 4 (PubMed, Embase, Ovid, Web of knowledge) | 21 | T2DM |
| Narian et al. (2016) [ |
NA | ~2015.07 | NA | Adults | 2 (MEDLINE, Embase) | 9 | CVD, All-cause mortality |
| Narian et al. (2017) [ |
NA | ~2015.07 | NA | Adults, adolescents, children | 2 (MEDLINE, Embase) | 12 | Metabolic Syndrome |
| Ruanpeng et al. (2017) [ |
NA | ~2015.05 | NA | Adults, adolescents | 3 (Embase, MEDLINE, Cochrane) | 13 | Obesity |
| Qin et al. (2020) [ |
NA | ~2019.09 | 6.8–19.7 | Healthy (18+) | 4 (PubMed, Embase, WoS, Open Grey) | 4–18 | All-cause mortality, T2DM, hypertension, obesity |
| Meng et al. (2021) [ |
NA | ~2020.6.20 | 5.5–34 | Healthy (18–79) | 3 (PubMed, Embase, and Ovid) | 8–17 | All-cause mortality, CVD, T2DM |
| Yin et al. (2021) [ |
PROSPERO CRD42019137454 | ~2019.12 | 9.8–28 | Healthy (35–75) | 2 (PubMed, Embase) | 4–10 | CVD mortality, CVD |
| Zhang et al. (2021) [ |
NA | ~2019.11.04 | NA | Adults, adolescents, children | 3 (PubMed, WoS, and Embase) | 4–16 | Metabolic syndrome |
| Zhang et al. (2021) [ |
NA | ~2020.03 | 5.9–31 | All adults (mean 42.8–74) | 7 (PubMed, Embase, WoS, Cochrane, ProQuest, |
2–10 | All-cause mortality, CVD mortality, cancer mortality |
| Bhagavathula et al. (2022) [ |
NA | ~2021.07.31 | 3–28 (mean 12.2) | Healthy (mean 55.6) | 3 (PubMed, WoS, Embase) | 4–5 | CVD mortality |
| Li et al. (2022) [ |
PROSPERO CRD 42019140581 | ~2020.01.01 | NA | Healthy adults | 4 (PubMed, Embase, WoS, Cochrane) | 14 | All-cause mortality, CVD mortality, cancer mortality |
| Pan et al. (2022) [ |
PROSPERO CRD42020152223 | ~2020.09.21 | 11–22 | Healthy (47–74) | 5 (PubMed, Embase, WoS, Cochranme, PsycINFO) | 4–11 | All-cause mortality, CVD mortality, cancer mortality |
| Taneri et al. (2022) [ |
PROSPERO CRD42020151201 | ~2021.01.29 | 11.6–28 | Healthy adults | 5 (MEDLINE, Embase, WoS, Cochrane, Google Scholar) | 3–12 | All-cause mortality |
| Yang et al. (2022) [ |
PROSPERO CRD4202020068 | ~2021.02.09 | 6–34 | Healthy (20+) | 2 (Embase, Ovid) | 2–12 | CVD mortality, CVD |
| Li et al. (2023) [ |
PROSPERO CRD42022307003 | ~2022.12 | 4–38 | Healthy (18+) | 4 (PubMed, Embase, WoS, Cochrane) | 3–17 | All-cause mortality, T2DM, Hypertension |
| Bhandari et al. (2024) [ |
PROSPERO CRD42020214679 | ~2023.12 | 18.5–34 | Healthy (30–75) | 5 (MEDLINE, Embase, CINAHL, WoS, Scopus) | 2 | CVD mortality |
| Ding et al. (2024) [ |
NA | ~2023.03 | NA | T2DM (18+) | 4 (PubMed, Embase, WoS, Cochrane) | 1–3 | All-cause mortality |
| Zhao et al. (2024) [ |
PROSPERO CRD42021259128 | ~2021.02.02 | NA | Adults, adolescents, children | 3 (PubMed, Embase, and WoS) | 23 | Hypertension |
The basis for the assumed mean change is the average change from baseline in the control (SSBs) group across studies. The corresponding mean difference (and its 95% CI) reflects the estimated effect of replacing SSBs with ASBs, given the assumed mean change in the comparison group. Some trials had unclear allocation concealment or blinding, which may affect the certainty of evidence (downgraded one level for risk of bias). Visual inspection of the funnel plot did not suggest substantial publication bias. ASB, artificially sweetened beverage; SSB, sugar-sweetened beverage; RCT, randomized controlled trial; CI, confidence interval; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; MA, meta-analysis; RoB, risk of bias; HbA1c, glycosylated hemoglobin; HOMA-IR, homeostatic model assessment of insulin resistance; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol. GRADE Working Group grades of evidence: High quality (Further research is very unlikely to change our confidence in the estimate of effect); Moderate quality (Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate); Low quality (Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate); Very low quality (We are very uncertain about the estimate).
The basis for the estimated effect sizes (minimum and maximum risk ratios from the included systematic reviews) reflects the association between higher intake of SSBs or ASBs and various health outcomes, compared with lower intake or non-consumers, based on prospective cohort studies. All included systematic reviews/meta-analyses were derived from NRS, which start at a low level of certainty in the GRADE approach. Certainty of evidence was further downgraded for risk of bias (confounding, lack of protocol registration, incomplete adjustment), inconsistency (heterogeneity across studies), and imprecision (wide or borderline confidence intervals). For SSBs and type 2 diabetes mellitus incidence, the certainty was upgraded by one level due to consistent evidence of a dose-response relationship (per serving/day increase associated with higher risk). No upgrading was applied for ASBs outcomes due to lack of consistent dose-response evidence. SSB, sugar-sweetened beverage; ASB, artificially sweetened beverage; NRS, non-randomized study; SR, systematic review; MA, meta-analysis; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; RoB, risk of bias; CVD, cardiovascular disease. GRADE Working Group grades of evidence: High quality (Further research is very unlikely to change our confidence in the estimate of effect); Moderate quality (Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate); Low quality (Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate); Very low quality (We are very uncertain about the estimate).
BMI, body mass index; ASB, artificially sweetened beverage; SSB, sugar-sweetened beverage; RCT, randomized controlled trial; NA, not available; CTRI, Clinical Trials Registry–India.
NA, not available; WoS, Web of Science; T2DM, type 2 diabetes mellitus; CVD, cardiovascular disease; PROSPERO, International Prospective Register of Systematic Reviews; CINAHL, Cumulative Index to Nursing and Allied Health Literature.
