High versus low-added sugar consumption for the primary prevention of cardiovascular disease

Abstract

Background: High intake of added sugar have been suggested to impact the risk for cardiovascular disease (CVD). Knowledge on the subject can contribute to preventing CVD.

Objectives: To assess the effects of a high versus low-added sugar consumption for primary prevention of CVD in the general population.

Search methods: We searched Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) on 2 July 2021. We also conducted a search of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) Search Portal for ongoing or unpublished trials. The search was performed together with reference checking, citation searching and contact with study authors to identify additional studies. We imposed no restriction on language of publication or publication status.

Selection criteria: We included randomised controlled trials (RCTs), including cross-over trials, that compared different levels of added sugar intake. Exclusion criteria were: participants aged below 18 years; diabetes mellitus (type 1 and 2); and previous CVD. Primary outcomes were incident cardiovascular events (coronary, carotid, cerebral and peripheral arterial disease) and all-cause mortality. Secondary outcomes were changes in systolic and diastolic blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting plasma glucose and adverse events (gastrointestinal symptoms and impaired dental health).

Data collection and analysis: We used the standard methodological procedures expected by Cochrane.

Main results: We included 21 RCTs (1110 participants completing the interventions) examining the effects of different levels of added sugar intake with a mean duration of 14 weeks. The study participants were generally described as healthy and the mean age ranged from 22 to 57 years. No studies reported on cardiovascular events or all-cause mortality. There was minimal effect of low intake of added sugar on total cholesterol levels (MD 0.11, 95% CI 0.01 to 0.21; I² = 0%; 16 studies; 763 participants; low certainty of evidence) and triglycerides (MD 0.10, 95% CI 0.03 to 0.17; I² = 3%; 14 studies; 725 participants) but no evidence of effect on LDL-cholesterol and HDL-cholesterol. There was minimal effect on diastolic blood pressure (MD 1.52, 95% CI 0.67 to 2.37; I² = 0%; 13 studies; 873 participants) and on systolic blood pressure (MD 1.44, 95% 0.08 to 2.80; I² = 27%, 14 studies; 873 participants; low certainty of evidence), but no evidence of effect on fasting plasma glucose. Only one study reported on dental health, with no events. No other trials reported adverse events (impaired dental health or gastrointestinal symptoms). All results were judged as low-quality evidence according to GRADE. The risk of bias was generally unclear, five studies were classified at an overall low risk of bias (low risk in at least four domains, not including other bias).

Authors' conclusions: No trials investigating the effect of added sugar on cardiovascular events or all-cause mortality were identified in our searches. Evidence is uncertain whether low intake of added sugar has an effect on risk factors for CVD; the effect was small and the clinical relevance is, therefore, uncertain. Practical ways to achieve reductions in dietary added sugar includes following current dietary recommendations. Future trials should have longer follow-up time and report on all-cause mortality and cardiovascular events in order to clarify the effect of added sugar on these outcomes. Future trials should also aim for more direct interventions and preferably be more independent of industry funding.

Trial registration: ClinicalTrials.gov NCT03679689 NCT03574987 NCT02548767 NCT03543644 NCT03259685.

Conflict of interest statement

Sara Bergwall has declared that she has no conflicts of interest.

Anna Johansson reports to work as a health professional related to the topic area of this review.

Emily Sonestedt has declared that she has no conflicts of interest.

Stefan Acosta has declared that he has no conflicts of interest.

Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Figures

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Figure 1. Study flow diagram

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Figure 2. Risk of bias summary: review authors' judgment about each risk of bias domain for each included study.

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Figure 3. Risk of bias graph: review authors' judgements about each risk of bias domain presented as percentages across all included studies.

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Figure 4: Funnel plot for studies that reported total cholesterol.

1.1. Analysis

Comparison 1: Effects of high vs low‐added sugar consumption, Outcome 1: Systolic blood pressure (mmHg)

1.2. Analysis

Comparison 1: Effects of high vs low‐added sugar consumption, Outcome 2: Diastolic blood pressure (mmHg)

1.3. Analysis

Comparison 1: Effects of high vs low‐added sugar consumption, Outcome 3: Total cholesterol (mmol/L)

1.4. Analysis

Comparison 1: Effects of high vs low‐added sugar consumption, Outcome 4: LDL‐cholesterol (mmol/L)

1.5. Analysis

Comparison 1: Effects of high vs low‐added sugar consumption, Outcome 5: HDL‐cholesterol (mmol/L)

1.6. Analysis

Comparison 1: Effects of high vs low‐added sugar consumption, Outcome 6: Triglycerides (mmol/L)

1.7. Analysis

Comparison 1: Effects of high vs low‐added sugar consumption, Outcome 7: Fasting plasma glucose (mmol/L)

2.1. Analysis

Comparison 2: Subgroup analysis ‐ Isocaloric intake or ad libitum, Outcome 1: Systolic blood pressure (mmHg)

2.2. Analysis

Comparison 2: Subgroup analysis ‐ Isocaloric intake or ad libitum, Outcome 2: Diastolic blood pressure (mmHg)

2.3. Analysis

Comparison 2: Subgroup analysis ‐ Isocaloric intake or ad libitum, Outcome 3: Total cholesterol (mmol/L)

2.4. Analysis

Comparison 2: Subgroup analysis ‐ Isocaloric intake or ad libitum, Outcome 4: LDL‐cholesterol (mmol/L)

2.5. Analysis

Comparison 2: Subgroup analysis ‐ Isocaloric intake or ad libitum, Outcome 5: HDL‐cholesterol (mmol/L)

2.6. Analysis

Comparison 2: Subgroup analysis ‐ Isocaloric intake or ad libitum, Outcome 6: Triglycerides (mmol/L)

2.7. Analysis

Comparison 2: Subgroup analysis ‐ Isocaloric intake or ad libitum, Outcome 7: Fasting plasma glucose (mmol/L)

3.1. Analysis

Comparison 3: Subgroup analysis ‐ Solid and liquid or liquid state, Outcome 1: Systolic blood pressure (mmHg)

3.2. Analysis

Comparison 3: Subgroup analysis ‐ Solid and liquid or liquid state, Outcome 2: Diastolic blood pressure (mmHg)

3.3. Analysis

Comparison 3: Subgroup analysis ‐ Solid and liquid or liquid state, Outcome 3: Total cholesterol (mmol/L)

3.4. Analysis

Comparison 3: Subgroup analysis ‐ Solid and liquid or liquid state, Outcome 4: LDL‐cholesterol (mmol/L)

3.5. Analysis

Comparison 3: Subgroup analysis ‐ Solid and liquid or liquid state, Outcome 5: HDL‐cholesterol (mmol/L)

3.6. Analysis

Comparison 3: Subgroup analysis ‐ Solid and liquid or liquid state, Outcome 6: Triglycerides (mmol/L)

3.7. Analysis

Comparison 3: Subgroup analysis ‐ Solid and liquid or liquid state, Outcome 7: Fasting plasma glucose (mmol/L)

4.1. Analysis

Comparison 4: Subgroup analysis ‐ Difference in weight change, Outcome 1: Systolic blood pressure (mmHg)

4.2. Analysis

Comparison 4: Subgroup analysis ‐ Difference in weight change, Outcome 2: Diastolic blood pressure (mmHg)

4.3. Analysis

Comparison 4: Subgroup analysis ‐ Difference in weight change, Outcome 3: Total cholesterol (mmol/L)

4.4. Analysis

Comparison 4: Subgroup analysis ‐ Difference in weight change, Outcome 4: LDL‐cholesterol (mmol/L)

4.5. Analysis

Comparison 4: Subgroup analysis ‐ Difference in weight change, Outcome 5: HDL‐cholesterol (mmol/L)

4.6. Analysis

Comparison 4: Subgroup analysis ‐ Difference in weight change, Outcome 6: Triglycerides (mmol/L)

4.7. Analysis

Comparison 4: Subgroup analysis ‐ Difference in weight change, Outcome 7: Fasting plasma glucose (mmol/L)

5.1. Analysis

Comparison 5: Subgroup analysis ‐ Healthy or high risk population, Outcome 1: Systolic blood pressure (mmHg)

5.2. Analysis

Comparison 5: Subgroup analysis ‐ Healthy or high risk population, Outcome 2: Diastolic blood pressure (mmHg)

5.3. Analysis

Comparison 5: Subgroup analysis ‐ Healthy or high risk population, Outcome 3: Total cholesterol (mmol/L)

5.4. Analysis

Comparison 5: Subgroup analysis ‐ Healthy or high risk population, Outcome 4: LDL‐cholesterol (mmol/L)

5.5. Analysis

Comparison 5: Subgroup analysis ‐ Healthy or high risk population, Outcome 5: HDL‐cholesterol (mmol/L)

5.6. Analysis

Comparison 5: Subgroup analysis ‐ Healthy or high risk population, Outcome 6: Triglycerides (mmol/L)

5.7. Analysis

Comparison 5: Subgroup analysis ‐ Healthy or high risk population, Outcome 7: Fasting plasma glucose (mmol/L)

6.1. Analysis

Comparison 6: Subgroup analysis ‐ Intervention

6.2. Analysis

Comparison 6: Subgroup analysis ‐ Intervention

6.3. Analysis

Comparison 6: Subgroup analysis ‐ Intervention

6.4. Analysis

Comparison 6: Subgroup analysis ‐ Intervention

6.5. Analysis

Comparison 6: Subgroup analysis ‐ Intervention

6.6. Analysis

Comparison 6: Subgroup analysis ‐ Intervention

6.7. Analysis

Comparison 6: Subgroup analysis ‐ Intervention

7.1. Analysis

Comparison 7: Subgroup analysis ‐ Industry funding, Outcome 1: Systolic blood pressure (mmHg)

7.2. Analysis

Comparison 7: Subgroup analysis ‐ Industry funding, Outcome 2: Diastolic blood pressure (mmHg)

7.3. Analysis

Comparison 7: Subgroup analysis ‐ Industry funding, Outcome 3: Total cholesterol (mmol/L)

7.4. Analysis

Comparison 7: Subgroup analysis ‐ Industry funding, Outcome 4: LDL‐cholesterol (mmol/L)

7.5. Analysis

Comparison 7: Subgroup analysis ‐ Industry funding, Outcome 5: HDL‐cholesterol (mmol/L)

7.6. Analysis

Comparison 7: Subgroup analysis ‐ Industry funding, Outcome 6: Triglycerides (mmol/L)

7.7. Analysis

Comparison 7: Subgroup analysis ‐ Industry funding, Outcome 7: Fasting plasma glucose (mmol/L)

8.1. Analysis

Comparison 8: Sensitivity analysis ‐ Low risk of bias, Outcome 1: Systolic blood pressure (mmHg)

8.2. Analysis

Comparison 8: Sensitivity analysis ‐ Low risk of bias, Outcome 2: Diastolic blood pressure (mmHg)

8.3. Analysis

Comparison 8: Sensitivity analysis ‐ Low risk of bias, Outcome 3: Total cholesterol (mmol/L)

8.4. Analysis

Comparison 8: Sensitivity analysis ‐ Low risk of bias, Outcome 4: LDL‐cholesterol (mmol/L)

8.5. Analysis

Comparison 8: Sensitivity analysis ‐ Low risk of bias, Outcome 5: HDL‐cholesterol (mmol/L)

8.6. Analysis

Comparison 8: Sensitivity analysis ‐ Low risk of bias, Outcome 6: Triglycerides (mmol/L)

8.7. Analysis

Comparison 8: Sensitivity analysis ‐ Low risk of bias, Outcome 7: Fasting plasma glucose (mmol/L)

9.1. Analysis

Comparison 9: Sensitivity analysis ‐ Cross‐overs excluded, Outcome 1: Systolic blood pressure (mmHg)

9.2. Analysis

Comparison 9: Sensitivity analysis ‐ Cross‐overs excluded, Outcome 2: Diastolic blood pressure (mmHg)

9.3. Analysis

Comparison 9: Sensitivity analysis ‐ Cross‐overs excluded, Outcome 3: Total cholesterol (mmol/L)

9.4. Analysis

Comparison 9: Sensitivity analysis ‐ Cross‐overs excluded, Outcome 4: LDL‐cholesterol (mmol/L)

9.5. Analysis

Comparison 9: Sensitivity analysis ‐ Cross‐overs excluded, Outcome 5: HDL‐cholesterol (mmol/L)

9.6. Analysis

Comparison 9: Sensitivity analysis ‐ Cross‐overs excluded, Outcome 6: Triglycerides (mmol/L)

9.7. Analysis

Comparison 9: Sensitivity analysis ‐ Cross‐overs excluded, Outcome 7: Fasting plasma glucose (mmol/L)