Low/no calorie sweeteners and cardiovascular health: What does the evidence say?

Highlights:

  • The burden of cardiovascular disease is rising sharply. Global prevalence has nearly doubled in the past 30 years and is projected to increase by a further 90% by 2050, underscoring the need for healthier dietary patterns, including lower sugar intake.
  • Low/no calorie sweeteners show neutral effects on cardiometabolic risk markers. The latest systematic reviews and meta-analyses of human clinical studies confirm no significant impact on blood cholesterol, triglycerides, glycaemia, blood pressure, or liver enzymes.
  • When used as sugar substitutes, particularly in beverages, low/no calorie sweeteners can contribute to modest reductions in body weight, fat mass, liver fat, and post-prandial glucose, changes that collectively support heart health.

Cardiovascular disease (CVD) remains a leading global health challenge1, with its prevalence nearly doubling over the past three decades and projected to rise by a further 90% between 2025 and 2050.2 Given this staggering global burden, dietary strategies to mitigate cardiovascular risk, including sugar reduction, are more critical than ever.

Low/no calorie sweeteners (LNCS) have become increasingly popular as alternatives to sugar. They provide a sweet taste with little to no calories, making them a useful dietary tool for reducing sugar intake.3 However, their impact on heart health remains controversial.

Excess sugar intake and cardiovascular risk

Abnormal blood lipids, such as high total cholesterol, elevated low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), and high triglycerides, hypertension, increased body weight and abnormal glucose control are all major risk factors for CVD, including heart attack and stroke. Reducing added sugar is widely recommended for improving cardiometabolic health, and many turn to LNCS as sugar substitutes. But how do LNCS affect cardiometabolic risk?

Sweeteners and cardiometabolic risk: Findings from the latest systematic reviews

The role of LNCS in cardiometabolic health has been extensively studied. Systematic reviews and meta-analyses of randomised controlled trials (RCTs), including a review by the World Health Organization (WHO)4, consistently demonstrate a neutral effect of LNCS on key intermediate CVD markers, such as blood lipids5, glucose control6,7, blood pressure8 and liver enzymes9.

The most recent systematic review and meta-analysis by Najafi et al. (2025) pooled evidence from 28 RCTs involving adults worldwide.10 The aim was to determine whether LNCS influence key lipid markers linked to CVD. Results confirmed previous findings supporting that LNCS do not affect blood lipid levels in adults. No significant effect was observed for total cholesterol, LDL-C, HDL-C, VLDV-C, and serum triglycerides.

Notably, LNCS have also shown modest benefits in reducing liver fat, fat mass, and body weight, particularly when they replace sugars in beverages.11 In addition, it is well established that, compared to sugars, LNCS cause a lower blood glucose rise after consumption.12 This evidence reinforces that LNCS, when used as sugar substitutes, may confer modest advantages in cardiometabolic risk reduction.3

Is epidemiological evidence conflicting?

While human intervention studies consistently show neutral or modestly beneficial effects of LNCS, findings from observational studies are more mixed. Traditional cohort analyses, which often rely on single baseline dietary assessments, suggest that higher LNCS intake may be linked with increased risk of CVD. However, more recent and methodologically robust prospective cohort studies using repeated dietary measures and substitution analyses report neutral or even protective associations, in line with evidence from RCTs.3

A systematic review of 14 such cohort studies found that increases in LNCS intake were linked to lower body weight and waist circumference, with no adverse effects on type 2 diabetes.13 Importantly, substituting sugar-sweetened beverages with LNCS beverages was associated with a lower risk of obesity, coronary heart disease, and total and CVD mortality, again without evidence of harm to cardiometabolic health.

What does this mean for heart health?

Taken together, the evidence suggests that LNCS are metabolically neutral with respect to cardiovascular risk factors (lipid profile, blood pressure, and glucose control), and have modest benefits associated with small reductions in body weight, fat mass, and liver fat, and lower post-prandial glycaemia when used as substitutes for sugars, particularly in beverages.3

For health professionals, this means that while they may not provide direct cardiovascular benefits, LNCS can help patients reduce free sugar intake, supporting weight management and glucose control, and ultimately heart health, when used as part of a healthy diet and overall lifestyle.

  1. World Heart Day 2025. Available at: https://world-heart-federation.org/world-heart-day/
  2. Chong B, Jayabaskaran J, Jauhari SM, et al. Global burden of cardiovascular diseases: projections from 2025 to 2050. Eur J Prev Cardiol. 2025 Aug 25;32(11):1001-1015. doi: 10.1093/eurjpc/zwae281
  3. Sievenpiper JL, Purkayastha S, Grotz VL, et al. Dietary Guidance, Sensory, Health and Safety Considerations When Choosing Low and No-Calorie Sweeteners. Nutrients. 2025 Feb 25;17(5):793. doi: 10.3390/nu17050793
  4. Rios-Leyvraz M, Montez J. Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis. World Health Organization (WHO) 2022. https://apps.who.int/ iris/handle/10665/353064 License: CC BY-NC-SA 3.0 IGO
  5. Movahedian M, Golzan SA, Ashtary-Larky D, Clark CCT, Asbaghi O, Hekmatdoost A. The effects of artificial- and stevia-based sweeteners on lipid profile in adults: a GRADE-assessed systematic review, meta-analysis, and meta-regression of randomised clinical trials. Crit Rev Food Sci Nutr. 2023;63(21):5063-5079. doi: 10.1080/10408398.2021.2012641
  6. Greyling A, Appleton KM, Raben A, Mela DJ. Acute glycemic and insulinemic effects of low-energy sweeteners: a systematic review and meta-analysis of randomised controlled trials. Am J Clin Nutr. 2020;112(4):1002-1014
  7. Zhang R, Noronha JC, Khan TA, et al. The Effect of Non-Nutritive Sweetened Beverages on Postprandial Glycemic and Endocrine Responses: A Systematic Review and Network Meta-Analysis. 2023;15(4):1050
  8. Pham H, Phillips LK, Jones KL. Acute Effects of Nutritive and Non-Nutritive Sweeteners on Postprandial Blood Pressure. 2019;11(8):1717
  9. Golzan SA, Movahedian M, Haghighat N, et al. Association between non-nutritive sweetener consumption and liver enzyme levels in adults: a systematic review and meta-analysis of randomised clinical trials. Nutr Rev. 2023;81(9):1105-1117
  10. Najafi A, Moghtaderi F, Seyedjafari B, et al. The effects of non-nutritive sweeteners on lipid profile in adults: a systematic review and meta-analysis of randomized controlled clinical trials. Sci Rep. 2025 Jul 1;15(1):21106. doi: 10.1038/s41598-025-00612-3
  11. McGlynn ND, Khan TA, Wang L, et al. Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-analysis. JAMA Netw Open 2022;5(3):e222092
  12. EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to intense sweeteners. EFSA Journal. 2011;9(6):2229. [26 pp.]. Available at: https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2011.2229
  13. Lee JJ, Khan TA, McGlynn N, et al. Relation of Change or Substitution of Low- and No-Calorie Sweetened Beverages With Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Prospective Cohort Studies. Diabetes Care. 2022;45(8):1917-1930.
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