Artificial sweeteners & cardiovascular disease
| Educator
11th Oct, 2022Quick read


Artificial sweetener intake has been associated with an increased risk of cardiovascular disease (CVD) in a recent large-scale, prospective study (1). Total artificial sweetener intake from all sources, including beverages, tabletop sweeteners and dairy products, was associated with an overall increased risk of CVD and cerebrovascular disease  (1). Aspartame intake was associated with an increased risk of cerebrovascular events, while acesulfame potassium and sucralose were associated with increased coronary heart disease risk.

Artificial sweeteners are present in thousands of food and beverage brands worldwide, especially ultra-processed foods such as artificially sweetened beverages, snacks, and low-calorie ready-to-go meals or dairy products. Artificial sweeteners are also directly used by consumers as tabletop sweeteners instead of sugar. The amount of non-nutritive sweeteners in packaged foods and drinks has grown significantly over the last decade (2). However, their use remains controversial, and they are being reevaluated by the European Food Safety Authority (3), the World Health Organization (WHO) (4), and other health agencies.


Table 1. Commonly used artificial sweeteners in Australia (5)


Additive Number

Brand names



Equal®, Equal Spoonful®, Hermesetas®, Nutrasweet®

Acesulfame potassium (aka acesulfame K)


Hermesetas®, Sunnett®












Sweet 'N Low, Sucaryl®, Sugarella®, Sugarine®, Sweetex®



Splenda®, Hermesetas®


Cardiovascular diseases (CVDs) are the leading cause of death worldwide (6). The impact of artificial sweetener intake on hard endpoints such as CVD risk cannot be assessed directly through randomised controlled trials for ethical reasons. Observational prospective studies have used artificially sweetened beverage consumption (millilitres (mL) or servings/day) as a proxy for indirectly investigating the association between artificial sweetener intake (mg/day) and CVD risk, with conflicting results (7,8,9,10,11). Systematic reviews and meta-analyses have suggested direct associations between artificially sweetened beverages and CVD risk (12,13). A WHO 2022 report on the health effects of artificial sweeteners observed associations between consumption of beverages with artificial sweeteners (used as a proxy) and some intermediate markers of CVD (4), including a modest increase in the unfavourable total cholesterol to HDL cholesterol ratio, and an increased risk of hypertension. The report also identified an increase in CVD mortality, and the incidence of cardiovascular events and strokes associated with a greater intake of soft drinks containing artificial sweeteners. However, prospective studies remain limited, and the evidence for these associations is still considered low by WHO (4). Artificially sweetened beverages only represent part of the total artificial sweetener intake, therefore it is crucial to consider all dietary sources in causal studies.

The current study used quantitative data to investigate the associations between consumption of artificial sweeteners (mg/day) from all dietary sources (beverages, tabletop sweeteners, dairy products, etc.), overall intake, and type (aspartame, acesulfame potassium, and sucralose), and risk of CVD (overall, coronary, and cerebrovascular). Just over half of the artificial sweetener intake in the study came from drinks, with the rest coming from tabletop sweeteners and foods (1).

The large-scale study included 103,388 French adults from the NutriNet-Sante cohort, with an average age of 42 years. The majority of the participants were females (79.8%). A total of 37.1% of participants reported consumption of artificial sweeteners. The sweeteners assessed were mainly aspartame (58% of sweetener intake), acesulfame potassium (29%), and sucralose (10%), with the other 3% made up of various other sweeteners including cyclamates and saccharin.

Over an average nine year follow-up, artificial sweetener intake was associated with a 9% overall increased risk of cardiovascular events and an 18% increased risk of cerebrovascular events. Cardiovascular and cerebrovascular events included myocardial infarction, acute coronary syndrome, angioplasty, angina, stroke, and transient ischemic attack. Aspartame intake was associated with a 17% increased risk for cerebrovascular events, while acesulfame potassium and sucralose were associated with a 40% increased risk for CVDs.

The average intake of artificial sweeteners among those who reported consuming them was 42.46 mg/day, corresponding to approximately one individual packet of tabletop sweetener or 100 mL of diet soda. A dose-effect association was observed, with a higher risk of cardiovascular events with higher consumption. Higher consumption in this study was a mean of 77 mg/day of artificial sweetener, which corresponds to approximately 200 mL of diet soda.


Potential underlying mechanisms

Various early markers of and risk factors for cardiovascular health have been investigated in relation to the consumption of artificial sweeteners or artificially sweetened beverages.

  • Prospective cohort studies have reported associations between artificially sweetened beverage consumption and increased risk of obesity or weight gain (4,7,14,15); however, the impact of artificial sweeteners on weight gain is debated (4,7,8).
  • Artificially sweetened beverages were associated with an increased risk of metabolic syndrome in various study designs (16,17,18,19), including a multicentre randomised trial. Associations were observed with increased hypertension (4,20,21), type 2 diabetes, (4,22,23) and hypertriglyceridemia (4,18).
  • Vascular dysfunction, which contributes to CVD onset and development, has been observed after the ingestion of artificial sweeteners in experimental studies (24,25).
  • Artificial sweetener consumption might be associated with increased inflammation, a risk factor for CVD (26).
  • Gut microbiota perturbation in association with consumption of artificial sweeteners or artificially sweetened beverages (27,28,29,30) could increase glucose intolerance (27), but the results remain conflicting (30).
  • Artificial sweeteners interact with intestinal sweet taste receptors (31), which play a part in insulin secretion and glucose absorption.

Most studies suggest adverse effects, and few suggested neutral or beneficial properties of artificial sweeteners (32,33,34,35). Although study results are mixed, the literature generally supports a potential involvement of artificial sweeteners in cardiovascular health, with plausible mechanisms (7,8,36).

It is worth noting that different types of artificial sweeteners might not have the same metabolic effects (26). For example, acesulfame potassium is absorbed from the small intestine and distributed to the blood and tissues through the systemic circulation before being excreted in urine. Sucralose passes through digestion and is almost entirely excreted in the stools, therefore, only a small part is absorbed from the gastrointestinal tract. The aspartame molecule is broken down into different amino acids: aspartic acid and phenylalanine are sent to the systemic circulation, while methanol is metabolised by the liver (26). These differences might partly explain conflicting results in the literature.



While this study has many strengths, it cannot on its own prove a causal relationship between artificial sweetener intake and increased cardiovascular risk. Dietary studies, which rely on self-reporting of food and drink intake, are always hard to interpret. This study used a more reliable dietary assessment method, with repeated 24-hour dietary records validated by interviews with a trained dietitian and against blood and urinary biomarkers. Models were adjusted for a wide range of potential sociodemographic, anthropometric, dietary, and lifestyle confounders. However, the high risk of residual confounding from behaviour modification and reverse causality cannot be ruled out: individuals who are at risk for CVD might consume artificial sweeteners as a strategy to mitigate this risk.

Nonetheless, this study finds an important and statistically significant association which shows robustness in all models after adjusting for many other possible confounding factors. The insight that artificial sweeteners may be implicated in cardiovascular and cerebrovascular disease s would suggest limiting their intake until conclusive evidence of their benefit or harm is available.

1Debras C, Chazelas E, Sellem L, Porcher R, Druesne-Pecollo N, Esseddik Y, et al. Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort. BMJ. 2022 Sep 7;378:e071204.
2Russell C, Baker P, Grimes C, Lindberg R, Lawrence MA. Global trends in added sugars and non-nutritive sweetener use in the packaged food supply: drivers and implications for public health. Public Health Nutr. 2022 Jul 28;1–13.
3European Food Safety Authority (EFSA). Outcome of the public consultation on a draft protocol for assessing exposure to sweeteners as part of their safety assessment under the food additives re-evaluation programme. EFSA Supporting Publications. 2020;17(8):1913E.
4Rios-Leyvraz M, Montez J, World Health Organization. Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis [Internet]. 2022 [cited 2022 Sep 26]. Available from:
5NSW Ministry of Health. Sweeteners (sugar alternatives) [Internet]. NSW Government; 2020 [cited 2022 Sep 26]. Available from:
6Joseph P, Leong D, McKee M, Anand SS, Schwalm JD, Teo K, et al. Reducing the Global Burden of Cardiovascular Disease, Part 1: The Epidemiology and Risk Factors. Circ Res. 2017 Sep 1;121(6):677–94.
7Azad MB, Abou-Setta AM, Chauhan BF, Rabbani R, Lys J, Copstein L, et al. Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. CMAJ. 2017 Jul 17;189(28):E929–39.
8Toews I, Lohner S, Küllenberg de Gaudry D, Sommer H, Meerpohl JJ. Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies. BMJ. 2019 Jan 2;364:k4718.
9Hinkle SN, Rawal S, Bjerregaard AA, Halldorsson TI, Li M, Ley SH, et al. A prospective study of artificially sweetened beverage intake and cardiometabolic health among women at high risk. Am J Clin Nutr. 2019 Jul 1;110(1):221–32.
10Mullee A, Romaguera D, Pearson-Stuttard J, Viallon V, Stepien M, Freisling H, et al. Association Between Soft Drink Consumption and Mortality in 10 European Countries. JAMA Intern Med. 2019 Nov 1;179(11):1479–90.
11Chazelas E, Debras C, Srour B, Fezeu LK, Julia C, Hercberg S, et al. Sugary Drinks, Artificially-Sweetened Beverages, and Cardiovascular Disease in the NutriNet-Santé Cohort. J Am Coll Cardiol. 2020 Nov 3;76(18):2175–7
12Meng Y, Li S, Khan J, Dai Z, Li C, Hu X, et al. Sugar- and Artificially Sweetened Beverages Consumption Linked to Type 2 Diabetes, Cardiovascular Diseases, and All-Cause Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies. Nutrients. 2021 Jul 30;13(8):2636.
13Yin J, Zhu Y, Malik V, Li X, Peng X, Zhang FF, et al. Intake of Sugar-Sweetened and Low-Calorie Sweetened Beverages and Risk of Cardiovascular Disease: A Meta-Analysis and Systematic Review. Adv Nutr. 2021 Feb 1;12(1):89–101.
14Miller PE, Perez V. Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies. Am J Clin Nutr. 2014 Sep;100(3):765–77.
15Qin P, Li Q, Zhao Y, Chen Q, Sun X, Liu Y, et al. Sugar and artificially sweetened beverages and risk of obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies. Eur J Epidemiol. 2020 Jul;35(7):655–71.
16Narain A, Kwok CS, Mamas MA. Soft drink intake and the risk of metabolic syndrome: A systematic review and meta-analysis. Int J Clin Pract. 2017 Feb;71(2).
17Zhang X, Li X, Liu L, Hong F, Zhao H, Chen L, et al. Dose-response association between sugar- and artificially sweetened beverage consumption and the risk of metabolic syndrome: a meta-analysis of population-based epidemiological studies. Public Health Nutr. 2021 Aug;24(12):3892–904.
18Ferreira-Pêgo C, Babio N, Bes-Rastrollo M, Corella D, Estruch R, Ros E, et al. Frequent Consumption of Sugar- and Artificially Sweetened Beverages and Natural and Bottled Fruit Juices Is Associated with an Increased Risk of Metabolic Syndrome in a Mediterranean Population at High Cardiovascular Disease Risk. J Nutr. 2016 Aug;146(8):1528–36.
19Crichton G, Alkerwi A, Elias M. Diet Soft Drink Consumption is Associated with the Metabolic Syndrome: A Two Sample Comparison. Nutrients. 2015 May 13;7(5):3569–86.
20Cohen L, Curhan G, Forman J. Association of sweetened beverage intake with incident hypertension. J Gen Intern Med. 2012 Sep;27(9):1127–34.
21Kim Y, Je Y. Prospective association of sugar-sweetened and artificially sweetened beverage intake with risk of hypertension. Arch Cardiovasc Dis. 2016 Apr;109(4):242–53.
22Drewnowski A, Rehm CD. The use of low-calorie sweeteners is associated with self-reported prior intent to lose weight in a representative sample of US adults. Nutr Diabetes. 2016 Mar 7;6:e202.
23Fagherazzi G, Gusto G, Affret A, Mancini FR, Dow C, Balkau B, et al. Chronic Consumption of Artificial Sweetener in Packets or Tablets and Type 2 Diabetes Risk: Evidence from the E3N-European Prospective Investigation into Cancer and Nutrition Study. Ann Nutr Metab. 2017;70(1):51–8.
24Risdon S, Meyer G, Marziou A, Riva C, Roustit M, Walther G. Artificial sweeteners impair endothelial vascular reactivity: Preliminary results in rodents. Nutr Metab Cardiovasc Dis. 2020 May 7;30(5):843–6.
25Jang W, Jeoung NH, Cho KH. Modified apolipoprotein (apo) A-I by artificial sweetener causes severe premature cellular senescence and atherosclerosis with impairment of functional and structural properties of apoA-I in lipid-free and lipid-bound state. Mol Cells. 2011 May;31(5):461–70.
26Basson AR, Rodriguez-Palacios A, Cominelli F. Artificial Sweeteners: History and New Concepts on Inflammation. Front Nutr. 2021;8:746247.
27Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181–6.
28Suez J, Korem T, Zilberman-Schapira G, Segal E, Elinav E. Non-caloric artificial sweeteners and the microbiome: findings and challenges. Gut Microbes. 2015;6(2):149–55.
29Ruiz-Ojeda FJ, Plaza-Díaz J, Sáez-Lara MJ, Gil A. Effects of Sweeteners on the Gut Microbiota: A Review of Experimental Studies and Clinical Trials. Adv Nutr. 2019 Jan;10(Suppl 1):S31–48.
30Plaza-Diaz J, Pastor-Villaescusa B, Rueda-Robles A, Abadia-Molina F, Ruiz-Ojeda FJ. Plausible Biological Interactions of Low- and Non-Calorie Sweeteners with the Intestinal Microbiota: An Update of Recent Studies. Nutrients. 2020 Apr 21;12(4):E1153.
31Pepino MY. Metabolic effects of non-nutritive sweeteners. Physiol Behav. 2015 Dec 1;152(Pt B):450–5.
32Pang MD, Goossens GH, Blaak EE. The Impact of Artificial Sweeteners on Body Weight Control and Glucose Homeostasis. Front Nutr. 2020;7:598340.
33Peters JC, Beck J, Cardel M, Wyatt HR, Foster GD, Pan Z, et al. The effects of water and non-nutritive sweetened beverages on weight loss and weight maintenance: A randomized clinical trial. Obesity (Silver Spring). 2016 Feb;24(2):297–304.
34McGlynn ND, Khan TA, Wang L, Zhang R, Chiavaroli L, Au-Yeung F, 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 Mar 1;5(3):e222092.
35Lee JJ, Khan TA, McGlynn N, Malik VS, Hill JO, Leiter LA, 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 Aug 1;45(8):1917–30.
36Olivier B, Serge AH, Catherine A, Jacques B, Murielle B, Marie-Chantal CL, et al. Review of the nutritional benefits and risks related to intense sweeteners. Arch Public Health. 2015;73:41.