new research on artificial sweeteners

Spate of new research points to the potential harms of artificial sweeteners

New research adds to mounting evidence that artificial sweeteners may be harmful to your health.

A study published Wednesday in the BMJ, which involved more than 100,000 adults in France, found a potential link between consumption of artificial sweeteners and heart disease.

The results showed that participants who consumed large amounts of aspartame — found in the tabletop sweeteners Equal and NutraSweet as well as cereals, yogurt, candy and diet soda — had a higher risk of stroke than people who didn’t consume the sweetener.

Similarly, people who consumed high quantities of sucralose — found in Splenda as well as baked goods, ice cream, canned fruit, flavored yogurt and syrups — and acesulfame potassium, often used in "sugar-free" soda, had a higher risk of coronary heart disease.

"Artificial sweeteners may not be a safe alternative to sugar," said Mathilde Touvier, the study’s author and a research director at the French National Institute for Health and Medical Research.

Last month, a smaller study found that consuming non-nutritive sweetener — sugar substitutes that contain few calories or nutrients — could alter a person's gut microbes and potentially elevate blood sugar levels. High blood sugar can increase one's risk of diabetes, heart disease or stroke.

Prior to that, a June lab study found that artificial sweeteners prompted gut bacteria to invade cells in the intestine wall, which could ultimately raise one's risk of infection or organ failure.

Other previous research has linked artificial sweeteners to obesity , high blood pressure, diabetes and increased cancer risk as well.

"The more data that comes out showing these adverse health effects, the less we're going to want to encourage people to switch from added sugars to non-nutritive sweeteners," said Dr. Katie Page, an associate professor of medicine at the University of Southern California.

But the healthiest course of action, Page said, isn't to opt for regular sugar instead.

"We really need to encourage people to eat sugar in more moderation and try to decrease sugar consumption," she said. "And the way to do that isn’t to consume more non-nutritive sweeteners."

Some sweeteners thought of as natural aren't preferable either, Page said.

"I definitely would not switch to agave," she said. "I know people think that’s healthy, but it actually has a very high fructose content."

An emerging link between sweeteners and heart disease

As a category, artificial sweeteners are low- or no-calorie additives often found in soft drinks and other highly processed foods like yogurt, granola bars, cereal or microwaveable meals. They're also sold as tabletop sweeteners like Equal, Splenda, Sweet ‘N Low and Truvia.

The sweeteners were originally billed as a healthier replacement for sugar, which is known to promote obesity and diabetes and can increase one's risk of heart disease if consumed in excess.

Touvier said her study is the first to directly assess how overall dietary consumption of artificial sweeteners impacts one’s risk of heart disease. Previous studies mostly looked at how artificially sweetened beverages impact heart disease risk.

Her team defined a large amount of sweetener as around 77 milligrams per day, on average, which is a little less than two packets of tabletop sweetener.

More than half of the participants' artificial sweetener consumption came from soft drinks, while 30% came from tabletop sweeteners. Another 8% came from sweetened dairy products like yogurt or cottage cheese with fruit topping.

Sucralose is the most commonly consumed artificial sweetener worldwide, Page said, whereas "aspartame has kind of gotten out of favor, so people aren’t consuming it as much."

She said sodas are the biggest source of artificial sweeteners in our food supply, though "a lot of the non-nutritive sweeteners people are consuming are coming from foods that you might think of as healthy."

Two prime examples: flavored yogurts and sports drinks.

The best alternative to sugary food, Page said, is naturally sweet fruit. If water isn't a satisfying substitute for soft drinks or juice, she suggested carbonated water without artificial sweeteners.

Sweeteners could disrupt your metabolism and elevate blood sugar

A growing body of research suggests that artificial sweetener may disrupt the body's ability to properly metabolize glucose, which can be a risk factor for diabetes and cardiovascular health issues. 

For the study published last month, Israeli researchers asked 120 people to consume four artificial sweeteners — aspartame, saccharin, stevia and sucralose — for two weeks. Participants consumed six sachets of sweetener per day, which is within the Food and Drug Administration’s acceptable intake.

The researchers observed changes in the makeup and function of participants' gut microbes, which help break down food and ward off disease-causing bacteria. The changes were not seen in people who did not consume artificial sweeteners.

"All four sweeteners changed the microbiome, each in their unique way," said Eran Elinav, the study's author and a microbiome researcher at the Weizmann Institute of Science.

Two sweeteners in particular, sucralose and saccharin (found in Sweet ‘N Low), altered some people's ability to process glucose.

"It changed the way the bugs in their gut are functioning and that, in turn, led to increases in their glucose levels, which is of course not a good thing," Page said.

The researchers even transferred samples of gut microbes from the study participants with significant metabolism changes into mice. The mice, too, developed blood sugar alterations, Elinav said.

"That's pretty good evidence suggesting that [artificial sweeteners] have some type of effect on metabolism and on the gut microbiome," Page said.

Page said her team is now studying how artificial sweeteners affect children's risk of metabolic conditions like diabetes.

"There's been very, very few studies in children and there's data showing that the increases in non-nutritive sweetener consumption are even higher among children and adolescents," she said.

Aria Bendix is the breaking health reporter for NBC News Digital.

• - Google Chrome

Intended for healthcare professionals

• Access provided by Google Indexer
• My email alerts
• BMA member login
• Username * Password * Forgot your log in details? Need to activate BMA Member Log In Log in via OpenAthens Log in via your institution

Search form

• Advanced search
• Search responses
• Search blogs
• Artificial sweeteners...

Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort

• Related content
• Peer review
• Charlotte Debras , doctoral student 1 2 ,
• Eloi Chazelas , doctoral student 1 2 ,
• Laury Sellem , post-doctoral researcher in epidemiology 1 2 ,
• Raphaël Porcher , professor of biostatistics 3 4 ,
• Nathalie Druesne-Pecollo , doctor and operational coordinator 1 2 ,
• Younes Esseddik , senior IT manager 1 ,
• Fabien Szabo de Edelenyi , data manager 1 ,
• Cédric Agaësse , dietitian (manager) 1 ,
• Alexandre De Sa , dietitian 1 ,
• Rebecca Lutchia , dietitian 1 ,
• Léopold K Fezeu , doctor and senior researcher in nutritional epidemiology 1 2 ,
• Chantal Julia , doctor and professor in nutrition 1 5 ,
• Emmanuelle Kesse-Guyot , doctor and senior researcher in nutritional epidemiology 1 2 ,
• Benjamin Allès , researcher in nutritional epidemiology 1 ,
• Pilar Galan , doctor and senior researcher in nutritional epidemiology 1 2 ,
• Serge Hercberg , professor of nutrition and hospital practitioner in public health 1 2 5 ,
• Mélanie Deschasaux-Tanguy , doctor and researcher in nutritional epidemiology 1 2 ,
• Inge Huybrechts , doctor, senior researcher in nutritional epidemiology 2 6 ,
• Bernard Srour , doctor and post-doctoral researcher in epidemiology 1 2 ,
• Mathilde Touvier , doctor and senior researcher in nutritional epidemiology 1 2
• 1 Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Centre, University of Paris (CRESS), Bobigny, France
• 2 French network for Nutrition and Cancer Research (NACRe network), Jouy-en-Josas, France
• 3 Université de Paris, CRESS UMR1153, INSERM, INRA, Paris, France
• 4 Centre d’Épidémiologie Clinique, AP-HP, Hôtel-Dieu, Paris, France
• 5 Public Health Department, Avicenne Hospital, AP-HP, Bobigny, France
• 6 International Agency for Research on Cancer, World Health Organization, Lyon, France
• Correspondence to C Debras c.debras{at}eren.smbh.univ-paris13.fr (or @NutriNetSante on Twitter)
• Accepted 1 July 2022

Objectives To study the associations between artificial sweeteners from all dietary sources (beverages, but also table top sweeteners, dairy products, etc), overall and by molecule (aspartame, acesulfame potassium, and sucralose), and risk of cardiovascular diseases (overall, coronary heart disease, and cerebrovascular disease).

Design Population based prospective cohort study (2009-21).

Setting France, primary prevention research.

Participants 103 388 participants of the web based NutriNet-Santé cohort (mean age 42.2±14.4, 79.8% female, 904 206 person years). Dietary intakes and consumption of artificial sweeteners were assessed by repeated 24 h dietary records, including brand names of industrial products.

Main outcomes measures Associations between sweeteners (coded as a continuous variable, log10 transformed) and cardiovascular disease risk, assessed by multivariable adjusted Cox hazard models.

Results Total artificial sweetener intake was associated with increased risk of cardiovascular diseases (1502 events, hazard ratio 1.09, 95% confidence interval 1.01 to 1.18, P=0.03); absolute incidence rate in higher consumers (above the sex specific median) and non-consumers was 346 and 314 per 100 000 person years, respectively. Artificial sweeteners were more particularly associated with cerebrovascular disease risk (777 events, 1.18, 1.06 to 1.31, P=0.002; incidence rates 195 and 150 per 100 000 person years in higher and non-consumers, respectively). Aspartame intake was associated with increased risk of cerebrovascular events (1.17, 1.03 to 1.33, P=0.02; incidence rates 186 and 151 per 100 000 person years in higher and non-consumers, respectively), and acesulfame potassium and sucralose were associated with increased coronary heart disease risk (730 events; acesulfame potassium: 1.40, 1.06 to 1.84, P=0.02; incidence rates 167 and 164; sucralose: 1.31, 1.00 to 1.71, P=0.05; incidence rates 271 and 161).

Conclusions The findings from this large scale prospective cohort study suggest a potential direct association between higher artificial sweetener consumption (especially aspartame, acesulfame potassium, and sucralose) and increased cardiovascular disease risk. Artificial sweeteners are present in thousands of food and beverage brands worldwide, however they remain a controversial topic and are currently being re-evaluated by the European Food Safety Authority, the World Health Organization, and other health agencies.

Trial registration ClinicalTrials.gov NCT03335644

Introduction

The harmful effects of added sugars on various health outcomes including cardiometabolic disorders have been extensively studied, meta-analysed 1 2 and are currently recognised as major risk factors by public health authorities. In particular, the World Health Organization recommends that less than 5% daily energy intake should come from free sugar. 3 Artificial sweeteners emerged as an alternative to added sugar that enabled the sweet taste to be reproduced without using sugar and therefore reduced calorie content from free sugar, which was highly appreciated by consumers. 4 Artificial sweeteners currently represent a $7200m (£5900m; €7000m) market globally, with a 5% annual growth projected to attain $9700m by 2028. 5 An extensive number of brands worldwide contain these food additives, especially ultra-processed foods such as artificially sweetened beverages, some snacks, and low calorie ready-to-go meals or dairy products; overall more than 23 000 products worldwide contain artificial sweeteners. 6 Artificial sweeteners are also directly used by consumers as table top sweeteners instead of sugar. Acceptable daily intakes for each artificial sweetener have been set by the European Food Safety Authority (EFSA), the United States Food and Drug Administration, or the Joint Expert Committee on Food Additives. Nonetheless, they remain a topic of controversy and are currently undergoing a re-evaluation by several health authorities, including the EFSA 7 and WHO. 8

Some experimental in vivo and in vitro studies, observational studies, and human randomised controlled trials investigated early markers of cardiovascular health, for example, weight status, 9 10 11 12 hypertension, 13 inflammation, 14 vascular dysfunction, 15 16 or gut microbiota perturbation 17 18 19 20 in association with consumption of artificial sweeteners or artificially sweetened beverages. Most of these studies suggested adverse effects, 11 12 13 14 15 16 17 18 19 20 and few suggested neutral or beneficial properties. 9 10 Although the results were mixed, this literature generally supports a potential involvement of artificial sweeteners in cardiovascular health, with plausible mechanisms. 21 22 23

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. 24 Randomised controlled trials have not directly assessed the impact of artificial sweetener intake on hard endpoints such as CVD risk for ethical reasons. Similarly, observational prospective studies have not directly investigated the association between artificial sweetener intake (mg/day) and CVD risk, but several have used artificially sweetened beverage consumption (millilitres or servings/day) as a proxy to explore these associations with conflicting results. 22 23 25 26 27 28 29 30 31 32 33 34 One of these studies was performed in the NutriNet-Santé cohort 28 and found that sugary drinks and artificially sweetened beverages were associated with increased CVD risk. Systematic reviews and meta-analyses 35 36 have suggested direct associations between artificially sweetened beverages and CVD risk. The WHO 2022 report on the health effects of artificial sweeteners notably observed associations between consumption of beverages with artificial sweeteners (used as a proxy) and some intermediate markers of CVD, 8 including a modest increase in the unfavourable total cholesterol to HDL cholesterol ratio (meta-analysis of four randomised control trials), and an increased risk of hypertension (meta-analysis of four prospective studies). The international health authority also identified an increase in CVD mortality, and in the incidence of cardiovascular events and strokes associated with greater intake of soft drinks containing artificial sweeteners (meta-analysis of four randomised control trials). However, prospective studies remain limited and the level of evidence for these associations is still considered low by WHO. 8 Additionally, because artificially sweetened beverages only represent part of the total artificial sweetener intake, it is crucial to consider all dietary sources in causal studies.

In this context, our objective was to conduct a large scale prospective study using quantitative data to investigate the associations between consumption of artificial sweeteners (mg/day) from all dietary sources (beverages but also table top sweeteners, dairy products, etc), overall and by type (aspartame, acesulfame potassium, and sucralose), and risk of CVD (overall, coronary, and cerebrovascular). Our study was performed within the population based NutriNet-Santé cohort, which includes detailed information on commercial names and brands of industrial food consumed.

Study population and data collection

This study was based on the prospective NutriNet-Santé e-cohort, launched in France in May 2009, with an open ongoing enrolment of volunteers. The main objective was to investigate the relations between nutrition and health. 37 Participants are French adults, aged 18 years or older, with internet access, recruited from the general population by means of multimedia campaigns. They are followed through their personal account created at inclusion on the study website ( https://etude-nutrinet-sante.fr/ ). Immediately after enrolment, each person completes five online questionnaires about diet (24 h dietary records, detailed below), health (eg, personal and familial history, prescription drug use), anthropometric data (height and weight 38 39 ), lifestyle and sociodemographic data (eg, date of birth, sex, education level, professional occupation, smoking status, number of children 40 ), and physical activity. Physical activity levels were defined based on the validated seven day assessment International Physical Activity Questionnaire (IPAQ). 41 All activities declared by participants were converted into metabolic equivalent of task (MET) minutes per week according to the compendium of physical activities. 42 Three levels of physical activity were defined: low (<600 MET-min/week), moderate (600-1500 MET-min/week), and high (>1500 MET-min/week) using standardised IPAQ processing guidelines. 41 For instance, 600 MET-min/week is equivalent to 150 min/week of moderate intensity (4 METs) physical activity or 75 min/week of high intensity (8 METs) physical activity.

Each person included in the NutriNet-Santé cohort provides informed consent electronically. The study is registered at ClinicalTrials.gov ( NCT03335644 ), conducted according to the Declaration of Helsinki guidelines, and approved by the Institutional Review Board of the French Institute for Health and Medical Research (IRB-Inserm) and the Commission Nationale de l’Informatique et des Libertés (CNIL No 908450/909216).

Dietary assessment

Three non-consecutive days of 24 h dietary records were randomly assigned over a two week period, at baseline, and every six months thereafter. During those recording days (two weekdays and one weekend day) participants indicated all foods and beverages consumed during the three main meals and any other eating occasions, and in what quantities, using validated photographs and standard serving containers 43 or by directly entering the amount (in grams or millilitres). All 24 h dietary records provided during the first two years of each person’s follow-up were averaged to obtain baseline diet. This represents a reliable estimate of consumption habits, while respecting the prospective design and guaranteeing sufficient delay between consumption and CVD outcomes. Intakes of energy, alcohol, and nutrients were assessed using the NutriNet-Santé food composition table (≈3500 food/beverage items 44 ). Nutritional contributions of mixed dishes were estimated by standard French recipes defined by nutrition professionals. Dietary assessment through these 24 h dietary records were validated against interviews by a trained dietitian 45 and against blood and urinary biomarkers. 46 47 The basal metabolic rate and the Goldberg cut-off method enabled any under reporting to be identified 48 49 50 ; participants who under reported were excluded from the analyses. Supplementary method 1 gives details of methods used to identify under reporting.

Artificial sweetener intakes

Chazelas and colleagues described the quantitative evaluation of food additive consumption in participants of the NutriNet-Santé cohort. 51 Briefly, food additive intakes, including artificial sweeteners, were assessed through the interactive online 24 h dietary record tool, in which commercial names and brands of industrial products consumed could be recorded. The presence of food additives was first determined for each food and beverage using ingredients lists available from three large scale food composition databases: Open Food Facts ( https://world.openfoodfacts.org/ ) 6 ; the French food safety agency database Oqali ( https://www.oqali.fr/oqali_eng/ ) 52 ; and Mintel’s Global New Products Database. 53 Doses of additives were determined by around 2700 assays performed by accredited laboratories, requested by the Nutritional Epidemiology Research Team or by a consumer association (UFC Que Choisir). These quantitative data were completed by average doses per food group provided by EFSA and the Joint FAO/WHO Expert Committee on Food Additives. 54 Food additive composition data were matched by date to account for possible industrial reformulations and changes in additive composition (date of consumption was considered to match the product to the closest consumption data). Supplementary method 2 gives additional information on food additive and artificial sweetener intake assessment.

For this study, we were able to estimate intakes of aspartame (European food additive identification number E951), acesulfame potassium (E950), sucralose (E955), cyclamates (E952), saccharin (E954), thaumatin (E957), neohesperidine dihydrochalcone (E959), steviol glycosides (E960), and salt of aspartame-acesulfame potassium (E962) and to create a sum variable labelled total artificial sweeteners.

Cardiovascular disease determination

Throughout follow-up, biannual health questionnaires and a permanently open personal health interface on the study account allowed participants to report any new health events, medical treatments, and examinations. For each incident CVD event declared, participants were contacted by a physician of the team and asked to provide any relevant medical records (eg, radiological reports, electrocardiogram, angioplasty). When necessary, the study physicians contacted the patient’s physician or any hospitals providing treatment to collect additional information. These medical data were reviewed by physician experts. An investigation was also conducted by the physicians of the NutriNet-Santé study by contacting the participant’s family or their physician when no connection to the study website was made for more than a year. Beyond this proactive health follow-up, data were paired with the medico-administrative databases of the national health insurance system database (SNIIRAM) and the national mortality registry (CépiDC), thereby limiting potential bias due to people with CVD not reporting their disease to the study investigators (further information available in supplementary method 3). International classification of diseases clinical modification, 10th revision, was used to classify CVD. 55 For this study, first incidence of CVD, coronary heart disease (myocardial infarction, code I21; acute coronary syndrome, code I21.4; angioplasty, code Z95.8; angina pectoris, code I20.0), or cerebrovascular disease (stroke, code I64; transient ischaemic attack, codes G45.8 and G45.9) diagnosed between inclusion and 5 October 2021 were considered as events and investigated in the analyses.

Statistical analyses

Participants with at least two valid dietary records during the first two years of follow-up were included in the analysis. Those with prevalent CVD or pre-existing diabetes were excluded. To limit reverse causality bias (particularly sensitive when sugar was substituted by artificial sweeteners), participants with CVD diagnosed during the first two years of follow-up were also excluded. Supplementary figure 1 presents a flowchart showing detailed selection of the study population.

We classified participants into three categories of artificial sweetener consumption: non-consumers, lower consumers (participants with artificial sweetener intake below the sex specific median among consumers), and higher consumers. Baseline characteristics (sociodemographic, health, lifestyle, dietary intakes) were assessed for each category and compared using χ 2 tests for categorical variables and analysis of variance tests for continuous variables ( table 1 ).

Baseline characteristics of the study population, NutriNet-Santé cohort, France, 2009-21 (n=103 388)

• View inline

Associations between artificial sweeteners, overall and the most represented (aspartame, acesulfame potassium, and sucralose, consumed by more than 5% of participants), and CVD (overall, coronary heart disease, and cerebrovascular disease) were investigated using multivariable adjusted Cox proportional hazard models ( table 2 ). Participants contributed person time from their inclusion in the cohort until the date of CVD, date of last follow-up, date of death, or 5 October 2021, whichever occurred first. We first tested dose-response analyses using the restricted cubic spline (RCS) functions with the SAS macro developed by Desquilbet and Mariotti. 56 Given the logarithmic profile of the associations suggested by the RCS curves (supplementary fig 2) and to account for the large proportion of non-consumers (especially for each specific artificial sweetener), artificial sweetener intakes were log transformed (log10 of sweetener consumption in mg/g+1) to compute continuous models (+1 was uniformly added to all consumptions because log(0) is not allowed). The continuous model was used as the primary analyses to obtain hazard ratios and 95% confidence intervals. Supplementary tables 1 and 2 present models using three categories (non-consumers, lower consumers, and higher consumers, separated by the sex specific median) and four categories (non-consumers and sex specific consumers in thirds) of sweetener consumption.

Associations between intake of total artificial sweeteners, aspartame, acesulfame potassium, and sucralose and overall cardiovascular diseases, coronary heart diseases and cerebrovascular diseases, NutriNet-Santé cohort, France, 2009-21 (n=103 388)

The main models were adjusted for several variables suspected or known to be associated with diet and with CVD risk: sociodemographic (age, sex, educational level), lifestyle (smoking status, number of smoked cigarettes, physical activity), and health (family history of CVD) factors, and food groups and nutrients for which a role in CVD cause has been strongly suggested 57 58 59 60 61 62 63 64 65 : energy intake without alcohol, alcohol, sugar, sodium, saturated fatty acids, polyunsaturated fatty acids, fibre, fruit and vegetables, and red and processed meat. We added a table showing the rationale for selection of each covariate and information on how they were collected and measured (supplementary method 4). Analyses by specific artificial sweeteners (aspartame, acesulfame potassium, and sucralose) were additionally adjusted for other artificial sweetener intakes. Multiple imputation by chained equations 66 was applied to handle any missing values for covariates (15 imputed datasets; supplementary method 5). Cox proportional hazard assumption was verified using the rescaled Schoenfeld type residual method (supplementary fig 3). Competing risks were accounted for in all analyses using cause specific Cox models, 67 with death considered a competing risk for CVDs, coronary heart diseases, and cerebrovascular diseases. Additionally, cerebrovascular events were considered competing risks for coronary heart diseases and vice versa. Supplementary table 3 presents results from competing events. Cumulative incidence graphs were also plotted using the Fine and Gray model (presented in supplementary fig 4).

Associations were computed separately for each type of cerebrovascular or coronary disease event: myocardial infarction, acute coronary syndrome, angioplasty, angina pectoris, stroke and transient ischaemic event (supplementary table 4), and for all CVDs except transient ischaemic events. We also investigated associations between CVD risk and artificial sweeteners from beverages and from solid food (supplementary table 5). Substitution analyses were performed by entering added sugars and artificial sweeteners into the model. Hazard ratios and 95% confidence intervals for substituting artificial sweeteners for added sugars were estimated using the difference in coefficients obtained from this model. Supplementary method 6 presents these analyses. Formal interactions between body mass index (<25 or ≥25) and artificial sweeteners were tested for each outcome by entering the product of the two variables into Cox models.

We performed a sensitivity analysis in which we doubled the requested minimal number of 24 h dietary records (excluding participants with less than four records; supplementary table 6). Additionally, we computed models with artificial sweetener intakes coded as time dependent variables across the whole follow-up period (supplementary table 6). Other sensitivity analyses were also performed, with further adjustments for prevalent dyslipidaemia, for healthy and western dietary patterns (derived by principal components analysis) instead of food groups, added sugar intakes instead of sugar, proportion of ultra-processed foods in the diet, weight loss or calorie restricted diet, weight variation during follow-up, number of 24 h dietary records, body mass index, and social desirability score 68 ; and analyses without excluding prevalent diabetes (details presented in supplementary table 6). All tests were two sided, and P<0.05 was considered statistically significant. We used the statistical analysis software SAS, version 9.4 for analyses.

Patient and public involvement

The research question developed in this article corresponds to a concern expressed by some participants involved in the NutriNet-Santé cohort, and by the public in general. Participants in the study are thanked in the Acknowledgments section.

Descriptive characteristics

Overall, 103 388 participants were selected from the NutriNet-Santé cohort. Mean age at baseline was 42.2 years (standard deviation 14.4), 79.8% were women, and the mean number of 24 h dietary records during the first two years of follow-up was 5.6 (standard deviation 3.1). Supplementary figure 5 shows the distribution of the number of 24 h dietary records per person. Among the overall cohort, 0.94% (n=1639) participants have died since their inclusion (981 in the present population study) and 9.4% (n=16 306) dropped out because they did not want to receive any more questionnaires. A total of 37.1% of participants consumed artificial sweeteners. The average intake of artificial sweeteners was 15.76 mg/day among all participants and 42.46 mg/day among consumers only, which corresponds to approximately one individual packet of table top sweetener or 100 mL of diet soda. 69 70 Among participants who consumed artificial sweeteners, mean intakes for lower and higher consumer categories were 7.46 and 77.62 mg/day, respectively. Compared with non-consumers, higher consumers (unadjusted comparisons) tended to be younger, have a higher body mass index, were more likely to smoke, be less physically active, and to follow a weight loss diet; they had lower total energy intake, and lower alcohol, lipid (saturated and polyunsaturated), fibre, carbohydrate, fruit and vegetable intakes, and higher intakes of sodium, red and processed meat, dairy products, and beverages with no added sugar ( table 1 ). Aspartame, acesulfame potassium, and sucralose contributed to 58%, 29%, and 10% of total artificial sweetener intakes, respectively ( fig 1 ). Soft drinks with no added sugar accounted for 53% of artificial sweeteners; table top sweeteners were also an important vector (30%), as well as artificially sweetened flavoured dairy products (eg, yoghurts, cottage cheese, 8%; fig 2 ). As shown in supplementary figure 6, food group contributions varied for each artificial sweetener; for example, table top sweeteners contributed to 48% of aspartame intake, followed by soft drinks with no added sugar (41%), whereas acesulfame potassium and sucralose were both mainly provided by the consumption of soft drinks with no added sugar (76% and 78%, respectively). Participants who consumed artificial sweeteners tended to consume more than one type of the main artificial sweeteners, and 7.23% of the total participants consumed all three of the main types (supplementary fig 7).

Relative contribution of each specific artificial sweetener to the total intake of artificial sweeteners (%), NutriNet-Santé cohort, France, 2009-21 (n=103 388). *Cyclamates (E952), saccharin (E954), thaumatin (E957), neohesperidine dihydrochalcone (E959), steviol glycoside (E960), aspartame-acesulfame salt (E962)

• Download figure
• Open in new tab
• Download powerpoint

Relative contribution of each food group to the total intake of artificial sweeteners (%), NutriNet-Santé cohort, France, 2009-21 (n=103 388). *Used as tablets, liquid, or powder, added by the participants in yoghurts, hot drinks and so on, or for cooking. †High protein food substitutes, sugary foods, cookies, biscuits, cakes, pastries, breakfast cereals, sauces, savoury foods, ultra-processed fish products

Associations between artificial sweetener intakes and cardiovascular diseases

During follow-up (904 206 person years; median follow-up duration 9.0 years, interquartile range 7.5-10.1 years), 1502 incident cardiovascular events occurred, among which there were 730 coronary heart disease events (143 myocardial infarction, 75 acute coronary syndrome, 477 angioplasty, and 277 angina pectoris events) and 777 cerebrovascular disease events (203 strokes and 598 transient ischaemic events). Mean age at CVD event was 62.7 years (standard deviation 12.9). The RCS analyses suggested a log shaped association (increased risk followed by a plateau; P for non-linearity=0.067, 0.494, 0.016, and 0.021 for total artificial sweetener, aspartame, acesulfame potassium, and sucralose, respectively, for the overall CVD model; supplementary fig 2).

Total artificial sweetener intake was associated with increased risk of CVD (hazard ratio 1.09, 95% confidence interval 1.01 to 1.18, P=0.03; table 2 ); absolute incidence rate in higher consumers (above the sex specific median) was 346 per 100 000 person years, and in non-consumers it was 314 per 100 000 person years. Artificial sweeteners were more particularly associated with cerebrovascular disease risk (1.18, 1.06 to 1.31, P=0.002; incidence rates 195 and 150). Aspartame intake was associated with increased risk of cerebrovascular events (1.17, 1.03 to 1.33, P=0.02; incidence rates 186 and 151), and acesulfame potassium and sucralose were associated with increased coronary heart disease risk (acesulfame potassium: 1.40, 1.06 to 1.84, P=0.02; incidence rates 167 and 164; sucralose: 1.31, 1.00 to 1.71, P=0.05; incidence rates 271 and 161). Results were similar when artificial sweetener intakes were coded as time dependent variables (supplementary table 6). For each type of cerebrovascular disease or coronary heart disease, direct associations were observed between sucralose and risk of angioplasties (n=477; 1.60, 1.17 to 2.21, P=0.004) and between total artificial sweeteners and transient ischaemic events (n=598; 1.18, 1.05 to 1.33, P=0.006). For artificial sweeteners from beverages or solid food, associations were statistically significant between sweeteners from beverages and CVD risk (P=0.02) and between aspartame from beverages and coronary heart disease risk (P=0.03). Associations were borderline between acesulfame potassium and sucralose from beverages and coronary heart diseases (P=0.06 and P=0.08, respectively), and between aspartame, acesulfame potassium, and sucralose from solid food sources and cerebrovascular diseases (P=0.006, P=0.01, and P=0.002, respectively; supplementary table 5). Substitution analyses did not suggest a benefit for substituting artificial sweeteners for added sugars for CVD risk (hazard ratio 1.00, 95% confidence interval 0.99 to 1.01, P=0.28), cerebrovascular disease risk (1.00, 0.99 to 1.01, P=0.89), or coronary heart disease risk (1.00, 0.99 to 1.01, P=0.13; supplementary method 6). The results were stable across all sensitivity analyses tested (supplementary table 6). The artificial sweetener by body mass index variable was not statistically significant for overall cardiovascular disease, coronary heart disease, and cerebrovascular disease (all P>0.05), suggesting no interaction on the multiplicative scale.

Principal findings

In the NutriNet-Santé cohort, total artificial sweetener intake was associated with increased risk of overall CVD and cerebrovascular disease. Aspartame intake was associated with increased risk of cerebrovascular events, and acesulfame potassium and sucralose were associated with increased coronary heart disease risk. Our results suggest no benefit from substituting artificial sweeteners for added sugar on CVD outcomes.

Strengths and limitations of this study

This study was based on a large sample size (n=103 388) and prospectively investigated the associations between artificial sweetener intake from all dietary sources and CVD risk. There is no perfect measure of dietary consumption, therefore classification bias cannot be ruled out. However, the assessment of artificial sweetener consumption performed in this study was a comprehensive assessment at the individual level in a large scale population based cohort. The NutriNet-Santé study is an epidemiological cohort with precise and high quality dietary data. Dietary records have previously been validated by interviews with a trained dietitian 33 and against blood and urinary biomarkers for energy and nutrient intakes. 34 35 Epidemiological studies worldwide generally use food frequency questionnaires (known to be less precise than repeated 24 h dietary records 71 ) or a limited number of records or recalls at baseline.

The main vectors of artificial sweeteners are products that are generally consumed on a regular basis as part of daily dietary habits, including artificially sweetened beverages, table top sweeteners, and dairy products. Occasional artificial sweetener consumption is not likely to have a strong impact on CVD risk, and so even if some consumption might have been missed, it would probably have had a low impact on the study results. If there was a classification bias, it was non-differential due to the prospective design. Additionally, a sensitivity analysis was performed in the subgroup of participants with at least four records (mean 7.8, standard deviation 2.4, n=57 668), which doubled the minimal number of 24 h dietary records needed to be included in the analysis, and the results remained similar. Twenty four hour dietary recording days were decided in advance, which might have influenced the behaviour of participants on these days; however, adjustment for social desirability bias did not modify the findings, and the comprehensive recording enabled memory bias to be limited. In contrast to previous observational studies, artificially sweetened beverages were not used as a proxy to estimate artificial sweetener intakes. Detailed information on the brands of food or beverage consumed are collected as part of the NutriNet-Santé study. The dynamic date-to-date matching performed between the interactive web based 24 h dietary records and specific ingredient lists allowed the additive composition of industrial products to be identified, accounting for potential reformulations. 51

Some limitations should be discussed. Residual confounding cannot be totally excluded and no causal relation can be established with results from a unique observational study. However, models were adjusted for a wide range of potential sociodemographic, anthropometric, dietary, and lifestyle confounders. Further adjustment for the proportion of ultra-processed food in the diet was conducted, ensuring that the associations observed were not entirely driven by following an ultra-processed diet in general. 72 Additionally, reverse causality could lead to higher artificially sweetened food and beverage consumption among participants who were overweight or obese, and already had poorer cardiovascular health at baseline before CVD diagnosis. 73 74 However, this factor probably does not entirely explain the observed associations because we excluded CVD events occurring during the first two years of follow-up and we also tested models adjusted for baseline body mass index, weight loss diet, and weight change during follow-up, which did not substantially change the results.

Caution is needed to generalise these results to the whole French population. As generally observed in volunteer based cohorts, participants from the NutriNet-Santé study were more often women, with higher educational and socio-professional levels, and they were more likely to have a health conscious lifestyle and good dietary behaviours. 75 Therefore, artificial sweetener intake among NutriNet-Santé participants could be lower compared with French adults in general. Mean intakes of aspartame and acesulfame potassium for consumers in the cohort were 0.49 and 0.22 mg/kg body weight/day, respectively versus 1.29 and 0.73 mg/kg body weight/day, respectively estimated in the French population. 76 These intakes suggest that the associations found in our study between artificial sweetener consumption and risk of CVD might be underestimated. However, our assessment was more accurate than the one previously performed for the general French population, 76 which was based on three days of dietary records by participants at most, and brand specific composition was not accounted for.

The order of magnitude obtained for the associations in this study is in line with the one traditionally observed in nutritional epidemiology studies for commonly consumed dietary factors, 72 77 78 and with the findings of WHO in its recent report, 8 which was based on meta-analyses of prospective cohort studies investigating intake of beverages containing artificial sweeteners. 25 26 27 28 29 30 31 32 Furthermore, in terms of public health perspectives, the opportunity of preventing even a moderate proportion of CVD events through reduced artificial sweetener intake is of high interest given the extensive use of these substances in products on the global market. Associations were consistent across the many sensitivity analyses we performed; they were also consistent with previous epidemiological literature on proxies of sweetener intakes (eg, artificially sweetened beverages) and in line with mechanistic insights from experimental studies. All observed associations between sweetener intakes and CVD events went in the same (positive) direction, which is not in favour of random findings observed by chance.

The two complementary methods (self-reporting and medico-administrative databases) ensured good identification of CVD outcomes. However, the possibility of missing some events cannot be entirely ruled out. Additionally, despite efforts to identify transient ischaemic attacks as objectively as possible (based on medical or hospital reports, if possible a specialised neurological diagnosis, computed tomography or magnetic resonance imaging scan, or symptoms precisely described by the participant or a person close to them), these CVD events could not be diagnosed with the same certainty as for strokes or myocardial infarctions because they generally do not reveal sequelae on brain imaging. Finally, limited statistical power might have prevented us from detecting some associations for specific CVD pathologies.

Comparison with other studies

Observational prospective studies on the associations between artificial sweeteners, assessed from the whole diet (in mg/day), and CVD risk are lacking; therefore, no direct comparison was possible. However, several studies have been conducted 25 26 27 28 29 30 31 32 33 34 and meta-analysed 8 22 35 36 73 79 using artificially sweetened beverage consumption as a proxy (in mL or serving/day) and CVD risk. In line with recent results from the NutriNet-Santé study, 28 multiple cohorts found associations between artificially sweetened beverages and CVD. Higher artificially sweetened beverage consumption was associated with increased risks of stroke and cardiovascular events in the Women’s Health Initiative, 26 29 which is consistent with prospective investigations from the Nurses’ Health Study, the Health Professional Follow-up Study (HPFS), 25 30 the Framingham Offspring cohort, 31 and the Northern Manhattan Study. 27 Similarly, meta-analyses reported increased risks of stroke, vascular events, coronary heart diseases, CVDs, and CVD mortality. 35 36 73 79 Consistent with our findings, no association was observed for coronary heart diseases in the HPFS. 33 These studies mostly took place in the United States 35 and have not been as extensively explored in European populations. In line with our results, the recent WHO meta-analyses 8 reported positive associations between the intake of beverages containing artificial sweeteners and cardiovascular events overall (hazard ratio 1.32, 95% confidence interval 1.17 to 1.50, three prospective studies 26 27 28 ) and more specifically for the incidence of stroke (1.19, 1.09 to 1.29, five prospective studies 25 27 29 31 32 ), but not for coronary heart disease (1.16, 0.97 to 1.39, four prospective studies 27 29 33 80 ).

Meta-analyses performed by Azad and colleagues 22 also suggested associations between high intake of drinks with non-nutritive sweeteners and higher risk of strokes 25 and cardiovascular events, 26 27 but no significant associations were found for coronary heart diseases. 33 80 However, other studies suggested associations between artificially sweetened beverages and stroke but also coronary heart diseases. 29 Differences between results for coronary heart and cerebrovascular diseases could be because these pathologies have different causes and therefore, although they might share common nutritional determinants, others might play a different role in the development of these diseases. Each type of artificial sweetener might not have the same metabolic effect. 14 For instance, after ingestion, acesulfame potassium is absorbed from the small intestine and distributed to the blood and tissues through the systemic circulation and then excreted in urine. However, sucralose passes through digestion and is almost entirely excreted in the stools; only a small part is absorbed from the gastrointestinal tract. The aspartame molecule is broken down in different amino acids: aspartic acid and phenylalanine are sent to the systemic circulation while methanol is metabolised by the liver. 14 Because this study quantified the intake of each specific sweetener and investigated the association with CVD risk, overall and by type, future epidemiological studies and experimental data will be needed to further investigate a potential differential effect of artificial sweeteners according to cerebrovascular or coronary CVD types.

Furthermore, according to WHO 8 and as mentioned in the systematic reviews by Toews and colleagues and Zhang and colleagues, 23 73 randomised controlled trials investigating the long term effects of artificial sweeteners on the risk of hard endpoints such as CVD are lacking. However, some have studied early markers of cardiovascular health, such as weight variations, hypertension, or blood glucose level. 81 82 Most of these studies were conducted among participants with particular conditions (eg, people who were overweight or those with prevalent hypertension) 22 and were of short duration (follow-up around six months), with a level of evidence ranging from very low to moderate. 23 83 Additionally, it should be noted that many studies investigating the health effects of artificial sweeteners are funded by the industry, notably several randomised control trials included in reviews and meta-analyses. Azad and colleagues reported that industry sponsored randomised controlled trials suggest greater weight loss results compared with studies not financed by industry. 22 For instance, a systematic review has specifically studied the issue of conflict of interest in this field 84 and revealed that reviews sponsored by the artificial sweetener industry were more inclined to show beneficial weight loss effects. Therefore, no firm conclusion could be drawn from randomised controlled trials about the cardiometabolic impact of artificial sweeteners. However, several of these randomised controlled trials observed increased associations with several cardiometabolic outcomes, suggesting mechanistic plausibility for an impact of artificial sweeteners on cause of CVD.

Mechanistic plausibility from experimental studies

In some prospective cohort studies, associations have been reported between artificially sweetened beverage consumption and increased risk of obesity or weight gain. 8 22 85 86 Low calorie sweeteners (from beverages, table top sweeteners, and foods) were associated with obesity in the National Health and Nutrition Examination Survey 87 and abdominal obesity in the Baltimore Longitudinal Study of Ageing. 88 A cross-sectional study also found that consumers of diet soft drinks had greater waist circumference. 89 In the PREDIMED study (multicentre randomised trial) there was a positive association between artificially sweetened beverages and abdominal obesity. 90 Therefore, part of the associations between artificial sweeteners and CVD risk observed in our study might be because of weight gain. However, the associations observed here are probably not entirely driven by increased body weight. The impact of artificial sweeteners on weight gain is debated. 8 9 22 23 Some randomised controlled trials found no effect on body weight when replacing sugar sweetened beverages with artificially sweetened versions, 91 and others suggested decreased body weight, body mass index, fat mass, and waist circumference. 83 85 Adjustment for baseline body mass index and weight gain during follow-up did not modify the findings.

Other underlying mechanisms could be causally involved. 92 93 Meta-analyses suggest associations between artificially sweetened beverages and metabolic syndrome, 94 95 a cardiometabolic risk factor defined by dyslipidaemia, abdominal obesity, high blood glucose, insulin resistance, and hypertension. 96 Artificially sweetened beverages were associated with increased risk of metabolic syndrome 89 90 97 in a cohort study, 97 a cross-sectional study, 89 and a multicentre randomised trial. 90 More specifically, associations were observed with increased hypertension, 8 98 99 type 2 diabetes, 8 87 100 and hypertriglyceridemia. 8 90 Another potential pathway could involve the interaction of artificial sweeteners with intestinal sweet taste receptors, 92 which play a part in insulin secretion and glucose absorption. Experimental studies (rodent models) suggest that glucose and energy homoeostasis could be altered by artificial sweeteners. 11 101 Ingestion of sugar by animals accustomed to artificial sweeteners could lead to low glucagon like peptide 1 levels (which normally stimulate insulin secretion) and induce hyperglycaemia, 101 which could also be observed in humans. 92 Additionally, the alteration of gut microbiota by some artificial sweeteners could increase glucose intolerance, 17 but the results remain conflicting. 20 Vascular dysfunction, which contributes to CVD onset and development, after the ingestion of artificial sweeteners, has been observed in experimental studies (rodent models) 15 and in vitro (human cellular model), 16 and could also play a part in the risk of CVD. Finally, Basson and colleagues 14 suggest that artificial sweetener consumption might be associated with increased inflammation, a risk factor for CVD. 96

Policy implications and conclusions

In conclusion, these findings suggest that higher artificial sweetener consumption might be associated with increased risk of CVDs. Further well designed, large scale prospective studies need to confirm these results and experimental studies should be conducted to clarify biological pathways. In the meantime, this study provides key insights into the context of artificial sweetener re-evaluation by the EFSA, WHO, and other health agencies worldwide. Our results indicate that these food additives, consumed daily by millions of people and present in thousands of foods and beverages, should not be considered a healthy and safe alternative to sugar, in line with the current position of several health agencies. 23 102

What is already known on this topic

The harmful effects of added sugars have been established for several chronic diseases, leading food industries to use artificial sweeteners as alternatives in a wide range of foods and beverages

The safety of artificial sweeteners is debated and study findings remain divided about their role in the cause of various diseases

The negative influence of these food additives on cardiovascular disease has been suggested in experimental studies, but data from human studies remain limited and previous observational studies have focused solely on artificially sweetened beverages used as a proxy

What this study adds

In this large scale, prospective cohort of French adults, artificial sweeteners (especially aspartame, acesulfame potassium, and sucralose) were associated with increased risk of cardiovascular, cerebrovascular, and coronary heart diseases

The results suggest that artificial sweeteners might represent a modifiable risk factor for cardiovascular disease prevention

The findings indicate that these food additives, consumed daily by millions of people and present in thousands of foods and beverages, should not be considered a healthy and safe alternative to sugar, in line with the current position of several health agencies

Ethics statements

Ethical approval.

Electronic informed consent is provided by each person included in the NutriNet-Santé cohort. The study is registered at https://clinicaltrials.gov/ct2/show/NCT03335644 , conducted according to the Declaration of Helsinki guidelines and approved by the Institutional Review Board of the French Institute for Health and Medical Research (IRB-Inserm) and the Commission Nationale de l’Informatique et des Libertés (CNIL No 908450/909216).

Data availability statement

Researchers from public institutions can submit a collaboration request including information on the institution and a brief description of the project to [email protected]. All requests will be reviewed by the steering committee of the NutriNet-Santé study. If the collaboration is accepted, a data access agreement will be necessary and appropriate authorisations from the competent administrative authorities might be needed. In accordance with existing regulations, no personal data will be accessible.

Acknowledgments

We thank Thi Hong Van Duong, Régis Gatibelza, Jagatjit Mohinder, Aladi Timera, Rizvane Mougamadou (computer scientists), Julien Allegre, Nathalie Arnault, Laurent Bourhis, Nicolas Dechamp (data manager/statisticians), Merveille Kouam (health event validator), and Maria Gomes (Nutrinaute support) for their technical contribution to the NutriNet-Santé study. We sincerely thank all the volunteers of the NutriNet-Santé cohort.

Contributors: CD, EC, MDT, BS, MT: designed the study; EC, NDP, YE, FSdE, CA, ADS, RL, SH: developed the additives composition database and matched consumption/composition data; CA: coordinated dietitian work; FSdE: data management work; NDP, YE: global technical work; NDP, YE, EC, MT: supervised this technical work; CD: performed statistical analysis; EC, MDT, BS, MT: supervised statistical analysis; CD: drafted the manuscript; MT: supervised the writing. All authors contributed to the data interpretation and revised each draft for important intellectual content. All authors read and approved the final manuscript. CD and MT had full access to all the data in the study, MT takes responsibility for the integrity of the data and the accuracy of the data analysis; she is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

Funding: The NutriNet-Santé study was supported by the following public institutions: Ministère de la Santé, Santé Publique France, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national de recherche pour l’agriculture, l’alimentation et l’environnement (INRAE), Conservatoire National des Arts et Métiers (CNAM) and Université Sorbonne Paris Nord. CD was supported by a grant from the French National Cancer Institute (INCa, grant No 2019-158). EC was supported by a doctoral fellowship from Université Sorbonne Paris Nord to Galilée Doctoral School. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (consolidator grant agreement No 864219), the French National Cancer Institute (INCa_14059), the French Ministry of Health (arrêté 29.11.19) and the IdEx Université Paris Cité (ANR-18-IDEX-0001). This project was awarded the NACRe (French network for Nutrition and Cancer Research) Partnership Label and was awarded the Bettencourt Schueller foundation prize Coup d’élan pour la recherche française 2021. Researchers were independent from funders. The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from Ministère de la Santé, Santé Publique France, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national de recherche pour l’agriculture, l’alimentation et l’environnement (INRAE), Conservatoire National des Arts et Métiers (CNAM) and Université Sorbonne Paris Nord, European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université Paris Cité for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

Dissemination to participants and related patient and public communities: The results of the present study will be disseminated to the NutriNet-Santé participants through the cohort website, where lay summaries of all publications are posted ( https://etude-nutrinet-sante.fr/link/zone/43-Publications ). Additionally, results will be disseminated in public seminars and by a press release from the Journal or the French Medical Institute for Health and Medical Research, in association with Inrae, Cnam and Sorbonne Paris Nord communication and direction boards. This press release will be posted on their website and sent to their journalist contact book in France, Europe, and abroad (translated in English) as well as through their social medias Facebook and Twitter.

Provenance and peer review: Provenance and peer review: Not commissioned; externally peer reviewed.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .

• González-Padilla E ,
• Johnson L ,
• Sonestedt E
• Tayyiba M ,
• Agarwal A ,
• ↵ WHO. Guideline: Sugars intake for adult and children. Geneva: World Health Organization; 2015. http://public.eblib.com/choice/publicfullrecord.aspx?p=2033879
• Bachmanov AA ,
• Floriano WB ,
• ↵ Market Data Forecast. Global artificial sweetener market by type (aspartame, acesulfame-K, monosodium glutamate, saccharin, and sodium benzoate), by application (bakery items, dairy products, confectionery, beverages, and other), by distribution channel (supermarkets & hypermarkets, departmental stores, convenience stores, and others) and by regional analysis (North America, Europe, Asia Pacific, Latin America, and Middle East & Africa) - global industry analysis, size, share, growth, trends, and forecast (2022-2027). 2022. https://www.marketdataforecast.com/
• ↵ Open Food Facts 2020. https://world.openfoodfacts.org/discover
• European Food Safety Authority (EFSA)
• ↵ Rios-Leyvraz M, Montez J. Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis. Geneva: World Health Organization; 2022. https://www.who.int/publications/i/item/9789240046429
• Goossens GH ,
• Peters JC ,
• Davidson TL ,
• Martin AA ,
• Swithers SE
• Ballard CR ,
• Foletto KC ,
• Basson AR ,
• Rodriguez-Palacios A ,
• Cominelli F
• Marziou A ,
• Roustit M ,
• Jeoung NH ,
• Zilberman-Schapira G ,
• Ruiz-Ojeda FJ ,
• Plaza-Díaz J ,
• Sáez-Lara MJ ,
• Plaza-Diaz J ,
• Pastor-Villaescusa B ,
• Rueda-Robles A ,
• Abadia-Molina F ,
• Ruiz-Ojeda FJ
• Bruyère O ,
• Catherine A ,
• Abou-Setta AM ,
• Chauhan BF ,
• Küllenberg de Gaudry D ,
• Meerpohl JJ
• Bernstein AM ,
• de Koning L ,
• Rexrode KM ,
• Rubenstein L ,
• Robinson J ,
• Gardener H ,
• Markert M ,
• Wright CB ,
• Elkind MSV ,
• Chazelas E ,
• Mossavar-Rahmani Y ,
• Kamensky V ,
• Manson JE ,
• Himali JJ ,
• Beiser AS ,
• Romaguera D ,
• Pearson-Stuttard J ,
• Kellogg MD ,
• Willett WC ,
• Hinkle SN ,
• Bjerregaard AA ,
• Hercberg S ,
• Castetbon K ,
• Czernichow S ,
• Lassale C ,
• Touvier M ,
• Kesse-Guyot E ,
• Vergnaud AC ,
• Marshall AL ,
• Sjöström M ,
• Ainsworth BE ,
• Haskell WL ,
• Herrmann SD ,
• le Moullec N ,
• Deheeger M ,
• Preziosi P ,
• ↵ Unité de recherche en épidémiologie nutritionnelle (Bobigny). Table de composition des aliments, Etude NutriNet-Santé. [Food composition table, NutriNet-Santé study] (in French). Paris: Les éditions INSERM/Economica; 2013.
• Laporte F ,
• Camilleri GM ,
• Deschamps V ,
• Goldberg GR ,
• Druesne-Pecollo N ,
• Esseddik Y ,
• ↵ Observatoire de l’alimentation (Oqali). OQALI - Home page. https://www.oqali.fr/oqali_eng/
• ↵ Global New Products Database (GNPD). Banque de données mondiale de nouveaux produits, suivi des tendances nouveaux produits et innovations. 2022. https://www.gnpd.com/sinatra/anonymous_frontpage/
• ↵ Food and Agriculture Organization/World Health Organization (FAO/WHO). Codex General Standard for Food Additives (GSFA, Codex STAN 192-1995). Codex Alimentarius Commission; 2019. https://www.fao.org/fao-who-codexalimentarius/sh-proxy/en/?lnk=1&url=https%253A%252F%252Fworkspace.fao.org%252Fsites%252Fcodex%252FStandards%252FCODEX%2BSTAN%2B192-1995%252FCXS_192e.pdf
• Desquilbet L ,
• Rodgers JLR ,
• Bolleddu SI ,
• ↵ World Health Organization. Global action plan for the prevention and control of noncommunicable diseases 2013-2020. 2013;55.
• MacLehose RF ,
• Roetker NS ,
• Lloyd-Jones DM ,
• D’Agostino RB Sr . ,
• Flanders WD ,
• Merritt R ,
• Guasch-Ferré M ,
• Martínez-González MA ,
• PREDIMED Study Investigators
• Threapleton DE ,
• Greenwood DC ,
• Evans CEL ,
• Cleghorn CL ,
• Nykjaer C ,
• Woodhead C ,
• Knuppel A ,
• Sterne JAC ,
• Carlin JB ,
• Andersen PK ,
• Geskus RB ,
• de Witte T ,
• Tournois J ,
• ↵ Franz M. Amounts of sweeteners in popular diet sodas. Diabetes Self-Management. 2010. https://static.diabetesselfmanagement.com/pdfs/DSM0310_012.pdf
• ↵ US Food and Drug Administration. Additional information about high-intensity sweeteners permitted for use in food in the United States. 2018. https://www.fda.gov/food/food-additives-petitions/additional-information-about-high-intensity-sweeteners-permitted-use-food-united-states
• ↵ Zhang YB, Jiang YW, Chen JX, Xia PF, Pan A. Association of consumption of sugar-sweetened beverages or artificially sweetened beverages with mortality: a systematic review and dose–response meta-analysis of prospective cohort studies. Adv Nutr. 2021. [ https://academic.oup.com/advances/advance-article/doi/10.1093/advances/nmaa110/5909627
• Andreeva VA ,
• Salanave B ,
• Connolly A ,
• McCaffrey T ,
• McGlynn ND ,
• Laviada-Molina H ,
• Molina-Segui F ,
• Pérez-Gaxiola G ,
• Mandrioli D ,
• Kearns CE ,
• Miller PE ,
• Drewnowski A ,
• Shardell M ,
• Crichton G ,
• Alkerwi A ,
• Ferreira-Pêgo C ,
• Bes-Rastrollo M ,
• PREDIMED Investigators
• Ebbeling CB ,
• Feldman HA ,
• Steltz SK ,
• Robinson LM ,
• Schiano C ,
• Grimaldi V ,
• Scognamiglio M ,
• Dhingra R ,
• Sullivan L ,
• Jacques PF ,
• Winkelmayer WC ,
• Stampfer MJ ,
• Fagherazzi G ,
• Swithers SE ,
• Davidson TL
• ↵ Anses. Evaluation des bénéfices et des risques nutritionnels des édulcorants intenses. Maisons-Alfort: Anses; 2015. https://www.anses.fr/fr/system/files/NUT2011sa0161Ra.pdf

Do sweeteners increase your appetite? New evidence from randomised controlled trial says no

Replacing sugar with artificial and natural sweeteners in foods does not make people hungrier -- and also helps to reduce blood sugar levels, a significant new study has found.

The double blind randomised controlled trial found that consuming food containing sweeteners produced a similar reduction in appetite sensations and appetite-related hormone responses as sugary foods -- and provides some benefits such as lowering blood sugar, which may be particularly important in people at risk of developing type 2 diabetes.

The use of sweeteners in place of sugar in foods can be controversial due to conflicting reports about their potential to increase appetite. Previous studies have been carried out but did not provide robust evidence.

However, the researchers say their study, which meets the gold standard level of proof in scientific investigation, provides very strong evidence that sweeteners and sweetness enhancers do not negatively impact appetite and are beneficial for reducing sugar intake.

The trial was led by the University of Leeds in collaboration with the The Rhône-Alpes Research Center for Human Nutrition. It is the latest study to be published by the SWEET consortium of 29 European research, consumer and industry partners which is working to develop and review evidence on long term benefits and potential risks involved in switching over to sweeteners and sweetness enhancers in the context of public health and safety, obesity, and sustainability. It was funded by Horizon Europe.

Lead author Catherine Gibbons, Associate Professor in the University of Leeds' School of Psychology, said: "Reducing sugar consumption has become a key public health target in the fight to reduce the rising burden of obesity-related metabolic diseases such as type 2 diabetes.

"Simply restricting sugar from foods without substitution may negatively impact its taste or increase sweet cravings, resulting in difficulties sticking to a low-sugar diet. Replacing sugars with sweeteners and sweetness enhancers in food products is one of the most widely used dietary and food manufacturing strategies to reduce sugar intake and improve the nutritional profile of commercial foods and beverages."

Principal investigator Graham Finlayson, Professor of Psychobiology in the University of Leeds' School of Psychology, said: "The use of sweeteners and sweetness enhancers has received a lot of negative attention, including high profile publications linking their consumption with impaired glycaemic response, toxicological damage to DNA and increased risk of heart attack and stroke. These reports contribute to the current befuddlement concerning the safety of sweeteners and sweetness enhancers among the general public and especially people at risk of metabolic diseases.

"Our study provides crucial evidence supporting the day-to-day use of sweeteners and sweetness enhancers for body weight and blood sugar control."

The study, which is the first of its kind, looked at the effects of consuming biscuits containing either sugar or two types of food sweetener: natural sugar substitute Stevia, or artificial sweetener Neotame on 53 adult men and women with overweight or obesity.

Until now, virtually all studies of the effects of sweeteners and sweetness enhancers on appetite and glycaemia have been conducted using beverages as the vehicle. Few studies include volunteers with overweight or obesity and few have included volunteers of both sexes.

Most studies have only compared a single sweetener, mostly aspartame, with a control, and very few studies have examined the effect of repeated daily intake of a known sweetener or sweetness enhancer in the normal diet.

The new trial took place at the University of Leeds and the Rhône-Alpes Research Center for Human Nutrition (CRNH-RA), France between 2021 and 2022. Participants were all aged 18 to 60, with overweight or obesity.

The trial consisted of three two-week consumption periods, where participants consumed biscuits with either fruit filling containing sugar; natural sugar substitute Stevia, or artificial sweetener Neotame, each separated by a break of 14-21 days. Day 1 and day 14 of the consumption periods took place in the lab.

Participants were instructed to arrive in the lab after an overnight fast, a blood sample was taken to establish baseline levels of glucose, insulin and appetite-related hormones. They were also asked to rate their appetite and food preferences.

After consuming the biscuits, they were asked to rate how full they felt over several hours. Glucose and insulin levels were measured, as were ghrelin, glucagon-like peptide 1 and pancreatic polypeptide -- hormones associated with the consumption of food.

The results from the two sweetener types showed no differences in appetite or endocrine responses compared to sugar, but insulin levels measured over two hours after eating were reduced, as were blood sugar levels.

SWEET project joint co-ordinator Professor Anne Raben, from the University of Copenhagen, Denmark, said: "The findings show that sweeteners are a helpful tool to reduce intake of added sugar without leading to a compensatory increase in appetite or energy intake, thereby supporting the usefulness of sweeteners for appetite, energy and weight management."

• Diet and Weight Loss
• Food Additives
• Food and Agriculture
• Agriculture and Food
• Sugar substitute
• Blood sugar
• Diabetic diet
• Low-carb diets

Story Source:

Materials provided by University of Leeds . Note: Content may be edited for style and length.

Journal Reference :

• Catherine Gibbons, Kristine Beaulieu, Eva Almiron-Roig, Santiago Navas-Carretero, J. Alfredo Martínez, Beverley O’Hara, Dominic O’Connor, Julie-Anne Nazare, Alain Le Bail, Cécile Rannou, Charlotte Hardman, Moon Wilton, Louise Kjølbæk, Corey Scott, Hariklia Moshoyiannis, Anne Raben, Joanne A. Harrold, Jason C.G. Halford, Graham Finlayson. Acute and two-week effects of neotame, stevia rebaudioside M and sucrose-sweetened biscuits on postprandial appetite and endocrine response in adults with overweight/obesity—a randomised crossover trial from the SWEET consortium . eBioMedicine , 2024; 105005 DOI: 10.1016/j.ebiom.2024.105005

Cite This Page :

Explore More

• Fussy Eater? Most Parents Play Short Order Cook
• Precise Time Measurement: Superradiant Atoms
• Artificial Cells That Act Like Living Cells
• Affordable and Targeted Anticancer Agent
• This Alloy Is Kinky
• Giant Galactic Explosion: Galaxy Pollution
• Flare Erupting Around a Black Hole
• Two Species Interbreeding Created New Butterfly
• Warming Antarctic Deep-Sea and Sea Level Rise
• Octopus Inspires New Suction Mechanism for ...

Trending Topics

Strange & offbeat.

• International edition
• Australia edition
• Europe edition

Artificial sweeteners linked to increased risk of heart disease, study finds

Research involving 103,000 French adults shows sweeteners ‘should not be considered a healthy and safe alternative to sugar’

Artificial sweeteners are linked to an increased risk of heart disease and “should not be considered a healthy and safe alternative to sugar”, according to researchers.

The harmful effects of added sugars have been long established for multiple chronic diseases, leading food companies to use artificial sweeteners instead in a wide range of food and drinks consumed daily by millions of people worldwide.

However, their use has come under increased scrutiny in recent years, although study findings have been divided about their part in various diseases.

Their role in cardiovascular disease has previously been suggested in experimental studies, but data from human studies was limited and previous observational studies focused solely on artificially sweetened drinks used as a proxy.

Now the findings from a large-scale prospective cohort study suggest a potential direct association between higher consumption of artificial sweetener and an increased risk of cardiovascular disease.

“Our results indicate that these food additives, consumed daily by millions of people and present in thousands of foods and beverages, should not be considered a healthy and safe alternative to sugar, in line with the current position of several health agencies,” the researchers wrote in the BMJ.

In the study, of 103,000 French adults, artificial sweeteners were associated with increased risk of cardiovascular, cerebrovascular, and coronary heart diseases. “The results suggest that artificial sweeteners might represent a modifiable risk factor for cardiovascular disease prevention,” they wrote.

The research, led by experts from the Sorbonne Paris Nord University, examined intake of sweeteners from all dietary sources, including drinks, tabletop sweeteners and dairy products, and compared it with their risk of heart or circulatory diseases.

Participants had an average age of 42, and four in five were women. Sweetener intake was tracked using diet records.

The participants noted everything they ate, including which brand, for 24 hours, with their diet diary repeated three times at six-month intervals – twice on weekdays and once on a weekend day. Some 37% of them consumed artificial sweeteners.

During an average follow-up period of about a decade, 1,502 cardiovascular events were recorded, including heart attacks, stokes, mini strokes and angina.

Artificial sweetener consumption was linked to a 9% higher risk of cardiovascular disease, the BMJ reported. When researchers looked at specific types of illness, they found artificial sweetener consumption was linked to an 18% higher risk of cerebrovascular disease – conditions that affect the blood flow to the brain.

A specific type of sweetener – aspartame – was associated with a 17% increased risk of cerebrovascular events, while acesulfame potassium and sucralose were linked to increased risk of coronary heart disease.

The study was observational, so cannot establish cause, nor rule out the possibility that other unknown factors may have affected the results. Nevertheless, the researchers said, it was a large study that assessed artificial sweetener intake using precise, high-quality dietary data, and the findings were in line with other studies linking artificial sweeteners with markers of poor health. Further studies were needed, they said.

• Medical research
• Heart disease
• Food & drink industry
• Food safety

More on this story

Aspartame is safe in limited amounts, say experts after cancer warning

Aspartame a ‘possible carcinogen’ but safe to consume in moderation, WHO says

Should you kick your Diet Coke habit? As a public health expert, I’m not too worried

Aspartame sweetener to be declared possible cancer risk by who, say reports.

Replacing sugar with sweeteners does not affect weight control in long term, WHO says

The price of ‘sugar free’: are sweeteners as harmless as we thought?

No evidence of sugar substitutes' health benefits, finds study

Should link between dementia and artificial sweeteners be taken with a pinch of salt?

Most viewed.

Appointments at Mayo Clinic

• Nutrition and healthy eating
• Artificial sweeteners and other sugar substitutes

Learn about the pros and cons of sugar substitutes, also called artificial sweeteners.

Almost everyone likes a sugary snack. But if you often have foods and drinks with lots of added sugar, the empty calories can add up. Added sugar can play a part in weight gain. It also may raise your risk of serious health problems, such as diabetes and heart disease.

You might try to stay away from table sugar by using less processed sweeteners such as honey and molasses. But these also are forms of added sugar. They add calories to your diet.

Some people use products called sugar substitutes, also known as artificial sweeteners. They taste sweet like sugar but have fewer calories. Some have no calories.

Uses for sugar substitutes

Many sugar substitutes taste sweeter than sugar. So very little is needed to sweeten foods and drinks. Other sugar substitutes called sugar alcohols are not as sweet as sugar.

Sugar substitutes are in many kinds of foods and drinks labeled sugar-free or diet. That includes soft drinks, candy and baked goods.

Some sugar substitutes also are sold on their own in packets or other containers. These can be added to foods or drinks at home.

Safety of sugar substitutes

Government health agencies oversee ingredients that product-makers add to food. These agencies check ingredients, such as sugar substitutes, before foods or drinks that contain them can go on sale. In the United States, the Food and Drug Administration (FDA) allows the following sugar substitutes to be used:

• Acesulfame potassium (Sweet One, Sunett).
• Aspartame (NutraSweet, Equal).
• Neotame (Newtame).
• Saccharin (Sweet'N Low).
• Sucralose (Splenda).
• Luo han guo (Monk Fruit in the Raw).
• Purified stevia leaf extracts (Truvia, PureVia, others).

Other countries, such as those in the European Union, have more sugar substitute options than does the United States.

The FDA allows product-makers to use sugar alcohols, such as sorbitol and xylitol, too. The agency doesn't consider sugar alcohols to be food additives.

The FDA and food safety agencies in other countries also suggest how much of a sugar substitute you can safely have each day. This amount is called the acceptable daily intake (ADI). It varies by a person's weight and the type of sugar substitute used. Acceptable daily intakes aren't the same everywhere. They're different in the United States and Europe, for example.

In general, artificial sweeteners are safe in limited amounts for healthy people, including pregnant people. But limit or cut out sugar substitutes:

• If you're living with a rare genetic disease called phenylketonuria. Foods and drinks with aspartame can lead to serious health problems.
• If you have a bowel disease. Using sugar substitutes might make your symptoms flare up.

Dietary guidelines for Americans say adults shouldn't give sugar substitutes to children under 2 years old. In general, experts need to do more studies to learn what long-term health effects sugar substitutes might have on children. Most studies have looked at the effects in adults.

Health benefits linked to sugar substitutes

If you replace added sugar with sugar substitutes, it could lower your risk of getting tooth decay and cavities.

Sugar substitutes also don't raise the level of sugar in the blood.

For adults and children with overweight or obesity, sugar substitutes also might help manage weight in the short term. That's because sugar substitutes often are low in calories or have no calories. But it's not clear whether sugar substitutes can help people manage their weight over the long term.

Over time, it's most important to eat a healthy diet and get exercise.

Health concerns linked to sugar substitutes

Health agencies have clarified that sugar substitutes do not cause serious health problems.

Sugar substitutes also are not linked to a higher risk of cancer in people. Studies dating back to the 1970s linked the artificial sweetener saccharin to bladder cancer in rats. Since then, research has shown that those findings don't apply to people.

Some research on long-term, daily use of artificial sweeteners suggests a link to a higher risk of stroke, heart disease and death overall. But other things people do, or healthy habits that people don't do, may be the cause of the higher risk.

Other research is looking at long-term use of sugar substitutes and the gut. Many focus on how the gut and brain communicate. Researchers are checking to see if sugar substitutes affect cravings for sweets, the way people feel hunger and how the body manages blood sugar.

Sugar alcohols, stevia and luo han guo can cause bloating, gas and diarrhea. The amount of sugar alcohol that causes these symptoms varies from person to person.

In general, it is safest to take in small amounts of sugar substitutes. And it's best to use sugar substitutes for a short time, or just every once in a while. So try to cut back if you use them a few times a day.

The bottom line

Artificial sweeteners can be a short-term way to help some people lessen their use of sugar and lose or manage weight. In general, sugar substitutes are safe for healthy adults.

But be aware of how sugar substitutes affect your food and drink choices. These ingredients may get your tastebuds used to sweetness. And that can make drinking enough water a challenge.

Products made with sugar substitutes also may give you the wrong message about processed foods. A snack labeled low sugar or no sugar may not be the most nutritious choice. Whole foods, such as fruits and vegetables, usually have the best mix of nutrients for the body.

But artificial sweeteners can help some people enjoy sweetness without excess calories. And if used in moderation, artificial sweeteners can be part of a healthy diet.

There is a problem with information submitted for this request. Review/update the information highlighted below and resubmit the form.

From Mayo Clinic to your inbox

Sign up for free and stay up to date on research advancements, health tips, current health topics, and expertise on managing health. Click here for an email preview.

Error Email field is required

Error Include a valid email address

To provide you with the most relevant and helpful information, and understand which information is beneficial, we may combine your email and website usage information with other information we have about you. If you are a Mayo Clinic patient, this could include protected health information. If we combine this information with your protected health information, we will treat all of that information as protected health information and will only use or disclose that information as set forth in our notice of privacy practices. You may opt-out of email communications at any time by clicking on the unsubscribe link in the e-mail.

Thank you for subscribing!

You'll soon start receiving the latest Mayo Clinic health information you requested in your inbox.

Sorry something went wrong with your subscription

Please, try again in a couple of minutes

• Know your limit for added sugars. Centers for Disease Control and Prevention. https://www.cdc.gov/healthyweight/healthy_eating/sugar.html. Accessed Nov. 14, 2022.
• Artificial sweeteners and cancer. National Cancer Institute. https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheet. Accessed Nov. 14, 2022.
• Nutrition for life: Sugar substitutes. American Diabetes Association. https://professional.diabetes.org/sites/professional.diabetes.org/files/pel/source/sugar_substitutes.pdf. Accessed Nov. 11, 2022.
• Additional information about high-intensity sweeteners permitted for use in food in the United States. U.S. Food and Drug Administration. https://www.fda.gov/food/food-additives-petitions/additional-information-about-high-intensity-sweeteners-permitted-use-food-united-states. Accessed Nov. 11, 2022.
• How sweet it is: All about sugar substitutes. U.S. Food and Drug Administration. https://www.fda.gov/consumers/consumer-updates/how-sweet-it-all-about-sugar-substitutes. Accessed Nov. 11, 2022.
• Heuberger R. Overview of non-nutritive sweeteners. https://www.uptodate.com/contents/search. Accessed Nov. 11, 2022.
• Rios-Leyvraz M, et al. Health effects of the use of non-sugar sweeteners. World Health Organization. https://www.who.int/publications/i/item/9789240046429. Accessed Nov. 11, 2022.
• 2020-2025 Dietary Guidelines for Americans. U.S. Department of Health and Human Services and U.S. Department of Agriculture. https://www.dietaryguidelines.gov. Accessed Nov. 11, 2022.
• Garner C. Nutrition in pregnancy: Assessment and counseling. https://www.uptodate.com/contents/search. Accessed Nov. 11, 2022.
• Baker-Smith C, et al. The use of nonnutritive sweeteners in children. Pediatrics. 2019; doi:10.1542/peds.2019-2765.
• Phenylketonuria (PKU). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/phenylketonuria/symptoms-causes/syc-20376302. Accessed Nov. 14, 2022.
• High-intensity sweeteners. U.S. Food and Drug Administration. https://www.fda.gov/food/food-additives-petitions/high-intensity-sweeteners. Accessed Nov. 11, 2022.
• Weight-loss basics. Mayo Clinic. https://www.mayoclinic.org/healthy-lifestyle/weight-loss/basics/weightloss-basics/hlv-20049483. Accessed Nov. 15, 2022.

Products and Services

• Available Health Products from Mayo Clinic Store
• A Book: Mayo Clinic on High Blood Pressure
• A Book: Mayo Clinic Family Health Book, 5th Edition
• A Book: The Mayo Clinic Diet Bundle
• The Mayo Clinic Diet Online
• A Book: Live Younger Longer
• A Book: Cook Smart, Eat Well
• A Book: Mayo Clinic Book of Home Remedies
• Newsletter: Mayo Clinic Health Letter — Digital Edition
• A Book: Mayo Clinic on Digestive Health
• Health foods
• Alcohol use
• Alkaline water
• Autism spectrum disorder and digestive symptoms
• Breastfeeding nutrition: Tips for moms
• Caffeine: How much is too much?
• Is caffeine dehydrating?
• Calorie calculator
• Can whole-grain foods lower blood pressure?
• Carbohydrates
• Chart of high-fiber foods
• Cholesterol: Top foods to improve your numbers
• Coconut water: Is it super hydrating?
• Coffee and health
• Diet soda: How much is too much?
• Dietary fats
• Dietary fiber
• Prickly pear cactus
• Does soy really affect breast cancer risk?
• Don't get tricked by these 3 heart-health myths
• High-protein diets
• How to track saturated fat
• Is there a special diet for Crohn's disease?
• Monosodium glutamate (MSG)
• Nuts and your heart: Eating nuts for heart health
• Omega-3 in fish
• Omega-6 fatty acids
• Phenylalanine
• Portion control
• Taurine in energy drinks
• Underweight: Add pounds healthfully
• Daily water requirement

Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission.

• Opportunities

Mayo Clinic Press

Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press .

• Mayo Clinic on Incontinence - Mayo Clinic Press Mayo Clinic on Incontinence
• The Essential Diabetes Book - Mayo Clinic Press The Essential Diabetes Book
• Mayo Clinic on Hearing and Balance - Mayo Clinic Press Mayo Clinic on Hearing and Balance
• FREE Mayo Clinic Diet Assessment - Mayo Clinic Press FREE Mayo Clinic Diet Assessment
• Mayo Clinic Health Letter - FREE book - Mayo Clinic Press Mayo Clinic Health Letter - FREE book
• Healthy Lifestyle

Make twice the impact

Your gift can go twice as far to advance cancer research and care!

• Share full article

Advertisement

Supported by

World Health Organization Warns Against Using Artificial Sweeteners

Continued consumption doesn’t reduce weight and could increase the risk of Type 2 diabetes, cardiovascular diseases and mortality in adults, the W.H.O. said on Monday.

By April Rubin

The World Health Organization on Monday warned against using artificial sweeteners to control body weight or reduce the risk of noncommunicable diseases, saying that long-term use is not effective and could pose health risks.

These alternatives to sugar, when consumed long term, do not serve to reduce body fat in either adults or children, the W.H.O. said in a recommendation , adding that continued consumption could increase the risk of Type 2 diabetes, cardiovascular diseases and mortality in adults.

“The recommendation applies to all people except individuals with pre-existing diabetes and includes all synthetic and naturally occurring or modified nonnutritive sweeteners that are not classified as sugars found in manufactured foods and beverages, or sold on their own to be added to foods and beverages by consumers,” the W.H.O. said.

The W.H.O. recommendation is based on a review of available evidence, the agency said, and is part of a set of guidelines for healthy diets being rolled out.

Some examples of the sweeteners include aspartame, saccharin, sucralose and stevia. The W.H.O.’s announcement contradicts previous studies that have said these sweeteners don’t offer any health benefits but also do not cause harm.

Nutrition research is constantly evolving and findings are being updated with stronger data, said Stephanie McBurnett, a registered dietitian and nutrition educator with the Physicians Committee for Responsible Medicine. Examining the effects of saturated fats and other parts of people’s diets may provide more insight into the overall reasons behind some health issues that have been blamed on sugar.

“It’s not surprising to me that the World Health Organization didn’t find really any difference in health benefits between a regular soda and a diet soda,” said Ms. McBurnett, who is also a licensed dietitian and nutritionist. “They’re both processed foods.” She added, “If you look at what’s driving these chronic diseases like heart disease, diabetes, obesity, sugar is not always the only factor.”

The recommendation from the W.H.O. does not directly affect any individual country’s policy. The U.S. Food and Drug Administration, for example, might take this guidance into account and institute its own concerns or tweak labeling, Ms. McBurnett said. But it is not under any obligation to do so, either.

The F.D.A. did not immediately respond to a request for comment.

The International Sweeteners Association, a nonprofit organization that represents the industry, called the W.H.O.’s recommendation a disservice to consumers.

“Low/no calorie sweeteners are one of the most thoroughly researched ingredients in the world and continue to be a helpful tool to manage obesity, diabetes and dental diseases,” the association said in a statement. “They offer consumers an alternative to reduce sugar and calorie intake with the sweet taste they know and expect.”

The W.H.O.’s recommendation is currently considered conditional, the organization said.

“This signals that policy decisions based on this recommendation may require substantive discussion in specific country contexts, linked for example to the extent of consumption in different age groups,” the statement said.

The recommendation doesn’t extend as far as personal care and hygiene products that include artificial sugars such as toothpaste, skin creams and medications, the W.H.O. said. It also doesn’t include low-calorie sugars and sugar alcohols, which come from sugar itself.

“People need to consider other ways to reduce free sugars intake, such as consuming food with naturally occurring sugars, like fruit, or unsweetened food and beverages,” said Francesco Branca, the W.H.O. director for nutrition and food safety. He said that non-sugar sweeteners “are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health.”

April Rubin is a breaking news reporter and a member of the 2022-2023 New York Times fellowship class. More about April Rubin

A Guide to Sugar and Other Sweeteners

One of the best things you can do for your health is to cut back on foods with added sugar . Here’s how to get started .

A W.H.O. agency  has classified aspartame as a possible carcinogen . If the announcement has you worried, consider these alternatives to diet soda .

A narrative that sugar feeds cancer has been making the rounds for decades. But while a healthy diet is important, you can’t “starve a tumor.”

Sugar alcohols are in many sugar-free foods. What are they, and are they better than regular sugar ?

Many parents blame sugar for their children’s hyperactive behavior . But the myth has been debunked .

Are artificial sweeteners a healthy alternative to sugar? The W.H.O. warned against using them , saying that long-term use could pose health risks.

Low-Calorie Sweeteners

The health effects of low-calorie/artificial sweeteners are inconclusive, with research showing mixed findings.

Low-calorie sweeteners (LCS) are sweeteners that contain few to no calories but have a higher intensity of sweetness per gram than sweeteners with calories—like table sugar , fruit juice concentrates, and corn syrups. Other names for LCS are non-nutritive sweeteners, artificial sweeteners, sugar substitutes, and high-intensity sweeteners.

LCS are found in many beverages and foods like frozen desserts, yogurt, candies, baked goods, chewing gum, breakfast cereals, gelatins, and puddings. Foods and beverages containing LCS sometimes carry the label “sugar-free” or “diet.” Some LCS can be used as general purpose sweeteners.

Because LCS are many times sweeter than table sugar, they can be used in smaller amounts to achieve the same level of sweetness as sugar. People may use LCS in place of sugar to consume fewer calories or less sugar or to better control their blood glucose if they have diabetes or prediabetes.

There are six LCS approved as food additives by the U.S. Food and Drug Administration (FDA). [1] Numerous studies have been conducted on each type to identify possible toxic effects. They are all sweeter than table sugar (sucrose) but contain few or no calories. They include:

*An Acceptable Daily Intake is the maximum amount of a substance that can be consumed daily over the course of a person’s lifetime with no appreciable health risk, and is based on the highest intake that does not lead to observable adverse effects. Calculations are based on a 132 pound individual. ** People with a rare hereditary disease known as phenylketonuria (PKU) have difficulty breaking down phenylalanine, a component of aspartame, and should limit their intake of phenylalanine from all sources, including aspartame. †The inclusion of brand-names on this list is for reference only and does not constitute an endorsement. The Nutrition Source does not endorse specific brands.

Two other LCS are permitted for specific conditions of use in the food supply through the FDA’s GRAS (“Generally Recognized as Safe”) notification program:

• Steviol glycosides are found in foods and beverages in the U.S. under the names Rebaudioside A (or Reb A), Stevioside, Rebaudioside D, or steviol glycoside mixtures that contain Rebaudioside A and/or Stevioside as the main ingredients. Commercial brand names include Truvia® and PureVia®. At 200-400 times sweeter than sugar, the Acceptable Daily Intake is 9 packets daily.
• Stevia leaf and unrefined stevia extracts are not considered GRAS and are not allowed in the U.S. for use as sweeteners.
• Monk fruit is 100-250 times sweeter than sugar.
• An Acceptable Daily Intake has not yet been determined.

Sugar Alcohols

Sugar alcohols, or polyols, are not classified as LCS but have slightly less calories than table sugar. The sweetness of sugar alcohols varies from 25-100% as sweet as sugar. They do not promote tooth decay or cause sharp rises in blood glucose. Examples are sorbitol, xylitol, lactitol, mannitol, erythritol, and maltitol. They are found in sugar-free candies, cookies, ice cream, beverages, and chewing gums. They are also used in toothpastes and medicines like cough syrups.

In some people, eating high quantities of certain sugar alcohols can cause loose stools or diarrhea. They are absorbed slowly and may cause extra water to be drawn into the intestines. [2] With continued use, people may improve their tolerance.

More research is needed on the longer-term use of sugar alcohols. An observational three-year study found an association between erythritol as an added sweetener and cardiovascular disease (CVD) events, such as stroke and heart attack, in patients with heart disease or risk factors for CVD (e.g., diabetes, high blood pressure). [3] When comparing patients with the lowest and highest blood levels of erythritol, the latter had twice the risk of developing a CVD event. It is noted that the researchers only checked blood erythritol once at the start of the study. They further investigated with a separate lab study, and found that exposing human platelets to erythritol increased the risk of blood clot formation. Erythritol occurs naturally in small amounts in fruits, wine, and beer. But the amount of erythritol used as an additive in low-calorie beverages, ice cream, chewing gums, and candies is much higher.

Low-Calorie Sweeteners and Health

The health effects of LCS are inconclusive, with research showing mixed findings. Research is also looking at potential differences in effects from the various types of LCS. The following reviews research specific to LCS beverages.

• A large observational study of French women showed that both sugar-sweetened beverages (SSBs) and LCS beverages were linked with an increased risk of developing type 2 diabetes. [4] The authors noted that a high intake of SSBs has been associated with weight gain, possibly due to lower satiety and increased blood sugar and insulin levels, leading to insulin resistance. LCS beverages may also cause weight gain by stimulating appetite and a sweet preference in some people.
• In a detailed analysis of data from the Health Professionals Follow-up Study, the positive association observed between LCS beverage intake and type 2 diabetes incidence was largely explained by higher baseline BMI and metabolic conditions, which might have led to increased use of LCS beverages in the first place. [6]
• In three large prospective cohort studies of U.S. men and women, intake of SSBs was associated with an average 3-pound weight gain within each 4-year time period. Substituting the same amount of SSBs with water or LCS beverages was associated with less weight gain (about 1 pound) within each 4-year time span. [7]
• For adults trying to wean themselves from sugary soda, diet soda is a possible short-term substitute, best used in small amounts over a short period of time. For children, the long-term effects of consuming LCS beverages are unknown, so it’s best for kids to limit their intake. [8]

Weight Control

Long-term observational studies show that regular consumption of LCS beverages reduces calorie intake and promotes less weight gain or weight maintenance, but other research shows no effect, and some studies even show weight gain. [9] Randomized controlled trials also show mixed findings, although most have shown a modest reduction in weight. [10] Most of these studies are short-term with a small number of participants, making it difficult to provide definitive conclusions on LCS beverages and weight control. Different comparisons among studies may also produce different results; for example, was LCS beverage intake being compared with SSBs, juice, or water?

The human brain responds to sweetness with signals to eat more. By providing a sweet taste without any calories, however, LCS beverages may cause us to crave more sweet foods and drinks, which can add up to excess calories. Although hypothetical and not proven in human studies, research is actively looking at proposed mechanisms of LCS beverages that may affect appetite and weight:

• Do repeated exposures to the sweet taste of LCS promote a preference for sweets in the diet?
• Does the sweet taste of LCS stimulate an insulin response even though blood glucose does not change, leading to an increased appetite and food intake?
• If LCS beverages (as compared with SSBs) do not release hormones in the stomach that signal satisfaction, may a person increase their food intake due to hunger?
• Animal studies have shown that LCS can change gut microbiota, leading to weight gain and increased blood glucose levels. Would a similar effect be found in human studies?

At the University of California-San Diego, researchers performed functional MRI scans as volunteers took small sips of water sweetened with sugar or sucralose. Sugar activated regions of the brain involved in food reward, while sucralose didn’t. [11] It is possible, the authors say, that sucralose “may not fully satisfy a desire for natural caloric sweet ingestion.” So, while sugar signals a positive feeling of reward, LCS may not be an effective way to manage a craving for sweets.

The use of LCS is associated with perceived health risks such as cancer, partially due to earlier research and policy measures concerning the artificial sweeteners saccharin and aspartame. However, these findings were disregarded after extensive review. Since then, there have been no large or long-term human studies to indicate a link between LCS and cancer.

• The Act was based on early studies that found a cancer connection, but only in a specific type of rat. Out of 20 studies in laboratory rats that were given high dosages of saccharin for more than one year, none found an increased incidence of bladder cancers, except one, that used a particular breed of male rat susceptible to bladder infections . [12] Scientists determined that the rats naturally had high amounts of protein and calcium phosphate in their urine, which when combined with saccharin, could produce substances that damaged bladder tissue, leading to increased risk of cancer.
• However, in 2000 the saccharin warning labels were removed because scientists from the National Institute for Environmental Health Sciences determined, after reviewing additional research, that humans do not have this same reaction in urine and therefore would not be at increased risk for bladder cancer. In 2001, the FDA declared saccharin safe for consumption and in 2010 the Environmental Protection Agency stated that saccharin was no longer considered a potential hazard to human health. [13] Additional research in humans using retrospective records of the use of LCS (specifically artificial sweeteners) and rates of bladder cancer has found no association. [11] Saccharin remains the oldest and most researched LCS.
• That said, aspartame has been linked with other side effects, such as headaches and migraines in some adults and children. Numerous complaints have been made to the FDA about side effects of headache and dizziness after consuming aspartame. Though isolated case reports have confirmed headaches due to aspartame intake, randomized clinical trials have shown mixed results. [15, 16]
• In 2023, the International Agency for Research on Cancer, the World Health Organization, and the Joint Expert Committee on Food Additives released a risk assessment of aspartame and cancer. [17]   It classified aspartame as a Group 2B carcinogen having “limited evidence” for cancer in humans, specifically liver cancer. Their prior recommendation of an acceptable daily intake of aspartame of 40 mg/kg of body weight did not change, as they acknowledged that their research review did not provide differing evidence to alter this guideline, and affirmed that an intake within this range is safe. For a 150-pound (68 kg) woman, this would mean a limit of 2,727 mg of aspartame daily, equivalent to about eleven 12-ounce cans of diet soda (one can contains about 250 mg). They stated that the evidence on cancer risk in humans based on animal and human studies was not convincing, and that more research, specifically longer-term studies with follow-up and randomized controlled trials, were needed.

Scientific Advisory

A 2011 statement from the American Heart Association and American Diabetes Association concluded that when used judiciously, non-nutritive sweeteners (including low-calorie sweeteners, artificial sweeteners, and non-caloric sweeteners) might help with weight loss or control, and could also have beneficial metabolic effects. The statement also points out, however, that these potential benefits will not be fully realized if there is a compensatory increase in energy intake from other sources—ultimately saying that at this time there is insufficient data to make a conclusive determination about using non-nutritive sweeteners; more research is needed. [18]

The American Heart Association and American Diabetes Association followed this with a 2018 scientific advisory specific to LCS beverages and cardiometabolic health. [8] The report cited the decline in consumption of both SSBs and LCS beverages in the United States, suggesting that it is possible to reduce SSBs without necessarily increasing LCS beverage intake. The advisory outlined the following summary points:

• Children should not drink LCS beverages in the long-term because of unknown effects. If there is a potential increased risk in adults of metabolic syndrome, type 2 diabetes, and cardiovascular events with diet beverage intake, the risk could be heightened in a child due to their smaller body size and earlier exposure.
• For adults who are regular high consumers of SSBs, LCS beverages may be a useful temporary replacement strategy to reduce intake of SSBs. This may be particularly helpful for those who are used to a sweet-tasting beverage and for whom water, at least initially, is an undesirable option.
• Alternatives to LCS beverages and SSBs, such as plain, carbonated, or unsweetened flavored waters , should be encouraged for all.
• The potential benefits from LCS beverages as replacements for SSBs will not be fully realized if their use is offset by an increase in calorie intake from other foods or beverages. Additionally, an overall healthful dietary pattern is recommended.
• Further research on the effects of LCS beverages on weight control, cardiometabolic risk factors, and risk of cardiovascular disease and other chronic diseases is needed.

Unpacking WHO guidelines on non-sugar sweeteners

• U.S. Food and Drug Administration. Additional Information about High-Intensity Sweeteners Permitted for Use in Food in the United States https://www.fda.gov/food/ingredientspackaginglabeling/foodadditivesingredients/ucm397725.htm . Accessed 8/13/2018.
• Mäkinen KK. Gastrointestinal disturbances associated with the consumption of sugar alcohols with special consideration of Xylitol: scientific review and instructions for dentists and other health-care professionals. International journal of dentistry . 2016;2016.
• Witkowski M, Nemet I, Alamri H, Wilcox J, Gupta N, Nimer N, Haghikia A, Li XS, Wu Y, Saha PP, Demuth I. The artificial sweetener erythritol and cardiovascular event risk. Nature Medicine . 2023 Feb 27:1-9.
• Fagherazzi G, Vilier A, Saes Sartorelli D, Lajous M, Balkau B, Clavel-Chapelon F. Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l’Education Nationale–European Prospective Investigation into Cancer and Nutrition cohort–. The American journal of clinical nutrition . 2013 Jan 30;97(3):517-23.
• Imamura F, O’connor L, Ye Z, Mursu J, Hayashino Y, Bhupathiraju SN, Forouhi NG. Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. Br J Sports Med . 2016 Apr 1;50(8):496-504.
• De Koning L, Malik VS, Rimm EB, Willett WC, Hu FB. Sugar-sweetened and artificially sweetened beverage consumption and risk of type 2 diabetes in men–. The American journal of clinical nutrition . 2011 Mar 23;93(6):1321-7.
• Pan A, Malik VS, Hao T, Willett WC, Mozaffarian D, Hu FB. Changes in water and beverage intake and long-term weight changes: results from three prospective cohort studies. International journal of obesity . 2013 Oct;37(10):1378.
• Johnson RK, Lichtenstein AH, Anderson CA, Carson JA, Després JP, Hu FB, Kris-Etherton PM, Otten JJ, Towfighi A, Wylie-Rosett J, American Heart Association Nutrition Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Quality of Care and Outcomes Research; and Stroke Council. Low-Calorie Sweetened Beverages and Cardiometabolic Health: A Science Advisory From the American Heart Association. Circulation . 2018 Aug 28;138(9):e126-40.
• Bellisle F, Drewnowski A. Intense sweeteners, energy intake and the control of body weight. European journal of clinical nutrition . 2007 Jun;61(6):691.
• Borges MC, Louzada ML, de Sá TH, Laverty AA, Parra DC, Garzillo JM, Monteiro CA, Millett C. Artificially sweetened beverages and the response to the global obesity crisis. PLoS medicine . 2017 Jan 3;14(1):e1002195.
• Frank GK, Oberndorfer TA, Simmons AN, Paulus MP, Fudge JL, Yang TT, Kaye WH. Sucrose activates human taste pathways differently from artificial sweetener. Neuroimage . 2008 Feb 15;39(4):1559-69.
• Weihrauch MR, Diehl V. Artificial sweeteners—do they bear a carcinogenic risk?. Annals of Oncology . 2004 Oct 1;15(10):1460-5.
• U.S. Environmental Protection Agency. EPA Removes Saccharin from Hazardous Substances Listing. https://archive.epa.gov/epapages/newsroom_archive/newsreleases/ea895a11ea50a56d852577f9005e2690.html .  Accessed 9/20/18.
• Marinovich M, Galli CL, Bosetti C, Gallus S, La Vecchia C. Aspartame, low-calorie sweeteners and disease: regulatory safety and epidemiological issues. Food and chemical toxicology . 2013 Oct 1;60:109-15.
• Zaeem Z, Zhou L, Dilli E. Headaches: a review of the role of dietary factors. Current neurology and neuroscience reports . 2016 Nov 1;16(11):101.
• Taheri S. Effect of exclusion of frequently consumed dietary triggers in a cohort of children with chronic primary headache. Nutrition and health . 2017 Mar;23(1):47-50.
• World Health Organization. Aspartame hazard and risk assessment results released . Accessed 7/14/2023.
• Gardner C, Wylie-Rosett J, Gidding SS, Steffen LM, Johnson RK, Reader D, Lichtenstein AH. Nonnutritive sweeteners: current use and health perspectives: a scientific statement from the American Heart Association and the American Diabetes Association. Circulation . 2012 Jul 24;126(4):509-19.

Last reviewed July 2023

Terms of Use

The contents of this website are for educational purposes and are not intended to offer personal medical advice. You should seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The Nutrition Source does not recommend or endorse any products.

Science-Based Medicine

Exploring issues and controversies in the relationship between science and medicine

New Review of Artificial Sweeteners

A new review of research finds a modest but inconsistent benefit from consuming artificial sweeteners over sugar. Their conclusion of a possible backfire effect, however, does not seem to be supported by the studies they review.

A new systematic review of artificial sweeteners published in the Canadian Medical Association Journal concludes:

Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk.

Unsurprisingly, this is how the results are being widely reported in the media – that artificial sweeteners “may” increase body weight. I had to take a close look at this review, since a 2015 review of the same question came to a different conclusion. I discussed the 2015 review at the time . Had there been new research that essentially flipped the conclusion?

A brief overview of artificial sweetener research

I gave a summary of the research in my 2015 discussion, which you can read if you are interested in the details. Briefly, there are several types of research looking at the effects of consuming low energy sweeteners (LES), also called non-nutritive sweeteners (NNS). The first is animal research. These studies show some interesting possibilities, that consuming LES may lead to greater calorie consumption overall in some settings. However, these studies tend to be contrived in terms of what the rats eat and the applicability to humans is uncertain.

Human trials are largely divided into cohort studies, in which people are followed over long periods of time, and randomized trials, in which subjects are randomized to consuming water, LES, or sugary drinks. The cohort studies tend to show a small correlation between consuming LES and greater BMI or other measures of obesity. However, these studies show correlation only and are not able to determine causation. It is highly probable that people consume diet drinks because they are overweight, and not the other way around.

The best data is probably randomized controlled trials. These studies vary from short term (as little as one meal) to long term (six months) and have the advantage of randomizing subjects, and therefore we are better able to draw conclusions about causation. In the 2015 review they found a consistent but small benefit to consuming LES over drinks containing sugar, and even over consuming water. While this data is far from definitive, it does suggest a role for consuming LES beverages in weight management.

It is also probably true that effects depend on individual variables, as is true of weight management in general. There are many variables, including psychological ones, that are difficult to pin down. For example, there is a possible unintended consequence that when people do one thing for their health that takes will power, they then feel empowered to indulge in something they know is not good for them. So if they put Splenda in their coffee, they can have that piece of cake.

Further, most attempts at weight loss fail. It is therefore not surprising that attempts at weight loss with LES also have modest benefits. If the research shows any benefit of substituting LES for sugar, it is likely useful.

The new Canadian review

The new review from the CMAJ looked at two different kinds of studies, cohort studies and randomized controlled trials (they did not review animal studies like the 2015 review). In line with the 2015 review, they found that the nonrandomized cohort studies showed a modest correlation with consuming LES and being overweight. They also included several secondary health outcomes, like blood pressure, heart disease, and diabetes. These do not add much to the analysis, in my opinion, because they are all consequences of being overweight, and are therefore just measuring the same thing. There is no reason to conclude or even suspect that LES directly causes any of these secondary outcomes.

So this much of their conclusions is nothing new, and contains the same limitations. We can show correlation only, not causation, and there is a good reason to suspect that the causation is from being overweight to consuming LES. Yet reporting (starting with the study itself) focuses on the less plausible hypothesis that consuming LES causes weight gain.

Further, I think that the results of the randomized trials essentially completely trump the results of the cohort studies, because they are randomized. Here is where the conclusions differ from the 2015 review. The 2015 review concluded:

Overall, the balance of evidence indicates that use of LES in place of sugar, in children and adults, leads to reduced EI (energy intake) and BW (body weight), and possibly also when compared with water.

The 2017 Canadian review concluded:

Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management…

The first thing I thought was – were there new studies since the 2015 review that warrants a different conclusion? The CMAJ review reports that there were new studies since the previous review and lists them. I looked through the new studies and found only one that is a relevant randomized controlled trial, this one published in 2016 that concluded:

NNS beverages were superior for weight loss and weight maintenance in a population consisting of regular users of NNS beverages who either maintained or discontinued consumption of these beverages and consumed water during a structured weight loss program. These results suggest that NNS beverages can be an effective tool for weight loss and maintenance within the context of a weight management program.

There was also a late 2015 study comparing LES to water, and found:

Replacement of DBs with water after the main meal may lead to greater weight reduction during a weight-loss program.

The other new studies were either cohort studies or looked at secondary outcomes. Neither of these two studies seem to warrant a reversal of the conclusion that consuming LES has a moderate benefit for weight loss. The first study actually supports a benefit for LES, and the second study is about replacing LES with water, and is not a comparison with sugary drinks.

Where does that leave us?

In the end the conclusions of this review are not dramatically different than the 2015 review – there is only a difference in emphasis which I think reflects the biases of the authors of each review. This is unavoidable because the data is complex, there is no perfect type of data, and the results are mixed and modest. There is therefore a lot of room for interpretation.

The Canadian reviewers acknowledge that the long term randomized trials did show a benefit for consuming LES, but they pointed out that these studies tended to have industry sponsorship. That is a legitimate point, as prior research shows a correlation between industry sponsorship and favorable outcomes, but in itself does not nullify the research findings.

I think the bottom line is that weight loss is difficult and complex. The effects of all interventions are modest and inconsistent. There are many variables, and no study will ever be able to control for all of them. The net effect of consuming LES vs sugary drinks or water is likely dependent on the individual and the situation.

But I do think we can draw a couple of conclusions from all the available research. The first question is this – is there a health or weight disadvantage to consuming sugar? I think the answer here is a clear yes. Sugary drinks contain many calories that add to total calorie consumption and are counterproductive if your goal is calorie control for weight management. Replacing high calorie sugary drinks with low calorie drinks is therefore advantageous.

The second question is this – is there an unintended backfire effect to consuming LES, because it tricks the brain into being more hungry or some other hormonal or metabolic effect? Here I think the answer is probably no, and the new Canadian review does not change this conclusion. Randomized controlled trials in humans supersede cohort studies and animal studies in addressing this question. Those studies find, if anything, a modest benefit to consuming LES. It is obviously possible to disagree about whether or not this benefit is real, given that there are inconsistencies in the data. The randomized trials clearly do not show any disadvantage – no backfire effect.

What I think this means is that, if you are trying to lose weight replacing sugary drinks with low calorie drinks can be a helpful part of your overall strategy. It will not be a panacea, or make weight loss easy. The research shows the most effective strategies involve making permanent changes to your lifestyle regarding food consumption and exercise. Avoiding sugary drinks can be part of those lifestyle changes, and you should not fear drinking LES because of an alleged backfire effect. The research, including this recent review, does not show such an effect in humans.

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe , and the author of the NeuroLogicaBlog , a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses , and published a book on critical thinking - also called The Skeptics Guide to the Universe .

View all posts

• Posted in: Nutrition
• Tagged in: low energy sweeteners , obesity , systematic review

Posted by Steven Novella