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The Sweet Dilemma: Sugar and Artificial Sweeteners Through the Lens of Recent Peer-Reviewed Evidence

🤖 This report was entirely produced by an AI agent on behalf of the author. It is intended as an educational introduction to the topic.

Research period: 2023–2026 peer-reviewed literature. Sources: 35 peer-reviewed studies from PubMed/MEDLINE, WHO guidelines, IARC monographs, AHA scientific statements, and EFSA opinions.

Executive Summary

The scientific landscape on sugar and artificial sweeteners has shifted dramatically in recent years. A convergence of large-scale umbrella reviews, prospective cohorts, mechanistic studies, and a landmark natural experiment published between 2023 and 2026 has reframed the debate. The evidence now points to a clear hierarchy of risk: sugar-sweetened beverages represent the most well-established harm, artificial sweeteners occupy a contested middle ground with emerging concerns about cardiometabolic and microbiome effects, and the food matrix—whether sugar comes in liquid form or whole fruit—may matter as much as the total grams consumed. In May 2023, the World Health Organization (WHO) took the unprecedented step of recommending against the use of non-sugar sweeteners for weight control, citing lack of long-term benefit and potential undesirable effects. Two months later, the International Agency for Research on Cancer (IARC) classified aspartame as a Group 2B “possibly carcinogenic to humans,” creating a public health flashpoint that remains unresolved. This article synthesizes the latest evidence from both sides of the sweetener divide.

I. The Sugar Problem: What the Latest Evidence Shows

A. Scale of Harm: Umbrella Reviews

The most comprehensive assessment of dietary sugar and health outcomes to date is the BMJ umbrella review by Huang et al. (2023), which synthesized 73 meta-analyses covering 83 health outcomes. The study found significant harmful associations between dietary sugar and 18 endocrine/metabolic outcomes, 10 cardiovascular outcomes, 7 cancer outcomes, and 10 other outcomes including neuropsychiatric, dental, and hepatic conditions. The authors wrote:

“Each 250 mL/day increment of sugar sweetened beverage consumption was associated with a 17% and 4% higher risk of coronary heart disease… and all cause mortality.”

“Every 25 g/day increment of fructose consumption was associated with a 22% higher risk of pancreatic cancer.”

The review concluded: “High dietary sugar consumption is generally more harmful than beneficial for health, especially in cardiometabolic disease. Reducing the consumption of free sugars or added sugars to below 25 g/day (approximately 6 teaspoons/day) and limiting the consumption of sugar sweetened beverages to less than one serving/week… are recommended.”

Source: Huang Y, Chen Z, Chen B, et al. “Dietary sugar consumption and health: umbrella review.” BMJ (2023). DOI: 10.1136/bmj-2022-071609 | PMID: 37019448

A parallel umbrella review in Clinical Nutrition ESPEN by Tran et al. (2023) examined 16 meta-analyses on sugar-sweetened beverages (SSBs) and metabolic syndrome. The highest versus lowest SSB intake was associated with:

The authors noted that “the quality of evidence was predominantly deemed as highly suggestive and convincing” and concluded that “more rigorous and targeted policy interventions are warranted to curtail SSBs consumption.”

Source: Tran QD, Nguyen THH, Le CL, et al. “Sugar-sweetened beverages consumption increases the risk of metabolic syndrome and its components in adults.” Clinical Nutrition ESPEN (2023). DOI: 10.1016/j.clnesp.2023.08.001 | PMID: 37739720

B. Type 2 Diabetes: Dose-Response and Causal Evidence

A 2025 dose-response meta-analysis in Advances in Nutrition by Della Corte et al. analyzed 29 prospective cohorts (up to 541,288 participants) and found:

“Each additional serving of SSB and fruit juice was associated with a higher risk of T2D (risk ratio [RR]: 1.25; 95% CI: 1.17, 1.35 and RR: 1.05… respectively; moderate certainty).”

Critically, the study found that 20 g/day intakes of total sugar and sucrose were inversely associated with T2D risk, leading the authors to conclude that “dietary sugar consumed as a beverage (SSB and fruit juice) is associated with incident T2D risk. The results do not support the common assumption that dietary sugar… irrespective of type and amount, is consistently associated with increased T2D risk.”

Source: Della Corte KA, Bosler T, McClure C, et al. “Dietary Sugar Intake and Incident Type 2 Diabetes Risk: Dose-Response Meta-Analysis.” Advances in Nutrition (2025). DOI: 10.1016/j.advnut.2025.100413 | PMID: 40122386

Perhaps the most compelling causal evidence comes from a natural experiment published in Science by Gracner et al. (2024), which exploited the end of UK sugar rationing in September 1953. Using UK Biobank data, the researchers found:

“Early-life rationing reduced type 2 diabetes and hypertension risk by about 35 and 20% and delayed disease onset by 4 and 2 years, respectively.”

The protection was evident with in utero exposure and increased with postnatal restriction, “especially after 6 months, when eating of solid foods likely began. In utero sugar rationing alone accounted for about one-third of the risk reduction.” Rationing kept sugar intake within current dietary guidelines; consumption nearly doubled after it ended. This quasi-experimental design provides some of the strongest causal evidence available for early-life sugar exposure and chronic disease.

Source: Gracner T, Boone C, Gertler PJ. “Exposure to sugar rationing in the first 1000 days of life protected against chronic disease.” Science (2024). DOI: 10.1126/science.adn5421 | PMID: 39480913

The PURE prospective cohort published in The Lancet Diabetes and Endocrinology (Miller et al., 2024) examined 127,594 adults across 20 countries over 11.8 years and found:

“A diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs 1; HR 1.15 [95% CI 1.03-1.29]).”

The effect was stronger with higher BMI (HR 1.23 vs 1.10; p interaction=0.030), suggesting that “consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes.”

Source: Miller V, Jenkins DA, Dehghan M, et al. “Associations of glycaemic index and glycaemic load with risk of type 2 diabetes (PURE).” The Lancet Diabetes and Endocrinology (2024). DOI: 10.1016/S2213-8587(24)00069-X | PMID: 38588684

C. Cardiovascular Disease

A 2025 umbrella meta-analysis in Nutrition Journal by Jamali et al. synthesizing 19 meta-analyses (67 datasets) found:

“SSB intake linked to a 9% higher overall mortality risk (RR: 1.09) and a 10% increased CVD mortality risk (RR: 1.10).”

Both SSBs and artificially sweetened beverages (ASBs) were associated with hypertension (RR 1.12–1.19), coronary heart disease (1.09–1.20), metabolic syndrome (1.19–1.31), and stroke (1.06–1.25). The authors described “a clear link between the intake of sweetened beverages and elevated risks of mortality and major cardiovascular outcomes.”

Source: Jamali M, Anvarifard P, Hosseini B, et al. “Sweetened beverages and cardiovascular outcomes: an umbrella review.” Nutrition Journal (2025). DOI: 10.1186/s12937-025-01242-1 | PMID: 41225521

The food matrix study by van Oeteren et al. (2025) in Clinical Nutrition provides a crucial nuance. Using the Maastricht Study cohort (n=5,426–6,471) plus a randomized crossover trial (n=21), the researchers found:

“The intake of fructose from sugar-sweetened beverages, but not from fruits or fruit juice, was associated with higher… blood pressure, and greater risk of hypertension (OR: 1.29, 95% CI 1.12; 1.50 per 10g fructose).”

In the crossover trial, pure fructose yielded the greatest serum fructose excursions and higher systolic BP (+1.8 mmHg) compared to other matrices. The authors concluded: “The relevance of the food matrix on fructose dynamics and blood pressure, independent of the caloric value of fructose.”

Source: van Oeteren MAJ, de Groot DM, Buziau AM, et al. “The effects of dietary fructose on blood pressure are modified by the food matrix.” Clinical Nutrition (2025). DOI: 10.1016/j.clnu.2025.10.017 | PMID: 41202663

A meta-analysis by Guntari et al. (2025) in Food and Nutrition Research found that short-term added sugars (fructose, sucrose, F/G mixtures) had minimal effects on fasting blood glucose, insulin, triglycerides, and HDL-c, but “significant increases in TC and LDL-c were observed, particularly with fructose and sucrose, indicating adverse effects on lipid metabolism.” High-fructose corn syrup interventions showed “marked increases in uric acid.”

Source: Guntari P, Junaida A, Palupi E, et al. “Fructose-containing sugars and metabolic risk: a systematic review and meta-analysis.” Food and Nutrition Research (2025). DOI: 10.29219/fnr.v69.11062 | PMID: 41323133

D. Cancer Risk

A landmark prospective cohort study in JAMA by Zhao et al. (2023) followed 98,786 postmenopausal women from the Women’s Health Initiative for a median of 20.9 years and found:

">=1 SSB serving/day vs <=3/month: significantly higher risk of liver cancer (adjusted HR, 1.85 [95% CI, 1.16-2.96])… and chronic liver disease mortality (adjusted HR, 1.68 [95% CI, 1.03-2.75])."

Notably, artificially sweetened beverages showed no significant association in this study. This was the first major prospective evidence linking SSBs to liver cancer and chronic liver disease mortality.

Source: Zhao L, Zhang X, Coday M, et al. “Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality.” JAMA (2023). DOI: 10.1001/jama.2023.12618 | PMID: 37552302

E. Cognitive Effects

A systematic review and meta-analysis by Gillespie et al. (2023) in Nutrients analyzed 77 studies (65 RCTs, n=3,831; 9 cross-sectional, n=11,456; 3 cohort, n=2,059) and found:

“All cohort studies and eight of the nine cross-sectional studies found significant positive correlations between added sugar consumption and risk of cognitive impairment.”

Importantly, “four studies identified reduced risk of cognitive impairment associated with natural fructose-containing foods” — suggesting that harm is specific to added/free sugars, not intrinsic fruit sugars. The authors noted “the potentially detrimental effect of excessive, long-term, or prenatal added sugar consumption on cognitive function.”

Source: Gillespie KM, White MJ, Kemps E, et al. “The Impact of Free and Added Sugars on Cognitive Function: A Systematic Review and Meta-Analysis.” Nutrients (2023). DOI: 10.3390/nu16010075 | PMID: 38201905

F. Mechanistic Insights: The Gut Microbiome Connection

A 2025 study in Cell Metabolism by Zhang et al. examined the gut-microbiome-metabolite pathway linking SSBs to diabetes in Hispanic/Latino adults. Higher SSB intake was associated with:

“Lower abundances of several short-chain-fatty-acid producers… and higher abundances of fructose- and glucose-utilizing Clostridium bolteae and Anaerostipes caccae.”

Fifty-six serum metabolites correlated with both SSB intake and a microbiota score. “Higher glycerophospholipid and BCAA derivative levels and lower AAA derivative levels were associated with higher incident diabetes risk,” providing “a potential role of gut microbiota in the association between SSB intake and diabetes.”

Source: Zhang Y, Luo K, Peters BA, et al. “Sugar-sweetened beverage intake, gut microbiota, circulating metabolites, and diabetes risk.” Cell Metabolism (2025). DOI: 10.1016/j.cmet.2024.12.004 | PMID: 39892390

G. Pediatric Impact

A review by Calcaterra et al. (2023) in Nutrients focusing on children and adolescents with obesity found:

“The leading mechanism linking SSB intake to the risk of gaining weight is decreased satiety and incomplete compensatory reduction in energy intake at meals following ingestion of liquid calories.”

The review confirmed that “consumption of SSBs had a significant impact on the prevalence of obesity and related metabolic risks, including insulin resistance, type 2 diabetes, hypertension and metabolic syndrome.”

Source: Calcaterra V, Cena H, Magenes VC, et al. “Sugar-Sweetened Beverages and Metabolic Risk in Children and Adolescents with Obesity.” Nutrients (2023). DOI: 10.3390/nu15030702 | PMID: 36771409

II. Artificial Sweeteners: The Promise and the Concern

A. The WHO’s 2023 Guideline — A Watershed Moment

In May 2023, the WHO released a guideline on the use of non-sugar sweeteners (NSS) that sent shockwaves through the food industry. The guideline stated:

“The World Health Organization (WHO) has released a new guideline on non-sugar sweeteners (NSS), which recommends against the use of NSS to control body weight or reduce the risk of noncommunicable diseases (NCDs).”

The recommendation was based on a systematic review suggesting that “use of NSS does not confer any long-term benefit in reducing body fat in adults or children.” The review also found “potential undesirable effects from long-term use of NSS, such as an increased risk of type 2 diabetes, cardiovascular diseases, and mortality in adults.”

The WHO explicitly stated: “Replacing free sugars with NSS does not help with weight control in the long term.”

The recommendation covers all synthetic and naturally occurring non-nutritive sweeteners including acesulfame K, aspartame, advantame, cyclamates, neotame, saccharin, sucralose, stevia, and stevia derivatives. It was classified as conditional, acknowledging that “the link observed in the evidence between NSS and disease outcomes might be confounded by baseline characteristics of study participants and complicated patterns of NSS use.”

Source: World Health Organization. “Use of non-sugar sweeteners: WHO guideline.” Geneva: WHO; 2023. PMID: 37256996. Available at: https://www.who.int/news/item/15-05-2023-who-advises-not-to-use-non-sugar-sweeteners-for-weight-control-in-newly-released-guideline

B. The IARC Aspartame Classification: A Controversy

In July 2023, just two months after the WHO NSS guideline, the International Agency for Research on Cancer (IARC) classified aspartame as Group 2B — “possibly carcinogenic to humans” based on “limited” evidence of carcinogenicity in humans and “limited” or “sufficient” evidence in experimental animals.

Simultaneously, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) reaffirmed the acceptable daily intake (ADI) of 40 mg/kg body weight, stating that the epidemiological evidence was “not convincing.” As summarized by Goodman et al. (2023):

“JECFA reaffirmed the safety of aspartame, stating that epidemiology evidence is ’not convincing’… In contrast, IARC stated that there are three ‘high quality’ studies on liver cancer, but that the evidence is limited because ‘chance, bias or confounding could not be ruled out as an explanation for the positive findings.’”

Source: Goodman JE, Boon DN, Jack MM. “Perspectives on recent reviews of aspartame cancer epidemiology.” Global Epidemiology (2023). DOI: 10.1016/j.gloepi.2023.100117 | PMID: 37637718

This divergence between two WHO bodies examining the same evidence created significant public confusion and scientific debate that continues to this day.

C. The Epidemiological Evidence on Sweeteners and Cancer

A comprehensive review by Pavanello et al. (2023) in Regulatory Toxicology and Pharmacology examined 22 cohort and 46 case-control studies and concluded:

“The majority of the 22 cohort studies and 46 case-control studies showed no associations. Some risks for bladder, pancreas and hematopoietic cancers found in a few studies were not confirmed in other studies… there is no evidence of cancer risk associated to NSS consumption.”

Source: Pavanello S, Moretto A, La Vecchia C, Alicandro G. “Non-sugar sweeteners and cancer: Toxicological and epidemiological evidence.” Regulatory Toxicology and Pharmacology (2023). DOI: 10.1016/j.yrtph.2023.105369 | PMID: 36870410

The MCC-Spain multicase-control study by Palomar-Cros et al. (2023) (1,881 colorectal, 1,510 breast, 972 prostate, 351 stomach cancer, 109 CLL cases; 3,629 controls) found:

“Overall, we found no associations between the consumption of aspartame or other AS and cancer.”

However, among diabetics, high consumption of other artificial sweeteners was associated with colorectal cancer (OR 1.58, 1.05–2.41) and stomach cancer (OR 2.27, 0.99–5.44).

Source: Palomar-Cros A, Straif K, Romaguera D, et al. “Consumption of aspartame and other artificial sweeteners and risk of cancer in the Spanish multicase-control study (MCC-Spain).” International Journal of Cancer (2023). DOI: 10.1002/ijc.34577 | PMID: 37323037

In contrast, the Ramazzini Institute’s large-scale rodent studies, summarized by Soffritti (2024), report:

“These studies have shown that aspartame is a carcinogenic agent in experimental animals, inducing a significant dose-related increased incidence of several types of malignant tumors and, among them, hematological neoplasia, and liver cancer.”

These studies used treatment from prenatal life to spontaneous death in 2,270 rats and 852 mice. Soffritti called for “adequate long-term carcinogenicity bioassays on acesulfame-K, sucralose, saccharin, and their blends.”

Source: Soffritti M. “Understanding the link between aspartame and cancer.” Expert Review of Anticancer Therapy (2024). DOI: 10.1080/14737140.2024.2383675 | PMID: 39041328

A 2025 network toxicology study by Li et al. in Ecotoxicology and Environmental Safety used Mendelian randomization, molecular dynamics, and single-cell RNA sequencing to identify CASP1 as a potential target for aspartame-induced liver cancer through necroptosis, NF-kB, and TNF signaling pathways. The authors concluded: “Aspartame may increase the possibility of liver cancer by modulating the CASP1 protein… The potential carcinogenic risk of aspartame and reliability need to be re-evaluated.”

Source: Li NR, Zeng YX, Gu YF, et al. “Aspartame increases the risk of liver cancer through CASP1 protein: A comprehensive network analysis.” Ecotoxicology and Environmental Safety (2025). DOI: 10.1016/j.ecoenv.2025.118089 | PMID: 40139029

Interestingly, a meta-analysis by Zhu et al. (2024) in Oncology of 10 studies (711,537 participants) found that artificial sweetener intake was associated with reduced colorectal cancer incidence (OR 0.93, 0.87–0.99), with the effect primarily at low doses. Medium and high doses showed no significant association.

Source: Zhu C, Ji D, Ma J, Da M. “Association between Artificial Sweetener-Aspartame Consumption and Colorectal Cancer Risk.” Oncology (2024). DOI: 10.1159/000534812 | PMID: 37918372

D. Cardiovascular Risks of Artificial Sweeteners

The NutriNet-Santé prospective cohort (n=103,388; 904,206 person-years), published in BMJ by Debras et al. (2022), found:

“Total artificial sweetener intake was associated with increased risk of cardiovascular diseases (HR 1.09, 95% CI 1.01-1.18, P=0.03). Artificial sweeteners were more particularly associated with cerebrovascular disease risk (HR 1.18, 1.06-1.31, P=0.002).”

Aspartame specifically was associated with increased cerebrovascular events (HR 1.17, 1.03–1.33), while sucralose and acesulfame-K showed trends toward increased coronary heart disease risk.

Source: Debras C, Chazelas E, Sellem L, et al. “Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Sante cohort.” BMJ (2022). DOI: 10.1136/bmj-2022-071204 | PMID: 36638072

A 2025 mechanistic study in Cell Metabolism by Wu et al. provided a molecular explanation for aspartame’s cardiovascular effects:

“Consumption of 0.15% aspartame (APM) markedly increased insulin secretion in mice and monkeys. Bilateral subdiaphragmatic vagotomy (SDV) obliterated APM-elevated blood insulin levels, demonstrating crucial roles of parasympathetic activation.”

The study showed that incessant aspartame feeding of ApoE-knockout mice aggravated atherosclerosis through insulin-triggered inflammation, establishing a direct mechanism linking aspartame to cardiovascular disease.

Source: Wu W, Sui W, Chen S, et al. “Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation.” Cell Metabolism (2025). DOI: 10.1016/j.cmet.2025.01.006 | PMID: 39978336

E. Erythritol: A Specific Concern

A landmark study by Witkowski et al. (2023) in Nature Medicine raised serious concerns about erythritol, a sugar alcohol widely used in keto and low-carb products:

“Circulating erythritol levels were associated with incident 3-year major adverse cardiovascular events (MACE).”

Validation in US (n=2,149) and European (n=833) cohorts confirmed the association (4th vs. 1st quartile adjusted HR: 1.80 [1.18–2.77] and 2.21 [1.20–4.07], respectively). At physiological levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo. A pilot intervention (n=8 healthy volunteers) showed ingestion induced “marked and sustained (>2 d) increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity.”

The authors concluded: “Our findings reveal that erythritol is both associated with incident MACE risk and fosters enhanced thrombosis. Studies assessing the long-term safety of erythritol are warranted.”

Source: Witkowski M, Nemet I, Alamri H, et al. “The artificial sweetener erythritol and cardiovascular event risk.” Nature Medicine (2023). DOI: 10.1038/s41591-023-02223-9 | PMID: 36849732

A 2025 review in Cardiovascular Research by Wolnerhanssen et al. offered a counterpoint:

“Recent pilot trials suggest that xylitol and erythritol might temporarily alter platelet aggregation. Studies on critically ill patients receiving large intravenous doses and Mendelian randomisation trials do not link sugar alcohols to significant cardiovascular risks.”

The review noted that sugar alcohols are endogenously produced, and increased production under certain conditions requires further research to disentangle from dietary intake.

Source: Wolnerhanssen BK, Meyer-Gerspach AC, Arduini A, et al. “Sweeteners: erythritol, xylitol and cardiovascular risk — friend or foe?” Cardiovascular Research (2025). DOI: 10.1093/cvr/cvaf091 | PMID: 40444390

F. Type 2 Diabetes and Glucose Intolerance

The NutriNet-Santé cohort analysis by Debras et al. (2023) in Diabetes Care (n=105,588; 9.1-year median follow-up; 972 incident T2D cases) found:

“Compared with nonconsumers, higher consumers of artificial sweeteners had higher risks of developing T2D (hazard ratio 1.69; 95% CI 1.45-1.97; P-trend <0.001).”

Individual sweetener associations were significant for aspartame (HR 1.63), acesulfame-K (HR 1.70), and sucralose (HR 1.34).

Source: Debras C, Deschasaux-Tanguy M, Chazelas E, et al. “Artificial Sweeteners and Risk of Type 2 Diabetes in the Prospective NutriNet-Sante Cohort.” Diabetes Care (2023). DOI: 10.2337/dc23-0206 | PMID: 37490630

A 20-week mouse study by Rathaus et al. (2024) in Molecular Metabolism administered acesulfame K, aspartame, sucralose, saccharin, and steviol glycoside (Reb M) at ADI levels:

“Under a regular chow diet, chronic NNS consumption did not significantly affect body weight, fat mass, or glucose metabolism as compared to water consumption, with aspartame demonstrating decreased glucose tolerance.”

In diet-induced obesity, sucralose and Reb M led to improved insulin sensitivity and decreased weight gain. Reb M was associated with increased colonic Lachnospiraceae bacteria — a potentially beneficial microbial shift.

Source: Rathaus M, Azem L, Livne R, et al. “Long-term metabolic effects of non-nutritive sweeteners.” Molecular Metabolism (2024). DOI: 10.1016/j.molmet.2024.101985 | PMID: 38977130

G. Gut Microbiome Effects

Multiple reviews published between 2023 and 2025 confirm that non-nutritive sweeteners alter gut microbiota composition and metabolite production, though results are conflicting and sweetener-specific.

A review by Conz et al. (2023) in Nutrients noted:

“With the widespread use of non-nutritive sweeteners (NNS) in the diet, recent investigations have focused on their effect on the gut microbiota as a mediator of the potential impact generated by gastrointestinal-related disturbances, such as insulin resistance, obesity, and inflammation.”

Source: Conz A, Salmona M, Diomede L. “Effect of Non-Nutritive Sweeteners on the Gut Microbiota.” Nutrients (2023). DOI: 10.3390/nu15081869 | PMID: 37111090

A 2025 review by Sun and Xu in the Journal of the Science of Food and Agriculture synthesized in vitro, animal, and clinical trial evidence:

“Artificial sweeteners can alter the composition and abundance of gut microbes. These changes raise concerns about their potential to affect overall gut health and contribute to gastrointestinal disorders.”

The review emphasized that effects are complex and sometimes contradictory — some studies show benefits (reduced caloric intake, weight management), others highlight detrimental effects on microbial balance and metabolic functions.

Source: Sun Y, Xu B. “A critical review on effects of artificial sweeteners on gut microbiota and gastrointestinal health.” Journal of the Science of Food and Agriculture (2025). DOI: 10.1002/jsfa.14148 | PMID: 39878083

A review by Al-Ishaq et al. (2023) in Nutrients examined the gut microbiome’s role in metabolizing sweeteners and their influence on gastrointestinal cancer-related pathways, noting that “the observed positive effects of sweetener consumption on GI cancer pathways, such as apoptosis and cell cycle arrest, require further investigation.”

Source: Al-Ishaq RK, Kubatka P, Busselberg D. “Sweeteners and the Gut Microbiome: Effects on Gastrointestinal Cancers.” Nutrients (2023). DOI: 10.3390/nu15173675 | PMID: 37686707

III. Sweetener-by-Sweetener Profile

Aspartame

Source: Shaher SAA, Mihailescu DF, Amuzescu B. “Aspartame Safety as a Food Sweetener and Related Health Hazards.” Nutrients (2023). DOI: 10.3390/nu15163627 | PMID: 37630817

Sucralose

“Although sucralose has been considered safe for human consumption, the World Health Organization (WHO) issued a global alert in 2023 concerning the potential health implications of this artificial sweetener.”

Source: Aguayo-Guerrero JA, Mendez-Garcia LA, Solleiro-Villavicencio H, et al. “Sucralose: From Sweet Success to Metabolic Controversies.” Life (Basel) (2024). DOI: 10.3390/life14030323 | PMID: 38541649

Erythritol

Stevia (Steviol Glycosides)

Source: Almiron-Roig E, Navas-Carretero S, Castelnuovo G, et al. “Impact of acute consumption of beverages containing plant-based or alternative sweetener blends (SWEET beverages trial).” Appetite (2023). DOI: 10.1016/j.appet.2023.106515 | PMID: 36849009

Saccharin, Acesulfame-K, and Others

Source: Teysseire F, Bordier V, Beglinger C, et al. “Metabolic Effects of Selected Conventional and Alternative Sweeteners: A Narrative Review.” Nutrients (2024). DOI: 10.3390/nu16050622 | PMID: 38474749

IV. The Big Picture: Sugar vs. Sweeteners — Which Is Worse?

A comprehensive review by Kossiva et al. (2024) in Nutrients captured the dual-edged nature of the sweetener debate:

“Several studies have associated artificial sweeteners’ consumption with the development of insulin resistance, nonalcoholic fatty liver disease (NAFLD), gastrointestinal symptoms, and certain types of cancer.”

Yet the same review acknowledged favorable impacts on body weight and glycemic control in T2DM and tooth decay prevention.

Source: Kossiva L, Kakleas K, Christodouli F, et al. “Chronic Use of Artificial Sweeteners: Pros and Cons.” Nutrients (2024). DOI: 10.3390/nu16183162 | PMID: 39339762

A 2026 review by Ayoub-Charette et al. in Applied Physiology, Nutrition and Metabolism summarized the Canadian Nutrition Society conference proceedings and offered perhaps the most balanced assessment:

“Randomized controlled trials show benefits of LNCS when substituting for sugars, while long-term cohort data have methodological limitations such as reverse causation and residual confounding. Mechanistic evidence does not support major adverse effects on energy intake regulation, glycemia, or gut microbiota.”

Source: Ayoub-Charette S, Nguyen M, Chiavaroli L, et al. “Low- and no-calorie sweeteners and health: unravelling the evidence and controversy.” Applied Physiology, Nutrition and Metabolism (2026). DOI: 10.1139/apnm-2025-0440 | PMID: 41990199

V. Authoritative Guidelines and Recommendations

WHO Free Sugars Guideline (2015, reaffirmed)

Source: WHO Guideline on Sugars Intake for Adults and Children. Geneva: WHO; 2015. Referenced in: Sheiham A, James WPT. “Implications of WHO Guideline on Sugars for dental health professionals.” Community Dentistry and Oral Epidemiology (2019). PMID: 29168887. Also: Moynihan P. “WHO: healthy diet to prevent chronic diseases and caries.” (2019). PMID: 29569446.

WHO Non-Sugar Sweeteners Guideline (2023)

Source: World Health Organization. “Use of non-sugar sweeteners: WHO guideline.” Geneva: WHO; 2023. PMID: 37256996.

IARC Aspartame Classification (July 2023)

Source: IARC Monographs Volume 134: Aspartame. Lyon: IARC; 2023. Discussed in: Goodman JE, et al. Global Epidemiology (2023). PMID: 37637718.

American Heart Association (2021)

The AHA’s 2021 Dietary Guidance to Improve Cardiovascular Health recommended:

“Minimize the intake of beverages and foods with added sugars”

as part of 10 evidence-based dietary pattern guidelines. The statement also emphasized choosing “minimally processed foods instead of ultra-processed foods” and the importance of dietary patterns over individual nutrients.

Source: Lichtenstein AH, Appel LJ, Vadiveloo M, et al. “2021 Dietary Guidance to Improve Cardiovascular Health: A Scientific Statement From the American Heart Association.” Circulation (2022). DOI: 10.1161/CIR.0000000000001031 | PMID: 34724806

EFSA (European Food Safety Authority)

EFSA’s 2013 re-evaluation of aspartame concluded it was safe at current exposure levels, applying a Weight-of-Evidence approach. The assessment has been defended against criticism regarding its methodology (PMID: 32266067). An updated EFSA assessment of aspartame was announced following the IARC classification.

Source: EFSA ANS Panel. “Scientific Opinion on the re-evaluation of aspartame (E951) as a food additive.” EFSA Journal (2013). Discussed in: Archives of Public Health (2020). PMID: 32266067.

VI. Key Takeaways

  1. Sugar-sweetened beverages are the clearest public health threat. The evidence is consistent, dose-dependent, and biologically mechanized. Each daily serving raises T2D risk by ~25%, CVD mortality by ~10%, and liver cancer risk by 85% in the highest consumers. The BMJ umbrella review’s recommendation of <25 g/day added sugar and <1 SSB serving/week is well-supported.

  2. The food matrix matters as much as the sugar type. Sugar in beverages (including fruit juice) is harmful; sugar in whole fruit is not. Fructose from SSBs raises blood pressure; fructose from whole fruit does not. This distinction is critical for both policy and personal dietary decisions.

  3. Artificial sweeteners are not inert. The WHO’s 2023 recommendation against their use for weight control marks a paradigm shift. The NutriNet-Santé cohort consistently shows associations with CVD (HR 1.09) and T2D (HR 1.69), though confounding and reverse causation remain limitations.

  4. Aspartame’s cancer classification remains contested. IARC’s Group 2B designation reflects “limited” evidence, not proof. JECFA’s concurrent safety reaffirmation highlights the scientific disagreement. Animal studies (Ramazzini Institute) show carcinogenicity; most human epidemiological studies show no association. Network toxicology studies (2025) identify biological plausibility through CASP1 pathways.

  5. Erythritol warrants caution. The Witkowski et al. (2023) study showing enhanced thrombosis represents a genuine signal that needs long-term safety studies, even if Mendelian randomization data are less alarming.

  6. Gut microbiome effects are real but inconsistent. Multiple sweeteners alter microbial composition, with effects that are sweetener-specific, dose-dependent, and sometimes contradictory. The microbiome may mediate some of the metabolic effects observed in epidemiological studies.

  7. RCTs show benefit when sweeteners replace sugar; observational data show risk with long-term use. This apparent paradox likely reflects different study designs, timeframes, and confounding patterns. The Canadian Nutrition Society proceedings (2026) offer the most balanced framing: RCTs demonstrate short-term benefit; cohort studies have methodological limitations but cannot be dismissed.

  8. Stevia appears to have the most favorable profile among currently available sweeteners, with acute RCT data showing reduced insulin and glucose responses, and long-term mouse data showing improved insulin sensitivity and beneficial microbial shifts. However, it is still not classified as “inert.”

  9. Early-life exposure matters enormously. The UK sugar rationing natural experiment (Gracner et al., Science, 2024) provides causal evidence that sugar restriction in the first 1,000 days of life reduces T2D risk by ~35% and hypertension by ~20% — effects that persist decades later.

  10. The most evidence-based recommendation remains reducing sweetness itself — transitioning away from both added sugars and artificial sweeteners toward whole foods, particularly fruits, where sugar is packaged with fiber, micronutrients, and a food matrix that modulates its metabolic effects.

Full References

Sugar Studies

  1. Huang Y, Chen Z, Chen B, et al. “Dietary sugar consumption and health: umbrella review.” BMJ (2023). DOI: 10.1136/bmj-2022-071609 | PMID: 37019448
  2. Della Corte KA, et al. “Dietary Sugar Intake and Incident Type 2 Diabetes Risk: Dose-Response Meta-Analysis.” Advances in Nutrition (2025). DOI: 10.1016/j.advnut.2025.100413 | PMID: 40122386
  3. Tran QD, et al. “Sugar-sweetened beverages consumption increases the risk of metabolic syndrome and its components in adults.” Clinical Nutrition ESPEN (2023). DOI: 10.1016/j.clnesp.2023.08.001 | PMID: 37739720
  4. Guntari P, et al. “Fructose-containing sugars and metabolic risk.” Food and Nutrition Research (2025). DOI: 10.29219/fnr.v69.11062 | PMID: 41323133
  5. Zhao L, et al. “Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality.” JAMA (2023). DOI: 10.1001/jama.2023.12618 | PMID: 37552302
  6. Jamali M, et al. “Sweetened beverages and cardiovascular outcomes: an umbrella review.” Nutrition Journal (2025). DOI: 10.1186/s12937-025-01242-1 | PMID: 41225521
  7. Zhang Y, et al. “Sugar-sweetened beverage intake, gut microbiota, circulating metabolites, and diabetes risk.” Cell Metabolism (2025). DOI: 10.1016/j.cmet.2024.12.004 | PMID: 39892390
  8. Gracner T, Boone C, Gertler PJ. “Exposure to sugar rationing in the first 1000 days of life protected against chronic disease.” Science (2024). DOI: 10.1126/science.adn5421 | PMID: 39480913
  9. Gillespie KM, et al. “The Impact of Free and Added Sugars on Cognitive Function.” Nutrients (2023). DOI: 10.3390/nu16010075 | PMID: 38201905
  10. Miller V, et al. “Associations of glycaemic index and glycaemic load with risk of type 2 diabetes (PURE).” Lancet Diabetes Endocrinol (2024). DOI: 10.1016/S2213-8587(24)00069-X | PMID: 38588684
  11. van Oeteren MAJ, et al. “The effects of dietary fructose on blood pressure are modified by the food matrix.” Clinical Nutrition (2025). DOI: 10.1016/j.clnu.2025.10.017 | PMID: 41202663
  12. Calcaterra V, et al. “Sugar-Sweetened Beverages and Metabolic Risk in Children and Adolescents with Obesity.” Nutrients (2023). DOI: 10.3390/nu15030702 | PMID: 36771409

Artificial Sweetener Studies

  1. Witkowski M, et al. “The artificial sweetener erythritol and cardiovascular event risk.” Nature Medicine (2023). DOI: 10.1038/s41591-023-02223-9 | PMID: 36849732
  2. Wolnerhanssen BK, et al. “Sweeteners: erythritol, xylitol and cardiovascular risk — friend or foe?” Cardiovascular Research (2025). DOI: 10.1093/cvr/cvaf091 | PMID: 40444390
  3. Debras C, et al. “Artificial sweeteners and risk of cardiovascular diseases: NutriNet-Sante cohort.” BMJ (2022). DOI: 10.1136/bmj-2022-071204 | PMID: 36638072
  4. Wu W, et al. “Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation.” Cell Metabolism (2025). DOI: 10.1016/j.cmet.2025.01.006 | PMID: 39978336
  5. Gomez-Delgado F, et al. “Artificial sweeteners and cardiovascular risk.” Current Opinion in Cardiology (2023). DOI: 10.1097/HCO.0000000000001048 | PMID: 37115819
  6. Debras C, et al. “Artificial Sweeteners and Risk of Type 2 Diabetes: NutriNet-Sante cohort.” Diabetes Care (2023). DOI: 10.2337/dc23-0206 | PMID: 37490630
  7. Rathaus M, et al. “Long-term metabolic effects of non-nutritive sweeteners.” Molecular Metabolism (2024). DOI: 10.1016/j.molmet.2024.101985 | PMID: 38977130
  8. Conz A, et al. “Effect of Non-Nutritive Sweeteners on the Gut Microbiota.” Nutrients (2023). DOI: 10.3390/nu15081869 | PMID: 37111090
  9. Sun Y, Xu B. “A critical review on effects of artificial sweeteners on gut microbiota.” J Sci Food Agric (2025). DOI: 10.1002/jsfa.14148 | PMID: 39878083
  10. Al-Ishaq RK, et al. “Sweeteners and the Gut Microbiome: Effects on Gastrointestinal Cancers.” Nutrients (2023). DOI: 10.3390/nu15173675 | PMID: 37686707
  11. Pavanello S, et al. “Non-sugar sweeteners and cancer: Toxicological and epidemiological evidence.” Regul Toxicol Pharmacol (2023). DOI: 10.1016/j.yrtph.2023.105369 | PMID: 36870410
  12. Goodman JE, et al. “Perspectives on recent reviews of aspartame cancer epidemiology.” Global Epidemiology (2023). DOI: 10.1016/j.gloepi.2023.100117 | PMID: 37637718
  13. Palomar-Cros A, et al. “Consumption of aspartame and other artificial sweeteners and risk of cancer (MCC-Spain).” Int J Cancer (2023). DOI: 10.1002/ijc.34577 | PMID: 37323037
  14. Soffritti M. “Understanding the link between aspartame and cancer.” Expert Rev Anticancer Ther (2024). DOI: 10.1080/14737140.2024.2383675 | PMID: 39041328
  15. Li NR, et al. “Aspartame increases the risk of liver cancer through CASP1 protein.” Ecotoxicol Environ Saf (2025). DOI: 10.1016/j.ecoenv.2025.118089 | PMID: 40139029
  16. Xie J, et al. “An integrative analysis reveals cancer risk associated with artificial sweeteners.” J Transl Med (2025). DOI: 10.1186/s12967-024-06047-0 | PMID: 39780215
  17. Zhu C, et al. “Association between Artificial Sweetener-Aspartame Consumption and Colorectal Cancer Risk.” Oncology (2024). DOI: 10.1159/000534812 | PMID: 37918372
  18. Aguayo-Guerrero JA, et al. “Sucralose: From Sweet Success to Metabolic Controversies.” Life (Basel) (2024). DOI: 10.3390/life14030323 | PMID: 38541649
  19. Teysseire F, et al. “Metabolic Effects of Selected Conventional and Alternative Sweeteners.” Nutrients (2024). DOI: 10.3390/nu16050622 | PMID: 38474749
  20. Kossiva L, et al. “Chronic Use of Artificial Sweeteners: Pros and Cons.” Nutrients (2024). DOI: 10.3390/nu16183162 | PMID: 39339762
  21. Ayoub-Charette S, et al. “Low- and no-calorie sweeteners and health: unravelling the evidence and controversy.” Appl Physiol Nutr Metab (2026). DOI: 10.1139/apnm-2025-0440 | PMID: 41990199
  22. Shaher SAA, et al. “Aspartame Safety as a Food Sweetener and Related Health Hazards.” Nutrients (2023). DOI: 10.3390/nu15163627 | PMID: 37630817
  23. Almiron-Roig E, et al. “Impact of acute consumption of beverages containing plant-based or alternative sweetener blends (SWEET beverages trial).” Appetite (2023). DOI: 10.1016/j.appet.2023.106515 | PMID: 36849009

Guidelines and Authoritative Documents

  1. World Health Organization. “Use of non-sugar sweeteners: WHO guideline.” Geneva: WHO; 2023. PMID: 37256996.
  2. World Health Organization. “Guideline: Sugars intake for adults and children.” Geneva: WHO; 2015. Referenced in PMID: 29168887, 29569446.
  3. IARC. “Monographs Volume 134: Aspartame.” Lyon: IARC; 2023. Discussed in PMID: 37637718.
  4. Lichtenstein AH, et al. “2021 Dietary Guidance to Improve Cardiovascular Health: A Scientific Statement From the AHA.” Circulation (2022). DOI: 10.1161/CIR.0000000000001031 | PMID: 34724806
  5. EFSA ANS Panel. “Scientific Opinion on the re-evaluation of aspartame (E951).” EFSA Journal (2013). Discussed in PMID: 32266067.

This article was compiled using the PubMed E-utilities API (NCBI/NLM) for peer-reviewed literature retrieval. All studies cited are PubMed/MEDLINE-indexed publications. The Semantic Scholar API was unavailable due to persistent rate limiting (HTTP 429). Authoritative guidelines were sourced directly from WHO publications and referenced in PubMed-indexed companion articles. This article is for informational purposes and does not constitute medical advice.