Skip to main content Accessibility help

Biomarker approaches to assessing intakes and health impacts of sweeteners: challenges and opportunities

  • Alison M. Gallagher (a1) and Caomhán Logue (a1)


The term ‘sweeteners’ encompasses both nutritive and non-nutritive sweeteners, which when added to food/beverages, can enhance the flavour and other functional properties of food/beverage products. This review considers how dietary biomarker approaches may enhance current understanding of nutritive sweetener (namely free sugars) and non-nutritive or low-energy sweetener (LES) intakes and how these may impact health. Recent public health strategies to reduce free sugar consumption will help contribute to challenging sugar intake targets. Robust evaluation is needed to determine the effectiveness of these approaches to reducing free sugar consumption. LES provides a sweet taste without the addition of appreciable energy and can help maintain the palatability of reformulated products. All LES undergo rigorous safety evaluations prior to approval for use. Whilst intervention data suggest LES can be beneficial for health (relating to weight status and glycaemic control), debate persists on their use and findings from population-based research are mixed, in part because of potential contributing factors such as reverse causality. Additionally, assessments often consider only certain sources of LES (e.g. LES-beverages) and/or LES as a homogeneous group despite differing biological fates, thus not adequately capturing intakes of individual LES or allowing for reliable estimation of overall intakes. Urinary biomarker approaches developed/investigated for sweetener consumption have the potential to overcome existing limitations of dietary data by providing more objective intake data, thereby enhancing population-based research. In conclusion, such biomarker approaches to the concomitant study of free sugars and LES intakes are timely and represent interesting developments in an area of significant public health interest.


Corresponding author

*Corresponding author: Alison M. Gallagher, email


Hide All
1.World Health Organisation (2015) Guidelines on sugars intake for adults and children. (accessed February 2019).
2.World Health Organisation (2018) Overweight and obesity. (accessed February 2019).
3.World Health Organisation (2016) Global report on diabetes. (accessed February 2019).
4.Scientific Advisory Committee on Nutrition (2015) SACN Carbohydrates and Health Report. London: Public Health England. (accessed February 2019).
5.Public Health England (2018) National Diet and Nutrition Survey. Results from Years 7 and 8 (combined) of the Rolling Programme (2014/2015 to 2015/2016). (accessed February 2019).
6.European Food Safety Authority (2010) Scientific Opinion on Dietary Reference Values for carbohydrates and dietary fibre. EFSA Journal 8, 1462.
7.US Department of Health and Human Services and US Department of Agriculture (2015) 2015–2020 Dietary Guidelines for Americans, 8th ed. (accessed February 2019).
8.Public Health England (2017) Sugar Reduction: Achieving the 20%. A technical report outlining progress to date, guidelines for industry, 2015 baseline levels in key foods and next steps. (accessed February 2019).
9.Public Health England (2018) Sugar reduction and wider reformulation: report on progress towards the first 5% reduction and next steps. (accessed February 2019).
10.Tappy, L, Morio, B, Azzout-Marniche, D et al. (2018) French Recommendations for Sugar Intake in Adults: A Novel Approach Chosen by ANSES. Nutrients 10, pii: E989.
11.Erickson, J & Slavin, J (2015) Total, added, and free sugars: Are restrictive guidelines science-based or achievable? Nutrients 7, 28662878.
12.French Agency for Food, Environmental and Occupational Health and Safety (2017) Opinion of ANSES concerning the establishment of sugar intake recommendations [Avis de l'ANSES relatif à l’établissement de recommandations d'apports en sucres]. (accessed February 2019).
13.European Food Safety Authority (2018) Protocol for the scientific opinion on the Tolerable Upper Intake Level of dietary sugars. EFSA J 16, 5393.
14.Magnuson, BA, Carakostas, MC, Moore, NH et al. (2016) Biological fate of low-calorie sweeteners. Nutr Rev 74, 670689.
15.Benford, DJ (2000) The Acceptable Daily Intake: A Tool for Ensuring Food Safety. Brussels, Belgium: ILSI Europe.
16.European Parliament and Council (2008) Regulation (EC) No. 1333/2008 of 16 December 2008 on food additives. Official J Eur Union L237, 312.
17.Gibson, S, Ashwell, M, Arthur, J et al. (2017) What can the food and drink industry do to help achieve the 5% free sugars goal? Perspect Public Health 137, 237247.
18.Martyn, D, Darch, M, Roberts, A et al. (2018) Low-/no-calorie sweeteners: a review of global intakes. Nutrients 10, pii: E357.
19.Sylvetsky, AC, Welsh, JA, Brown, RJ et al. (2012) Low-calorie sweetener consumption is increasing in the United States. Am J Clin Nutr 96, 640646.
20.Sylvetsky, AC, Jin, Y, Clark, EJ et al. (2017) Consumption of low-calorie sweeteners among children and adults in the United States. J Acad Nutr Diet 117, 441448.
21.Logue, C, Dowey, LC, Strain, JJ et al. (2016) The potential application of a biomarker approach for the investigation of low-calorie sweetener exposure. Proc Nutr Soc 75, 216225.
22.Sylvetsky, AC, Blau, JE & Rother, KI (2016) Understanding the metabolic and health effects of low-calorie sweeteners: methodological considerations and implications for future research. Rev Endocr Metab Disord 17, 187194.
23.Sylvetsky, AC, Walter, PJ, Garraffo, HM et al. (2017) Widespread sucralose exposure in a randomized clinical trial in healthy young adults. Am J Clin Nutr 105, 820823.
24.Sylvetsky, AC, Gardner, AL, Bauman, V et al. (2015) Nonnutritive sweeteners in breast milk. J Toxicol Environ Health A 78, 10291032.
25.Lange, FT, Scheurer, M & Brauch, HJ (2012) Artificial sweeteners – a recently recognized class of emerging environmental contaminants: a review. Anal Bioanal Chem 403, 25032518.
26.Rogers, PJ, Hogenkamp, PS, de Graaf, C et al. (2016) Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies. Int J Obes (Lond) 40, 381394.
27.Azad, MB, Abou-Setta, AM, Chauhan, BF et al. (2017) Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. Canadian Med Assoc J 189, E929E939.
28.Imamura, F, O'Connor, L, Ye, Z et al. (2016) 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 50, 496504.
29.Weihrauch, MR & Diehl, V. (2004) Artificial sweeteners – do they bear a carcinogenic risk? Annals Oncol 15, 14601465.
30.La Vecchia, C (2013) Low-calorie sweeteners and the risk of preterm delivery: results from two studies and a meta-analysis. J Family Plann Reprod Health Care 39, 1213.
31.EFSA Panel on Dietetic Products, Nutrition, and Allergies (2011) Scientific Opinion on the substantiation of health claims related to intense sweeteners and contribution to the maintenance or achievement of a normal body weight (ID 1136, 1444, 4299), reduction of post-prandial glycaemic responses (ID 4298), maintenance of normal blood glucose concentrations (ID 1221, 4298), and maintenance of tooth mineralisation by decreasing tooth demineralisation (ID 1134, 1167, 1283) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J 9, 2229. (accessed February 2019).
32.Anton, SD, Martin, CK, Han, H et al. (2010) Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite 55, 3743.
33.Bellisle, F (2015) Intense sweeteners, appetite for the sweet taste, and relationship to weight management. Curr Obes Rep 4, 106110.
34.Rogers, PJ (2018) The role of low-calorie sweeteners in the prevention and management of overweight and obesity: evidence v. conjecture. Proc Nutr Soc 77, 230238.
35.Burke, MV & Small, DM (2015) Physiological mechanisms by which non-nutritive sweeteners may impact body weight and metabolism. Physiol Behav 152(Pt B), 381388.
36.Mattes, RD & Popkin, BM (2009) Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. Am J Clin Nutr 89, 114.
37.Suez, J, Korem, T, Zeevi, D et al. (2014) Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514, 181186.
38.O'Connor, L, Imamura, F, Lentjes, MA et al. (2015) Prospective associations and population impact of sweet beverage intake and type 2 diabetes, and effects of substitutions with alternative beverages. Diabetologia 58, 14741483.
39.Nichol, AD, Holle, MJ & An, R (2018) Glycemic impact of non-nutritive sweeteners: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr 72, 796804.
40.French Agency for Food, Environmental and Occupational Health and Safety (2015) Opinion on the assessment of the nutritional benefits and risks related to intense sweeteners. (accessed February 2019).
41.Toews, I, Lohner, S, Küllenberg de Gaudry, D et al. (2019) Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies. Br Med J 364, k4718.
42.Logue, C, Dowey, LRC, Strain, JJ et al. (2017) Application of liquid chromatography-tandem mass spectrometry to determine urinary concentrations of five commonly used low-calorie sweeteners: a novel biomarker approach for assessing recent intakes? J Agric Food Chem 65, 45164525.
43.Rothwell, JA, Madrid-Gambin, F, Garcia-Aloy, M et al. (2018) Biomarkers of intake for coffee, tea, and sweetened beverages. Genes Nutr 13, 15.
44.Jahren, AH, Saudek, C, Yeung, EH et al. (2006) An isotopic method for quantifying sweeteners derived from corn and sugar cane. Am J Clin Nutr 84, 13801384.
45.Hedrick, VE, Davy, BM, Wilburn, GA et al. (2016) Evaluation of a novel biomarker of added sugar intake (δ 13C) compared with self-reported added sugar intake and the Healthy Eating Index-2010 in a community-based, rural U.S. sample. Public Health Nutr 19, 429436.
46.Luceri, C, Caderni, G, Lodovici, M et al. (1996) Urinary excretion of sucrose and fructose as a predictor of sucrose intake in dietary intervention studies. Cancer Epidemiol, Biomarkers Prev 5, 167171.
47.Tasevska, N, Runswick, SA, McTaggart, A et al. (2005) Urinary sucrose and fructose as biomarkers for sugar consumption. Cancer Epidemiol, Biomarkers Prev 14, 12871294.
48.Tasevska, N (2015) Urinary sugars - a biomarker of total sugars intake. Nutrients 7, 58165833.
49.Campbell, R, Tasevska, N, Jackson, KG et al. (2017) Association between urinary biomarkers of total sugars intake and measures of obesity in a cross-sectional study. PLoS One 12, e0179508.
50.Gibbons, H, McNulty, BA, Nugent, AP et al. (2015) A metabolomics approach to the identification of biomarkers of sugar-sweetened beverage intake. Am J Clin Nutr 101, 471477.
51.Beckmann, M, Joosen, AM, Clarke, MM et al. (2016) Changes in the human plasma and urinary metabolome associated with acute dietary exposure to sucrose and the identification of potential biomarkers of sucrose intake. Mol Nutr Food Res 60, 444457.
52.COMA (1991) Dietary Reference Values for Food Energy and Nutrients for the United Kingdom. London: HMSO.
53.Institute of Medicine (2005) Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: National Academies Press.
54.European Food Safety Authority (2009) Review of labelling reference intake values for selected nutritional elements. EFSA J 1008, 114.
55.Bates, B, Lennox, A, Prentice, A et al. (2014) National Diet and Nutrition Survey: results from Years 1 to 4 (combined) of the rolling programme for 2008 and 2009 to 2011 and 2012. (accessed February 2019).
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Proceedings of the Nutrition Society
  • ISSN: 0029-6651
  • EISSN: 1475-2719
  • URL: /core/journals/proceedings-of-the-nutrition-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed