Risk assessment of nutrients: There must be a threshold for their effects.

Tzitzo, Veenendaal, 3904 DM, the Netherlands. Electronic address: Michiel.lowik@tzitzo.nu. Novo Nordisk Foundation, Hellerup, Denmark. Electronic address: ara@novo.dk. Faculty of Medicine, Imperial College London, London, W12 0NN, United Kingdom. Electronic address: a.boobis@imperial.ac.uk. Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom. Electronic address: P.C.Calder@soton.ac.uk. School of Life Sciences, Technical University of Munich, 85354, Freising, Germany. Electronic address: contact@hdaniel.de. Division of Toxicology, Wageningen University & Research, Wageningen, 6700 EA, the Netherlands. Electronic address: ivonne.rietjens@wur.nl. Departments of Medicine and of Nutritional Sciences and Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5Ss 1A8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, St. Michael's Hospital, Toronto, ON, M5C 2T2, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, M5C 2T2, Canada. Electronic address: john.sievenpiper@alumni.utoronto.ca. Food Safety & Nutrition Consultancy, Zeist, 3703 EE, the Netherlands. Electronic address: FSNConsultancy@hotmail.com.

Regulatory toxicology and pharmacology : RTP. 2024;:105539

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Abstract

Nutrients serve physiological functions in a dose-dependent manner and that needs to be recognized in risk assessment. An example of the consequences of not properly considering this can be seen in a recent assessment by the European Food Safety Authority (EFSA). EFSA concluded in 2022 that the intake of added and free sugars should be "as low as possible in the context of a nutritionally adequate diet". That conclusion of EFSA is based on the effects on two surrogate endpoints for an adverse effect found in randomized controlled trials with high sugars intake levels: fasting glucose and fasting triglycerides. The lowest intake levels in these trials were around 10 energy% and at this intake level there were no adverse effects on the two outcomes. This indicates that the adverse effects of sugars have an observable threshold value for these two endpoints. The most appropriate interpretation from the vast amount of data is that currently no definitive conclusion can be drawn on the tolerable upper intake level for dietary sugars. Therefore, EFSA's own guidance would lead to the conclusion that the available data do not allow the setting of an upper limit for added sugars and hence, that more robust data are required to identify the threshold value for intake of sugars.