Background
Escalating rates of overweight and obesity are a threat to the health of billions of people across the globe. In 2016, more than 1.9 billion adults aged 18 years and older were overweight (1). Of these, more than 600 million were obese. In 2020, more than 38 million children under 5 years of age were overweight – an increase of nearly 6 million during the past 20 years (2). High body mass index (BMI) was responsible for an estimated 4 million deaths in 2017 (3), with greater increases in BMI in the overweight and obesity range leading to a greater risk of mortality (4). Obesity is also a risk factor for many noncommunicable diseases (NCDs), including cardiovascular diseases (CVDs), type 2 diabetes and certain types of cancer. NCDs are the leading causes of death globally and were responsible for an estimated 41 million (71%) of the 55 million deaths in 2019 (5). Obesity and certain NCDs also increase the likelihood of becoming severely ill from COVID-19 infection (6–10).
A high level of free sugars intake is associated with poor dietary quality (11), obesity (12) and risk of NCDs (13), and the World Health Organization (WHO) has issued guidance on limiting free sugars intake to reduce the risk of unhealthy weight gain and dental caries (14). Since the release of the WHO guideline on free sugars intake, interest in the potential utility of non-sugar sweeteners (NSS)1 to reduce sugars intake at the population level has increased.
Referred to by a variety of names, including high-intensity sweeteners, low- or no-calorie sweeteners, non-nutritive sweeteners, non-caloric sweeteners and sugar-substitutes, NSS have been developed as an alternative to free sugars. They are widely used as an additive in pre-packaged foods, beverages and personal care products (e.g. toothpaste, mouthwash), as well as added to foods and beverages directly by the consumer. Because of their ability to impart sweet taste without calories, NSS are generally marketed as aiding weight loss or maintenance of healthy weight. They are incorporated into prepared and packaged foods and beverages in a number of ways, including individually, in combinations of different NSS or in combination with free sugars (15). NSS are also frequently recommended as a means of controlling blood glucose levels in individuals with diabetes. NSS include a wide variety of synthetically derived chemicals and natural extracts that may or may not be chemically modified, and are generally many times sweeter than sugars, which allows them to be added to foods and beverages in very small quantities. Common NSS include acesulfame K, aspartame, advantame, cyclamates, neotame, saccharin, sucralose, stevia and stevia derivatives; certain D-amino acids, and several plant proteins and other extracts also impart a sweet taste.
NSS elicit sweet taste through binding and activation of sweet-taste receptors located in the oral cavity, with subsequent signalling to the brain (16). Sweet-taste receptors have more recently been found at sites outside the oral cavity, including the gastrointestinal tract, pancreas, brain and adipose tissue (17), and may be involved in various metabolic effects of NSS observed in a large body of in vitro, animal and human studies (18–22).
Individual NSS undergo toxicological assessment by various authoritative bodies, such as the Joint Food and Agriculture Organization of the United Nations (FAO)/WHO Expert Committee on Food Additives (JECFA), to establish safe levels of intake (i.e. acceptable daily intake, or ADI). Although results of randomized controlled trials (RCTs) have generally suggested that NSS may have limited impact on glucose metabolism and result in lower body weight (when coupled with energy restriction) in the short term, there is no clear consensus on whether NSS are effective for long-term weight loss or maintenance, or if they are linked to other long-term health effects at intakes within the ADI. In addition, although individual NSS interact with the same sweet-taste receptor to elicit sweet taste and likely result in the same physiological effects to some extent, they are not a homogeneous class of compounds: each has a unique chemical structure, which is reflected in different sweetness intensities, organoleptic properties and routes of processing by the body (15). As a result of these differences, individual NSS may have different physiological effects in humans (19).
Global trends in NSS use are unclear because NSS have yet to appreciably enter some markets, and robust longitudinal intake data are not readily available for many low-and middle-income countries (LMICs) (23, 24). Nevertheless, available data indicate that the number of foods and beverages containing NSS and NSS use are significant in diverse settings worldwide (23–28). Although intake rarely appears to exceed the ADI (29), NSS availability and use (predominantly in the form of consumption of beverages containing NSS) appear to be increasing in many locations - for example, in New Zealand, Norway, Slovenia and the United States of America (the United States) (30–34). This corresponds with a decline in consumption of sugar-sweetened beverages - for example, in the United States and Norway (31, 33). Evidence suggests that the shift from free sugars to NSS occurring in the United States and elsewhere may also be occurring in other countries as global efforts to reduce the intake of free sugars intensify, particularly in settings that are implementing multiple policy actions to reduce free sugars intake (23).
Rationale
Following the work of the 1989 WHO Study Group on Diet, Nutrition and the Prevention of Chronic Diseases (35), and the 2002 Joint WHO/FAO Expert Consultation on Diet, Nutrition and the Prevention of Chronic Diseases (36), WHO guidance on free sugars intake was updated and released in 2015 (14). Since the release of that guideline, interest has increased in guidance on whether incorporating NSS into policy actions and interventions aimed at reducing free sugars intake may be effective and appropriate. At the same time, NSS availability and their use by consumers have increased. Therefore, it was considered important to review the evidence in a systematic manner, and issue WHO guidance on NSS use through the WHO guideline development process.
Scope
This guideline is an extension of the larger effort to update the dietary goals for the prevention of obesity and diet-related NCDs originally established by the 1989 WHO Study Group on Diet, Nutrition and the Prevention of Chronic Diseases (35) and updated by the 2002 Joint WHO/FAO Expert Consultation on Diet, Nutrition and the Prevention of Chronic Diseases (36). It is intended to complement other WHO guidance on healthy diets, particularly the WHO guideline on sugars intake (14). The recommendation in this guideline is intended for the general population of children and adults, including pregnant women. The guidance in this guideline is based on evidence of health effects of NSS use at levels already considered safe by JECFA)2, and is not intended to update or replace existing guidance on safe or maximal levels of intake. Safe levels of intake are based on toxicological assessments of individual NSS, which are undertaken by authoritative bodies before individual NSS are approved for commercial use.3 Because the work of the Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health is focused on providing guidance on the prevention of unhealthy weight gain and diet-related NCDs, providing guidance on the management of diabetes in individuals with pre-existing diabetes is beyond the scope of this guideline.
Objective
The objective of this guideline is to provide evidence-informed guidance on the use of NSS. The recommendation in this guideline can be used by policy-makers and programme managers to address NSS use in their populations through a range of policy actions and public health interventions.
The WHO recommendation on NSS use is an important element of WHO’s efforts in implementing the NCD agenda and achieving the “triple billion” targets set by the 13th General Programme of Work (2019–2023), including 1 billion more people enjoying better health and well-being. In addition, the recommendation and other elements of this guideline will support:
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implementation of the political declarations of the United Nations (UN) high-level meetings on the prevention and control of NCDs held in New York in 2011 and 2018, and the outcome document of the high-level meeting of the UN General Assembly on NCDs (A/RES/68/300) held in New York in July 2014;
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implementation of the WHO Global Action Plan for the Prevention and Control of Noncommunicable Diseases 2013–2030, which was adopted by the 66th World Health Assembly held in May 2013 (the timeline was extended to 2030 at the 72nd World Health Assembly held in May 2019);
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implementation of the recommendations of the high-level Commission on Ending Childhood Obesity established by the WHO Director-General in May 2014;
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Member States in implementing the commitments of the Rome Declaration on Nutrition and recommended actions in the Framework for Action, including a set of policy options and strategies to promote diversified, safe and healthy diets at all stages of life - these were adopted by the Second International Conference on Nutrition (ICN2) in 2014 and endorsed by the 136th Session of the WHO Executive Board held in January 2015 and the 68th World Health Assembly held in May 2015, which called on Member States to implement the commitments of the Rome Declaration across multiple sectors;
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achievement of the goals of the UN Decade of Action on Nutrition (2016–2025), declared by the UN General Assembly in April 2016, which include increased action at the national, regional and global levels to achieve the commitments of the Rome Declaration, through implementing policy options included in the Framework for Action and evidence-informed programme actions; and
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the 2030 Agenda on Sustainable Development and achieving the Sustainable Development Goals, particularly Goal 2 (Zero hunger) and Goal 3 (Good health and well-being).
Target audience
This guideline is intended for a wide audience involved in the development, design and implementation of policies and programmes in nutrition and public health. The end users for this guideline are thus:
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policy-makers at the national, local and other levels;
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managers and implementers of programmes relating to nutrition and NCD prevention;
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nongovernmental and other organizations, including professional societies, involved in managing and implementing programmes relating to nutrition and NCD prevention;
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health professionals in all settings;
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scientists and others involved in nutrition and NCD-related research;
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educators teaching nutrition and prevention of NCDs at all levels; and
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representatives of the food industry and related associations.
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For the purposes of this guideline, NSS are defined as all synthetic and naturally occurring or modified non-nutritive sweeteners that are not classified as sugars. Sugar alcohols and low-calorie sugars are not considered to be NSS.
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