Comments were received from the following external peer reviewers on the draft WHO Guideline: Sugars intake for adults and children

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1 Comments were received from the following external peer reviewers on the draft WHO Guideline: Sugars intake for adults and children Peer reviewers Professor Annie S. Anderson Professor Wulf Becker Dr Hasan Hutchinson Dr Jenny Reid Professor W. Murray Thomson Dr Paula R. Trumbo Affiliation Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, UK Chief nutritionist, Risk Benefit Assessment Department, National Food Agency, Uppsala, Sweden Director General, Office of Nutrition Policy and Promotion, Health Canada, Ottawa, Canada Manager, Food Science and Risk Assessment, Ministry for Primary Industries, Wellington, New Zealand Professor of Dental Epidemiology and Public Health Division of Health Sciences, School of Dentistry, Dunedin, New Zealand Acting Director for Nutrition Programs, Office of Nutrition, Labeling and Dietary Supplements, Food and Drug Administration, College Park, Maryland, USA Summaries of comments received Assessment and response The guideline is nicely put together and is an easy read considering the technical nature of the work. Overall, the recommendations are clear. We acknowledge the rigorous approach used by WHO to develop the recommendations and determine their strength which took into account various relevant considerations. The NUGAG was composed of experts in different relevant topics and fields of expertise. A definition of free sugars would be useful near the start of the document (and how this has been differentiated from total sugars). The guideline indicates that the inclusion criterion for GRADE evidence was confined to Comment noted. The definition of free sugars has been included in the beginning of the guideline where the term free sugars first appears. The descriptions of different types of sugars are also included in the Background section of the final guideline. As noted in the comment, the inclusion and exclusion criteria used in selecting studies were 1

2 RCT and cohort studies (apart from the estimates of decreasing intake where ecological evidence was utilised). It might be useful for this inclusion/exclusion (study type) to be clarified within the guideline. In a similar vein it would be useful to confirm the inclusion criteria for length of follow up in cohort studies and minimum follow up in RCTs. Whilst all of these details are in the full review papers, some minimal details really should be provided in the body of this guideline. The proposed recommendation to limit intake of free sugars to less than 10% of total energy intake is in line with the recent 5th edition of the Nordic Nutrition Recommendations (NNR 2012). However, the NNR recommendation refers to added sugars defined as refined sugars such as sucrose, fructose, glucose, starch hydrolysates (glucose syrup, high fructose syrup), and other isolated sugar preparations used as such or added during food preparation and manufacturing. The basis for the recommendation is several fold: ensuring adequate intake of micronutrients and especially dietary fibre (nutrient density), supporting a healthy dietary pattern, and preventing weight gain, type 2 diabetes and dental caries. There is a general methodological problem in assessing intake of added sugar, and the various definitions of sugar complicate the interpretation of the studies. Whether or not to include sugars from fruit juice, for example, is more an issue of management and formulation of food based dietary guidelines. In Sweden, fruit juice is covered in the advice on consumption of fruit and vegetables (500g/d), where it is stated that up to 1 dl of fruit juice can be included. It may not be helpful to say that people who need to increase caloric intake should not increase free sugars per se. If extra calories are needed they must come from somewhere and it would be unwise to recommend increases in described in detail in the background systematic reviews. However, these are also included in the guideline itself as well, in the form of PICO questions which are described in detail in Annex 6 of the guideline. Comment noted. In order to avoid unintended consequences, it is indicated clearly in the Translation and implementation section of the guideline that this guideline should be used in conjunction with other nutrient guidelines and dietary goals, in particular 2

3 protein, fat or alcohol. This leaves us with intrinsic sugars (as in milk and fruit) and complex carbohydrate as the most desirable nutrient to increase (and whole grains are clearly desirable) a footnote to this effect would make the statement on increasing caloric intake more useful. Without a statement to this effect there may well be an unintended consequence of increasing saturated fat (typically cream, butter and other high dairy fats) intake as currently recommended by one high profile low sugar fan in the UK. The focus of the recommendations is free sugars, rather than added sugars or total sugars. Many well known consensus and policy reports make recommendations about added sugars or total sugars. The 2 systematic reviews that form the basis for the draft recommendations included studies that examined the effect of total sugars, added sugars, and/or free sugars. It is not clear how and why WHO isolated the effect of free sugars in the systematic reviews in order to substantiate the draft recommendations. those related to fats and fatty acids (including saturated fatty acids and trans fatty acids), to guide effective public health nutrition policies and programmes to promote a healthy diet. This is a nutrient guideline which needs to be translated into culturally and contextually specific food based dietary guidelines that take into account locally available food and dietary customs at the country level. Information on how the recommendations of the guideline can be translated into action is provided in the Translation and implementation section of the guideline. In recent year, more countries have started to refer to free sugars when developing and updating their dietary guidance. During the initial scoping of the guideline, it was decided to review the literature to identify studies not only of free sugars but also more broadly of total sugars. As a result, some studies assessing total sugars were initially identified in addition to those assessing free sugars. Regarding the studies actually included in the systematic review and metaanalyses, all of the studies for body weight assessed free sugars intake (either through free sugars containing foods or sugar sweetened beverages). Of those studies included in the GRADE analysis assessing the effect of reducing or increasing free sugars intake on dental caries, six measured free sugars directly, one measured free sugars retrospectively (Rugg Gunn et al. [1984]) and one measured total sugars (Burt et al. [1988]). Based on evidence from Rugg Gunn et al. it was considered that the total sugars measured in the Burt et al. study were representative of free sugars intake. Detailed consideration of this assessment is provided in the footnotes of the relevant GRADE evidence profile (Annex 1) in the guideline. Regarding the GRADE analysis for the 10% threshold, one study measured free sugars retrospectively (Rugg Gunn et al. [1984]); all others 3

4 measured free sugars directly. The studies included in the GRADE analysis for the 5% threshold all measured per capita availability of sucrose only, and it is considered that at the time the data was collected for the studies, sucrose was the primary source of free sugars in the diet in the population being studied. The inclusion of fruit juice in the proposed recommendation raises concern. Because fruit juice is regularly consumed and its consumption contributes to micronutrients intake, fruit juice is different than other free sugars. Fruit juice intake contributes significantly to nutrient intake adequacy in some countries. In addition, there is evidence that low to moderate intake of fruit juice is not associated with increased risk of weight gain, although excess intake seems to be associated with higher body weight. A stronger rationale for the selection of free sugars for the recommendation could address this concern. In considering which type of sugars should appear on food labelling, there is a practical concern of how national authorities would determine compliance with a free sugars declaration on foods that contain a combination of added sugars and certain (but not all) sugars naturally present due to the addition of fruit juices and concentrates. At the 38 th Session of the Codex Committee on Food Labelling (2010), the Committee discussed the mandatory labelling of added sugars on foods where nutrient declaration is applied in the Codex guidelines on Nutrition Labelling (CAC/GL , Section ). The Committee agreed not to include added sugars in the list of nutrients in section for several reasons, primarily as there are no analytical methods to differentiate between intrinsic and added sugars. In addition to this, the It should be noted that the guideline is not recommending to avoid fruit juices, but is recommending to reduce the intake of free sugars, of which fruit juices are a part. Fruit juices were only one of several exposures which the systematic reviews had explored as noted in the PICO questions described in detail in Annex 6 of the guideline, and in the systematic reviews by Te Morenga et al. (2013) and Moynihan and Kelly (2014). In addition, as also mentioned in the comment, it should be noted that some studies are now indicating a positive association between excess intake of fruit juices and higher body weight. Essential nutrients including vitamins and minerals can be consumed through a wide variety of whole and fresh foods that are naturally low in free sugars, rather than through excess intake of fruit juices. As noted in the comment, listing of sugars in nutrition labelling was not mandatory in the Codex guidelines on nutrition labelling until recently. WHO is actively engaged in providing technical and scientific advice to the work of the Codex, including the updating and revising of the guideline on nutrition labelling which was conducted in The updated guideline now includes mandatory declaration of total sugars in the listing of nutrients and this is in line with the guidance provided by the 2007 FAO/WHO Scientific Update on Carbohydrates in Human Nutrition. In the paper prepared by Cummings & Stephen for the 2007 FAO/WHO Scientific Update on Carbohydrates in Human Nutrition, they stated that the term total sugars is probably the most useful way to describe and measure sugars for labelling purposes. The key point they highlighted is related to measurement 4

5 WHO representative recommended declaration of total sugars was more suitable for the purposes of labelling. It is unclear what is the basis for limiting the review to only that of free sugars. It is more straightforward to enforce regulations for total sugars or added sugars. National authorities responsible for helping consumers make informed choices to meet dietary recommendations will need to consider whether the amount of free, added, or total sugars should be targeted through public health interventions. Therefore, it would be helpful if the guideline included more information to justify the choice of free sugars over added or total sugars. and labelling. It may be difficult to distinguish sugars present in the different compartments of a food or meal (i.e. intracellular or extracellular, from milk or fruit or vegetables). Therefore, Cummings & Stephen noted that the first step in any analysis and for labelling should be total sugars. But with regard to the physiology, the rate of digestion and absorption are determined by the physical properties of the food/meal in which the sugars are found. Therefore, consuming sugars as whole fruit (i.e. intrinsic sugars) would be different from consuming sugars as fruit juices (i.e. free sugars) in terms of the glycaemic, insulinaemic and satiety responses. Thus analytically these sugars are not different, but physiologically they are. As defined in the guideline, free sugars include monosaccharides and disaccharides added to foods and beverages by the manufacturer, cook or consumer, and sugars naturally present in honey, syrups, fruit juices and fruit juice concentrates. The recommendations of the guideline focus on the effect of free sugars because free sugars form a large part of total sugars and there is no reported evidence of adverse effects of consumption of intrinsic sugars and sugars naturally present in milk. Furthermore, added sugars are generally limited to sugars that are added to foods and beverages during processing or preparation and often does not include sugars naturally present in honey, syrups, fruit juices and fruit juice concentrates which are included in the definition of free sugars. But excess intake of these sugars are also of concern. As noted in various comments received through public consultation, improved communication to consumers and development of effective communication strategies and materials could facilitate the understanding of the recommendations which will lead to effective translation of the recommendations and implementation of the guideline. 5

6 A research question for the purpose of establishing intake guidance could be worded more flexibly to allow for the derivation of an objective maximum intake level that is based on the strongest scientific evidence, rather than choosing 10% of energy. Because the systematic review authors were asked to review a predetermined upper limit level, their findings do not independently confirm that this is the best upper intake level. In addition, although studies presented on both weight gain and dental caries clearly showed that decreasing sugar intake leads to health benefits, the studies showed a doseresponse effect, not a threshold effect. The strong recommendation to restrict intake of free sugars to below 10% of energy is based on 5 observational dental caries studies in children (rated as providing moderate evidence). It should be made clearer that the quantitative limit of 10% is based on these 5 observational dental Initial set of questions were generated using the population, intervention, comparison and outcome (PICO) format and reviewed by the WHO Secretariat and the WHO Steering Committee for Nutrition Guideline Development before they were made available for public comment. These draft set of PICO questions was then presented to the WHO Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health, together with the comments received from public consultation, for review and finalization, in order to determine the scope of the evidence to be used in informing development of the guideline. Inclusion and exclusion criteria used in selecting studies was guided by the PICO questions which are described in detail in Annex 6. As noted in Annex 6 as well as in the GRADE tables in Annex 1, the questions were not limited to the assessment of any predetermined threshold, but included the question on the effect of a decreased or increased intake of free sugars in adults and children (i.e. Tables 1 4 in Annex 1). Reviewing of the effect of restricting the intake of free sugars to below 10% was conducted with a view to update the existing guidance of less than 10% of total energy intake. No dose response was described in the systematic review conducted by Te Morenga et al. (2013), however, there was a consistent positive effect of higher sugars intakes on body weight at all levels of intake. Similarly, based on the systematic review conducted by Moynihan and Kelly (2014), studies showed a positive association between sugars intake and dental caries. After careful reviews, the NUGAG Subgroup on Diet and Health considered that the available evidence was sufficient to support recommendations on thresholds for free sugars intake as described in the guideline. All the studies reviewed and how the evidence was evaluated are described in the respective systematic reviews as well as in the relevant sections in the guidelines, including the GRADE evidence profiles included in the guideline (Annex 1). 6

7 caries studies. National authorities will need to consider developing guidance for consumers on how much sugar is a lot or a little, so guidance on quantitative limits are useful; however, it would be easier to justify support for the WHO level if its validity and generalizability to a range of jurisdictions was clearer. The purpose of providing conditional recommendations for consuming below 5% of energy is unclear and could cause more confusion than benefit, especially when such a recommendation is based on very low quality evidence using ecological studies that were conducted a long time ago i.e. pre/post World War II, at a time where there was no/limited use of fluoridated toothpaste and were also conducted in one country (Japan). Furthermore, the basis of the conclusion about the absence of harm is not clear. In addition, in many populations, this limit may represent a substantial reduction in free sugars from current status. Further investigation is required to assess the feasibility of meeting such recommendation. For example, would a limit of 5% still allow for the consumption of adequate nutrients? How the recommendations are translated and implemented will vary from country to country and individual to individual in accordance with respective context. Guidance on how the recommendations can be translated and implemented is provided in the "Translation and implementation" section of the guideline, including examples of measures and interventions which are already being implemented by different countries. A number of issues are considered when developing the recommendations and determining the strength of those recommendations. These include: quality of evidence, values ad preferences, trade off between benefits and harm and costs and feasibility as indicated in Annex 7 of the guideline. Taking these issues into consideration, the recommendation on a further reduction of the intake of free sugars to below 5% of total energy intake was considered to be a conditional recommendation. According to the WHO Handbook for Guideline Development (2014), conditional recommendations are made when there is less certainty about the balance between the benefits and harms or disadvantages of implementing a recommendation. This means that policy making will require substantial debate and involvement of various stakeholders for translating them into action. This is clearly noted in the recommendation section in the guideline in order to facilitate the understanding of the recommendations and ensure the effective translation, adaptation and implementation of the recommendations for each country s context. WHO issues conditional recommendations on topics of public health importance even when the quality of evidence may not be strong. There are many examples of WHO guidelines in various areas of work which contain conditional recommendations. Regarding the question on the absence of harm, review of the literature did not identify any reports on adverse health effects of consuming free sugars at a level of less than 5% of total energy intake. 7

8 Therefore, in the final guideline, the statement has been modified as No evidence for harm associated with reducing the intake of free sugars to less than 5% of total energy intake was identified to accurately reflect the assessment. Furthermore, it should be noted that there is no nutrient requirement for sugars and it is considered feasible to achieve the recommendations in this guideline while respecting national dietary customs, because a wide variety of whole and fresh foods are naturally low in sugars. The draft guideline indicates WHO commissioned several systematic reviews and meta analyses to address the PICO questions and 2 systematic reviews to assess the effects of increasing or decreasing intake of free sugars on excess weight gain and dental caries. It would be helpful if the draft guideline referred to the results of other relevant systematic reviews published before the dental caries and body weight reviews were commissioned. It would be particularly important to know whether or not the findings are consistent with the WHO commissioned systematic review results. We note that at least two relevant sugars systematic reviews, one on blood pressure and one on blood lipids, are currently in progress. The evidence base for the draft recommendations could be enhanced with the inclusion of the findings from these reviews. As stated in the guideline, when determining the scope of the guideline, the WHO Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health decided unhealthy weight gain and dental caries as the priority health outcomes to be focused on when undertaking the systematic reviews. This was in recognition of the rapidly growing epidemic of overweight and obesity around the globe and its role as a risk factor for several NCDs. In addition, dental caries is the most common NCD, and the cost of its treatment places a heavy burden on health care budgets in many countries. But a need for systematic reviews and metaanalyses related to free sugars intake and blood lipid levels, blood pressure and diabetes related outcomes (i.e. glucose, insulin, metabolic syndrome, prediabetes and insulin resistance) is suggested in the Implications for future research section of the guideline. As noted in the comment, while the finalization of the guideline was underway, a new systematic review was published in May 2014 by Te Morenga et al. which provided evidence that free sugars may influence cardiometabolic risk factors independently of changes in body weight, suggesting that a reduction in free sugars intake may also be beneficial for reducing risk of cardiovascular diseases. Another recent observational study by Yang et al. (2014) identified a significant relationship between added sugar consumption and increased risk for cardiovascular disease mortality, noting that those consuming less than 10% of calories as added sugars had lower risk 8

9 than those consuming more. Thus, these new publications also support the recommendation to reduce intake of free sugars for health benefits which the guideline highlights. It is not clear why only certain groups of studies in the body weight systematic review were included in the GRADE evidence profile tables (Annex 1). For example, clinical studies using isocaloric diets and observational studies in adults were excluded. Furthermore, it is not clear which observational body weight studies in children were included in the evidence profile (Table 4) and how they correspond to the studies reported in the systematic review. The WHO Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health carefully considered all of the evidence as described in the Summary of evidence section of the guideline including the isocaloric and cohort studies in adults. The results of the meta analysis of the isocaloric studies are described in the Summary of evidence section of the guideline and acknowledged in the Remarks section of the guideline, with the remark that The excess body weight associated with free sugars intake results from excess energy intake. Given that the evidence suggests free sugars intake contributes to body weight through changes in total energy intake, this is the focus of the recommendations and therefore the 11 isoenergetic exchange RCTS were not included for GRADE analysis and were not used in formulating the recommendations. Furthermore, GRADE methodology indicates that when one has results from both RCTs and cohort studies, and provided the results aren t vastly different between the two types of studies (and this is the case for the studies in adults regarding free sugars intake), convention is to use the results from the higher quality studies. In this case (and in most cases in general) the higher quality studies are the RCTs. In fact, GRADE conventions indicate that RCTs start out as high quality evidence and cohort studies start out as low quality evidence; the evidence can then be upgraded or downgraded according to various measures of confidence in the studies. In the case of free sugars intake in adults, the RCTS were determined to be of higher quality than the cohort studies. For these reasons, the cohort studies in adults were not included for GRADE analysis and were not used in formulating the recommendations. The detailed information on the five cohort studies in children that were included in the GRADE analysis in Table 4 and subsequently used in the formulation 9

10 of the recommendations can be found in the systematic review conducted by Te Morenga et al. (2013). More information on how, why and which studies were pooled in the GRADE evidence profile are described in the Summary of evidence section and each of the GRADE tables included in Annex 1 of the guideline. In the table describing the effect of free sugars reduction to below 10% energy (Table 5 in the Annex), only the results of the 5 observational studies in children were included. It is not clear why the other studies included in the systematic review were not a part of this table. A clear rationale why not all studies were considered and why the recommendations focus only on free sugars and not on sugars intake in general is missing. It is unusual to combine the scientific evidence for two completely unrelated endpoints body weight and dental caries. This did not appear to be the case for the 2012 WHO reviews on sodium and potassium. In these reviews, the key endpoints considered were generally related to cardiovascular disease (CVD) risk, including surrogate endpoints of CVD risk (e.g. blood pressure), while other evidence was available (e.g. potassium and kidney stones). The evidence to support a strong recommendation for potassium and sodium seems to be much greater than for free sugars. For potassium and sodium, there was high quality evidence that could be used for making other considerations in the strength of the recommendation (e.g. trade off between benefits and harm). How, why and which studies were pooled in the GRADE evidence profile are described in the Summary of evidence section and each of the GRADE tables included in Annex 1 of the guideline. Five of the eight cohort studies enabled the comparison of dental caries development when free sugars intake was equivalent to an amount less than 10% of total energy intake or more than 10% of total energy intake. The detailed information on these five studies can be found in the systematic review conducted by Moynihan and Kelly (2014). The recommendations of the guideline focus on the effect of free sugars because free sugars form large part of total sugars and there is no reported evidence of adverse effects of consumption of intrinsic sugars and sugars naturally present in milk. As stated in the guideline, when determining the scope of the sugars guideline, the WHO Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health decided unhealthy weight gain and dental caries as the priority health outcomes to be focused on when undertaking the systematic reviews. This was in recognition of the rapidly growing epidemic of overweight and obesity around the globe and its role as a risk factor for several NCDs. In addition, dental caries is the most common NCD, and the cost of its treatment places a heavy burden on health care budgets in many countries. The same process was implemented when updating the sodium and potassium guidelines to determine the scope of the guidelines and those health outcomes were identified by the NUGAG Subgroup on Diet and Health as priority outcomes upon which to focus. When developing the recommendations for the sugars guideline and determining the 10

11 strength of those recommendations, the same process was implemented as that of the sodium and potassium guidelines and a number of issues were considered including quality of evidence, values and preferences, trade off between benefits and harm, and costs and feasibility as indicated in Annex 7 of the guideline. The draft guidelines provides the following statement.it was decided that excess weight gain and dental caries should be the key outcomes of concern in relation to free sugars intake. Diabetes and CVD, and the risk of developing those NCDs, are often mediated through the effects of, for example, overweight and obesity. Therefore, measures aimed at reducing overweight and obesity are likely to also reduce, for example, the risk of developing type 2 diabetes and CVD, and the complications associated with those diseases. (page 9). This statement comes across as if it was concluded, in advance, that the evidence for free sugar consumption and body weight would be strong, and therefore the review of type 2 diabetes and CVD was not needed. There is evidence to suggest that sugars may have a more direct role in type 2 diabetes risk via increased insulin resistance, a surrogate endpoint for type 2 diabetes risk, possibly due to increased glycaemic index/load. It seems as if the fundamental basis for addressing free sugars is because they are ingredients that are present (but not always) in foods that are not nutrient dense (e.g. sugarsweetened beverages). If this is the fundamental concern, then it may be more appropriate to evaluate the strength of the evidence between free sugars consumption and intake of essential As stated in the guideline, when determining the scope of the sugars guideline, the WHO Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health decided unhealthy weight gain and dental caries as the priority health outcomes to be focused on when undertaking the systematic reviews. The statement cited in the comment was the decision made by the NUGAG Subgroup on Diet and Health when determining the scope and the priority health outcomes to be focused on when evaluating the evidence. While the finalization of the guideline was underway, a new systematic review was published in May 2014 by Te Morenga et al. which provided evidence that free sugars may influence cardiometabolic risk factors independently of changes in body weight, suggesting that a reduction in free sugars intake may also be beneficial for reducing risk of cardiovascular diseases. Another recent observational study by Yang et al. (2014) identified a significant relationship between added sugar consumption and increased risk for cardiovascular disease mortality, noting that those consuming less than 10% of calories as added sugars had lower risk than those consuming more. Thus, these new publications also support the recommendation to reduce intake of free sugars for health benefits which the guideline highlights. The scope of the guideline and priority questions to be addressed (i.e. PICO questions) were determined by the WHO Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health and these are noted in detail in Annex 6 of the guideline. 11

12 vitamins and minerals, and their role in nutrient inadequacy, which is of concern in many developing countries. Implementation of a strong recommendation would imply the need for performance measures. In terms of implementing a dietary recommendation, this could trigger the need to monitor the uptake of the recommendation. Due to the limitations in distinguishing between naturally occurring sugars and added sugars in food composition tables, monitoring the impact of the proposed guideline on dietary intake and making comparisons across countries will be challenging. Consideration should be given to how countries can implement this recommendation to assess free sugar intake when food composition databases do not currently distinguish between intrinsic and added sugars. It could be helpful if WHO included considerations for implementation of the recommendations to help address these challenges. One of the proposed research questions suggest the need for further evidence on the role of free sugars on NCD risk factors (including body weight) and quantitative thresholds above which risks increase. This appears to undermine the strength of the quantitative limit recommendations. It would be helpful if this research question explained the nature of the evidence needed regarding the free sugar thresholds for increased risk of unhealthy weight gain, obesity, and other related NCDs. The focus of the proposed research regarding behavioural change approaches is on sugarsweetened beverages only and not all sources of added or free sugars. Since the draft recommendations apply to all foods, it is not immediately clear why the sugar sweetened Information on how the recommendations can be implemented and translated into action is noted in the Translation and implementation section of the guideline, including examples of measures and interventions which are already being implemented by countries. Furthermore, how the impact of the guideline can be assessed is described in the Monitoring and evaluation of guideline implementation section in the guideline. There may be various challenges in adopting and adapting the guideline, but WHO will be happy to work with Member States in translating and implementing the recommendations of this guideline into effective public health policies and strategies as well as programmatic action in accordance with respective countries context, as appropriate. As noted in the Remarks section of the guideline, thresholds were determined based on the evidence from analysis of the impact of free sugars intake on dental caries which was identified by the WHO Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health as a priority health outcome for developing recommendations for free sugars. Therefore, to strengthen the evidence base of the recommendation, in particular related to unhealthy weight gain and obesity, a need for assessing thresholds above which the consumption of free sugars increase the risk of unhealthy weight gain, obesity and other related NCDs was included as a need for future research. To clarify, the paragraph was reworded and in the final guideline, it is noted as, Need to evaluate different behavioural change approaches to promote the reduction of free sugars intake; in particular, the intake of sugar sweetened beverages, which is identified as a behavioural risk 12

13 beverages are singled out. As well, consideration should be given to research that will support behaviour change. Research on changing the social (including information and media) and physical (including food) environments to support lower consumption of added / free sugars within the context of overall healthy eating patterns would be beneficial for informing policies and programs at the population level. We congratulate the panel on a fine, evidencebased piece of work which should be of considerable use in the global fight against both obesity and dental caries. We also commend the decision to concentrate on those two conditions. The rationale for doing so is clearly expressed and very sound. The reference for caries tracking from childhood to adulthood should be complemented by the paper by Broadbent et al. (J Dent Res 2008; 87: 69 72), which clearly tracks life course trajectories for caries into the fourth decade of life. The trials included in Annex Tables 1 3 were conducted in a manner in which a significant difference in total energy intake between the experimental and control group was permitted and was increased or decreased depending on whether free sugars intake was increased or decreased. It is unclear what these studies were trying to evaluate and conclude that would not be concluded for any other food or beverage that provides calories. Annex Tables 1 3 received a moderate quality rating. factor contributing to calorie overconsumption, especially among children. Comment noted. Comment noted. The suggested reference was reviewed and was added to the list together with other relevant references which are already cited in the guideline. The evidence for the effect of sugars on body weight is largely derived from randomized controlled trials of studies involving free living subjects. The intention in these randomized trials was to compare the effects of altering the proportion of total energy provided by free sugars without altering overall macronutrient distribution. When energy intakes were strictly controlled there was no effect of sugars on body weight. When not strictly controlled those consuming higher sugars diets did not adequately compensate for the additional energy provided by increased sugars by reducing intake of other energy sources. Similarly when subjects reduced their sugars intake they did not adequately compensate for the reduction by increasing intake of other energy sources. Details of the studies reviewed can be found in the systematic review by Te Morenga et al. (2013) which also provides 13

14 references and information for all individual studies included in the systematic review. Tables in Annex 1 are GRADE evidence profiles which contain the assessment of the quality of the evidence and a summary of findings across studies for each important or critical outcome and each key question. Outcomes are listed in rows and the judgements made about the factors that determine the quality of the body of evidence are described or each outcome, along with a summary of the effect estimates for each. The draft guideline states that a meta analysis of 11 trials that examined isoenergetic exchanges of dietary sugars with other carbohydrates showed no change in body weight (0.04 kg [95% CI: ]). It is unclear as to why these studies were not included in the Annex. Replacement of free sugars with another energy source (e.g., starch/complex carbohydrate) is still answering the question What is the effect of a decrease or increase in free sugars in adults? It appears that the observational studies cited in Te Morenga et al. (2013) for adults were not included because a sufficient number of clinical trials were available for adults. Thus while this may be part of the protocol discussed in the WHO Handbook for Guideline Development, it is not accurate to state that the recommendations were based on the totality of the evidence. The results of the meta analysis of these 11 studies are described in the Summary of evidence section of the guideline and acknowledged in the Remarks section of the guideline, with the remark that The excess body weight associated with free sugars intake results from excess energy intake. Given that the evidence suggests free sugars intake contributes to body weight through changes in total energy intake, this is the focus of the recommendations and therefore the 11 isoenergetic exchange RCTS were not included for GRADE analysis and were not used in formulating the recommendations. Furthermore, it is accurate to say that the recommendations were based on the totality of evidence reviewed as the WHO Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health carefully considered all of the evidence as described in the Summary of evidence section of the guideline including the cohort studies in adults. GRADE methodology indicates that when one has results from both RCTs and cohort studies, and provided the results aren t vastly different between the two types of studies (and this is the case for the studies in adults regarding free sugars intake), convention is to use the results from the higher quality studies. In this case (and in most cases in general) the higher quality studies are the RCTs. In fact, GRADE conventions indicate that RCTs start out as high quality evidence and cohort studies start out as low quality evidence; the evidence can then be upgraded or downgraded according to various measures of confidence in the studies. In the 14

15 case of free sugars intake in adults, the RCTS were determined to be of higher quality than the cohort studies. For these reasons, the cohort studies in adults were not included for GRADE analysis and were not used in formulating the recommendations. Prospective cohorts used for children should measure total free sugars intake, rather than from specific sources. Otherwise, it is unclear if an increase or decrease in a specified source of free sugars is off set by another source of free sugars (unless adjusted for these other sources). Furthermore, it is stated that physical activity is a risk factor for obesity. Therefore, credible cohorts included in a systematic review should adjust for physical activity. A number of these studies did not adjust for physical activity. Finally, it seems as if energy intake from all sources, other than free sugars (often called residual energy), should be adjusted for. Energy intake and energy output (e.g., physical activity) are the key components of energy balance. The evidence for the effect of sugars on body weight is largely derived from randomized controlled trials of studies involving free living subjects. The intention in these randomized trials was to compare the effects of altering the proportion of total energy provided by free sugars without altering overall macronutrient distribution. When energy intakes were strictly controlled there was no effect of sugars on body weight. When not strictly controlled those consuming higher sugars diets did not adequately compensate for the additional energy provided by increased sugars by reducing intake of other energy sources. Similarly when subjects reduced their sugars intake they did not adequately compensate for the reduction by increasing intake of other energy sources. Cohort studies in adults were not included in the GRADE analysis and were not used in formulation of the recommendations. Most of the 21 cohort studies in children included sugar sweetened beverages exclusively as the exposure but some of those with solid food exposures (e.g. snacks, candies, chocolates) demonstrated a positive association with body weight. The cohort studies that were included in the GRADE analysis and subsequently used in the formulation of the recommendations all reported sugar sweetened beverage exposures. Of these studies, all but one adjusted for total energy intake and more than half adjusted for some aspect of physical activity. As described in the comment, the guideline notes the importance of energy balance for avoiding unhealthy weight gain and also notes that increasing or decreasing free sugars is associated with parallel changes in body weight and the relationship is present regardless of the level of intake of free sugars. Therefore, the guideline recommends a reduced intake of free sugars throughout the lifecourse for both adults and 15

16 children. All grade evidence profiles were of moderate or low quality and none of them being noted as having a large effect size. Would the recommendation be strong for free sugars based only on body weight? It is stated that Because there is no evidence of adverse effects of consumption of intrinsic sugars, recommendations focus on the effect of consumption of free sugars. This statement is not correct. There have been studies conducted on fruit juices, as well as studies to conclude that the incidence of dental caries is not different between the consumption of free versus natural sugars. A publication (Sheiham, 2001) cited by Moynihan and Kelly (2014) states that both the frequency of consumption and total amount of sugars is important in the aetiology of caries. Furthermore, there is evidence to suggest that starches can increase the risk of dental caries. The US Food and Drug Administration concluded in its scientific review and establishment of health claim regulation for dietary noncariogenic carbohydrate sweeteners (21 CFR ) that the development of dental caries is the result of an interaction between sugars (i.e., not just free) and other fermentable carbohydrates, such as refined flour and oral bacteria in a suitable environment. The Institute of Medicine (IOM, 2002) also noted that fermentable natural sugars, such as cow s milk and fruit juices, can result in early childhood dental caries. The basis for focusing on free sugars needs to be better justified. It is unclear why the clinical trials cited for children by Moynihan and Kelly (2014) were not considered. When developing the recommendations and determining the strength of those recommendations, not only the quality of evidence, but also a number of issues are considered which include values and preferences, trade off between benefits and harm and costs and feasibility as indicated in Annex 7 of the guideline. It should be noted that the focus of the guideline is related to the intake of free sugars, which fruit juices are part of, but not the intake of intrinsic sugars which are found in whole fruit and vegetables as there is no reported evidence of adverse effects of consumption of intrinsic sugars. As noted in the comment, some studies show positive association between fruit juice consumption and development of dental caries. There is also convincing evidence that nonprocessed starches are not associated with dental caries. Plaque ph and enamel slab experiments suggest that processed starches are acidogenic, but these data are not backed up with epidemiological studies. There are very few longitudinal data on the impact of processed starches on caries increment and only one paper has shown a non significant trend (p<0.1) (Chankanka et al. 2011). With respect to amount vs. frequency of sugars intake and risk of dental caries, the evidence review shows that both are important. But few studies have measured both variables simultaneously to enable the relative importance of these variables to be judged while there is a greater wealth of evidence pertaining to amount of sugars and dental caries. The studies that have measured both frequency and amount of sugars simultaneously in the same population (e.g. Rugg Gunn et al. [1984], Rodrigues et al. [1999]) have found that the two variables are correlated. Reducing the frequency of free sugars intake in the absence of a reduction of amount will not only not reduce the risk of dental caries, but also of unhealthy weight gain and NCDs as a whole. Regarding the effects of viscosity of food and 16

17 consumption of starches, the evidence review was also conducted by the 2002 WHO/FAO Expert Consultation and data did not suggest their more decisive role than the amounts of sugars consumed. Regarding the clinical trials in children mentioned in the comment, only one nonrandomized intervention trial in children was identified in the review by Moynihan and Kelly (2014). This trial was determined to have design flaws which precluded its use in GRADE analysis. In reviewing the 8 prospective cohorts cited in Moynihan and Kelly (2014) and used in Annex Table 1, it appears as if some of these cohorts measured total sugar intake. If this is the case, it does not seem appropriate to use such studies to evaluate the evidence for free sugars intake and dental caries risk. The statement by Moynihan and Kelly (2014) (Table 4 footnote) that free sugars made up a sizeable portion of total sugars, the proportion of free sugars increasing as total sugars intake increased does not seem to be an adequate justification for including these studies. During the initial scoping of the guideline, it was decided to review the literature to identify studies not only of free sugars but also more broadly of total sugars. As a result, some studies assessing total sugars were initially identified in addition to those assessing free sugars. Regarding the studies actually included in the systematic review and metaanalyses, all of the studies for body weight assessed free sugars intake (either through free sugars containing foods or sugar sweetened beverages). Of those studies included in the GRADE analysis assessing the effect of reducing or increasing free sugars intake on dental caries, six measured free sugars directly, one measured free sugars retrospectively (Rugg Gunn et al. [1984]) and one measured total sugars (Burt et al. [1988]). Based on evidence from Rugg Gunn et al. it was considered that the total sugars measured in the Burt et al. study were representative of free sugars intake. Detailed consideration of this assessment is provided in the footnotes of the relevant GRADE evidence profile (Annex 1) in the guideline. Regarding the GRADE analysis for the 10% threshold, one study measured free sugars retrospectively (Rugg Gunn et al. [1984]); all others measured free sugars directly. The studies included in the GRADE analysis for the 5% threshold all measured per capita availability of sucrose only, and it is considered that at the time the data was collected for the studies, sucrose was the primary source of free sugars in the diet in the population being studied. 17

18 The draft guidelines make a strong recommendation to restrict intake of free sugars to below 10% of energy intake based on moderate evidence in five prospective cohort studies. It is assumed that these studies specifically evaluated the relationship between free sugars intake and risk of dental caries, and adjusted for important confounders. The Institute of Medicine evaluated the role of sugar consumption in dental caries risk when attempting to set a Tolerable Upper Intake Level (UL) for sugars (IOM, 2002). It was concluded that dental caries is a disorder of multifactorial causation and noted that because dental caries is influenced by a number of factors (frequency of meals and snacks, tooth brushing frequency, water fluoridation, fluoride supplementation, and fluoride tooth paste), it was not possible to determine a UL for sugars at which increased risk of dental caries can occur. The proposed guideline to further limit intake free sugars to less than 5% of total energy intake is based on ecological data (per capita availability) and is of low quality. It is not compatible with the definition of free sugars. The choice to include this guideline is a matter of management, but not strictly science based. A more detailed reasoning behind the inclusion of this proposed conditional guideline would be helpful. The use of a conditional guideline (although sufficiently described in the document) may be difficult to interpret in relation to a strong recommendation. One concern is that a conditional guideline based on such weak evidence might introduce doubts on whether WHO guidelines are based on solid scientific evidence. As noted in the comment, it is recognized that various factors affecting risk of dental caries (i.e. frequency of sugars consumption, stickiness or viscosity of foods, acidity of foods and beverages, fluoride exposure, level of oral hygiene, etc.) will influence levels of dental caries in populations. However, there is not strong evidence that these factors have a significant role to play in caries risk, independent of free sugars. The relationship between sugars intake and dental caries persists in the presence of exposure to fluoride, for instance. The cohort studies in the GRADE analysis all considered exposure to fluoride which did not differ between both lower and higher sugars groups. As noted in the guideline, the quality of evidence is one factor, though an important factor, to be considered when determining the strength of a recommendation using GRADE methodology. These include values and preferences, trade off between benefits and harm, and costs and feasibility. These are all described in the guideline and further information on the WHO guideline development process can also be found in the WHO handbook for guideline development (2014). Clear definitions of strong and conditional recommendations are also included in the guideline as well as in the WHO handbook for guideline development (2014). WHO issues conditional recommendations on topics of public health importance even when the quality of evidence may not be strong. There are many examples of WHO guidelines in various areas of work which contain conditional recommendations. A conditional recommendation is one where the desirable effects of adhering to the recommendation probably outweigh the undesirable effects but these trade offs could not be clarified; therefore, stakeholder dialogue and 18