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Background/Objectives: Global burdens of cardiovascular disease (CVD), diabetes and cancer are on the rise. Little quantitative data are available on the global impact of diet on these conditions. The objective of this study was to develop systematic and comparable methods to quantitatively assess the impact of suboptimal dietary habits on CVD, diabetes and cancer burdens globally and in 21 world regions. Subjects/Methods: Using a comparative risk assessment framework, we developed methods to establish for selected dietary risk factors the effect sizes of probable or convincing causal diet--disease relationships, the alternative minimum-risk exposure distributions and the exposure distributions. These inputs, together with disease-specific mortality rates, allow computation of the numbers of events attributable to each dietary factor. Results: Using World Health Organization and similar evidence criteria for convincing/probable causal effects, we identified 14 potential diet--disease relationships. Effect sizes and ranges of uncertainty will be derived from systematic reviews and meta-analyses of trials or high-quality observational studies. Alternative minimum-risk distributions were identified based on amounts corresponding to the lowest disease rates in populations. Optimal and alternative definitions for each exposure were established based on the data used to quantify harmful or protective effects. We developed methods for identifying and obtaining data from nationally representative surveys. A ranking scale was developed to assess survey quality and validity of dietary assessment methods. Multi-level hierarchical models will be developed to impute missing data. Conclusions: These new methods will allow, for the first time, assessment of the global impact of specific dietary factors on chronic disease mortality. Such global assessment is not only possible but is also imperative for priority setting and policy making. European journal of Clinical Nutrition (2012) 66, 119-129; doi: 10.1038/ejcn.2011.147; published online 14 September 2011 Keywords: global burden of disease; diet; cardiovascular disease; diabetes; cancer, Introduction The worldwide burdens of chronic diseases, including cardiovascular disease (CVD), type II diabetes and cancer, are on the rise. It is expected that by 2020, almost 75% of all [...]