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There exists minimal evidence from high-quality, randomized controlled trials that supports any one eating pattern for the prevention of disease or mortality. Observational research regarding low-carbohydrate nutrition and disease prevention is limited by the use of a “low-carbohydrate diet score” that is applied to populations containing few people who are restricting carbohydrate intake substantially. Observational research shows mixed results regarding the relationship between a low-carbohydrate eating pattern and risk for cardiovascular disease (CVD), type 2 diabetes, and certain cancers. Common themes in some of these studies are that plant-based low-carbohydrate patterns are associated with lower risk whereas high-glycemic index/load patterns are associated with higher risk. Randomized controlled trials of low-carbohydrate eating patterns (compared with control diets) have shown greater improvement in several intermediate risk factors, including blood pressure, serum HDL cholesterol, serum triglycerides, and hemoglobin A1c. There is a need for randomized controlled trials that investigate the relationship between low-carbohydrate eating patterns and disease incidence or mortality as a primary outcome.