Twin-Based Randomized Controlled Trials in Nutritional Research: A Scoping Review

Abstract

Establishing causality in nutritional science is difficult. Human diets are complex, and individuals vary substantially in how they respond to dietary exposures. The nutrition literature mostly relies on observational studies, which are vulnerable to confounding and measurement error. Twin-based randomized controlled trials (RCTs), especially the co-twin control design, offer a compelling methodological solution to many of these challenges. This design enables researchers to distinguish genetic from environmental influences on health outcomes. The present scoping review was conducted to systematically map twin RCTs in nutrition science, evaluate their methodological approaches, and identify gaps and opportunities for future research. A comprehensive search across clinical trial registries and electronic databases yielded only 13 eligible studies, demonstrating that co-twin randomized dietary interventions remain rare relative to standard study designs using nontwins or twins assigned to the same arm. The interventions used in these eligible RCTs could be classified into four groups: dietary pattern interventions, nutrient- or supplement-based interventions, dietary component modification, and behavioral or multimodal interventions. This limited number of studies may be explained by recruitment challenges and concerns about generalizability. Greater international collaboration, standardized trial protocols, and integration of emerging technologies could expand the utility of twin designs in nutrition science.