The Causal Role of Fruit and Vegetable Intake in Multiple Diseases and Disorders: A Systematic Review and Meta-analysis of Mendelian Randomization Studies

Fruit and vegetable intake is widely believed to be protective against diseases and disorders. However, most research relies on observational studies, which are susceptible to confounders and reverse causality. Mendelian randomization (MR) offers a novel approach to assess causality with less of these biases by using genetic variants as instrumental variables. This systematic review and meta-analysis aimed to synthesize findings from MR studies investigating the causal effects of dried fruit, fresh fruit, cooked vegetable, and salad/raw vegetable intake on various diseases and disorders. De novo (new) MR analyses were conducted to strengthen the existing evidence. A systematic search of PubMed, Scopus, EMBASE, Web of Science, and Google Scholar identified MR studies using genetic variants as instruments for fruit and vegetable intake. As of July 18, 2024, 54 papers were included. Each relationship was classified as having robust protective, robust harmful, suggestive, insufficient, or nonevaluable effects. Dried fruit intake has robust protective effects against multiple outcomes, particularly in the musculoskeletal, digestive, and respiratory systems. Fresh fruit intake was strongly associated with lower risks of depression, kidney stones, and Barrett’s esophagus. Salad/raw vegetable intake has robust protective effects against angina pectoris, Barrett’s esophagus, and keratinocyte skin cancer. In contrast, cooked vegetable intake was linked to robust harmful effects on depression, bipolar disorder, hip osteoarthritis, and ventral hernia, with no robust evidence supporting protective effects. Dried fruit intake had the strongest protective effects among the four exposures, offering robust benefits against multiple diseases. However, the findings challenge mainstream beliefs about cooked vegetable intake.