Substitution of Dairy Products and Risk of Death and Cardiometabolic Diseases: A Systematic Review and Meta-Analysis of Prospective Studies

Substitution models in epidemiologic studies specifying both substitute and substituted food in relation to disease risk may be useful to inform dietary guidelines. A systematic review of prospective observational studies was performed to quantify the risks of all -cause mortality, cardiovascular disease, and type 2 diabetes (T2D) associated with the substitution of dairy products with other foods and between different dairy products. We systematically searched MEDLINE, Embase, and Web of Science until 28th June, 2023. We calculated summary relative risks (SRRs) and 95% con fi dence intervals (95% CI) in random-effects meta-analyses. We assessed the risk of bias with the Risk Of Bias In Non-randomized Studies - of Exposure (ROBINS -E) tool and certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development, and Evaluations (GRADE) approach. Fifteen studies (with 34 publications) were included. There was moderate CoE that the substitution of low-fat dairy with red meat was associated with a higher risk of mortality, coronary artery disease, and T2D [SRR (95% CI): 1.11 (1.06, 1.16), 1.13 (1.08, 1.18), and 1.20 (1.16, 1.25)]. A higher risk of mortality and T2D was also observed when substituting low-fat dairy with processed meat [SRR (95% CI): 1.19 (1.11, 1.28) and 1.41 (1.33, 1.49); moderate CoE]. A lower mortality risk was associated with the substitution of dairy and yogurt with whole grains [SRR (95% CI): 0.89 (0.84, 0.93) and 0.91 (0.85, 0.97)], and butter with olive oil [SRR (95% CI): 0.94 (0.92, 0.97); all moderate CoE]. Mainly no associations were observed when substituting dairy products against each other on disease and mortality risk. Our fi ndings indicate associations between substituting dairy with red or processed meat and higher disease risk, whereas its substitution with whole grains was associated with a lower risk. However, there is little robust evidence that substituting whole-fat with low-fat dairy is associated with disease risk. (CRD42022303198).