Science

Melissa M Lane, Elizabeth Gamage, Shutong Du, Deborah N Ashtree, Amelia J McGuinness, Sarah Gauci, Phillip Baker, Mark Lawrence, Casey M Rebholz, BernardSrour, Mathilde Touvier, Felice N Jacka, Adrienne O’Neil, Toby Segasby, Wolfgang Marx

Objective
To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defi ned by the Nova food classifi cation system, andadverse health outcomes.

Design
Systematic umbrella review of existing meta-analyses.

Data sources
MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manual searches of reference lists from 2009 to June 2023.

Eligibility criteria for selecting studies
Systematic reviews and meta-analyses of cohort, case-control, and/or cross sectional study designs. To evaluate the credibility ofevidence, pre-specifi ed evidence classifi cation criteria were applied, graded as convincing (“class I”), highly suggestive (“class II”), suggestive (“class III”), weak (“class IV”), orno evidence (“class V”). The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework,categorised as “high,” “moderate,” “low,” or “very low” quality.

Results
The search identifi ed 45 unique pooled analyses, including 13 dose-response associations and 32 non-dose-response associations (n=9 888 373). Overall, directassociations were found between exposure to ultra-processed foods and 32 (71%) health parameters spanning mortality, cancer, and mental, respiratory, cardiovascular,gastrointestinal, and metabolic health outcomes. Based on the pre-specifi ed evidence classifi cation criteria, convincing evidence (class I) supported direct associationsbetween greater ultra-processed food exposure and higher risks of incident cardiovascular disease related mortality (risk ratio 1.50, 95% confi dence interval 1.37 to 1.63;GRADE=very low) and type 2 diabetes (dose-response risk ratio 1.12, 1.11 to 1.13; moderate), as well as higher risks of prevalent anxiety outcomes (odds ratio 1.48, 1.37 to1.59; low) and combined common mental disorder outcomes (odds ratio 1.53, 1.43 to 1.63; low). Highly suggestive (class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all cause mortality (risk ratio 1.21, 1.15 to 1.27; low), heart disease related mortality (hazard ratio 1.66,1.51 to 1.84; low), type 2 diabetes (odds ratio 1.40, 1.23 to 1.59; very low), and depressive outcomes (hazard ratio 1.22, 1.16 to 1.28; low), together with higher risks ofprevalent adverse sleep related outcomes (odds ratio 1.41, 1.24 to 1.61; low), wheezing (risk ratio 1.40, 1.27 to 1.55; low), and obesity (odds ratio 1.55, 1.36 to 1.77; low). Ofthe remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (class III-IV) and 13 were graded as no evidence (class V). Overall, using the GRADEframework, 22 pooled analyses were rated as low quality, with 19 rated as very low quality and four rated as moderate quality.

Conclusions
Greater exposure to ultra-processed food was associated with a higher risk of adverse health outcomes, especially cardiometabolic, common mental disorder,and mortality outcomes. These fi ndings provide a rationale to develop and evaluate the eff ectiveness of using population based and public health measures to target andreduce dietary exposure to ultra-processed foods for improved human health. They also inform and provide support for urgent mechanistic research.