Aluminium adjuvants in vaccines and potential health effects: systematic review.

Abstract

To systematically review and critically appraise human evidence on potential health effects of aluminium adjuvanted vaccines. Systematic review following PRISMA (preferred reporting items for systematic review and meta-analysis) 2020 guidelines. Six databases and trial registries were searched from inception to 3 March 2023 then updated to 27 November 2025. Reference lists of eligible studies were also screened. Human studies assessing health outcomes after aluminium adjuvanted vaccination, including randomised controlled trials, cohort studies, case series, and ecological studies. Investigational vaccines, case reports, and review articles were excluded. Two reviewers screened studies (with AI assistance for the 2023-25 update), extracted data, and assessed risk of bias (using RoB 2.0, ROBINS-I, or an adapted tool for case series). Certainty of evidence was rated using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). The review included 59 studies (37 case series, 11 randomised controlled trials, nine cohort studies, two ecological studies). High quality evidence from randomised controlled trials and large cohorts consistently showed no association between aluminium adjuvanted vaccines and serious or long term health outcomes, such as asthma, autism spectrum disorders, or other chronic conditions. Studies on macrophagic myofasciitis were generally small and methodologically limited, and did not provide credible evidence of a causal association (very low certainty). Localised persistent nodules or granulomas were observed infrequently after diphtheria-tetanus-pertussis vaccines, consistent with delayed type hypersensitivity (<1%, self-limited; moderate to low certainty). For common adverse events (eg, headache, myalgia), high certainty randomised controlled trials found no consistent increase in risk with aluminium adjuvanted formulations. When differences were observed, they were small and predominantly mild to moderate in severity. Evidence was dominated by methodologically limited studies, with most case series and ecological studies at serious or critical risk of bias. Conclusions are primarily supported by higher quality randomised controlled trials and cohort evidence. Current evidence does not support causal associations between aluminium adjuvanted vaccines and serious or long term health outcomes. The most consistently documented reactions were persistent nodules or granulomas that are uncommon, local, and self-limited hypersensitivity reactions. These findings are broadly consistent with post-licensure surveillance findings. The predominance of methodologically limited studies for some outcomes highlights the need for higher quality research. PROSPERO CRD42023462831.