The role of specific nutrients in preventing immune system and blood cell disorders: an umbrella review

Introduction. Nutritional deficiencies affecting the immune and haematopoietic systems represent a well-known global public health challenge: only the iron deficiency anaemia affects 1.62 billion individuals, especially in vulnerable populations. However, the protective effect that nutrition might give on disorders of these systems is still poorly understood. This umbrella review aims to synthesise the available evidence on the effectiveness of nutritional interventions in the primary prevention of blood and immune disorders, with a focus on the role of essential micronutrients and bioactive compounds. Materials and methods. The protocol for this review was registered on PROSPERO (registration number 535785). A systematic search was conducted on PubMed, Web of Science, Embase and Cochrane until April 2024, using MeSH terms and keywords related to nutritional interventions, preventive effects and immune and haematopoietic system disorders. The search strategy followed the PRISMA guidelines for umbrella reviews. Two independent review teams performed the screening and data extraction, while a third reviewer resolved any disputes. Methodological quality was assessed using the JBI Critical Appraisal Checklist, risk of bias was analysed using the tools ROBINS-E for non-experimental studies, ROBIS for systematic reviews and RoB 2 for RCTs. The quality of evidence was assessed according to the GRADE approach. Results. Of the 1028 articles identified, 13 met the inclusion criteria after systematic screening. Considering specific infection rates, vitamin D supplementation showed a significant protective effect (OR 0.88, 95% CI 0.81-0.96), with particular efficacy in deficient subjects (< 25 nmol/L). Zinc showed significant preventive efficacy (RR 0.68, 95% CI 0.58- 0.80), especially in nasal formulations. Multiple micronutrient interventions demonstrated synergistic effects in reducing iron deficiency (RR 0.44, 95% CI 0.32-0.60) and vitamin A deficiency (RR 0.42, 95% CI 0.28-0.62). The methodological quality of the included studies was high, with JBI scores ranging from 9.5 to 11/11, indicating a solid evidence base. Conclusion. The evidence supports the effectiveness of nutritional interventions in boosting the immune system, with particular relevance for vitamin D and zinc supplementation. The multiple micronutrient approach emerges as a promising strategy, especially in more-at-risk populations. Both individualised approaches and public health interventions are recommended. Future research should focus on optimising nutrient combinations and identifying predictive biomarkers of response for the primary prevention of blood and immune disorders