Hypersensitivity reactions associated with nutraceuticals and dietary supplements: A narrative review

The global use of nutraceuticals and dietary supplements-including vitamins, minerals, probiotics, and botanical extracts-has increased substantially, driven largely by consumer perceptions of safety and health benefits. However, their potential to cause hypersensitivity reactions (HSRs) is underrecognized. This review synthesizes published case reports, case series, systematic reviews, and pharmacovigilance data to characterize HSRs linked to these products, identify risk factors, and examine diagnostic and regulatory challenges. We classified reactions as immediate (< 1-6 h after administration), non-immediate (> 1-6 h after administration to several weeks). Immediate HSRs, including anaphylaxis, have been reported after vitamins B complex, short-chain galacto-oligosaccharides (GOS), whole-food supplements such as spirulina, natto (poly[γ-glutamic acid]) and royal jelly, and botanical/plant derived products; diagnosis commonly used skin-prick and intradermal testing and basophil activation tests. Non-immediate HSRs-ranging from maculopapular eruptions to severe cutaneous adverse reactions-have been associated with cobalamin, chromium picolinate, alpha-lipoic acid, diindolylmethane (DIM), glucosamine/chondroitin, and euglena; diagnosis often relies on patch testing, lymphocyte transformation assays, and cautious drug provocation when indicated. These products can also cause allergic contact dermatitis, and occupational sensitization (e.g., rhinitis/asthma) has been reported in workers exposed to psyllium and Aspergillus oryzae-derived lactase. Diagnostic accuracy is limited by nonstandardized reagents, variable test concentrations, complex product formulations, and cross-reactivity (notably within botanical families such as Asteraceae and among plant proteins/legumes), complicating interpretation and increasing risk for atopic individuals. Evidence remains dominated by case-based reports and passive surveillance. To reduce risk, we recommend heightened clinician awareness, development of standardized diagnostic reagents and protocols, mandatory adverse-event reporting, clearer ingredient labeling, and premarket allergenicity assessment.