Safety Considerations for Natural Products with Adaptogenic and Immunomodulating Activities

Area of Science:

• Pharmacovigilance and Natural Product Research
• Integrative and Complementary Medicine Safety

Background:

• Adaptogenic and immunomodulatory natural products are widely used in Eurasian traditional medicine.
• Safety profiles, especially adverse events (AEs) and serious adverse events (SAEs), are insufficiently understood.
• This includes herbal remedies, fungi, and animal-derived substances.

Purpose of the Study:

• To assess the safety profiles of adaptogenic and immunomodulatory natural products.
• Utilized a scoping review of human studies and analysis of WHO-UMC VigiBase individual case safety reports (ICSRs).

Main Methods:

• Conducted a scoping review of PubMed (1980-2024) following PRISMA-ScR guidelines.
• Included randomized/non-randomized trials and case reports focusing on safety outcomes.
• Analyzed 45,042 ICSRs from VigiBase for 49 natural products, categorizing by product type, AE, and demographics.

Main Results:

• Identified 51 natural products; 285 clinical trials and 119 case studies for single-ingredient products; 54 trials and 21 case studies for multi-ingredient products.
• Common AEs: gastrointestinal, dermatological, hepatic, cardiovascular, and immunological.
• SAEs were rare but reported for specific products; 15.8% of single-ingredient ICSRs were SAEs, including fatalities, though causality was unclear.

Conclusions:

• Comprehensive overview of safety profiles reveals variability in product composition and lack of standardization.
• Incomplete reporting in studies and underreporting in pharmacovigilance databases hinder accurate risk assessment.
• Further high-quality research, improved pharmacovigilance, and clear safety warnings are essential for consumer protection.