Adverse event occurrence (oral or enteral supplement)

Method

Occurrence of any adverse event in a trial of an orally or enterally administered supplement — gastrointestinal upset, elevated liver enzymes, insomnia, raised blood pressure and similar — as the proportion of participants recording at least one event. Whether events were solicited on a checklist or reported spontaneously is recorded on the edge and changes the rate several-fold.

The method is part of the endpoint identity. Studies measuring the same quantity by a different method are held as separate endpoints.

Notes

Confused with the procedural complication rate, which counts harms of an invasive procedure on an entirely different hazard scale; aggregating adverse events across intervention classes produces a number with no interpretable denominator. Also distinct from serious adverse event incidence, which applies a regulatory severity threshold most events here do not meet, and from withdrawal due to adverse events, which counts a decision rather than an event. SIGN NOTE: this is a harm and improves by FALLING, while the responder-rate and clinical-effective-rate proportions computed from the very same trials improve by RISING — same unit, opposite polarity.

Findings

2 findings from 2 compounds, strongest first.

• curcumin — increases

  BLikelyGrade B, Likely. Human evidence, limited replication or design limits.Finding

  “Meta-analysis of adverse reactions associated with curcumin indicated a statistically significant increase in adverse events compared to placebo (SMD = 2.40, 95 % CI: 1.37 to 4.21, I2 = 44.1 %) (Supplementary 4 - SFigure 3).”

  Study

  meta-analysis

  Population

  adults in randomised trials of oral curcumin supplementation for cognitive ageing; secondary endpoint

  Effect 2.4 standardised mean difference, 95% CI 1.37 to 4.21

  Targeting cognitive aging with curcumin supplementation: A systematic review and meta-analysis.2025PMID:40579315

• Withania somnifera — no detected effect on

  BLikelyGrade B, Likely. Human evidence, limited replication or design limits.FindingNull result

  “The relative risk (RR) of experiencing at least one AE in the ARE group compared with PL was 0.67 (95% CI: 0.42–1.06), suggesting a numerically lower, though not statistically significant, AE incidence in the Ashwagandha group.”

  Study

  RCT

  Participants

  1,002

  Duration

  8 weeks

  Dose

  300 mg capsule orally twice daily (600 mg/day), after breakfast and after dinner, for 8 weeks

  Population

  adults aged 18 to 65 with reported stress and anxiety (HAM-A total 14-30, Cohen PSS 13 or above), enrolled at 15 sites across India, Australia, the United States, Portugal and Africa

  Effect 0.67 risk ratio, 95% CI 0.42 to 1.06

  Safety of 8-Week Administration With Ashwagandha (Withania somnifera) Root Extract in Adults With Stress and Anxiety: Findings From a Prospective, Randomized, Multi-Center, Double-Blinded, Placebo-Controlled Study.2026PMID:41943502Industry funded