Endpoint

Adverse event occurrence (oral or enteral supplement)

CAT:outcome/supplement-adverse-event-incidencereported in risk ratio7 findings from 7 compounds

What moved it

7 findings · 7 compounds · 5 null · by evidence strength

Compound	Direction	Findings	Strongest evidence
all-cis-docosa-4,7,10,13,16,19-hexaenoic acid	no effect	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
curcumin	up	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
riboflavin	no effect	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
Withania somnifera	no effect	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
Zn(2+)	no effect	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
Bacopa monnieri	up	1	Evidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.
melatonin	no effect	1	Evidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.

Reported to move it

2 findings

curcumin — increases
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.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).”
Quoted verbatim from Targeting cognitive aging with curcumin supplementation: A systematic review and meta-analysis..
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:40579315Permalink
Bacopa monnieri — increases
Very limitedEvidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.Finding
“Bacopa monnieri supplementation was generally well-tolerated, with no serious adverse reactions, although there was a greater frequency of self-reported adverse reactions in the Bacopa monnieri group (p = 0.024), primarily comprising digestive complaints and headaches.”
Quoted verbatim from The Effects of a Bacopa monnieri Extract (Bacumen®) on Cognition, Stress, and Fatigue in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Trial..
Study

RCT
Duration

3 months
Dose

300 mg daily
Population

Adults aged 40-70 years with self-reported memory and attention problems
The Effects of a Bacopa monnieri Extract (Bacumen®) on Cognition, Stress, and Fatigue in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.2025PMID:41091332Permalink

Measured, no effect detected

5 findings

all-cis-docosa-4,7,10,13,16,19-hexaenoic acid — no detected effect on
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.FindingNull result
“Overall, there were no significant differences in the incidence, type, or severity of adverse effects reported in the placebo or DHA group.”
Quoted verbatim from Safety and efficacy of docosahexaenoic acid supplementation during neoadjuvant breast cancer therapy: Findings from the phase II, double-blind, randomized controlled DHA-WIN trial..
Study

RCT
Duration

4 months
Dose

4.4 g/day DHA-enriched algae triacylglycerol (11 x 400 mg capsules/day), oral, concurrent with 6 cycles (18 weeks) of neoadjuvant chemotherapy
Population

women with stage I-III non-metastatic breast cancer undergoing neoadjuvant chemotherapy
Safety and efficacy of docosahexaenoic acid supplementation during neoadjuvant breast cancer therapy: Findings from the phase II, double-blind, randomized controlled DHA-WIN trial.2025PMID:40490846Industry fundedPermalink
riboflavin — no detected effect on
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.FindingNull result
“The evidence suggests that riboflavin may result in little to no difference in adverse events (odds ratio (OR) 1.92, 95% CI 0.16 to 22.56; P = 0.60; 1 study, 54 participants; low‐certainty evidence;.”
Quoted verbatim from Riboflavin supplements for blood pressure lowering in adults..
Study

meta-analysis
Participants

54
Population

Adults with a history of migraine, riboflavin 400 mg/day for 12 weeks versus placebo (Schoenen 1998); this was the only one of the four included RCTs that reported adverse-event data.
Effect 1.92 odds ratio, 95% CI 0.16 to 22.56
Riboflavin supplements for blood pressure lowering in adults.2025PMID:41123035Permalink
Zn(2+) — no detected effect on
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.FindingNull result
“The meta-analysis of adverse event rates showed no statistically significant difference between the zinc supplementation group and the placebo group (odds ratio [OR] = 2.536; 95% CI = 0.78 to 8.26; p = 0.122; I2 = 0%) Figure 9.”
Quoted verbatim from Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis..
Study

meta-analysis
Population

Women aged 13 to 27 years with primary dysmenorrhea; pooled across six randomised trials of zinc supplementation (gluconate or sulfate) against placebo
Effect 2.536 odds ratio, 95% CI 0.78 to 8.26
Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis.2024PMID:39683510Industry fundedPermalink
Withania somnifera — no detected effect on
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.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.”
Quoted verbatim from 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..
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 fundedPermalink
melatonin — no detected effect on
Very limitedEvidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.FindingNull result
“17 randomised controlled trials with 651 participants showed no evidence of adverse effects of melatonin with short term use (three months or less).”
Quoted verbatim from Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis..
Study

meta-analysis
Participants

651
Population

participants in randomised controlled trials of short-term melatonin (three months or less)
Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis.2006PMID:16473858Permalink

How it is measured

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 with each finding and changes the rate several-fold.