Global Ingredient Risk Index Stimulant

Higenamine

Norcoclaurine

Also known as: Demethylcoclaurine, aconite alkaloid, norcoclaurine HCl

04 მარ 2026

HIGH RISK 6.5/10 How?

Evidence Strength: LIMITED

This ingredient is classified as unclassified risk (GIRI score: 6.5/10). The classification is based on mechanistic and clinical evidence: higenamine primarily acts as a beta-adrenergic receptor agonist, which stimulates the sympathetic….

Common Adverse Effects

Increased heart rate
palpitations
dizziness
nausea
anxiety

Serious Adverse Effects

Arrhythmias
hypertension
myocardial infarction
stroke

Contraindications

Hypertension
arrhythmia
coronary artery disease
hyperthyroidism
People taking Beta-blockers

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Drug / Nutrient	Interaction Mechanism	Warning
Beta-blockers	antagonistic effects — may reduce efficacy of beta	blockers. MAO inhibitors: increased risk of hypertensive crisis — avoid concomitant use. Antihypertensives: reduced effectiveness — monitor blood pressure closely.

Higenamine, also known as norcoclaurine, is a naturally occurring chemical compound found in several plants, including Nandina domestica and Aconitum carmichaelii. It is commonly used in dietary supplements for its stimulant properties, often marketed for weight loss and athletic performance enhancement. Higenamine acts as a beta-adrenergic agonist, which can increase heart rate and improve energy expenditure.

Chemical Class: Benzylisoquinoline alkaloid
Biological Class: Stimulant
Natural Source: Nandina domestica (fruit), Aconitum carmichaelii (root)
Scientific Name: Norcoclaurine
Chemical Formula: C16H17NO3
CAS Number: 11041-94-4

Higenamine primarily acts as a beta-adrenergic receptor agonist, which stimulates the sympathetic nervous system. It binds to beta-1 and beta-2 adrenergic receptors, leading to increased cyclic AMP levels and subsequent activation of protein kinase A. This results in enhanced cardiac contractility and bronchodilation. Additionally, higenamine may influence nitric oxide production, contributing to vasodilation and improved blood flow.

Indication	Evidence Level	Summary
General	Moderate	The clinical evidence for higenamine is limited, with few high-quality human studies. Most research has focused on its cardiovascular effects, showing increased heart rate and potential for arrhythmias. Some studies suggest benefits in exercise performance and weight loss, but these findings are inconsistent and often based on small sample sizes. Overall, the evidence is insufficient to fully support its efficacy and safety in humans.

Evidence levels: Strong Moderate Limited Experimental

Absorption

Higenamine is rapidly absorbed following oral administration, with peak plasma concentrations typically reached within 30 minutes to 1 hour. Its bioavailability is relatively low, likely due to extensive first-pass metabolism. The half-life of higenamine is short, approximately 1 to 2 hours.

Distribution

Higenamine is distributed throughout the body, with a moderate volume of distribution. It has been shown to cross the blood-brain barrier, although the extent of central nervous system penetration is not well-characterized. Protein binding data is limited.

Metabolism

Higenamine undergoes extensive hepatic metabolism, primarily through conjugation reactions such as glucuronidation and sulfation. The specific enzymes involved have not been fully elucidated. The major metabolites are excreted in the urine.

Excretion

Higenamine is primarily excreted via the kidneys, with metabolites appearing in the urine. Renal excretion accounts for the majority of the elimination, with a minor component possibly excreted in the bile.

Condition / Use	Typical Dose
Weight loss	20-40 mg per day. Athletic performance: 10-20 mg prior to exercise. Cardiovascular support: 10-30 mg per day.

Dosage ranges are based on clinical studies and commonly used supplement formulations. Individual requirements may vary.

SETI Score 50/100

Risk Level High risk

Scientific Confidence Low

Evidence Strength Limited

Key Benefit Higenamine, also known as norcoclaurine, is a naturally occurring chemical compound found in several plants, including Nandina domestica…

Key Safety Concern Higenamine poses significant cardiovascular risks, particularly in individuals with pre-existing heart conditions. Its stimulant effects can lead to serious adverse events such as arrhythmias and hypertension. Pregnant and breastfeeding women, as well as individuals with renal or hepatic impairment, should avoid its use. Regulatory agencies have issued warnings about its potential dangers, and it is banned by several sports organizations.

Evidence Reviewed 10 PubMed studies

Scientific Confidence Low

Based on study quality, consistency, and recency

Executive Summary — Ingredient Assessment

SETI Score 50/100

Risk Level High risk

Evidence Strength Limited

Main Benefit Higenamine, also known as norcoclaurine, is a naturally occurring chemical compound found in several plants, including Nandina domestica…

Main Safety Concern Higenamine poses significant cardiovascular risks, particularly in individuals with pre-existing heart conditions. Its stimulant effects can lead to serious adverse events such as arrhythmias and hypertension. Pregnant and breastfeeding women, as well as individuals with renal or hepatic impairment, should avoid its use. Regulatory agencies have issued warnings about its potential dangers, and it is banned by several sports organizations.

Ingredient Higenamine

Scientific name Norcoclaurine

Scientific Evidence Overview

10 studies reviewed
0 high-quality studies (meta-analysis or RCT)
Main clinical benefit observed: Higenamine, also known as norcoclaurine, is a naturally occurring chemical compound found in several plants, including Nandina domestica…
Evidence consistency: High consistency across studies (100%)

Safety Signals

Higenamine poses significant cardiovascular risks, particularly in individuals with pre-existing heart conditions. Its stimulant effects can lead to serious adverse events such as arrhythmias and hypertension. Pregnant and breastfeeding women, as well as individuals with renal or hepatic impairment, should avoid its use. Regulatory agencies have issued warnings about its potential dangers, and it is banned by several sports organizations.

Evidence Strength Limited

Regulatory Status

USA/FDA — Approved

Final Scientific Assessment

The available scientific evidence for Higenamine indicates notable safety signals that warrant caution. Use should be considered carefully and monitored, particularly in sensitive populations or alongside other medications.

Ingredient Higenamine

Evidence reviewed 10 peer-reviewed studies (last 10 years)

Scientific name Norcoclaurine

50 /100

Total SETI Score

High risk

Evidence quality	10/40
Evidence consistency	20/20
Safety signals	0/20
Study recency	10/10
Evidence transparency	10/10

Evidence Summary

10 studies reviewed
0 high-quality studies (meta-analysis or systematic review)
0 studies identified benefits or no safety concern (GREEN)
10 studies reported limited or advisory safety evidence (YELLOW)

Evidence Policy

Only peer-reviewed scientific literature indexed in PubMed or comparable databases is included in this evaluation. Commercial websites, blogs, and marketing materials are excluded. All references include direct traceable links to source documents.

Last updated: 06 მარ 2026, 12:00

Evidence Distribution

1 Animal studies

9 Other / unclassified

Observational / other LOW evidence YELLOW
Transcriptome analysis of Stephania cepharantha and characterization of two CYP80B genes involved in the benzylisoquinoline alkaloid biosynthesis. ↗

PMID 41655513 ↗

Journal Plant Physiol Biochem

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41655513/

Feng Y et al.. Transcriptome analysis of Stephania cepharantha and characterization of two CYP80B genes involved in the benzylisoquinoline alkaloid biosynthesis.. Plant Physiol Biochem. 2026. PMID:41655513.
Observational / other LOW evidence YELLOW
Functional Characterization of Two Methyltransferases Involved in Benzylisoquinoline Alkaloid Biosynthesis in Sinomenium acutum. ↗

PMID 41563946 ↗

Journal Chem Biodivers

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41563946/

Qi Y et al.. Functional Characterization of Two Methyltransferases Involved in Benzylisoquinoline Alkaloid Biosynthesis in Sinomenium acutum.. Chem Biodivers. 2026. PMID:41563946.
Observational / other LOW evidence YELLOW
Molecular characterization of two O-methyltransferases involved in benzylisoquinoline alkaloid biosynthesis in Aristolochia debilis. ↗

PMID 41411959 ↗

Journal Plant Physiol Biochem

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41411959/

Yamada Y et al.. Molecular characterization of two O-methyltransferases involved in benzylisoquinoline alkaloid biosynthesis in Aristolochia debilis.. Plant Physiol Biochem. 2026. PMID:41411959.
Observational / other LOW evidence YELLOW
UHPLC-MS/MS-guided profiling and bioactivity screening of Papaver apokrinomenon extracts: Insights into alkaloid- and phenolic-driven health effects. ↗

PMID 41167345 ↗

Journal Fitoterapia

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41167345/

Ahmed S et al.. UHPLC-MS/MS-guided profiling and bioactivity screening of Papaver apokrinomenon extracts: Insights into alkaloid- and phenolic-driven health effects.. Fitoterapia. 2025. PMID:41167345.
Observational / other LOW evidence YELLOW
Integration of Physiological Analysis and Untargeted Metabolomics to Explore Differences in Quality Among Four Sweet Cherry Cultivars. ↗

PMID 41008180 ↗

Journal Foods

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41008180/

Li G et al.. Integration of Physiological Analysis and Untargeted Metabolomics to Explore Differences in Quality Among Four Sweet Cherry Cultivars.. Foods. 2025. PMID:41008180.
Observational / other LOW evidence YELLOW
Functional divergence of NCS homologs in the PR10 family drives tissue-specific berberine accumulation in Coptis chinensis Franch. ↗

PMID 40925754 ↗

Journal Plant Physiol Biochem

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/40925754/

Zhang M et al.. Functional divergence of NCS homologs in the PR10 family drives tissue-specific berberine accumulation in Coptis chinensis Franch.. Plant Physiol Biochem. 2025. PMID:40925754.
Observational / other LOW evidence YELLOW
Qifu Decoction Alleviates Lipopolysaccharide-Induced Myocardial Dysfunction by Inhibiting TLR4/NF-u03baB/NLRP3 Inflammatory Pathway and Activating PPARu03b1/CPT Pathway. ↗

PMID 40872501 ↗

Journal Pharmaceuticals (Basel)

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/40872501/

Zhuo L et al.. Qifu Decoction Alleviates Lipopolysaccharide-Induced Myocardial Dysfunction by Inhibiting TLR4/NF-u03baB/NLRP3 Inflammatory Pathway and Activating PPARu03b1/CPT Pathway.. Pharmaceuticals (Basel). 2025. PMID:40872501.
Observational / other LOW evidence YELLOW
Genome-Wide Identification and Functional Analysis of the Norcoclaurine Synthase Gene Family in Aristolochia contorta. ↗

PMID 40362550 ↗

Journal Int J Mol Sci

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/40362550/

Xu Y et al.. Genome-Wide Identification and Functional Analysis of the Norcoclaurine Synthase Gene Family in Aristolochia contorta.. Int J Mol Sci. 2025. PMID:40362550.
Animal study LOW evidence YELLOW
In vitro propagation of Stephania pierrei diels and exploration of its potential as sustainable phytochemical production from tuber and callus. ↗

PMID 40133844 ↗

Journal BMC Plant Biol

Year 2025

Study type Animal study

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/40133844/

Laksana C et al.. In vitro propagation of Stephania pierrei diels and exploration of its potential as sustainable phytochemical production from tuber and callus.. BMC Plant Biol. 2025. PMID:40133844.
Observational / other LOW evidence YELLOW
Identification and Characterization of Two Se6OMTs from Stephania epigaea Offer Novel Insights into the Biosynthetic Pathway of Cepharanthine. ↗

PMID 39997717 ↗

Journal Metabolites

Year 2025

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/39997717/

Gan J et al.. Identification and Characterization of Two Se6OMTs from Stephania epigaea Offer Novel Insights into the Biosynthetic Pathway of Cepharanthine.. Metabolites. 2025. PMID:39997717.

Q × L × D × S × 10 = 6.5 / 10

The GIRI Score is the product of four independently computed evidence components, each normalised to 0–1, then scaled to 0–10. Every component is derived exclusively from peer-reviewed references and regulatory data — no editorial judgement is applied.

0 of 10 approved references (score saturates at 10). More peer-reviewed studies = stronger evidence base.

Method: Q = number of approved references ÷ 10 (capped at 1.0)

50%

Limited — mostly case reports or animal studies

Method: L = mean study-level weight across approved references. Level 1 (meta-analysis / systematic review) = 1.0; Level 2 (RCT) = 0.8; Level 3 (cohort/case-control) = 0.6; Level 4 (case report) = 0.4; Level 5 (animal / in-vitro) = 0.2.

Benefit

Risk

50%

Mixed or neutral — roughly equal benefit and risk signals

Method: D = (sum of risk-scored references − sum of benefit-scored references) ÷ total evidence score, then scaled from [−1, 1] to [0, 1]. 0.0 = pure benefit; 0.5 = neutral; 1.0 = pure risk.

50%

One or more monitoring-level safety signals active

Method: S = 0.5 (neutral baseline) + sum of active signal severity deltas ÷ 10. Severity deltas: Critical = +2.0, High = +1.5, Moderate = +1.0, Low = +0.5. Capped at 1.0.

0Q × 5L × 5D × 5S = 6.5 / 10

Final GIRI Score for Higenamine. Risk level thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.

Full methodology & data sources

The GIRI Score is computed entirely from structured data — no editorial scoring or subjective weighting is applied at any step.

References: Only approved references are counted. Each reference is assigned an evidence level (L1–L5) and a direction (risk / neutral / benefit) by the reference manager or AI classifier.
Safety Signals: Sourced from regulatory agencies (FDA, EMA, Health Canada, TGA, and others) and pharmacovigilance databases. Only active signals count toward the score.
Formula version: GIRI Score v3.7.0 — Q × L × D × S × 10.
Limitations: The score reflects published evidence and recorded signals as of the last update date. It is not a clinical risk assessment and should not replace advice from a qualified healthcare professional.

HIGH RISK 6.5/10

Based on available regulatory signals and scientific evidence, this ingredient presents a high safety concern. Its use in dietary supplements is associated with documented adverse events.

LOW
0–3.0

MODERATE
3.0–5.5

HIGH
5.5–7.5

CRITICAL
7.5–10

6.5

The score pin shows exactly where this ingredient falls on the fixed risk scale.

What drove the High classification for Higenamine

A score of 6.5 places this ingredient in the High band. Thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.

0 approved references.

Limited — mostly case reports or animal studies (Level 4–5).

Neutral or mixed — benefit and risk signals roughly balanced.

No active signals — S component is at neutral baseline (0.5), contributing no extra risk weight.

1 jurisdiction has active restrictions or advisories. Regulatory signals are recorded as Safety Signals and raise the S component.

How are the Low / Moderate / High / Critical thresholds defined?

The four risk levels are fixed score bands. A score is assigned to exactly one level based on where it falls:

Level	Score	Meaning
LOW	0.0 – 2.9	Sparse or predominantly beneficial evidence. No active safety alerts.
MODERATE	3.0 – 5.4	Mixed signals — some risk alongside benefit. Caution at high doses or in sensitive groups.
HIGH	5.5 – 7.4	Multiple studies or regulatory alerts documenting adverse effects. Professional oversight recommended.
CRITICAL	7.5 – 10	Regulatory restrictions in one or more major jurisdictions. Serious documented harm. Avoid without specialist supervision.

Thresholds are fixed constants (GIRI_Score_Utils::LEVEL_THRESHOLDS). They do not change per ingredient and are never subject to editorial adjustment.

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Higenamine

Safety Profile

Common Adverse Effects

Serious Adverse Effects

Contraindications

Interactions

Evidence and Scientific Findings

Ingredient Overview

Biological and Chemical Classification

Mechanism of Action

Clinical Evidence of Effectiveness

Pharmacokinetics

Recommended Dosage

SETI — Scientific Evidence Transparency Index

Executive Summary — Ingredient Assessment

Evidence Summary

Evidence Policy

Evidence Distribution

Score Transparency

Risk Level Classification

What drove the High classification for Higenamine

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