Elderberry

Metadata

Approved Indications

Commission E (Germany)

• Elderflower (Sambuci flos): Approved for diaphoretic therapy of the common cold. No known contraindications listed.
• Elderberry fruit (Sambuci fructus): No specific Commission E monograph for the fruit.

ESCOP

• Elderflower: Treatment of feverish common cold conditions
• Elderberry fruit: No separate ESCOP monograph identified [NEEDS-RESEARCH]

EMA/HMPC

• Elderflower (Sambuci flos): EU herbal monograph adopted. Traditional use for relief of early symptoms of common cold. Revision updated 2024.
• Elderberry fruit (Sambuci fructus): No EU herbal monograph adopted. The HMPC concluded that the requirements for establishing a monograph were not fulfilled because complete information on traditional use with a specified posology (dose regimen) over 30 years was lacking. A public statement was issued instead. [Source: EMA/HMPC/44208/2012]

Agreement/Disagreement Across Bodies

• Significant gap: Despite strong clinical trial evidence, elderberry fruit has the weakest European regulatory endorsement of any herb in this module. The regulatory bodies recognize elderflower but not elderberry fruit.
• Irony: The clinical trial evidence is actually stronger for the fruit than for the flower, but the regulatory framework favors documented traditional use over clinical trial data for the “traditional use” pathway.

Conditions Treated

• Influenza A and B (treatment, symptom reduction, duration shortening)
• Common cold / URTI (treatment)
• General immune support during respiratory illness season
• [Traditional/folk use]: Febrile conditions, as diaphoretic (flower), mild laxative (fruit)

Mechanism of Action

Active Compounds

Immune Mechanisms

1. Direct antiviral activity: Elderberry flavonoids bind to and inhibit H1N1 and other influenza virus strains by blocking viral neuraminidase and hemagglutinin, preventing viral attachment and entry into host cells. In vitro, Sambucol inhibited replication of influenza A (H3N2, H1N1) and B strains. [Source: Zakay-Rones 1995, Pubmed 9395631]
2. Cytokine modulation: Sambucol activated production of inflammatory cytokines (IL-1-beta, TNF-alpha, IL-6, IL-8) in healthy donors. This pro-inflammatory activation during early infection may enhance innate immune clearance. [Source: Barak 2001, Pubmed 11399518]. However, in pro-inflammatory environments, elderberry extract reduced TNF-alpha and IFN-gamma, suggesting bidirectional immunomodulation. [Source: Tandfonline, 2021]
3. NK cell activation: Enhancement of natural killer cell activity documented in vitro
4. Secretory IgA: Some evidence for enhanced mucosal immunity [NEEDS-RESEARCH]

COVID-19 Cytokine Storm Concern

During the COVID-19 pandemic, concerns were raised that elderberry’s pro-inflammatory cytokine activation could theoretically worsen cytokine storm in severe COVID-19. This concern was largely theoretical and not supported by clinical evidence. Elderberry’s immunomodulatory effects appear context-dependent (pro-inflammatory in healthy tissue, anti-inflammatory in already-inflamed tissue). [Source: PMC9744084]

Clinical Evidence Summary

Meta-Analysis (Hawkins et al., 2019)

• 5 RCTs, n=936 adults
• Effect size: d=1.717 (large) for reduction of upper respiratory symptom duration
• Conclusion: Elderberry supplementation substantially reduces upper respiratory symptoms compared to placebo
• Subgroup findings: Larger effect for influenza (4 days shorter) than common cold (2 days shorter)
• [Source: Pubmed 30670267]

Key Individual Trials

Rapid Review (Porter & Bode, 2017)

• Across 5 clinical studies involving 936 adults, mono-herbal elderberry preparations taken within 48 hours of onset may reduce duration and severity of cold and influenza symptoms
• Noted that benefit was most consistent when elderberry was started early in the illness [Source: PMC7443157]

European vs. US/Anglophone Consensus

Safety Profile

Contraindications

• Allergy: Rare allergic reactions to Sambucus nigra
• Raw/unripe berries: Contain cyanogenic glycosides (sambunigrin). MUST be cooked or processed before consumption. Raw berries, bark, leaves, and unripe fruit can cause nausea, vomiting, diarrhea, and in serious cases, cyanide toxicity.
• Autoimmune disease: Theoretical concern due to immune stimulation, similar to Echinacea. No clinical data supporting harm. [UNCERTAIN]

Drug Interactions

• Immunosuppressants: Theoretical antagonism (as with other immunomodulators)
• Diabetes medications: Some evidence elderberry may lower blood glucose; additive hypoglycemia possible [UNCERTAIN]
• Diuretics: Elderberry has mild diuretic properties; additive effect possible
• Overall: Drug interaction risk is LOW based on available evidence

Side Effects

• Gastrointestinal symptoms (nausea, vomiting, abdominal cramps) — primarily from raw/undercooked preparations
• Properly processed commercial preparations (Sambucol, standardized extracts): Very well tolerated
• Hepatic and renal safety markers unaffected in clinical studies

Pregnancy/Lactation

• Pregnancy: Insufficient data. Not formally recommended by any regulatory body during pregnancy. No human teratogenicity data available. Traditional use as food suggests likely safety of properly processed fruit, but medicinal doses are not validated. [NEEDS-RESEARCH]
• Lactation: Insufficient data. Traditionally consumed as food during lactation without known adverse effects.

Clinical Dosage

Sambucol and Standardized Extracts

• Sambucol syrup: 15 mL (1 tablespoon) four times daily for adults (per Zakay-Rones 2004 protocol)
• Standardized elderberry extract capsules: 300-600 mg daily (prophylaxis); up to 900 mg daily divided in 3 doses (treatment)
• Duration: 3-5 days for acute treatment; up to 2-3 weeks for prophylaxis during travel or flu season

Traditional Preparations (European)

• Elderberry juice/syrup: 10-15 mL daily (traditional German/Scandinavian use)
• Elderflower tea: 3-5 g dried flowers per cup, 2-3 times daily (diaphoretic)
• Elderflower tincture: 1.5-3 mL three times daily

Key Commercial Products

• Sambucol Original (Pharma Care): Standardized elderberry extract with 38% elderberry extract; the most-studied product
• Sambucol Black Elderberry (various formulations): Lozenges, gummies, syrups
• Rubini elderberry extract: Concentrated 33:1 extract; 230 mg daily
• Nature’s Way Sambucus: US market standardized extract

Sources

• Hawkins J et al. “Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: A meta-analysis of randomized, controlled clinical trials.” Complement Ther Med. 2019;42:361-365. (Pubmed 30670267)
• Zakay-Rones Z et al. “Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections.” J Int Med Res. 2004;32(2):132-140. (Pubmed 15080016)
• Zakay-Rones Z et al. “Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract during an outbreak of influenza B Panama.” J Altern Complement Med. 1995;1(4):361-369. (Pubmed 9395631)
• Barak V et al. “The effect of Sambucol on the production of human cytokines.” Eur Cytokine Netw. 2001;12(2):290-296. (Pubmed 11399518)
• Porter RS, Bode RF. “A Review of the Antiviral Properties of Black Elder (Sambucus nigra L.) Products.” Phytother Res. 2017;31(4):533-554.
• EMA/HMPC Public Statement on Sambucus nigra L., fructus (EMA/HMPC/44208/2012)
• EMA/HMPC Monograph on Sambucus nigra L., flos (revision 2024)
• Ulbricht C et al. “An evidence-based systematic review of elderberry and elderflower by the Natural Standard Research Collaboration.” J Diet Suppl. 2014;11(1):80-120.

Connections

• Echinacea: Often combined in OTC products; complementary mechanisms (elderberry = direct antiviral; echinacea = immunomodulatory)
• Andrographis: Comparable clinical evidence quality for URTI; both lack full EU monograph
• Pelargonium: Complementary indication (elderberry for flu/cold onset; Pelargonium for acute bronchitis)