Health Care Professional Information

Scientific Name
Sambucus nigra
Common Name

Elder, elderberry, European elderberry, black elder, black elderberry, sambucus

Brand Name

Sambucol®, Sambu®, Sambu® Guard, SambuActin™, Eldertussin™, Theramax®, Zumka™

Clinical Summary

Elderberries come from a family of flowering shrubs known as Sambucus or elder. They are native to Europe but have become naturalized in many parts of the world including the United States. Cultivated for medicinal and food purposes, the fruit is used to produce jams, syrups, and wine. Elderberry flowers and fruit are incorporated in remedies to reduce cold and flu symptoms, for inflammation and respiratory diseases (1) (2) (3), and as a laxative (4). The berries are a rich source of anthocyanins and other phenolics and nutrients (2). Several species of Sambucus produce elderberries with similar chemical compositions including American Elder (Sambucus canadensis) and Blue Elder (Sambucus caerulea) (1), but European Elder (Sambucus nigra) is the type most studied and used in supplements.

In vitro studies demonstrate that elderberries possess antiviral (5), antibacterial (3), antidiabetic (6), immunomodulatory (7), antioxidant, anti-inflammatory, and chemopreventive properties (1) (2) (8), although inhibition of cancer cell growth was shown to be weak (9). Elderberry flavonoids and proanthocyanidins were shown to block HIV1 infection, and may have additive effects with existing HIV drugs such as enfuvirtide (10). Elderberry also conferred protective effects against oxidative stressors in endothelial cells (8). However, in vitro studies did not find elderberry to be vasoprotective (11) and randomized trials found it ineffective for both cardiovascular disease biomarkers (12) and improving cholesterol levels (13). Small randomized trials found that elderberry significantly reduced influenza symptoms (14), and was safe and effective in a preparation for chronic constipation (4), but more studies are needed before any conclusions can be drawn.

Unsubstantiated claims that elderberry prevents or treats various diseases including AIDS, diabetes and flu have recently been halted by the FDA (15). This is particularly important as patients may forego or avoid legitimate treatments.

Purported Uses
  • Bacterial Infections
  • Cancer
  • Circulatory disorders
  • Cold and flu symptoms
  • Constipation
  • HIV/AIDS
  • Inflammation
  • Respiratory infections
  • Sinusitis
Constituents
  • Flavonoids: kaempferol, quercetin, anthocyanins (primarily cyanidin-3-glucoside and cyanidin-3-sambubioside), proanthocyanidins, flavonoid glycosides, quercetin glycosides (rutin, hyperoside, isoquercetrin), rutoside
  • Flavonols: Quercetin-3-O-rutinoside, quercetin-3-O-glucoside
  • Phenols: Caffeic, chlorogenic, and caffeoylquinic acids
  • Lectins: Agglutinin
  • Lipophilic compounds: Iridoid monoterpene glycosides, phytosterols
  • Volatile oils: Triterpenes, sesquiterpenes
  • Alkaloids: Hydrocyanic acid, sambucine
  • Cyanohydrins, cyanogenic glycosides (sambunigrin) (1) (2) (11) (16) (17) (18)
Mechanism of Action

Elderberry inhibits H1N1 activities by binding to H1N1 virions and blocking host cell recognition and entry (5). It may also prevent HIV1 infection by binding to viral glycoproteins such as gp120 (10), but additional investigations are required to clarify those mechanisms (3). Elderberry’s anti-inflammatory effects may result from increased cytokine production (19) or inhibition of nuclear transcription factor kappaB and phosphatidylinositol 3-kinase (20). Its antidiabetic properties occur via activation of peroxisome proliferator-activated receptor gamma and stimulation of insulin-dependent glucose uptake (6). Another study indicates its chemopreventive potential is related to induction of quinone reductase as well as cyclooxygenase-2 and ornithine decarboxylase inhibition (2).

Pharmacokinetics

Total anthocyanins (TA, cyanidin-3-sambubioside and cyanidin -3-glucoside) were evaluated at two different single oral doses: 30 mL (278 mg TA) or 200 mL (1852 mg TA). The fraction of orally administered TA excreted unchanged was 0.39% (30 mL) and 0.27% (200 mL) within 7 hours, indicating low bioavailability. Elimination half-life was 1.85 h (278 mg) vs 2.57 h (1852 mg), with median TA renal clearances of 196 and 169 mL/min, respectively (21). Low urinary excretion (< 1%) of anthocyanidin glycosides also indicates high metabolization before entry into the circulation (22).

Warnings
  • Raw or unripe elderberries contain cyanogenic glycosides and must be cooked sufficiently to avoid risk of cyanide toxicity.
  • Elderberry leaves and stems also contain cyanogenic glycosides and should not be ingested.
  • Consuming elder bark, leaves and raw elderberries has caused poisoning.
    (23) (16)
Contraindications
  • Avoid use during pregnancy or if lactating due to risk of toxicity and potential GI distress (24).
  • Since elderberry may strengthen or modulate the immune system (7), it should be avoided in patients with autoimmune disorders such as rheumatoid arthritis, multiple sclerosis, and lupus, or those taking immunosuppressants.
Adverse Reactions

Infrequent: Type 1 allergy (25), gastrointestinal (GI) distress (23).
Case Report: Eleven people experienced nausea and vomiting, eight of whom had acute GI and neurologic symptoms after ingesting an elderberry juice made from raw elderberries, leaves, and branches. Other symptoms included dizziness and numbness and one person who had consumed the most juice was hospitalized (23).

Herb-Drug Interactions

Antidiabetic drugs: Elderberry has hypoglycemic activity and may have additive effects with antidiabetic drugs (6).
Diuretics: Elderberry promotes urination and may have additive effects with diuretics (26).
Laxatives: Elderberry may have additive effects (4) (24).
Cytochrome P4503A4 substrates: A commercial product containing Echinacea purpurea and Sambucus nigra was found to inhibit CYP3A4 activity, although the inhibitory potency seems to be exerted by E. purpurea. Until more is known, elderberry should be used with caution with CYP3A4 substrates (27).

Literature Summary and Critique

Curtis PJ, et al. Cardiovascular disease risk biomarkers and liver and kidney function are not altered in postmenopausal women after ingesting an elderberry extract rich in anthocyanins for 12 weeks. J Nutr. 2009 Dec;139(12):2266-71.
A randomized, placebo-controlled study evaluated the effect of chronic consumption of anthocyanin-rich elderberry on biomarkers of cardiovascular disease (CVD) risk as well as liver and kidney function in 52 healthy postmenopausal women (n=26 each in treatment and placebo groups). After a 12-wk intervention with elderberry extract 500 mg/d or placebo, there was no significant change in biomarkers for CVD risk. Liver and kidney function remained within safe ranges. The study concluded that chronic consumption of elderberry extract was safe but ineffective in altering CVD biomarkers in healthy postmenopausal women.

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 Mar-Apr;32(2):132-40.
This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of oral elderberry syrup for treating influenza A and B infections. Sixty patients who had influenza-like symptoms for 48 hours or less received elderberry syrup 15 mL 4 times per day for 5 days or placebo. Symptoms were relieved on average 4 days earlier and use of rescue medication was significantly less in those receiving elderberry extract compared with placebo. The authors concluded that elderberry extract may offer a safe and cost-effective treatment for influenza, but larger confirmatory studies are needed.

Murkovic M, et al. Effects of elderberry juice on fasting and postprandial serum lipids and low-density lipoprotein oxidation in healthy volunteers: a randomized, double-blind, placebo-controlled study. Eur J Clin Nutr. 2004;58:244-9.
This randomized, placebo-controlled trial investigated the effect of elderberry juice on cholesterol and triglyceride concentrations and antioxidant status in young volunteers. Thirty-four subjects took 400-mg capsules t.i.d. for 2 weeks containing 10% anthocyanes equivalent to 5 mL elderberry juice. A 14-subject subgroup continued for an additional week to test for LDL oxidation resistance. Changes in cholesterol concentrations in the elderberry group compared with placebo were small and nonsignificant; resistance to LDL oxidation did not change within 3 weeks. In a single-dose experiment, 6 subjects took one 50-mL dose of elderberry juice (equivalent to 10 capsules) along with a high-fat breakfast to investigate the short-term effects on serum lipid concentrations. Postprandial triglyceride concentrations were not significantly different when participants were evaluated with and without elderberry juice. The investigators concluded that elderberry at a low dose exhibited minor effects on serum lipids and antioxidative capacity, and that longer-term studies with higher doses should be evaluated for efficacy and safety.

Dosage (Inside MSKCC Only)
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References
  1. Scopel M, Mentz LA, Henriques AT. Comparative analysis of Sambucus nigra and Sambucus australis flowers: development and validation of an HPLC method for raw material quantification and preliminary stability study. Planta Med. Jul 2010;76(10):1026-1031.
  2. Thole JM, Kraft TF, Sueiro LA, et al. A comparative evaluation of the anticancer properties of European and American elderberry fruits. J Med Food. Winter 2006;9(4):498-504.
  3. Krawitz C, Mraheil MA, Stein M, et al. Inhibitory activity of a standardized elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses. BMC Complement Altern Med. 2011;11:16.
  4. Picon PD, Picon RV, Costa AF, et al. Randomized clinical trial of a phytotherapic compound containing Pimpinella anisum, Foeniculum vulgare, Sambucus nigra, and Cassia augustifolia for chronic constipation. BMC Complement Altern Med. 2010;10:17.
  5. Roschek B, Jr., Fink RC, McMichael MD, et al. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry. Jul 2009;70(10):1255-1261.
  6. Christensen KB, Petersen RK, Kristiansen K, et al. Identification of bioactive compounds from flowers of black elder (Sambucus nigra L.) that activate the human peroxisome proliferator-activated receptor (PPAR) gamma. Phytother Res. Jun 2010;24 Suppl 2:S129-132.
  7. Waknine-Grinberg JH, El-On J, Barak V, et al. The immunomodulatory effect of Sambucol on leishmanial and malarial infections. Planta Med. May 2009;75(6):581-586.
  8. Youdim KA, Martin A, Joseph JA. Incorporation of the elderberry anthocyanins by endothelial cells increases protection against oxidative stress. Free Radic Biol Med. Jul 1 2000;29(1):51-60.
  9. Jing P, Bomser JA, Schwartz SJ, et al. Structure-function relationships of anthocyanins from various anthocyanin-rich extracts on the inhibition of colon cancer cell growth. J Agric Food Chem. Oct 22 2008;56(20):9391-9398.
  10. Fink RC, Roschek B, Jr., Alberte RS. HIV type-1 entry inhibitors with a new mode of action. Antivir Chem Chemother. 2009;19(6):243-255.
  11. Bell DR, Gochenaur K. Direct vasoactive and vasoprotective properties of anthocyanin-rich extracts. J Appl Physiol. Apr 2006;100(4):1164-1170.
  12. Curtis PJ, Kroon PA, Hollands WJ, et al. Cardiovascular disease risk biomarkers and liver and kidney function are not altered in postmenopausal women after ingesting an elderberry extract rich in anthocyanins for 12 weeks. J Nutr. Dec 2009;139(12):2266-2271.
  13. Murkovic M, Abuja PM, Bergmann AR, et al. Effects of elderberry juice on fasting and postprandial serum lipids and low-density lipoprotein oxidation in healthy volunteers: a randomized, double-blind, placebo-controlled study. Eur J Clin Nutr. Feb 2004;58(2):244-249.
  14. Zakay-Rones Z, Thom E, Wollan T, 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. Mar-Apr 2004;32(2):132-140.
  15. U.S. Food and Drug Administration. FDA seizes elderberry juice concentrate at Kansas company [September 2, 2011 press release]. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm257781.htm?utm_campaign=Google257782&utm_source=fdaSearch&utm_medium=website&utm_term=elderberry&utm_content=257781.
  16. Dellagreca M, Fiorentino A, Monaco P, et al. Synthesis of degraded cyanogenic glycosides from Sambucus nigra. Nat Prod Res. Jun 2003;17(3):177-181.
  17. Barros L, Duenas M, Carvalho AM, et al. Characterization of phenolic compounds in flowers of wild medicinal plants from Northeastern Portugal. Food Chem Toxicol. May 2012;50(5):1576-1582.
  18. Schmitzer V, Veberic R, Slatnar A, et al. Elderberry (Sambucus nigra L.) wine: a product rich in health promoting compounds. J Agric Food Chem. Sep 22 2010;58(18):10143-10146.
  19. Barak V, Birkenfeld S, Halperin T, et al. The effect of herbal remedies on the production of human inflammatory and anti-inflammatory cytokines. Isr Med Assoc J. Nov 2002;4(11 Suppl):919-922.
  20. Harokopakis E, Albzreh MH, Haase EM, et al. Inhibition of proinflammatory activities of major periodontal pathogens by aqueous extracts from elder flower (Sambucus nigra). J Periodontol. Feb 2006;77(2):271-279.
  21. Frank T, Janssen M, Netzet G, et al. Absorption and excretion of elderberry (Sambucus nigra L.) anthocyanins in healthy humans. Methods Find Exp Clin Pharmacol. Oct 2007;29(8):525-533.
  22. Frank T, Sonntag S, Strass G, et al. Urinary pharmacokinetics of cyanidin glycosides in healthy young men following consumption of elderberry juice. Int J Clin Pharmacol Res. 2005;25(2):47-56.
  23. Centers for Disease Control and Prevention. Poisoning from elderberry juice—California. MMWR Morb Mortal Wkly Rep. Apr 6 1984;33(13):173-174.
  24. Tsui B, Dennehy CE, Tsourounis C. A survey of dietary supplement use during pregnancy at an academic medical center. Am J Obstet Gynecol. Aug 2001;185(2):433-437.
  25. Forster-Waldl E, Marchetti M, Scholl I, et al. Type I allergy to elderberry (Sambucus nigra) is elicited by a 33.2 kDa allergen with significant homology to ribosomal inactivating proteins. Clin Exp Allergy. Dec 2003;33(12):1703-1710.
  26. Beaux D, Fleurentin J, Mortier F. Effect of extracts of Orthosiphon stamineus Benth, Hieracium pilosella L., Sambucus nigra L. and Arctostaphylos uva-ursi (L.) Spreng. in rats. Phytother Res. May 1999;13(3):222-225.
  27. Schroder-Aasen T, Molden G, Nilsen OG. In vitro Inhibition of CYP3A4 by the Multiherbal Commercial Product Sambucus Force and its Main Constituents Echinacea purpurea and Sambucus nigra. Phytother Res. Feb 8 2012.
  28. Zakay-Rones Z, Varsano N, Zlotnik M, et al. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. J Altern Complement Med. Winter 1995;1(4):361-369.
  29. Chen JK, Chen TT. Chinese Medical Herbology and Pharmacology. California: Art of Medicine Press; 2004.

Consumer Information

How It Works

Bottom line: Although elderberry may reduce flu symptoms, there is insufficient evidence to support its use to treat any condition.

Elderberry flowers and fruit are found in remedies to reduce cold and flu symptoms, and a few small studies have demonstrated that effect. The berries are rich in nutrients, but raw elderberries are inedible and must be properly cooked before they can be ingested.

Several components in elderberry may also block infection, but more studies are needed. Laboratory studies indicate that the chemopreventive properties of elderberry are weak, and elderberry has not been found effective for cardiovascular disease or to improve cholesterol levels. Unsubstantiated claims that elderberry prevents or treats AIDS, diabetes, or other diseases have recently been halted by the FDA. Importantly, patients should not forego or avoid legitimate treatments, and consult their physicians about the use of elderberry when being treated for various conditions.

Purported Uses
  • To prevent cancer
    Laboratory studies indicate weak chemopreventive properties.
  • To prevent heart disease or lower cholesterol
    Clinical trials have not shown elderberry to be effective.
  • To reduce cold and flu symptoms
    A few small studies have shown that elderberry may reduce flu symptoms.
  • To treat constipation
    A small randomized trial of a compound largely used in Brazil that contains elderberry did find it to be an effective laxative for the treatment of constipation. However, there are no studies isolating elderberry itself as safe and effective for constipation, or whether the other components in the laxative preparation are safe for use by cancer patients.
  • To promote urination
    Laboratory studies indicate that elderberry has diuretic effects.
  • To prevent or treat HIV/AIDS
    Preliminary laboratory studies have found that several components in elderberry may block HIV1 infection, suggesting possible uses along with other proven treatments, but human studies are needed to confirm this activity.
  • To support or stimulate the immune system
    Laboratory and animal studies show that elderberry may affect the immune system.
  • To reduce inflammation
    Elderberry does have anti-inflammatory activities, but clinical trials have yet to be conducted.
  • To prevent or reduce respiratory infections or sinusitis
    Laboratory studies show activity against human respiratory bacterial pathogens and viruses, but clinical trials have yet to be conducted.
Research Evidence

Heart disease prevention
A randomized, placebo-controlled study was done to find out whether elderberry could affect biomarkers for heart disease in 52 healthy postmenopausal women. Patients who took elderberry extract for 12 weeks had no significant change in their biomarkers compared with patients who took a placebo. The study found elderberry to be ineffective in changing the biomarkers for heart disease in healthy postmenopausal women.

Influenza treatment
A randomized, double-blind, placebo-controlled study evaluated oral elderberry syrup for treating 2 types of influenza infections. Sixty patients who had influenza-like symptoms for 48 hours or less received elderberry syrup 15 mL 4 times per day for 5 days or placebo. Symptoms were relieved on average 4 days earlier and use of rescue medication was significantly less in those receiving elderberry extract compared with placebo. Elderberry extract may offer a safe and cost-effective treatment for influenza, but larger confirmatory studies are needed.

Lowering cholesterol
A randomized, placebo-controlled trial of elderberry juice on cholesterol levels in 34 young volunteers found only small, nonsignificant changes in cholesterol concentrations in the elderberry group compared with placebo. In addition, elderberry had no effect on cholesterol levels when taken with a high-fat meal.

Patient Warnings

Raw or unripe elderberries contain toxic compounds known as cyanogenic glycosides and must be cooked sufficiently to avoid risk of cyanide toxicity. Elderberry leaves and stems also contain these compounds and should not be ingested at all. Consuming elder bark, leaves and raw elderberries have caused poisoning and hospitalization.

Do Not Take If

Patients should avoid taking elderberry if they:

  • Take antidiabetic medications, as elderberry may increase their effects.
  • Take diuretic or laxative medications, as elderberry may increase their effects.
  • Are pregnant or lactating, due to risk of toxicity and potential gastrointestinal (GI) distress.
  • Have autoimmune disorders such as rheumatoid arthritis, multiple sclerosis, or lupus, or take prescription medications to decrease immune activity, as elderberry can strengthen the immune system.
Side Effects
  • Allergic reactions
  • GI distress
  • Case Report: After ingesting an elderberry juice made from raw elderberries, leaves, and branches, 11 people experienced nausea and vomiting, 8 of whom had acute GI and neurologic symptoms. Other symptoms included dizziness and numbness and one person was hospitalized.
E-mail your questions and comments to aboutherbs@mskcc.org.