Elderberry

• How It Works

  Elderberry may reduce flu symptoms, but sufficient evidence is lacking 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.
• 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.
• Brand Name

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

• Scientific Name

  Sambucus nigra

• Clinical Summary

  Elderberry belongs to 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⁾. 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 it 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
• 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⁾. An elderberry extract improved metabolic disturbances in a murine model of obesity by lowering serum triglycerides, inflammatory markers and insulin resistance ⁽³⁰⁾. Its antidiabetic properties occur via activation of peroxisome proliferator-activated receptor gamma and stimulation of insulin-dependent glucose uptake ⁽⁶⁾. Elderberry may also influence HDL dysfunction associated with chronic inflammation by affecting hepatic gene expression in hyperlipidemic mice ⁽³¹⁾. Another study indicates its chemopreventive potential is related to induction of quinone reductase as well as cyclooxygenase-2 and ornithine decarboxylase inhibition ⁽²⁾.

• 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⁾.

• 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: https://wayback.archive-it.org/7993/20170111235612/http://www.fda.gov/N…

  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.

  30. Farrell NJ, Norris GH, Ryan J, Porter CM, Jiang C, Blesso CN. Black elderberry extract attenuates inflammation and metabolic dysfunction in diet-induced obese mice. Br J Nutr. 2015 Oct 28;114(8):1123-31.

  31. Farrell N, Norris G, Lee SG, Chun OK, Blesso CN. Anthocyanin-rich black elderberry extract improves markers of HDL function and reduces aortic cholesterol in hyperlipidemic mice. Food Funct. 2015 Apr;6(4):1278-87.