Elderberry

Scientific Name(s): Sambucus nigra L. (European elder) and Sambucus nigra ssp canadensis (American elder). Family: Caprifoliaceae.

Common Name(s): Sweet elder , common elder , elderberry , sambucus , Sambucol

Uses

Limited clinical trials have been conducted. Elderberry extracts may have some value in the treatment of influenza and appear to have antioxidant potential.

Dosing

The bioavailability of active constituents in elderberry extracts is considered to be poor. Trials are lacking to provide dosing information. For the treatment of influenza, 15 mL of syrup taken 4 times per day for 5 days has been used in clinical trials.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Consumption of uncooked berries may result in vomiting and diarrhea. Commercial preparations generally do not cause adverse reactions at the recommended dosage. Type 1 allergy to elderberry (positive skin prick tests) has been recorded.

Toxicology

Poisonous alkaloids, lectins, and cyanogenic glycosides are present in some plant parts. Short-term use of elderberry extract preparations appears to be relatively safe; however, long-term toxicological studies are lacking.

Botany

The American elder is a tall shrub that grows to 4 m, and is native to North America. The European elder grows to approximately 10 m and has been naturalized to the United States. The tree has light brown/grey bark and narrow, dark green leaves. Clusters of white-cream flowers have a particular fragrance and develop into dark purple-black berries. 1 , 2

History

Elder flowers and berries have been used in traditional medicine and as a flavoring for centuries. In folk medicine, the flowers have been used for their diuretic and laxative properties and as an astringent. Various parts of the elder have been used to treat cancer and many other unrelated disorders. Distilled elder flower water has been used as a scented vehicle for topical preparations, and extracts are used to flavor foods as well as alcoholic beverages. The fruits have been used to make elderberry wine. 3

Chemistry

European elder flowers contain approximately 0.3% of an essential oil composed of free fatty acids and alkanes. The triterpenes alpha- and beta-amyrin, ursolic acid, oleanic acid, betulin, betulic acid, and a variety of other minor components have been identified. 4 The elder leaf contains sambunigrin, a cyanogenic glucoside (0.042% by weight). 5 Leaves of S. nigra express 2 classes of thaumatin-like proteins. The fruit-specific, thaumatin-like proteins accumulate only during the final stages of fruit ripening. 6

The fruit of the elderberry contains phenolics, including quercetin, kaempferol, rutin, and phenolic acids and anthocyanins. High-performance liquid chromatography and mass spectrometry have been used to identify individual anthocyanins, which give the berry its color, and include cyanidin 3-sambubioside-5-diglucoside, cyanidin-3,5-diglucoside, cyanidin 3-sambubioside, and cyanidin 3-glucoside. 7 , 8 The total anthocyanin content varies during the growing season and by cultivar. Vitamins A and C are also present, and antioxidant capacity of the berry has been estimated to be similar to that of black raspberries, blackberries, and other dark-fleshed small fruit. 9 , 10

The Sambucus species has been studied for its lectin composition, which has hemagglutinin characteristics useful in blood typing. 7 , 11

Uses and Pharmacology

Antiviral effects

In vitro studies have shown that elderberry extracts exert activity against the influenza virus A (including H1N1) and B and the herpes simplex virus. Laboratory studies also suggest an inhibitory effect on the infectivity of the HIV virus. 12 , 13 , 14 , 15 , 16

Animal data

Research reveals no animal data regarding the use of elderberry extracts for antiviral effects.

Clinical data

Although in vitro data are promising, few clinical trials have been conducted examining the efficacy of elderberry extracts for the treatment of influenza. 15 , 16 When used within the first 48 hours of onset of symptoms, elderberry extracts reduced the duration of influenza versus placebo. 12 , 17 Anecdotal reports exist for elderberry use in HIV. 16

Diabetes
Animal data

A stimulatory effect on insulin secretion by the polyphenolic content of elderberry fruit has been shown in diabetic rats. 18 In vitro studies using rat abdominal muscle showed increased insulin secretion in response to flower extracts. 19 , 20

Clinical data

Although traditionally used for diabetes, clinical trials are lacking. Elderberry has been evaluated in combination with asparagus for weight reduction. 21 , 22

Hyperlipidemia
Animal data

Research reveals no animal data regarding the use of elderberry extracts for lipid-lowering effects.

Clinical data

In a placebo-controlled study among healthy volunteers, there was only a small and statistically insignificant change in cholesterol in the elderberry-treated group compared with placebo. The dosage used in the study may have been too low (anthocyanin 10%). 23 No change was found in healthy volunteers consuming 500 mg of anthocyanins daily for 12 weeks in another study. 24

Other effects

Elder flowers are considered to have diuretic and laxative properties; however, the specific compounds responsible for these activities have not been well established. 2 , 25

The compound sambuculin A and a mixture of alpha- and beta-amyrin palmitate demonstrated hepatoprotective properties against carbon tetrachloride-induced liver damage. 26

Effects on anti-inflammatory markers including increased cytokine production have been demonstrated in vitro. 24 , 27

Antioxidant activity of elderberry extracts has been evaluated and is estimated to be similar to that of black raspberries, blackberries, and other dark-fleshed small fruit. 9 , 10 , 18 , 23 , 28 , 29

Induction of quinine reductase and cyclo-oxygenase-2 has been suggested to be responsible for anticancer effects in vitro. 30

Dosage

The bioavailability of active constituents in elderberry extracts is considered to be poor. 16 , 31 , 32

Fruit syrups are commonly standardized to 30% to 38% elderberry extract. Powdered extracts are available as capsules and in liquid form.

Doses of 500 mg of anthocyanins per day were taken for 12 weeks in healthy volunteers, with no effect on cardiovascular disease biomarkers. 24

Influenza

15 mL of syrup taken 4 times per day for 5 days has been used in clinical trials. 12

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented. Elderberry may potentiate the effects of insulin.

Adverse Reactions

Consumption of uncooked berries may result in vomiting and diarrhea. Commercial preparations are generally considered relatively free from adverse effects at the recommended dosage. No adverse events were reported in a clinical trial evaluating the efficacy of elderberry extract in the treatment of influenza, 12 or in healthy volunteers consuming elderberry extract standardized to 500 mg of anthocyanins per day for 12 weeks. 24

Type 1 allergy to elderberry (positive skin prick tests) has been recorded. 16

Toxicology

Poisonous alkaloids, lectins, and cyanogenic glycosides are present in some plant parts. While elderberries are safe to consume, particularly when cooked, leaves and stems should not be crushed when making elderberry juice. Uncooked berries may produce nausea. A report of severe illness (nausea, vomiting, weakness, dizziness, numbness, and stupor) following the ingestion of juice prepared from elderberries exists. 16 , 33

Toxicity in children who used peashooters made from elderberry stems has been reported. 3

No effects were recorded on kidney and liver function markers in healthy volunteers consuming elderberry extract standardized to 500 mg of anthocyanins per day for 12 weeks. 24 Long-term toxicological studies are lacking. 16

Bibliography

1. Sambucus nigra L. USDA, NRCS. 2011. The PLANTS Database ( http://plants.usda.gov , 04 April 2011). National Plant Data Team, Greensboro, NC 27401-4901 USA.
2. Wright CI, Van-Buren L, Kroner CI, Koning MM. Herbal medicines as diuretics: a review of the scientific evidence. J Ethnopharmacol . 2007;114(1):1-31.
3. Duke JA. CRC Handbook of Medicinal Herbs . Boca Raton, FL: CRC Press; 1985.
4. Inoue T, Sato K. Triterpenoids of Sambucus nigra and S. canadensis . Phytochemistry . 1975;14:1871.
5. Leung AY. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics . New York, NY: Wiley; 1980.
6. Van Damme EJ, Charels D, Menu-Bouaouiche L, et al. Biochemical, molecular and structural analysis of multiple thaumatin-like proteins from the elderberry tree ( Sambucus nigra L.). Planta . 2002;214(6):853-862.
7. Mach L, Scherf W, Ammann M, et al. Purification and partial characterization of a novel lectin from elder ( Sambucus nigra L.) fruit. Biochem J . 1991;278(pt 3):667-671.
8. Schmitzer V, Veberic R, Slatnar A, Stampar F. Elderberry ( Sambucus nigra L.) wine: a product rich in health promoting compounds. J Agric Food Chem . 2010;58(18):10143-10146.
9. Ozgen M, Scheerens JC, Reese RN, Miller RA. Total phenolic, anthocyanin contents and antioxidant capacity of selected elderberry ( Sambucus canadensis L.) accessions. Pharmacogn Mag . 2010;6(23):198-203.
10. Lee J, Finn CE. Anthocyanins and other polyphenolics in American elderberry ( Sambucus canadensis ) and European elderberry ( S. nigra ) cultivars. J Sci Food Agric . 2007;87(14):2665-2675.
11. Kaku H, Peumans WJ, Goldstein IJ. Isolation and characterization of a second lectin (SNA-II ) present in elderberry ( Sambucus nigra L.) bark. Arch Biochem Biophys . 1990;277(2):255-262.
12. Zakay-Rones Z, Thom E, Wollan T, Wadstein J. 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.
13. 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.
14. Roschek B Jr, Fink RC, McMichael MD, Li D, Alberte RS. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry . 2009;70(10):1255-1261.
15. Guo R, Pittler MH, Ernst E. Complementary medicine for treating or preventing influenza or influenza-like illness. Am J Med . 2007;120(11):923-929.e3.
16. Vlachojannis JE, Cameron M, Chrubasik S. A systematic review on the sambuci fructus effect and efficacy profiles. Phytother Res . 2010;24(1):1-8.
17. 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 . 1995;1(4):361-369.
18. Ciocoiu M, Mirón A, Mares L, et al. The effects of Sambucus nigra polyphenols on oxidative stress and metabolic disorders in experimental diabetes mellitus. J Physiol Biochem . 2009;65(3):297-304.
19. Gray AM, Abdel-Wahab YH, Flatt PR. The traditional plant treatment, Sambucus nigra (elder), exhibits insulin-like and insulin-releasing actions in vitro. J Nutr . 2000;130(1):15-20.
20. Christensen KB, Petersen RK, Kristiansen K, Christensen LP. Identification of bioactive compounds from flowers of black elder ( Sambucus nigra L.) that activate the human peroxisome proliferator-activated receptor (PPAR) gamma. Phytother Res . 2010;24(suppl 2):S129-S132.
21. Chrubasik C, Maier T, Dawid C, et al. An observational study and quantification of the actives in a supplement with Sambucus nigra and Asparagus officinalis used for weight reduction. Phytother Res . 2008;22(7):913-918.
22. Hasani-Ranjbar S, Nayebi N, Larijani B, Abdollahi M. A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity. World J Gastroenterol . 2009;15(25):3073-3085.
23. 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 . 2004;58(2):244-249.
24. 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 . 2009;139(12):2266-2271.
25. 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.
26. Lin CN, Tome WP. Antihepatotoxic principles of Sambucus formosana . Planta Med . 1988;54(3):223-224.
27. Barak V, Birkenfeld S, Halpern T, Kalickman I. The effect of herbal remedies on the production of human inflammatory and anti-inflammatory cytokines. Isr Med Assoc J . 2002;4(suppl 11);919-922.
28. Roy S, Khanna S, Alessio HM, et al. Anti-angiogenic property of edible berries. Free Radic Res . 2002;36(9):1023-1031.
29. Nalliah RE, Phillips JS, Gaier AJ, Gochenaur KE, Bell DR. Experimental in vitro arterial reactivity and tissue culture solutions alter the time-dependent stability of anthocyanins from elderberry, chokeberry, and bilberry extracts. Int J Food Sci Nutr . 2009;60(suppl 1):209-219.
30. Thole JM, Kraft TF, Sueiro LA, et al. A comparative evaluation of the anticancer properties of European and American elderberry fruits. J Med Food . 2006;9(4):498-504.
31. Frank T, Janssen M, Netzet G, Christian B, Bitsch I, Netzel M. Absorption and excretion of elderberry ( Sambucus nigra L.) anthocyanins in healthy humans. Methods Find Exp Clin Pharmacol . 2007;29(8):525-533.
32. Bitsch R, Netzel M, Sonntag S, Strass G, Frank T, Bitsch I. Urinary excretion of cyanidin glucosides and glucuronides in healthy humans after elderberry juice ingestion. J Biomed Biotechnol . 2004;2004(5):343-345.
33. Centers for Disease control (CDC). Poisoning from elderberry juice-California. MMWR Morb Mortal Wkly Rep . 1984;33(13):173-174.

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