Elderberry

Elderberry (Sambucus nigra L.): A Comprehensive Reference

1. Identity and Botanical Classification

Scientific Name and Taxonomy

Elderberry, known botanically as Sambucus nigra L., is native to Europe as far east as Turkey. The Latin specific epithet nigra means "black," referring to the deeply dark colour of the berries. The English term for the tree is not believed to derive from the word "old," but from the Anglo-Saxon æld, meaning fire, because the hollow stems of the branches were used as bellows to blow air into a fire.

Although the European subspecies, S. nigra ssp. nigra, has been widely studied for its composition, other subspecies such as the American elderberry (S. nigra ssp. canadensis) and the blue elderberry (S. nigra ssp. cerulea) have also become contenders in the elderberry supply chain. Elderberry, the fruit of Sambucus nigra, has become a popular inclusion in foods, beverages, supplements, and more in recent years.

Botanical Description and Natural Source

The fruit is a glossy, dark purple to black berry 3–5 mm in diameter, produced in drooping clusters in late autumn. The dark color of elderberry fruit occurs from its rich phenolic content, particularly from anthocyanins. Elderberries are rich in vitamins and antioxidants that are beneficial to human health and have long been used in different food products. The most extensively utilized elderberries are produced from wild-growing elderberry shrubs, which contain more bioactive components than their cultivars.

Common Forms and Preparations

Elderberry comes in syrups, gummies, capsules, lozenges, and liquid extracts. Syrup is the most widely studied form and remains the most popular choice; it is easy to dose, absorbs quickly, and most clinical trials showing benefits used syrup or liquid extract preparations. Gummies and capsules are convenient alternatives, especially for travel or daily use, though they vary more in how much active elderberry they actually contain.

Beyond concentrated supplements, cooked ripe berries are used as ingredients in jams, wines, juices, and culinary sauces. The dark blue or purple berries are mildly poisonous in their raw state, but are edible after cooking. They can be used to make jam, jelly, chutney, and Pontack sauce.

2. Traditional and Historical Use

Prehistory and Antiquity

Proof of elderberry cultivation has been found at Stone Age sites in Italy and Switzerland, which speaks to its value. Documentation by the Greeks, Romans, and later cultures shows that elderberry was an extremely beneficial plant used as food and medicine. Use of elderberry in the Americas dates as far back as 1300–1000 BCE.

European Folk Medicine

Sambucus nigra, the elderberry, has long been used for its medicinal properties in treating numerous diseases. Based on this traditional knowledge, its different pharmacological activities have been the focus of active research. All parts of the tree have long been used in traditional medicine: the bark, the leaves, the flowers, and the fruit.

Elderberries have a rich history in traditional medicine, particularly in European and Native American cultures. Preparations were used to treat a wide range of ailments including colds, flu, fever, respiratory infections, and skin conditions. Elderflower tea was often used as a diaphoretic to induce sweating and reduce fever. Elderberry syrup was a common remedy for coughs and sore throats. In some cultures, elderberry juice was used as a blood purifier and tonic.

The elderberry has a rich history in folklore and traditions, where it is often associated with mystical qualities and spiritual significance. Across Europe, the elderberry bush was considered sacred, a plant of protection and healing. In Norse mythology, elderberries were associated with the goddess Freya, the deity of love, fertility, and magic. The plant was believed to possess protective qualities, and branches were often placed near homes to ward off evil spirits.

Native American Traditions

North America's indigenous people were the first harvesters and tenders of blue elderberry in California, and many Native persons across the state continue to gather, cultivate, and use elderberry. Various parts of the plant are used for food, medicine, dye color for baskets, pipes, game pieces, and musical instruments.

Traditionally, elder flowers were used medicinally—in teas for treating fevers and other ailments, or in a hot bath to induce sweating—and its berries were dried to store into the winter, when they were later cooked into a rich, sweet sauce. All parts of the plant were used by indigenous peoples, whether for food, medicine, or enjoyment.

Preparations Used Traditionally

Elderberries and elderflowers were used to create teas, poultices, and tinctures for various ailments. Agricultural extension groups have documented the plant's historical uses in indigenous and rural communities, underscoring its role as a natural remedy.

The bark and leaves of the elder tree were also used medicinally, but due to their potential toxicity, their use was more cautious and often reserved for specific conditions under the guidance of experienced herbalists.

3. Key Constituents and Active Compounds

Anthocyanins

The bioactive compounds found in elderberry are primarily polyphenols and anthocyanins. Compared with other fruit, elderberry is a very rich source of anthocyanins (approximately 80% of the polyphenol content). These polyphenols are the principals that essentially contribute to the high antioxidant and anti-inflammatory capacities and the health benefits of elderberry fruit extract.

The fruit of Sambucus nigra contains anthocyanins, especially cyanidin-3-glucoside and cyanidin-3-sambubioside. Blood plasma samples collected between 10 minutes and 24 hours after the consumption of elderberry extract exhibited at least five additional anthocyanin-like compounds, primarily cyanidin-3-sambubioside and cyanidin-3-glucoside.

Flavonols and Phenolic Acids

The main polyphenols in elderberry fruit are chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, quercetin, quercetin-3-rutinoside (rutin), quercetin-3-glucoside (isoquercitrin), kaempferol-3-rutinoside, kaempferol-3-glucoside (astragaline), isorhamnetin-3-rutinoside, and isorhamnetin-3-glucoside. The primary flavonol in this plant is rutin, while the other flavonols, isoquercitrin and astragaline, occur in elderberries in smaller amounts.

Other Bioactive Compounds

Elderberry plant (Sambucus nigra) is a good source of protein, free and conjugated forms of amino acids, unsaturated fatty acids, fibre fractions, vitamins, antioxidants, and minerals. Analysis of elderberry showed that it contains high biological activity components, primarily polyphenols, mostly anthocyanins, flavonols, phenolic acids and proanthocyanidins, as well as terpenes and lectins.

Fruits also contain fiber, glucose, fructose, potassium, malic acid, citric acid, phosphorus, magnesium, vitamin C, calcium, sodium, iron, thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), biotin (vitamin B7), manganese, zinc, and a small amount of essential oil.

Toxic Constituents: Cyanogenic Glycosides

Components of the elderberry plant, including its fruit, contain diverse phytochemicals such as alkaloids, lectins, and cyanogenic glycosides, which may be toxic if consumed raw. The seeds and all green parts of the plant contain cyanogenic glycosides. Immature or green fruits contain a high amount of sambunigrin (0.8%), a toxic principle. Seeds are particularly toxic, having been found to contain sambunigrin, prunasoside, sambunigroside, and cardiotoxic hemagglutinins.

4. Mechanisms of Action

Antiviral Mechanisms

The anti-influenza activity of elderberry and its bioactive compounds, as well as their antiviral mechanisms of action, are still under investigation, and different theories have been proposed: (a) neutralizing the activity of the viral glycoproteins, hemagglutinin (HA) and neuraminidase (NA), and (b) activating the healthy immune system and increasing production of inflammatory cytokines.

The antiviral mechanism of elderberry can be explained by blocking the function of the HA glycoprotein spikes found on the surface of influenza viruses. Several authors described a direct antiviral effect showing that the main anthocyanin present in black elderberry, cyanidin-3-sambubioside, can bind and inhibit the active pocket of the viral enzyme neuraminidase and therefore inhibit the viral replication process in vitro. Additionally, Roschek et al. reported that in vitro, flavonoids present in elderberry fruits can directly bind to H1N1 influenza virus particles, thereby inhibiting host cell entry.

Two specific elderberry flavonoids—5,7-dihydroxy-4-oxo-2-(3,4,5-trihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxycyclohexanecarboxylate and 5,7,3',4'-tetra-O-methyl quercetin—can block virus-host attachment. Elderberry flavonoids bind to and prevent H1N1 infection in vitro.

Immune Modulation

Elderberry, a rich source of flavonoids, has been shown to exert protective effects against influenza virus by stimulating the immune system of the host through enhancing the production of cytokines. The expression of inflammatory cytokines such as IL-6, TNF-α, and IFN-γ was highly increased in the presence of elderberry water extract and polysaccharide-enriched fractions. From these data, researchers conclude that the polysaccharides present in water-derived elderberry fractions induce potent immune-modulatory effects, which represents the basis for a strong immune-mediated response to viruses including influenza.

One study found that elderberry extract reduced the secretion of pro-inflammatory cytokines TNF-α and IFN-γ, leading to a shift towards the Th2-helper cell response and showing antiviral efficacy against the MVA virus. Mechanistically, elderberry extract exerts both pro- and anti-inflammatory properties based on the secreted cytokines after stimulation, suggesting an overall modulation of the immune system.

Antioxidant Activity

Anthocyanins are well-known functional compounds that reduce oxidative stress by scavenging free radicals, which makes them potential chemopreventive agents. As excellent food colorants with antioxidative properties, anthocyanins are a good alternative to synthetic dyes due to their safety as well as potential nutritional and therapeutic effect.

5. Scientific Evidence by Area of Use

5.1 Upper Respiratory Infections: Influenza and the Common Cold

Overview of Evidence

Elderberry is promoted as a dietary supplement for colds, flu, and other conditions. It has also been promoted for COVID-19, but there is no good evidence to support its use for that purpose. A small number of studies have evaluated elderberry for colds, flu, and other upper respiratory infections.

Key Randomized Controlled Trials

There are four published peer-reviewed randomized double-blind placebo-controlled clinical trials with established relevance. Two, in 27 and 60 patients respectively, demonstrated shortening of the duration of proven influenza by approximately 4 days with elderberry extract supplementation versus placebo (p<0.001 in both studies).

Another trial evaluated 64 patients with three or more flu-like symptoms. By 48 hours of supplementation, 9 patients (28%) in the elderberry extract group were void of all symptoms, and 19 patients (60%) showed complete relief from some symptoms. No patient in the placebo group achieved complete recovery, and only 5 patients (16%) showed improvement in one or two symptoms (p<0.001 for all symptoms). Most patients in the placebo group remained the same or worsened over the 48-hour monitoring period.

A randomized, double-blind placebo-controlled clinical trial of 312 economy class passengers travelling from Australia to an overseas destination investigated a standardized membrane-filtered elderberry extract for beneficial effects on physical, especially respiratory, and mental health. Cold episodes, cold duration, and symptoms were noted in a daily diary and assessed using the Jackson score. The placebo group participants had a significantly longer duration of cold episode days (117 vs. 57, p=0.02), and the average symptom score over these days was also significantly higher (583 vs. 247, p=0.05).

Meta-Analysis

A meta-analysis published in 2019 provides evidence that elderberry supplementation at the onset of upper respiratory symptoms substantially reduces overall symptom duration as compared to a control group, with an effect size of 1.717. This analysis included 89 participants in the elderberry group and 91 participants in the control group for a total of 180 participants.

A 2019 meta-analysis of four studies found that supplementation with black elderberry (Sambucus nigra) was significantly effective at reducing the total duration and severity of upper respiratory symptoms compared with placebo.

Systematic Review (Wieland et al., 2021)

Elderberry has traditionally been used to prevent and treat respiratory problems. During the COVID-19 pandemic, there has been interest in elderberry supplements to treat or prevent illness, but also concern that elderberry might overstimulate the immune system and increase the risk of "cytokine storm." The review aimed to determine benefits and harms of elderberry for the prevention and treatment of viral respiratory infections, and to assess the relationship between elderberry supplements and negative health impacts associated with overproduction of pro-inflammatory cytokines.

The 2021 systematic review concluded that elderberry may be a safe option for treating viral respiratory illness, and found no evidence that it overstimulates the immune system. However, as noted by NCCIH, a small number of studies in people have evaluated elderberry for flu and other upper respiratory infections; however, conclusive evidence from high-quality clinical trials is lacking. A 2020 review of studies concluded that although there is a hypothetical benefit of elderberry for the treatment of viral infections, there isn't enough conclusive evidence from high-quality clinical trials.

Evidence Strength and Limitations

The majority of elderberry clinical research has focused on reducing the duration and severity of influenza symptoms. The evidence is mixed, with three company-funded trials showing benefit and one independent trial showing no benefit. A review found that black elderberry was associated with clinically meaningful reductions in symptom severity and illness duration, although evidence for its preventive efficacy remains limited. The overall body of evidence is preliminary: existing trials are small, and many have been funded by manufacturers of elderberry products, introducing a risk of bias.

5.2 Cardiovascular Health

Elderberry has conferred protective effects against oxidative stressors in endothelial cells in vitro. However, it did not demonstrate vasoprotective effects, and randomized trials found it ineffective in improving cardiovascular disease biomarkers or for improving cholesterol levels. Doses of 500 mg of anthocyanins per day were taken for 12 weeks in healthy volunteers, with no effect on cardiovascular disease biomarkers. Evidence for direct cardiovascular benefit in humans remains insufficient based on available trials.

5.3 Antidiabetic Effects

Research underscores the potential of elderberry flower extracts, particularly those rich in chlorogenic acid, as natural agents for managing blood glucose levels, warranting further exploration of their use in antidiabetic applications. Results highlight the promising antidiabetic potential of examined extracts, specifically their ability to inhibit enzymes involved in carbohydrate digestion, such as α-glucosidase and α-amylase. These findings are primarily from in vitro or animal studies; robust human clinical trial data supporting antidiabetic use is currently lacking.

5.4 Antioxidant and Anti-inflammatory Activity

A large body of literature pertaining to in vitro, in vivo, and human trials has demonstrated the health functions of elderberry based on the attenuation of oxidative stress via its antioxidative effect and its anti-inflammatory properties. The antioxidant and protective potential of elderberry has been established in respiratory ailments, colds, cardiovascular diseases, diabetes, and obesity. Moreover, a significant impact on the immune system, antiviral and antibacterial activity, as well as protection against UV radiation has been confirmed. Despite the promising results, additional studies are needed to understand interactions with other compounds that may affect the activity of elderberry components.

5.5 Anticancer and Antimicrobial Properties

In vitro studies demonstrate that elderberries possess antiviral, antibacterial, antidiabetic, immunomodulatory, antioxidant, anti-inflammatory, and chemopreventive properties, although inhibition of cancer cell growth was shown to be weak. Flavonoids and proanthocyanidins were shown to block HIV-1 infection in vitro, and may have additive effects with existing AIDS drugs such as enfuvirtide. These findings are limited to laboratory models and have not been validated in human clinical trials.

5.6 Other Preliminary Areas

Small studies found elderberry to be safe and effective in a preparation for chronic constipation and in reducing episodes of tonsillitis in children. These represent highly preliminary findings in limited study populations. Elderberry exhibits various health functions in vitro and in vivo, including neuroprotective activities, and their potential molecular mechanisms are associated with regulating key signaling pathways. Neuroprotective applications remain at the in vitro and animal model stage.

6. Body Systems Associated with Elderberry

• Immune system: Immunomodulatory and immunostimulatory effects via cytokine regulation and activation of dendritic cells and T-cells.
• Respiratory system: The most clinically studied area; associated with reductions in cold and flu symptom duration and severity.
• Cardiovascular system: Potential attenuation of cardiovascular disorders is proposed, but human trial data do not confirm significant benefit in biomarkers.
• Metabolic/endocrine system: The compounds in elderberries, such as polyphenols, may be beneficial for managing diabetes and its complications. Researchers have done several studies to investigate the plant's antidiabetic properties.
• Gastrointestinal system: Certain compounds in the flowers have a mild laxative effect.
• Integumentary system: Historically used topically for skin conditions; compounds found throughout the plant, when used externally, show a mild antifungal effect.

7. Dosage Forms and Dosages Reported in Clinical Studies

Most studies administer elderberry in lozenge, capsule, syrup, or juice forms, with doses ranging from 175 to 900 mg/day (15 to 177 mL in liquid forms) over periods of 48 hours to four weeks when used for treatment, and for up to 12 weeks when used as a preventive measure.

• Syrup (influenza treatment): 15 mL of syrup taken 4 times per day for 5 days has been used in clinical trials.
• Lozenges (influenza treatment): A study among 64 patients found that an elderberry lozenge containing 175 mg of elderberry extract (ViraBLOC), taken within 24 hours of developing flu symptoms four times daily for two days, significantly reduced fever, headache, muscle aches, nasal congestion, and cough compared to placebo.
• Capsules/extract (air-travel respiratory health): 600 mg/day starting 10 days before travel, followed by 900 mg/day starting the day before travel and continued for 4 or 5 days post-flight.
• Anthocyanins (cardiovascular study): Doses of 500 mg of anthocyanins per day were taken for 12 weeks in healthy volunteers, with no effect on cardiovascular disease biomarkers.
• General range across studies: Most clinical studies used elderberry extract equivalent to roughly 600 to 900 milligrams per day for adults, typically divided into multiple doses throughout the day.
• Children's syrup (flu): One tablespoon (15 mL) of a specific elderberry juice-containing syrup has been taken twice daily for 3 days in studies involving children.

No official Recommended Dietary Allowance (RDA) or Tolerable Upper Intake Level (UL) has been established for elderberry, as it is classified as a dietary supplement and food, not an essential nutrient.

8. Safety Considerations and Interactions

Toxicity of Raw Plant Parts

Unripe or uncooked parts of the elder tree (including leaves, stems, and berries) can be dangerous if ingested, as they contain toxins such as sambunigrin, a cyanogenic glycoside. The toxins can lead to nausea, vomiting, diarrhea, and more serious consequences if ingested in large quantities. While cooking eliminates the toxin, it may be difficult to know if this is done appropriately when made at home or using other non-regulated homemade products.

Raw unripe elderberries and other parts of the elder tree, such as the leaves and stem, contain toxic substances (e.g., sambunigrin) that can cause nausea, vomiting, and diarrhea; cooking eliminates this toxin.

Autoimmune Disease and Immunosuppressant Medications

Elderberry should not be used in patients with autoimmune diseases and/or those taking immunosuppressant medications. For those with overactive immune responses, elderberry poses unique challenges. Its immune-boosting properties could counteract medications designed to suppress defense mechanisms.

Drug Interactions

Pazopanib, a cancer drug, is metabolized in the liver via the cytochrome P450 (CYP) 3A4 enzyme pathway. Potent inhibitors of CYP3A4 are avoided for concurrent use with pazopanib. Small in vitro studies on elderberry extracts have shown weak inhibition of CYP3A4. A case report described a sarcoma patient who developed severe gastrointestinal symptoms and elevated liver enzymes while concurrently taking pazopanib and elderberry, though there are limited published data to further elucidate or predict clinically significant interactions with elderberry.

Elderberry has hypoglycemic activity and may have additive effects with antidiabetic drugs; however, clinical relevance has yet to be determined. Elderberry promotes urination and may have additive effects with diuretics; clinical relevance has yet to be determined.

Given elderberry's potential as an immunostimulant, clinicians should exercise caution when recommending it to patients undergoing immunotherapy, due to the theoretical risk of increased immunotherapy-related adverse events.

Pregnancy and Lactation

Little is known about whether it's safe to use elderberry for health purposes during pregnancy or while breastfeeding. Information regarding safety and efficacy in pregnancy and lactation is lacking.

General Short-Term Safety

Elderberry supplements seem to have few risks when used daily for up to five days. The safety of its long-term use is unknown. Overall, elderberry, when consumed as a supplement at the normal dose range of 175 to 1200 mg, appears to be a safe option when used appropriately.

Market Context

Sales of elderberry supplements skyrocketed to $320 million over the year 2020, according to an American Botanical Council (ABC) report, attributable to the purported immune-enhancing effects of elderberry.

References

• PMC: Bioactive properties of Sambucus nigra L. as a functional ingredient for food and pharmaceutical industry
• PMC: Elderberries—A Source of Bioactive Compounds with Antiviral Action
• PMC: Development of Potential Therapeutic Agents from Black Elderberries (the Fruits of Sambucus nigra L.)
• Journal of Agricultural and Food Chemistry: Elderberry (Sambucus nigra L.): Bioactive Compounds, Health Functions, and Applications
• Annual Reviews: Elderberry, an Ancient Remedy: A Comprehensive Study of Bioactive Compounds in Three Sambucus nigra L. Subspecies
• PMC: Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review (Wieland et al., BMC Complement Med Ther, 2021)
• PubMed: Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: A meta-analysis (Hawkins et al., Complement Ther Med, 2019)
• PMC: Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers (Tiralongo et al., 2016)
• PMC: Elderberry Extract Outpatient Influenza Treatment for Emergency Room Patients — Randomized, Double-Blind, Placebo-Controlled Trial
• ScienceDirect: Anti-influenza activity of elderberry (Sambucus nigra), Journal of Functional Foods, 2019
• NCCIH: Elderberry — Usefulness and Safety
• NCCIH: The Common Cold and Complementary Health Approaches — What the Science Says
• PMC: Elderberry Extracts: Characterization of the Polyphenolic Chemical Composition, Quality Consistency, Safety, Adulteration, and Attenuation of Oxidative Stress- and Inflammation-Induced Health Disorders
• PMC: Polysaccharides from European Black Elderberry Extract Enhance Dendritic Cell Mediated T Cell Immune Responses
• PMC: Elderberry interaction with pazopanib in a patient with soft-tissue sarcoma: A case report and literature review
• PMC: Sambucus nigra L. (fam. Viburnaceae) in Sicily: Distribution, Ecology, Traditional Use and Therapeutic Properties
• ScienceDirect: Advanced research on the antioxidant and health benefit of elderberry (Sambucus nigra) in food – a review
• PMC: Antidiabetic Potential of Black Elderberry Cultivars Flower Extracts: Phytochemical Profile and Enzyme Inhibition
• Memorial Sloan Kettering Cancer Center: Elderberry — Integrative Medicine
• Examine.com: Elderberry — Benefits, Dosage, and Side Effects
• Drugs.com: Elderberry Uses, Benefits & Dosage
• UC ANR: Cultural Significance of Elderberry — California Elderberries
• Penn State Extension: Elderberry in the Garden and the Kitchen
• Taylor & Francis: A new high-quality elderberry plant extract exerts antiviral and immunomodulatory effects in vitro and ex vivo
• Pharmacy Times: Pharmacist Review of Drug-Herb Interactions in Cancer Treatment
• Wikipedia: Sambucus nigra