Accurate Education – Elderberry

Elderberry

Elderberry is found in many medicinal products and is currently one of the most-used medicinal plants worldwide as an antiviral herb. The flowers and berries (blue and black only) are used most often medicinally. They contain flavonoids, which have been found preclinically to possess a variety of biochemical and pharmacological actions, including antioxidant and immunologic properties. These properties along with clinical studies suggest that elderberry may be beneficial for reducing the duration of viral respiratory illnesses and for reducing their symptoms. This has led to the premise that elderberry may also offer some potential benefit for use in COVID-19 *

 
 
See also:

 

Supplements

Curcumin

Quercetin

Zinc

Vitamin C

Green Tea

Resveratrol

  

Terms:

 

Complementary and Alternative Medicine (CAM)

CAM is defined by the National Center for Complementary and Integrative Health (NCCIH) as, “those treatments and healthcare practices that are not presently considered to be part of conventional medicine, not taught widely in medical schools, not generally used in hospitals, and not usually reimbursed by medical insurance companies.”

 For more info: Complementary and Alternative Medicine (CAM)

 

Immunoadjuvants

The nutraceutical and botanical substances reviewed here are considered to be immunoadjuvants, or “substances that accelerate, prolong, or enhance antigen-specific immune responses by potentiating or modulating the immune response.”

  

Nutraceutical

The term “nutraceutical,” derived from “nutrition” and “pharmaceutical,” refers to a product that is isolated from herbs, botanicals or foods that has physiological benefit by supporting the structure or function of the body or providing protection against diseases. Nutraceuticals are directed at improving health, preventing or reducing the impact of disease, suppressing the aging process and increasing life expectancy.

  

* This document is only intended to identify modalities that may boost your immune system. It is not meant to recommend any treatments, nor have any of these modalities been proven effective against coronavirus. Always consult your physician or healthcare provider prior to using any of these modalities.

 

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Elderberry

Elderberry has been used for centuries and is currently one of the most-used medicinal plants worldwide, mostly to treat respiratory illnesses such as cold and flu. It is also believed that Elderberry may have anti-inflammatory, antiviral, and anticancer properties. The flowers and berries (blue and black only) are the plant parts used most often medicinally. They contain flavonoids, which have been found preclinically to possess a variety of biochemical and pharmacological actions, including antioxidant and immunologic properties.

 

Therapeutic Benefits of Elderberry

 Protection Against COVID-19

In the recent times of the COVID-9 pandemic, Elderberry has gained attention as a supplement that may offer benefit for reducing the risk and/or severity of the corona virus infection (SARS-CoV-2).

 

As a brief summary of Elderberry’s potential benefit agains COVID-19, Elderberry has strong evidence that it may reduce the inflammatory process and limit the severity of disease progression largely by these 2 mechanisms:

 

(1) Elderberry may inhibit COVID-19 replication and thereby limiting SARS-CoV-2 colonization from progressing to development of illness and possibly reducing the severity of illness.

 

(2) One of the primary reasons that infection with SARS-CoV 2 can be deadly is that it can trigger overwhelming inflammation and destruction of lung tissue that fatally disrupts air exchange. Elderberry may suppress this complication by preventing activation of the NLRP3 inflammasomes and decrease activation of NF-kB inflammatory pathways to reduce severity of COVID-19 disease.

 

Interest in Elderberry as a therapeutic agent against COVID-19 was born from mounting evidence that Elderberry is effective against colds and influenza (see below).

For more information about elderberry pertinent to COVID-19, see: COVID-19 (CAM Tx).

   

 Colds, Influenza and other Viral Infections

Elderberry has been used for centuries throughout the world, mostly to treat respiratory illnesses such as cold and flu. Evidence suggests that constituents in elder flower and berries may help reduce swelling in mucous membranes, such as the sinuses, and help relieve nasal congestion.

 

 A meta-analysis published in 2019 evaluating a total of 180 participants concluded that supplementation with elderberry was found to substantially reduce upper respiratory symptoms in routine cases of the common cold and influenza. While the extent of black Elderberry’s antiviral effects are not fully known, antiviral and antimicrobial properties have been found in Elderberry extracts.

  

An Israeli randomized, double-blind, placebo-controlled study of Sambucol in the treatment of influenza in 40 otherwise healthy individuals (children and adults) not previously vaccinated against the flu offers evidence of Sambucol’s benefit for influenza. In subjects who were analyzed, convalescent phase serologies demonstrated higher antibody titers to influenza B in the group treated with Sambucol, although statistically significant changes were lacking and only demonstrated a trend in favor of the treatment group. Follow-up of symptoms was adequately recorded over six days, and significant improvement in symptoms was observed in 93.3% of treated patients within two days, vs. the control group, in which it took six days to see improvement in 92.7% of patients. A complete cure was seen within 2–3 days in Sambucol-treated patients (90%), whereas six days were needed in the placebo group. Although randomization and blinding were adequately described, this study was limited by the small sample size, lack of intent-to-treat analysis, and use of influenza B rather than influenza A titer measurement.

 

Elderberry benefits with other corona viruses

Elderberry has been studied in other corona viruses including Human coronavirus NL63 (HCoV-NL63), one of the main circulating HCoVs in the fall and winter worldwide, causes respiratory tract illnesses like runny nose, cough, bronchiolitis and pneumonia and was responsible for a recent severe respiratory illness outbreak in a long-term care facility in Louisiana in winter 2017. Among the 20 cases aged from 66 to 96 in this outbreak, 6 patients developed pneumonia and had to be hospitalized and 3 patients died.

 

Product Variability

Elderberry Species and Cultivars – Why it Matters

Different elderberry products may vary widely in their quality based on their bioactive constituent content. Factors that come into play included the species variety, the source of extract, be it flower, stem or fruit, the conditions where it was grown and variables related to the product’s storage. It is important to keep these facts in mind when reviewing a publication reporting on elderberry’s therapeutic benefits or when selecting an elderberry product for consumption.

 

Elderberry Species

There are several species of elder, but Sambucus nigra, or European elder (also called black elder), is the one used most often for medicinal purposes. American elder or common elder (S. canadensis) and European elder (S. nigra) are often discussed simultaneously in the literature, since they have many of the same uses and contain common constituents. Other species with similar chemical components include antelope brush (Sambucus tridentata), blue elderberry (Sambucus caerulea), danewort (Sambucus ebulus), red-fruited elder (Sambucus pubens, Sambucus racemosa), and Sambucus formosana. Different species may have different constituents and different levels of constituents. Dwarf elder (Sambucus ebulus) should be avoided because it can be toxic. Additionally, raw or unripe fruit, as well as the leaves, seeds, and bark, contain a chemical related to cyanide, which is poisonous so one must use a trusted preparation of elder.

 

Elderberry Cultivars

A cultivar is a plant variety that has been cultivated by selective breeding in order to enhance certain properties of the plant such as size of fruit, resistance to freezing or pesticides or levels of specific chemical constituents. Elderberry shrubs grow in the wild, but there are also elderberry cultivars, the most popular of which are ”Sampo”, ”Samyl”, ”Alleso”,”Korsor”, and ”Haschberg.”  Elderberry is grown mainly for its fruit, which can be used to produce juices, soft and alcoholic beverages, marmalades, or colorants. Berries are rich in various bioactive compounds, the most important of which are polyphenols, including anthocyanins, and other phenolic compounds including caffeic acid, chlorogenic acid and quercetin derivatives. Compared with plants growing in the wild, cultivars bear more abundant crops of larger and heavier berries.

 

One study compared the mineral content and bioactive properties of flowers and fruit coming from wild elderberry plants with those of flowers and fruit harvested from elderberry cultivars grown in an orchard. Fruit showed significantly higher antioxidant activity than flowers, whereas the total phenolic content varied depending on the growing location or cultivar. The material obtained from selected cultivars growing in an orchard had higher antioxidant activity and polyphenol and anthocyanin content than the material obtained from wild plants. Fruit of the ”Haschberg” cultivar and flowers of the ”Sampo” cultivar had the best bioactive properties of the studied samples.

 

Elderberry Product Storage

Elderberry Storage is another variable that influences the quality of an eldeberry product. There can be a significant decline in bioactive content from three months to six months, and also from six months to nine months of frozen storage. As much as 80% bioactivity can be lost in 9 months of frozen storage.

For an excellent resource, see:

An Evidence-Based Systematic Review of Elderberry and Elderflower (Sambucus Nigra) by the Natural Standard Research Collaboration – PubMed – 2014

  

Available Products

“Sambucol” (Razei Bar Industries, Jerusalem, Israel) This standardized elderberry product is a syrup containing elderberry juice, raspberry extract, glucose, citric acid, and honey), is a 38% standardized black elderberry extract containing three flavonoids.

“Sambucol Active Defense” contains a 38% standardized black elderberry extract, plus vitamin C, zinc, propolis, and a proprietary blend of Echinacea angustifolia and Echinacea purpurea.

Rubini BioFlavonoides Elderberry Extract (Zertifikationsnr: IT-CDX 5987) is a monotherapy derived from elderberries, with no additives from animals or col- orings, and no preservatives

Sinupret (Quanterra Sinus Defense) is an herbal mixture of 18 mg of flos Sambucus nigra (elderflower), 18 mg of herba Verbenae off. (vervain wort), 6 mg of radix Gentianae luteae (gentian root), 18 mg of flos Primulae veris cum

 

Dose

Per IFM: 500 mg per day (of USP standard of 17% anthocyanosides)

Sambucol:

1 tbsp (15ml) four times daily for treatment of influenza symptoms

2 tsp (10ml) once a day for preventative management

 

With natural products it is often not clear what the optimal doses are to balance effectiveness and safety. Preparation of products may vary from manufacturer to manufacturer, and from batch to batch within one manufacturer. Because it is often not clear what the active component(s) of a product is, standardization may not be possible, and the clinical effects of different brands may not be comparable. Therefore, along with the notes above outlining the variability amongst elderberry plants and plant parts, caution is advised in the choice of product and it is recommended to use only standardized products such as Sambucol.

 

Mechanism of Action

A placebo controlled, double-blind study of Sambucol documented a rapid recovery from influenza and associated with the inhibition of replications of multiple strains of the flu virus. In this study the mechanism of action is believed to be rendering viruses nonfunctional by staining and coating them.

 

Elderberry modulate cellular defense and repair mechanisms and viral-induced pathological cellular processes. Caffeic acid significantly inhibited the replication of HCoV-NL63 and specifically blocked virus attachment.  Caffeic acid has also been reported to possess antiviral activity against hepatitis B and C viruses, influenza A virus, and herpes simplex virus. Other phenolic acid constituents found in elderberry, chlorogenic acid and gallic acid, have also been demonstrated to suppress replication of influenza A virus, enterovirus 71 and hepatitis B and C viruses.

 

Quercetin, also present in elderberry, promotes viral eradication or inactivation by inhibiting viral replication and reduces viral-induced pathological cellular processes. Quercetin functions as both an antioxidant and an anti-inflammatory as well a NRF2 activator. NRF2 (Nuclear factor erythroid 2-related factor 2) is a protein that regulates the expression of antioxidants that protect against oxidative damage triggered by injury and inflammation. NRF2 activation has been reported to suppress the NLRP3 inflammasome, leading to decreased production of IL-1𝛽, the master regulatory cytokine that activates other cells to produce other inflammatory cytokines. 

(see Quercetin and NRF2 Activators)

 

Pharmacology

The flowers and leaves contain flavonoids, including quercetin (up to 3%), rutin, hyperoside and anthocyanins, as well as essential oils that are responsible for the muscat aroma characteristic of elder flowers. In the elderberry stems a pre-clinical study evaluating six phenolic acid constituents in a Sambucus FormosanaNakai stem ethanol extract, caffeic acid, chlorogenic acid and gallic acid sustained anti-HCoV-NL63 activity that was ranked in the following order of virus yield reduction: caffeic acid > chlorogenic acid > coumaric acid. The results revealed that Sambucus FormosanaNakai stem ethanol extract displayed strong anti- HCoV-NL63 potential and the caffeic acid had the highest anti-HCoV-NL63 potency and could be the vital component with anti-HCoV-NL63 activity.

 

Risk of Harm

Mild; caution w/autoimmune disease; uncooked/unripe plant parts toxic; USDA rated as Generally Recognized As Safe (GRAS)

 

Resources

Institute of Functional Medicine

  1. What is Functional Medicine?

 

References

Elderberry – Overviews

  1. An Evidence-Based Systematic Review of Elderberry and Elderflower (Sambucus Nigra) by the Natural Standard Research Collaboration – PubMed – 2014
  2. Astragalus Root and Elderberry Fruit Extracts Enhance the IFN-β Stimulatory Effects of Lactobacillus acidophilus in Murine-Derived Dendritic Cells – 2012
  3. A Systematic Review on the Sambuci Fructus Effect and Efficacy Profiles – 2010
  4. The Efficacy of Administering Fruit-Derived Polyphenols to Improve Health Biomarkers, Exercise Performance and Related Physiological Responses – 2019
  5. Elderberry (Sambucus Nigra L.) Wine- A Product Rich in Health Promoting Compounds – 2010
  6. The Phenolic Contents and Antioxidant Activities of Infusions of Sambucus nigra L – 2017

 

Elderberry – COVID-19

  1. The Institute for Functional Medicine COVID-19- Botanical and Nutraceuticial Recommendations for Patients (A Checklist)
  2. The Functional Medicine Approach to COVID-19- Virus-Specific Nutraceutical and Botanical Agents – 2020
  3. The Pathogenesis and Treatment of the `Cytokine Storm’ in COVID-19 – 2020
  4. In the News: Coronavirus and “Alternative” Treatments | NCCIH – 2020
  5. Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1β Production – 2016
  6. Potential Inhibitor of COVID-19 Main Protease (Mpro) From Several Medicinal Plant Compounds by Molecular Docking Study – 2020

Elderberry – Colds, Flu and Other Viral Infections

  1. Colds and Influenza – A Review of Diagnosis and Conventional, Botanical, and Nutritional Considerations – 2007
  2. Vaccines for the common cold – 2017
  3. Elderberry Flavonoids Bind to and Prevent H1N1 Infection in Vitro – PubMed – 2009
  4. Inhibitory activity of a standardized elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses – 2011
  5. Black Elderberry (Sambucus Nigra) Supplementation Effectively Treats Upper Respiratory Symptoms- A Meta-Analysis of Randomized, Controlled Clinical Trials – 2019
  6. A Review of the Antiviral Properties of Black Elder (Sambucus Nigra L.) Products – 2017
  7. Antiviral activity of Sambucus FormosanaNakai ethanol extract and related phenolic acid constituents against human coronavirus NL63 – 2019
  8. Randomized Study of the Efficacy and Safety of Oral Elderberry Extract in the Treatment of Influenza A and B Virus Infections – 2004
  9. Antiviral effect of phytochemicals from medicinal plants – Applications and drug delivery strategies – 2020

Elderberry – Varieties and Cultivars

  1. Effect of Harvesting Year and Elderberry Cultivar on the Chemical Composition and Potential Bioactivity- A Three-Year Study – 2019
  2. The Content of Selected Minerals, Bioactive Compounds, and the Antioxidant Properties of the Flowers and Fruit of Selected Cultivars and Wildly Growing Plants of Sambucus nigra L. – 2020
  3. Impact of Frozen Storage on the Anthocyanin and Polyphenol Content of American Elderberry Fruit Juice – 2015

 

Elderberry – Inflammation and Inflammasomes

  1. NF-κB signaling in inflammation – 2017
  2. Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1β Production – 2016
  3. Inhibition of microglial activation by elderberry extracts and its phenolic components – 2015

 

Nutraceuticals – Overviews

  1. New Concepts in Nutraceuticals as Alternative for Pharmaceuticals
  2. Examining the quality of evidence to support the effectiveness of interventions – an analysis of systematic reviews – 2016

  

COVID-19 – CAM Treatment, Botanicals

  1. Implication of Fructans in Health – Immunomodulatory and Antioxidant Mechanisms – 2015
  2. Fructose and Fructans: Opposite Effects on Health? – PubMed – 2015
  3. Antiviral effect of phytochemicals from medicinal plants – Applications and drug delivery strategies – 2020

 

 

Emphasis on Education

 

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

 

For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.

 

Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.

 

For more information, please contact Accurate Clinic.

 

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