What is elderberry

Elderberry (Sambucus nigra) or European elder is a deciduous shrub that grows to a height of 4-6 m and produces violet-black drupes which grow in clusters, holding hundreds of berries and are only edible when fully ripe ¹. Currently, elderberry (the dried or cooked fruit) and elder flower (elderflower) are used as dietary supplements for flu, common cold, constipation, and other conditions ², ³. A recent systematic review looked at elderberry for the treatment of upper respiratory symptoms and suggested that elderberry could be helpful in shortening the duration of colds or influenza ⁴. While herbal supplements including elderberry have been marketed to boost immunity from respiratory illness, the U.S. Federal Drug Administration (FDA) has issued warning letters to supplement producers who are marketing such products with claims that they prevent, treat, or cure COVID-19, as this has not been proven ⁵.

Other parts of the elderberry plant, such as the green stems and branches, are not edible and not recommended for human consumption. The dried elderberry flowers (elder flower) and the dried ripe or fresh elderberries of the European elder tree are used in teas, extracts, and capsules. Various parts of the plant have been used for their laxative, diuretic, expectorant, or purgative properties to treat respiratory and pulmonary disorders as well as fever and rheumatism ⁶. Recently, extracts of the elderberries from some varieties of both European and Canadian elderberry demonstrated significant chemopreventive potential against the initiation and promotion stages of carcinogenesis ⁷. However, more information is required in order to understand the mechanistic and molecular aspects of their antitumor activities.

Elderberry contains anthocyanins, a subset of flavonoids which may have immunomodulating (substance that regulates the immune system) and possibly anti-inflammatory effects ⁸. Anthocyanins can attach to (and render ineffective) viral glycoproteins that enable viruses to enter host cells, thereby potentially having an inhibitory effect on viral infection ⁹. Extracts of elderberry have demonstrated in-vitro (test tube studies) to have inhibitory effects on influenza A and influenza B viruses ¹⁰ as well as H1N1 “swine” flu virus ¹¹. In addition to this direct action on viruses, elderberry may have an effect on the immune system through cytokines ⁹. There is some evidence that elderberry increases the production of inflammatory cytokines (i.e., TNF-alpha, interleukins) although there is also evidence suggesting that cytokine production is decreased ¹⁰. In some cases of COVID-19, proinflammatory cytokines are overproduced and the patient experiences what has been called a ‘cytokine storm’ (when the cytokines begin to attack the cells and tissues of the body) which increases risk of multi-organ failure and death ¹². There is therefore concern in COVID-19 that the potential benefits of elderberry in inhibiting viral replication may be negated by potential harms from cytokine release and immune system hyperresposiveness ⁹.

Elderberries are being increasingly produced and consumed in North America. Both elderberry flowers and fruits are used to produce juices, syrup, wines, jams, jellies, colorants, pies, infusions and a variety of dietary supplements ¹³, ¹⁴. Recently, there has been increasing demand for nonfermented elderberry juice concentrates as a nutraceutical or dietary supplement ¹⁵. Many people in the United States consume herbal dietary supplements with a belief that they offer safe and effective options to help them maintain health and wellness, and elderberry herbal supplement sales nearly doubled in the United States between 2017 and 2018 ¹⁶.

The American elderberry (Sambucus nigra subsp. canadensis) is native to, and most often cultivated in North America. The European elderberry (Sambucus nigra subsp. nigra) has been developed into an economically-important horticultural crop in Europe, but most European cultivars do not perform well in the midwestern USA. In central Europe, the most common species are black elderberry (Sambucus nigra L.), red elderberry (Sambucus racemosa L.), and dwarf elderberry (Sambucus ebulus L.). Black elderberry is the most widespread, being found across Europe, central and western Asia, and northern Africa ¹⁷. From spring until summer the corymbs are in flower. While the majority of elderberry products marketed in North America are produced in Europe from the European elderberry (Sambucus nigra L. subsp. nigra; syn. S. nigra L.), cultivation and processing of American elderberry [S. nigra L. subsp. canadensis (L.) Bolli; syn. S. canadensis L.] is increasing ¹⁸. More research has been published on the medicinal attributes of the European subspecies contrasted with the North American ¹⁹, ²⁰. Thus, some processing firms prefer fruit from the European subspecies, even if cultivated in North America.

European Elderberry Syrup Recipe

• Measure 2 cups of dried elderberries and add 4 cups boiling water into a heat-tempered bowl large enough to accommodate the boiling water, cover, and let sit for 12 hours.
• After 12 hours, pour the softened berry mixture into a blender and blend vigorously.
• Pour the berry mixture into a fine mesh sieve, cheesecloth, or jelly bag and express the juice.
• Simmer the juice on low heat for 1-2 hours. Stir frequently to avoid burning. Reduce juice until it reaches 1.5-2 cups and is highly concentrated.

Note: reduction time when using reconstituted dried berries is much faster than when reducing the pressed juice of the fresh berries.

• Filter through a cheesecloth-lined colander or sieve into a ceramic bowl.
• Pour filtered juice back into clean, large glass measuring cup. Add 1 cup of honey or food-grade glycerin.
• Pour into sterilized jar for storing. Label and date.

Note: European elderberry syrup is best kept refrigerated. Dosage of the syrup is 1 tablespoon each dose, taken 2 or 3 times daily.

[Source ²¹ ]

Figure 1. Elderberry

Figure 2. Elderberry plant

Figure 3. Ederberry phenolic constituents

Figure 4. Ederberry flower phenolic constituents

Elderberry benefits

Elderberries are dark violet-black drupes which grow in clusters and owe their color to the anthocyanins; a group of phenolic compounds which, amongst flavonoids, are abundant in elderberries and considered the active antioxidant activity of elderberries ²². Moreover, elderberries also contain a variety of nutrients ranging from various vitamins (A, B1, B2, B6, B9, C and E), trace elements such as Cu, Zn, Fe and minerals such as K, Ca and Mg to phytochemicals such as carotenoids, phytosterols and polyphenols. These additional constituents and activities make elderberries a likely candidate for beneficial nutritional and/or medical supplementation not only for respiratory, but also for cardiovascular and mental health ²³, ²⁴, ¹⁰.

It is well known that dietary anthocyanins or anthocyanin-enriched extracts reduce the actions of oxidative stress, proliferation, inflammation, and angiogenesis, all processes involved in cancer progression ²⁵. It has been reported that the incorporation of anthocyanins by endothelial cells enhanced their resistance to the damaging effects of reactive oxygen species (ROS) ²⁶. In addition, anthocyanin extracts from black soybean increased the survival of U-87 MG cells accompanied by decreased levels of reactive oxygen species ²⁷.

However, recent systematic review did not find any evidence on the impact of elderberry on clinically relevant outcomes related to inflammation, however, it found three studies examining ex vivo (outside of the living body) effects of elderberry in healthy adults ⁹. While there were some statistically significant reductions in cytokines indicating that elderberry likely has some effect on inflammatory markers, the evidence was underwhelming in the studies with interventions of longer duration, suggesting that this effect may abate over time with repeated dosing. The comparison to diclofenac in the small study using single doses of elderberry or diclofenac, however, does provide some context for the reader as diclofenac is recognized as a potent non-steroidal anti-inflammatory drug, and the study suggests that elderberry is as effective or less effective than diclofenac in IL-1 reduction over time ²⁴. Based on the ex vivo evidence, there does not currently appear to be any reason for concern about elderberry products and risk of overstimulation of the immune system ⁹. However, in order to determine the clinical significance of elderberry’s effect on inflammation and cytokine storm, future trials must involve patients with inflammatory conditions and evaluate more meaningful clinical outcomes associated with inflammation in addition to surrogate markers such as cytokine serum concentrations.

Several epidemiologic and experimental studies have demonstrated the health-promoting benefits provided by regular berry consumption, including some against the incidence of certain cancers ²⁸. Depending on the diet, the daily intake of anthocyanins in humans has been estimated to range from several milligrams to hundreds of milligrams ²⁹. For example, the total mean intake of anthocyanins from a Western diet was estimated at 12.5 mg/d ³⁰ comparatively to 64.9 mg/d from a Mediterranean diet ³¹. An enhanced intake of dietary anthocyanins may be occurring with the consumption of commercially available anthocyanin extract. At least 14.5 mg of anthocyanins can be obtained in one single teaspoon (5 mL) of concentrated elderberry extract. Oral consumption of berry phytochemicals can directly be absorbed in the oral cavity and in the stomach as well as in the gastrointestinal tract ²⁸. In addition, anthocyanins can be taken up by human vascular endothelial cells ³² and have demonstrated ability to cross the blood-brain barrier (BBB) ³³. It is also worth pointing out the ability of flavonol rutin to also pass through the blood-brain barrier ³⁴. Moreover, anthocyanins are rapidly detected in plasma after consumption of elderberry extract ³⁵. Thus, integration of elderberries in the diet might be a comprehensive strategy for preventing the molecular events involved in chronic disease progression such as cancer ³⁶. Human clinical trials demonstrating the chemopreventive effects of berry preparations have focused mainly on black raspberries ³⁷. However, it is likely that other berry types such as elderberries may also be effective for chemoprevention in humans. Future studies are required to better understand the molecular mechanisms of action and effectiveness in vivo, as elderberry and elderflower extracts have potential indications as cancer chemopreventive agents.

The intake of anthocyanins, a subclass of flavonoids that confers the red, blue and purple colors to plant-based foods such as elderberries, apples and blackcurrants, has been shown in epidemiological studies to be negatively correlated with cardiovascular disease risk ³⁸. In vitro, anthocyanins also exhibit activities in keeping with a protective effect, such as reduced immune cell-activated radical, cytokine and adhesion molecule production ³⁹ and reduced nitric oxide activity ⁴⁰. However, to date there is limited evidence on the effects of consumption of physiologically-relevant doses of anthocyanins on biomarkers of cardiovascular disease risk and safety biomarkers ⁴¹.

In this randomized parallel placebo-controlled study ⁴² the effect of 12 weeks of consumption of 500 mg anthocyanins (present predominantly in the cyanidin glycoside form; from elderberry/day, on biomarkers of cardiovascular disease risk and liver and kidney function was examined in fifty-two healthy women (anthocyanins, n 26; placebo, n 26). Eligible participants were post-menopausal women (no menstruation for ≥12 months) under 70 years of age, not taking hormone-replacement therapy (HRT) for ≥6 months and with body mass index (BMI) between 20 kg/m2 and 32 kg/m2. Fasting blood samples were collected at baseline and 12 weeks and used to assess a series of vascular biomarkers and liver and kidney function. In addition, platelet reactivity was assessed at 0 and 2 hours at both baseline and end of the study. The results of that study ⁴² suggest that biomarkers of liver and kidney function and cardiovascular disease risk (blood pressure, lipid fractions and inflammatory biomarkers; also platelet reactivity) were not modified by 12 weeks of anthocyanins-rich elderberry consumption. In conclusion, these data suggest that daily consumption of physiologically-relevant doses of elderberry extract did not induce detrimental changes to liver and kidney function, but also did not alter biomarkers of cardiovascular disease risk ⁴².

The elderberry plant has long been used in herbal medicine in Asia, North Africa, Europe and America and has been used in the formulation of diverse medicinal preparations to prevent and/or control different diseases ⁴³. Prior to antibiotics, elderberry was found as one of the main ingredients in many preparations used by herbalists ⁴⁴, pharmacists, and physicians. Today, elderberry is employed as an alternative to conventional medicines and mainly in the form of an extract for treating the common cold ⁴⁵, influenza ⁴⁶, ⁴⁷, ⁴⁸, ⁴⁹ and Herpes virus infections ⁴⁵. Elderberry is often recommended for use as a complementary therapy together with the classic antioxidant nutrients, vitamin C and zinc, to support the natural process of recuperation ⁴⁵. Elderberries contain a variety of polyphenols, namely phenolic compounds such as anthocyanin derivatives, including cyanidin 3-glucoside, cyanidin 3-sambubioside, cyanidin 3-sambubioside-5-glucoside and cyanidin 3,5-diglucoside ⁵⁰; as well as triterpenic compounds such as ursolic and oleanolic acids, and sterols, as β-sitosterol were reported as elderberry bioactive components ⁵¹.

Two randomized, double-blind, placebo-controlled studies demonstrate the elderberry extract, Sambucol, effectively inhibits both influenza A and B strains when given orally to patients in the first 48 hours of influenza symptoms. In one study, 27 individuals (23 with laboratory confirmation of influenza B) experiencing typical early flu symptoms were given Sambucol (n=15) or placebo (n=12) daily for three days – two tablespoons (30 mL) for children or four tablespoons (60 mL) for adults – and symptoms were monitored for six days. Serum from all subjects was analyzed for antibodies to influenza A and B at the initial dose and during the convalescent phase. While differences in antibody titers between the two groups did not reach statistical ignificance, a trend in favor of the treatment group was observed. Clinically however, significant improvement in flu symptoms was observed in 14 of 15 subjects in the treatment group two days after initial dosing, with complete symptom resolution in 13 of 15 subjects after three days. In the placebo group, complete symptom resolution was only achieved by 4 of 12 subjects within three days and 5 of 12 subjects after five days ⁵². In a second study, 60 patients (ages 18-54 years) experiencing early influenza symptoms were given 15 mL (1 tablespoon) Sambucol or placebo syrup four times daily for five days; symptoms were monitored for eight days. In the treatment group, the majority of patients reported “pronounced improvement” after an average of 3-4 days, while the placebo group required 7-8 days to reach the same level of improvement ⁵³. Despite these preliminary research indicating that elderberry may relieve flu symptoms, the evidence is not strong enough to support its use for this purpose. These promising effects of elderberry fruit preparations from experimental and clinical studies should be backed by more rigorous studies before these preparations are recommended in the prevention of diseases and in treatment schedules like cancer.

A few studies have suggested that combination products containing elder flower and other herbs might be helpful for sinusitis, but because the products contain multiple ingredients, it’s unclear what role, if any, elder flower plays in their effects. There’s not enough information to show whether elder flower and elderberry are helpful for any other purposes.

Table 1. Elderberry (raw) nutrition facts

Nutrient	Unit	Value per 100 g	cup 145 g
Approximates
Water	g	79.8	115.71
Energy	kcal	73	106
Energy	kJ	305	442
Protein	g	0.66	0.96
Total lipid (fat)	g	0.5	0.72
Ash	g	0.64	0.93
Carbohydrate, by difference	g	18.4	26.68
Fiber, total dietary	g	7	10.2
Minerals
Calcium, Ca	mg	38	55
Iron, Fe	mg	1.6	2.32
Magnesium, Mg	mg	5	7
Phosphorus, P	mg	39	57
Potassium, K	mg	280	406
Sodium, Na	mg	6	9
Zinc, Zn	mg	0.11	0.16
Copper, Cu	mg	0.061	0.088
Selenium, Se	µg	0.6	0.9
Vitamins
Vitamin C, total ascorbic acid	mg	36	52.2
Thiamin	mg	0.07	0.102
Riboflavin	mg	0.06	0.087
Niacin	mg	0.5	0.725
Pantothenic acid	mg	0.14	0.203
Vitamin B-6	mg	0.23	0.334
Folate, total	µg	6	9
Folic acid	µg	0	0
Folate, food	µg	6	9
Folate, DFE	µg	6	9
Vitamin B-12	µg	0	0
Vitamin A, RAE	µg	30	44
Retinol	µg	0	0
Vitamin A, IU	IU	600	870
Lipids
Fatty acids, total saturated	g	0.023	0.033
04:00:00	g	0	0
06:00:00	g	0	0
08:00:00	g	0	0
10:00:00	g	0	0
12:00:00	g	0	0
14:00:00	g	0	0
16:00:00	g	0.018	0.026
18:00:00	g	0.005	0.007
Fatty acids, total monounsaturated	g	0.08	0.116
16:1 undifferentiated	g	0	0
18:1 undifferentiated	g	0.08	0.116
20:01:00	g	0	0
22:1 undifferentiated	g	0	0
Fatty acids, total polyunsaturated	g	0.247	0.358
18:2 undifferentiated	g	0.162	0.235
18:3 undifferentiated	g	0.085	0.123
18:04:00	g	0	0
20:4 undifferentiated	g	0	0
20:5 n-3 (EPA)	g	0	0
22:5 n-3 (DPA)	g	0	0
22:6 n-3 (DHA)	g	0	0
Fatty acids, total trans	g	0	0
Cholesterol	mg	0	0
Amino Acids
Tryptophan	g	0.013	0.019
Threonine	g	0.027	0.039
Isoleucine	g	0.027	0.039
Leucine	g	0.06	0.087
Lysine	g	0.026	0.038
Methionine	g	0.014	0.02
Cystine	g	0.015	0.022
Phenylalanine	g	0.04	0.058
Tyrosine	g	0.051	0.074
Valine	g	0.033	0.048
Arginine	g	0.047	0.068
Histidine	g	0.015	0.022
Alanine	g	0.03	0.043
Aspartic acid	g	0.058	0.084
Glutamic acid	g	0.096	0.139
Glycine	g	0.036	0.052
Proline	g	0.025	0.036
Serine	g	0.032	0.046
Other
Alcohol, ethyl	g	0	0
Anthocyanidins
Cyanidin	mg	485.3	703.6
Petunidin	mg	0	0
Delphinidin	mg	0	0
Pelargonidin	mg	0	0
Flavonols
Isorhamnetin	mg	5.4	7.9
Kaempferol	mg	0.6	0.8
Quercetin	mg	26.8	38.8
Proanthocyanidin
Proanthocyanidin dimers	mg	10.6	15.4
Proanthocyanidin trimers	mg	5.6	8.2
Proanthocyanidin 4-6mers	mg	10.8	15.7
Proanthocyanidin 7-10mers	mg	0	0
Proanthocyanidin polymers (>10mers)	mg	0	0

[Source: United States Department of Agriculture Agricultural Research Service ⁵⁴ ]

Table 2. Elderberry tea nutrition facts

Nutrient	Unit	TEA BAG 2 g	Value per 100 g
Approximates
Energy	kcal	0	0
Protein	g	0	0
Total lipid (fat)	g	0	0
Carbohydrate, by difference	g	0	0
Sugars, total	g	0	0
Minerals
Sodium, Na	mg	0	0

[Source: United States Department of Agriculture Agricultural Research Service ⁵⁴]

Elderberry health benefits summary

Based on evidence from one large study of healthy adults, elderberry may not reduce the risk of developing the common cold, although it remains possible that colds developed during elderberry supplementation may be shorter and less severe than colds developed on placebo ⁹. However, there is insufficient information to be certain about these effects. There are two recently completed but not yet published studies testing Sambucol for cold or influenza symptoms ⁵⁵, ⁵⁶.

Based on three studies testing elderberry versus placebo for its effect on symptoms of influenza, it is possible that illness may be shorter and less severe with elderberry than with placebo. However, the estimates of quicker recovery are very uncertain because the studies to date have been small and are not without problems in conduct (e.g., incomplete outcome data, selective presentation of outcomes) and the estimate of mean difference in days to recovery displays high heterogeneity. Although no serious adverse events were reported in any study, the limited attention to adverse events overall means that it is very uncertain about types and rates of more minor adverse events.

Based on one study comparing a mixed herbal product incorporating elderberry (Echinaforce® Hotdrink) to oseltamivir, there may be a slightly higher rate of recovery with oseltamivir at one day after beginning treatment, but little or no difference between treatments in rates of recovery at five and ten days. There may be a lower risk of complications or adverse events with the herbal preparation compared to oseltamivir, and it appears to be a viable option for treatment. There are recently completed or ongoing clinicalstudies comparing mixed elderberry products to placebo for respiratory symptoms ⁵⁷, ⁵⁶. Information from these studies will further clarify the potential role of these mixed products containing elderberry in respiratory illness. Overall, further research is needed to establish whether elderberry (in different forms and at different doses) is effective in either preventing or ameliorating respiratory illnesses (including not only common cold and influenza but also illnesses resulting from COVID-19 coronaviruses) in populations of different ages and different baseline health statuses ⁹.

In conclusion, elderberry is a promising intervention for reducing the severity and duration of influenza and the common cold, and it does not appear associated with serious adverse effects ⁹. However, the current evidence base is limited in both size and quality. The results of ongoing and recently completed but not yet published clinical studies ⁵⁵, ⁵⁶ may provide more conclusive evidence on potential benefits and harms and allow exploration of subgroup factors.

Elderberry side effects

The leaves, stems, raw and unripe berries, and other plant parts of the elder tree contain a toxic substance and, if not properly prepared, may cause nausea, vomiting, and severe diarrhea. Because the substance may also be present in the flower, consuming large amounts of the flower might be harmful; however, no illnesses caused by elder flower have been reported.

It is also important to remember, when gathering elderberries, that the blue elderberries are the only edible variety, and only the berries at that. Red elderberry (Sambucus racemosa), which is also found in the West, contains hydrocyanic acid and sambucine that produce cyanide in the body unless the berries are sufficiently cooked. Even the stems, roots and leaves of the blue elderberry (such as S. mexicana) are considered poisonous and can cause nausea or worse or produce severe purging. Don’t consume red elderberries in any form!

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