Respect your elders: Checking in with elderberry

When a wellness ingredient can claim consistent therapeutic use for close to several millennia, it’s fair to say that 1) it’s no longer an up-and-comer, and 2) it must be doing something right.

Such is certainly the case with elderberry (Sambucus nigra), which was as much of an herbal staple in Ancient Greece as it is in our own COVID-cursed era.

And as it happens, the pace of science both supporting elderberry’s benefits and elucidating its actions has ramped up significantly even over the past few years, with PubMed listing more than 400 published studies on elderberry (or elder berry, as it sometimes appears; more on that later) from the last half-decade alone.

Looking back a full decade to 2012, Holly E. Johnson, PhD, chief science officer, American Herbal Products Association (AHPA; Silver Spring, MD), notes that roughly 50 to 80 elderberry studies have hit publications each year since, “many of which investigate its bioactivity and mechanistic influences on the immune system,” she adds.

So with elderberry’s fortunes rising along with the research, can we expect the good luck to continue? If brands make the most of this powerful botanical, we sure can.

Sales Spike

According to the American Botanical Council’s (ABC; Austin, TX) annual HerbalGram Herb Market Report, mass-market elderberry sales grew first from about $51 million in 2018 to nearly $108 million in 2019, and then to almost $276 million in 2020—an almost stratospheric rise that, in light of the pandemic, was clearly no coincidence. And while the ABC hasn’t crunched 2021’s numbers yet, Stefan Gafner, PhD, ABC’s chief science officer, is confident remarking that the past three years’ domestic growth alone “has been quite impressive.”

Nutritional Outlook interviewed Chris Tower when he was vice president of sales and business development at Artemis International (Fort Wayne, IN). (In August, Tower joined Euromed USA Inc. as general manager.) Tower confirmed that demand for Artemis’s ElderCraft elderberry extract “was off the charts” during that same period, he claimed, adding that, “for perspective, we exhausted our two-year safety stock of frozen berries within calendar 2020 and had to implement a carefully managed allocation process to fulfill sales commitments to customers through the first quarter of 2021.”

While a “relative ebb” had finally descended on the frenzy by 2021’s Q2, with summer ’22 now in full swing and families on the move, Tower declared, “ElderCraft sales and new-product launches have significantly surged again. And flu season is still on the horizon.”

Nothing New

Of course, all of this is in keeping with elderberry’s track record of periodic surges—a track record that traces back ages.

“Elderberries have a long history of medicinal use,” Gafner points out. “Traditionally, the berry was used for a number of issues, mostly in the form of a juice or syrup as a mild laxative, diuretic, and diaphoretic—perspiration-promoting—agent for the common cold.”

As recently as the flu season of 2018-2019, which Melanie Bush, Artemis’s vice president of science and research, describes as “particularly bad,” “mainstream awareness of elderberry had already been rising, dovetailing nicely with its emerging public reputation as a helpful remedy” for such illness outbreaks.

Subject of Inquiry

That awareness merely solidified with COVID-19, and for good reason: “These little dark berries are all about immune support,” Bush says. But don’t take her word for it; survey the science.

Bush notes, for example, that a human pilot study¹ conducted in the early-2000s concluded that elderberry can reduce influenza-symptom severity and duration, with a subsequent study² published less than a decade later demonstrating elderberry extract’s direct antiviral and antibacterial action in a lab setting.

Those findings paved the way for a now oft-cited large-scale human clinical trial³ involving long-haul flight passengers confirming elderberry’s ability to reduce symptom severity and duration in upper respiratory tract infections like colds and flu.

And in 2019, a meta-analysis⁴ evaluating all clinical data generated to date leveled this “clinically relevant verdict,” says Bush: “Supplementation with elderberry extract reduces symptom duration and severity in colds and influenza. There you have it.”

Behind the Magic

What more could anyone want? Well, mechanistic data wouldn’t hurt, and that’s just what more recent research is delivering.

Consider that some of the main bioactives in European black elderberry are anthocyanin flavonoids, Bush explains, with cyanidin-3-sambubioside predominant among them. Studies now show that cyanidin-3-sambubioside appears to block the binding of influenza viral glycoproteins to host cells, she says, thus blocking virus entry and replication.⁵

“Additionally,” Bush continues, “polysaccharides from elderberry were identified as having immune-boosting properties⁶—evidence that was corroborated in a brand-new study in which the polysaccharides in ElderCraft extract exerted direct immune-stimulating properties in dendritic cells and cytokines.”⁷

Finally, she points to new studies nearing completion and publication that demonstrate ElderCraft’s inhibition of SARS-CoV-2 replication in vitro, as well as its support for a healthy immune system “by way of exerting prebiotic benefits in humans for a healthy gut,” she says.

Take Care

Tower noted that because elderberry’s anthocyanins are relatively heat-sensitive and can degrade at temperatures above 90°C—conditions frequently encountered in conventional processing methods—Artemis extracts its ingredient using a proprietary water-extraction and ultrafiltration-concentration process called Iprona Polyphenol Technology (IPT).

“The IPT process’s uniqueness in large part retains and concentrates the full embodiment of our whole fresh and frozen Haschberg European black elderberry fruit,” Tower claimed. That leaves the finished ingredient “highly stable” in its dried extract form, he said, as well as highly water-soluble, palatable, and “organoleptically representative of fresh elderberry fruit.”

Those advantages have helped the ingredient chart an “exceptionally robust” course into formulations ranging from gummies and syrups to soft gels, capsules, chewable tablets, RTD beverages, teas, effervescent powders, and more, said Tower. “And on an even more niche level,” he noted, “ElderCraft formulates well into liposomal suspensions and functional chewing gum.”

Buyer Beware

Again, to ensure that these formulations deliver the potency consumers expect, Bush suggests that brands insist on elderberry extracts standardized to anthocyanin content and “made with gentle processing that retains other important bioactives within the fruit matrix.” But beyond that, she says, brands should also be on high alert for adulteration.

“When an ingredient’s star rises and it becomes popular,” she explains, “there’s always risk of bad actors getting a piece of the action through dishonest practices like adulteration. Unfortunately, elderberry is no exception.” The result, she says: “Misbranding is an issue in the market, as low-grade elderberry ingredients get passed off as more premium extracts.”

Most clinical data pertain to extracts from the plant’s berry, and not to those from other plant parts, for example. But given that the going rate for destemmed elderberries can be as much as times ten times that of berries with the stems attached⁸, shady suppliers have an incentive to get in on that action even while selling stem-on berries. Thus, Gafner concedes that though he’s seen little indication of flowers, leaves, or other structures winding up in elderberry products, “brands that economize may inadvertently buy product that’s not all berry.”

But the “bigger concern” for Gafner and others is intentional adulteration with extracts from lower-cost plants containing similar anthocyanins—say, black rice. It’s a temptation that pandemic- and now harvest-induced supply shortages have exacerbated⁹, he says, and recent studies do, in fact, hint that such adulteration of elderberry supplements “appears to be quite common.”^10,11

Gafner’s advice is therefore not buying based on price. “And make sure your extract is authentic,” he says. “If you don’t have an in-house laboratory, you should use a reputable contract-analytical laboratory to authenticate the material.”

Trust Is All

Tower agreed. “Adulteration of elderberry—particularly extracts—remains so commonplace that ‘buyer beware’ should be the default position,” he wagered. “When sourcing and qualifying elderberry ingredients, it’s essential to work with leading, transparent, trusted suppliers with clear chain-of-custody oversight from harvest through manufacture, and comprehensive shared quality parameters, including species authentication.”

Again, standardization to anthocyanins is key, he said, adding that brands should “pointedly question suppliers offering high-ratio ‘so-called’ extracts at a low cost.”

Bush agrees, and notes that Artemis has worked with accredited labs and organizations like the ABC, with whom it helped produce industry guidance through ABC’s Botanical Adulterants Prevention Program (BAPP). She adds that the United States Pharmacopeia (USP) also hopes to support brands’ efforts to “do their due diligence” with an update to its monograph of standardized methods for quantitatively and qualitatively analyzing elderberry ingredients.

But ultimately, she says, “In today’s business climate, it’s essential to work with trusted suppliers who specialize in European black elderberry. Transparent chain-of-custody documentation, from field to final product, should come standard, as should control over raw-material quality.” Like elderberry’s benefits themselves, such advice is timeless.

References

1. Zakay-Rones Z et al. “Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections.” The Journal of International Medical Research, vol. 32, no. 2 (March-April 2004): 132-140
2. Krawitz C et al. “Inhibitory activity of a standardized elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses.” BMC Complementary and Alternative Medicine. Published online February 25, 2011.
3. Tiralongo E et al. “Elderberry supplementation reduces cold duration and symptoms in air-travelers: a randomized, double-blind placebo-controlled clinical trial.” Nutrients, vol. 8, no. 4 (March 24, 2016): 182
4. Hawkins J et al. “Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: a meta-analysis of randomized, controlled clinical trials.” Complementary Therapies in Medicine, vol. 42 (February 2019): 361-365
5. Swaminathan K et al. “Binding of a natural anthocyanin inhibitor to influenza neuraminidase by mass spectrometry.” Analytical and Bioanalytical Chemistry, vol. 405, no. 20 (August 2013): 6563-6572
6. Kinoshita E et al. “Anti-influenza virus effects of elderberry juice and its fractions.” Bioscience, Biotechnology, and Biochemistry, vol. 76, no. 9 (2012): 1633-1638
7. Stich L et al. “Polysaccharides from European black elderberry extract enhance dendritic cell mediated T cell immune responses.” International Journal of Molecular Sciences, vol. 23, no. 7 (April 1, 2022): 3949
8. Athearn K et al. “Elderberry and Elderflower (Sambucus spp): Markets, Establishment Costs, and Potential Returns.” University of Florida website. Published March 17, 2021.
9. “2021 Harvest Review.” SVZ International BV website. Published October 4, 2021
10. Güzelmeriç E et al. “Quali/quantitative research on herbal supplements containing black elder (Sambucus nigra L.) fruits.” Journal of Research in Pharmacy, vol. 25, no. 3 (2021): 238-248
11. Avula B et al. “Chemical profiling and UHPLC-QToF analysis for the simultaneous determination of anthocyanins and flavonoids in Sambucus berries and authentication and detection of adulteration in elderberry dietary supplements using UHPLC-PDA-MS.” Journal of Food Composition and Analysis, vol. 110 (July 2022)