Immune-health roundtable: Ingredients backed by science

April 24, 2020

Immune health is one of the top dietary supplement categories, as more consumers each year are interested in maintaining not only their own health but their children’s, too. But now that consumers’ concerns have turned toward COVID-19, immune-health supplements are even more popular, as consumers are looking for ways to stay healthy amid this uncertain time. Although supplements cannot prevent, treat, or cure any disease, there are many dietary supplement ingredients that have documented research on their ability to support the immune system and overall health.

Nutritional Outlook spoke with several ingredient suppliers with a longstanding presence in the dietary supplements industry about their concerns during the COVID-19 pandemic, including immune-boosting ingredients backed by science.


Nutritional Outlook: Do you expect to see an increase in the number of companies making immune-health claims for their ingredients or finished products during the COVID-19 pandemic? 

Mark LeDoux, chairman and CEO, Natural Alternatives International (NAI; Carlsbad, CA): There is no shortage of companies or advertisers who are seeking to capitalize on consumers’ concerns raised by this pandemic, but that does not give them license to make unsubstantiated claims regarding products. There are multiple substances that can be shared with consumers deploying recognized nutrients that possess well-validated structure and function claims, and companies should be mindful of their legal responsibilities in communicating with consumers.

John Quilter, vice president and general manager, Kerry (Beloit, WI): Unsurprisingly, there’s much more focus on immune health now. It’s not necessarily that companies are making new claims, but many are taking the opportunity to promote immune-health products in their portfolios or emphasizing immune-health benefits over other selling points.

Chris Tower, vice president of sales and business development, Artemis International (Fort Wayne, IN): Yes, absolutely. The COVID-19 pandemic has catalyzed consumers' fears and, subsequently, the immune-boosting health category has become the latest trend in the dietary supplement arena, acutely on an unprecedented historic level. Clearly this has proven out with the latest SPINS data upon the onset of the pandemic.

My concern in times like this is overhyping ingredients—over-promotion among companies that is far beyond scientifically substantiated efficacy, which provokes unrealistic expectations among consumers. This fuels an increased demand and increased numbers of new consumers into the supplement category for the first time. I’ve witnessed over the past two decades that industry-related acute demand like this can often result in a relative long-term proportional correction in the demand curve, and usage of these related products will settle back to normalized demand.


Nutritional Outlook: How concerned are you about companies making irresponsible or illegal claims that supplement products or ingredients can prevent, treat, or cure COVID-19?

LeDoux: There have been multiple warning letters issued by FDA to companies promoting their products as intended to treat, cure, prevent, or mitigate disease—in this case COVID-19. But we are always concerned with bad actors in the industry. With the reduction in FDA inspections, we fear this gives license to unscrupulous entities trying to commercialize products without adequate GMP safeguards in their sourcing, production, and labeling. Has there been enough action on the enforcement end (e.g., FDA warning letters) to root out bad actors? The Office of Dietary Supplements has been aggressively seeking to warn companies and individuals in this space, but until products are seized and financial assets frozen through court order, I fear there will be continued mischief. 

Quilter: It’s a major concern. It’s always important to avoid exaggerated claims, but even more so at times of heightened public worry. There’s a huge difference between pointing out that a well-supported immune system is the best defense against health challenges and suggesting that a product can prevent COVID-19.

We’ve been very careful about the way we’ve talked about our immune-health ingredient Wellmune during this crisis. It’s backed by more than a dozen clinical studies, which demonstrate its ability to help strengthen the immune systems of people of all ages. However, there’s currently no research demonstrating its effectiveness against coronavirus specifically, and we’ve been very upfront about that.

Tower: I am extremely concerned. Fortunately, FDA and FTC are quickly acting with warning letters, and I have a high degree of confidence this is being backed up with enforcement. In perspective, the past two years we’ve witnessed a myriad of multiple disease state illegal claims among cannabis supplement companies/products, and though it may be easy to dismiss this as a result of new players entering the supplement industry and riding the cusp of the CBD wave, it’s encouraging to see FDA enforcing illegal disease state claims in violation of DSHEA structure-function claim limitations. There is zero tolerance for this. What is surprising is seeing established industry veterans stretching the limits—we’ve seen bridging into direct disease (anti-viral) claims and even directly marketing their products as a treatment or prevention of COVID-19.


Nutritional Outlook: What kinds of immune-health ingredients should product marketers and formulators be relying on and trust during this time?

Melanie Bush, director of science, Artemis International: Product formulators should take great care in selecting top-notch quality ingredients with proven efficacy to ensure they are providing the best products that will truly help their customers. Now is not the time for pop-up ingredients that are believed to have some immune-supporting potential or other versions that lack proper vetting. Tried-and-true ingredients with a strong history of use, clean and clear supply chains, and proper scientific validation of efficacy have always been, and continue to be, the best choices for formulators. 

For example, European black elderberry (Sambucus nigra) has been used for centuries to ward off ailments. Quality ingredients have been validated with clinical studies and maintain a controlled supply chain from the growers on up. A boom in elderberry sales due to a mainstream awareness of its potent immune-supporting properties has caused a number of new elderberry varieties and offerings to pop up in the market, often at a lower cost. Buyers and formulators should watch for potential adulteration and not to assume all elderberry is created equal.

Kim Edwards, global product manager, Kemin Human Nutrition & Health (Des Moines, IA): Marketers and formulators should look at ingredients that are clinically demonstrated to safely enhance the immune system. Several surveys have identified overall health and well-being, digestion, and immune health as top reasons consumers take supplements—consumers are looking to stay healthy year-round. Solutions that fit into a wholesome lifestyle approach, along with good nutrition, are desirable to support their health.

LeDoux: Responsible companies should rely on well-documented research that has undergone gold-standard tests, (e.g., double-blind, placebo-controlled investigations). Vitamins C and D, and minerals such as zinc, have well-documented findings that suggest they benefit the human immune system.

Aparna Parikh, head of global marketing communications, Lonza (Basel, Switzerland): We believe brand trust is built on robust evidence and consistent high quality and compliance. A consumer-driven product design approach is increasingly important since it takes into account consumers’ needs and preferences—from their health goals to what they look for on a product label before making a purchase. Results from a 2018 report conducted by the Natural Marketing Institute and Lonza show clinical proof of efficacy is very important to 52% of U.S. supplement users in their quest for greater safety and confidence when purchasing supplement products. Aligning with consumer needs through science-backed, high-quality ingredients should always be the aim for product marketers and formulators.

We’ve further noted that 80% of U.S. supplement users think it’s important to know the source of ingredients when making a purchasing decision. As such, it’s increasingly important for brands to explore immune-health ingredient options that not only offer a science-based mechanism of action, but are also plant-based, clean-label, or naturally derived.

Quilter: The ingredients you can rely on and trust are the ones backed by gold-standard science. The best strategy is always a commitment to safety and efficacy backed by high-quality research. Consumers now face a cacophony of claims, which can make them confused, cynical, or both. Scientific backing from peer-reviewed studies helps them understand the real benefits of immune health products, ultimately simplifying their purchase decisions.


Nutritional Outlook: Is there a sufficient number of ingredients on the market with strong scientific research showing they benefit immune health in healthy humans?

Bush: There is definitely a spread across the market between clinically validated, high-quality ingredients and often less expensive offerings that might be lacking in terms of true validation, levels of actives, or analytical quality testing. Often, branded ingredients have gone through the steps to have substantial backing in the form of research and clinical trials to differentiate them from more general offerings in the market. It is difficult to say what number is sufficient in terms of substantiated ingredients in the marketplace, as they ideally all should be. 

LeDoux: Indeed, there are. As indicated earlier, the use of certain vitamins and minerals in addition to herbal compounds such as elderberry have been studied for many years for their capacity to reduce the severity of symptoms associated with colds1 and influenza. Of note is the fact in 1997 we knew elderly subjects who supplemented with zinc (20 mg/day) and selenium (100 mcg/day) for two months had significantly less infectious events over a two-year period2. These results indicate that supplementation with low doses of vitamins and trace elements is able to rapidly correct corresponding deficiencies in the institutionalized elderly.

Quilter: If you look how important scientific substantiation is to consumers, it would be fair to say there aren’t enough immune-health products backed by robust research. We recently surveyed over 11,000 consumers in 14 different countries (Kerry Global Consumer Survey – Digestive & Immune Health, 2019). Nearly four in 10 (39%) said seeing claims based on research or scientific data would make them more likely to buy a healthy lifestyle product. This figure rose to above half in some regions, with 51% of consumers in Brazil and Thailand considering research data a top purchase driver.


Nutritional Outlook: Aside from your company’s ingredients, what are the most promising dietary supplement ingredients for immune health? 

LeDoux: An abundance of evidence has accumulated over the past 50 years demonstrating the antiviral activity of zinc via numerous mechanisms3. Beta-glucans are also an area worthy of significant consideration, given their well-studied positive effects on the human immune system and their capacity to increase immunoglobulins essential for robust immune function4. Acetyl-L-cysteine (NAC) is also promising in this fight. This molecule inhibits virus replication and expression of pro-inflammatory molecules, which leads to inflammation, tissue damage, and respiratory demise5.


Nutritional Outlook: Which of your ingredients support immune health, and what scientific evidence do you have to substantiate their efficacy? 

Bush: While there are several dark berries such as aronia and black currant with preliminary research indicating anti-viral and/or immune-promoting activity, the shining star within the berry category in terms of immune support properties is the European black elderberry.  Artemis’s ElderCraft line of European black elderberry standardized extracts are made using the premium Haschberg variety of Sambucus nigra black elderberries and have been scientifically validated in numerous studies, including human clinicals. In a 2016 human study, ElderCraft was shown to significantly reduce the duration and severity of cold/flu symptoms in long-haul flight passengers1. The gentle extraction process used to make ElderCraft extracts without any harsh chemical solvents retains key natural compounds that support its anti-viral and immune-supporting qualities.

Edwards: Kemin offers BetaVia Complete, a nutrient-rich, dried whole-algae (Euglena gracilis) fermentate containing beta-1,3 glucan (>50%), protein, fatty acids, vitamins, minerals, and carotenoids. Clinical and preclinical research supports marketing claims for immunity, the digestive tract, and respiratory tract health.

In vitro research demonstrates innate immune cells (macrophages, dendritic cells) bind [with] or phagocytize BetaVia Complete, triggering a release of chemical messengers called cytokines that play a critical role in balancing and coordinating healthy immune responses. In a randomized, double-blind, placebo-controlled 90-day study of healthy, active adults, participants taking BetaVia Complete reported 3.3 fewer sick days, 70% fewer upper respiratory tract infection (URTI) symptoms, 10 fewer URTI symptom days, and significantly lower overall severity of URTI symptoms6.

LeDoux: The role of carnosine, a dipeptide consisting of beta-alanine and L-histidine, has promise. In a study published in the Journal of General Virology7, it markedly ameliorated H9N2 swine influenza virus-induced lung injury. The problem with administering supplemental carnosine is that it addresses the situation uneconomically—there is ample L-histidine available in the human body but a paucity of beta-alanine. By ingesting supplemental beta-alanine, the body can then manufacture the dipeptide of carnosine internally, addressing needs brought on by oxidation of healthy tissues in the lungs due to viral load and resulting immunological response. We offer a sustained-release form of beta-alanine, SR CarnoSyn, that ensures carnosine generates naturally in the body for an efficacious dosage to improve health.

Parikh: Lonza’s proprietary ResistAid arabinogalactan is a naturally derived, sustainably produced ingredient, extracted from North American Larch trees using a gentle, water-based method. It has been clinically demonstrated to potentially support natural immune function by different mechanisms of actions: indirect action through modulation of the gut microbiota and directly through support of the innate and adaptive immune system. These mechanisms have been demonstrated to support increased beneficial immune cell populations and also to help modulate and deliver an appropriate immune response. Based on two randomized, double-blind, placebo-controlled human trials, ResistAid has been shown to further support the immune system when added to vaccines8,9. In addition, healthy subjects consuming 4.5 g of ResistAid experienced fewer symptoms of respiratory tract infections compared to placebo10.

Quilter: Wellmune is our proprietary baker’s yeast beta-1,3/1,6 glucan; it is clinically proven to help support the immune system and is backed by over a dozen clinical studies. Most recently, a scientific review of the role of beta glucans in immune health highlighted their benefits for healthy populations that have increased risk of respiratory infections11. The review focused on their mechanism of action as immunomodulators, exploring the theory that they train the body’s immune cells, triggering changes that help fight off pathogens. It also highlighted several studies providing evidence of Wellmune’s ability to support overall immune health in a range of healthy populations:

• Children supplementing with Wellmune were significantly healthier during the cold and flu season. Wellmune was reported to decrease the incidence and duration of common colds by 66% compared to a placebo group.12
• Children consuming follow-up formula fortified with Wellmune experienced a significant decrease in the incidence and duration of acute respiratory infection compared with those who were given an unfortified milk beverage.13
• Wellmune significantly reduced the drop in T cells and monocytes commonly seen after an intense exercise session.14
• There was a significant decrease in post-marathon upper respiratory tract infection symptomatic days among runners who supplemented with Wellmune.15
• Supplementation with Wellmune can reduce ragweed allergy symptoms and alleviate symptom severity.16

We also offer GanedenBC30, a spore-forming probiotic with benefits for immune health as well as digestive health. A study on seniors found daily consumption can increase beneficial groups of bacteria in the human gut and potentially increase production of anti-inflammatory cytokines.17


Nutritional Outlook: What are your hopes and concerns for the immune-health supplements category during this pandemic? 

LeDoux: My hope is that people retain hope and good common sense. While the recommendations from the CDC should be followed, good nutrition, including supplementation when warranted, good hydration, and practicing proper hygiene are also essential. The industry also needs to do its part in self-policing and testing as well as verifying purity, potency, and stability of the products that are being produced. This pandemic has given the industry the opportunity to work directly with healthcare professionals to help provide products as part of a comprehensive approach to healthcare. Doctors now recognize the value of various supplements in the treatment and care of their patients—it is our responsibility to make sure they have access to the finest products possible in a timely manner.

Parikh: We expect for the immune-health category to remain a high priority for consumers over the months and years to come. This is, in part, due to the current global situation but more broadly driven by growing awareness around immunity and how to support it. For manufacturers, it’s essential to continue to invest in innovation, propelled by a consumer-driven and robust scientific approach—this can enable a more diverse range of immune-health solutions designed to support specific consumer needs and values.

For supplement manufacturers, the challenge right now, and always, is to present options that are backed by robust science to help consumers choose the best option for them. 

Quilter: Demand for products with immune-health benefits is going to increase, and we hope leaders in the category will demonstrate moral responsibility. At this time of uncertainty, it’s more important than ever that our industry behaves responsibly and demonstrates a commitment to safety, efficacy, and scientific research.

Tower: My concern over adulteration of Sambucus nigra is amplified 400%, which is a direct reflection of the increase in sales at retail in the United States since the onset of COVID-19 in March. Last year, we witnessed increasing indications of adulteration—we tied this to elderberry’s steady rise in popularity the past few years based on clinical studies. Now, with the unprecedented COVID-19 fervor and subsequent 400% increase in demand for elderberry, there now exists a shortage of supply to satisfy this demand. Coupled by FDA temporarily suspending GMP inspections, we are encountering the perfect storm of adulteration of European black elderberry. We are seeing this problem increasing on the bulk ingredient supply-side and now migrating into consumer products at retail.

Raising awareness of the problem, continuously, is important, and applying proper fit-for-purpose analytical tools as means to identify and protect against this level of adulteration is critical.


1. Tiralongo E et al. “Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial.” Nutrients, vol. 8, no. 4 (2016): 182

2. Girodon F et al. “Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial.” Annals of Nutrition & Metabolism, vol. 41, no. 2 (1997): 98-107

3. Read SA et al. “The role of zinc in antiviral immunity.” Advanced Nutrition, vol. 10, no. 4 (2019): 696-710

4. Imran Bashir KM et al. “Clinical and Physiological Perspectives of β-Glucans: The Past, Present, and Future.” International Journal of Molecular Sciences, vol. 18 (2017): 1906

5. Geiler J et al. “N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus.” Biochemical Pharmacology, vol. 79, no. 3 (2010): 413-420

6. Evans M et al. “Effect of a Euglena gracilis Fermentate on Immune Function in Healthy, Active Adults: A Randomized, Double-Blind, Placebo-Controlled Trial” Nutrients, vol. 11, no. 12 (2019): 2926

7. Xu T et al. “Carnosine markedly ameliorates H9N2 swine influenza virus-induced acute lung injury.” Journal of General Virology, vol. 96, no. 10 (2015): 2939-2950

8. Udani JK et al. “Immunomodulatory Effects of ResistAid™: A Randomized, Double-Blind, Placebo-Controlled, Multidose Study.” Journal of the American College of Nutrition, vol. 32, no. 5 (2013):331-338

9. Udani JK et al. “Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers.” Nutrition Journal, vol. 9 (2010)

10. Riede L et al. “Larch arabinogalactan effects on reducing incidence of upper respiratory infections.” Current Medical Research and Opinion, vol. 29, no. 3 (2013)

11. Castro ED et al. “Beta‐1,3/1,6‐glucans and Immunity: State of the Art and Future Directions.” Molecular Nutrition and Food Research, Published ahead of print on March 29, 2020

12. Meng F “Baker’s Yeast Beta-Glucan Decreases Episodes of Common Childhood Illness in 1 to 4 Year Old Children during Cold Season in China.” Journal of Nutrition & Food Sciences, vol. 6, no. 4 (2016)

13. Fei L et al. “Follow-up Formula Consumption in 3- to 4-Year-Olds and Respiratory Infections: An RCT.” Pediatrics, vol 133, no. 6 (2014)

14. Carpenter KC et al. “Baker's yeast β-glucan supplementation increases monocytes and cytokines post-exercise: implications for infection risk?” British Journal of Nutrition, vol 109, no. 3 (2013): 478-486

15. McFarlin BK et al. “Baker's Yeast Beta Glucan Supplementation Increases Salivary IgA and Decreases Cold/Flu Symptomatic Days After Intense Exercise.” Journal of Dietary Supplements, vol. 10, no. 3 (2013): 171-183

16. Talbott SM et al. “Beta-Glucan supplementation, allergy symptoms, and qualityof life in self-described ragweed allergy sufferers.” Food Science & Nutrition, vol. 1, no. 1 (2012): 90-101

17. Nyangale EP et al. “Bacillus coagulans GBI-30, 6086 Modulates Faecalibacterium prausnitzii in Older Men and Women.” The Journal of Nutrition, vol. 145, no. 7: 1446-1452