Natural immune support comes of age.

The Participants Are:

• Hank Cheatham, Vice President, Daiwa Health Development, Gardena, CA, www.dhdmed.com and www.dhdusa.net

• Christopher Detzel, PhD, Director of Research & Development, Entera Health, Ankeny, IA, www.enterahealth.com

• Juliana Erickson, Senior Marketing Manager, Consumer Health & Nutrition, Lonza, Basel, Switzerland, www.lonza.com

• Tim Hammond, Vice President of Marketing and Sales, Bergstrom Nutrition, Vancouver, WA, bergstromnutrition.com

• Julie Impérato, Marketing Manager, Nexira, Rouen Cedex, France, www.nexira.com

• Rick Kozlenko, PhD, DPM, MPH, Science Advisor, GCI Nutrients, Burlingame, CA, https://gcinutrients.com

• Tom Laaman, PhD, Director of Sales, Specialty Enzymes & Probiotics, Chino, CA, specialtyenzymes.com

• Dan Lifton, President, Maypro Ventures, Purchase, NY, maypro.com

• Stephen Lukawski, Head Consultant and Partner, Fruit d’Or Nutraceuticals, Villeroy, Quebec City, Canada, www.crannaturelle.ca

• Sam Michini, Vice President of Marketing and Strategy, Deerland Probiotics & Enzymes, Kennesaw, GA, www.deerland.com

• Bryan See, Business Development Manager, ExcelVite, Perak, Malaysia, www.excelvite.com

• Guy Woodman, General Manager, EuromedUSA, Bridgeville, PA, www.euromedusa.com

The immune-boosting category, a few decades ago, was centered on the popularity of only a handful of botanicals and nutrients, such as echinacea, goldenseal, elderberry and vitamin C.

Now Echicacea purpurea is endangered in Florida and Michigan, wild goldenseal is endangered around the world and elderberry needs to be carefully harvested in order to not impact a species dependent on the plant, the valley longhorn elderberry beetle.

In the meantime, germ anxiety is bestride the land, with hand sanitizers and surface disinfectants seemingly everywhere.

In this context, then, what immune-boosting ingredients and formulas are the natural products industry equipped to offer? Also, what are the considerations and market dynamics that manufacturers need to keep in mind?

NIE: The immune category has grown by leaps and bounds. In what ways has the immune category changed and in what ways has it stayed the same?

Lifton: There is still a vital place for immune-boosting staples, like vitamin C and zinc, in addition to sustainable cultivation of botanicals, like echinacea.

Just like the 1990s—or even way back with patent remedies in the 1890s—consumers still don’t want to be dragged down by a cold, if they can avoid it, or to have it drag out, if they do get it. So in those ways, it’s the same.

Where it has changed is in the understanding of the multidirectional and adaptogenic properties of some of these specially developed formulations, namely the development and isolation of powerful science-backed immune boosters from mushrooms, fruit polyphenols, probiotics and other sources.

Detzel: I believe we are in an exciting time for immune health. There is a growing understanding of how often, and significantly, we can impact our own immunity with small lifestyle changes.

I think immune health has always been top of mind for consumers, but the general consumer is beginning to understand there are more options for long-term immune support versus reactionary treatments when the body becomes unbalanced and sickness arises.

The increased understanding of gut health and how taking care of inflammation and gastrointestinal distress can impact the immune system is providing increased credibility for oral supplements to improve immune health.

Impérato: Immune health is still an important category on the market. In fact, 87 percent of consumers are interested in products with immune health benefits. Traditionally, consumers use immune products to fight infections. Today, they also want to fight external challenges faced by the body, such as stress or air pollution.

Laaman: The paradigm has changed dramatically with the growing popularity of probiotics. More and more condition-specific research on probiotics is being conducted, much of which relates directly to immune health. The relationship between gut health and immune function is now much more clearly established. Research clearly shows probiotics impact gut health, and also demonstrate a positive impact on immune function, and overall health and well-being.

Kozlenko: The market still offers many conventional remedies, such as echinacea, vitamin C and goldenseal. But now there’s a newer impetus in applying technologies to traditional remedies, for example, such as botanicals from ayurveda.

Cheatham: The immune category for natural products has been focused on cold/flu, allergies and other common maladies. Popular dietary supplements included vitamin C and traditional herbs such as echinacea, goldenseal, elderberry and astragalus.

This product category has grown significantly with the introduction of “nutraceuticals,” a term coined in 1989.

A wide range of nutraceuticals have been shown to [play] crucial roles in immune status and susceptibility to certain disease states.

Scientific research has expanded to measure nutraceutical ingredients as providing immune-enhancing properties to help the body deal with a host diseases and inflammatory conditions well beyond simple herbal remedies.

See: Immunity is one of the top three reasons why consumers take supplements, according to a 2016 Harvard Opinion Research Program study.

The immune category is now trending toward personalized nutrition, where companies provide specialized offerings to individuals based on a better understanding of their health status and predispositions.

These customized formulas are designed to help consumers achieve optimum wellness, which may include strengthened immunity.

Lukawski: Today, the immune health category is more robust as new consumers are recognizing the benefits of natural botanicals, particularly black elderberry.

New delivery systems such as gummies and capsules are available giving consumers more choices.

Consumers have a better selection of immune health products than ever before.

NIE: What is the state of the market for natural ingredients and products for immune support?

Michini: If you look on the shelves of any mass-market supermarket or warehouse store, you now see a bevy of beverages devoted to immune wellness, many of those featuring probiotics. Standing in the grocery store checkout line, you’re likely to see items like probiotic shots, some of which are simply called “immunity.”

And what this illustrates is how powerful the lure is of anything that can help boost immunity: people know that their immune systems are attacked daily and every little bit—beyond pills—helps.

Millennials want healthier grab-and-go options, and are willing to pay a premium for them.

Erickson: Natural and naturally derived ingredients are currently leading innovation in the immune health category. For example, our market research data indicates that 38 percent of U.S. dietary supplement users look for supplements that are from “natural sources,” a growth of 59 percent in the last 10 years.

Woodman: The U.S. market for immune health products is robust due to the prevalence of viral and bacterial pathogens we are exposed to in our daily lives. For example, the most recent report from the American Botanical Council (ABC) noted sales for echinacea-containing supplements were up 11.5 percent in 2017 compared to 2016. Immune supplements containing echinacea are some of the most popular supplements for immune health.

Detzel: Within the past couple of years, immune health has cemented its position as one of the top three reasons adults took supplements.

With the increased mainstream acceptance of immune and gut health concepts, there is a premium being placed on science-backed ingredients. Consumers expect immune support supplements to be backed by clinical evidence of efficacy.

I believe over the next several years the immune health category will continue to grow as the benefits of decreasing inflammation and improving immune function are shown to have long-term health benefits and support healthy aging.

Impérato: There is a growing awareness and interest in combing digestive and immune health benefits. Consumers are more aware of the link between gut and immunity. After the skin, our intestine is the main natural barrier against external factors. Products combining gut health and immune claims are well understood by consumers.

Cheatham: The market for natural ingredients and especially for immune support products is growing. The demand for immune products is increasing because of Baby Boomers and the aging population seeking preventative methods to extend life span, to maintain a healthy quality of life and to avoid potentially deadly diseases. Skyrocketing health care costs and toxic side effects from prescription drugs are other significant factors for consumers to feel the need to pursue natural remedies to enhance their immune response.

NIE: Which consumer segments/demographics are most concerned with immune health?

Erickson: Immune health is a key concern across all demographic groups. However, younger segments are also starting to feel the effects of stress and a busy work and social life, and are looking for products that address these needs. According to our consumer research data, there has been 162 percent growth in the number of Millennials turning to supplements to boost immunity between 2009 and 2017.

For younger segments in particular, it is important that supplements address their growing health concerns while offering a convenient solution that fits into busy lifestyles. Delivery format is therefore a key consideration for consumers—with soft chews, nutritional bars and gummies presenting viable alternative options for millennials to consume on-the-go.

Detzel: Each segment of the population can relate to improving immunity; whether it be school-aged children fighting the common cold, to individuals combating the immune suppressive effects of their stressful lives, to reducing low-level inflammation in an elderly population to support healthy aging; each of these groups understand the importance of a well-functioning immune system for maintaining a healthy, active lifestyle.

Lukawski: We believe Millennials are the greatest potential market for immune health. Millennials focus on prevention and are looking to make decisions based on their active lifestyles. They look for products that deliver quality as promised. They will stop purchasing if the products do not work.

NIE: Broadly speaking, what are the latest sorts of developments in natural ingredients and products for immunity?

Impérato: Probiotics have a strong presence on the market and they are followed by prebiotics which can be considered as the most growing ingredient on the market.

Koslenko: Of course, new ingredients that have effects on immunity are exciting, but perhaps the most important developments, from my perspective, are more behind the curtain—[harnessing research to uncover] cellular pathways and mechanisms of action in immunity.

A new AI [artificial intelligence] patented system of rapid research recovery relevant to a specific topic of research inquiry is now available through a company called CytoSolve. With key algorithms, it can rapidly, cost-effectively, provide statistical relevance, billions of pieces of information, research, biochemical, pharmacological and physiological principles, into a statistically relevant foundation to back your ingredient, drug or question.

This tool [could] have an immense [impact] in better solidifying our understanding of many aspects of immunity.”

NIE: Now that we are in the Age of the Microbiome, what impact has this had on research and development for immune-supportive ingredients and products?

Woodman: The human microbiome has an important immune modulating effect. Digestive tract microbiota alterations elicit effects on our immune system. This can include reduced tolerance to food antigens, intestinal inflammation and enhanced gut permeability. These metabolic influences are known to influence autoimmune disorders and health conditions like prediabetes.

Probiotics are an important addition to digestive health. Euromed developed Cynamed, which combines artichoke phenolic compounds with long-chain inulin for microbiome health.

The ingredient increased Bifidobacterium and Lactobacillus amount and also increased short chained organic acids an indicator of microbiome activity. The experiment was conducted using a testing model called simulator of the human intestinal microbial ecosystem (SHIME).

Lifton: It seems that it is finally understood that Hippocrates wasn’t too far off the mark, 2,500 years ago, when he famously said that “All diseases begin in the gut.”

While every single disease may not originate there, it is now recognized that health and microbial balance are at the very core of health.

Research has been looking at ways to protect probiotics, and keep them viable, from store shelf all the way through their gastrointestinal odyssey.

Michini: There is a great deal of research in numerous aspects of the microbiome—its composition, what affects it (promotes homeostasis or causes imbalances), and how it impacts human health, wellness [deterioration] and disease.

We are understanding more clearly that no system works alone. It is influenced by others and, in some cases, the relationships are strong. Such is the case between the GI [gastrointestinal] tract and the immune system.

The intestines contain more immune cells than the entire rest of the human body. In many cases, immune dysfunction begins with a “failure to communicate” in the human gut. Considering 80 percent of the immune system is in the digestive tract, maintaining a healthy gut is a major focal point in the pursuit to support overall health and immunity.

When the digestive system is functioning properly, it serves as a barrier to bacteria, viruses and pathogens. Poor digestion leaves the body and the immune system with a lack of nutritional factors that support immune function and the function of the entire body.

Detzel: The microbiome is hot right now and there is so much hype around the microbiome that even the general consumer understands there is massive potential to improve health through microbiome therapeutics.

I think the potential of the microbiome has everyone excited and there is a lot of R&D on how products affect the microbiome happening throughout the industry.

Entera Health is invested heavily in this area of research to understand the interplay of gut mucosal inflammation, composition of the microbiome and health outcomes.

The biggest challenge for microbiome research will be to show that the microbiome is driving health outcomes rather than the microbiome changes as health improves.

The ability to show the microbiome controls health will lead to some very interesting and easy to understand label claims for the average consumer.”

NIE: There was a time when manufacturers were experimenting with sublingual pump spray delivery of immune-boosting ingredients. What are the most interesting delivery forms for immune-support products these days?

Laaman: The main consideration, aside from consumer preferences, is product stability. Product stability is crucial whether you are discussing an herbal supplement, probiotic, digestive enzymes or other ingredients. It is important to understand that active ingredients are often not as stable in liquid form as they are in solid or powder forms.

In addition, processing treatments such as heat and pressure can also impact stability of key ingredients.

Even where and how products are stored have an impact on the stability of some ingredients.

Some ingredients are more stable than others in broader settings. For example, bacillus probiotics are much more stable than other strains, able to withstand greater heat and acid, and even able to hold up in liquids.”

Michini: Stick packs offer a tasty and convenient option for those looking to give their immune system an effective boost each day. These formulations can be powders that are poured into bottled water for a drink mix, or even directly poured onto the tongue for an even quicker experience. Flavor options for these types of delivery systems are endless, opening up a plethora of ways to delight the consumer.

Again, probiotic “shot beverages” are hot. Just a gulp or two and you’ve received probiotics that help boost immune (and related digestive) function, and there’s no full beverage can or bottle commitment.

We’re also seeing success with chocolate as a delivery system. Dark chocolate already has antioxidant benefits. Chocolate and probiotics really do go well together. This is because of the beneficial bacteria that live toward the end of the digestive tract. This bacteria ferments both the antioxidants, and the fiber in cocoa. This fermentation creates anti-inflammatory compounds.

Combining certain probiotics with chocolate multiplies the benefits of chocolate. This is because these probiotics work best at the end of the digestive tract. They crowd out bad bacteria and replace them with good bacteria. More friendly bacteria aids the cocoa fermentation process.

Cheatham: While the traditional pill and capsule formats remains the most popular, new products embracing alternative formats are starting to emerge within the industry. These delivery methods include gummies and soft chews, melt-in-mouth granules and liquid formats, such as sublingual pump sprays. Liquid and sublingual use is more widespread in Europe and other international markets than in the U.S.

Detzel: We have seen a rise [in the popularity] of sachets and stick packs; customers cater to the busy life of consumers and make products available without having to carry a large jug everywhere. The hottest trend we have seen are gummy applications. Gummy product forms provide a unique combination of tastes great as well as high consumer compliance for daily consumption.

NIE: Specifically, what ingredient or group of ingredients are you most excited about, and why?

Lifton: I’m excited about many of Maypro’s proprietary branded ingredients, including L-92, a patented food ingredient that has been studied in both adults and children.

Made from Lactobacillus acidophilus of human origin, L-92 is leading the innovation in the field of “zombie probiotics”—intentionally heat-sterilized dead bacteria which have been shown to down-regulate an overactive immune system more effectively than their “live” original.

Erickson: Natural and naturally derived ingredients are the most exciting segment for immune health right now. Our ResistAid ingredient is part of this category—it’s produced via a proprietary water-based extraction process from North American larch trees, and consists of arabinogalactan (soluble polysaccharide).

See: I am excited about our ingredients—EVTene, which is a natural mixed-carotene complex comprising alpha-carotene, beta-carotene and small amount of gamma-carotene and lycopene.

EVTene is extracted from non-GMO (genetically modified organism), sustainable Malaysian palm oil and its mixed-carotene composition is similar to that of carrots.

Lukawski: I am excited about cranberry—beyond UTI (urinary tract infection) applications—and wild blueberry for gut health, immune health, oral care and cognitive health.

I am also excited about elderberry syrup from Norm’s Farms, without the added sugars and calories. Too many elderberry syrup products contain high levels of sugars and calories, which defeats all the benefits that elderberry syrup can offer.

Organic elderberry juice powder from INS Farms is the first-ever organic elderberry juice powder that is 100 percent water soluble and carrier free. No more maltodextrin or MGOH2 [magnesium hydroxide].

NIE: What kind of research on immune health ingredients are manufacturers and suppliers most interested in?

Cheatham: Manufacturers and suppliers are interested in immune health ingredients that are supported by strong scientific research and human clinical trials.

The most credible research will measure improvement in quantitative biomarkers such as elevations in leukocytes and reduction in tumor sizes. Such scientific research is stronger than the conclusions reached solely on self-assessment studies.

Manufacturers are also interested in immune modulating ingredients, such as rice bran arabinoxylan compound (RBAC), which will not overstimulate the immune system or possibly lead to an autoimmune disorder.

Detzel: Manufacturers are most interested in anything that can be shown to impact gut health and support the beauty-from-within and healthy aging concepts that are dominating media outlets. These include CBD, functional foods and even products like mushroom extracts and polyphenols. Those compounds which affect the gut-brain axis, and the microbiome, are the targets our collaborators are currently aiming to better understand.

See: There is interest in research related to either boosting the immune system or reducing the duration or severity of symptoms.

Woodman: Manufacturers are seeking published human efficacy studies that support structure-function health claims in their marketing materials. Within that category, research supporting a benefit for microbiome health are of particular interest.

Laaman: Formulators are most interested in research that is sophisticated and detailed enough to answer fundamental scientific questions.

Unfortunately, some of the larger companies that sponsor scientific research are only interested in making a claim about their individual ingredient and therefore their research is very shallow. They are not conducting rigorous research that answers fundamental questions and moves science forward to benefit people and society on a deeper, less profit-motivated level.

NIE: Summarize the research behind your main product or ingredient.

Impérato: Nexira promotes its new branded ingredient Immunell combining a natural yeast extract and prebiotic acacia fiber.

Manufactured in France, Immunell is a natural and safe ingredient derived from a yeast (Saccharomyces cerevisiae) containing nucleotides. With a high purity rate, higher than 60 percent of nucleotides, Immunell is a unique source of the four semi-essential nucleotides (adenine, cytosine, guanine and uracil) and formulated with prebiotic acacia fiber.

Naturally occurring in food and breast milk and found in all living cells of the body, nucleotides are semi-essential molecules supporting organ growth, immune system and intestinal function.

For infant nutrition, nucleotides have demonstrated an enhancement of innate and humoral immunity, an improvement of transit and a support of growth. For sports nutrition, nucleotides have demonstrated a restoration of immune markers impairments induced by a strenuous workout. For people with IBS [irritable bowel syndrome], nucleotides improve discomfort above baseline and placebo.

Michini: DE111 has been shown via clinical work to provide three clear benefits for human health.

Regarding bowel regularity, one study showed that those taking DE111 (1 billion CFU) increased proportion of normal stools by 10 percent, while those in the placebo group decreased.

Regarding microflora and digestive health, one clinical study showed that those taking DE111 experienced increases in levels of B. subtilis and Bifidobacterium, while also lowering levels of unwanted bacteria such as E. coli.

Regarding sports nutrition, one study of female collegiate athletes found that DE111 improved body composition, specifically reduction of body fat percentage, and better ability to deadlift more weight than women in the placebo group. A corresponding study of collegiate male athletes showed that those taking DE111 exhibited better tissue recovery than the placebo group. Also, the DE111 group had a statistically significant decrease in the pro-inflammatory tumor necrosis factor alpha.

Cheatham: There are over 40 research studies and clinical trial investigating Rice Bran Arabinoxylan Compound (RBAC). It is confirmed that RBAC can more than triple natural killer (NK) cell function and increase the activity and the count of B-cells, T-cells, helper-cells, macrophage and cytokines, when needed. RBAC is also shown in scientific study to be a true immune modulator and will not overstimulate the immune system.

Hammond: Bergstrom Nutrition’s OptiMSM, a branded form of methylsulfonylmethane (MSM), benefits the immune system by lowering chronic inflammation through modulating levels of cytokines and supporting a healthy inflammatory response. MSM also supports levels of glutathione, an antioxidant that plays a fundamental role in immune function, and prevents immunosuppression caused by exhaustive and strenuous activity.

Detzel: Our company has been in the animal nutrition business for 30-plus years. Over this time, we have conducted extensive research resulting in over 300 peer-review publications on the use of spray-dried plasma in maintaining animal health and nutrition. The publications have shown plasma can lead to improvements in immune function, growth rate, joint mobility and gastrointestinal function across many different species.

Given our success in animal health and nutrition, we developed a concentrated plasma protein product for human health applications.

ImmunoLin is a bovine plasma derived product delivering a concentrated source of bioactive immunoglobulin G (IgG) to the gastrointestinal tract. The manufacturing process has been developed to allow the IgG to retain the native biological activity.

Our most recent clinical study in metabolic endotoxemia, a condition where a high-calorie, high-fat Western diet leads to increased gut permeability and blood LPS levels. Results of this study demonstrated improved gut barrier function after supplementation for 30 days at doses of 1-2 g/day. We are super excited about these results demonstrating ImmunoLin is binding and neutralizing gut LPS and improving barrier function.

Woodman: Euromed’s former parent firm Madaus AG introduced the world’s first standardized Echinacea purpurea supplement Echinacin in 1935. Research on Echinacin has created a strong foundation for the echinacea category—one of the more recent studies noted that Echinacin reduces the likelihood of upper respiratory reinfection with viruses. Euromed obtains its E. purpurea from the same cultivation source in Germany as that used for Echinacin.

Laaman: Our ProbioSEB CSC3 is a unique addition to shelf-stable probiotics products. We combine three probiotic bacilli with notable clinical benefits into one highly stable product. The bacilli form endospores that protect them from harsh environments. ProbioSEB CSC3 contains B. coagulans, B. subtilis and B. clausii. Research shows each of the three species improve digestive health, modulate healthy immune function and numerous other benefits.

B. clausii has been shown promising results in promoting healthy gut flora during and after antibiotic use. B. coagulans has been shown to promote recovery from diarrhea and constipation. Bottom line, the bacilli in ProbioSEB CSC3 do everything Lactobacillus and Bifidobacterium can do, but are more useful to manufacturers, suppliers and consumers alike because they are shelf stable at room temperature, and demonstrate greater heat, liquid and acid stability to boot.

Erickson: Backed by a growing body of scientific evidence, Lonza’s ResistAid proprietary ingredient is a popular choice for supporting immunity in nutraceutical applications.

By modulating and supporting the appropriate immune response based on the immune stressor, the ingredient can help enhance antioxidant capacity and potentially improve immunity. Lonza’s ResistAid ingredient has three mechanisms of action: indirect action via gut microbiota-dependent pathways, direct action on the immune system via the gut-associated lymphoid tissue (GALT), and antioxidant action.

In addition, Lonza’s L-Optizinc zinc mono-L-methionine sulphate is another ingredient that has been shown in clinical trials to support immune health, thanks to its superior antioxidant properties compared to other forms of zinc.

Lifton: AHCC is a unique, cultured mushroom mycelia extract that’s rich in alpha glucans. It’s manufactured through a patented, extended liquid culturing process that makes its active components different from other mushroom extract products.

While most medicinal mushroom extracts have a molecular weight of more than 200,000 daltons, the presence of acylated alpha glucans with a molecular weight of around 5,000 daltons is considered one of the attributes of AHCC that provides it with superior absorption and strong clinical efficacy.

Supported by over 30 human clinical studies, AHCC is used in over 1,000 clinics across the globe. Studies on AHCC have been conducted at some of the most respected research institutions in the world. It is unique in that it modifies both the innate and adaptive immune response.

Human and animal research has shown that AHCC enhances immunity by increasing cytokine production, including IFN-γ and TNF-α; natural killer (NK) cell activity by 200 to 300 percent; macrophage populations by up to 100 percent; plus T cell numbers and activity. NIE

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