Some functional foods and dietary supplements are aimed at clear and obvious targets: Bone and joint strength? Sure, who wants to ache? Brain support? Of course, is there anyone out there not fearful of dementia? Cardiovascular fitness? Yes, no one wants to suffer or die unexpectedly.

Immune health may be subtle by comparison. With some exceptions, most people have at least moderate immune response mechanisms to keep illness at bay, or lessen its effects. When they do contract specific ailments—ranging from frequent colds to more serious conditions—they want immediate assistance in defending against that attacker.

A Healthy Market?
Immune support continues to be one of the stronger segments in the natural health marketplace. Demand for some immune system products has declined slightly in the past year or two. For example, Euromonitor reported that the growth rate of functional foods and beverages intended to provide immune support slipped a few points in 2015, but still managed to surpass $50 million for the year. Immune supplement sales, meanwhile, topped $1.5 billion, according to SPINS research.

Most experts agreed the category is primed for growth in the foreseeable future. Factors include “the aging population, increasing stresses on the immune system, and poor dietary and lifestyle habits” of so many Americans, said Nena Dockery, technical services manager for Stratum Nutrition, Carthage, MO.

Donald Cox, PhD, research director for Kerry’s Wellmune brand, is similarly bullish on immune health ingredients. Citing Euromonitor’s 2016 global survey, he said overall functional food and beverage sales are predicted to increase at a compound annual growth rate (CAGR) of 3.6% through 2021. Gilbia Portela, marketing manager at NutraQ, Oslo, Norway, added that immune support supplements had a CAGR of 9.5% from 2010 to 2015.

“What is driving this growth?” Mr. Cox asked. “It wasn’t too long ago that consumers of all ages and need-states were taking a reactive, quick-fix to their health and wellness. Today the story has evolved, and people are moving to a more proactive, preventive approach. This progressive alternative to health and wellness is also bringing long-term immune health to the forefront of consumer concerns.”

Michael Bush, president of Mayfield Heights, OH-based Ganeden, said, “We have already seen an increase in consumer demand for supported health benefits through the fortification of everyday foods and beverages as shoppers want to receive health benefits in products that are already part of their daily routine and fit easily into their lifestyle/dietary preferences.

Mr. Bush, who is also executive board president of the International Probiotics Association, cited one survey showing that “healthy consumers are at least 30% more willing to purchase a food or beverage if it claims immune support.”

Roots of Immune Issues
While the causes of immunological problems are varied, there is some agreement that chronic inflammation and stress-related factors often play a role. “Chronic inflammation can arise from environmental factors like toxins or lack of physical activity, and from dietary factors like high levels of sugar or toxins,” said Tim Hammond, vice president of sales and marketing, Bergstrom Nutrition, Vancouver, WA. “Stress itself, whether physical or psychological, has an immuno-suppressing effect and is ubiquitous in the fast-paced American culture.”

Everyone endures some level of stress, noted Ms. Portela. “Job pressures, money problems, family responsibilities, relationship problems, and health concerns are common sources of worry we can encounter along the way.” Stress has become so commonplace, she added, that the World Health Organization (WHO) regards it as the “health epidemic of the 21st century.”

“My philosophy regarding health is finding balance—being in harmony. When we fall out of harmony, we get sick,” said Jeff Chilton, president of Nammex, a Canada-based raw material supplier of mushroom extract powders. “I don’t relate to metaphors that view illness as a battle. I believe we’re part of a larger organism, and we’re all adapting to circumstance.

Sometimes something touches us and affects us in a way that causes stress and illness.” Because mushrooms are adaptogens, he believes they can work in the background to keep people in balance.

Anurag Pande, PhD, vice president of scientific affairs at Sabinsa, East Windsor, NJ, identified the following as “some of the best-known extracts to have immune health/adaptogenic effect: curcuminoids, Indian gooseberry fruits, ashwagandha, beta-glucan, and resveratrol. These [substances] can improve immune health and support resistance to common ailments, stress, fatigue, cold and cough, etc.” The mineral selenium also has immune support properties, he added.

Ingredients A to Z
There is no shortage of materials and ingredients that may bolster human immune systems. Here, in alphabetical order, are some to consider, as well as research that backs them up.

Adaptogens: These are natural substances believed to help the body adapt to stress and to exert a normalizing effect on bodily processes. Examples include ginseng, medicinal mushrooms, goji, ginkgo, ashwagandha, blueberries, ginger garlic, and more.

Amla (Indian gooseberry): This is one of several immune-supporting substances available from Sabinsa. Mr. Pande described the company’s Saberry as a proprietary standardized extract of fresh fruits of amla, which is regarded as an adaptogen that potentially increases the body’s resistance to stress, trauma, anxiety, and fatigue.

Antioxidants: Vitamin C and the mineral zinc are so commonplace they might almost be overlooked when filling out a nutraceutical immune support roster. Yet the National Center for Biotechnology Information (NCBI), a unit of the National Institutes of Health, said vitamin C was “found to improve components of the human immune system such as anti-microbial and natural killer cell activities, lymphocyte proliferation, chemotaxis, and delayed-type hypersensitivity.” Zinc deficiency, the researchers reported, has been shown to impair cellular mediators of innate immunity such as phagocytosis, natural killer cell activity, and the generation of oxidative burst.

Noting that resveratrol is a natural antioxidant found in grapes, Sabinsa said its Resvenox is trademarked trans-resveratrol extracted from the roots of Polygonum cuspidatum. Mr. Pande said Resvenox complements the antioxidant activity of other antioxidants and helps to fight against one of the more important stressors today—oxidative stress.

The Sabinsa executive also called attention to Selenium SeLECT, also called L-selenomethionine. “When L-selenomethionine is incorporated in proteins,” he said, “the resultant selenoproteins are used for transport and storage of selenium and function as an antioxidant.” This makes them an essential component in immune support.

Ashwagandha (Withania somnifera): Yet another immune support entry from Sabinsa, ashwagandha—also known as Indian ginseng or winter cherry—is the source for an extract standardized to withanolides, the active compounds responsible for its adaptogenic activity. Mr. Pande cited a study in which ashwagandha was found to improve the levels of the body’s intrinsic antioxidant system, including superoxide dismutase (SOD), catalase and glutathione peroxidase. (Nutrition and Cancer, 2002).

Beta-glucan: Defined by the NCBI as “naturally occurring polysaccharides,” beta-glucans are found in the cell walls of bacteria, fungi, yeasts, algae, lichens, and plants, such as oats and barley. According to Kerry’s Mr. Cox, Wellmune, the company’s “proprietary yeast beta 1,3/1,6 glucan has regulatory approval in major markets around the world, including GRAS status in the U.S. and novel food approval in Europe and China. Once Wellmune has been swallowed, immune cells in the gastrointestinal tract take it up and transport it to immune organs throughout the body. While in the immune organs, immune cells (macrophages) digest Wellmune into smaller fragments. The fragments bind to neutrophils—the most abundant immune cells in the body—via complement receptor 3 (CR3). Primed by Wellmune, neutrophils more quickly recognize and kill foreign challenges,” said Mr. Cox.

Nutramunity Beta-Glucan (NBG), NutraQ’s immune support ingredient, is a beta-1,3/1,6-glucan, which is a natural component of the inner cell wall of baker’s yeast (Saccharomyces cerevisiae). The company’s Ms. Portela said, “Positive effects of yeast beta-glucan on immune function in humans have been demonstrated in several randomized clinical trials [Samuelsen 2014]. Studies with physically and psychologically stressed subjects have shown that yeast beta-glucan can decrease susceptibility to upper respiratory symptoms [Talbott 2009, Talbott 2012], counteracting the negative effects of these types of stress on the immune system.

This suggests that even though yeast beta-glucan does not have a psychoactive effect, the improvement in physical well-being has a positive impact on mood. Yeast beta-glucan also increases the levels of Immunoglobulin A (IgA), an antibody that plays a critical role in infection defense in mucosal surfaces of the body, the main entry route for pathogens [Lehne 2005, McFarlin 2013].”

Moreover, she added, “Nutramunity food grade is easy to incorporate into a broad range of food and beverage products, such as convenience foods, baked goods and dairy products, and, as well, into medical foods, food for special dietary uses, and dietary supplements.”

Sabinsa’s beta-1,3 glucan, according to Mr. Pande, is “notable for its ability to modulate the immune system via stimulating, for example, anti-microbial activity by binding to receptors on macrophages and other white blood cells and activating them.”

Curcumin: Sabinsa’s Curcumin C3 Complex is a turmeric extract “known for its antioxidant, immunomodulatory, anti-inflammatory activities,” according to Mr. Pande. As a potent immunomodulator, it can affect B cells, T cells, macrophages, neutrophils and dendritic cells.

Echinacea: While most often looked to for its purported ability to shorten the duration of cold and flu symptoms, echinacea may also help boost the immune system and help the body fight infections. According to the University of Maryland Medical Center (UMMC), some herbalists recommend the herb to treat urinary tract infections, vaginal yeast (candida) infections, ear infections (also known as otitis media), athlete’s foot, sinusitis, hay fever (also called allergic rhinitis), as well as slow-healing wounds. Preliminary studies in the lab suggest echinacea may help inhibit colon tumors when combined with cichoric acid, according to the UMMC website.

Lysine: Eugene, OR-based Quantum Health has built a supplement line around the amino acid lysine, including such items as: Super Lysine + Ointment; Super Lip Care + Invisible Bandage; Super Lysine + Coldstick, a lip balm with SPF21; Super Lysine + Tablets; Super Lysine + Liquid extract; and SuperImmune +, a vegetarian version of Super Lysine + Tablets.

Other Quantum Health products include TheraZinc, which comes in lozenges or throat spray and delivers a clinical dose of zinc gluconate to boost the immune system, and Elderberry, which is available in standardized extract capsules, lozenges, liquid extract, or syrup. With regard to delivery formats, David Shaw, the company’s president and founder, said, “There is no one-size-fits-all. The best delivery systems should optimize both bioavailability and stability, but at the same time satisfy consumer demand for ease of use.” That being said, he suggested baby boomers are becoming “less enamored with taking handfuls of pills and moving more toward liquids and powders.

Methylsulfonylmethane (MSM): Bergstrom Nutrition produces OptiMSM, a branded form of MSM that benefits the immune system by lowering chronic inflammation through reducing levels of inflammatory cytokines and supporting a healthy inflammatory response. “MSM also supports glutathione levels, an internal antioxidant that is fundamental for immune function, and prevents immunosuppression caused by exhaustive and strenuous activity,” said Mr. Hammond.

Mushrooms: In addition to four trade-named products—Rei-Gen (Reishi), Shi-Gen (Shiitake), Rei-Shi-Gen (Reishi/Shiitake mix), Cordy-Gen (Bionectria ochroleuca)—Gourmet Mushrooms, Inc., of Sebastopol, CA, produces and markets more than 30 species of mushroom mycelial biomass under the Mycobiotic label. All are produced in California and are certified organic and kosher, according to David Law, president and CEO.

Noting that “healing power resides in our DNA,” Mr. Law said the mechanism of action for these products “appears to involve the promotion of better intercellular communications by influencing cytokine expressions in the cells of our bodies. Intercellular communication is vital to stem cell development (hemopoiesis),” he added.

While several hundred mushrooms have been shown in research to have immune-supporting actions, Mark Kaylor, a consultant to East Rutherford, NJ-based Mushroom Wisdom, insisted that Maitake D-Fraction, an extract taken from Maitake musrooms, “has demonstrated the strongest immune activity, even at doses much lower than other mushroom extracts.” Noting “literally thousands of studies” supporting the value of medicinal mushrooms, Mr. Kaylor singled out the “promising work showing the anti-apoptotic activity of Maitake D-Fraction, [which] was performed independently by Dr. Gabriela Balogh from Argentina and confirmed by researchers in Portugal.”

Mr. Chilton, of Nammex, described his company as “a raw material supplier of 100% pure mushroom extract powders to manufacturers and businesses selling to the retail market.” The complete line includes reishi, cordyceps, chaga, and lion’s mane, all of which have been validated in thousands of scientific papers published over the past 40 years, he said.

Nevertheless, Mr. Chilton paid special attention to a particular test being utilized during the past three years—the Megazyme beta-glucan test to evaluate mushroom and mycelium products. This test was recently peer-reviewed by AOAC International, the organization that codifies analytical standards. According to Mr. Chilton, “The importance of this research is monumental. Unless you have the known active compounds in your product, all other claims of product effectiveness are moot.”

Probiotics: “We see probiotics continuing to grow as an immune ingredient,” said Ganeden’s Mr. Bush. Noting that his company is best known for its patented GanedenBC30 (Bacillus coagulans GBI-30, 6086), he said, “Because of its stability, the strain is used in more than 750 food, beverage, sports nutrition, and companion animal products around the world. The efficacy of the strain is backed by 25 published and peer-reviewed studies showing digestive support, enhanced protein utilization, and, most important, immune support.”

Also, slated for availability at the end of this summer, Ganeden will be launching another patented ingredient: Staimune (inactivated Bacillus coagulans GBI-30, 6086). According to Mr. Bush, the new entry is intended to support immune health at cost-effective inclusion levels that don’t alter flavor or texture profiles. “We anticipate Staimune to be an industry-changing development, and extremely beneficial for use in products where traditional probiotics can’t survive (such as shelf-stable beverages),” he added.

Kearny, NJ-based Pharmachem Laboratories is the exclusive North American distributor for a line of probiotics from Italy-based Probiotical, including the Microbac Microencapsulation technology, which protects strains during manufacturing of finished products, resulting in lower overages needed, reduced costs, and increased shelf life. Ralf Jäger, PhD, the firm’s scientific adviser, said, “Probiotics have been shown to reduce the number, duration, and severity of upper respiratory tract infections (URTI) and gastrointestinal (GI) distress in the general population and in at-risk subgroups such as the elderly or children attending care centers.

In addition, probiotics have been shown to improve immune health in athletes.” The reason for this effectiveness, he said, is that “70% of your immune system is located in your gut, and preventing dysbiosis—an imbalance in your gut flora caused by too few beneficial bacteria and an overgrowth of bad bacteria, yeast, and/or parasites—is crucial for maintaining immune health.”

Stratum Nutrition’s Ms. Dockery described her company’s BLIS K12 ingredient as “an immune-health-promoting probiotic that—unlike most probiotics—exerts its beneficial effects in the oral cavity instead of the gastrointestinal tract.” According to Ms. Dockery, BLIS K12 promotes oral and upper respiratory health in two important ways. The first is competitive inhibition. “If beneficial bacteria are well-colonized in the oral cavity, there isn’t space for undesirable bacteria to colonize and cause harm,” she explained. “In addition, the K12 strain produces compounds called bacteriocins that target specific bacteria, including Streptococcus pyogenes, and puncture their cell walls, effectively destroying the undesirable strains.”

Pycnogenol: Derived from French maritime pine bark found along the coast of southwest France, Pycnogenol is a trademarked natural plant extract that has four key properties: it’s a potent antioxidant, acts as a natural anti-inflammatory, selectively binds to collagen and elastin, and it aids in production of nitric oxide (NO) for better circulation.

Marketed by Horphag Research, which has world headquarters in Geneva, Switzerland, and a U.S. office in Hoboken, NJ, Pycnogenol is supported by copious research, said Sébastien Bornet, the company’s vice president of global sales and marketing. He cited a 2014 study, “Improvement of common cold with Pycnogenol: a winter registry study” (Panminerva Medica), which found that the pine bark extract reduced common cold symptoms—sore throat, sneezing, runny nose, cough, temperature and headache—along with the severity and duration of the cold.

Unfolding Immunity Most experts continue to view the future of the immune ingredients category with great optimism, but they don’t all agree on what will drive this growth. “We anticipate continued increases in new immune health products—mainly in the form of functional foods and beverages with ingredients that may support immune health,” said Ganeden’s Mike Bush. Mark Kaylor, a consultant with Mushroom Wisdom, sees dangers to health as a prime motivating force. “Considering that our immune systems are probably under greater threat today than ever before, the immune category as a whole is likely to stay strong and even continue growing,” he said. Pharmachem Laboratories’ Ralf Jäger followed a more benign train of thought. He credited growing consumer awareness, scientific advances, better understanding of the mechanism of action, and further clinical validation for spurring sales of probiotics for immune support. Also, he pointed out, “Athletes are a new, and strong growing consumer group within the immune health category.” Two other companies—Quantum Health and Stratum Nutrition—also promote probiotics as a significant contributor to immune health. Quantum’s David Shaw said, “I believe that immune products that are condition-specific, that help manage targeted health issues, are driving the growth of this segment. I expect this trend to continue. For example, probiotics, which not long ago were used to improve overall digestive health, are now targeting skin health, prenatal care, oral hygiene, and even help common cold prevention.” Meanwhile, Stratum Nutrition’s Nena Dockery predicted two years of sustained strong growth, with products for immune health expected to remain in the top 10 of dietary supplements. “Probiotics in general are very strong,” she said, and it is “likely that their benefits will continue to expand beyond the intestinal tract.” The key to it all, suggested David Law, of Gourmet Mushrooms, is to think of immune health as the basis for virtually all healthcare. “We [should] take care of our bodies before any life-threatening ailments have the opportunity to evolve over time,” he said. He cited a Johns Hopkins Kimmel Cancer Center study published in March 2017 in which the scientists found that only 5% of cancer development could be attributed to heredity, while 29% comes from lifestyle choices and 65% from random DNA mutation. “It is the ability of our bodies to help DNA reparation or elimination of mutated cells (apoptosis) that will help us lead a long and healthy life,” Mr. Law concluded.

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Alan Richman, former editor/associate publisher of Whole Foods Magazine, is now a full-time, New Jersey-based freelance journalist focusing on the health and nutrition industry. A frequent contributor to Nutraceuticals World, he can be reached at arkr@comcast.net.