Supplements to support immune health are in high demand. Research from Euromonitor International showed products with “immune system” positioning accounted for 11.3% market share of supplements globally and were valued at close to US$2 billion total in 2015, with a compound annual growth rate (CAGR) of 10.7% from 2011 to 2015.

“To be successful, it will be important for food, beverage and supplement manufacturers to understand how their products fit within consumers’ ever-evolving definition of health and wellness,” said Megan De Stefano, global probiotics marketing leader, DuPont Nutrition & Health. “There are clearly strong trends in favor of natural immune health and rising sales in this category. However, there is still a gap between interest in functional foods and beverages and actual purchasing behavior.”

De Stefano referenced a 2013 U.S. consumer study from Datamonitor showing 88 percent of consumers were interested in purchasing functional foods and beverages to “improve immune system,” but only 40% were actively purchasing in this area.

This trend is echoed in Kemin’s Attitude and Usage Survey of U.S. supplement users. The survey showed 70% of U.S. supplement users stated they plan to take immune support supplements in the future, but only 27% of those surveyed stated they were currently taking immune support supplements.

Science is critical to engaging consumers interested in immune support solutions.

“Immune health shoppers are thoughtful and engaged, and therefore more likely to make an effort to evaluate the scientific evidence supporting the ingredients available to them,” said Donald Cox, Ph.D., research and development director, Wellmune and GanedenBC30, Kerry. Citing research from Nielsen, he added, “With 59% of consumers stating a product’s health and wellness benefits are influential in purchase decisions, research can help easily convey benefit messaging and can be a highly effective way to attract them.”

The gut’s role in immune health is gaining attention by scientists and consumers alike.

“The discovery of the role that the GI [gastrointestinal] tract plays in lifestyle, disease, immunity, inflammation, cognitive function, diabetes and so much more has advanced health and medicine, and helped to change the way we look at disease,” said Susan Hewlings, Ph.D., R.D., chief science officer, IgY Nutrition. “We no longer look at diseases as disconnected separate conditions; instead, there is awareness in the medical community and now the mainstream that these diseases are connected and need to be addressed as such.” Addressing GI tract health and potential dysbiosis—imbalance of the gut microbiota—is the place to start in improving overall health, she said, pointing to pre- and probiotics to help correct dysbiosis.¹

Immunoglobulin Y (IgY) antibodies found in chicken eggs (as IgY Max™, from IgY Nutrition) help change the composition and activity of the gut microbiome. These antibodies work by significantly reducing harmful bacterial adhesion and growth in the GI tract,² helping to minimize inflammation by decreasing cytokines³ and high-sensitivity C-reactive protein (hs-CRP), which increases in the blood with inflammation.

Antigen-specific IgY products have been shown to be effective in promoting gut function and immunity in humans,⁴ as well as in reducing the side effects of dysbiosis.⁵ IgY Max is a polyvalent, antigen-specific IgY product targeting 26 of the most common human-relevant pathogens.

Native lactoferrin from cow’s milk (as Proferrin®, from Ingredia) has been shown via internal, unpublished research to support gut health by renewing epithelial cells (growth and differentiation), an important barrier against infections. Additionally, internal research showed the ingredient’s ability to reduce the release of TNF-alpha (tumor necrosis factor), a pro-inflammatory marker.

Still buzzing with interest from consumers are probiotics, which can benefit immunity via impact on the gut microbiome.

“Over the past 15 to 20 years, research has shown the effects of certain probiotics at different levels,” said Bérengère Feuz, marketing manager, Lallemand Health Solutions:

Probiotics act as a first line of defense, Feuz explained. “By enhancing the natural gut microbiota, probiotics can help keep pathogens at bay through several actions, such as competitive exclusion.” Feuz cited Lallemand’s Lactobacillus helveticus Rosell®-52’s ability to bind to the attachment sites of pathogenic bacteria, such as enteropathogenic Escherichia coli on intestinal epithelial cells, as an example.

Probiotics have also been shown to improve the intestinal barrier function and enhance epithelium permeability and integrity, or enhance mucus production, Feuz added.

Recent research expanded the potential of probiotics to impact immunity. According to a 2017 publication, certain probiotic strains influenced both innate and acquired immune response at the gene expression level.⁶ The study used human expression microarray chips in an in vitro intestinal epithelial cell model to determine the impact of the strains on toll-like receptor 3 (TLR3)-mediated inflammation.

“These mechanistic data are important, but they need to be validated by clinical studies,” Feuz said.

Looking to individual strains, a clinical study investigated the benefits of individual probiotic strains on the occurrence of common infections (cold and flu) in stressed subjects more prone to infections and concluded a beneficial effect of the Bifidobacterium bifidum R0071 strain (reduction of the number of sick days).⁷  

Cazzola et al. showed children’s diet supplementation with a synbiotic formula (Bifidobacterium bifidum Rosell®-71, Bifidobacterium infantis Rosell®-33, Lactobacillus helveticus Rosell-52 and fructooligosaccharides [FOS]) for three months decreased the risk of occurrence of common infections by 25% vs. placebo. Other studies confirmed this synbiotic’s effects on children’s immunity, in particular through positive effect on immunosurveillance, like increased IgA expression in children with low IgA levels.^8,9

An internal, unpublished study showed benefits of another strain (Lactobacillus helveticus LAFTI® L10, from Lallemand) to support the immune response in stressed subjects. Three hundred students who normally suffer from at least two colds a year were included in the 10-week study. The study showed a significant reduction of the number of systemic symptoms by 12.2% in the probiotic group; moreover, the symptoms were less severe with the probiotic. As a result, the probiotic significantly reduced the need for medication: the total number of days with medication intake (mainly analgesics) was reduced by 23%. The same strain also recently showed benefits for training athletes in a randomized study.¹⁰

Results of a randomized, double-blind, placebo-controlled trial sought to evaluate the impact of probiotic strain Lactobacillus coryniformis K8 CECT5711 (from Biosearch Life) on immune response to the influenza vaccine and to assess effects on symptoms related to respiratory infections in 98 nursing home residents over age 65.¹¹ The administration of the probiotic during the two weeks prior to an influenza vaccination significantly increased the percentage of responders to the vaccine. The probiotic treatment also reduced the incidence of symptoms related to respiratory infections suffered during the five months after probiotic treatment, and resulted in 86% lower consumption of analgesics in the elderly group who received the probiotic strain.

In a double-blind study, a proprietary blend of probiotics (HOWARU® Protect Kids, from DuPont Nutrition & Health) supported respiratory health with symptom duration shortened from 6.5 to 3.5 days, a decrease in incidences of respiratory symptoms, an 80% reduction in antibiotic use and a reduction in the number of sick days by almost half, compared to placebo.¹²

In seniors, daily intake of Bifidobacterium lactis HN019™ (as HOWARU® Protect Senior, from DuPont Nutrition & Health) by healthy, elderly adults showed B. lactis HN019 enhanced cellular immune activity.¹³ All doses of the probiotic increased Bifidobacterium population significantly during intervention, when compared to pre-intervention levels. In the same study, potentially harmful bacteria (enterobacteria) decreased significantly in high- and medium-dose groups.

A combination of Bifidobacterium lactis Bi-07® and Lactobacillus acidophilus NCFM® (as HOWARU® Protect Sport, from DuPont Nutrition & Health) consumed daily over a five-month period was shown to reduce the risk of an upper respiratory illness and delay time to respiratory tract illness compared to placebo in physically active adults. The study showed significantly extended exercise duration and significantly improved training duration.¹⁴

A probiotic strain of Streptococcus salivarius (as BLIS K12™, from Stratum Nutrition), a species that is common in the mouths of healthy individuals, supports health through several ways, one of which is immune modulation, said Nena Dockery, technical services manager at Stratum Nutrition. One study demonstrated S. salivarius K12’s ability to stimulate an anti-inflammatory response that protected the oral cavity from inflammation and apoptosis induced by pathogens.¹⁵ In another study, K12 was shown to promote the production of interferon gamma (IFN-γ), an immune system protein (cytokine) that is known to contribute to non-specific immunity against many intracellular bacteria and viruses.¹⁶

A probiotic strain of Bacillus coagulans (as Bacillus coagulans GBI-30, 6086, from GanedenBC30®) offers immune-boosting properties. In a controlled study of 10 participants, 30 days of supplementation with the probiotic strain increased T cell production of TNF-alpha in participants after exposure to adenovirus and influenza A.¹⁷ Building on these results, researchers evaluated the effect of Ganeden BC30 on immunological marker levels following viral exposure, and found a statistically significant difference in interleukin-8 (IL-8) levels after influenza A exposure, along with IFN-y levels after adenovirus exposure.¹⁸

“In recent years, dead microbes have been also shown to exhibit beneficial effects that are equivalent to, or even greater than, live microbes,” said Yoshitaka Hirose, Ph.D., group manager, House Wellness Foods Corp.

Heat-killed Lactobacillus plantarum L-137 (HK L-137), an immunobiotic strain isolated from fermented food, induces IL-12 or type I interferon (IFN), which lead to a T helper (Th) 1 type immune response and subsequent antiallergic, antitumor or antiviral effects in mouse models, Hirose explained.^19,20,21 Further, oral intake of HK L-137 increased Th1-related immune functions, health-related quality of life, production of type 1 IFN and decreased the incidence of upper respiratory tract infection (URTI) in healthy subjects.^22,23,24

Absorbed by specialized immune tissue in the gut, a proprietary baker’s yeast beta 1,3/1,6 glucan (as Wellmune® from Kerry) binds to neutrophils, enabling them to move more quickly to recognize and kill foreign challenges. These effects are documented in several studies in a range of populations. In a clinical study of children in a daycare setting, Wellmune decreased episodes of common childhood illnesses and symptoms of illness, with 62% of children taking the ingredient reported as having “good” health versus 15 percent of children who did not consume Wellmune.²⁵

In high-stress populations, Wellmune significantly reduced URTI symptoms in a clinical study of medical students;²⁶ significantly decreased URTI symptoms while increasing vigor by 26% and improving well-being by 8.3% in stressed women;²⁷ reduced the number of individuals reporting URTI symptoms in stressed adults by 71% while decreasing fatigue and increasing vigor;²⁸ and reduced URTI symptoms while improving overall physical health in a two-week trial of Montana’s Wildland Firefighters.²⁹

Supporting athletes, Wellmune supplementation by marathon runners led to a 40 percent reduction in URTI symptoms,³⁰ while Wellmune decreased risk of immune system suppression in both recreational and elite athletes.^31,32 It also increased vigor and mental clarity while reducing fatigue, tension, confusion and URTI symptoms in marathon runners.³³

Beta-glucan from algae shares a common backbone of 1,3 linkages, “which act as immunomodulators because the human body recognizes it as ‘non-self’ or foreign,” explained Emily Pankow Fritz, Ph.D., technical services manager, Active Wellness, and Chris Sadewasser, technical service associate, Human Nutrition and Health, Kemin. “Non-self” substances are referred to as pathogen-associated molecular patterns (PAMPs) detected by specialized surface receptors of immune cells.^34,35,36 Through binding and engulfing beta-glucan, these specialized cell surface receptors induce signaling cascades that prime immune cells, Pankow Fritz and Sadewasser said.^37,38,39,40

Unpublished, in vitro studies of ingredients derived from Euglena gracilis fermentate powder (BetaVia Complete [containing more than 50% algae beta-glucan] and BetaVia Pure [containing more than 95% algae beta-glucan], from Kemin) show similarities to the activity of yeast-derived, immune-support ingredients. “BetaVia Pure and BetaVia Complete are recognized by cell surface receptors of key immune cells including macrophages and dendritic cells,” Pankow Fritz and Sadewasser said. “After being recognized by immune cells, BetaVia ingredients are phagocytosed and absorbed, resulting in cytokine and chemokine signaling that primes the immune system.” Research supporting the efficacy of beta glucan, available along with the in vitro data, supports that the beta (1,3) glucan in BetaVia Complete and BetaVia Pure can act as immunomodulators, Pankow Fritz and Sadewasser said.

Sulforaphane, the active component of broccoli sprout powder, increased the activity of Phase 2 enzymes that inactivate harmful chemicals and reinforce the body’s natural responses to oxidative stress.⁴¹ BroccoPhane® broccoli sprout powder from Bioriginal is standardized to contain a minimum of 4000 ppm of sulforaphane.

Glucosinolates, an antioxidant found in mature broccoli plants, enhanced the activity of liver and intestinal enzymes essential to the detoxification of potentially harmful chemicals and byproducts.⁴² Bioriginal’s BroccoSinolate 2.0® is standardized to 4% glucosinolates.

Glutathione is an antioxidant found naturally in nearly every cell of the body. Kyowa Hakko’s Setria® glutathione, made from a patented fermentation process, supports proper function of white blood cells, including T cell, stimulates the natural ability of some immune cells and can regenerate other antioxidants, such as vitamins C and E.⁴³

Supplementation with the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) can change composition of immune cells, said Mal Evans, Ph.D., scientific director at KGK Science, “which in turn can have effects on phagocytosis, T-cell signaling and antigen presentation capability.”⁴⁴

Beyond specialty nutrients, maintaining adequate levels of vitamins and minerals is critical to keeping the immune system strong.

“Sometimes, people don’t remember that regular vitamins and minerals can really help their immunity,” said Karen Dhanraj, technical marketing and sales manager, Lallemand Bio-Ingredients. (Stauber is the exclusive U.S. distributor of Lallemand’s nutraceutical line.) “For example, vitamin D can modulate the innate and adaptive immune systems, and cells of the immune system have been shown to respond to vitamin D.”^45,46

Other critical nutrients include selenium, which exerts effects on inflammation and immune responses;^47,48 vitamins B6 and B12, which have been shown to positively affect white blood cell counts;^49,50 copper, which is essential against immune defense, especially against bacterial infections;⁵¹ and zinc. Zinc-deficient patients have been shown to have severe immune dysfunctions, Dhanraj explained.⁵²