Overall, immune health continues to be a strong segment of the nutraceuticals industry, said Nena Dockery, technical services manager, Stratum Nutrition, Carthage, MO. According to a Persistence Market Research (PMR) report, the immune health supplement market is expected to flourish at a compound annual growth rate (CAGR) of 7% globally. “In U.S. dollars, this translates from a market value of around $14 billion to $25 billion by 2025,” said Ms. Dockery. “According to the report, much of the growth can be attributed to an increasing consumer awareness regarding the benefits of dietary supplements, along with a rise in the population of middle age and older individuals.”
Senior citizens make up the largest segment of consumers of immune support supplements, she added. “They are more prone to chronic diseases, at least partially due to weakening immune systems; and they are living longer. Therefore, there are more years to live with chronic disease, and the need for supplements to help minimize secondary infections and health challenges.”
Citing information from GlobalData, Donald Cox, PhD, R&D director for Wellmune & GanedenBC30, Kerry Functional Ingredients & Actives, Mayfield Heights, OH, said immune health is the second most sought-after benefit, with 87% of consumers interested in purchasing products with immune health benefits. “However, at the same time, there remains significant untapped potential, since only 48% of consumers were actively buying immune-health products in 2015, although this was up from 40% in 2011.”
Consumer awareness continues to grow about the importance of immune health and the connection to the digestive system, noted Juliana Erickson, senior marketing manager, Lonza Consumer Health & Nutrition, “particularly as people are leading increasingly busy, more hectic lives, leading to increased stress and the need to maintain energy levels.”
There’s also increased realization that absenteeism due to the common cold is having a significant economic impact on businesses, she added. “Employee absences peak in the winter months, when seasonal colds and flu are prevalent. This past flu season was particularly severe, with 4.2 million workers in the U.S. having an illness-related work absence in January 2018.” With more health-conscious consumers, people are adopting preventive approaches to strengthen their immunity year-round. “In addition, consumers in this area are willing to pay more for natural, non-GMO, organic labeled products—a merging of two key trends in supplements right now,” she added.
According to a global survey conducted by the Natural Marketing Institute (NMI) and commissioned by Lonza Consumer Health & Nutrition (CHN), 36% of U.S. consumers are very likely to purchase supplements that support immune health. “Growing consumer demand, coupled with an increased availability of immune health supplements in the mainstream, has meant that supplement manufacturers are having to innovate to stand out in the marketplace,” said Ms. Erickson.
Immunity is influenced by factors like food choices, exposure to pollutants, quality of sleep, stress, and gut health, noted Shaheen Majeed, president worldwide, Sabinsa, East Windsor, NJ. “Immune function impacts quality of life, so consumers are proactively searching for products to help them achieve their health and wellness goals.
Immune health is a key concern across all demographic groups, including families with children, athletes and weekend warriors, aging populations, and those who have a stressful lifestyle, Mr. Majeed said.
“For the elderly, there is a desire to stay healthy and active as long as possible, even as the odds of illness increase. As people age, they derive a lower percentage of nutrients from the food they eat, so supplementation becomes even more important over time. Younger generations who grew up as dietary supplement use became ubiquitous tend to think of supplements as a way to stay healthy, because who has time to be sick? Athletes as well look to supplement for stronger immune systems, in addition to their endurance and recovery regimens. And as healthcare has become more expensive, the desire to avoid the related bills is highly motivating to all age groups.”
Younger consumers are starting to feel the effects of stress and a busy work and social life, and are looking for products that address these needs, said Ms. Erickson. “According to the NMI data, there has been 162% growth in the number of millennials turning to supplements to boost immunity between 2009 and 2017.”
It’s important that supplements offer convenient solutions that fit into busy lifestyles, she continued. “Delivery format is therefore a key consideration for consumers, with soft chews, nutritional bars, and gummies presenting a viable option for millennials to consume on-the-go.”
Kerry’s Dr. Cox agreed that immune health products are ideal for targeting diverse markets and specific demographic groups. “This means that, instead of casting a wide net, manufacturers can create successful products by strategically targeting specific consumer niches. For parents with young children, keeping them well is a top concern, because it’s not just the children’s health at stake, it’s that of the entire family. When parents buy products to help their children grow up healthy and well, they want to feel confident that those products will benefit their children’s health and be something their kids actually want to consume. As a result, a growing number of parents are looking to proactively support their children’s health through functional foods, beverages, and supplements with immune health benefits.”
Seniors represent an important consumer segment in need of products that support health and wellness, he added. The global population over 60 is expected to grow by 56% by 2030, according to United Nations estimates, and functional products with immune health benefits represent a prime opportunity.
For athletes that face harsh environmental factors, such as increased exposure to crowds and travel exhaustion, as well as physical and psychological stress, these pressures can negatively impact the immune system and overall physical health, leading to missed training days or workouts and adverse effects on performance goals. “This concern among athletes presents a clear opportunity for innovators to achieve marketplace differentiation with sports nutrition products that offer proven immune-health benefits,” said Dr. Cox.
Stress affects everyone, irrespective of age, he continued. “One of the most detrimental effects of stress includes the suppression of the immune system and therefore a greater risk of illnesses, such as upper respiratory tract infections. Science-backed ingredients that are clinically proven to support the immune system during times of stress can be incorporated into immune health products to provide a compelling offer addressing this concern.”
John Sauve, vice president of marketing, Artemis International, Fort Wayne, IN, said frequent travelers and parents represent high potential targets/users of immunity-based products. “The motivation to ‘not get sick’ is a different one than ‘to stay healthy,’ as is ‘preventing’ versus ‘curing’ something. ‘I don’t want my kids getting sick’ might be a top motivator in the prevention column, and prevention is the dietary supplement playing field,” he noted.
Delivering on Expectations
Consumers generally expect the products they purchase have scientific backing that confirms their efficacy, said Lonza’s Ms. Erickson. “Particularly with people now taking the time to scour packaging labels before making a decision, it is important that manufacturers consider ingredients that have been proven with clinical evidence to uphold the highest safety and quality standards.”
In addition, consumers are coming to expect solutions that address several health concerns at one time with a single dose, to both reduce “pill burden” and complement their busy lifestyles.
“Manufacturers are therefore keen to explore innovative delivery format options that will allow them to formulate multiple incompatible ingredients at once, such as Lonza’s DUOCAP capsule-in-capsule technology.”
Ultimately, immune-support products are successful if consumers experience results, said Sabinsa’s Mr. Majeed. “Formulators should keep in mind that the end user expects that the ingredients of immune-health products should have proven safety and efficacy supported by clinical evidence.”
Ms. Dockery agreed that consumers demand results. “They want products that work. They expect to generally feel better, to suffer fewer viruses and infections, and be less susceptible to some chronic conditions. Most consumers understand that immune health products are designed to support and help maintain the body’s own self-healing mechanisms.”
With immune health a top desired benefit, trust plays an important role in reaching consumers, said Dr. Cox. “Consumers need to feel confident that a product will help to keep them feeling at their best. That is why we are seeing a growing interest in manufacturers using branded ingredients backed by clinical research to help formulate products that support immune health. Branded ingredients give consumers a clear point of reference when they’re browsing shelves crammed with products claiming to offer health benefits. They also help consumers understand exactly what a product has been fortified with and allow manufacturers to showcase research and information specific to the ingredient. This builds confidence in a product and then, once a consumer’s trust is gained, it helps to keep them loyal to a product they know works for them.”
Tips & Trends
It’s important for companies to seek out ingredients that have been proven through clinical research, said Melanie Bush, PhD, chief science officer, Artemis International. “Standardized extracts, for example, offer consistent and concentrated levels of actives that could be tied to studied dosages. Product quality also depends on the type of processing techniques that are used. For example, harsh extraction processes like solvent extractions can strip the natural nutrient profile from botanical products, whereas the gentler technique of membrane extraction used to make Artemis’ line of elderberry extracts (Berryceuticals) maintains more of the matrix of the fruit—which can affect bioactivity.”
She also noted a surge in creative delivery options as opposed to generic capsules and tablets. “The industries of dietary supplements and functional foods seem to be intersecting, with fun, flavorful supplements in unique forms in increasingly high demand (e.g., popping crystals, lollipops, etc.).”
With new technology and polymer science, the capabilities of traditional dosage forms, including capsules, are evolving at a rapid rate, according to Lonza’s Ms. Erickson. “For instance, Lonza CHN is using these advancements to offer manufacturers more options for clean label solutions, to address evolving consumer preferences, and enhance product performance, such as improving bioavailability and masking taste and odor.”
To further improve the delivery and efficacy of immune health supplements, and support manufacturers in overcoming stability challenges, Lonza CHN has developed its DRcaps capsules, which protect acid-sensitive ingredients, like probiotics, and provide a delayed release to allow for complete dissolution in the intestine.
“When it comes to meeting consumer preferences for more natural immune health supplements, plant-based, clean-label dosage forms are a vital component to support natural claims on the product label,” she added. “Lonza CHN offers a wide range of vegetarian delivery systems, such as its Vcaps Plus capsules, consisting of only hydroxypropylmethyl cellulose (HPMC) and water. The plant-based capsules enable vegetarian and organic labeling in the U.S., as well as halal and kosher options. Similarly, pullulan—made from naturally fermented tapioca—is a popular base for plant-based capsules among manufacturers seeking natural alternatives for consumers.”
As in any formulation containing multiple ingredients, formulators should be familiar with the way ingredients function and know as much as possible about their mode of action, said Stratum’s Ms. Dockery. “Even whether the ingredients are best taken with food or on an empty stomach is an important consideration. Usually, it is best to select a small combination of ingredients that function well together and add them in research-supported, efficacious amounts.”
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 Dr. Cox. More than half (62%) of consumers stated that a product’s impact on their health and well-being is influential in purchase decisions, according to a 2018 GlobalData consumer survey. “So scientific research can help convey benefit messaging and can be a highly effective way to attract them.”
Research can also help validate claims and build credibility across different regulatory agencies, consumer groups, and healthcare professionals, he added. “Research validates how an ingredient works, its efficacy, and safety. A well-researched ingredient provides measurements for standardization, which is required for establishing appropriate serving size, consistency in manufacturing, stability, and shelf-life testing.”
When selecting functional ingredients to add to a product formulation, key questions to consider, according to Dr. Cox, include: how will the ingredients behave in a food matrix; will they impact the final finished product in terms of taste, texture, or shelf life; are there stability concerns; and can the ingredient withstand the production process without an impact on quality. “Make sure you work with a partner who can help with this aspect of the product development process,” he said.
As with all ingredients, vetting suppliers and fit-for-purpose testing for identity, potency, and purity are crucial to providing consumers with safe and effective products, said Mr. Majeed. “Seek out products backed by published research, because many of your customers will search for that. Ask about chain of custody for an ingredient, because the more it changes hands, the more opportunity for adulteration. Fair-trade farming policies matter to many consumers, so that’s a bonus the marketing department will appreciate.”
Overall, consumers are checking packaging for signs that products are clean label and non-GMO, said Ms. Erickson. In fact, NMI data show there has been 103% growth among consumers turning to non-GMO claims in dietary supplements over the past four years. These trends are placing further demands on manufacturers to formulate with clean label delivery systems.
“As awareness continues to grow about the importance of healthy aging and how people can maintain optimum wellness throughout all life stages, we expect there will be a greater emphasis on taking a preventative approach to immune support. Even for younger consumers, immune health will sit alongside exercise as a key priority, and they are likely to take further measures to ensure they remain as healthy as possible. To meet these evolving demands, we also expect more research and robust clinical trials on immune health to be carried out, to support the growing number of health claims.”
Ingredients & Research
Ongoing research continues to support the efficacy of various ingredients in supporting immunity, including elderberry extracts, noted Artemis’ Mr. Sauve. “Given the severity and longevity of the flu season in 2017-2018, elderberry products leap-frogged forward in awareness, interest, and consumer use, resulting in overall record year-to-year increases in sales.”
Dr. Bush also noted that the bad flu season brought a heightened urgency among consumers to seek out products designed to boost the immune system. “Elderberry has had a centuries-old history of being an immune support remedy, especially helpful against influenza. Modern research and recent clinical studies have corroborated these benefits.”
For example, a human clinical study published in Nutrients in 2016 showed a significant reduction in the duration and severity of symptoms in air travelers who consumed a black elderberry extract supplied to the U.S. by Artemis under the Berryceuticals brand name.
“Elderberry is particularly high in a class of compounds called flavonoids, which have been attributed to antioxidant activity, and in the case of elderberry, more specific immune support properties,” said Dr. Bush. “Mechanisms of action such as cytokine stimulation and even blocking viruses from entering cells are all being explored as ways that black elderberry flavonoids have such a profound impact on health.”
Stratum’s Ms. Dockery noted that many immune health products contain familiar vitamins and minerals, such as zinc and vitamins C and D. In the herbal category, echinacea and astragalus have remained well-recognized for their immune boosting abilities, she added.
Stratum Nutrition offers two ingredients that have significant immune support characteristics, she added. Ahiflower seed oil is a vegan source of omega-3 fatty acids, as well as the omega-6 fatty acid gamma-linolenic acid (GLA). “Omega-3 fatty acids are well known for their beneficial effects throughout the body, including support for the gut-mediated immune system,” she said. “Another major benefit of omega-3 fatty acids is their capacity to modulate autoimmunity through their influence in downregulating pro-inflammatory cytokine production and suppression of hyper-reactive T-cells (Isr Med Assoc J, 2002).”
Vegetarian source Ahiflower contains essential omega-3 fatty acids, as well as alpha-linolenic acid (ALA) and stearidonic acid (SDA). “SDA converts more readily in the body to EPA than other vegetarian sources, such as flaxseed (J Nutr Sci, 2016),” Ms. Dockery said.
Stratum also offers BLIS K12, an oral probiotic derived from Streptococcus salivarius K12, a strain found in people who exhibit strong upper respiratory health and are more resistant to common throat and middle-ear infections, she added. BLIS K12 has been broadly studied in humans, including children, and is supported by multiple published clinical trials.
The most recent study demonstrated its efficacy in non-susceptible children to decrease the incidence of bacterial and viral throat and middle-ear infections (Minerva Pediatrica, 2018). This was a retrospective study involving 133 children of both genders, who were administered BLIS K12 during two separate 90-day periods, one during the winter months (October to December) and one during the late spring (April to June).
“The results from this trial coincided with results from previously published trials revealing a reduction in the number of both streptococcal and non-streptococcal pharyngotonsillar infections of about 90% following BLIS K12 supplementation,” Ms. Dockery noted. “Also, a significant reduction of about 70% was observed for acute otitis media. The same study demonstrated that prophylaxis with K12 significantly reduced the use of both antibiotics and anti-pyretics/anti-inflammatory drugs by more than 80% and significantly decreased the number of school or work days lost by children or adults by about 85% and 75%, respectively.”
For many consumers, natural ingredients suggest they are safe and well-tolerated, said Lonza’s Ms. Erickson. For example, NMI data indicates that 37% of U.S. consumers look for supplements that are from “natural sources.”
Backed by a growing bank of evidence, Lonza CHN’s ResistAid ingredient is produced via a patented water-based extraction process from North American larch trees. The ingredient consists of arabinogalactan (soluble polysaccharide) and bioactive polyphenolic flavonoids. By modulating and supporting the appropriate immune response based on the immune stressor, the ingredient can help enhance antioxidant capacity and potentially improve immunity, according to Ms. Erickson.
“ResistAid 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 attributed to polyphenolic flavonoids, such as taxifolin and quercetin,” she noted.
In addition, Lonza CHN’s L-Optizinc zinc mono-L-methionine has been shown in clinical trials to support immune health thanks to its antioxidant properties compared to other forms of zinc. A 1:1 complex of zinc and methionine, the L-Optizinc brand provides excellent absorption and retention across a range of dietary supplements, food, and beverages, she added.
A proprietary baker’s yeast (beta 1,3/1,6 glucan), Wellmune, supplied by Kerry, is a natural immune health ingredient backed by more than a dozen clinical studies demonstrating its ability to help strengthen the immune system, said Dr. Cox. “Wellmune has regulatory approval in major markets around the world, including Generally Recognized As Safe (GRAS) status in the U.S. and novel food approval in Europe and China. Focused on immune health benefits, products containing Wellmune are available in more than 60 countries.”
The scientific understanding of Wellmune’s efficacy and mechanism of action across different life stages and need states is documented in published, peer-reviewed clinical research. One recent study on adults of average fitness levels showed improvement in immune health both during and after strenuous exercise when taking Wellmune (Frontiers in Physiology, 2017). Another study expanded the understanding of how Wellmune works within the body to support overall health (Inflammatory Bowel Diseases, 2017).
Kerry also offers GanedenBC30 (Bacillus coagulans GBI-30, 6086). “This is a well-researched, branded probiotic ingredient that has been shown to support digestive and immune health. In a controlled study, GanedenBC30 was shown to help increase immune response to a viral challenge (Postgraduate Medicine, 2009),” said Dr. Cox.
Chronic stress, a poor diet, and other factors can weaken the immune system, making one more susceptible to viral and bacterial attack, noted Mr. Majeed. “Ayurvedic herbs have been used for centuries to help support immunity and to relieve some of the unpleasant symptoms associated with cold and flu viruses. They, along with antioxidants such as vitamin C and zinc, may be helpful in reducing the severity and duration of illness.”
Ingredients derived from herbs, probiotics, enzymes, vitamins, and minerals are all seeing success in the immune health marketplace, he continued. Sabinsa offers a range of innovative, science supported ingredients such as LactoSpore, Curcumin C3 Complex, Selenium SeLECT, Shagandha Ashwagandha extract USP 2.5%, Boswellin, DigeZyme, Andrographis paniculata extract, black cumin extract, and tulsi extract.
Shelf stable LactoSpore is a lactic-acid producing microbial preparation from Lactobacillus sporogenes (Bacillus coagulans MTCC 5856). “On activation in the acidic environment of the stomach, LactoSpore germinates and proliferates in the intestine, producing the favored L (+) form of lactic acid and effectively preventing the growth of harmful pathogens,” said Mr. Majeed.
The immunomodulatory effects of LactoSpore have been evaluated in combination with an aqueous extract of cinnamon (Cinnulin PF). The combination resulted in significant stimulation of phagocytic activity, thus indicating its role in immunomodulation (Am. J. Immunol, 2013).
The role of Curcumin C3 Complex in providing immunomodulatory benefits has been evaluated through its activity against auto-immune disorders such as oral lichen planus (OLP), a chronic autoimmune, mucocutaneous inflammatory disorder associated with the development of oral mucosal lesions that affects 1-2% of the population.
A total of 20 subjects with OLP scores in the range of 3-8 were included in a randomized, double-blind, placebo-controlled study with 6,000 mg/day dosage of Curcumin C3 Complex for 2 weeks. “In the results, the curcuminoids group showed a greater reduction in the symptoms associated with OLP as measured by Numerical Rating Scale (NRS), Erythema, Ulceration, and Modified Oral Mucositis Index (MOMI) score (Phytomedicine, 2012),” said Mr. Majeed.
Selenium SeLECT or L (+)-Selenomethionine is a stereospecific natural form of bioavailable selenium. Selenium, an essential micronutrient often not found in adequate amounts in the food supply, has been reported to play an important role in immune function. “Present in the form of a constituent amino acid, there is universal agreement that proper nutritional status of selenium is an important component of good heath,” he added.