By Mike Montemarano, Associate Editor10.08.21
Market dynamics within the immune health space are continuing to evolve as consumers shift from single-ingredient, headline-fueled trends into more comprehensive and personalized solutions. Variability in dosage technology, ingredient combinations, delivery methods, and research acumen of both leading and emerging ingredients continue to keep competition in the space robust.
Supporting the immune system has been a key entry point for the lion’s share of new supplement users of late. Many products have been re-formulated or re-marketed to include immune health credentials in order to respond to consumer needs and demands of the moment. This gives companies with unique immune health ingredients plenty of new entry points to feature science-backed ingredients that can be taken every day.
“Today’s consumers face a constant onslaught on their immune systems from the stresses of modern life, work, diet, and other lifestyle factors,” said Maria Stanieich, marketing manager for Kyowa Hakko. “According to a CRN Consumer Insights Report, immune health and overall wellness contribute to the top five reasons consumers are taking dietary supplements. The trend of consuming immune health ingredients is also shifting to year-round support as individuals look to proactively support the immune system.”
Competition within the category has become robust, presenting unique challenges. Supply chains for certain ingredients continue to be stressed. Product trends have shifted from more conventional, seasonal immune support to everyday regimens.
Everyday Support
COVID-19 has sparked consumer interest for products that can be taken every day to support base immune function. For the sake of convenience, people are also searching for products that offer additional health benefits.
For this reason, the segment has seen a great deal of products combine common immune health ingredients with broad-acting nutrients tied to adjacent categories, such as healthy aging, sports nutrition, mood and sleep, and more.
A wide net of health problems including digestive issues, stress, high intake of processed foods, and more can have cascading effects on healthy immune function. Personalized ingredient combinations that can attenuate unique external stressors on the immune system are having their day among cutting-edge immune product developers.
“Immunity has moved to a year-round category with a focus on mental, mood, and stress support, and an overall general health focus,” Stanieich said. While there is certainly room to innovate with lesser-known ingredients, she said it can be important to include high-familiarity ingredients alongside more novel elements of a formula.
“As individuals are pursuing active lifestyles, we are seeing a trend of greater focus on general and everyday health, maintaining an active lifestyle, and self-care than ever before,” Stanieich added. “Recent innovations incorporating novel ingredients have been a trend, but there is also a need for the more familiar and essential ingredients for everyday and overall health maintenance.”
A key to developing immune health ingredients in today’s environment is being able to substantiate that both innate and adaptive immune responses are stimulated positively, in order to appeal to those looking for both quick-response and long-term support, said John Deaton, vice president of science and technology for Deerland Probiotics and Enzymes.
He noted that a new clinical study on the company’s probiotic strain, Bacillus subtilis DE111, found that in 44 healthy adults, the strain displayed immunomodulatory and anti-inflammatory effects on several T cell subsets. In summary, the authors noted that supplementing with B. subtilis DE111 “modulates the host immune system through anti-inflammatory and suppressive action on both innate and adaptive cell types (Freedman, Int J Mol. Sci, 2021),” Deaton said.
Multifunctional product formulations are increasingly popular as well, he added. “As we are seeing more multi-functional beverages and supplements, such as immune-plus-antioxidant greens powders, the opportunities lie in combining ingredients that support immune function, such as probiotics, as well as digestive function, such as enzymes,” Deaton said. “In fact, the dual goal of supporting both immunity and digestion is a growth opportunity. For example, our new MuniSpore Bacillus clausii CS109 targets antioxidant activity starting in the gut. Research has shown that B. clausii CS109 as MuniSpore crowds out bacterial pathogens and maintains healthy gut flora, supports the normal immune reaction of intestinal cells, supports the body’s natural repair system through antioxidant activity, and maintains population in the GI tract through resporulation.”
Ongoing concerns about COVID-19, combined with a return to the classroom for students, children’s immune health is also rising as a point of concern to tackle in new products, Deaton said, noting that DE111 has been shown in two separate studies on young children to confer immune health benefits. One study (Slivnik, Journal of Probiotics and Health, 2020) found that DE111 substantially reduced incidence and/or duration of GI and respiratory infections in 81 children between ages 2 and 6 who attended daycare, with a 7.1% incidence in the treatment group versus 20.5% in the placebo group. Researchers also saw a reduction of GI infection duration with 8 days in the DE111 group compared to 28 days in the placebo group.
A second study, Deaton noted, concluded that 8 weeks of supplementation with DE111 modulated the gut microbiomes of 91 children between the ages of 2 and 6, including increased alpha-diversity, and changes to Firmicutes/Bacteroidetes ratios, suggestive of healthy gut function compared to placebo (Paytuvi-Gallart, Beneficial Microbes, 2020).
As a year-round concern, one possible game-changing endpoint for contemporary research could be the Scoring of Immunological Vigor (SIV) assessment, which Annie Eng, CEO of HP Ingredients, said was used to assess the efficacy of the company’s Adapticort Eurycoma longifolia extract. “In the study, 83 volunteers took either 200 mg of Adapticort or placebo per day, and were assessed using SIV, immunological grade, immunological age, and other immune parameters. At week 4, SIV and immunological grade were significantly higher in the [supplementation] group than those in the placebo group […] The results suggest that consuming 200 mg Adapticort per day may enhance comprehensive immunity in middle-aged adults.”
The Gut-Immune Axis
Even prior to the pandemic, the “biotics” space has been a promising research frontier not just for immune health, but for additional health benefits to metabolism, digestion, energy, mood, sleep, and more—all common issues that consumers may be struggling with today.
“Kyowa Hakko is among the first to provide the latest breakthrough approach in the emerging category of paraprobiotics [non-viable microbial cells or crude cell extracts],” said Stanieich.
Having recently launched Immuse, a proprietary Lactococcus lactis strain, the company has supported the ingredient with 11 human clinical trials, including nine efficacy and two safety studies, over long-term periods. The paraprobiotic has been shown to activate pDCs (plasmacytoid dendritic cells), which direct other immune cells to take action, which is a key differentiator that is not observed in other lactic acid bacterial strains.
“This new ingredient provides a novel approach to immune health product formulation as a standalone or in combination with other ingredients in dietary supplements and foods,” Stanieich said.
While immunomodulation may be an advanced concept to grasp, many consumers today have an awareness of the basic beneficial relationships between humans and gut bacteria. Nonetheless, making greater headway in substantiating products that link gut and immune health is much-needed for discerning shoppers.
“Postbiotics like EpiCor are a prime example,” said Cashtyn Lovan, marketing manager for Cargill. “While consumer awareness of the category is still in its early stages, postbiotics offer increased stability and consistency as compared to the more familiar probiotics; and some postbiotics, like EpiCor, are backed by science. Over a dozen published studies, including eight human clinical trials, support EpiCor’s health benefits related to both digestive and immune support.”
Ingredients that can enhance the activity of certain nutrients, and contribute to whether or not an individual “responds” to nutritional interventions, can lead the way to better immune product efficacy, noted Melanie Bush, vice president of science and research for Artemis International.
“A symbiotic is not merely a marketing term, it is a biologically active product,” Deaton said. “To achieve a symbiotic effect, a probiotic must be paired with a prebiotic with proven benefits to that strain.” PreforPro, for example, when combined with the probiotic strain B. lactis BL04, was shown in a recent clinical trial to modulate gut bacteria more than the probiotic strain alone after a 4 week supplementation period, Deaton noted (Grubb et al, Nutrients, 2020).
Additionally, “a 2019 study found that PreforPro supports gut microbiota proliferation and reduces other biochemical markers, including a reduction in the circulating pro-inflammatory cytokine IL-4, which is correlated with immune response,” Deaton noted (Febre et al, Nutrients, 2019).
The role that many nutrients have in gut function is relatively under-investigated as it relates to immune health. But many nutraceutical developers believe there will be a huge window of opportunity in the future for a wider array of ingredients when it comes to the gut-immune axis.
“One of the developments in this field is the concept that some nutrients in foods or supplements do not need to be absorbed in the upper gastrointestinal tract to have a beneficial health effect, but rather can interact with the gut or gut lining to cause a benefit,” said Justin Green, director of scientific affairs for Cargill’s health technologies business. “A phytonutrient that is not normally absorbed may still be important in nutrition or supplementation if it is converted into a compound that is absorbed and can have a beneficial effect. The impact of some food or supplements on the gut microbiota can also affect our immune system; after all, a large proportion of our immune system is in the gastrointestinal tract. This interaction can have effects on both the body’s overall immune response, including inflammation, and digestive health.”
EpiCor, Cargill’s postbiotic immune health ingredient, contains high concentrations of metabolites sourced from baker’s yeast. These metabolites and functional compounds are preserved after the yeast itself is killed off, resulting in a supplement which is considered a whole food since nothing is purified or extracted, Green said. “Lastly, over a dozen published studies, including multiple human clinical trials, show that EpiCor postbiotic supports the gut microbiome, immune health, and nasal comfort. All of that combined makes Epicor a postbiotic through ISAPP’s definition (Collabo, Endo et al., Gastroenterol Hepatol, 2021).”
The role that “dead” microbes play can also be highly comparable to the influence that live probiotics can have when it comes to this gut-immune axis, Green said, through a process that is essentially fermentation in order to derive short-chain fatty acids, polysaccharides, microbial cell fractions, functional proteins, and more even if the microbes are no longer spore-forming. “This has big ramifications on product development because these postbiotics are inherently easier to keep stable during processing and storage as they do not need to be kept alive.”
Three areas of research will advance the level at which microbiome-targeting supplements become personalized, Green said. “The first is the continuing determination of what a healthy microbiome consists of, both in terms of diversity and actual microorganism strains, and conversely, what non-beneficial microorganisms in a microbiome could cause health concerns. The second developing technology is the measurement of one’s personal microbiome.
Much like knowing one’s own DNA makeup is commonplace now, getting a clear picture of the microorganism population in one’s own gut will be an important aspect toward the goal of maintaining good health. The third emerging area of research is identifying nutritional interventions, such as specific postbiotics, that will push what one currently has for their microbiome to what one needs to better maintain the health conditions one is personally concerned with.”
Holistic Herbs
Herbal and botanical ingredients such as elderberry, which can offer not just immune health benefits but other wide-ranging functions as well, will continue to appeal to the holistic sensibilities of today’s immune health consumer, according to Bush. “There are multiple angles of support within the immune category that consumers are actively seeking: ingredients that will arm their immune system to function optimally; ingredients that can aid in recovery by alleviating symptoms; and ingredients that will help keep their body healthy in the long-term. The grand-slam ingredient is one that is able to help in all of these areas.”
Part of the reason for European black elderberry’s rise in popularity and presence across immune products, she continued, “is the scientific substantiation showing its ability to reduce the duration and severity of cold/flu symptoms as well as modulate the body’s immune responses. Additionally, the prebiotic benefits that berry flavonoids have been linked to can help improve the balance of microflora in the gut, thereby improving the overall state of digestive health and related immune health. This makes elderberry a multi-functional anti-viral/immune-supporting ingredient that consumers can get behind.”
Key elderberry studies Artemis noted include a large-scale human clinical study (Tiralongo et al., Nutrients, 2016) which found that the company’s ElderCraft extract could reduce the duration and severity of cold/flu symptoms in 312 long-haul flight passengers.
“Elderberry had already been ‘on the map’ for extensive historical use and preliminary studies that showed its immune-supporting potential, but this study took it to the next level,” Bush said. “A subsequent meta-analysis (Hawkins et al.) evaluating the entirety of the clinical evidence corroborated that elderberry did in fact have clinical significance.”
She noted two key focal points of future research that will serve as serious drivers for the ingredient: establishing mechanisms of action for the anti-viral properties exhibited by elderberry in clinical trials, and substantiating the effects that polyphenol-rich berries can have in digestive health applications.
“A healthy and balanced gut can greatly influence the strength of the body’s immune system and overall wellness,” Bush said. “Therefore, high-flavonoid berry ingredients like elderberry extracts can serve as both digestive and immune support ingredients and help tie the two markets together in future product developments.”
Modulating inflammation has been on-trend for several years, and the immune health category has made its link to immune health a central focus in preventive health strategies. “This is a newer endpoint that is exciting for R&D because conventional thinking is that inflammation is separate from immune function,” Eng said. “So this provides new opportunities for product development as supporting immune function via inflammation is a fresh, but scientifically-supported concept.”
ParActin, HP Ingredients’ patented, standardized Andrographis paniculata extract, has been the subject of research showing its ability to modulate the activity of immune cells and inhibit the expression of inflammatory cytokines, Eng said. ParActin “activates peroxisome proliferator-activated receptor (PPARy) which plays an important role in the immune response through its ability to inhibit the expression of inflammatory cytokines and to direct the differentiation of immune cells. Additionally, “andrographolide, the active compound in ParActin, was shown in a recently-published biochemical study (Biochemical and Biophysical Research Communications, 2020) to inhibit the main proteases of COVID-19 through covalent linkage. Researchers in China screened anti-viral drugs, biologics, and natural products and have found andrographolide to significantly decrease the expression of ACE-2 by 21.57 fold.”
Supply Chain Challenges
Challenges related to the supply of raw materials, both due to a huge increase in demand and ongoing pandemic-related shipping delays affecting all industries, are still expected in the future.
“There have been lasting impacts of the pandemic specifically in the global supply chain of raw materials,” Stanieich said. “Many industries have been impacted by supply shortages or unpredictable shipping delays ultimately affecting finished goods and price fluctuations. Many challenges still lie ahead in the supply chain, particularly in raw materials. The effects of the pandemic are sure to carry forward into 2022 and beyond as we all adapt to the short- and long-term impacts.”
It’s safe to assume that delays will be built into this supplement category for some time, Gallo said. “Whether it’s production delays due to a lack of employees, or freight delays due to a shortage of containers or truck drivers, the name of the game is longer lead times. Vertical integration from growing to processing and packaging is key to assure supply and keep lead times to a minimum. And with the cost of air and sea freight skyrocketing as well, this will likely cause increases in ingredient costs, at least in the near term.”
“As is the case with most industries, the supplement industry continues to experience supply chain challenges,” said Tod Burgess, vice president of procurement and product development for Deerland Probiotics and Enzymes. “Labor shortages and slower shipping contribute to longer lead times for basics like capsules, bottles, and lids.”
Healthy partnerships during these challenges have been critical for many companies, according to experts. “Brand marketers who work with well-established manufacturers that have good relationships with raw material suppliers will be in the best position for success,” Burgess said. “The key is open communication with your manufacturer and planning for longer lead times by placing orders several weeks ahead of what you may have grown accustomed to pre-2020. We expect this trend to continue through mid-2022.”
“In regards to the procurement of botanicals, despite the challenging times,” said Greg Ris, vice president of sales for Indena USA, “Indena’s selection of reliable and robust partners, which have been in place for decades, has been an added value for Indena. Furthermore, due to Indena’s longtime experience with herbal materials, we’rewell-acquainted with the sourcing activities to maintain enough stock which has allowed us to avoid or limit any shortage.”
Personalization
The immune health category will continue to adapt to broader shifts across all categories of the nutraceutical marketplace. A leading dynamic is the personalization of products. There are unique stressors to immune function which every consumer may face at varying degrees, including age, overall health, stress, genetic factors, digestive issues, and more.
Secondary functions in immune health supplements, or added ingredients, will be a leading gateway to help immune formulators develop products for specific target demographics. “Personalized nutrition and/or supplementation is the answer to filling the gap between the consumer taking a basic multivitamin vs. a customized supplement packet that is unique to their health needs,” Gallo said. “For supplements, this is achieved by the individual answering a series of questions that helps in the creation of a custom packet to meet the individual’s specific health needs. This would include vitamins and minerals that they might be deficient in, as well as herbs and botanicals, and even Ayurvedic ingredients, to help with issues such as sleep and anxiety which are increasingly linked to our immune health. We all have different diets, lives, and activity levels, and because of this, have different needs to support our immune systems.”
With growing need for healthy tools in daily life, “personalized solutions are in growing demand,” said Ris. “Indena’s research and development group has implemented a couple of agreements to develop a health intelligence platform that estimates a person’s biological identity card. In parallel, new formulative approaches will be created to increase the user-friendliness of our botanicals.”
“Ingredients that had the highest awareness for immune health with consumers—such as elderberry, vitamin C, and echinacea—were also some of those that benefitted most in increased sales,” he continued. “For 2021, all of the familiar ingredients remain strong in the market, but other ingredients have also been introduced with immune health benefits and are getting more attention. One of these ingredients is quercetin.”
Ris pointed to two preliminary studies published in the summer of 2021 (Di Pierro et al., Int. Journal of General Medicine, 2021) which indicated that, alongside medical intervention, quercetin supplementation appeared to have a positive influence in non-severe cases of COVID-19, regarding improvements in the time taken to test negative, as well as significant reductions in markers of reactive oxygen species and inflammation compared to conventional treatment alone. Additionally, “a published human pharmacokinetic study demonstrated that Quercefit optimized quercetin plasma levels after a single administration when compared to unformulated quercetin. This contributes to the efficacy of Quercefit in health conditions linked to oxidative stress, inflammation, and/or immune response as supported by human studies,” Ris said.
Mike Montemarano has been the Associate Editor of Nutraceuticals World since February 2020. He can be reached at MMontemarano@RodmanMedia.com.
Supporting the immune system has been a key entry point for the lion’s share of new supplement users of late. Many products have been re-formulated or re-marketed to include immune health credentials in order to respond to consumer needs and demands of the moment. This gives companies with unique immune health ingredients plenty of new entry points to feature science-backed ingredients that can be taken every day.
“Today’s consumers face a constant onslaught on their immune systems from the stresses of modern life, work, diet, and other lifestyle factors,” said Maria Stanieich, marketing manager for Kyowa Hakko. “According to a CRN Consumer Insights Report, immune health and overall wellness contribute to the top five reasons consumers are taking dietary supplements. The trend of consuming immune health ingredients is also shifting to year-round support as individuals look to proactively support the immune system.”
Competition within the category has become robust, presenting unique challenges. Supply chains for certain ingredients continue to be stressed. Product trends have shifted from more conventional, seasonal immune support to everyday regimens.
Everyday Support
COVID-19 has sparked consumer interest for products that can be taken every day to support base immune function. For the sake of convenience, people are also searching for products that offer additional health benefits.
For this reason, the segment has seen a great deal of products combine common immune health ingredients with broad-acting nutrients tied to adjacent categories, such as healthy aging, sports nutrition, mood and sleep, and more.
A wide net of health problems including digestive issues, stress, high intake of processed foods, and more can have cascading effects on healthy immune function. Personalized ingredient combinations that can attenuate unique external stressors on the immune system are having their day among cutting-edge immune product developers.
“Immunity has moved to a year-round category with a focus on mental, mood, and stress support, and an overall general health focus,” Stanieich said. While there is certainly room to innovate with lesser-known ingredients, she said it can be important to include high-familiarity ingredients alongside more novel elements of a formula.
“As individuals are pursuing active lifestyles, we are seeing a trend of greater focus on general and everyday health, maintaining an active lifestyle, and self-care than ever before,” Stanieich added. “Recent innovations incorporating novel ingredients have been a trend, but there is also a need for the more familiar and essential ingredients for everyday and overall health maintenance.”
A key to developing immune health ingredients in today’s environment is being able to substantiate that both innate and adaptive immune responses are stimulated positively, in order to appeal to those looking for both quick-response and long-term support, said John Deaton, vice president of science and technology for Deerland Probiotics and Enzymes.
He noted that a new clinical study on the company’s probiotic strain, Bacillus subtilis DE111, found that in 44 healthy adults, the strain displayed immunomodulatory and anti-inflammatory effects on several T cell subsets. In summary, the authors noted that supplementing with B. subtilis DE111 “modulates the host immune system through anti-inflammatory and suppressive action on both innate and adaptive cell types (Freedman, Int J Mol. Sci, 2021),” Deaton said.
Multifunctional product formulations are increasingly popular as well, he added. “As we are seeing more multi-functional beverages and supplements, such as immune-plus-antioxidant greens powders, the opportunities lie in combining ingredients that support immune function, such as probiotics, as well as digestive function, such as enzymes,” Deaton said. “In fact, the dual goal of supporting both immunity and digestion is a growth opportunity. For example, our new MuniSpore Bacillus clausii CS109 targets antioxidant activity starting in the gut. Research has shown that B. clausii CS109 as MuniSpore crowds out bacterial pathogens and maintains healthy gut flora, supports the normal immune reaction of intestinal cells, supports the body’s natural repair system through antioxidant activity, and maintains population in the GI tract through resporulation.”
Ongoing concerns about COVID-19, combined with a return to the classroom for students, children’s immune health is also rising as a point of concern to tackle in new products, Deaton said, noting that DE111 has been shown in two separate studies on young children to confer immune health benefits. One study (Slivnik, Journal of Probiotics and Health, 2020) found that DE111 substantially reduced incidence and/or duration of GI and respiratory infections in 81 children between ages 2 and 6 who attended daycare, with a 7.1% incidence in the treatment group versus 20.5% in the placebo group. Researchers also saw a reduction of GI infection duration with 8 days in the DE111 group compared to 28 days in the placebo group.
A second study, Deaton noted, concluded that 8 weeks of supplementation with DE111 modulated the gut microbiomes of 91 children between the ages of 2 and 6, including increased alpha-diversity, and changes to Firmicutes/Bacteroidetes ratios, suggestive of healthy gut function compared to placebo (Paytuvi-Gallart, Beneficial Microbes, 2020).
As a year-round concern, one possible game-changing endpoint for contemporary research could be the Scoring of Immunological Vigor (SIV) assessment, which Annie Eng, CEO of HP Ingredients, said was used to assess the efficacy of the company’s Adapticort Eurycoma longifolia extract. “In the study, 83 volunteers took either 200 mg of Adapticort or placebo per day, and were assessed using SIV, immunological grade, immunological age, and other immune parameters. At week 4, SIV and immunological grade were significantly higher in the [supplementation] group than those in the placebo group […] The results suggest that consuming 200 mg Adapticort per day may enhance comprehensive immunity in middle-aged adults.”
The Gut-Immune Axis
Even prior to the pandemic, the “biotics” space has been a promising research frontier not just for immune health, but for additional health benefits to metabolism, digestion, energy, mood, sleep, and more—all common issues that consumers may be struggling with today.
“Kyowa Hakko is among the first to provide the latest breakthrough approach in the emerging category of paraprobiotics [non-viable microbial cells or crude cell extracts],” said Stanieich.
Having recently launched Immuse, a proprietary Lactococcus lactis strain, the company has supported the ingredient with 11 human clinical trials, including nine efficacy and two safety studies, over long-term periods. The paraprobiotic has been shown to activate pDCs (plasmacytoid dendritic cells), which direct other immune cells to take action, which is a key differentiator that is not observed in other lactic acid bacterial strains.
“This new ingredient provides a novel approach to immune health product formulation as a standalone or in combination with other ingredients in dietary supplements and foods,” Stanieich said.
While immunomodulation may be an advanced concept to grasp, many consumers today have an awareness of the basic beneficial relationships between humans and gut bacteria. Nonetheless, making greater headway in substantiating products that link gut and immune health is much-needed for discerning shoppers.
“Postbiotics like EpiCor are a prime example,” said Cashtyn Lovan, marketing manager for Cargill. “While consumer awareness of the category is still in its early stages, postbiotics offer increased stability and consistency as compared to the more familiar probiotics; and some postbiotics, like EpiCor, are backed by science. Over a dozen published studies, including eight human clinical trials, support EpiCor’s health benefits related to both digestive and immune support.”
Ingredients that can enhance the activity of certain nutrients, and contribute to whether or not an individual “responds” to nutritional interventions, can lead the way to better immune product efficacy, noted Melanie Bush, vice president of science and research for Artemis International.
“A symbiotic is not merely a marketing term, it is a biologically active product,” Deaton said. “To achieve a symbiotic effect, a probiotic must be paired with a prebiotic with proven benefits to that strain.” PreforPro, for example, when combined with the probiotic strain B. lactis BL04, was shown in a recent clinical trial to modulate gut bacteria more than the probiotic strain alone after a 4 week supplementation period, Deaton noted (Grubb et al, Nutrients, 2020).
Additionally, “a 2019 study found that PreforPro supports gut microbiota proliferation and reduces other biochemical markers, including a reduction in the circulating pro-inflammatory cytokine IL-4, which is correlated with immune response,” Deaton noted (Febre et al, Nutrients, 2019).
The role that many nutrients have in gut function is relatively under-investigated as it relates to immune health. But many nutraceutical developers believe there will be a huge window of opportunity in the future for a wider array of ingredients when it comes to the gut-immune axis.
“One of the developments in this field is the concept that some nutrients in foods or supplements do not need to be absorbed in the upper gastrointestinal tract to have a beneficial health effect, but rather can interact with the gut or gut lining to cause a benefit,” said Justin Green, director of scientific affairs for Cargill’s health technologies business. “A phytonutrient that is not normally absorbed may still be important in nutrition or supplementation if it is converted into a compound that is absorbed and can have a beneficial effect. The impact of some food or supplements on the gut microbiota can also affect our immune system; after all, a large proportion of our immune system is in the gastrointestinal tract. This interaction can have effects on both the body’s overall immune response, including inflammation, and digestive health.”
EpiCor, Cargill’s postbiotic immune health ingredient, contains high concentrations of metabolites sourced from baker’s yeast. These metabolites and functional compounds are preserved after the yeast itself is killed off, resulting in a supplement which is considered a whole food since nothing is purified or extracted, Green said. “Lastly, over a dozen published studies, including multiple human clinical trials, show that EpiCor postbiotic supports the gut microbiome, immune health, and nasal comfort. All of that combined makes Epicor a postbiotic through ISAPP’s definition (Collabo, Endo et al., Gastroenterol Hepatol, 2021).”
The role that “dead” microbes play can also be highly comparable to the influence that live probiotics can have when it comes to this gut-immune axis, Green said, through a process that is essentially fermentation in order to derive short-chain fatty acids, polysaccharides, microbial cell fractions, functional proteins, and more even if the microbes are no longer spore-forming. “This has big ramifications on product development because these postbiotics are inherently easier to keep stable during processing and storage as they do not need to be kept alive.”
Three areas of research will advance the level at which microbiome-targeting supplements become personalized, Green said. “The first is the continuing determination of what a healthy microbiome consists of, both in terms of diversity and actual microorganism strains, and conversely, what non-beneficial microorganisms in a microbiome could cause health concerns. The second developing technology is the measurement of one’s personal microbiome.
Much like knowing one’s own DNA makeup is commonplace now, getting a clear picture of the microorganism population in one’s own gut will be an important aspect toward the goal of maintaining good health. The third emerging area of research is identifying nutritional interventions, such as specific postbiotics, that will push what one currently has for their microbiome to what one needs to better maintain the health conditions one is personally concerned with.”
Holistic Herbs
Herbal and botanical ingredients such as elderberry, which can offer not just immune health benefits but other wide-ranging functions as well, will continue to appeal to the holistic sensibilities of today’s immune health consumer, according to Bush. “There are multiple angles of support within the immune category that consumers are actively seeking: ingredients that will arm their immune system to function optimally; ingredients that can aid in recovery by alleviating symptoms; and ingredients that will help keep their body healthy in the long-term. The grand-slam ingredient is one that is able to help in all of these areas.”
Part of the reason for European black elderberry’s rise in popularity and presence across immune products, she continued, “is the scientific substantiation showing its ability to reduce the duration and severity of cold/flu symptoms as well as modulate the body’s immune responses. Additionally, the prebiotic benefits that berry flavonoids have been linked to can help improve the balance of microflora in the gut, thereby improving the overall state of digestive health and related immune health. This makes elderberry a multi-functional anti-viral/immune-supporting ingredient that consumers can get behind.”
Key elderberry studies Artemis noted include a large-scale human clinical study (Tiralongo et al., Nutrients, 2016) which found that the company’s ElderCraft extract could reduce the duration and severity of cold/flu symptoms in 312 long-haul flight passengers.
“Elderberry had already been ‘on the map’ for extensive historical use and preliminary studies that showed its immune-supporting potential, but this study took it to the next level,” Bush said. “A subsequent meta-analysis (Hawkins et al.) evaluating the entirety of the clinical evidence corroborated that elderberry did in fact have clinical significance.”
She noted two key focal points of future research that will serve as serious drivers for the ingredient: establishing mechanisms of action for the anti-viral properties exhibited by elderberry in clinical trials, and substantiating the effects that polyphenol-rich berries can have in digestive health applications.
“A healthy and balanced gut can greatly influence the strength of the body’s immune system and overall wellness,” Bush said. “Therefore, high-flavonoid berry ingredients like elderberry extracts can serve as both digestive and immune support ingredients and help tie the two markets together in future product developments.”
Modulating inflammation has been on-trend for several years, and the immune health category has made its link to immune health a central focus in preventive health strategies. “This is a newer endpoint that is exciting for R&D because conventional thinking is that inflammation is separate from immune function,” Eng said. “So this provides new opportunities for product development as supporting immune function via inflammation is a fresh, but scientifically-supported concept.”
ParActin, HP Ingredients’ patented, standardized Andrographis paniculata extract, has been the subject of research showing its ability to modulate the activity of immune cells and inhibit the expression of inflammatory cytokines, Eng said. ParActin “activates peroxisome proliferator-activated receptor (PPARy) which plays an important role in the immune response through its ability to inhibit the expression of inflammatory cytokines and to direct the differentiation of immune cells. Additionally, “andrographolide, the active compound in ParActin, was shown in a recently-published biochemical study (Biochemical and Biophysical Research Communications, 2020) to inhibit the main proteases of COVID-19 through covalent linkage. Researchers in China screened anti-viral drugs, biologics, and natural products and have found andrographolide to significantly decrease the expression of ACE-2 by 21.57 fold.”
Supply Chain Challenges
Challenges related to the supply of raw materials, both due to a huge increase in demand and ongoing pandemic-related shipping delays affecting all industries, are still expected in the future.
“There have been lasting impacts of the pandemic specifically in the global supply chain of raw materials,” Stanieich said. “Many industries have been impacted by supply shortages or unpredictable shipping delays ultimately affecting finished goods and price fluctuations. Many challenges still lie ahead in the supply chain, particularly in raw materials. The effects of the pandemic are sure to carry forward into 2022 and beyond as we all adapt to the short- and long-term impacts.”
It’s safe to assume that delays will be built into this supplement category for some time, Gallo said. “Whether it’s production delays due to a lack of employees, or freight delays due to a shortage of containers or truck drivers, the name of the game is longer lead times. Vertical integration from growing to processing and packaging is key to assure supply and keep lead times to a minimum. And with the cost of air and sea freight skyrocketing as well, this will likely cause increases in ingredient costs, at least in the near term.”
“As is the case with most industries, the supplement industry continues to experience supply chain challenges,” said Tod Burgess, vice president of procurement and product development for Deerland Probiotics and Enzymes. “Labor shortages and slower shipping contribute to longer lead times for basics like capsules, bottles, and lids.”
Healthy partnerships during these challenges have been critical for many companies, according to experts. “Brand marketers who work with well-established manufacturers that have good relationships with raw material suppliers will be in the best position for success,” Burgess said. “The key is open communication with your manufacturer and planning for longer lead times by placing orders several weeks ahead of what you may have grown accustomed to pre-2020. We expect this trend to continue through mid-2022.”
“In regards to the procurement of botanicals, despite the challenging times,” said Greg Ris, vice president of sales for Indena USA, “Indena’s selection of reliable and robust partners, which have been in place for decades, has been an added value for Indena. Furthermore, due to Indena’s longtime experience with herbal materials, we’rewell-acquainted with the sourcing activities to maintain enough stock which has allowed us to avoid or limit any shortage.”
Personalization
The immune health category will continue to adapt to broader shifts across all categories of the nutraceutical marketplace. A leading dynamic is the personalization of products. There are unique stressors to immune function which every consumer may face at varying degrees, including age, overall health, stress, genetic factors, digestive issues, and more.
Secondary functions in immune health supplements, or added ingredients, will be a leading gateway to help immune formulators develop products for specific target demographics. “Personalized nutrition and/or supplementation is the answer to filling the gap between the consumer taking a basic multivitamin vs. a customized supplement packet that is unique to their health needs,” Gallo said. “For supplements, this is achieved by the individual answering a series of questions that helps in the creation of a custom packet to meet the individual’s specific health needs. This would include vitamins and minerals that they might be deficient in, as well as herbs and botanicals, and even Ayurvedic ingredients, to help with issues such as sleep and anxiety which are increasingly linked to our immune health. We all have different diets, lives, and activity levels, and because of this, have different needs to support our immune systems.”
With growing need for healthy tools in daily life, “personalized solutions are in growing demand,” said Ris. “Indena’s research and development group has implemented a couple of agreements to develop a health intelligence platform that estimates a person’s biological identity card. In parallel, new formulative approaches will be created to increase the user-friendliness of our botanicals.”
“Ingredients that had the highest awareness for immune health with consumers—such as elderberry, vitamin C, and echinacea—were also some of those that benefitted most in increased sales,” he continued. “For 2021, all of the familiar ingredients remain strong in the market, but other ingredients have also been introduced with immune health benefits and are getting more attention. One of these ingredients is quercetin.”
Ris pointed to two preliminary studies published in the summer of 2021 (Di Pierro et al., Int. Journal of General Medicine, 2021) which indicated that, alongside medical intervention, quercetin supplementation appeared to have a positive influence in non-severe cases of COVID-19, regarding improvements in the time taken to test negative, as well as significant reductions in markers of reactive oxygen species and inflammation compared to conventional treatment alone. Additionally, “a published human pharmacokinetic study demonstrated that Quercefit optimized quercetin plasma levels after a single administration when compared to unformulated quercetin. This contributes to the efficacy of Quercefit in health conditions linked to oxidative stress, inflammation, and/or immune response as supported by human studies,” Ris said.
Mike Montemarano has been the Associate Editor of Nutraceuticals World since February 2020. He can be reached at MMontemarano@RodmanMedia.com.
