The pandemic has caused worldwide concern—and that stress has caused the greatest need ever for effective immune-support products.
Without a doubt, the current pandemic has changed how people worldwide view protecting their health. Immunity. Immune system. These terms are at the forefront of public consciousness more than ever before. But there’s something that the pandemic has also brought that affects the immune system and that needs to be more in the spotlight as well: the stress from the fear and the restrictions and the unknown future—which negatively impacts immune function.
The concept of formulating and marketing products that support the immune system by also supporting the stress response is one that makes sense and is scientifically sound.
Janice Rueda, PhD, vice president, nutrition science business development, Illinois-based ADM, said that the long-term consequences of COVID-19 are still unfolding, and now consumers are “hyper-aware of their personal health and are taking proactive measures to support their bodies’ natural defenses and overall well-being.
In fact, according to FMCG Gurus’ “12-Step Guide for Addressing COIVD-19 in 2020 and Beyond,” eight out of 10 consumers across the globe are concerned about the health implications of COVID-19, and 57 percent are more conscious of their immune system.
Therefore, Rueda noted that ADM anticipates rapidly increasing interest in supplements among consumers from all backgrounds and life stages who will demand more functional foods and beverages that benefit holistic wellness through mood improvement, stress reduction and that provide a source of sustained energy all to increase immune resistance. As such, she predicted, “The gut-brain axis is an area of interest for functional food and beverage developers as researchers continue to explore how modulating the human microbiome can affect mental health and emotions. We expect ingredients like prebiotics, probiotics, postbiotics and various other functional ingredients to play significant roles in product development.”
In agreement is Per Rehné, CEO of U.K.-based Clasado Biosciences, who views the COVID-19 outbreak as having a pervasive impact on all aspects of society, including mental health, as anxiety about contracting the disease has become widespread and intense. Lockdowns and home-schooling have also dramatically increased stress for people of all ages, including children. Social isolation and an unstable job market have also contributed directly to increased anxiety, depression, problems with sleep, stress, and other negative feelings in some individuals.
“As demonstrated by COVID-19, it is imperative to achieve a balanced immune response. An over-reactive or under-reactive immune system can be equally detrimental and lead to clinical complications, such as the severe acute respiratory syndrome and organ failures caused by SARS-CoV-2,” he stated. “Healthy gut microbiota may be pivotal in getting that balance right.”
Karen Dhanraj, technical marketing and sales manager, Lallemand Bio-Ingredients, Montreal, Quebec, Canada elaborated that the increased social isolation and attendant loneliness is associated not only with anxiety and depression, but “studies continue to link stress and mental health with the human immune system, showing that an early consequence of chronic stress exposure is suppression of the immune system. Studies have further demonstrated that psychological stress plays a vital role in the vulnerability, severity and recurrence of acute respiratory infection.”
Annie Eng, CEO of Florida-based HP Ingredients Inc., noted that feeling stress and nervousness increases the body’s release of the hormone cortisol, which when chronically flooding the body, will hamper immune function. Therefore, “achieving an anabolic balance instead of the catabolic balance will greatly strengthen immune resistance.” Dhanraj added that “at least one study has measured levels of cortisol in COVID-19 patients and found significantly higher levels in patients who died from COVID-19 compared to those who survived.”
John Quilter, vice president/general manager Kerry reported that on June 1, 2020, the International Committee of the Red Cross published its concerns about dramatically increased stress and its impact on health (“COVID-19: Global pandemic may increase stress exponentially”). Further, “in the past several decades, several studies have provided evidence of a link between stress and decreases in functional immune measures.”
Meanwhile, many people who overcome COVID-19 will likely be dealing with what Leslie Gallo, president, Artemis International, Inc., in Indiana called “‘aftershocks’ for months and possibly years to come—from PTSD (post traumatic stress disorder)-like issues of anxiety and depression (both COVID positive and those who are living with the daily fear of contracting the virus) to ongoing respiratory issues, fatigue, cardiac and kidney issues, muscle pain and other significant health and quality of life issues. Most of these resulting from high levels of inflammation due to the COVID virus that continue to challenge long after COVID is technically out of your system and some fear could be chronic long-term problems.”
Stress and Immunity
The crux of the matter here – is stress. Your immune-support formulas, with the appropriate and relevant ingredients can address immune sustenance via the stress-response pathways.
According to Quilter, acute or short-term stress can enhance immune response; and Dhanraj explained that cortisol in small amounts has an inflammation-control action which does boost immune function.
However, said Quilter, “chronic or long-term stress is linked to numerous immune health problems, including suppression and/or premature aging of the immune system.”
There are several stress pathways that negatively impact optimal immune function.
Dhanraj explained that regulation of the stress response involves the endocrine system, the central nervous system and the immune system. “Stress is perceived by the limbic system in the brain. After a stressful event, neurons activate the release hormones that affect the hypothalamus, which then activates a cascade of stress-response hormones. This cascade further stimulates the release of cortisol from the adrenal glands.
Through time, the body becomes accustomed to elevated cortisol in the blood, developing a type of resistance, resulting in increased sustained inflammation. As stress becomes chronic, the immune system becomes impaired as cortisol causes a reduction in the production of lymphocytes, specialized immune cells that help fight off infection. The lower the body’s lymphocyte level, the more one is at risk of infection by viruses, including coronaviruses.
Rehné pointed to the gut-brain axis’ impact on immune function. “The gut microbiome is affected by stress and, in turn, influences stress responsivity. One of the communication routes between the gut and the brain is the immune system. It is therefore not surprising that molecules released by the body in response to stress may be beneficial, improving immune response by limiting inflammation through short-term stressors,” he explained. “The effects of chronic psychological stress are strikingly different, leading to weakening the immune system, increased intestinal permeability and substantial changes to gut microbiome composition, which can all make us more prone to infections.”
And even though in many places fitness centers remain closed and social distancing is still required, people are still finding ways to work out and work out hard—creating a new type of stress, physical stress. According to John Deaton, vice president of science and technology for Georgia-based Deerland Probiotics & Enzymes, athletes, trainers and fitness enthusiasts, who tend to exercise or compete vigorously, can easily depresses immune function.
It is common for competitive athletes to become susceptible to infections resulting from mucosal and systemic immune suppression. Additionally, athletes who become overly fatigued tend to have altered circulating levels of pro and anti-inflammatory cytokines. For example, elite male rowers were found to have higher circulating tumor necrosis factor-alpha (TNF-α) levels.”
According to Deaton, Deerland has a published study showing that taking a probiotic daily may benefit athletes and trainers by boosting immunity and recovery following strenuous physical activity by reducing levels of TNF-α. The study sought to determine effects of 1 billion CFU Bacillus subtilis (DE111) probiotic in college-aged male athletes after 12 weeks. The double-blind, placebo-controlled randomized study gave 25 division 1 male baseball athletes either the probiotic or placebo and looked at their markers of immune and hormonal status via blood and salivary samples, pre- and post-training. After the three months of intense training in both groups, the researchers found TNF-α concentrations were significantly lower in the DE111 group compared to placebo.
Unsurprisingly, prebiotics have emerged as strong immune-regulatory ingredients.
ADM‘s Fibersol is a dietary fiber ingredient that, according to Rueda, is clinically shown to support the gut microbiome, which plays an important role in immune function and maintaining the integrity of the intestinal barrier “Our portfolio also includes plant-derived vitamin C, as well as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), which “help maintain immune function as building blocks for cells and signals of the immune system. They also play a role in maintaining healthy function of the body’s inflammatory response,” she described.
Bimuno, from Clasado, is a prebiotic ingredient containing a unique formulation of galactooligosaccharides (GOS), according to Rehné. “Although Bimuno has several modes of action, many of these are tightly linked to selectively increasing the growth of bifidobacteria in the large intestine. A higher presence of bifidobacteria in gut microbiota has been associated benefits on immune health and resilience as well as mitigating stress hormone levels, confirmed in clinical trials.”
Studies have shown that Bimuno reduces the adhesion of pathogens to gut cells and increases some substances to prevent invasion of pathogens. In a clinical study in the elderly Bimuno increased the phagocytic activity of white blood cells, i.e., engulfing bacteria for elimination, as well as stimulated the activity of another type of immune cell that targets and kills virally infected cells, he reported. Additionally, “an increase in anti-inflammatory and a reduction of pro-inflammatory molecules were observed, demonstrating Bimuno’s efficacy in managing immunosenescence-related chronic low-grade inflammation. These findings were confirmed in another clinical study in the elderly supporting Bimuno’s role in immune resilience,” he commented.
Another prebiotic is Wellmune from Kerry Group, a proprietary baker’s yeast beta 1,3/1,6 glucan that clinical studies show is taken up into the body through specialized immune tissue in the intestines, according to Quilter. There, he explained, “immune cells engulf it and break it down into smaller fragments which bind to neutrophils, the most abundant immune cells in the body. Primed by Wellmune, neutrophils move more quickly to recognize and kill foreign challenges.”
In one study, healthy subjects took Wellmune daily for 12 weeks during cold/flu season. The researchers found that as well as being less likely to miss work or school, the subjects reported an increase in general health markers, including physical energy and emotional well-being.
In another study researchers evaluated the effect of consuming Wellmune on symptoms associated with upper respiratory tract infection (URTI) and psychological well-being during periods of increased lifestyle stress. Subjects aged 18-65 consumed Wellmune or placebo for four weeks. Researchers reported that participants taking Wellmune reported a significant decrease in URTI symptoms, an 8.3 percent improvement in overall well-being, and a 26 percent increase in vigor. “The results were consistent with data from other studies demonstrating that Wellmune can support immune responses during periods of both physical and psychological stress,” Quilter remarked.
EpiCor from Iowa-based Cargill Health Technologies, is a whole food fermentate, and is a postbiotic ingredient clinically shown to support the immune system and positively modulate the gut microbiota, according to Justin Green, PhD, director of scientific affairs. “EpiCor is made through a natural, proprietary process and is inspired by a real-life health discovery story,” he explained. “Factory employees at our founding company’s animal feed manufacturing facility were taking fewer sick days than their office-bound colleagues. To understand why, the company commissioned pilot studies and learned that its fermented feed product supported the immune health of the factory workers exposed to the product. The company embarked on years of clinical research to show the safety and efficacy of this whole food fermentate for people—and EpiCor was born.”
To date, he noted, more than a dozen published studies show EpiCor helps support a healthy immune system and modulate gut microbiota. For example, in randomized double-blind, placebo-controlled human clinical trials, EpiCor was shown to support immune health year-round. In addition to its immune health benefits, other studies in both human clinical trials and model systems show that EpiCor also supports gut-microbiota modulation.
South Carolina-based Lonza’s proprietary ResistAid arabinogalactan extracted from North American Larch trees has been clinically demonstrated to support natural immune function by different mechanisms of action, according to Vaughn DuBow, marketing manager, Americas, Lonza Capsules & Health Ingredients. These MOA’s include “indirect action through modulation of the gut microbiota, and directly through support of the innate and adaptive immune system,” he explained. “These mechanisms have been demonstrated to support increased beneficial immune cell populations and also to help modulate and deliver an appropriate immune response.”
Two randomized double-blind placebo controlled human trials has shown ResistAid may support the immune system following a standardized immune challenge or stimulus, DuBow reported. In addition, healthy subjects consuming 4.5 g of ResistAid arabinogalactan experienced fewer symptoms of respiratory tract infections compared to placebo.”
Botanical ingredients also have scientifically shown value in supporting immune function during times of stress (physical, mental or emotional).
Artemis International’s European Black Elderberry is a rich source of flavonoids, which have been tied to positive antiviral and immune support outcomes, according to Melanie Bush, director of science. She pointed to a significant human clinical trial of 312 long-haul flight passengers who supplementation with Haschberg European Black Elderberry extract and experienced significantly reduced the duration and severity of colds. This study was highlighted in a subsequent meta-analysis last year that analyzed all of the relevant human trials with elderberry and concluded that “supplementation with a standardized elderberry extract is significantly effective at reducing the total duration and severity of upper respiratory symptoms, as compared to a placebo group.”
“Studies on black elderberry also indicate a modulation effect on cytokines, influencing the responsiveness and inflammation balance of the immune system,” Bush said. “In addition to the anthocyanin actives, high-molecular-weight-compounds found in ElderCraft black elderberry extract have also been tied to its immune-supporting and antiviral activity. One possible mechanism of action by these actives involves blocking attachment of viruses to cells, thereby hindering replication.”
Another botanical is HP Ingredients’ ParActin, a patented extract from Andrographis paniculata, standardized to 50 percent andrographolide. ParActin works by inhibiting NF-kB—key regulator of the human immune and inflammatory response system. When NF-kB is inhibited, pro-inflammatory cytokines and proteins such as COX2, prostaglandins, IL-6, IL-12, INF-a TNF-a are reduced.
ParActin also increases the Nrf2-Keap1-ARE (antioxidant response element), to augment the body’s natural antioxidant enzymes such as heme oxygenase-1, glutathione reductase, glutathione peroxidase and superoxide dismutase, among others, to help reduce oxidative stress and promote healthy autophagy function.
There are many published studies on the immune-support mechanism of action of andrographolide: it inhibits a pathogenic agent’s protein synthesis and expression, inhibits it from entering inside the cell wall, inhibits the agent’s DNA replications; reduces the agent’s receptor signaling, & decreases ACE2 expression.
The company’s Tongkat Ali, LJ100 has also been shown in studies to improve immune response. As Eng explained, “Cortisol exacerbates immunosenescence by inducing a shift from a CD4+ to CD8+ dominant pattern of immunity. In one study, 200 mg per day of LJ100 for one month significantly improved Scoring of Immunological Vigor, immunological grade, and immunological age by four years in human participants. Number of total, naïve, CD4+ T cells, and natural killer cells also significantly increased.”
Zembrin, from PLT Health Solutions in New Jersey, is a patented extract of the South African plant Sceletium tortuosum and has been clinically shown to work through improving cognitive flexibility, executive function and mood, according to Steve Fink, vice president, marketing, A recently published study investigating the effects of short-term supplementation with Zembrin on the “threat circuitry” of the brain showed reduced anxiety-related activity of the amygdala and its associated anxiety circuitry within two hours of consumption, he explained. Another study had participants consume Zembrin for one day or daily for six weeks and found that “anxiety score was not only improved within an experimental day but also decreased from the first day to the last day in a statistically significant manner in comparison to placebo.”
There are numerous studies showing that vitamin D is necessary for a healthy immune system and PLT Health Solutions’ Earthlight Vitamin D is produced from mushrooms via a patented process that exposes the mushrooms to light, and is thus a whole-foods highly concentrated vitamin D. In July, “Earthlight received approval of its Food Additive Petition from FDA (U.S. Food and Drug Administration), paving the way for it to be used in food and beverages produced and sold in the United States. The approval covers Earthlight’s use in a broad range of food and beverage products, ranging from breakfast cereals and bakery products to juices and meal replacements. The approval also covers use of Earthlight in five food categories that until now were not covered in the CFR for vitamin D fortification: fruit smoothies, soups and soup mixes, vegetable juices, extruded vegetable snacks and plant-based meat analogues,” Fink reported.
A Changed Category
The immune-support category—notably immune-stress-support—will be a different landscape post-COVID (whenever that will be). “Prior to COVID, most consumers felt that cold and flu season was the time to worry about your immune system,” commented Gallo. COVID created a different story. “As you can see by the sold-out position of so many immune products, consumers are scrambling to take whatever they can to support their immune system vitamins C and D, elderberry, echinacea, probiotics, mushrooms and antioxidants are all in limited stock.”
Unsurprisingly, Quilter underscored, there’s been a major acceleration of consumer interest in the role of nutrition in immunity. For example, there was a 670 percent increase in Google searches for “food” and “immune system” between February and March of this year, and in a recent FMCG Gurus report, 35 percent of global consumers said they have begun eating foods that boost their immune health more frequently since the pandemic. Kerry’s own 2019 global consumer survey showed that immune system support was the most common reasons consumers purchased healthy lifestyle products.
According to Rueda, consumer spending in the health and wellness category increased significantly during the pandemic, and developers can win with consumers here by highlighting efficacy on the label. A consumer survey in April of this year by Houlihan Lokey found that 62 percent of consumers cited efficacy as a key product feature influencing their willingness to pay a premium price.
“The key takeaway for the category is that the pandemic has shown that across the globe, consumers are seeking a greater working knowledge of immune health as a preventative action,” Rehné observed. “There is ample opportunity for brands in the immune health market to use this engagement to shape their products and marketing communications in favor of clarity and science-backed solutions that make a difference.”
When formulating new products for the reinvigorated immune category, DuBow observed that products that support wider responses to stress, such as mood, cognitive health and sleep, can also be beneficial as these responses have a significant effect on the immune system. Summarized Fink, “Today’s pandemic is nothing if not a long journey.” NIE
For More Information:
Artemis International Inc., www.artemis-international.com
Cargill Health Technologies, www.epicorhealth.com
Clasado Biosciences, www.clasado.com
Deerland Probiotics & Enzymes, www.deerland.com
HP Ingredients Inc., www.hpingredients.com
Lallemand Bio-Ingredients, www.bio-lallemand.com
Lonza Capsules & Health Ingredients, www.lonza.com
PLT Health Solutions, www.plthealth.com