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Ingredients and immunity: Supporting the systems that fight for good health

The immune response elicited by its complex systems varies from person to person—a matter of ongoing investigation among researchers. A particularly pertinent topic of this investigation: How great is the impact of genetics on immune response versus environment?

Sometimes cells “break.” They get damaged (a sunburn, for example) or they become unhealthy (an infection) which, left unchecked, can lead to sickness or other health concerns.

It’s the job of the immune system to ward off pathogens and, in the event of invasion, identify and destroy these “broken” cells, keeping the body healthy.

The immune system is a complex network of organs, cells, proteins and molecules. The immune system can be categorized into two parts: the innate (non-specific) and adaptive (specific) immune systems.1

The innate system is the body’s fast-acting first line of defense against germs and pathogens. It’s comprised of the skin, various mucous membranes, bacteria, proteins and scavenger cells found in the blood and tissues (macrophages, granulocytes and natural killer [NK] cells). The system calls on the acute-phase response and/or the inflammatory response to eliminate pathogens. These responses are initiated by chemical signals (cytokines) including interleukins for the acute-phase response and tumor necrosis factor-alpha (TNF-a) for the inflammatory response. Cytokines are also often considered biomarkers of disease.2

The adaptive immune system is also called “acquired” immunity based on its ability to learn about specific pathogens and develop antibodies in defense. The stars of adaptive immunity are T and B lymphocytes (T cells and B cells), which produce antibodies that bind to antigens (B cells) and directly attack affected cells (T cells), while also developing memory cells (T and B cells) that recall previously encountered pathogens. The activity of T cells is also called cell-mediated immunity, as T cells only recognize pathogens that have entered the body’s cells. In contract, B cells and antibodies interact with invaders that remain outside the body’s cells.

Antibodies created by B cells are known as immunoglobulins and are represented in five main classes: immunoglobulin G (IgG), M (IgM), A (IgA), D (IgD) and E (IgE).

Innate and adaptive systems provide different functions, but work together to support one another. T helper cells, for example, excrete cytokines that help to activate macrophages (of the innate system) and other lymphocytes.

The immune response elicited by these complex systems varies from person to person—a matter of ongoing investigation among researchers. A particularly pertinent topic of this investigation: How great is the impact of genetics (heritable influences) on immune response versus environment (non-heritable)?

In other words: How much of immunity is under the control of the individual? This question is equally important to natural product brands and developers looking to create or market products to support an individual’s immune system.

A groundbreaking study published in 2015 in Cell set out to answer this question by analyzing immunological parameters of identical (monozygotic [MZ]) and fraternal (dizygotic [DZ]) twins.3 In the study of 210 healthy twins between ages 8 and 82, researchers measured 204 parameters, including the frequency of different immune cell types—such as B cells and T cells—and levels of 43 cytokines, chemokines and other serum proteins that modulate the immune response. Results showed 77 percent of the parameters are dominated by non-heritable influences and 58 percent almost completely determined by non-heritable influences. Some of these parameters become more variable with age, suggesting the cumulative influence of environmental exposure.

Authors wrote: “In summary, our findings strongly suggest that a healthy human immune system adapts to non-heritable influences such as pathogens, nutritional factors and more, and that this overshadows the influences of most, although not all, heritable factors.”

These findings—though encouraging for consumers and product developers alike—aren’t altogether a surprise; a wide range of natural ingredients have ample scientific support backing immune-boosting effects.

And, according to a global survey commissioned by Lonza Consumer Health & Nutrition and conducted by the Natural Marketing Institute (NMI), consumer interest in the category is high. Survey results showed 66 percent of U.S. consumers are already using a supplement to manage immune health, and 33 percent of U.S. consumers are very likely to purchase supplements that support immune health.

Per Juliana Erickson, senior marketing manager, consumer health & nutrition, Lonza, natural solutions are a key focus for consumers looking for immune support.

“Natural and naturally derived ingredients are currently leading innovation in the immune health category,” she said, citing Lonza data showing 38 percent of U.S. dietary supplement users look for supplements that are from “natural sources,” a growth of 59 percent in the last 10 years. 

“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,” she said.

Innovation appears in many forms in the supplements market, but key is ensuring innovative solutions are effective as proven by scientific research.

A soluble polysaccharide extracted from North American larch trees (arabinogalactan as ResistAid®, from Lonza) has been shown to modulate and support both the innate and adaptive systems via direct and indirect pathways within the gastrointestinal (GI) tract.4 Among mechanisms, ResistAid indirectly supported the immune system via lactic acid-producing bacteria and bacterial constituents on immune cells, production of short chain fatty acids (SCFAs) and binding to SCFA receptors on leucocytes; directly by supporting the activity of NK cells, cytokines and macrophages;5,6,7 and via enhanced antioxidant capacity that may improve immunity.8

Beta glucan derived from Euglena gracilis algae (as BetaVia Complete or BetaVia Pure, from Kemin Human Nutrition and Health) has been shown in preclinical and clinical research to support immune health by priming immune cells and promoting immune cell signaling.9,10

In a new 90-day randomized, double-blind, placebo-controlled clinical trial awaiting publication, BetaVia Complete reduced upper respiratory tract infection (URTI) symptoms in healthy adults by 70 percent, lead to 3.3 fewer sick days and 10 fewer URTI symptoms compared to placebo. Information was collected via self-reporting using the Wisconsin Upper Respiratory Symptoms Survey (WURSS).

Probiotics Power

Authors of the Cell study pointed to various non-heritable influences on the immune system, including the microbiome.3 “The microbiome also clearly has a major influence on the immune system,”11 they wrote, “and shifts in its composition might cause significant changes in the immune system.”

Supplementation with probiotic bacteria has been shown to benefit immunity. According to a 2017 publication, certain probiotic strains influenced both innate and acquired immune response at the gene expression level.12 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.

A probiotic strain of Bacillus coagulans (as Bacillus coagulans GBI-30, 6086, from Kerry Functional Ingredients & Actives) offers immune-boosting benefits. 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.13 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.14

In recent research, daily consumption of GanedenBC30 by adults between ages 65 and 80 increased beneficial groups of bacteria in the human gut and potentially increases production of anti-inflammatory cytokines.15

A probiotic formulation containing Bifidobacterium lactis Bl-04™ (from DuPont Nutrition & Health) has been shown to support upper respiratory tract health and immunity by helping to produce higher levels of IL-8, an indicator of innate immune system activity.16 In a 2017 publication, Bl-04 at a dose of 2 billion colony forming units (CFU) per day influenced the inflammatory response to rhinovirus infection.17 Subjects who took the Bl-04 probiotic supplement had a decreased amount of rhinovirus in their nasal washes during infection.

Athlete Support

Strenuous activity has been linked to decreased immune performance, which makes immune support supplements of great importance to athletes.

“While exercise may boost immune function, strenuous training can exhaust the immune system and hinder the innate immune response,” said Tim Hammond, vice president of sales & marketing, Bergstrom Nutrition/OptiMSM®. “Viruses and bacteria may gain a foothold during this open window of altered immunity and lead to potential illness or downtime away from training.”

Methylsulfonylmethane (MSM as OptiMSM, from Bergstrom Nutrition) has been shown to support the innate immune system following exhaustive exercise,18 and showed lower serum levels of inflammatory markers post-exercise,19 which “indicated that OptiMSM conserved a natural and healthy immune system after physical stress,” Hammond said.

In a new study, a proprietary baker’s yeast beta 1,3/1,6 glucan (as Wellmune®, from Kerry) decreased severity of URTIs among marathoners and fewer missed post-marathon workouts for those consuming Wellmune daily in a dairy-based beverage.”20 The results provide a greater understanding of Wellmune’s ability to help strengthen the immune system when consuming the ingredient through a beverage product, said Don Cox, research and development director – Wellmune and GanedenBC30®, Kerry Functional Ingredients & Actives.

Absorbed by specialized immune tissue in the gut, Wellmune binds to neutrophils, enabling them to move more quickly to recognize and kill foreign challenges. Beyond athletes, these effects are documented in several studies in a range of populations including children in a daycare setting,21 high-stress populations22 and Montana’s Wildland Firefighters.23

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.24

Supplementation with probiotic strain L. helveticus LAFTI® L10 (from Lallemand Health Solutions) in elite athletes significantly shortened the average duration of URTI-like episodes by 3.4 days and significantly decreased the number of symptoms by around 29 percent in a 2016 publication by Marinkovic et al.25

Based on a sub-analysis of the 2016 study, Michalickova et al. published a second paper on LAFTI L10 in 2017 focused on the salivary biomarkers of immunity.26 Results showed total sIgA concentration was maintained in the LAFTI L10 group vs. a significant reduction of 35 percent in the placebo group. In 2018, A third study on the probiotic supplement in elite athletes and its impact on pro- and antioxidant markers in the blood found markers of oxidative stress were decreased in the LAFTI L10 group and not in the placebo.27

References

  1. “The innate and adaptive immune systems.” IQWiG (Institute for Quality and Efficiency in Health Care). 2006. Cologne, Germany.
  2. Villeda SA, Wyss-Coray T. “The circulatory systemic environment as a modulator of neurogenesis and brain aging.” Autoimmun Rev. 2013 Apr;12(6):674-7. DOI: 10.1016/j.autrev.20110.014.
  3. Brodin P et al. “Variation in the human immune system is largely driven by non-heritable influences.” Cell. 2015 Jan 15;160(0):37–47.
  4. Udani J et al. “Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers.” Nutr J. 2010;9:32.
  5. Roxas M, Jurenka J. “Colds and influenza: a review of diagnosis and conventional, botanical, and nutritional considerations.” Altern Med Rev. 2007;12(1):25–48.
  6. Choi EM et al. “Immunomodulating activity of arabinogalactan and fucoidan in vitro.” J Medical Food. 2005;8(4):446–453.
  7. Vos AP et al. “Immune-modulatory effects and potential working mechanisms of orally applied nondigestible carbohydrates.” Immunol. 2007;27(2):97–140.
  8. Teixeira S et al. (2005). Free Rad Biol Med 39:1099–1108
  9. Russo R et al. "Euglena gracilis paramylon activates human lymphocytes by upregulating pro‐inflammatory factors." Food Science & Nutrition. 2017;5(2):205-214.
  10. Kankkunen P et al. "(1, 3)-β-Glucans activate both dectin-1 and NLRP3 inflammasome in human macrophages." The Journal of Immunology. 2010;184(11):6335-6342.
  11. Hooper LV, Littman DR, Macpherson AJ. “Interactions between the microbiota and the immune system.” Science. 2012 Jun 8;336(6086):1268-73. DOI: 10.1126/science.1223490.
  12. Mac Pherson et al. “Genome-Wide Immune Modulation of TLR3-Mediated Inflammation in Intestinal  Epithelial Cells Differs between Single and Multi-Strain Probiotic Combination.” PLOS ONE. 2017;12(1):e0169847.
  13. Kimmel M et al. “A controlled clinical trial to evaluate the effect of GanedenBC(30) on immunological markers.” Methods Find Exp Clin Pharmacol. 2010 Mar;32(2):129-32. DOI: 10.1358/mf.2010.32.2.1423881.
  14. Kimmel M et al. “A controlled clinical trial to evaluate the effect of GanedenBC(30) on immunological markers.” Methods Find Exp Clin Pharmacol. 2010 Mar;32(2):129-32. DOI: 10.1358/mf.2010.32.2.1423881.
  15. Nyangale E et al. “Bacillus coagulans GBI-30, 6086 Modulates Faecalibacterium prausnitzii in Older Men and Women.” The Journal of Nutrition. 2015;145(7):1446–1452.
  16. West et al. “Probiotic supplementation for respiratory and gastrointestinal illness symptoms in healthy physically active individuals.” Clin Nutr. 2014 Aug;33(4):58 1-7.
  17. Turner RB et al. “Effect of probiotic on innate inflammatory response and viral shedding in experimental rhinovirus infection – a randomised controlled trial.” Beneficial Microbes. 2017;8(2):207-215.
  18. Godwin S et al. “MSM enhances LPS-induced inflammatory response after exercise.” J Int Soc Sports Nutr. 2015;12(Suppl 1): P48. DOI:10.1186/1550-2783-12-S1-P48.
  19. Van Der Merwe M, Bloomer RJ. “The Influence of Methylsulfonylmethane on Inflammation-Associated Cytokine Release before and following Strenuous Exercise.” J Sports Med. 2016;2016. DOI:10.1155/2016/7498359.
  20. Mah E etal. “Beverage Containing Dispersible Yeast β-Glucan Decreases Cold/Flu Symptomatic Days After Intense Exercise: A Randomized Controlled Trial.” Journal of Dietary Supplements. 2018. DOI:10.1080/19390211.2018.1495676.
  21. Meng F. “Baker’s Yeast Beta-Glucan Decreases Episodes of Common Childhood Illness in 1 to 4 Year Old Children during Cold Season in China.” Journal of Nutrition & Food Sciences. 2016;6:518.
  22. Talbott S, Talbott J. “Beta 1,3/1,6 Glucan Decreases Upper Respiratory Tract Infection Symptoms and Improves Psychological Well-being in Moderate to Highly-Stressed Subjects.” Agro FOOD Industry Hi-Tech. 2010;21:21-24.
  23. Domitrovich S, Domitrovich J, Ruby B. “Effects of an Immunomodulating Supplement on Upper Respiratory Tract Infection Symptoms in Wildland Firefighters.” Medicine & Science in Sports & Exercise. 2008;40:S353.
  24. West N et al. “Probiotic supplementation for respiratory and gastrointestinal illness symptoms in healthy physically active individuals.” Clinical Nutrition. 2014;33(4):581-87.
  25. Marinkovic D et al. “Lactobacillus helveticus Lafti® L10 supplementation reduces respiratory infection duration in a cohort of elite athletes: a randomized double-blind placebo-controlled trial.” Applied Physiology, Nutrition, and Metabolism. 2016. DOI: 10.1139/apnm-2015-0541.
  26. Michalickova D et al. “Lactobacillus helveticus LAFTI® L10 Supplementation Modulates Mucosal and Humoral Immunity in Elite Athletes”. Journal of Strength and Conditioning Research. 2017;31(1):62-70.
  27. Michalickova D et al. “Effects of Probiotic Supplementation on Selected Parameters of Blood Prooxidant Antioxidant Balance in Elite Athletes: A Double‐Blind Randomized Placebo‐Controlled Study.” Journal of Human Kinetics. 2018;64(1):111-122.

 

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