Can a Glycoprotein Found in Milk Support Immunity?

First published in Nutraceuticals Now by Marieke Schoemaker, Global Development Specialist – Adult Nutrition, FrieslandCampina Ingredients.

Consumers today are increasingly aware that the best medicine is preventative and are therefore taking a more active role in both preserving and improving their immune health. As such, they are also increasingly careful when choosing what goes into their bodies. A world of knowledge is just a click away, and they are easily able to find out everything about the ingredients in the products they consume, including functional food and drinks and supplements.

Before the COVID-19 pandemic, 47% of consumers said they regularly researched ingredients to help decide their best options.¹ As the pandemic struck, this preference took on new urgency and the focus turned to immune health support. In fact, the number of consumers that actively wanted to improve their immunity rose from 53% in 2019 to 70% in 2020.² Contemporary consumers want immune health solutions that contain scientifically proven ingredients, backed by clinical evidence.

Supporting immunity

Encompassing a complex set of defence mechanisms, the human immune system is honed to protect itself from both external and internal threats. Crucially, it must perform strongly enough to avoid infection, constantly alert and continually evolving to track down, identify and destroy new and recurring pathogens – while also distinguishing pathogens from harmless or beneficial substances.

However, the strength and variety of an immune response is completely unique to each person, depending not only on genetic factors, but also on environment, age, body composition and other factors.^3,4,5

This is why more consumers are relying on functional foods, drinks and supplements to obtain some of the nutritional benefits their diets may lack and to help support their immune systems.²

Lines of defence

In order to create solutions that address this need, manufacturers are taking a closer look at the sites where the human body is directly exposed to pathogens – such as the mucosal surfaces of the upper respiratory tract and the gut. The body protects these areas with the mucosal immune system, made up of a physical coating of mucus, layers of epithelial cells and lymphoid tissue cells – which play an important role in identifying pathogens and providing an appropriate immune response to them.

In addition, in order to function correctly, the gut mucosal immune system relies on the interaction between the intestinal immune system and gut microbiota. ‘Microbiota’, or the collection of microbial cells which live in and on the human body, although most abundantly in the gut, can synthesise vitamins⁶ and short-chain fatty acids⁷ to create beneficial nutrients that support the maturation of the intestinal immune system.⁸

The gastrointestinal tract provides an optimal environment in which gut microbiota thrive and are nourished. With the gut mucosal immune system and the broader immune system as a whole influenced by the interaction of microbiota with environmental factors, it is clear that diet is an essential element of supporting immunity.

The power of milk

As the first and only form of nutrition available to mammals when they are born, the importance of nutrient-dense mammalian milk cannot be overstated. The immune system needs to be ready for action from the moment of birth, so it is unsurprising that breast milk plays a vital role in supporting immune health from the very beginning. A key component of milk is protein – the building blocks for several bodily tissues as well as immune cells. Interestingly, some dairy proteins are not actually used as building blocks at all but have functional properties instead – take an immune active glycoprotein like lactoferrin, for example.

Lactoferrin is already much studied and is known primarily for its antibacterial effects.⁹ For example, its iron-binding capability enables it to compete with siderophilic bacteria to bind ferric iron,¹⁰ which can reduce the risk of bacterial infection.

However, it additionally offers strong antiviral activity against a broad spectrum of both naked and enveloped DNA and RNA viruses.¹¹ Effective in the inhibition of binding and invasion of these viruses, by binding the virus directly or by binding to the receptor the virus uses to gain access to target cells, lactoferrin can also boost innate immune responses to support antiviral defence.^12-18

The antiviral effects of lactoferrin have been explored in a number of clinical studies. A study of Australian adults who frequently suffer from common cold-associated symptoms, for example, showed that a combined daily dose of 400mg of bovine lactoferrin plus 200mg of whey protein significantly reduced the incidence of colds and the cumulative number of cold-related symptoms in comparison with a placebo.¹⁹ This suggests that the right dose of bovine lactoferrin may act as a prophylactic, reducing the symptoms and duration of upper respiratory tract infections.

Guarding the gut

Naturally, these clinical studies have also led to interest in lactoferrin’s potential benefits against GI infections. A limited number of studies in adults has so far been performed to investigate the effect of bovine lactoferrin supplementation on GI infection such as H. Pylori or Norovirus. So far, the evidence indicates that supplementation with bovine lactoferrin might suppress the colonisation of H. Pylori and may also play a role in suppressing infectious gastroenteritis.²¹

This hypothesis has been tested in a recent study considering the GI symptoms of childcare workers in Japan, who are exposed to a higher risk of infection when working with small children. The study showed that lactoferrin supplementation correlated with reduced acute GI symptoms in winter, as well as significantly shorter average duration of diarrhoea, as compared to a placebo.²²

The goodness of milk

Research is continuing apace, but already all the signs point to lactoferrin being a vital tool for any manufacturer in the immune health space.

This glycoprotein shows exciting potential for supporting immunity in both the gut and the upper respiratory tract – helping product development teams globally meet rising demand from health-conscious consumers.

As the world’s largest dairy cooperative, FrieslandCampina Ingredients has always strived to lead the way in illuminating the benefits of milk to customers, so they can pass on those benefits to their customers. With Biotis^® Immune Health, the company is leveraging its expertise in lactoferrin to expand customers opportunities in the adult immune health market.

References

1. Shoup, M.E. Consumers seek transparency online and in-store: FMI and label insight study, FoodNavigator USA, June 2020
2. FMCG Gurus, 2020
3. Ter Horst, R et al. Host and Environmental Factors Influencing Individual Human Cytokine Responses. Cell. 2016 Nov 3;167,4: 1111-1124.e13.
4. van Splunter, M et al. Bovine Lactoferrin Enhances TLR7-Mediated Responses in Plasmacytoid Dendritic Cells in Elderly Women: Results from a Nutritional Intervention Study With Bovine Lactoferrin, GOS and Vitamin D. Front Immunol. 2018 Nov 20;9:2677
5. Kiecolt-Glaser, J.K. et al. Psychoneuroimmunology: psychological influences on immune function and health. J Consult Clin Psychol. 2002 Jun;70,3:537-47.
6. Kau, A. L. et al. Human nutrition, the gut microbiome and the immune system. Nature 474, 2011.
7. Mcdermott A. J. & Huffnagle, G. B. The microbiome and regulation of mucosal immunity. Immunology 142, 2014.
8. Ximenez, C. & Torres, J. Development of Microbiota in Infants and its Role in Maturation of Gut Mucosa and Immune System, Archives of Medical Research, Volume 48, Issue 8, 2017, Pages 666-680
9. Paesano, R. et al. Body iron delocalization: the serious drawback in iron disorders in both developing and developed countries. Pathog Glob Health, 012.
10. Fransson, G. B. & Lonnerdal, B. Iron in human milk. J Pediatr 96, 1980.
11. Chen, K. M. et al. Bovine lactoferrin inhibits dengue virus infectivity by interacting with heparan sulfate, lowdensity lipoprotein receptor, and DCSIGN. Int J Mol Sci, 2017.
12. Kell, D. B. et al. The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria. Front Immunol, 2020.
13. Mirabelli, C. et al. Morphological Cell Profiling of SARS-CoV-2 Infection Identifies Drug Repurposing Candidates for COVID-19. bioRxiv : The Preprint Server for Biology, 2020.
14. Chang, R. Lactoferrin as potential preventative and adjunct treatment for COVID-19. Int J Antimicrob Agents. 2020 Sep;56,3,:106118.
15. Liao, Y. et al. Biochemical and molecular impacts of lactoferrin on small intestinal growth and development during early life. Biochem Cell Biol. 2012 Jun;90,3:476-84.
16. Suzuki, Y.A. et al. Cell. Mol. Life Sci. 62, 2560, 2005.
17. Ashida, K. et al. Cellular internalization of lactoferrin in intestinal epithelial cells. Biometals 17, 311–315, 2004.
18. Jiang, R. & Lonnerdal, B. Apo- and holo-lactoferrin stimulate proliferation of mouse crypt cells but through different cellular signaling pathways. Int J Biochem Cell Biol. 2012 Jan;44,1,:91-100.
19. Vitetta, L. et al. The Clinical Efficacy of a Bovine Lactoferrin/whey Protein Ig-Rich Fraction for the Common Cold: A Double Blind Randomized Study. Complementary Therapies in Medicine 21, 3. Elsevier Ltd: 164-71, 2013.
20. Okuda, M. et al. Bovine Lactoferrin is effective to suppress Helicobacter pylori colonization in the human stomach: A randomized, double-blind, placebo-controlled study. J Infect Chemother, 2005.
21. Wakabayashi, H. et al. Lactoferrin for prevention of common viral infections. J Infect Chemother, 2014.
22. Mizuki, M. et al. Effects of Lactoferrin on Prevention of Acute Gastrointestinal Symptoms in Winter: A Randomized, Double-Blinded, Placebo-Controlled Trial for Staff of Kindergartens and Nursery Schools in Japan Int J Environ Res Public Health, 2020.