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Exploring Immunity as a Growing Health Category in the Food Supplements Business

AUTHOR: Daria Šurić, MPharm

The immune health category has gained increased focus since the Covid-19 pandemic. Consumer interest in immune health is growing, with a demand for botanicals and gut microbiome products. Businesses have opportunities to enter and expand in this market.

Immunity is the body’s inherent capacity to counteract diseases, achieved through the immune system’s defence against an array of pathogens ranging from molecules to parasites. This defence is structured into two primary tiers.

The first, the innate immune system, furnishes an expedient initial barrier against a broad spectrum of pathogens. Constituents of this system encompass physical barriers, notably the skin, as well as non-specific chemical deterrents like lysozyme found in secretions. Additionally, nonpathogenic normal flora bacteria compete for resources with pathogenic counterparts. If these defences are breached, an inflammatory response ensues, luring immune cells to the infection site and dilating blood vessels for enhanced transportation. Interferons can be discharged to combat viruses and tumours, while the complement system engages pathogen membranes, either rupturing them or facilitating elimination by other immune elements. Activation of innate immune cells, such as phagocytes capable of ingesting and destroying invaders, natural killer cells which target virus-infected and tumour cells, and eosinophils that release substances detrimental to parasites, further contribute to this response.

The second tier, the adaptive immune system, necessitates time to react to pathogenic intrusion but subsequently orchestrates a precise counter to the invader. Unlike the nonspecific response of the innate system, the adaptive system’s reactions are pathogen-specific. Importantly, the adaptive system can recollect previous pathogens, enabling a quicker and more effective response upon re-encounter. Comprising T cells and B cells, the adaptive immune system is initiated upon antigen recognition. T cells, divided into cytotoxic (CD8+) and helper (CD4+) types, respectively eliminate virus-infected and cancer cells and modulate immune responses via cytokine secretion. B cells, on the other hand, generate pathogen-specific antibodies that can neutralize, engage the complement system, or enhance phagocytosis. These adaptive responses rely on antigens, recognized by T and B cells, to activate the immune process. Memory cells expedite future reactions, and regulatory T cells mitigate excessive responses. The synergy of these immune levels ensures comprehensive protection against a diverse range of threats, underscoring their indispensable roles in maintaining health. 

What factors can depress our immune system1?

 Older age: as we age, our internal organs may become less efficient; immune-related organs like the thymus or bone marrow produce fewer immune cells needed to fight off infections. Ageing is sometimes associated with micronutrient deficiencies, which may worsen a declining immune function. Environmental toxins (smoke and other particles contributing to air pollution, excessive alcohol): these substances can impair or suppress the normal activity of immune cells.

Excess weight: obesity is associated with low-grade chronic inflammation. Fat tissue produces adipocytokines that can promote inflammatory processes.

Poor diet: malnutrition or a diet lacking in one or more nutrients can impair the production and activity of immune cells and antibodies.

Chronic diseases: autoimmune and immunodeficiency disorders attack and potentially disable immune cells.

Chronic mental stress: stress releases hormones like cortisol that suppress inflammation (inflammation is initially needed to activate immune cells) and the action of white blood cells.

Lack of sleep and rest: sleep is a time of restoration for the body, during which a type of cytokine is released that fights infection; too little sleep lowers the amount of these cytokines and other immune cells1.

Immune health is gaining more importance for consumers and is no longer limited to cold and flu season but is now a year-round concern. Their perception of immunity is moving also toward allergy management and autoimmune diseases.

Consumers expect easier access to immune health products, diverse options, and personalized delivery formats. New formats like drops, bars, and gummies are emerging in the immune health market, together with already popular lozenges, and syrups. New ingredient technologies are getting more and more important, like the slow-release profile of the ingredients or liposomal form, especially vitamin C, but other vitamins and minerals are joining.

Immune health was the top claim in global supplement development in 2020. Natural vitamin C and zinc are popular, but there is growing interest in botanicals like black elderberry and black seed oil. Probiotics, prebiotics and postbiotics play a significant role in immune health due to their impact on the gut microbiome. Experts predict a shift towards multi-functional products that combine immune support with other health benefits. The association between gut and immune health is gaining importance. Also, products targeted to the combination of sleep and immune health are emerging.

 

Food supplements can help support the immune system by providing essential vitamins and minerals that may be lacking in the diet. Some of the main micronutrients that play a role in the immune response include vitamin A, vitamin C, vitamin D, vitamin E, vitamin B6, vitamin B12, folate, zinc, iron, and copper. Deficiencies in specific vitamins and minerals, including vitamin C, zinc, and others, may weaken immune system. Taking supplements containing these vitamins and minerals may help support immune system function.

In the following text, we will go through some food supplement ingredients targeting immune health, that deserve attention.

 Probiotics, prebiotics, and postbiotics

There have been several studies that suggest probiotics play a significant role in maintaining host health by regulating the immune response and defending against pathogens. Probiotics, prebiotics, and postbiotics can, directly and indirectly, regulate microbiota and immune response. Probiotics can improve intestinal microbiota homeostasis, maintain gut barrier integrity, and modulate immune response. In addition, postbiotics, such as the bioactive metabolites, produced by gut microbiota, and/or cell-wall components released by probiotics, also have been shown to inhibit pathogen growth, maintain microbiota balance, and regulate an immune response2.

In summary, probiotics have been shown to have a beneficial effect on the immune system by regulating the balance of gut microbiota, modulating immune response, and maintaining gut barrier integrity. However, further research is needed to fully understand the mechanisms by which probiotics exert their beneficial effects.

Astaxanthin

Astaxanthin is a natural, red-pigmented ketocarotenoid found in some types of microalgae and yeast. It is a powerful antioxidant that plays a role in protecting cells from free radicals and oxidative stress. Astaxanthin can influence immune system, helping to activate white blood cells (T-cells) and natural killer (NK) cells. Along with boosting the immune system, astaxanthin may also help to reduce inflammation3.

In a randomized, double-blind, placebo-controlled trial, 42 participants were allocated to take either 0, 2, or 8 mg of astaxanthin daily for 8 weeks. At the end of 8 weeks, lymphocyte proliferation induced by phytohemagglutinin was decreased in all groups, and the least in the 8 mg group, with concanavalin A, it was increased in only the 8 mg group and was increased in all groups, but the most in the 8 mg group for pokeweed mitogen (0 and 2 mg weren’t different). There was a statistically significant increase in T-cells in all groups and a greater increase in the astaxanthin groups. There was a reduction in total B cells in the 8 mg group, and none in the 2 mg group or the 0 mg group. Skin reaction in response to a tuberculin DTH test was increased in all groups after 48 and 78 hours, and the least increased by 8 mg after 72 hours, while the most increased by 2 mg. There was no statistically significant difference in TNA, while IFN-γ was increased the most by 6 mg, and not by 2 or 0, while IL-6 was increased the most by 8 mg and not by the others, and IL-2 wasn’t statistically significantly different. C-reactive protein was significantly reduced in all groups after 8 weeks, and most reduced by 2 mg. 8-hydroxy-2′-deoxyguanosine, a marker of DNA damage, was reduced considerably in the astaxanthin groups, and was reduced somewhat more after 8 weeks though the difference compared with 2 wasn’t statistically significant, and was the inverse of at 4 weeks. The authors reported no difference in the change in plasma 8-isoprostane. Therefore, the conclusion of the study was dietary astaxanthin decreases a DNA damage biomarker and acute phase protein and enhances immune response in young healthy females (4).

As for its future potential, astaxanthin’s popularity as a dietary supplement has been increasing due to its antioxidant properties and potential health benefits. In the future, continued research may shed more light on its role in immune health and other aspects of well-being.

 Lactoferrin

Lactoferrin is a protein found naturally in the milk of humans, cows, and other mammals. It is also found in other bodily fluids like saliva, tears, mucus, and bile. Lactoferrin has antimicrobial, anti-inflammatory and anti-oxidant properties, and helps the body transport and absorb iron. In humans, the highest concentrations of lactoferrin can be found in colostrum, which is a very nutrient-dense first form of breastmilk produced soon after a baby is born. Clinical trials in adults and children show that lactoferrin supplements can reduce respiratory tract infections, like the common cold. While a lot of work has looked at the effects of lactoferrin in laboratory experiments and animal studies, little research has been done in humans to understand how lactoferrin supplements alter immune function to provide this protection against respiratory infections.

Lactoferrin helps regulate iron levels by balancing the amount of iron in the blood and that present in tissues and cells. This is one way that Lactoferrin provides antibacterial and antiviral properties by removing free iron which these pathogens need to grow.

Due to its similarities to transferrin (which is the main iron transporting molecule in serum) α-LF possesses iron binding capabilities, and it can chelate two ferric irons (Fe3+). LF binds one ferric iron atom in each of its two lobes; however, an important attribute is that it does not release its iron, even at pH 3.5. This is of importance as this property assures iron sequestration in infected tissues where the pH is commonly acidic. In the context of its iron-binding capabilities, it means that when it binds ferric and siderophore-bound iron, it limits the availability of essential iron to microbes.

In healthy individuals, iron is largely intracellular and sequestered within ferritin or as a co-factor of cytochromes and FeS proteins, and as haem complexed to haemoglobin within erythrocytes. Circulating iron is rapidly bound by transferrin. When erythrocytes lyse and haemoglobin or haem is released into the circulation, their haemoglobin is captured by haptoglobin, and haem by hemopexin. Here, circulating serum ferroxidase ceruloplasmin is of importance, as LF can bind to ceruloplasmin, such that a direct transfer of ferric iron between the two proteins is possible. A direct transfer of ferric iron from ceruloplasmin to lactoferrin prevents both the formation of potentially toxic hydroxyl radicals and the utilization of iron by pathogenic bacteria. LF is, therefore, an important player in preventing bacteria from acquiring and sequestering iron, which [with the possible exception of Borrelia burgdorferi]; they require for growth and virulence. LF also acts as a biomarker, as it is commonly upregulated when the host is suffering from various kinds of disease5 (Figure 1).

Nigella sativa seed: a natural adjunct in allergic rhinitis management

The potential of Nigella sativa seeds in the realms of allergic rhinitis and immunity is garnering substantial attention within scientific discourse. Renowned for their diverse bioactive constituents, Nigella sativa seeds exhibit properties that suggest a role in both alleviating allergic rhinitis symptoms and enhancing the body’s immune mechanisms.

Nigella sativa seeds contain thymoquinone, a potent bioactive compound that has shown promise in modulating immune responses and attenuating allergic reactions. Studies have indicated thymoquinone’s ability to mitigate inflammation and suppress histamine release, which are pivotal factors in allergic rhinitis.

Moreover, Nigella sativa seeds possess antioxidant and immunomodulatory attributes, which contribute to their potential in bolstering overall immune function. By aiding in the regulation of immune cells and their responses, these seeds may play a role in maintaining immune homeostasis and potentially reducing the frequency or severity of allergic reactions.

However, while the preliminary research is encouraging, further in-depth investigations are necessary to fully elucidate the mechanisms behind Nigella sativa seeds’ effects on allergic rhinitis and immunity. Clinical trials and rigorous studies will provide a more comprehensive understanding of their potential benefits and therapeutic applications.

One study was done as a supplementary approach to allergic rhinitis management. This study investigated the effects of Nigella sativa seed supplementation on allergic rhinitis patients undergoing allergen-specific immunotherapy. The trial group consisted of 24 patients, with an average age of 34, who exhibited sensitivity to house dust mites and suffered from allergic rhinitis. A comparative control group of eight healthy volunteers, averaging 23 years of age, provided a baseline for evaluation.

The core of the study revolved around administering allergen-specific immunotherapy to all participants over a span of 30 days. Following this initial phase, 12 patients from the experimental group and all healthy volunteers were introduced to Nigella sativa seed supplementation. These individuals ingested a daily oral dose of 2 grams of Nigella sativa seed for an additional 30 days. Meanwhile, the remaining 12 patients continued solely on immunotherapy, and 7 experimental group participants received a placebo.

The study’s outcomes were both intriguing and significant. Participants who underwent specific immunotherapy witnessed a marked surge in the activities of polymorphonuclear leukocytes (PMNs), key players in the immune response. Their capacity to phagocytize and internally eliminate invading pathogens experienced a notable enhancement. Importantly, the incorporation of Nigella sativa seed supplementation acted as an accelerant, further augmenting these critical functions.

Venturing beyond PMNs, the study explored the realm of lymphocyte subsets. Notably, patients subjected to specific immunotherapy and Nigella sativa seed supplementation experienced a substantial increase in CD8 lymphocyte counts. This finding bears significance as CD8 lymphocytes play a pivotal role in orchestrating immune responses against various invaders, including virus-infected cells and malignant growths.

Even healthy volunteers – individuals not grappling with allergic rhinitis – reaped benefits from Nigella sativa seed supplementation. Their PMN functions exhibited a pronounced upswing post-supplementation. This discovery prompts a broader consideration of Nigella sativa seed’s potential beyond targeted interventions.

The findings of this study present compelling avenues for exploration. The amalgamation of Nigella sativa seed supplementation with specific immunotherapy offers a novel pathway for elevating immune responses in allergic rhinitis patients. As we unravel the underlying mechanisms, Nigella sativa seed stands poised to redefine our approach to managing allergic conditions6.

Another study aimed to identify the bioactive components in Nigella sativa seeds and investigate their immune-regulating properties. The researchers isolated and identified a new compound (3-methoxythymol-6-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside) and 11 known compounds from the seeds. They evaluated the immunomodulatory effects of these compounds on RAW 264.7 cells, a type of macrophage, through various assays including phagocytosis, nitric, cytokine release, mRNA transcription, and protein expression. The results  showed that monosaccharide derivatives in the seeds played bidirectional regulatory roles in immunity and anti-inflammation through the regulation of the NF-κB signalling pathways. The findings of the study, include the identification of the new compound and the effects of the compounds on cell viability, phagocytic activity, nitric oxide production, cytokine release, mRNA transcription, and protein expression. These findings suggest that Nigella sativa seeds could be used as dietary supplements for immune modulation7.

Nigella sativa seeds showcase promising potential as a supplement for immune system enhancement and allergy management. With their rich array of bioactive compounds, including thymoquinone, these seeds hold the prospect of bolstering immunity and alleviating allergic reactions. Further research is imperative to fully comprehend their precise mechanisms and establish their role as a valuable addition to immunity and allergy-focused supplementation.

 Sulforaphane

Sulforaphane is a compound found in cruciferous vegetables such as broccoli, cauliflower, and kale. It has been shown to have anti-inflammatory properties and may help boost the immune system. Sulforaphane exists in food in its food bound form known as glucoraphanin, a glycoside (bound to a sugar) or sulforaphane that is commonly seen as a prodrug or storage form of sulforaphane. Glucoraphanin is one of a few molecules known as isothiocyanates, existing mostly in cruciferous vegetables.

Sources of sulforaphane and/or glucoraphanin include:

  • broccoli (44-171 mg/100 g dry weight)
  • broccoli sprouts (1153 mg/100 g dry weight).

Sulforaphane is an active isothiocyanate, found in food via its storage form of glucoraphanin. The application of heat can enhance the absorption of sulforaphane, but the excessive application of heat can prevent most sulforaphane from being absorbed; a balancing act exists8.

Boiling broccoli in 1.5 L water appears to inactivate myrosinase after 1 minute, with the authors of this study concluding that without dipping broccoli into ice water after 30s of heating (to reduce heat application after being removed from liquid) that boiling is unlikely to be an effective method of preparation9. Steaming appears to be the best preservation method, with microwaving coming in second place; boiling broccoli appears to be a highly ineffective way to preserve sulforaphane content.

There are several studies that have investigated the effects of sulforaphane on immunity. One study showed that sulforaphane switches on a set of antioxidant genes and enzymes in specific immune cells, which then combat the injurious effects of molecules known as free radicals that can damage cells and lead to disease. However, more research is needed to fully understand the effects of sulforaphane on immunity.

A review published in the journal Molecules found that sulforaphane has the potential to enhance the natural immune system. The mechanism underlying the health-promoting effect of sulforaphane relates to its indirect action at the cellular level by inducing antioxidant and phase II detoxifying enzymes through the activation of transcription nuclear factor (erythroid-derived 2)-like (Nrf2)9 (Figure 2).

The summary provides information on several clinical trials investigating the effect of sulforaphane on immune system disorders. One mentioned trial studied the effects of broccoli sprout extract on allergy rhinitis in 47 adults (older adults with allergic rhinitis or healthy individuals). The trial lasted for 18 months, and the participants received broccoli sprout extract. The trial was completed, and it was found that sulforaphane reduced pro-inflammatory cytokines with and without combination with fluticasone9.

 Conclusion

The food supplements industry is increasingly focusing on immunity-related products, reflecting growing consumer demand for natural ways to support immune health. Ingredients like astaxanthin, sulforaphane, black seed oil, lactoferrin and many more have gained attention for their potential immuneenhancing properties. Manufacturers are leveraging scientific research to develop innovative formulations that harness these bioactive compounds, aiming to provide consumers with convenient and effective options to bolster their immune systems.

 

 References:

 

1 https://www.hsph.harvard.edu/nutritionsource/nutrition-and-immunity/

2 Liu, Y., Wang, J., & Wu, C. (2022). Modulation of Gut Microbiota and Immune System by Probiotics, Pre-biotics, and Post-biotics. Frontiers in Nutrition, 8, 634897. https://doi.org/10.3389/fnut.2021.634897

3 Astaxanthin: Health Benefits, Safety Information, Dosage, and More – WebMD. https://www.webmd.com/diet/health-benefits-astaxanthin.

4 Park JS, Chyun JH, Kim YK, Line LL, Chew BP. Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab (Lond). 2010;7:18. Published 2010 Mar 5. doi:10.1186/1743-7075-7-18

5 Kell DB, Heyden EL and Pretorius E (2020) The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria. Front. Immunol. 11:1221. doi: 10.3389/fimmu.2020.01221

6 Işik H, Cevikbaş A, Gürer US, et al. Potential adjuvant effects of Nigella sativa seeds to improve specific immunotherapy in allergic rhinitis patients. Med Princ Pract. 2010;19(3):206-211. doi:10.1159/000285289

7 Niu Y, Wang B, Zhou L, Ma C, Waterhouse GIN, Liu Z, Ahmed AF, Sun-Waterhouse D and Kang W (2021) Nigella sativa: A Dietary Supplement as an Immune-Modulator on the Basis of Bioactive

Components. Front. Nutr. 8:722813. doi: 10.3389/fnut.2021.722813

8 https://examine.com/supplements/sulforaphane/

9 Wang GC, Farnham M, Jeffery EH. Impact of thermal processing on sulforaphane yield from broccoli (Brassica oleracea L. ssp. italica). J Agric Food Chem. 2012;60(27):6743-6748. doi:10.1021/jf2050284

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