Fucoidan: The immune health evidence

Global interest in immune supplements reached unprecedented heights during 2020. The emergence of the COVID-19 pandemic resulted in increased consumer interest in immune health. Along with a focus on nutritious eating and exercise came a significant rise in the intake of immune-supporting dietary supplements.¹​

There has been an overwhelming focus on ingredients targeting immune function. Particular interest is being observed in natural ingredients that are backed by credible scientific evidence. One such example is fucoidan, a bioactive polysaccharide found naturally in the cell walls of brown seaweeds. High purity, certified organic fucoidans are well known for their beneficial effects in a range of human health conditions. Understandably, the focus on the immune health evidence supporting this innovative marine compound has intensified over the past 12 months. There has been particular interest in the growing body of research supporting the Maritech brand of fucoidan - the world’s only high purity, certified organic fucoidan with global regulatory acceptance.

A short introduction to fucoidan is presented in the video below. 

In order to defend the body against infection, the immune system operates in two different ways – through innate immunity and specific immunity. Innate immunity is the body’s first line of defence. It is fast acting, non-specific and able to combat a wide variety of potential pathogens. In contrast, specific immunity – that which the body acquires following exposure to specific pathogens – is marked by the clonal expansion of lymphocytes which act to neutralize or destroy target antigens.

High purity fucoidan has been shown to enhance both innate and specific immune responses in a range of models. It is a compound that may assist in boosting immune modulation, supporting immune function and dampening allergic responses. There are even research findings demonstrating direct anti-pathogenic, anti-viral and anti-cancer effects.

Vaccine response​

A compromised immune system can result in the body not being able to defend against illness. Immune responses to vaccines or infections are often compromised in older demographics. This inadequate response means that individuals may not be protected against common viruses, such as influenza, which can spread readily in public and aged care environments.

In a clinical setting, the ingestion of fucoidan has been shown to help boost the immune response to a seasonal influenza vaccination. A randomized, double-blind, placebo controlled investigation measured the antibody production of elderly men and women in response to a vaccination that included three different strains of influenza.²​ The group that had been taking oral fucoidan had substantially higher antibody titers against all three influenza strains, in addition to increased natural killer cell activity. A modest 300mg daily dose of fucoidan was required to induce the boosting effect.

There is significant potential for fucoidan to be used as a novel oral adjuvant to boost vaccine responses in the elderly and other vulnerable population groups. It is a subject of ongoing study by the world leading fucoidan research team at Marinova Pty Ltd in Australia.

Infection​

An investigation into the biological potential of Maritech fucoidan as an immune modulator has shown that oral ingestion of fucoidan increased the anti-pathogenic activity of both granulocytes and macrophages in healthy people.³​ Significant increases in cytotoxic T cell numbers and phagocytic capacity in monocytes were demonstrated in this clinical study. The data showed an increase in innate immunity and a general immune priming effect.

In other studies, fucoidans were shown to promote the maturation of dendritic cells, activate natural killer (NK) cells, promote cytotoxic activity and delay human neutrophil apoptosis.^4,5​ Data indicates the potential of fucoidan to act as an effective immune modulator.

A more recent study has shown that Maritech ​organic fucoidan restored the secretion of anti-microbial peptides in the gut of high performance athletes, thereby contributing to the regulation of mucosal immune health.⁶​ The Australian research assessed gut markers of immunity and inflammation, including lysozyme - a known indicator of innate immune function.

The intense physical activity of athletes is often associated with depressed lysozyme levels and changes in immune function. The research demonstrated a ~45% increase in fecal lysozyme in a group of elite athletes following a period of supplementation with Maritech organic fucoidan. Lysozyme levels in the elite athletes normalized and were restored to levels consistent with those of a healthy control group (Figure 1). The potential of fucoidan to restore beneficial anti-microbial activity suggests an exciting future role in the sports nutrition category.

Figure 1. Fecal lysozyme in healthy normals and elite athletes

Immune function is fundamentally dependent upon the release and mobilisation of stem cells from bone marrow. As stem cells are released from bone marrow, they differentiate into different types of immune cells including neutrophils, macrophages, cytotoxic natural killer (NK) cells, granulocytes and dendritic cells. Fucoidan has been reported to increase levels of the chemokine SDF1 in the blood and elicit the release of stem cells into the peripheral circulation when used intravenously in animal models.⁷​ In humans, it has been shown that the oral ingestion of Maritech fucoidan increased the number of CD34+ haemopoeitic stem cells.⁸​ The same study also showed fucoidan increased SDF1 and the number of CXCR4 receptors on stem cells, which may assist in the lodgement of those cells.

Fucoidans have been shown to inhibit the binding and entry of viruses and bacteria into cells. This has been demonstrated in a range of in vitro​ and in vivo​ studies. Fucoidans have been shown to block the entry of coated viruses into cells, potentially preventing or halting the progress of infections. Maritech fucoidan has demonstrated highly effective inhibitory activity against herpes simplex viruses (HSV1 and HSV2) and influenza viruses.^9,10  ​Fucoidan has also been shown to inhibit the binding of other pathogens to cells, including Helicobacter pylori​ (Figure 2).¹¹​

Figure 2. Inhibition of Helicobacter pylori​ 

Published research has also demonstrated that fucoidan reduced allergic responses after ingestion ​and even after topical application.^{12 -14}​ Fucoidan has been shown to suppress the over-expression of the antibody IgE in immune cells in people with allergic dermatitis and also decrease the actual number of cells producing IgE. This damping of allergic responses was associated with the upregulation of galactin-9, a protein integral to the regulation of cell-to-cell interactions.^{15, 16}​

Inflammation​

Recent research indicates fucoidan may play an important role in calming excessive inflammation that is often common following pathogen attack. Oral delivery of Maritech fucoidan was shown to inhibit lung damage and clinical signs of respiratory infection in vivo​ via indirect anti-inflammatory activity.¹⁷​

A recent UK study in a severe Influenza A (H1N1) mouse model demonstrated that orally administered Maritech fucoidan reduced both clinical symptoms and lung damage.¹⁷​ This research adds to previous data demonstrating that fucoidan inhibited damage in influenza models ​and indicates potential for fucoidan to be utilised in nutritional supplements for the management of viral infections where lung damage is occurring.¹⁸​ Importantly, even small reductions in lung damage can substantially reduce the overall disease burden.

Figure 3. Reduction in lung consolidation

In the figure above, lung consolidation was beneficially reduced by a low dose of Maritech fucoidan in a treatment model (infection started prior to the fucoidan being given). In the prevention model, where fucoidan was given prior to the infection, clinical signs of infection were reduced by the higher dose of Maritech fucoidan, as shown in the next figure.

Figure 4. Reduction in the clinical signs of infection

Compromised lung function is a feature of both infection driven and non-infective pathologies. Viral infections, including COVID-19, that affect lung function can cause both acute and long-term chronic damage. SARS-CoV-2 infection suppresses innate immunity and promotes an inflammatory response. Targeting these aspects of SARS-CoV-2 is not only important as the COVID-19 pandemic affects greater proportions of the population, but is also important in addressing regular colds and flu. In addition to dietary fucoidan being shown to attenuate pulmonary damage,¹⁷ ​clinical and animal studies investigating general immune functions have shown fucoidan to increase innate immunity and decrease inflammation^19, ​^20,​ ²¹​.

A recent review summarizes the current research on fucoidan with regard to viral lung infections and lung damage and highlights key areas for further research in this application.²²​

Sourcing high quality fucoidan​

Like all ingredients, fucoidans vary in quality. It is highly recommended that manufacturers verify the provenance and identity of their fucoidan ingredients prior to incorporating them into formulations. Superior fucoidan extracts are not commodity ingredients. They are high purity, certified organic extracts supported by global regulatory acceptance and credible scientific evidence.

The integrity of the entire supply chain can have significant impacts on the quality and efficacy of the final fucoidan extract. Brand owners should insist on fucoidan ingredients that have been derived from sustainably harvested seaweeds that have been grown in clean ocean waters - well away from human, agricultural and industrial contamination.

A further consideration is the fucoidan extraction process itself. Manufacturers of generic fucoidan ingredients typically utilise organic solvents in the extraction process. This has the potential to contaminate the natural compound and reduce bioactivity. Leading global suppliers have now adopted advanced filtration ‘green chemistry’ technologies to separate and purify fucoidan without the use of harsh solvents.

Maritech high purity fucoidan extracts are unique, certified organic ingredients that have been developed, tested and validated for nutritional, pharmaceutical, skincare, veterinary and medical device applications. Maritech extracts are derived from hand-harvested Undaria pinnatifida​ and Fucus vesiculosus​ seaweed. The proprietary Maritech aqueous extraction process produces fucoidan extracts that remain unadulterated in chemical structure and free from solvent residues.

All Maritech fucoidan extracts are certified organic, non-GMO, Kosher and Halal. They are produced in Australia in GMP, ISO9001 and HACCP accredited facilities. The extracts have global regulatory and safety acceptance including FDA notified GRAS (USA), TGA listable (Australia), NHP listed (Canada), KFDA registered (Korea) and EU novel foods approval.

The future​ ​

With the demand for ingredients targeting immune function reaching new heights, global interest in high purity, certified organic fucoidan extracts continues to grow.

Consumers are driving the push for verified and accredited ingredients backed by scientific evidence. High purity certified organic fucoidans offer versatility, efficacy and stability to suit a wide range of applications, making them ideal for new product innovators seeking a novel ingredient with a clear point of differentiation.

The world leading fucoidan research team at Marinova continues to expand its global scientific research program. The immune health benefits of fucoidan remain an active area of investigation, with further research outcomes expected to be released throughout 2021.

The potential immune supporting properties of fucoidan are outlined in the podcast below by Marinova’s Chief Scientist, Dr Helen Fitton.

For further details visit www.marinova.com.au​

References​

1. Nutrition Business Journal, October 2020.
2. Negishi H,​ ​Mori M, Mori H, Yamori Y. Supplementation of elderly Japanese men and women with fucoidan from seaweed increases immune responses to seasonal influenza vaccination. The Journal of Nutrition. 2013.
3. Myers S,  O’Connor J, Fitton H, Brooks L,  Rolfe M, Connellan P, Wohlmuth H,  Chera P, and Morris C. A combined Phase I and II open-label study on the immunomodulatory effects of seaweed extract nutrient complex. Biologics. 2011.
4. Kar S, Sharma G, Das P. Fucoidan cures infection with both antimony-susceptible and -resistant strains of Leishmania donovani​ through Th1 response and macrophage-derived oxidants. Journal of Antimicrobial Chemotherapy. 2011
5. Zhang W, Oda T, Yu Q, Jin J. Fucoidan from Macrocystis pyrifera​ has powerful immune-modulatory effects compared to three other fucoidans. Marine Drugs. 2015.
6. Cox A, Cripps A, Taylor P, Fitton H, West, N. Fucoidan supplementation restores fecal lysozyme concentrations in high-performance athletes: A pilot study. Marine Drugs. 2020.
7. Sweeney E, Lorat-Jacob H, Priestley G, Nakamoto B, Papayannopoulou T. Sulfated polysaccharides increase plasma levels of SDF-1 in monkeys and mice: Involvement in mobilization of stem/progenitor cells. Blood. 2002.
8. Irhimeh M, Fitton H, Lowenthal R. Fucoidan ingestion increases the expression of CXCR4 on human CD34+ cells. Experimental Hematology. 2007.
9. Thompson K, Dragar C. Antiviral activity of Undaria pinnatifida​ against herpes simplex virus.  Phytotherapy Research. 2004. 
10. Hayashi T. Studies on evaluation of natural products for antiviral effects and their applications. The Pharmaceutical Society of Japan. 2008.
11. Chua E, Verbrugghe P, Perkins T, Tay C. Fucoidans disrupt adherence of Helicobacter pylori​ to AGS cells in vitro. Evidence-Based Complementary and Alternative Medicine. 2015.
12. Mizuno M, Sakaguchi K, Sakane I. Oral Administration of Fucoidan Can Exert Anti-Allergic Activity after Allergen Sensitization by Enhancement of Galectin-9 Secretion in Blood. Biomolecules. 2020.
13. Yang JH. Topical application of fucoidan improves atopic dermatitis symptoms in NC/Nga mice. Phytother Res. 2012.
14. Tian T, Chang H, He K, Ni Y, Li C, Hou M, Chen L, Xu Z, Chen B, Ji M. Fucoidan from seaweed Fucus vesiculosus​ inhibits 2,4-dinitrochlorobenzene-induced atopic dermatitis. Int Immunopharmacol. 2019.
15. Iwamoto K, Hiragun T, Takahagi S, Yanase Y, Morioke S, Mihara S, Kameyoshi Y, Hide M. Fucoidan suppresses IgE production in peripheral blood mononuclear cells from patients with atopic dermatitis. Arch Dermatol Res. 2011
16. Tanino Y, Hashimoto T, Ojima T, Mizuno M. F-fucoidan from Saccharina japonica​ is a novel inducer of galectin-9 and exhibits anti-allergic activity. J Clin Biochem Nutr. 2016
17. Richards C, Williams N, Fitton H, Stringer D, Karpiniec S, Park A. Oral fucoidan attenuates lung pathology and clinical signs in a severe influenza A mouse model. Marine Drugs 2020.
18. Synytsya A, Bleha R, Synytsya A, Pohl R, Hayashi K, Yoshinaga K, Nakano T, Hayashi T. Mekabu fucoidan: structural complexity and defensive effects against avian influenza A viruses. Carbohydr Polym. 2014.
19. Kuznetsova, T.A.; Smolina, T.P.; Makarenkova, I.D.; Ivanushko, L.A.; Persiyanova, E.V.; Ermakova, S.P.; Silchenko, A.S.; Zaporozhets, T.S.; Besednova, N.N.; Fedyanina, L.N.; Kryzhanovsky, S.P. Immunoadjuvant Activity of Fucoidans from the Brown Alga Fucus evanescens​. Marine Drugs.​ 2020.
20. Fitton JH,; Stringer DN, Karpiniec SS. Therapies from Fucoidan: An Update. Marine Drugs. 2015.
21. Fitton, J.H.; Stringer, D.N.; Park, A.Y.; Karpiniec, S.S. Therapies from Fucoidan: New Developments. Marine Drugs.​ 2019.
22. Fitton, J.H.; Park, A.Y.; Karpiniec, S.S.; Stringer, D.N. Fucoidan and Lung Function: Value in Viral Infection. Marine Drugs.​ 2021.