Introduction

Fucoidans are believed to be connected to healthy aging through their multitude of biological effects, including their immune-boosting, anti-inflammatory, blood pressure lowering and cardioprotective properties [1]. These may contribute to the more favourable rates of disease and life expectancy observed in countries such as Japan, where kelp is routinely consumed [2]. In assisting the immune system, the additional antimicrobial effects of fucoidans may be a key mechanism. This article provides a brief focus on the therapeutic potential of fucoidans in the prevention and management of viral infections, with some references to advancing age.

Anti-viral effects

Viruses are microscopic, particle-like pathogens that invade the body via entry points such as the nose, mouth, and airways. Although transmission is random, the odds of cross-infection are greatly increased during cold/flu seasons, being in closer proximity and having compromised immunity, as is the case with the elderly. Once inside, viruses then gain further access to the other organs via the bloodstream, through a carefully orchestrated “virus life-cycle” that involves attaching to and crossing through cell membranes to replicate and spread to other sites [3]. Viruses achieve this by bypassing the immune system and hijacking the cell’s own machinery to reproduce, which ultimately destroys the cell and causes local tissue damage, inflammation, toxicity, and oxidative stress. The host immune system then reacts by mounting a local and systemic response of varying intensity, as indicated by symptoms such as fever, lethargy and swelling with pain in affected tissues.

Infographic on virus life cycle – something like this (see figure 2 in https://kids.frontiersin.org/articles/10.3389/frym.2020.00074)

Standard antiviral drugs have been engineered to block specific points of the virus life cycle. In a similar way, fucoidans are able to block the attachment and entry of some kinds of viruses. This has been shown for Herpes simplex viruses (HSVs), cytomegalovirus (CMV) [4], Influenza A virus [5], Dengue virus[6], HIV [7], and most recently SARS-CoV2 [8]. In this way, fucoidans behave as broad-spectrum antiviral compounds, with the capacity to interrupt the first steps of viral infection. In the case of Avian influenza virus, preclinical evidence has demonstrated that dosage escalation of mekabu (Undaria pinnatifida) fucoidan led to increases in the production of neutralizing antibodies to four different strains, while lowering post-infection viral loads in serum and lung fluids by more than 80% [9]. Furthermore, fucoidans have been shown to stimulate cytotoxic T-cells and natural killer (NK) cells, which help to recognise and eliminating virally infected cells [10].

As a support mechanism, the antioxidant properties of fucoidans have also been implicated in helping pro-oxidant/antioxidant balance at different infection stages and sites [11]. It is also worth noting that other trace compounds in fucoidan extracts, including iodine, may provide some nutrient level immune support roles. In combination, these properties may contribute to the effects listed below, with some highlighted in a report of improved lung pathology following fucoidan therapy, in a lab model of severe influenza infection [12].

• Slowing down viral replication
• Assisting in immune defence responses
• Preventing tissue damage
• Promoting recovery toward normal function
• Preventing relapses

Clinical evidence

In an open-label trial of a combination extract containing fucoidan with a micronutrient mix, involving healthy adults up to 65 years of age, supplement intake was associated with an immune stimulating effect [13]. This was indicated a rise in levels of cytotoxic T-, B- and NK cells, and phagocytes (debris removing cells), together with a decrease in pro-inflammatory IL-6 production after 4-weeks. Another randomized, placebo-controlled pilot study of Undaria fucoidan found that fucoidan users significantly higher levels of leucocyte progenitor cells, and a modest, dosage dependent increases in interferon-gamma (IFN-γ), which has distinct antiviral involvement [14]. These results suggest that fucoidan helps to target some of the immune pathways involved in viral infection, as described above.

A similar antiviral response was evident in a Japanese study involving elderly nursing home residents aged between 67-102 years old who underwent vaccination for influenza. Post-supplementation with Undaria fucoidan intake was associated with a significant elevation in antibody concentrations for 3 different influenza strains, compared to a placebo. For one flu strain vaccine, this effect was sustained for 20 weeks, while previously unvaccinated subjects showed a further enhanced stimulatory effect.

Figure 1. Improvement in antiviral antibodies following flu vaccination in elderly adults who were given fucoidan.

Fucoidan has also shown promise for more chronic and less common viral infections. A study of 15 Japanese subjects (42-86 years of age) with Hepatitis C virus infection, taking fucoidan over an 8-10-month period resulted in a progressive decline in viral RNA load, and improvements in liver enzyme profiles [15]. While in a group of 17 individuals (up to 72 years old) with infections from a range of Herpes virus strains, Undaria fucoidan intake led to a promotion of healing rates and inhibition of skin outbreaks, with pain reduction in some cases, as well as stimulation of T-cell activity [16].

In a group of adults (38-75yrs) suffering from human lymphotropic T-cell virus (HTLV) infection, a virus related to HIV which is associated with more severe immune system problems, fucoidan intake resulted in a significant decrease in viral DNA load [17]. Furthermore, in a sample of 11 individuals with newly acquired HIV infections (up to 60 years of age), fucoidan administration resulted in a mild improvement in CD4+ T-helper cell production (a type of white blood cell that assists in recognising infected cells) and a mild reduction in viral RNA after 3 months , interpreted as a stabilization of their condition, with no adverse effects reported [18].

Conclusion

Fucoidans from marine plants, such as brown seaweeds can inhibit a range of viruses and support the immune system to counteract viral infections. This may support their use as a protective phytomedicine, and more than just an active component of a functional food.

References

1. Fitton, H.J., et al., Therapies from Fucoidan: New Developments. Mar Drugs., 2019. 17(10): p. 571. doi: 10.3390/md17100571.
2. Iso, H. and Y. Kubota, Nutrition and disease in the Japan Collaborative Cohort Study for Evaluation of Cancer (JACC). Asian Pac J Cancer Prev, 2007. 8(Suppl): p. 35-80.
3. Watanabe, T., S. Watanabe, and Y. Kawaoka, Cellular networks involved in the influenza virus life cycle. Cell Host Microbe., 2010. 7(6): p. 427-39. doi: 10.1016/j.chom.2010.05.008.
4. Lee, J.B., et al., Novel antiviral fucoidan from sporophyll of Undaria pinnatifida (Mekabu). Chem Pharm Bull (Tokyo). 2004. 52(9): p. 1091-4. doi: 10.1248/cpb.52.1091.
5. Hayashi, K., et al., Anti-influenza A virus characteristics of a fucoidan from sporophyll of Undaria pinnatifida in mice with normal and compromised immunity. Microbes Infect., 2013. 15(4): p. 302-9. doi: 10.1016/j.micinf.2012.12.004. Epub 2013 Jan 30.
6. Hidari, K.I., et al., Structure and anti-dengue virus activity of sulfated polysaccharide from a marine alga. Biochem Biophys Res Commun., 2008. 376(1): p. 91-5. doi: 10.1016/j.bbrc.2008.08.100. Epub 2008 Aug 30.
7. McClure, M.O., et al., Investigations into the mechanism by which sulfated polysaccharides inhibit HIV infection in vitro. AIDS Res Hum Retroviruses., 1992. 8(1): p. 19-26. doi: 10.1089/aid.1992.8.19.
8. Kwon, P.S., et al., Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro. Cell Discov., 2020. 6(1): p. 50. doi: 10.1038/s41421-020-00192-8. eCollection 2020.
9. Synytsya, A., et al., Mekabu fucoidan: structural complexity and defensive effects against avian influenza A viruses. Carbohydr Polym., 2014. 111:633-44.(doi): p. 10.1016/j.carbpol.2014.05.032. Epub 2014 May 23.
10. Lee, H.H., et al., Undaria pinnatifida Fucoidan-Rich Extract Recovers Immunity of Immunosuppressed Mice. J Microbiol Biotechnol., 2020. 30(3): p. 439-447. doi: 10.4014/jmb.1908.08026.
11. Schwarz, K.B., Oxidative stress during viral infection: a review. Free Radic Biol Med, 1996. 21(5): p. 641-9. doi: 10.1016/0891-5849(96)00131-1.
12. Richards, C., et al., Oral Fucoidan Attenuates Lung Pathology and Clinical Signs in a Severe Influenza a Mouse Model. Mar Drugs., 2020. 18(5): p. 246. doi: 10.3390/md18050246.
13. Myers, S.P., et al., A combined Phase I and II open-label study on the immunomodulatory effects of seaweed extract nutrient complex. Biologics, 2011. 5:45-60.(doi): p. 10.2147/BTT.S12535. Epub 2011 Feb 15.
14. Irhimeh, M.R., J.H. Fitton, and R.M. Lowenthal, Fucoidan ingestion increases the expression of CXCR4 on human CD34+ cells. Exp Hematol., 2007. 35(6): p. 989-94. doi: 10.1016/j.exphem.2007.02.009.
15. Mori, N., et al., Beneficial effects of fucoidan in patients with chronic hepatitis C virus infection. World J Gastroenterol., 2012. 18(18): p. 2225-30. doi: 10.3748/wjg.v18.i18.2225.
16. Cooper, R., et al., GFS, a preparation of Tasmanian Undaria pinnatifida is associated with healing and inhibition of reactivation of Herpes. BMC Complement Altern Med., 2002. 2:11.(doi): p. 10.1186/1472-6882-2-11. Epub 2002 Nov 20.
17. Araya, N., et al., Fucoidan therapy decreases the proviral load in patients with human T-lymphotropic virus type-1-associated neurological disease. Antivir Ther, 2011. 16(1): p. 89-98. doi: 10.3851/IMP1699.
18. Teas, J. and M.R. Irhimeh, Dietary algae and HIV/AIDS: proof of concept clinical data. J Appl Phycol., 2012. 24(3): p. 575-582. doi: 10.1007/s10811-011-9766-0. Epub 2011 Dec 29.

from an Expert Author

George Thouas

BSc, MRepSc, PhD – Biomedical Scientist

George has worked as a medical researcher for 17 years in the university sector, at both Monash University health institutes, and The University of Melbourne. He spent 12 of those years in reproductive health and fertility research, in roles such as Clinical Research Associate, Clinical Embryologist, Post-graduate Demonstrator, Lecturer, and later as a Senior Research Fellow and Lab Manager. His doctoral thesis investigated the effects of mitochondrial damage in the oocyte. He also worked on improving the nutrient and growth requirements for in vitro fertilization and embryo development.

George has authored and coauthored more than 50 publications, including 1 book, 5 book chapters, 30 peer-reviewed journal reports and reviews, 6 patents, international scientific conference proceedings and health practitioner journal articles.

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