Extensive research has been undertaken on the immune-modulatory properties of fucoidan. Published papers have reported that fucoidan may exert a range of beneficial effects on the human immune system, including the reduction of allergic responses and the activation of dendritic cells, natural killer cells and T cells. It has also been shown that fucoidan has the potential to boost important anti-viral and anti-tumour responses.
Boosting immune responses
Immune responses to vaccines or infections can be compromised, particularly during ill health and in older people. In a clinical setting, ingestion of fucoidan was shown to help boost the immune responses to seasonal influenza vaccinations (Negishi, 2013). The ingestion of fucoidan has also been shown to increase the anti-pathogenic activity of granulocytes and macrophages in healthy people (Myers, 2011). Increased immune activity after fucoidan ingestion can even eliminate the tropical protozoan parasite Leishmania, as seen in a mouse model (Kar, 2011). Fucoidans can also promote the maturation of dendritic cells, activate NK cells and promote cytotoxic activity (Zhang, 2015).
Supporting immune function
Fucoidan has been shown to restore the secretion of anti-microbial peptides and contribute to the regulation of mucosal immune health (Cox, 2020). An Australian study 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 associated with 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 high purity fucoidan. Lysozyme levels in the elite athletes normalized and were restored to levels consistent with those of a healthy control group.
Damping allergic responses
Published research has reported that fucoidan can reduce allergic responses after ingestion (Maruyama, 2015) and even after topical application (Yang, 2012). Fucoidan can suppress the over-expression of the antibody IgE in immune cells in people with allergic dermatitis and can also decrease the actual number of cells producing IgE (Iwamoto, 2011). It has been proposed that the mechanism of action for this damping of allergic responses is via upregulation of galactin-9, a protein integral to the regulation of cell-to-cell interactions (Tanino, 2016, Mizuno 2020).
Stem cell modulation
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 all the 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 (Sweeney, 2002). In humans, it has been shown that the oral ingestion of fucoidan over a period of days increases the number/release of CD34+ haemopoeitic stem cells (Irhimeh, 2007). 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 can block the entry of coated viruses to cells, thereby preventing or halting the progress of infections. Fucoidan has been shown to be a highly effective inhibitor of Herpes Simplex viruses (HSV1 and HSV2) (Thompson, 2004) and influenza viruses (Hayashi, 2008). Oral delivery of fucoidan also inhibits lung damage and clinical signs of respiratory infection in vivo via indirect anti-inflammatory activity. Research in a severe Influenza A H1N1 mouse model using orally administered fucoidan (equivalent to 1-2g day human dose) showed attenuation of both clinical signs and lung damage (Richards, 2020). The mechanism of action appeared to be modulation of pathology, rather than inhibition of virus, indicating that fucoidan has utility regardless of the pathogen causing damage.
Fucoidan has also demonstrated protection against Herpes virus infection (Hayashi, 2008; Hayashi, 2008). In vitro, fucoidan has been shown to inhibit several different strains of influenza, including H1N1 (Hayashi, 2008; Wang, 2017), H5N1 (Makarenkova, 2010), H5N3 and H7N2 (Synytsa, 2014) and parainfluenza (Taoda, 2008). Clinically, fucoidan reduced pro-viral loads in patients with HTLV-1 (Araya, 2011) and showed benefits for patients with chronic hepatitis C (Mori, 2012). Fucoidan has also been shown to exhibit activity against Newcastle virus (Elizondo-Gonzalez, 2012), canine distemper (Trejo-Avila, 2014) and even the measles virus (Morán-Santibañez, 2016).
Compromised lung function is a feature of both infection driven and non-infective pathologies. Viral infections, including the pandemic strain SARS-CoV-2, 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 pandemic affects greater proportions of the population, but is also important in addressing regular colds and flu. In clinical and animal studies investigating general immune functions fucoidans have been shown to increase innate immunity and decrease inflammation (Kuznetsova 2020, Fitton 2015, Fitton 2019). In addition, dietary fucoidan has been shown to attenuate pulmonary damage in a model of acute viral infection (Richards 2020). A recent review (Fitton 2021) 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.