Fucoidan

• How It Works

  Fucoidan has anticancer properties, but this has not yet been studied in humans.

  Fucoidan is a complex polysaccharide found in many species of brown seaweed. It has been shown to slow blood clotting. Laboratory studies suggest that it can prevent the growth of cancer cells and has antiviral, neuroprotective, and immune-modulating effects. Studies in humans have not yet been conducted to determine whether these same anticancer effects may occur. One human study suggests fucoidan may help to enable longer courses of chemotherapy, but more studies are needed to confirm safety and effectiveness. Because of its anti-clotting property, fucoidan may increase the side effects of “blood-thinning” drugs.

• Purported Uses
  • To boost the immune system
    In vitro data suggest a role for fucoidan in boosting host defense mechanisms. Several human studies also suggest it may help stimulate immune functioning and boost antibody production after vaccination.
  • To reduce inflammation
    Several in vitro and animal studies suggest that fucoidan has anti-inflammatory properties. Human studies are needed.
  • To prevent cancer
    Several in vitro and animal studies show that fucoidan has antitumor properties. Clinical trials have not been conducted.
  • To lower blood pressure
    A study in overweight and obese adults suggests that fucoidan use over a sustained period may decrease diastolic blood pressure and as well as “bad” cholesterol levels. Studies to confirm these results are needed.
  • To prevent blood clots
    Laboratory studies suggest that fucoidan has anticoagulant and antithrombotic effects. A study in humans also suggests it slows the production of blood clots. As such, fucoidan may interfere with blood-thinning medication.
  • To prevent infections
    Laboratory and animal studies indicate that fucoidan has antiviral properties.
• Do Not Take If

  You are taking anticoagulants such as warfarin and heparin: Because fucoidan can slow the blood-clotting process, it may increase bleeding risk when used with these drugs.

• Clinical Summary

  Fucoidan is a sulfated polysaccharide found in the cell walls of many species of brown seaweed. In vitro studies show that fucoidan has antitumor, antiangiogenic ^{(2) (3) (4) (5) (6) (7)}, antiviral ^(15) (16), anti-arthritic ⁽¹⁸⁾, and immunomodulatory ⁽¹⁷⁾ effects. Fucoidan also exhibited neuroprotective ^(11) (12), radioprotective ⁽¹³⁾, and antiulcer ⁽¹⁴⁾ properties.

  In animal models, fucoidan exerts anti-inflammatory effects to protect against various organ injuries ^{(19) (20) (21)}. Oral administration of fucoidan extracts also improved inflammatory pathology associated with acute colitis ⁽²²⁾. Although a high molecular weight fucoidan did not improve outcomes in mice following intracerebral hemorrhage, it is suggested that low-molecular-weight fucoidans have increased therapeutic potential and should be evaluated for this purpose ⁽²³⁾.

  In humans, dietary fucoidan modulates platelet aggregation via anti-thrombotic effects ⁽²⁴⁾. In overweight or obese adults, fucoidan administration over 3 months decreased diastolic blood pressure and low-density lipoprotein cholesterol concentrations, and increased insulin secretion ⁽²⁵⁾. Fucoidan administration also decreased pro-viral load in a small group of patients with human T-lymphotropic virus type-1-associated neurological disease ⁽²⁶⁾. The consumption of fucoisan for a 1-month period prior to seasonal influenza vaccination may boost antibody production after vaccination in immune-compromised elderly ⁽²⁷⁾.

  Preclinical data suggest that fucoidan can help relieve cyclophosphamide-induced intestinal mucosal injury by altering gut flora, resulting in reduced inflammation and increased expression of tight junction proteins ⁽³⁰⁾. Oral ingestion of fucoidan in a small group of volunteers was found to improve mobilization of hematopoietic progenitor stem cells with high levels of CXCR4 expression ⁽²⁸⁾. In advanced stage colorectal cancer patients receiving chemotherapy, fucoidan coadministration enabled patients to continue chemotherapy and regulated fatigue ⁽²⁹⁾; fucoidan also reduced the levels of pro-inflammatory cytokines in another study of advanced cancer patients ⁽³¹⁾.

  Because fucoidan demonstrates anticoagulant ^(8) (9) and antithrombotic ⁽¹⁰⁾ activities, it may have additive effects when taken with anticoagulants.

• Food Sources

  Several species of brown seaweed

• Purported Uses
  • Anticancer effects
  • Hypertension
  • Immunostimulation
  • Inflammation
  • Infections
  • Prevent blood clots
• Mechanism of Action

  In vitro, a low-molecular-weight fucoidan inhibited human rheumatoid arthritis fibroblast synoviocytes and triggered apoptosis via decreased expression and secretion of metalloproteinase (MMP)-1, MMP-3, and MMP-9, as well as suppression of NF-kappaB binding activity, p65 nuclear translocation, and IkappaB-alpha degradation ⁽¹⁸⁾. In animal models fucoidan treatment protected against liver injury via suppression of the inflammatory signaling pathway, inflammatory mediators, and inflammatory cell infiltration ⁽²⁰⁾. It also reduced production of cyclooygenase-2 and nitric oxide, while increasing the expression of the hepatoprotective enzyme hemeoxygenase-1 on murine liver and HepG2 cells ⁽²¹⁾. Fucoidan suppressed inflammation in an ultraviolet B-irradiated mouse model as evidenced by decreased thickness of the prickle cell layer and decreased MMP-1 ⁽¹⁹⁾.

  In humans, dietary fucoisan shortens lysis time of the thrombus by elevating prostacyclin (PGI2) secretion caused by increased H2O2 production in the blood ⁽²⁴⁾. Various antitumor, antiviral and immune-modulating effects of fucoidan are attributed to the stimulation of natural killer (NK) cells, downregulation of transcription factor AP-I involved in cellular proliferation, and to the downregulation of IGF-IR signaling through the main IRS-1/PI3K/AKT pathway ^{(2) (3) (32)}. In melanoma cells, fucoidan increased the antitumor effects of lapatinib via inhibition of ERBB3, known to promote melanoma metastasis ⁽³³⁾. It was also shown to reduce tumor-promoting M2 macrophages and in combination with etoposide, to prevent HCT116 tumorigenicity in human colorectal cells ⁽³⁴⁾. Neuroprotective effects are attributed to suppression of tumor necrosis factor-alpha (TNF-alpha)- and interferon-gamma (IFN-gamma)-induced nitric oxide production in C6 glioma cells ⁽¹¹⁾ and to its antioxidative effects ⁽¹²⁾. Fucoidan inhibits metastasis by preventing adhesion of tumor cells to the extracellular matrix. This is achieved by blocking the fibronectin cell-binding domain, necessary for formation of adhesion complexes ⁽⁴⁾. It also induced apoptosis of human T-cell leukemia virus type I (HTLV-1) that causes adult T-cell leukemia by inactivating NF-kB, which regulates antiapoptotic proteins ⁽³⁾. In a murine model, fucoidan suppressed angiogenesis induced by sarcoma 180 cells ⁽⁵⁾.

• Contraindications

  Because of its anticoagulant property ^(8) (9), fucoidan may have additive effects with anticoagulants such as warfarin and heparin.

• Adverse Reactions

  Diarrhea, which improved immediately after stopping fucoidan administration ⁽²⁶⁾.

• Herb-Drug Interactions

  Anticoagulants such as warfarin and heparin: Due to its anti-thrombotic effects, fucoidan may increase bleeding risk ⁽²⁴⁾.

• References

  1. Giraux JL, Matou S, Bros A, Tapon-Bretaudiere J, Letourneur D, Fischer AM. Modulation of human endothelial cell proliferation and migration by fucoidan and heparin. Eur J Cell Biol 1998; 77(4):352-359.

  2. Maruyama H, Tamauchi H, Hashimoto M, Nakano T. Antitumor activity and immune response of Mekabu fucoidan extracted from Sporophyll of Undaria pinnatifida. In Vivo 2003; 17(3):245-249.

  3. Haneji K, Matsuda T, Tomita M et al. Fucoidan extracted from Cladosiphon okamuranus tokida induces apoptosis of human T-cell leukemia virus type 1-infected T-cell lines and primary adult T-cell leukemia cells. Nutr Cancer 2005; 52(2):189-201.

  4. Liu JM, Bignon J, Haroun-Bouhedja F et al. Inhibitory effect of fucoidan on the adhesion of adenocarcinoma cells to fibronectin. Anticancer Res 2005; 25(3B):2129-2133.

  5. Koyanagi S, Tanigawa N, Nakagawa H, Soeda S, Shimeno H. Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities. Biochem Pharmacol 2003; 65(2):173-179.

  6. Alekseyenko TV, Zhanayeva SY, Venediktova AA, et al. Antitumor and antimetastatic activity of fucoidan, a sulfated polysaccharide isolated from the Okhotsk Sea Fucus evanescens brown alga. Bull Exp Biol Med. 2007 Jun;143(6):730-2.

  7. Nagamine T, Hayakawa K, Kusakabe T, et al. Inhibitory effect of fucoidan on Huh7 hepatoma cells through downregulation of CXCL12. Nutr Cancer. 2009;61(3):340-7.

  8. Colliec S, Fischer AM, Tapon-Bretaudiere J, et al. Anticoagulant properties of a fucoïdan fraction. Thromb Res. 1991 Oct 15;64(2):143-54.

  9. Irhimeh MR, Fitton JH, Lowenthal RM. Pilot clinical study to evaluate the anticoagulant activity of fucoidan. Blood Coagul Fibrinolysis. 2009;20: 607-610.

  10. Church FC, Meade JB, Treanor RE, Whinna HC. Antithrombin activity of fucoidan. The interaction of fucoidan with heparin cofactor II, antithrombin III, and thrombin. J Biol Chem. 1989 Feb 25;264(6):3618-23.

  11. Do H, Pyo S, Sohn EH. Suppression of iNOS expression by fucoidan is mediated by regulation of p38 MAPK, JAK/STAT, AP-1 and IRF-1, and depends on up-regulation of scavenger receptor B1 expression in TNF-alpha- and IFN-gamma-stimulated C6 glioma cells. J Nutr Biochem. 2010 Aug;21(8):671-9.

  12. Luo D, Zhang Q, Wang H, et al. Fucoidan protects against dopaminergic neuron death in vivo and in vitro. Eur J Pharmacol. 2009 Sep 1;617(1-3):33-40.

  13. Byon YY, Kim MH, Yoo ES, et al. Radioprotective effects of fucoidan on bone marrow cells: improvement of the cell survival and immunoreactivity. J Vet Sci. 2008 Dec;9(4):359-65.

  14. Choi JI, Raghavendran HR, Sung NY, et al. Effect of fucoidan on aspirin-induced stomach ulceration in rats. Chem Biol Interact. 2010 Jan 5;183(1):249-54.

  15. Lee JB, Hayashi K, Hashimoto M, Nakano T, Hayashi T. Novel antiviral fucoidan from sporophyll of Undaria pinnatifida (Mekabu). Chem Pharm Bull (Tokyo). 2004 Sep;52(9):1091-4.

  16. Hayashi K, Nakano T, Hashimoto M, Kanekiyo K, Hayashi T. Defensive effects of a fucoidan from brown alga Undaria pinnatifida against herpes simplex virus infection. Int Immunopharmacol. 2008 Jan;8(1):109-16.

  17. Raghavendran HR, Srinivasan P, Rekha S. Immunomodulatory activity of fucoidan against aspirin-induced gastric mucosal damage in rats. Int Immunopharmacol. 2011 Feb;11(2):157-63.

  18. Shu Z, Shi X, Nie D, et al. Low-Molecular-Weight Fucoidan Inhibits the Viability and Invasiveness and Triggers Apoptosis in IL-1beta-Treated Human Rheumatoid Arthritis Fibroblast Synoviocytes. Inflammation. Oct 2015;38(5):1777-1786.

  19. Maruyama H, Tamauchi H, Kawakami F, et al. Suppressive Effect of Dietary Fucoidan on Proinflammatory Immune Response and MMP-1 Expression in UVB-Irradiated Mouse Skin. Planta Med. Oct 2015;81(15):1370-1374.

  20. Li XJ, Ye QF. Fucoidan reduces inflammatory response in a rat model of hepatic ischemia-reperfusion injury. Can J Physiol Pharmacol. Nov 2015;93(11):999-1005.

  21. Lim JD, Lee SR, Kim T, et al. Fucoidan from Fucus vesiculosus protects against alcohol-induced liver damage by modulating inflammatory mediators in mice and HepG2 cells. Mar Drugs. Feb 2015;13(2):1051-1067.

  22. Lean QY, Eri RD, Fitton JH, et al. Fucoidan Extracts Ameliorate Acute Colitis. PLoS One. 2015;10(6):e0128453.

  23. Burchell SR, Iniaghe LO, Zhang JH, et al. Fucoidan from Fucus vesiculosus Fails to Improve Outcomes Following Intracerebral Hemorrhage in Mice. Acta Neurochir Suppl. 2016;121:191-198.

  24. Ren R, Azuma Y, Ojima T, et al. Modulation of platelet aggregation-related eicosanoid production by dietary F-fucoidan from brown alga Laminaria japonica in human subjects. Br J Nutr. Sep 14 2013;110(5):880-890.

  25. Hernandez-Corona DM, Martinez-Abundis E, Gonzalez-Ortiz M. Effect of fucoidan administration on insulin secretion and insulin resistance in overweight or obese adults. J Med Food. Jul 2014;17(7):830-832.

  26. Araya N, Takahashi K, Sato T, 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):89-98.

  27. Negishi H, Mori M, Mori H, et al. Supplementation of elderly Japanese men and women with fucoidan from seaweed increases immune responses to seasonal influenza vaccination. J Nutr. Nov 2013;143(11):1794-1798.

  28. Irhimeh MR, Fitton JH, Lowenthal RM. Fucoidan ingestion increases the expression of CXCR4 on human CD34+ cells. Exp Hematol. Jun 2007;35(6):989-994.

  29. Ikeguchi M, Yamamoto M, Arai Y, et al. Fucoidan reduces the toxicities of chemotherapy for patients with unresectable advanced or recurrent colorectal cancer. Oncol Lett. Mar 2011;2(2):319-322.

  30. Shi H, Chang Y, Gao Y, et al. Dietary fucoidan of Acaudina molpadioides alters gut microbiota and mitigates intestinal mucosal injury induced by cyclophosphamide. Food Funct. 2017 Sep 20;8(9):3383-3393.

  31. Takahashi H, Kawaguchi M, Kitamura K, et al. An Exploratory Study on the Anti-inflammatory Effects of Fucoidan in Relation to Quality of Life in Advanced Cancer Patients. Integr Cancer Ther. 2017 Feb 1:1534735417692097. doi: 10.1177/1534735417692097. [Epub ahead of print]

  32. Kim IH, Nam TJ. Fucoidan downregulates insulin-like growth factor-I receptor levels in HT-29 human colon cancer cells. Oncol Rep. 2018 Mar;39(3):1516-1522.

  33. Thakur V, Lu J, Roscilli G, et al. The natural compound fucoidan from New Zealand Undaria pinnatifida synergizes with the ERBB inhibitor lapatinib enhancing melanoma growth inhibition. Oncotarget. 2017 Mar 14;8(11):17887-17896.

  34. Chen LM, Liu PY, Chen YA, Tseng HY, Shen PC, Hwang PA, Hsu HL. Oligo-Fucoidan prevents IL-6 and CCL2 production and cooperates with p53 to suppress ATM signaling and tumor progression. Sci Rep. 2017 Sep 19;7(1):11864.