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Complex seaweed-derived compounds known as fucoidans support immune function and longevity
Picture a frozen earth 635 million years ago, the planet at last beginning to thaw from an extraordinary ice age that blanketed land and sea. As the permafrost softens and melts, new life emerges from the ocean depths: sea plants.[1] The earth’s first “complex” multicellular creatures, these sea plants are the ancestors of the familiar seaweeds of today, with their branches, splayed fans, and ribbony blossoms, a grand harbinger of the flowering of plant and animal life to come. And the biochemical solutions they have crafted to survive the salty, turbulent seas, at times swarming with microorganisms, offer surprising help for some of our own health challenges.[2]
Seaweeds contain large amounts of uniquely structured long chain sugars, or polysaccharides, with many immune benefits.[3] Seaweed polysaccharides come in a variety of arrangements and molecules, varying by seaweed type, and each appears to have its own set of healing properties.[4]
Fucoidans as physiologically active polysaccharides
A significant body of seaweed research focuses on fucoidans, polysaccharides rich in a sugar called fucose. Fucoidans are commonly found in the cell walls of Undaria pinnatifida, a large brown kelp native to Japan, and in other seaweeds such as Fucus vesiculosus (also known as bladderwrack).[5],[6] Fucoidans are such an important component of seaweeds that they constitute up to 30% of their dry weight.[7]
Fucoidans constitute up to 30% of the dry weight of seaweed, an important component of the Okinawan diet – one of the healthiest diets in the world.
Nearly 1,500 peer-reviewed studies have been published on fucoidans, half of those in the last decade alone.[8] Interest in fucoidans surged when scientists began to study the world’s longest living people on the island of Okinawa, some of whom were over a century old.[9],[10] The Okinawan diet, which includes more than a dozen varieties of seaweed, is now considered one of the healthiest diets in the world.[11] A survey of more than 100,000 participants across Japan showed that the consumption of seaweed and several other traditional foods – such as rice and tofu – is correlated with lower all-cause mortality.[12]
Fucoidans have been called “a treasure trove of physiologically active polysaccharides,”[13] with biological effects including immune modulation,[14] antibacterial and antiviral properties,[15],[16] anti-inflammatory activity,[17] modulation of gut flora,[18] and even antithrombotic (anti-clotting) and anticancer properties.[19],[20]
Fucoidans enhance immune function
Fucoidans enhance immune function and stimulate both innate and adaptive immunity.[5] Specifically, fucoidans modulate two prominent classes of T-cells: Th1 cells, which attack intracellular bacteria and viruses, and Th2 cells, which fight helminths (worms) and other extracellular pathogens.[21] Fucoidans also downregulate excessive Th2 responses, which can lead to allergies and inflammation. And they work not only when taken orally, but also topically for skin irritation.[22]
Fucoidans may protect the brain and nervous system from chronic inflammation, particularly supporting specialized cells called microglia.
Fucoidans also increase natural killer cell activity, stimulate immune cells called macrophages, and promote the maturation of specialized immune cells (dendritic cells).[23],[24] Some fucoidans also mobilize stem cells and increase their numbers in the blood.[25]
Fucoidans may exert anti-aging activity by increasing the expression of the sirtuins.[26] Sirtuins are cellular enzymes that help to regulate immune system function[27] and are also being studied for their anti-aging potential. It is thought that a boost in sirtuin activity may explain in part how calorie restriction extends life span.[28]
Finally, fucoidans are potent anti-inflammatory molecules.[29] Fucoidans may protect the brain and nervous system from chronic inflammation, particularly supporting specialized cells called microglia.[30]
Fucoidans as antibacterial agents
Helicobacter pylori (H. pylori) colonizes the stomach of half the world’s humans, and can cause chronic gastritis, peptic ulcer disease, gastric (stomach) cancer, and gastric MALT lymphoma.[31] Unfortunately, the efficacy of standard triple antibiotic combination therapy has declined in recent years to only 70%, despite the use of these multiple medications simultaneously.[32],[33] Growing evidence suggests that fucoidans may boost antibiotic efficacy in resolving H. pylori infection.
Growing evidence suggests that fucoidans may boost antibiotic efficacy in resolving H. pylori infection.
In one study, three different fucoidan extracts (from Fucus vesiculosus and Undaria pinnatifida) were shown to significantly reduce the numbers of H. pylori bacteria adhering to human gastric epithelial cells in vitro.[34] It was suggested that fucoidans attach to H. pylori bacteria, and either dislodge them from the gastric cells, or simply prevent them from adhering. Additional studies have shown that fucoidan binds to several proteins on the outer membrane of H. pylori,[35] and that the anti-H. pylori adhesion activity was fucoidan-specific, not due to an unspecific colloidal effect.
Antiviral effects of fucoidans
Just as fucoidan inhibits bacteria from attaching to cells, it can bind to cell surface proteins that viruses use to enter cells, including herpes simplex viruses (HSV), which cause oral and genital herpes. Many herpes strains are now resistant to acyclovir, the most common antiviral drug used to combat infection.[36] Therefore, a natural product that could protect against infection or reduce the viral burden would be of great interest.
Fucoidan exhibited “excellent in vitro antiviral activity,” the researchers concluded, and was “significantly more active against clinical strains of HSV-2 than HSV-1.”
An extract of 75% pure fucoidan was tested in vitro against 32 clinical strains of HSV, including 14 strains of HSV-1 and 18 strains of HSV-2.[37] HSV-1 tends to cause oral herpes lesions, while HSV-2 causes genital herpes lesions.[38] Fucoidan exhibited “excellent in vitro antiviral activity,” the researchers concluded, and was “significantly more active against clinical strains of HSV-2 than HSV-1.” This finding has also been confirmed in animal studies. In a 2008 study, oral administration of fucoidan protected mice from infection with HSV-1, as judged by survival rates and lesion scores.[39]
Fucoidans also may protect against potentially deadly viruses such as hepatitis C,[40] which can cause liver cancer, and a retrovirus known as HTLV-I,[41] which has been implicated in several diseases including T-cell lymphoma.
Summary
Fucoidans constitute up to 30% of the dry weight of seaweed, an important component of the Okinawan diet – one of the healthiest diets in the world. The consumption of seaweed and other traditional foods is associated with healthy aging, lower levels of inflammation, and low mortality from all causes. Fucoidans offer a remarkable range of biological activities, ranging from immune support to the prevention of bacterial and viral infections. This ‘food’ from the sea is truly one of the ocean’s great medicinal gifts.
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[2] Percival E. The polysaccharides of green, red and brown seaweeds: their basic structure, biosynthesis and function. Br Phycol J. 1979;14(2):103-17.
[3] Da VD, Viswanathan P. Seaweed polysaccharides – new therapeutic insights against the inflammatory response in diabetic nephropathy. Antiinflamm Antiallergy Agents Med Chem. 2017;15(3):178-90.
[4] Ruocco N, et al. Polysaccharides from the marine environment with pharmacological, cosmeceutical and nutraceutical potential. Molecules. 2016 Apr 27;21(5).
[5] Fitton J. Therapies from fucoidan; multifunctional marine polymers. Marine Drugs. 2011;9: 1731-60.
[6] Berteau O, Mulloy B. Sulfated fucans, fresh perspectives: structures, functions, and biological properties of sulfated fucans and an overview of enzymes active toward this class of polysaccharide. Glycobiology. 2003;13(6):29-40.
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[8] Fitton JH, et al. Therapies from fucoidan: an update. Mar Drugs. 2015 Sep; 13(9): 5920-46.
[9] Sho H. History and characteristics of Okinawan longevity food. Asia Pac J Clin Nutr. 2001;10(2):15964.
[10] Willcox BJ, et al. Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world’s longest-lived people and its potential impact on morbidity and life span. Ann N Y Acad Sci. 2007 Oct;1114:434-55.
[11] Willcox D, et al. The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load. J Am Coll Nutr. 2009 Aug;28 Suppl:500S-16S.
[12] Iso H, Kubota Y. Nutrition and disease in the Japan Collaborative Cohort Study for Evaluation of Cancer (JACC). Asian Pac J Cancer Prev. 2007;8 Suppl:35-80.
[13] Kusaykin M, et al. Structure, biological activity, and enzymatic transformation of fucoidans from the brown seaweeds. Biotechnol J. 2008;3(7):904-15.
[14] Zapopozhets TS, et al. Antibacterial and immunomodulating activity of fucoidan. Antibiot Khimioter. 1995; 40:9-13.
[15] Hirmo S, et al. Inhibition of heparan sulfate and other glycosaminoglycans binding to Helicobacter pylori by various polysulfated carbohydrates. FEMS Immunol Med Microbiol. 1995;10;301-6.
[16] Adhikari U, et al. Structure and antiviral activity of sulfated fucans from Stoechospermum marginatum. Phytochemistry. 2006;67:2474-82.
[17] Cumashi A, et al. A comparative study of the anti-inflammatory, anticoagulant, anti-angiogenic, and anti-adhesive activities of nine different fucoidans from brown seaweeds. Glycobiology. 2007;17:541-52.
[18] Shang Q, et al. Dietary fucoidan modulates the gut microbiota in mice by increasing the abundance of Lactobacillus and Ruminococcaceae. Food Funct. 2016 Jul 13;7(7):3224-32.
[19] Millet J, et al. Antithrombotic and anticoagulant activities of a low molecular weight fucoidan by the subcutaneous route. Thromb Haemost. 1999;81:391-5.
[20] Atashrazm F, et al. Fucoidan and cancer: a multifunctional molecule with anti-tumor potential. Mar Drugs. 2015 Apr 14;13(4):2327-46.
[21] Kar S, et al. Fucoidan cures infection with both antimony-susceptible and -resistant strains of Leishmania donovani through Th1 response and macrophage-derived oxidants. J Antimicrob Chemother. 2011 Mar;66(3):618-25.
[22]Yang JH. Topical application of fucoidan improves atopic dermatitis symptoms in Nc/Nga mice. Phytother Res. 2012;26(12):1898-903.
[23] Shimizu J, et al. Proportion of murine cytotoxic t cells is increased by high molecular-weight fucoidan extracted from Okinawa mozuku (Cladosiphon okamuranus). J Health Sci. 2005;51(3):394-7.
[24] Hu Y, et al. Fucoidan enhances dendritic cell-mediated T-cell cytotoxicity against NY-ESO-1 expressing human cancer cells. Biochem Biophys Res Commun. 2010; 392(3):329-34.
[25] Irhimeh MR, et al. Fucoidan ingestion increases the expression of CXCR4 on human CD34+ cells. Exp Hematol. 2005;35:989-94.
[26] Wang T, et al. Low-molecular-weight fucoidan attenuates mitochondrial dysfunction and improves neurological outcome after traumatic brain injury in aged mice: involvement of Sirt3. Cell Mol Neurobiol. 2016 Nov;36(8):1257-68.
[27] Kong S, et al. Sirtuin 1 in immune regulation and autoimmunity. Immunol Cell Biol. 2012 Jan;90(1):6-13.
[28] Guarente L. Sirtuins in aging and disease. Cold Spring Harb Symp Quant Biol. 2007;72:483-8.
[29] Semenov AV, et al. Sulfated polysaccharides as inhibitors of receptor activity of P-selectin and P-selectin-dependent inflammation. Quest Med Chem. 1999;2:135-43.
[30] Park HY, et al. Anti-inflammatory effects of fucoidan through inhibition of NFκB, MAPK and Akt activation in lipopolysaccharide-induced BV2 microglial cells. Food Chem Toxicol. 2011 Aug;49(8):1745-52.
[31] Marshall BJ, Windsor HM. The relation of Helicobacter pylori to gastric adenocarcinoma and lymphoma: pathophysiology, epidemiology, screening, clinical presentation, treatment, and prevention. Med Clin North Am. 2005 Mar;89(2):313-44.
[32] Mégraud F. H pylori antibiotic resistance: prevalence, importance, and advances in testing. Gut. 2004;53(9):1374-84.
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[34] Chua EG, et al. Fucoidans disrupt adherence of Helicobacter pylori to AGS Cells in vitro. Evid Based Complement Alternat Med. 2015;2015:120981.
[35] Shibata H, et al. Inhibitory effect of Cladosiphon fucoidan on the adhesion of Helicobacter pylori to human gastric cells. J Nutr Sci Vitaminol.1999;45(3):325-36.
[36] Pottage JC Jr, Kessler HA. Herpes simplex virus resistance to acyclovir: clinical relevance. Infect Agents Dis. 1995 Sep;4(3):115-24.
[37] Thompson KD, Dragar C. Antiviral activity of Undaria pinnatifida against herpes simplex virus. Phytother Res. 2004 Jul;18(7):551-5.
[38] Web MD. Herpes Simplex: Herpes Type 1 and 2 [Internet]; 2016 [cited 2017 Jul 28]. Available from: http://www.webmd.com/genital-herpes/pain-management-herpes
[39]Hayashi K, et al. Defensive effects of a fucoidan from brown alga Undaria pinnatifida against herpes simplex virus infection. Int Immunopharmacol. 2008 Jan;8(1):109-16.
[40] Mori N, et al. Beneficial effects of fucoidan in patients with chronic hepatitis C virus infection. World J Gastroenterol.2012;18(18):2225-30.
[41] 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):89-98.
The information provided is for educational purposes only. Consult your physician or healthcare provider if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.
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