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Fucoidan

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Fucoidan is a long chain sulfated polysaccharide found in various species of brown algae. Commercially available fucoidan is commonly extracted from the seaweed species Fucus vesiculosus (wracks), Cladosiphon okamuranus, Laminaria japonica (kombu, sugar kelp) and Undaria pinnatifida (wakame).[1][2] Variant forms of fucoidan have also been found in animal species, including the sea cucumber.[3]

Fucoidan occurs in the cell walls of the seaweed plant and serves to protect it from external stresses. The same protective benefits that are of value to the seaweed plant have also found to be of potential benefit for both human and animal health. Fucoidan extracts are utilised in a range of therapeutic health care preparations, being incorporated as high value ingredients in nutritional, medical device, skincare and dermatological products.[4]

The bioactivity of fucoidan extracts is largely determined by the fucoidan extraction method[5] and the seaweed species from which it is extracted. Fucoidan extraction methods, purity, bioactivity, global regulatory approvals and source seaweed species vary between fucoidan producers.

History

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Fucoidan-containing seaweeds have a rich history of medicinal and therapeutic use. The earliest records have been unearthed at Monte Verde in Chile, where archaeological digs have uncovered evidence of their use dating to circa 12000 BC.[6] Early therapeutic use was also evident in ancient Greek and Roman civilizations. In the 17th century, the English botanist John Gerard noted the use of seaweed to treat a wide variety of ailments.

Fucoidan itself was not isolated and described until the early 1900s.[7] In 1913, Swedish Professor Harald Kylin became the first to describe the slimy film found on many seaweeds as ‘fucoidin’ or ‘fucoijin’. The substance subsequently became known as ‘fucoidan’ based on the international naming convention on sugars.[8] Research in the early 20th century focused on extracting crude extracts and reconciling some of the conflicting views on fucoidan. Methods of extracts and isolation of fucoidan from brown seaweeds were determined on laboratory scale by Black et al. at the Institute of Seaweed Research in the UK.[9]

Global research opportunities expanded once fucoidan became commercially available in the 1970s from Sigma Inc. Anti-cancer effects were amongst the first to be reported by Japanese researchers,[10] followed by effects on immune modulation[11] and then anti-tumour,[12] anti-viral[13] and anti-inflammatory responses.[14]

Today, fucoidan continues to be used as a complementary therapy in many parts of Asia, namely Japan and Korea, where it is not uncommon for it to be recommended to patients undergoing treatment for cancer. Interest in, and use of, fucoidan is growing rapidly across the western world as scientific research gains momentum and global regulatory approvals expand. The use of fucoidan as a novel ingredient in dietary supplements, skincare products and functional foods and beverages is increasing.[4]

Active research into the health benefits of fucoidan continues across a range of health indications including anti-cancer, immune modulation, anti-viral, digestive health, anti-inflammation, wound healing and anti-ageing applications.[15][16]

Medicinal purposes

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On Pain

A recent meta-analysis showed that preventive treatment with fucoidan led to a significant reduction in pain in animal models.[17] Additionally, several preclinical studies have observed that fucoidan treatment reduces pain associated with various conditions.[17] Finally, fucoidan has also been tested in several clinical trials, showing some degree of analgesic efficacy, although most were small pilot studies.[17] Considering all the above information, it can be concluded that fucoidan is a promising therapeutic strategy for pain treatment.

Research

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Over 2300 scientific peer-reviewed papers now indicate various bioactive functions of fucoidan. Research has predominantly focussed on the areas of anti-cancer, anti-viral, anti-inflammation or pain[17], immunity, gut and digestive health, wound healing and anti-ageing. Emerging areas of scientific research include microbiome, renal disease, dental health, biomaterials, drug delivery, neuroprotection,[15] coagulation and cardiovascular applications.[18]

Active fucoidan research occurs in Australia, Japan, Korea, Russia and China in addition to Europe and the Americas.[1]

Research lists as fucoidan sources a number of common marine algae familiar to the Japanese diet, including kombu, wakame, hijiki, mozuku,[2] and gagome (Kjellmaniella),[23][24] and other algae such as wracks (Fucus distichus ssp. evanescens)[24] and marine animals, including abalone, scallops, sea urchin, and sea cucumber.[25]

Chemistry

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Fucoidans are sulfated polysaccharides derived primarily from brown algae. The main sugar found in the polymer backbone is fucose, hence the name fucoidan. Other sugars are often present alongside fucose, including galactose, xylose, arabinose and rhamnose. The relative content of these sugars in fucoidan varies significantly between species of algae and can also be affected by the extraction method.[1] The same holds true for the degree of sulfation and other structural features such as acetylation that are only found in fucoidans from certain species. The polymer backbone is negatively charged owing to the presence of sulfate groups and is thus balanced by the presence of metal cations.

The molecular weight of fucoidans is typically high (ca. 50-1000 kDa) and the distribution polydisperse. Extraction techniques that minimise polymer degradation tend to preserve this feature, while other methods can be used to target more specific molecular weight fractions (e.g. 8 kDa). These low molecular weight fractions are generally low yielding and tend to be used for functional research.

Full chemical characterisation is complicated by the number of structural features present in fucoidan. As such, accurate fucoidan analysis involves the use of a number of assays, to quantify the carbohydrates, sulfation, acetylation, molecular weight and cations. These are determined using a number of techniques, including UV-Vis spectrometry, High Performance Liquid Chromatography (HPLC), Atomic Absorption Spectrometry (AAS) and Inductively-Coupled Plasma Spectrometry (ICP). Gas Chromatography (GC) is also often used to determine the sugar composition of the carbohydrate backbone.

Fucoidan product

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Fucoidan can be utilised as a stand-alone ingredient or readily incorporated with other ingredients. Delivery formats vary from capsules and tablets to creams, gels, liquids and serums.

Fucoidan is currently utilised in a wide range of products currently on the market such as dietary supplements, skincare products, medical devices, functional food and beverages and animal health products. Fucoidan is also utilised in medical and pharmaceutical research.

Safety and quality control

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Fucoidan is a natural seaweed compound that has been shown to be non-toxic and non-allergenic. Clinical testing has confirmed that high purity, certified organic fucoidan extracts are safe for human consumption. Specifically, Undaria pinnatifida (wakame seaweed) and Fucus vesiculosus are approved for consumption by the United States Food and Drug Administration (FDA), who classify fucoidan as a biocompatible, biodegradable and non-toxic dietary supplement that is “Generally Regarded As Safe” (GRAS).[26]

In recent years, certain fucoidan extracts in particular have attained regulatory approvals in a number of global jurisdictions, mainly for use in food and dietary supplements. Some extracts are consumed via energy drinks or within vitamin-enriched powdered supplement packets that are mixed into water.

A 2019 peer review noted that, as fucoidan’s global awareness and approval continues to rise, the variation in product quality has shifted—both positively and negatively— with some brands manufacturing products devoid of any actual fucoidan extract, yet using the word “fucoidans” to appear attractive to consumers.[15]

Studies have indicated several instances of fucoidan product manufacturers engaging in false advertising, with tests on several commercially available brands of fucoidan supplements showing the presence of different polysaccharides altogether. Some of the tested brand-names listed “fucoidans” as the primary ingredient on their product’s nutrition label and outer packaging, yet the presence of glucose or cellulose was revealed.

Manufacturers (and consumers) are encouraged to verify the provenance and identity of fucoidan ingredients before incorporating them into formulations, and to support the purchasing of products strictly from reputable producers, brand-names and companies.

Sustainability

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Leading fucoidan producers demonstrate a strong commitment to the sustainable and ethical sourcing of seaweed from which to extract fucoidan. They are able to demonstrate quality and transparency across the supply chain, from the seaweed harvesting process through to fucoidan manufacturing methods, energy consumption, quality assurance and waste management.

As the commercial use of seaweed gains momentum across the globe, and novel applications rise to the fore, it is important that sustainable management practices are maintained.[27] Global fucoidan producers currently vary in their seaweed harvesting practices, locations and standards, including harvesting wild stocks vs farmed seaweeds, and harvesting in clean ocean waters vs those prone to various forms of contamination.

See also

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References

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  1. ^ a b c Fitton, J Helen (2011). "Therapies from Fucoidan; Multifunctional Marine Polymers". Marine Drugs. 9 (10): 1731–1760. doi:10.3390/md9101731. PMC 3210604. PMID 22072995.
  2. ^ a b Berteau & Mulloy (2003)[19] apud Otari & Jadhave (2021), p. 129[20]
  3. ^ Atashrazm, Farzaneh (2015). "Fucoidan and Cancer: A Multifunctional Molecule with Anti-Tumor Potential". Marine Drugs. 13 (4): 2327–2346. doi:10.3390/md13042327. PMC 4413214. PMID 25874926.
  4. ^ a b Fitton, J Helen (2015). "Therapies from Fucoidan: An Update". Marine Drugs. 13 (9): 5920–5946. doi:10.3390/md13095920. PMC 4584361. PMID 26389927.
  5. ^ Ale, Marcel (2011). "Important determinants for fucoidan bioactivity: a critical review of structure-function relations and extraction methods for fucose-containing sulfated polysaccharides from brown seaweeds". Marine Drugs. 9 (10): 2106–2130. doi:10.3390/md9102106. PMC 3210621. PMID 22073012.
  6. ^ Dillehay, Tom (2008). "Seaweed, Food, Medicine, and the Peopling of South America". Science. 320 (5877): 784–786. doi:10.1126/science.1156533. PMID 18467586. S2CID 25648338.
  7. ^ Kylin, Harald (1913). "Zur biochemie der meeresalgen". Hoppe-Seyler's Z. Physiol. 83 (3): 171–197. doi:10.1515/bchm2.1913.83.3.171.
  8. ^ McNeely, W (1959). Industrial gums. Academic Press. pp. 117–125.
  9. ^ Black, W (1951). "Manufacture of algal chemicals. IV†—Laboratory-scale isolation of fucoidin from brown marine algae". J. Appl. Chem. 1 (3): 122–129. doi:10.1002/jsfa.2740030305.
  10. ^ Yamamoto, I (1974). "Antitumor effect of seaweeds. I. Antitumor effect of extracts from Sargassum and Laminaria". Jpn J Exp Med. 66 (6): 543–6. PMID 4455962.
  11. ^ Sugawara, I (1982). "Polysaccharides with sulfate groups are human T-cell mitogens and murine polyclonal B-cell activators (PBAs). I. Fucoidan and heparin". Cell Immunol. 74 (1): 162–71. doi:10.1016/0008-8749(82)90016-8. PMID 6760994.
  12. ^ Teas, J (1984). "Dietary seaweed (Laminaria) and mammary carcinogenesis in rats". Cancer Research. 44 (7): 2758–61. PMID 6426785.
  13. ^ Nakashima, H (1987). "Sulfation of polysaccharides generates potent and selective inhibitors of human immunodeficiency virus infection and replication in vitro". Jpn J Cancer Res. 78 (11): 1164–8. PMID 2447045.
  14. ^ Chong, AS (1986). "Cell surface receptors for sulphated polysaccharides: a potential marker for macrophage subsets". Immunology. 58 (2): 277–84. PMC 1452651. PMID 3011656.
  15. ^ a b c Fitton, J Helen (2019). "Therapies from Fucoidan: New Developments". Marine Drugs. 17 (10): 571. doi:10.3390/md17100571. PMC 6836154. PMID 31601041.
  16. ^ Luthuli, S (2019). "Therapeutic Effects of Fucoidan: A Review on Recent Studies". Marine Drugs. 17 (9): 487. doi:10.3390/md17090487. PMC 6780838. PMID 31438588.
  17. ^ a b c d Huerta, Miguel Á; Tejada, Miguel Á; Nieto, Francisco R. (July 2024). "Fucoidan as a Promising Drug for Pain Treatment: Systematic Review and Meta-Analysis". Marine Drugs. 22 (7): 290. doi:10.3390/md22070290. ISSN 1660-3397. PMC 11277653. PMID 39057399.
  18. ^ Yao, Yuan; Yim, Evelyn K. F. (2021-10-15). "Fucoidan for cardiovascular application and the factors mediating its activities". Carbohydrate Polymers. 270: 118347. doi:10.1016/j.carbpol.2021.118347. ISSN 0144-8617. PMC 10429693. PMID 34364596.
  19. ^ Berteau, Olivier [in French]; Mulloy, Barbara (2003). "Sulfated fucans, fresh perspectives: structures, functions, and biological properties of sulfated fucans and an overview of enzymes active toward this class of polysaccharide". Glycobiology. 13 (6): 29R–40R. doi:10.1093/glycob/cwg058. PMID 12626402.
  20. ^ Otari, Sachin V.; Jadhave, Jyoti P. (2021). "Chapter 6. Seaweed-Based Biodegradable Biopolymers, Composite, and Blends with Applications". In Pant, Deepak; Bhatia, Shashi Kant; Patel, Anil K.; Giri, Anand (eds.). Bioremediation using weeds: Energy, Environment, and Sustainability. Springer Nature. p. 34. ISBN 9789813365520.
  21. ^ Pereira, Leonel (2020). "8 Colloid Producing Seaweeds: Agrophytes, Carrageenophytes and Alginophytes Biodiversity". In Kim, Se-Kwon (ed.). Encyclopedia of Marine Biotechnology. John Wiley & Sons. p. 280. ISBN 9781119143796.
  22. ^ Katayama, Shigeru; Nishio, Toshihiro; Iseya, Zensuke; Saeki, Hiroki (April 2009). "Effects of manufacturing factors on the viscosity of a polysaccharide solution extracted from Gagome kjelllmaniella crassifolia". Fisheries Science. 75 (2): 491–497. Bibcode:2009FisSc..75..491K. doi:10.1007/s12562-009-0070-8.
  23. ^ Encyclopedia of Marine Biotechnology (2020) s.v. Saccharina sculpera syn. Kjellmaniella crassifolia,[21] citing Katayama et al. (2009).[22]
  24. ^ a b Yamada (2006), p. 50.
  25. ^ Yamada (2006), pp. 46–47.
  26. ^ Citkowska, Aleksandra; Szekalska, Marta; Winnicka, Katarzyna (5 August 2019). "Possibilities of Fucoidan Utilization in the Development of Pharmaceutical Dosage Forms". Marine Drugs. 17 (8): 458. doi:10.3390/md17080458. PMC 6722496. PMID 31387230.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ^ Monagail, M (2017). "Sustainable harvesting of wild seaweed resources". European Journal of Phycology. 52 (4): 371–390. Bibcode:2017EJPhy..52..371M. doi:10.1080/09670262.2017.1365273. hdl:10379/12542. S2CID 90699130.
Bibliography
  •  This article incorporates text by Miguel Á. Huerta, Miguel Á. Tejada, and Francisco R. Nieto available under the CC BY 4.0 license.
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