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.
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]
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.
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]
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 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.
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.
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.
Polysaccharides, or polycarbohydrates, are the most abundant carbohydrates found in food. They are long-chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with water (hydrolysis) using amylase enzymes as catalyst, which produces constituent sugars. They range in structure from linear to highly branched. Examples include storage polysaccharides such as starch, glycogen and galactogen and structural polysaccharides such as hemicellulose and chitin.
Kelps are large brown algae or seaweeds that make up the order Laminariales. There are about 30 different genera. Despite its appearance, kelp is not a plant but a stramenopile, a group containing many protists.
Carrageenans or carrageenins are a family of natural linear sulfated polysaccharides. They are extracted from red edible seaweeds. Carrageenans are widely used in the food industry, for their gelling, thickening, and stabilizing properties. Their main application is in dairy and meat products, due to their strong binding to food proteins. Carrageenans have emerged as a promising candidate in tissue engineering and regenerative medicine applications as they resemble animal glycosaminoglycans (GAGs). They are used for tissue engineering, wound coverage, and drug delivery.
Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars. It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have over 100 individual sugars, each of which can be sulfated in variable positions and quantities. Chondroitin sulfate is an important structural component of cartilage, and provides much of its resistance to compression. Along with glucosamine, chondroitin sulfate has become a widely used dietary supplement for treatment of osteoarthritis, although large clinical trials failed to demonstrate any symptomatic benefit of chondroitin.
Fucoxanthin is a xanthophyll, with formula C42H58O6. It is found as an accessory pigment in the chloroplasts of brown algae and most other heterokonts, giving them a brown or olive-green color. Fucoxanthin absorbs light primarily in the blue-green to yellow-green part of the visible spectrum, peaking at around 510-525 nm by various estimates and absorbing significantly in the range of 450 to 540 nm.
Konbu is edible kelp mostly from the family Laminariaceae and is widely eaten in East Asia. It may also be referred to as dasima or haidai.
Ascophyllum nodosum is a large, common cold water seaweed or brown alga (Phaeophyceae) in the family Fucaceae. Its common names include knotted wrack, egg wrack, feamainn bhuí, rockweed, knotted kelp and Norwegian kelp. It grows only in the northern Atlantic Ocean, along the north-western coast of Europe including east Greenland and the north-eastern coast of North America. Its range further south of these latitudes is limited by warmer ocean waters. It dominates the intertidal zone. Ascophyllum nodosum has been used numerous times in scientific research and has even been found to benefit humans through consumption.
Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on N-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) linked core of fucoidan is a suspected carbohydrate antigen for IgE-mediated allergy.
Alginic acid, also called algin, is a naturally occurring, edible polysaccharide found in brown algae. It is hydrophilic and forms a viscous gum when hydrated. When the alginic acid binds with sodium and calcium ions, the resulting salts are known as alginates. Its colour ranges from white to yellowish-brown. It is sold in filamentous, granular, or powdered forms.
Heparinoids are glycosaminoglycans which are chemically and pharmacologically related to heparin. They include oligosaccharides and sulfated polysaccharides of plant, animal, or synthetic origin. Multiple scientific studies have been conducted on heparinoids.
Sulfation is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected less directly. Regardless of the mechanism, the installation of a sulfate-like group on a substrate leads to substantial changes.
Mastocarpus stellatus, commonly known as carrageenan moss or false Irish moss, is a species in the Rhodophyceae division, a red algae seaweed division, and the Phyllophoracea family. M. stellatus is closely related to Irish Moss. It grows in the intertidal zone. It is most collected in North Atlantic regions such as Ireland and Scotland, together with Irish moss, dried, and sold for cooking and as the basis for a drink reputed to ward off colds and flu. Marine biologists have completed studies on the medicinal reputation of M. stellatus to discover the full potential of its pharmaceutical benefits. Additionally, marine biologists have conducted research on its potential to serve as an alternative to plastic. The application of M. stellatus in these different industries is correlated with the seaweed's adaptations which developed in response to the environmental stressors present around its location on the rocky intertidal.
Udotea is a genus of green algae in the family Udoteaceae.
Extracellular polymeric substances (EPSs) are natural polymers of high molecular weight secreted by microorganisms into their environment. EPSs establish the functional and structural integrity of biofilms, and are considered the fundamental component that determines the physicochemical properties of a biofilm. EPS in the matrix of biofilms provides compositional support and protection of microbial communities from the harsh environments. Components of EPS can be of different classes of polysaccharides, lipids, nucleic acids, proteins, lipopolysaccharides, and minerals.
Turbinaria is a genus of brown algae (Phaeophyceae) found primarily in tropical marine waters. It generally grows on rocky substrates. In tropical Turbinaria species that are often preferentially consumed by herbivorous fishes and echinoids, there is a relatively low level of phenolics and tannins.
Seaweed, or macroalgae, refers to thousands of species of macroscopic, multicellular, marine algae. The term includes some types of Rhodophyta (red), Phaeophyta (brown) and Chlorophyta (green) macroalgae. Seaweed species such as kelps provide essential nursery habitat for fisheries and other marine species and thus protect food sources; other species, such as planktonic algae, play a vital role in capturing carbon and producing at least 50% of Earth's oxygen.
Edible seaweed, or sea vegetables, are seaweeds that can be eaten and used for culinary purposes. They typically contain high amounts of fiber. They may belong to one of several groups of multicellular algae: the red algae, green algae, and brown algae. Seaweeds are also harvested or cultivated for the extraction of polysaccharides such as alginate, agar and carrageenan, gelatinous substances collectively known as hydrocolloids or phycocolloids. Hydrocolloids have attained commercial significance, especially in food production as food additives. The food industry exploits the gelling, water-retention, emulsifying and other physical properties of these hydrocolloids.
Beta porphyranase is an enzyme responsible for the degradation of porphyran, which composes the cell wall of red algae. So far only five β-porphyranases have been identified: PorA and PorB are found in the marine bacteria Zobellia galactinovirans. A wild-type porphyranase activity has been found in Pseudoalteromonas atlantica. BpGH16B and BpGH86A have been found in the human gut bacterium, Bacteroides plebeius, of Japanese individuals.
Medicinal fungi are fungi that contain metabolites or can be induced to produce metabolites through biotechnology to develop prescription drugs. Compounds successfully developed into drugs or under research include antibiotics, anti-cancer drugs, cholesterol and ergosterol synthesis inhibitors, psychotropic drugs, immunosuppressants and fungicides.
Ulva australis, the southern sea lettuce, is a species of bright green coloured seaweed in the family Ulvaceae that can be found in waters around Australia and was first described by Swedish botanist Johan Erhard Areschoug. It is an edible green algae, although sometimes designated as a seaweed. General characteristics of Ulva australis include a smooth surface, distromatic blades, lobed fronds, and thallus color from dark green to light grass green. It can be either free floating or attached by a single holdfast. Its cells appear to be irregularly arranged, have rounded edges, and have shapes such as rectilinear, square, and pentagonal.
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