The sea is a cruel mistress, especially if you are a species of seaweed. Marine algae face many threats. These include grazing by aquatic herbivores, competition for space by multiple organisms, osmotic stress, high levels of UV and, in the shallow waters, oxygen. They also have to defend themselves against hordes of potential pathogens. Each drop of seawater contains an average one million bacteria (1) and far more than that near sewage outfalls or where people are swimming. Each drop also contains at least 10 million viruses (2), but these are mostly phages which target the bacteria rather than seaweeds or swimmers. Unless, of course, you are swimming near a sewage outfall, in which case you really need to come in out of the water NOW.
Terrestrial plants don’t have it easy but life is definitely harder underwater; and because sedentary seaweeds are sitting targets, they specialise in chemical self-defence. They produce at least 18 different classes of compounds with antibacterial and anti-viral activity (3-9), and these tend to be highly bioactive because they have to overcome dilution in seawater (5, 6). They also produce antioxidants, photo-protectants, osmo-protectants and other defence compounds with multiple potential clinical applications (4, 7) including the treatment of infections (9) and cancer (ie 10). In short, seaweeds are the new pharmacological frontier and the basis of what is now known as blue biotechnology, with corals and sponges playing supporting roles.
One group of compounds with strong anti-bacterial activity are the phlorotannins, which are condensed polyphenols and structurally distinct from the polyphenols which occur in terrestrial plants (11). Like many members of this class they are potent anti-inflammatory agents (12, 13), but almost uniquely among the polyphenols, they are lipid-soluble. They are also potent antioxidants (14), and not only protect omega 3 HUFA’s while these remain in the algae but also chaperone them through the entire marine ecosystem, including the bodies of the krill, pelagic fish, marine mammals and apex predators such as humans. This property, plus their strong anti-inflammatory activity, explains why eating oily fish is healthy while eating fish oil capsules is not (15, 16).
The omega 3’s and phlorotannins are important but fairly well established so I will focus on another fascinating class of algal secondary metabolites, the polysulphated oligosaccharides.
The three main types are fucoidans (major sugar l-fucose), carrageenans (d-galactose) and ulvans (rhamnose/xylose). All of these have different and also overlapping biological effects which include antioxidant, anti-inflammatory, anticancer, anticoagulant/antithrombotic, retina-protective, immunomodulatory and gastrointestinal / prebiotic activity, and renal sparing and lipid lowering effects; plus strong antibacterial, antiprotozoan and anti-viral activity (ie 17, 18).
The fucoidans are the most intensively researched group, and currently hot precisely because of their anti-viral uses. Their anti-viral actions include a decoy effect, whereby viruses bind to fucoidan instead of their ‘intended’ cell docking sites. Earlier this year fucoidans were shown to bind Covid spike protein and block Covid-19 infection in vitro far more effectively than remdesivir, the current pharma standard (19).
In short, marine algae are a nutritional treasure chest and the fucoidans are doubloons.
There is no point in reviewing the considerable body of mechanistic and ex vivo data if you cannot absorb fucoidans, which are quite large molecules; but the evidence clearly shows that when seaweed is eaten it is digested and the fucoidans are indeed absorbed, in limited amounts (20). And once absorbed, they get busy.
They exert a range of anti-cancer effects including the inhibition of proliferation, the induction of apoptosis and mid-cell cycle arrest, and anti-metastatic activity (21-24). For those interested in knowing more about mechanism, the first two papers document the effects of fucoidan on the PI3K/AKT, MAPK and caspase pathways and the latter two document inhibition of VEGF and MMP activity.
This does not mean that cancer patients should wander down to the shoreline and start grazing. All seaweeds are edible, but some only once (25). And even if you do find a commonly eaten variety, that’s not the end of the story. The fucoidans are a very diverse group of compounds with significant differences in structure (and therefore biological activity) between different species of seaweed, and even in the same species when harvested during different seasons or conditions (26, 27). The extraction method used is important too (28, 29), because higher molecular weight fractions are generally more effective at killing cancer cells than the low weight molecular extracts (30). On the other hand, lower weight fractions make better sunscreen (31).
It is probably best to interrogate the literature and find out whether there is a seaweed or an extract that might be relevant to you (ie 32), and then approach a reputable supplier of marine algal extracts. If you prefer pharmaceuticals, cancer is big business and scientists are tinkering with fucoidan molecules to make them more effective, and of course patentable (33). Seaweed-based drugs are definitely on the horizon, even if they are not yet in port.
Moving on to another general property of the fucoidans, they are highly effective anti-adhesins. Seaweeds utilize these compounds to prevent fouling, but you can use them to remove and prevent plaque (a bacterial biofilm) from forming on your teeth. Given our growing understanding of the role of periodontal disease in driving neurodegenerative and other serious diseases, a plaque remover you can consume with your cornflakes makes really good sense.
The fucoidans’ anti-bacterial and anti-biofilm effects are, at least in theory, exactly what you need if you suffer from dental plaque, tartar, periodontal disease and fear of dental hygienists. Recent research shows that this promise holds true in clinical practice (34-36), and I have confirmed it to my own satisfaction by using plaque-disclosing tablets to monitor the effects of different fucoidan extracts in my shaving mirror. You can use these to watch your own plaque disappear, as fucoidans will be incorporated into the next version of the formulation ‘Xtend’.
Fucus vesiculosus (bladder wrack) is a particularly good source (34, 35).
There is another type of infection where these marine compounds may be life-saving. Numbers of people with prosthetic hips, knees and heart valves are increasing rapidly, and one thing all these implants have in common is that they are not immuno-competent. I have heard from several colleagues of sudden deaths occurring years after surgery in such patients. After other causes had been excluded, autopsy revealed biofilm and other signs of infection on the prosthesis. The surgeon who originally implanted the prosthesis never even hears about this problem, as it can occur many years after surgery. This may reflect very slow-growing infections, or it may be to do with cumulative risk over time. Potentially pathogenic bacteria exist in all tissues, including the brain and bloodstream, and a temporary dip in immunity may be enough to allow a prosthetic infection to begin. Antibiotics cannot be prescribed for decade-long prophylaxis. Natural anti-adhesins such as the fucoidans are safe, however, and in my view likely to improve the surgeon’s long-term outcomes.
The fucoidans may be useful to surgeons in the shorter term too, because there is some evidence that their combination of anti-adhesin and anti-inflammatory effects reduces the risk of post-surgical adhesions (37). With fucoidan pharmacokinetics in mind, these compounds will work most effectively if taken in multiple doses throughout the day, or more simply, taken with every meal. Given that after surgery (or physio) to remove or break adhesions those adhesions often reform, anything that reduces the risk of adhesion and re-adhesion is worth trying. From limited personal experience, the fucoidans could be helpful in this respect.
The anti-adhesin property of the fucoidans has other applications. They can be used to modify blood clotting; given our pro-inflammatory and pro-clotting diet, the fucoidans’ ability to reduce the tendency of blood platelets to stick to each other (38) is generally desirable. There is also some anti-coagulant activity (39). The mechanism overlaps slightly with that of heparin, a somewhat analogous polysulphated oligosaccharide co-polymer with an amino-sugar backbone comprised of n-acetyl glucosamine.
More futuristically, but remaining with the anti-adhesin theme, the fucoidans are able to dislodge resting stem cells from the bone marrow, releasing them into the circulation (40). This effectively activates them, allowing them to undertake repairs and regenerative work in other tissues. This will not be very effective if your tissues are packed with senescent cells, which should ideally be selectively removed first, or at least simultaneously. We are actively developing this approach and will introduce a new set of pharmaconutritional tools in 2021.
But wait – there’s more. There is accumulating evidence that the fucoidans are neuroprotective (41-43). More specifically, this has been shown to occur pre-clinically in the hippocampus (41), and as any specialist in Alzheimer’s will tell you, hippocampal preservation is a profoundly important gero-suppressant action. There is evidence too, for a combination of prebiotic and directly anti-inflammatory activity in the gut (44-45), and clinically significant renal sparing (46). Finally, when used topically, the fucoidans are an effective treatment for herpes infection (47-49). And naturally, they are safe. In the USA fucoidans have GRAS status and in the EU they are accepted as novel foods, both for consumption at up to 250 mg/day.
And more … Because the seaweeds not only produce highly effective anti-adhesins, they also make the best water-proof adhesives known to man. I remember watching Atlantic breakers beating on the rocks of Surtsey, throwing spray 15 meters into the air and revealing, between each hamar blow, kelp clinging to the basalt. Seaweeds produce a glue that performs better in aquatic environments than any other, a glue formed from a different set of polysaccharides (50) which will one day be used by sailors, marine engineers and dentists and surgeons too.
There is a widely held idea that sea water helps wounds to mend, but it ain’t necessarily so. Being full of bacteria, sea water can actually increase inflammation and slow the healing process (51). Tap water may be a better bet (52). Seaweeds, on the other hand, contain healing compounds by the score. Technically, they are not phyto- but algonutrients.
I don’t much enjoy reading – or writing – paeans to a specific berry or herb. The supplement space is full of companies hawking extracts of red wine, green tea or the latest indigenous super-fruit. This is an outdated and largely discredited approach which apes the pharmaceutical model, and has little to do with the burgeoning science of pharmaconutrition. Just this once, however, I thought it worth reviewing a polyphyletic group of over 13,000 different species which has so much to offer.
- Amsler CD. Algal Chemical Ecology. Volume 468 Springer; Berlin, Germany: 2008.
- Parsons R, Breitbart M, Lomas M, Carlson CA. Ocean time-series reveals recurring seasonal patterns of virioplankton dynamics in the northwestern Sargasso Sea. ISME J 6, 273–284 (2012).
- Blunt JW, Munro MHG, Copp BR, Keyzers RA, Prinsep MR. Marine natural products. Nat. Prod. Rep. 2015;32:116–211.
- Mayer A, Rodríguez AD, Taglialatela-Scafati O, Fusetani N. Marine pharmacology in 2009–2011: Marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of action. Mar. Drugs. 2013;11:2510–2573.
- Chojnacka K, Kim S-K. Marine Algae Extracts. Wiley-VCH; Weinheim, Germany: 2015. Introduction of Marine Algae Extracts; pp. 1–14.
- Hughes CC, Fenical W. Antibacterials from the Sea. Chemistry. 2010;16:12512–12525.
- Morán-Santibañez K, Cruz-Suárez LE, Ricque-Marie D, Robledo D, Freile-Pelegrín Y, Peña-Hernández MA, Rodríguez-Padilla C, Trejo-Avila LM. Synergistic Effects of Sulfated Polysaccharides from Mexican Seaweeds against Measles Virus. Biomed Res Int. 2016;2016:8502123.
- Kim S.K., Mendis E. Bioactive compounds from marine processing byproducts-a review. Food Res. Int. 2006;39:383–393.
- Shannon E, Abu-Ghannam N. Antibacterial Derivatives of Marine Algae: An Overview of Pharmacological Mechanisms and Applications. Mar Drugs. 2016 Apr 22;14(4):81. Review
- Simmons TL, Andrianasolo E, McPhail K, Flatt P, Gerwick WH. Marine natural products as anticancer drugs. Mol Cancer Ther. 2005 Feb; 4(2):333-42. Review
- Shibata T, Kawaguchi S, Hama Y, Inagaki M, Yamaguchi K, Nakamura T. Local and chemical distribution of phlorotannins in brown algae. J Appl Phycol. 2004; 16:291–6
- Sugiura Y, Tanaka R, Katsuzaki H, Imai K, Matsushita T. The anti-inflammatory effects of phlorotannins from Eisenia arborea on mouse ear edema by inflammatory inducers. J Funct Food 5(4), October 2013, 2019-2023
- Phasanasoophon K, Kin SM. Anti-Inflammatory Activity of the Phlorotannin Trifuhalol A Using LPS-Stimulated RAW264.7 Cells Through NF-κB and MAPK Main Signaling Pathways. Nat Prod Comm 2019, https://doi.org/10.1177/1934578X19849798
- Wang T, Jónsdóttir R, Liu H, Gu L, Kristinsson HG, Raghavan S, Olafsdóttir G. Antioxidant capacities of phlorotannins extracted from the brown algae Fucus vesiculosus.J Agric Food Chem. 2012 Jun 13;60(23):5874-83.
- Clayton PR, Ladi S. From alga to omega; have we reached peak (fish) oil? J R Soc Med. 2015 Sep;108(9):351-7.
- Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KHO, AlAbdulghafoor FK, Summerbell CD, Worthington HV, Song F, Hooper L. Omega 3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2018, Issue 7. Art. No.: CD003177.
- Patel S. Therapeutic importance of sulfated polysaccharides from seaweeds: updating the recent findings. 3 Biotech. 2012 Sep; 2(3): 171–185.
- Fitton HJ, Stringer DS, Park AY, Karpiniec SN. Therapies from Fucoidan: New Developments. Mar Drugs. 2019 Oct 9;17(10):571.
- Kwon PS, Oh H, Kwon SJ, Jin W, Zhang F, Fraser K, Hong JJ, Linhardt RJ, Dordick JS. Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro. Cell Discov. 2020 Jul 24;6:50.
- Imbs TI, Zvyagintseva TN, Ermakova SP. . Is the transformation of fucoidans in human body possible? Int J Biol Macromol. 2020 Jan 1;142:778-781.
- van Weelden G, Bobiński M, Okła K, van Weelden WJ, Romano A, Pijnenborg JMA. Fucoidan Structure and Activity in Relation to Anti-Cancer Mechanisms. Mar Drugs. 2019 Jan 7; 17(1):32 Review
- Sanjeewa KKA, Lee JS, Kim WS, Jeon YJ. The potential of brown-algae polysaccharides for the development of anticancer agents: An update on anticancer effects reported for fucoidan and laminaran. Carbohydr Polym. 2017 Dec 1; 177():451-459. Review
- Huang TH, Chiu YH, Chan YL, et al. Prophylactic administration of fucoidan represses cancer metastasis by inhibiting vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in Lewis tumor-bearing mice. Mar Drugs. 2015;13(4):1882-1890
- Atashrazm F, Lowenthal RM, Woods GM, Holloway AF, Dickinson JL. Fucoidan and cancer: a multifunctional molecule with anti-tumor potential. Mar Drugs. 2015;13(4):2327-46.
- Mozzachiodi R, Scuri R, Roberto M, Brunelli M. Caulerpenyne, a toxin from the seaweed Caulerpa taxifolia, depresses afterhyperpolarization in invertebrate neurons. Neuroscience. 2001;107(3):519-26.
- Fletcher HR, Biller P, Ross AB, Adams JMM. The seasonal variation of fucoidan within three species of brown macroalgae. Algal Res.-Biomass Biofuels Bioprod. 2017;22:79–86.
- Ale M.T., Meyer A.S. Fucoidans from brown seaweeds: An update on structures, extraction techniques and use of enzymes as tools for structural elucidation. RSC Adv. 2013;3:8131–8141.
- Marais MF, Joseleau JP. A fucoidan fraction from Ascophyllum nodosum. Carbohydr Res. 2001 Nov 8; 336(2):155-9.
- Ponce NM, Pujol CA, Damonte EB, Flores ML, Stortz CA. Fucoidans from the brown seaweed Adenocystis utricularis: extraction methods, antiviral activity and structural studies. Carbohydr Res. 2003 Jan 20; 338(2):153-65.
- Sanjeewa KKA, Lee JS, Kim WS, Jeon YJ. The potential of brown-algae polysaccharides for the development of anticancer agents: An update on anticancer effects reported for fucoidan and laminaran. Review. Carbohydr Polym. 2017 Dec 1; 177():451-459.
- Kim YI, Oh WS, Song PH, Yun S, Kwon YS, Lee YJ, Ku SK, Song CH, Oh TH. Anti-Photoaging Effects of Low Molecular-Weight Fucoidan on Ultraviolet B-Irradiated Mice. Mar Drugs. 2018 Aug 18; 16(8):286
- Moussavou G, Kwak DH, Obiang-Obonou BW, Maranguy CA, Dinzouna-Boutamba SD, Lee DH, Pissibanganga OG, Ko K, Seo JI, Choo YK. Anticancer effects of different seaweeds on human colon and breast cancers. Mar Drugs. 2014 Sep 24;12(9):4898-911.
- Cho ML, Lee BY, You SG. Relationship between oversulfation and conformation of low and high molecular weight fucoidans and evaluation of their in vitro anticancer activity. Molecules. 2010 Dec 30; 16(1):291-7.
- Oka S, Okabe M, Tsubura S, Mikami M, Imai A. Properties of fucoidans beneficial to oral healthcare. Odontology. 2020 Jan; 108(1):34-42.
- Jun JY, Jung MJ, Jeong IH, Yamazaki K, Kawai Y, Kim BM. Antimicrobial and Antibiofilm Activities of Sulfated Polysaccharides from Marine Algae against Dental Plaque Bacteria. Mar Drugs. 2018 Aug 27; 16(9):.
- Zhang S, Zhang H, Jin Z, Wang S, Wang Y, Zhu L, Sun W, Yan B.J. Fucoidan inhibits tooth movement by promoting restorative macrophage polarization through the STAT3 pathway. Cell Physiol. 2020 Sep;235(9):5938-5950.
- Charboneau AJ, Delaney JP, Beilman G. Fucoidans inhibit the formation of post-operative abdominal adhesions in a rat model. PLoS One. 2018 Nov 21;13(11):e0207797.
- Zhao X, Guo F, Hu J, Zhang L, Xue C, Zhang Z, Li B. Antithrombotic activity of oral administered low molecular weight fucoidan from Laminaria Japonica. Thromb Res. 2016 Aug; 144():46-52.
- Kim S-K, Wijesekara I. Anticoagulant effect of marine algae. Adv Food Nutr Res. 2011;64:235-44.
- Irhimeh MR, Fitton JH, Lowenthal RM. Fucoidan ingestion increases the expression of CXCR4 on human CD34+ cells. Exp Hematol. 2007 Jun; 35(6):989-94.
- Kim H, Ahn JH, Song M, Kim DW, Lee TK, Lee JC, Kim YM, Kim JD, Cho JH, Hwang IK, Yan BC, Won MH, Park JH. Pretreated fucoidan confers neuroprotection against transient global cerebral ischemic injury in the gerbil hippocampal CA1 area via reducing of glial cell activation and oxidative stress. Biomed Pharmacother. 2019 Jan; 109():1718-1727.
- Alghazwi M, Smid S, Karpiniec S, Zhang W. Comparative study on neuroprotective activities of fucoidans from Fucus vesiculosus and Undaria pinnatifida. Int J Biol Macromol. 2019 Feb 1; 122():255-264.
- 43.Besednova NN, Somova LM, Guliaev SA, Zaporozhets TS. Neuroprotective effects of sulfated polysaccharides from seaweed. Vestn Ross Akad Med Nauk. 2013;(5):52-9.
- Xue M, Ji X, Liang H, Liu Y, Wang B, Sun L, Li W. The effect of fucoidan on intestinal flora and intestinal barrier function in rats with breast cancer. Food Funct. 2018 Feb 21; 9(2):1214-1223.
- Cox AJ, Cripps AW, Taylor PA, Fitton JH, West NP. Fucoidan Supplementation Restores Fecal Lysozyme Concentrations in High-Performance Athletes: A Pilot Study. Mar. Drugs 2020, 18(8), 412; https://doi.org/10.3390/md18080412 – 04 Aug 2020
- Wang J, Geng L, Yue Y, Zhang Q. Use of fucoidan to treat renal diseases: A review of 15 years of clinic studies. Review. Prog Mol Biol Transl Sci. 2019; 163():95-111.
- Tsubura S.S.A. Case report using 4% fucoidan cream for recurrent oral herpes labialis: Patient symptoms markedly improved in terms of time to healing and time to loss of discomfort. Dent. Open, J. 2017;4:19–23.
- 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.
- Baba M, Snoeck R, Pauwels R, de Clercq E. Sulfated polysaccharides are potent and selective inhibitors of various enveloped viruses, including herpes simplex virus, cytomegalovirus, vesicular stomatitis virus, and human immunodeficiency virus. Antimicrob Agents Chemother. 1988 Nov;32(11):1742-5.
- Won-Sik H, Sheung-Jun O, Young-Mi K, Ye-Jin K, Min-Seon P, Koang-Chul W. Base Study Related with Development of Natural Bio-Adhesives Using Seaweeds. J Conservation Sci. (2018), 34(6), 595-604 [Article in Korean].
- Fan Z-f, Wang J-h, Li Z-q, Yi C-h. Influence of sea water immersion on inflammation and healing of the wounds in scalded rats. Zhonghua Shao Shang Za Zhi. 2006 Jun;22(3):215-7. [Article in Chinese]
- Weiss S, Oldham G, Lin M, Foster T, Quinn JV. Water is a safe and effective alternative to sterile normal saline for wound irrigation prior to suturing: a prospective, double-blind, randomised, controlled clinical trial. BMJ Open. 2013 Jan 16;3(1):e001504.