Wakame and Fucoidan

Fucoidan is a sulfated polysaccharide found in brown seaweed that varies in molecular weight and composition. Wakame (Undaria pinnatifida) is a brown seaweed commonly consumed in Japan and is a main ingredient in miso soup and is also served as a salad. 

Recently it as been reported that fucoidan can inhibit SARS-CoV-2 replication in vitro:

https://www.nature.com/articles/s41421-020-00192-8

Of course it remains to be demonstrated in humans, but it's a start. 

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Wakame fucoidan could be useful for Covid-19 since it inhibits thrombosis without increasing bleeding time:

https://pubmed.ncbi.nlm.nih.gov/22084059/

The  Min et al. (2011) study also found in comparison to wakame fucoidan, fucoidan from bladder wrack inhibited thrombus formation, but bleeding time was prolonged (but not as much as for heparin).  An important caveat when considering the therapeutic potential of seaweed/fucoidan is that there are differences in biological activities in fucoidans from different species as well as different molecular weight fractions from within species. This is reviewed by Fitton et al. (2015):

"... any potential therapeutic application requires a specific, validated assessment of a characterised fucoidan. ... fucoidan fractions require screening for activity to optimise any particular bioactivity and while activity is not necessarily linked to sulfation, sugar content or molecular weight, useful trend data can be found."

https://www.mdpi.com/1660-3397/13/9/5920/htm 

{ Also see below regarding concerns raised by Nishiguchi et al. (2014) regarding the purity of commercially available fucoidan. }

[ Update 2021-01-25 ]

Mini-review on fucoidan and lung function in viral infection:

https://pubmed.ncbi.nlm.nih.gov/33374149/

"Inhibitory activity specifically against SARS-CoV-2 infection in vitro has been noted for linear fucans from a sea urchin, galactans from red seaweed Botryocladia occidentalis, and a highly purified fucoidan fraction from Saccharina japonica [15,16]. However, commercially available fucoidans from Fucus vesiculosus and Undaria pinnatifida were not active in vitro[17]. In addition, computational screening of marine compounds from natural sources has indicated that polyphenolics (commonly co-extracted with fucoidan) from seaweeds may have inhibitory activity [18] although this has not been confirmed with experimental studies."

Saccharina japonica is kombu - which is used to make dashi, the broth base for miso soup.

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Fucoidan can inhibit the development of autoimmunity:

https://pubmed.ncbi.nlm.nih.gov/31889967/

https://pubmed.ncbi.nlm.nih.gov/19655293/  [EAE is a model for multiple sclerosis]

This is notable since Covid-19 induces the production of autoantibodies in some patients:

 https://www.nytimes.com/2020/10/27/health/covid-antibodies-autoimmunity.html

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Japan's COVID-19 per capita death rate is quite low compared to the US, around 50x lower, which is remarkable in light of its population's age structure (assuming the reported figures are accurate). Mask wearing is a likely factor as well as relatively wide access to advanced medical care, but it is fun to speculate on the possible influence of functional foods. Natto consumption has been suggested as beneficial due to its vitamin K2 content - though it also contains nattokinase (which is anti-thrombotic), PQQ and spermidine:

 https://www.theguardian.com/science/2020/jun/05/vitamin-k-could-help-fight-coronavirus-study-suggests

Yakult probiotic beverage is popular in Japan and has been shown in a clinical trial to reduce the rate of respiratory tract infections in middle-aged males (n=96):

https://pubmed.ncbi.nlm.nih.gov/26419583/

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There has been discussion of the potential for Covid-19 to increase risk of Parkinson's and parkinsonism:

https://www.frontiersin.org/articles/10.3389/fneur.2020.01044/full

https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd202211 

Fucoidan was found to block the damaging effects of MPP+ and rotenone on dopaminergic neurons in cell culture and animal models of Parkinson's: 

https://pubmed.ncbi.nlm.nih.gov/31480724/

https://pubmed.ncbi.nlm.nih.gov/30090649/

Unfortunately these types of studies often fail to translate to humans and note that Japan's rate of Parkinson's is not known for being much lower than other countries *; however, it is known for the sex ratio being flipped relative to other nations, with more women than men affected (possibly related to the consumption of soy products? differences in smoking rates? Sake consumption (agmatine)?).

* correction - Japan's age standardized prevalence rates are actually quite low compared to other industrialized nations. https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(18)30295-3/fulltext

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Studies of animal models of depression demonstrate fucoidan has anti-depressant effects:

"... chronic fucoidan administration not only dose-dependently reduced stress-induced depressive-like behaviors in the TST, FST, sucrose preference test (SPT), and novelty-suppressed feeding test (NSFT), but also alleviated the downregulation of brain-derived neurotrophic factor (BDNF)-dependent synaptic plasticity via inhibiting caspase-1-mediated inflammation in the hippocampus of mice."

https://pubmed.ncbi.nlm.nih.gov/31668812/

https://pubmed.ncbi.nlm.nih.gov/23090005/

Seaweed consumption was found to be inversely associated with depressive symptoms in pregnant Japanese women: 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161851/

The authors of the study do not mention fucoidan, but instead suggest the association, if causal, may be due to the antioxidant and anti-inflammatory effects of fucoxanthin and dieckol.

Siddiqui et al. (2017) reported anti-depressent effects and increases in brain levels of monoamines (serotonin, dopamine, and noradrenaline) in rats after 28 days of oral administration of methanolic extracts of three brown seaweed species - Sargassum swartzii, Stoechospermum  marginatum, and Nizamuddinia zanardinii.

https://pubmed.ncbi.nlm.nih.gov/28406051/

Of the potential active constituents, they wrote:

"For instance, methanolic extract of SS and SM is known to possess important bioactive group of compounds acknowledged as sulfated polysaccharides and fucoxanthines." https://www.tandfonline.com/doi/pdf/10.1080/09168451.2017.1313697 

However,  Nishiguchi et al. (2014) indicate that fucoidan is not present in methanolic extracts (if I'm interpreting this correctly; if not, please leave a comment) and raise concerns about the interpretation of studies utilizing commercially available fucoidan:

"Since only the F. vesiculosus fucoidan among these polysaccharides showed antibacterial activity, we then examined the antibacterial and cytotoxic activities after fractionation of the fucoidan with methanol-extraction, confirming such activities have derived from methanol-extractable impurities. In agreement with previous re-ports, methanol insoluble fraction containing fucoidan stimulated RAW264.7 cells inducing nitric oxide (NO) and tumor necrosis factor-α (TNF-α), whereas methanol ex-tractable fraction showed no such activities. Accordingly, we recommend commercially available fucoidan should be more purified before biochemical use to avoid misleading of its biological activities."  

https://www.researchgate.net/publication/278397256_Reevaluation_of_bactericidal_cytotoxic_and_macrophage-stimulating_activities_of_commercially_available_Fucus_vesiculosus_fucoidan/link/5975d379a6fdcc8348951693/download

There is the potential for additive or synergistic effects of the multiple bioactive constituents of seaweeds. Consuming seaweeds as whole foods may be preferable to supplements, except in cases where a particular supplement has demonstrated efficacy in a clinical trial. On the other hand, seaweeds can contain high levels of heavy metals such as arsenic, cadmium, and lead. Further, they may contain radioactive isotopes, such as Cesium-137, which has a half-life of 30 years and was released in the Fukushima nuclear disaster. Both whole seaweed and seaweed extracts could contain harmful contaminants. It may be prudent to avoid products made from seaweeds harvested near the Fukushima disaster site.

https://onlinelibrary.wiley.com/doi/full/10.1111/1541-4337.12523#crf312523-bib-0176

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Galactofucan sulfate (sulfated galactofucan) mobilizes hematopoietic progenitor stem cells:

https://pubmed.ncbi.nlm.nih.gov/17533053/

Fucoidan promotes survival of mesenchymal stem cells:

"... fucoidan protects MSCs from ischemia-induced cell death by modulation of apoptosis-associated proteins and cellular ROS levels through regulation of the MnSOD and Akt pathways..."

https://pubmed.ncbi.nlm.nih.gov/26163916/ 

This may have relevance not only to stem cell therapies but also to physiological stem cell migration, a nightly occurrence. While the functional significance of physiological stem cell migration has not yet been fully elucidated, it is thought to play a role in adult tissue homeostasis and repair. 

 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783855/

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The role of algal fucoidans in potential anti-allergic therapeutics [ published Oct 2020; paywalled]

 https://pubmed.ncbi.nlm.nih.gov/33031853/

"Fucoidans suppress the allergic responses and block the leukocyte accumulation. Fucoidans inhibit IgE-expressing and IgE-secreting B cells. Fucoidans modulate TH1/TH2 balance toward TH1 domination and induce dendritic cell function."

 

This seems to be in contradiction of fucoidan's reported ability to suppress autoimmunity mentioned above, since Th1 response is associated with autoimmunity, whereas Th2 is associated with atopy. 

 

https://arthritis-research.biomedcentral.com/articles/10.1186/ar1703

 

However, many people suffering from autoimmune disorders simultaneously suffer from allergies, so apparently there is more than Th1/Th2 balance at work.

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Supplementation of elderly Japanese men and women with fucoidan from seaweed increases immune responses to seasonal influenza vaccination - https://pubmed.ncbi.nlm.nih.gov/24005608/

 

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Fucoidan inhibits NLRP3 inflammasome activation by stimulating mitophagy:

 

Fucoidan Inhibits NLRP3 Inflammasome Activation by Enhancing p62/SQSTM1-Dependent Selective Autophagy to Alleviate Atherosclerosis - https://www.hindawi.com/journals/omcl/2020/3186306/