Fucoidan: The Magic of Brown Seaweed
*This article is not medical advice. Before starting on any health related regimen, seek the advice of your Primary Care Physician or an M.D.
Fucoidan
Fucoidan is a compound found in many species of brown seaweed (brown algae), and it is consumed in large quantities by some populations in Japan (think the Blue Zone, Okinawa Japan). The health benefits associated with fucoidan are astounding. It has been shown to have potent antioxidant activity in addition to exhibiting anticoagulant, antiviral, immunomodulatory, antitumor, and other health-benefitting activity.
"For the past decade fucoidans isolated from different species have been extensively studied due to their varied biological activities, including anticoagulant and antithrombotic, antivirus, antitumor and immunomodulatory, anti-inflammatory, blood lipids reducing, antioxidant and anticomplementary properties, activity against hepatopathy, uropathy and renalpathy, gastric protective effects and therapeutic potential in surgery."[6]
Key Points About Fucoidan:
Helps support intracellular glutathione levels
Rescues the cystine/glutamate anti-porter (SLC7A11) that exports glutamate out of the cell, and transfers cystine into cysteine into the cell, to manage reduced glutathione levels inside the cell. [1] (What does it 'rescue' it from? Our best friend, Ochratoxin A).
Stimulates glutathione peroxidase 4 (GPX4), the primary gene that detoxes hydrogen peroxide in the mitochondria
Calms NMDA receptor over-acitvation from Ca2+ and glutamate excititoxicity
Fucoidan stimulates glutathione peroxidase 4 (GPX4), the principal gene inside the mitochondria that neutralizes the free radical hydrogen peroxide via the SLC7A11 pathway, and also neutralizes NMDA receptor activation caused by excess glutamate and Ca2+.
"The Ca2+ responses induced by NMDA were 100% suppressed by fucoidan, and those induced by Bay K8644 90% in the cortical neurons."[2]
"....fucoidan inhibited glutamate-induced Ca2+ responses by 50%, NMDA-induced ones by 100%,"[2]
Protects against the effects of iron overload
"Protective effect of fucoidan against iron overload and ferroptosis-induced liver injury in rats exposed to alcohol"[3]
Stimulates important anti-oxidant genes like SIRT1, SIRT3, SOD2, and GSR
Fucoidan alleviated the liver oxidative damage induced by long-term alcohol exposure in rats.
Helps gut health and prevents biofilm formation from pathogens [9]
Potent anticoagulant activity
Antiviral properties
Anti-prion properties
Stimulates key anti-oxidant genes (GPX4, SOD2, GSR) and autophagy genes (SIRT1, SIRT3)
Immunomodulatory properties
Reduces blood lipids, inflammation, blood glucose, and complement activity
Protects against Alzheimers [4]
Increases GLP1 and insulin release resulting in better better glucose control
Lowers NLRP3 inflammasome [11]
In some circles, some folks swear by brown seaweed. Especially in chronic mold illness. There has been debate as to why some feel so good when eating brown seaweed or taking fucoidan supplements.
What does Fucoidan do ?
1. Rescues the cystine/glutamate anti-porter (SLC7A11) - that exports glutamate out of the cell and transfers cystine into cysteine into the cell to manage reduced glutathione levels inside the cell. What does it 'rescue' it from ? Our best friend, Ochratoxin A. [1]
2. Stimulates GPX4
3. "The Ca2+ responses induced by NMDA were 100% suppressed by fucoidan, and those induced by Bay K8644 90% in the cortical neurons."[2]
4. "....fucoidan inhibited glutamate-induced Ca2+ responses by 50%, NMDA-induced ones by 100%,"[2]
5. "Protective effect of fucoidan against iron overload and ferroptosis-induced liver injury in rats exposed to alcohol"[3]
6. Fucoidan alleviated the liver oxidative damage induced by long-term alcohol exposure in rats.
7. Fucoidan treatment could regulate the hepatic hepcidin/intestinal DMT1/FPN1 axis to control iron absorption and maintain iron homeostasis.
8. Fucoidan could protect hepatocytes from ferroptosis through upregulating p62/Nrf2/Keap1/SLC7A11 pathway.
9. Protects against Alzheimers....[4]
10. Protects against pathogenic biofilms [9]
11. Activates autophagy genes SIRT1, and SIRT3
12. Increases GLP1, and insulin release resulting in better better glucose control
13. Lowers NLRP3 inflammasome [11]
THE SECTION IMMEDIATELY ABOVE SEEMED REDUNDENT AND WAS VERY SIMILAR TO THE ONE BEFORE IT. I TRIED TO CONDENSE EVERYTHING BY COMBINING INFORMATION FROM BOTH INTO THE FIRST ONE, BUT I WAS HESITANT TO DELETE ANYTHING. PLEASE REVIEW.
Sirtuin & Autophagy Activator
"Some of this therapeutic activity is accomplished by upregulation of cytoprotective molecular pathways capable of restoring the enzymatic antioxidant activity and normal mitochondrial functions. Sirtuin-3 has been discovered as a key player for achieving the neuroprotective role of fucoidan by managing these pathways, whose ultimate goal is retrieving the entirety of the antioxidant response and preventing apoptosis of neurons, thereby averting neurodegeneration and brain injuries. Another pathway whereby fucoidan exerts neuroprotective capabilities is by interactions with P-selectin on endothelial cells, thereby preventing macrophages from entering the brain proper. Furthermore, beneficial influences of fucoidan have been established in hepatocytes after xenobiotic induced liver injury by decreasing transaminase leakage and autophagy as well as obtaining optimal levels of intracellular fiber, which ultimately prevents fibrosis. The hepatoprotective role of this marine polysaccharide also includes a sirtuin, namely sirtuin-1 overexpression, which alleviates obesity and insulin resistance through suppression of hyperglycemia, reducing inflammation and stimulation of enzymatic antioxidant response."[5]
Fucoidan and Anticoagulant Activity
Potent anticoagulant activity
"Fucoidans have a wide variety of biological activities, but their potent anticoagulant action is by far the most widely studied."[6]
Potent antithrombotic activity
"Fucoidans also express antithrombotic activity when tested on in vivo models of venous and arterial thrombosis in experimental animals. A sulfated galactofucan isolated from the brown alga Spatoglossum schroederi showed no anticoagulant activity on several in vitro assays. Nevertheless, it had a potent antithrombotic activity on an animal model of experimental venous thrombosis. This effect is time-dependent, reaching the maximum 8 h after its administration compared with the more transient action of heparin. The effect was not observed with the desulfated molecule. Furthermore, the sulfated galactofucan was 2-fold more potent than heparin in stimulating the synthesis of an antithrombotic heparan sulfate by endothelial cells."[6]
Antiviral Activity
Cytoprotective effect
"The antivirus effects of fucoidan on infection due to poliovirus III, adenovirus III, ECHO6 virus, coxsackie B3 virus and coxsackie A16 are remarkable. Fucoidan can inhibit the development of cytopathic effect (CPE) and protect cultural cells from infection caused by above viruses.”
Inhibitory effect
“Herpes is an infection that is caused by a herpes simplex virus (HSV). Fucoidans from Adenocytis utricularis, Undaria pinnatifida (Mekabu), Stoechospermum marginatum, Undaria pinnatifida, Cystoseira indica and Undaria pinnatifida show antiviral activities against HSV-1 and HSV-2 without cytotoxicity for Vero cell cultures. Furthermore, fucoidans show inhibitory activities against the replication of several enveloped virus such as human immunodeficiency and human cytomegalovirus."[6]”
Prion Disease Protection
Potential prophylactic effect
"Doh-ura et al. reported that fucoidan from popularly eaten brown algae had antiprion activity and delayed disease onset when it was ingested after the enteral prion infection. Dietary seaweed fucoidan delays the onset of disease of enterally infected mice with scrapie when given orally for 6 days after infection, but not when given before the infection. Daily uptake of fucoidan might be prophylactic against prion diseases caused by ingestion of prion-contaminated materials, although further evaluation of its pharmacology remains to be done"[6]
Immune Modulation
Restoration of immune functions
"Fucoidan of L. japonica can restore the immune functions of immunosuppressed mice, and it was an immunomodulator acting directly on macrophage and T lymphocyte. It can also promote the recovery of immunologic function in irradiated rats. The mechanism is associated with the arrest of lymphocyte apoptosis by fucoidan. Fucoidan can induce the production of interleukin-1 (IL-1) and interferon-γ (IFN-γ) in vitro, enhance the functions of T lymphocyte, B cell, macrophage and natural killer cell (NK cell) and promote the primary antibody response to sheep red blood cell (SRBC) in vivo. High molecular-weight fucoidan prepared from Okinawa mozuku (Cladosiphon okamuranus) promotes an increase in the proportion of murine cytotoxic T cells. Fucoidan from F. vesiculosus has immunostimulating and maturing effects on dendritic cells (DCs), which are powerful antigen-presenting cells, via a pathway involving at least nuclear factor-κB (NF-κB)"[6]
Antoixidant Activity Against Superoxide, Hydrogen Peroxide
Protection from free radicals
"Lots of studies show that fucoidan presents significant antioxidant activity in experiments in vitro. It is an excellent natural antioxidant and has great potential for preventing free radical-mediated diseases. Fucoidan from L. japonica can prevent the increase of lipid peroxide (LPO) in serum, liver and spleen of diabetic mice obviously. However, no inhibition effect was found on both spontaneous lipid peroxidation of homogenates and that induced by Cys/FeSO4 in vitro. Thus, fucoidan had strong scavenging effect on superoxide radical, its effect on hydroxyl radical was weak; it had less influence on 1,1-diphenyl-2-picryl-hydrazyl (DPPH). It inhibited H2O2-induced hemolysis of rat erythrocytes effectively and showed significant protective effect on lipid peroxidation of liver homogenate in rat induced by FeSO4-ascorbic acid. Micheline et al. reported that fucoidan (homofucan) from F. vesiculosus and fucans (heterofucans) from Padina gymnospora had an inhibitory effects on the formation of hydroxyl radical and superoxide radical. Fucan showed low antioxidant activity relative to fucoidan.
Antioxidant activity relates to the molecular weight and sulfate content of fucoidan. Fucoidan fractions from L. japonica had excellent scavenging capacities on superoxide radical and hypochlorous acid, except the highly sulfated fraction L-B. In LDL oxidation system, low molecular weight fractions L-A and L-B exhibited great inhibitory effects on LDL oxidation induced by Cu2+, however F-A and F-B had little inhibitory effects in this system due to their large molecular weights.” [6]
Blood Lipids
Lipid lowering effects
"Fucoidan of L. japonica remarkably decreased total cholesterol, triglyceride and LDL-C, and increase HDL-C in serum of mice with hypercholesterolemia and rats with hyperlipidaemia, and efficiently prevented the formation of experimental hypercholesterolemia in mice. It can also remarkably reduce the contents of cholesterol and triglyceride in serum of patients with hyperlipidaemia, without side-effect of damaging liver and kidney. Low molecular sulfated fucan (average Mw=8000 Da) prepared from L. japonica can distinctly reduce blood lipids of hyperlipidemic rats"[6]
Anticomplementary Activity
Complement inhibitor
"Algal fucoidan from A. nodosum has been first described as an anticomplementary molecule by Blondin et al.. Since this first report, other fucoidans from fucales (F. evanescens) and from other brown algae of Laminariale order have been also described as inhibitors of the complement. Tissot et al. have reviewed the research progress of anticomplementary activity of fucoidans"[6]
Inflammation, iNOS, and LPS
Inhibition of nitric oxide
"Yang et al. evaluated the effect of fucoidan on the expression of inducible nitric oxide synthase (iNOS) in a macrophage cell line, RAW264.7. Low concentration range of fucoidan (10 μg/ml) increased the basal expression level of iNOS in quiescent macrophages. They found for the first time that fucoidan inhibited the release of nitric oxide (NO) in RAW264.7 cells stimulated with lipopolysaccharide (LPS). This inhibitory effect on activator protein 1 (AP-1) activation by fucoidan might be associated with its NO blocking and anti-inflammatory effects"[6]
Cystine/Glutamine Antiporter and Prevents Ferroptosis (Ochratoxin A and PatulinInduces Cystine/Glutamine Antiporter and Prevents Ferroptosis (Ochratoxin A and Patulin
Lipid Peroxidation/Ferroptosis
Inhibition of ferroptosis
"Ferroptosis is caused by lipid peroxidation, and Chinese herbal medicine can be used to treat ferroptosis-related diseases. Some researchers showed that fucoidan inhibited iron overload induced by long-term alcohol exposure and protected hepatocytes from ferroptosis. Specifically, fucoidan attenuated alcohol-induced liver oxidative damage in rats by upregulating the p62/Nrf2/SLC7A11 pathway and lowering serum ferritin levels, thereby inhibiting ferroptosis. The environmental pollutant di (2-ethylhexyl) phthalate (DEHP) is a threat to human health. In rats, Dai found that DEHP exposure disrupted iron ion homeostasis, increased lipid peroxidation, and inhibited cysteine/glutamate antiporter, whereas lycopene supplementation dramatically suppressed these ferroptosis characteristics"[8]
In Summary
Fucoidan prevents the Fenton reaction (i.e. oxidative stress from hydroxyl radicals) when excess iron is present, stabilizes intracellular glutathione, lowers intracellular glutamate, calms the NMDA receptors, andlowers intracellular Ca2+. It upregulates SIRT 1 and SIRT 3, both of which are important in antioxidant pathways SOD2, GSR, etc. It also has a number of other effects, including immune modulation, gut health, coagulation, inflammation, and lipid modulation. For folks who are sulfur sensitive, fucoidan may be something to be careful with. Instead, Mangiferin (a specific extract from Mango) may be used as an alternative. Mangiferin is discussed in another blog article.
References:
Ferroptosis as a Potential Therapeutic Target of Traditional Chinese Medicine for Mycotoxicosis: A Review. Wenli Ding,1,† Luxi Lin. Toxics. 2023 Apr; 11(4): 395.Published online 2023 Apr 21. doi: 10.3390/toxics11040395PMCID: PMC10142935PMID: 37112624
2. Inhibitory effects of fucoidan on NMDA receptors and l-type Ca2+ channels regulating the Ca2+ responses in rat neurons. By Hong Wu,a,b Shuibo Gao,a and Susumu Terakawab . Pharm Biol. 2019; 57(1): 1–7. Published online 2019 Feb 8. doi: 10.1080/13880209.2018.1548626. PMCID: PMC6374951. PMID: 30734636
3. Protective effect of fucoidan against iron overload and ferroptosis-induced liver injury in rats exposed to alcohol. Xue, et. al. Biomedicine & Pharmacotherapy. Volume 153, September 2022, 113402. https://doi.org/10.1016/j.biopha.2022.113402
4. Fucoidan serves a neuroprotective effect in an Alzheimer’s disease model. By Mamangam Subaraja. Front. Biosci. (Elite Ed) 2020, 12(1), 1–34; https://doi.org/10.2741/E855 Published: 1 January 2020
5. Potential Beneficial Actions of Fucoidan in Brain and Liver Injury, Disease, and Intoxication—Potential Implication of Sirtuins. Jasmina Dimitrova-Shumkovska,1,* Ljupcho Krstanoski,1 and Leo Veenman2,*Mar Drugs. 2020 May; 18(5): 242. Published online 2020 May 5. doi: 10.3390/md18050242. PMCID: PMC7281157. PMID: 32380741
6. Fucoidan: Structure and Bioactivity. By Bo Li,* Fei Lu, Xinjun Wei, and Ruixiang ZhaoMolecules. 2008 Aug; 13(8): 1671–1695. Published online 2008 Aug 12. doi: 10.3390/molecules13081671. PMCID: PMC6245444. PMID: 18794778.
7. Therapeutic Effects of Fucoidan: A Review on Recent Studies. By Sibusiso Luthuli,† Siya Wu,† Yang Cheng, et. al. Mar Drugs. 2019 Sep; 17(9): 487. Published online 2019 Aug 21. doi: 10.3390/md17090487. PMCID: PMC6780838. PMID: 31438588
8. Ferroptosis as a Potential Therapeutic Target of Traditional Chinese Medicine for Mycotoxicosis: A Review. Wenli Ding,1,† Luxi Lin. Toxics. 2023 Apr; 11(4): 395.Published online 2023 Apr 21. doi: 10.3390/toxics11040395PMCID: PMC10142935PMID: 37112624
9. Guo et al., 2023, Cell Reports 42, 112754 July 25, 2023 ª 2023 The Author(s). https://doi.org/10.1016/j.celrep.2023.112754
10. Foods 2024, 13, 3460. https://doi.org/10.3390/foods13213460
11. Fucoidan Inhibits NLRP3 Inflammasome Activation by Enhancing p62/SQSTM1-Dependent Selective Autophagy to Alleviate Atherosclerosis. By Yufei Cheng. Oxid Med Cell Longevity. 2020 Aug 6;2020:3186306. doi: 10.1155/2020/3186306