The Little-Known Longevity Factor in the Japanese Diet (Fucoidan)

By Tiesha Johnson, RN

Over the past decade, a quiet revolution in aging research has unfolded, its focus centered on little-known molecules known as fucoidans. These molecules play a crucial role across a broad range of physiological mechanisms.

Fucoidans are found almost exclusively in certain kinds of seaweed. Their anti-aging potential emerged in several analyses of the Japanese diet, particularly among inhabitants of the island of Okinawa, long known for its high concentration of people at least a century old (centenarians).1-5

Virtually no one in the West obtains enough of these critical molecules, which have been shown to facilitate tissue regeneration, immune function, and cell-to-cell communication.6-8

In this article, you will discover how fucoidans work to combat cancer, metabolic syndrome, and other degenerative disorders.9,10

Filling the Nutritional Gap

The Japanese enjoy a long life expectancy that is among the highest in the world.3,11 For many years, life expectancy at birth on the islands that comprise the Okinawa prefecture was even higher than on the mainland.1-5 At the same time, the Japanese enjoy far lower incidence of most chronic, age-related diseases than Western populations.5,12,13 Multiple factors contribute to their successful aging and healthy life span, including a diet low in calories and rich in fruits, vegetables, and fish.2,5 In addition, in Japan, there is a widely held cultural belief that “food is medicine.”1 However, one dietary factor stands out that is virtually unique to the Japanese diet: regular consumption of seaweed, as much as 4-6 grams per day.10

There are many varieties of edible seaweed, which in Japan go by the common names of wakame, mekabu, and kombu, among others. Strictly speaking, “seaweed” is not a plant but rather an amalgam of algae, or single- and multi-cellular marine organisms that group into clumps or mats.14 These particular species contain high concentrations of long chain molecules collectively known as fucoidans.15

Scientists have discovered that fucoidans are a source of necessary components of cell-surface molecules that facilitate cell-to-cell signaling, the core regulatory process responsible for everything from immunity and cardiovascular function to healthy cellular proliferation.6,16-19 Researchers believe that the shorter life and health spans observed in Western populations result in part from the near-total absence of dietary fucoidans.1,2


How Fucoidans Work

Much of the world’s literature on fucoidans originates in Japan, given their abundance in the Japanese diet. Even some drug companies are investigating their therapeutic potential.15

The strongest scientific evidence on fucoidans is derived from studies of the species Undaria pinnatifida.20 It has been shown that fucoidan-rich Undaria, once ingested, can bind to toxins such as dioxin within the mammalian body and facilitate its excretion. The effect is noteworthy enough that some clinicians believe it could hold promise as a therapeutic intervention in humans exposed to dioxin.21

Laboratory and animal studies further reveal that fucoidans prevent certain infectious diseases, and block cancer cells from spreading and trigger their early death.9,10

Fucoidans also modulate growth factors required for healing and tissue regeneration, while blocking those associated with visible aging.22,23 This is largely the result of their immune-modulating capabilities: they simultaneously downregulate inflammation while boosting appropriate recognition and destruction of invaders.7,24

Immune Modulator, Cancer Fighter

Through their beneficial interaction with cell surface proteins, fucoidans exert beneficial effects on cells within the immune system, where glycoproteins serve as vital receptors and detectors of changes in the internal environment. Undaria extracts stimulate beneficial immune responses while suppressing those that could lead to tissue damage.

Immune stimulation by fucoidans enhances activity of both the cellular and the antibody-based components of the immune system, boosting protection not only against bacteria and viruses, but also against many nascent cancers.25-29 In one animal model, Undaria fucoidans enhanced survival and inhibited tumor growth in experimentally induced cancer, the result of enhanced activity of cancer-destroying natural killer cells.14,30

In early stage, experimental cell studies, fucoidans demonstrated potential for preventing infection with numerous malevolent microorganisms, including the malaria parasite and herpes viruses. In laboratory studies, they block cell surface receptors those invaders need in order to attach themselves and enter human cells, preventing infection from taking hold.31,32 Viruses in particular can attach to a cell membrane receptor and then enter the cell interior, where their genetic material replicates and produces destructive effects on host cells.

Undaria fucoidan extract has been shown to inhibit replication of herpes by stimulating ingestion of the virus by macrophage cells and boosting numbers of antibody-producing B cells.33,34 All of these experiments show great promise for future applications of fucoidans in protecting against various pathogens.

In an early phase, open-label trial, oral Undaria fucoidan was administered to 15 individuals of various ages (from under age 10 to age 72) suffering from herpetic infections including herpes type 1 (cold sores), herpes type 2 (genital herpes), herpes zoster (chicken pox; shingles), and Epstein-Barr virus (mononucleosis). The Undaria dosage approximated typical daily seaweed intake in Japan. Undaria increased the healing rates of active herpes virus infections in all 15 subjects. Individuals with chicken pox and shingles noted reduced pain and more rapid resolution of skin lesions. In the laboratory, scientists found that the Undaria extract increased the growth of infection-fighting T-cells in cell culture. The scientists postulated that Undaria’s ability to increase T-cell growth in the laboratory may be related to its ability to enhance immunity in human subjects.20

WHAT YOU NEED TO KNOW: FUCOIDANS

Over the past decade, a quiet revolution in the science of anti-aging has unfolded, centered on the discovery of beneficial molecules that facilitate core physiological mechanisms and ward off degenerative disease.
The study of their effects has given rise to the field of glycobiology.
Fucoidans are long-chain molecules found primarily in seaweed.
Researchers believe that fucoidans are partly responsible for the extraordinary longevity observed in Japanese populations, where organic, unpolluted seaweeds form a significant dietary component.
Fucoidans enhance immune function, combating infectious diseases and cancer.
Fucoidans show great promise in thwarting viral infection by preventing binding to host cells and blocking viral replication in laboratory research.
Fucoidans also combat metabolic syndrome and cardiovascular disease by modulating glucose and insulin levels, disrupting formation of advanced glycation end products (AGEs), and lowering triglycerides.
Laboratory studies of the same fucoidan preparation revealed potent antiviral activities against human herpes virus types 1 and 2, and against cytomegalovirus, a common infection in individuals with compromised immune systems.31,35 Animal studies reveal that Undaria fucoidans prevent virus binding with host cells and inhibit viral replication, while simultaneously stimulating host-defensive immune responses.36,37

Undaria extracts have also been shown to enhance the natural cancer cell-destroying activity of immune cells in experimental animals, while increasing survival rates.14,19,30 In one animal model, it suppresses proliferation of tumors of the breast—a telling finding given that breast cancer rates in humans are substantially lower in Japan than in US populations.38,39 Importantly, while the extracts induce apoptosis in cancer cells in the lab, they have no such cell-destructive effects on healthy human mammary tissue.39

Combating Cardiovascular Disease and Metabolic Syndrome

Incidence of metabolic syndrome is on the rise around the world, though its prevalence lags behind in some Asian countries that consume a traditional diet rich in seaweed. This phenomenon has recently been attributed in part to the high dietary intake of Undaria and other brown seaweeds.10 Metabolic syndrome, triggered by—and also a cause of—accumulated advanced glycation end products (AGEs), is associated with type 2 diabetes and high cardiovascular disease risk.40-43 Fucoidans hold tremendous promise in disrupting the processes that lead to metabolic syndrome and its cardiovascular consequences.10

Undaria exerts anti-diabetic effects by stabilizing and slowing the digestion of starch from processed carbohydrates, which may reduce the likelihood of dangerous postprandial glucose and insulin spikes.44


Undaria Pinnatifida
Diabetic patients also suffer from diminished peripheral blood flow, leading to skin ulceration and poor wound healing. In one compelling study, researchers discovered that fucoidan supplementation could restore normal control of capillary blood flow in diabetic animals.45 Some of this benefit may arise from the fact that fucoidans can inhibit binding of AGEs to the cellular receptors that trigger many of their damaging effects.46

Undaria also defuses cardiac risk factors by stimulating enzymes that break down fats in the liver and lower triglyceride levels.47 Undaria operates synergistically with fish oils to protect cardiovascular health.48

Cardiovascular disease risk is directly related to blood pressure. In a landmark 2009 study, consumption of dried Undaria at 4-6 grams per day (typical for the Japanese diet) significantly reduced systolic blood pressure in all patients. Individuals who consumed 4 grams of Undaria daily for 1 month, followed by 6 grams of Undaria for an additional month, saw their systolic blood pressure decrease by 10.5 mmHg. This effect occurred primarily in those who had high-normal baseline blood pressure levels.10

Relieving Arthritis Pain

Fucoidans may also prove a potent intervention to combat arthritis. There are many different kinds of arthritis, with a variety of causes. Their unifying characteristic is painful joint swelling with inflammation and increased production of pro-inflammatory cytokines (cell-signaling molecules).

Fucoidan treatment reduces cytokine production and infiltration of white blood cells in experimental arthritis, thereby reducing overall severity.49-51 Fucoidans also reduce pain perception.52 Selectin inhibition by fucoidans also reduces the severity of early bacterially induced arthritis.53 Together these properties make fucoidans tremendously promising in the management of painful arthritis.51

Summary

Researchers believe fucoidans are partly responsible for the extraordinary longevity observed in Japanese populations, where organic, unpolluted seaweeds form a significant dietary component.

Fucoidans enhance immune function, combat infectious diseases, and support defense against cancer. Fucoidans also combat metabolic syndrome and cardiovascular disease by modulating glucose and insulin, disrupting formation of advanced glycation end products, and lowering triglyceride levels. In human studies, fucoidans (extract from seaweed) demonstrate beneficial effects at doses of 75-300 mg daily.20,54

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1-866-864-3027.

References
1. Sho H. History and characteristics of Okinawan longevity food. Asia Pac J Clin Nutr. 2001;10(2):159-64.

2. Yamori Y, Miura A, Taira K. Implications from and for food cultures for cardiovascular diseases: Japanese food, particularly Okinawan diets. Asia Pac J Clin Nutr. 2001;10(2):144-5.

3. Miyagi S, Iwama N, Kawabata T, Hasegawa K. Longevity and diet in Okinawa, Japan: the past, present and future. Asia Pac J Public Health. 2003;15 Suppl:S3-9.

4. Murakami A, Ishida H, Kobo K, et al. Suppressive effects of Okinawan food items on free radical generation from stimulated leukocytes and identification of some active constituents: implications for the prevention of inflammation-associated carcinogenesis. Asian Pac J Cancer Prev. 2005 Oct-Dec;6(4):437-48.

5. Willcox DC, Willcox BJ, Todoriki H, Suzuki M. The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load. J Am Coll Nutr. 2009 Aug;28 Suppl:500S-16S.

6. Haltiwanger RS, Lowe JB. Role of glycosylation in development. Annu Rev Biochem. 2004;73:491-537.

7. Witvrouw M, De Clercq E. Sulfated polysaccharides extracted from sea algae as potential antiviral drugs. Gen Pharmacol. 1997 Oct;29(4):497-511.

8. O’Leary R, Rerek M, Wood EJ. Fucoidan modulates the effect of transforming growth factor (TGF)-beta1 on fibroblast proliferation and wound repopulation in in vitro models of dermal wound repair. Biol Pharm Bull. 2004 Feb;27(2):266-70.

9. Kim EJ, Park SY, Lee JY, Park JH. Fucoidan present in brown algae induces apoptosis of human colon cancer cells. BMC Gastroenterol. 2010;10:96.

10. Teas J, Baldeon ME, Chiriboga DE, Davis JR, Sarries AJ, Braverman LE. Could dietary seaweed reverse the metabolic syndrome? Asia Pac J Clin Nutr. 2009;18(2):145-54.

11. Available at: http://www.indexmundi.com/map/?v=30. Accessed February 24, 2011.

12. Ross PD, Norimatsu H, Davis JW, et al. A comparison of hip fracture incidence among native Japanese, Japanese Americans, and American Caucasians. Am J Epidemiol. 1991 Apr 15;133(8):801-9.

13. Skibola CF. The effect of Fucus vesiculosus, an edible brown seaweed, upon menstrual cycle length and hormonal status in three pre-menopausal women: a case report. BMC Complement Altern Med. 2004 Aug 4;4:10.

14. Maruyama H, Tamauchi H, Iizuka M, Nakano T. The role of NK cells in antitumor activity of dietary fucoidan from Undaria pinnatifida sporophylls (Mekabu). Planta Med. 2006 Dec;72(15):1415-7.

15. Li B, Lu F, Wei X, Zhao R. Fucoidan: structure and bioactivity. Molecules. 2008;13(8):1671-95.

16. Sawa M, Hsu TL, Itoh T, et al. Glycoproteomic probes for fluorescent imaging of fucosylated glycans in vivo. Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12371-6.

17. Nairn AV, Kinoshita-Toyoda A, Toyoda H, et al. Glycomics of proteoglycan biosynthesis in murine embryonic stem cell differentiation. J Proteome Res. 2007 Nov;6(11):4374-87.

18. Freguin-Bouilland C, Alkhatib B, David N, et al. Low molecular weight fucoidan prevents neointimal hyperplasia after aortic allografting. Transplantation. 2007 May 15;83(9):1234-41.

19. Furusawa E, Furusawa S. Anticancer activity of a natural product, viva-natural, extracted from Undaria pinnantifida on intraperitoneally implanted Lewis lung carcinoma. Oncology. 1985;42(6):364-9.

20. Cooper R, Dragar C, Elliot K, Fitton JH, Godwin J, Thompson K. GFS, a preparation of Tasmanian Undaria pinnatifida is associated with healing and inhibition of reactivation of Herpes. BMC Complement Altern Med. 2002 Nov 20;2:11.

21. Morita K, Nakano T. Seaweed accelerates the excretion of dioxin stored in rats. J Agric Food Chem. 2002 Feb 13;50(4):910-7.

22. Fukuta K, Nakamura T. Induction of hepatocyte growth factor by fucoidan and fucoidan-derived oligosaccharides. J Pharm Pharmacol. 2008 Apr;60(4):499-503.

23. Moon HJ, Lee SH, Ku MJ, et al. Fucoidan inhibits UVB-induced MMP-1 promoter expression and down regulation of type I procollagen synthesis in human skin fibroblasts. Eur J Dermatol. 2009 Mar-Apr;19(2):129-34.

24. Tanaka K, Ito M, Kodama M, et al. Sulfated polysaccharide fucoidan ameliorates experimental autoimmune myocarditis in rats. J Cardiovasc Pharmacol Ther. 2010 Dec 30.

25. Zapopozhets TS, Besednova NN, Loenko Iu N. Antibacterial and immunomodulating activity of fucoidan. Antibiot Khimioter. 1995 Feb;40(2):9-13.

26. Kuznetsova TA, Zaporozhets TS, Besednova NN, et al. Immunostimulating and anticoagulating activity of fucoidan from brown algae Fucus evanescens of Okhotskoe sea. Antibiot Khimioter. 2003;48(4):11-3.

27. Itoh H, Noda H, Amano H, Ito H. Immunological analysis of inhibition of lung metastases by fucoidan (GIV-A) prepared from brown seaweed Sargassum thunbergii. Anticancer Res. 1995 Sep-Oct;15(5B):1937-47.

28. Choi EM, Kim AJ, Kim YO, Hwang JK. Immunomodulating activity of arabinogalactan and fucoidan in vitro. J Med Food. 2005 Winter;8(4):446-53.

29. Kim MH, Joo HG. Immunostimulatory effects of fucoidan on bone marrow-derived dendritic cells. Immunol Lett. 2008 Jan 29;115(2):138-43.

30. Maruyama H, Tamauchi H, Hashimoto M, Nakano T. Antitumor activity and immune response of Mekabu fucoidan extracted from sporophyll of Undaria pinnatifida. In Vivo. 2003 May-Jun;17(3):245-9.

31. Lee JB, Hayashi K, Hashimoto M, Nakano T, Hayashi T. Novel antiviral fucoidan from sporophyll of Undaria pinnatifida (Mekabu). Chem Pharm Bull (Tokyo). 2004 Sep;52(9):1091-4.

32. Dalton JP, Hudson D, Adams JH, Miller LH. Blocking of the receptor-mediated invasion of erythrocytes by Plasmodium knowlesi malaria with sulfated polysaccharides and glycosaminoglycans. Eur J Biochem. 1991 Feb 14;195(3):789-94.

33. 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.

34. Maruyama H, Tanaka M, Hashimoto M, Inoue M, Sasahara T. The suppressive effect of Mekabu fucoidan on an attachment of Cryptosporidium parvum oocysts to the intestinal epithelial cells in neonatal mice. Life Sci. 2007 Jan 30;80(8):775-81.

35. Thompson KD, Dragar C. Antiviral activity of Undaria pinnatifida against herpes simplex virus. Phytother Res. 2004 Jul;18(7):551-5.

36. Chen JH, Lim JD, Sohn EH, Choi YS, Han ET. Growth-inhibitory effect of a fucoidan from brown seaweed Undaria pinnatifida on Plasmodium parasites. Parasitol Res. 2009 Jan;104(2):245-50.

37. Harden EA, Falshaw R, Carnachan SM, Kern ER, Prichard MN. Virucidal activity of polysaccharide extracts from four algal species against herpes simplex virus. Antiviral Res. 2009 Sep;83(3):282-9.

38. Funahashi H, Imai T, Tanaka Y, et al. Wakame seaweed suppresses the proliferation of 7,12-dimethylbenz(a)-anthracene-induced mammary tumors in rats. Jpn J Cancer Res. 1999 Sep;90(9):922-7.

39. Funahashi H, Imai T, Mase T, et al. Seaweed prevents breast cancer? Jpn J Cancer Res. 2001 May;92(5):483-7.

40. Rader DJ.Effect of insulin resistance, dyslipidemia, and intra-abdominal adiposity on the development of cardiovascular disease and diabetes mellitus. Am J Med. 2007 Mar;120(3 Suppl 1):S12-8.

41. Robert L, Labat-Robert J. The metabolic syndrome and the Maillard reaction. An introduction. Pathol Biol (Paris). 2006 Sep;54(7):371-4.

42. Soldatos G, Cooper ME, Jandeleit-Dahm KA. Advanced-glycation end products in insulin-resistant states. Curr Hypertens Rep. 2005 Apr;7(2):96-102.

43. Otani H.Oxidative Stress as Pathogenesis of Cardiovascular Risk Associated with Metabolic Syndrome. Antioxid Redox Signal. 2010 Dec 2.

44. Goni I, Valdivieso L, Gudiel-Urbano M. Capacity of edible seaweeds to modify in vitro starch digestibility of wheat bread. Nahrung. 2002 Feb;46(1):18-20.

45. Nellore K, Harris NR. Inhibition of leukocyte adherence enables venular control of capillary perfusion in streptozotocin-induced diabetic rats. Microcirculation. 2004 Dec;11(8):645-54.

46. Tamura Y, Adachi H, Osuga J, et al. FEEL-1 and FEEL-2 are endocytic receptors for advanced glycation end products. J Biol Chem. 2003 Apr 11;278(15):12613-7.

47. Murata M, Ishihara K, Saito H. Hepatic fatty acid oxidation enzyme activities are stimulated in rats fed the brown seaweed, Undaria pinnatifida (wakame). J Nutr. 1999 Jan;129(1):146-51.

48. Murata M, Sano Y, Ishihara K, Uchida M. Dietary fish oil and Undaria pinnatifida (wakame) synergistically decrease rat serum and liver triacylglycerol. J Nutr. 2002 Apr;132(4):742-7.

49. Bartlett MR, Warren HS, Cowden WB, Parish CR. Effects of the anti-inflammatory compounds castanospermine, mannose-6-phosphate and fucoidan on allograft rejection and elicited peritoneal exudates. Immunol Cell Biol. 1994 Oct;72(5):367-74.

50. Cardoso ML, Xavier CA, Bezerra MB, et al. Assessment of zymosan-induced leukocyte influx in a rat model using sulfated polysaccharides. Planta Med. 2010 Feb;76(2):113-9.

51. Myers SP, O’Connor J, Fitton JH, et al. A combined phase I and II open label study on the effects of a seaweed extract nutrient complex on osteoarthritis. Biologics. 2010 Mar 24;4:33-44.

52. McNamee KE, Burleigh A, Gompels LL, et al. Treatment of murine osteoarthritis with TrkAd5 reveals a pivotal role for nerve growth factor in non-inflammatory joint pain. Pain. 2010 May;149(2):386-92.

53. Verdrengh M, Erlandsson-Harris H, Tarkowski A. Role of selectins in experimental Staphylococcus aureus-induced arthritis. Eur J Immunol. 2000 Jun;30(6):1606-13.

54. Myers SP, O’Connor J, Fitton JH, et al. A combined phase I and phase II open label study on the immunomodulatory effects of a seaweed nutrient complex. Biologics: Targets and Therapy. 2010 Feb;2010(4):33-44.



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