Sulfated Polysaccharides: Immune Boosters Extracted from Sea Life

A Novel Galactofucan Sulfate Extract Enhances Immunity, Inactivates Viruses Naturally and Reduces Inflammation.

Interest in fucoidans surged when scientists began to study the world’s longest living people on the island of Okinawa… the Okinawan diet, which includes more than a dozen varieties of seaweed, is now considered one of the healthiest diets in the world.

Picture a frozen earth 635 million years ago, and envision the planet at last beginning to thaw from an extraordinary ice age that blanketed land and sea. As the permafrost begins to soften and melt, new life emerges from the ocean depths. It takes the form of sea plants, according to fossil finds discovered by scientists in 2011 in southern China.[1]

These sea plants were likely the earth’s first “complex” multicellular creatures—a grand harbinger of the flowering of plant and animal life to come. They are the ancestors of the familiar seaweeds of today, with their branches, splayed fans, and ribbony blossoms. And the solutions they have crafted to survive the salty, turbulent seas, at times swarming with microorganisms, offer surprising help for some of our own health challenges.[2]

It turns out that seaweeds contain large amounts of uniquely structured long chain sugars, or polysaccharides, with many immune benefits.[3] Polysaccharides are chains of single sugar molecules joined together, and include everything from the pectin in apples to glycogen, a form of sugar stored in your liver.[4] Seaweed polysaccharides come in a variety of arrangements and molecules, varying by seaweed type, and each appears to have its own set of healing capacities.[5]

A significant body of seaweed research focuses on fucoidans, sulfated polysaccharides rich in a sugar called fucose. Fucoidans are commonly found in the cell walls of brown macroalgae isolated from Undaria pinnatifida, a large brown kelp native to Japan, and can also be found in other seaweeds such as Fucus vesiculosis (also known as bladderwrack).[6]^,[7]  Fucoidans are such an important component of seaweeds that they constitute up to 30% of their dry weight.[8]

Nearly 1500 peer-review studies have been published on fucoidans, and half of those in the last decade alone.[9] Interest in fucoidans surged when scientists began to study the world’s longest living people on the island of Okinawa, some of whom were over a century old.[10]^,[11] The Okinawan diet, which includes more than a dozen varieties of seaweed, is now considered one of the healthiest diets in the world.[12] Dietary seaweed intake is correlated with lower all-cause mortality.[13]

Fucoidans have been called “a treasure trove of physiologically active polysaccharides.”[14] Their structures are surprisingly diverse, with variable sugar compositions that have different effects on our physiology.¹² These include immune modulation[15], antibacterial and antiviral properties[16]^,[17], anti-inflammatory ability[18], modulation of gut flora[19], as well as antithrombotic and anticancer .[20]^,[21]

Fucoidans enhance immune function and stimulate both innate and adaptive immunity—in other words, they increase both our first line of defense, and our delayed, more specific memory driven immune response.⁶ T cells are impacted by fucoidan. T cells have numerous forms but two significant ones are : Th1 cells, which attack intracellular bugs such as bacteria and viruses, and Th2 cells, which fight helminths and other extracellular pathogens. Fucoidans modulate both Th1 and Th2 helper cells. [22] Animal studies demonstrate that by stimulating Th1 cells, fucoidan can help eliminate infections such as Leishmania spp., which infects up to 12 million people in 98 different countries around the world.[23] In turn, they also downregulate excessive Th2 responses, which can lead to allergies and inflammation. Oral consumption of fucoidans has been shown to relieve pulmonary inflammation in mice,[24] while topical application relieves   murine dermatitis as well.[25]

Fucoidans also increase natural killer cell activity, stimulate immune cells called macrophages, and help specialized immune training cells (dendritic cells) to mature.[26]^,[27] At doses of 300 mg a day for four weeks a fucoidan extract stimulated the vaccine response to influenza in 70 volunteers over age 60. [28] In this population, fucoidan was shown to increase antibody titers to three strains of the flu.

Fucoidans are antiviral, protecting against different types of viral infections.[29] They directly inhibit herpes simplex virus 1 and 2.[30] Fucoidans also help protect against potentially deadly viruses, such as hepatitis C[31], and a retrovirus known as HTLV1.[32] Fucoidans inhibit the adhesion of hantavirus to cells in vitro.[33]

Some fucoidans mobilize stem cells and increase their number in the blood.[34] Fucoidans might even exert anti-aging activity, by increasing the expression of the sirtuins.[35] Sirtuins are being studied for their anti-aging potential; it is thought that a boost in sirtuin activity may in part explain how calorie restriction extends life span.[36] Finally, fucoidans are potent anti-inflammatory molecules.[37] Fucoidans may also protect the brain and nervous system from chronic inflammation, particularly via specialized cells called microglia.[38] Thus fucoidan may, some researchers believe, “offer substantial therapeutic potential for treatment of neurodegenerative diseases.”

A Novel Aqueous Fucoidan Extract Balances the Immune System

    “The role of marine compounds as therapeutic agents has immense potential, and it’s great to be at the cutting edge of this research,”

says Stephen Myers, PhD, ND, BMed, of Southern Cross University in New South Wales, Australia. “Fucoidans have immense potential as immune-modulators and anti-inflammatory agents. The research on their benefits is only in its infancy, and we are going to see a wide range of uses for these compounds in future therapeutic applications.”[39]

New research is emerging on the immune and antiviral benefits of fucoidan isolated from either Undaria pinnatifida seaweed (also known as wakame) or Fucus vesiculosis (also known as bladderwrack). The fucoidan extract is prepared using a novel aqueous extraction process that produces largely unaltered fucoidan fractions with consistent, measurable bioactivity. They yield specific and reproducible benefits in cellular, animal and clinical studies.

A unique blend of fucoidan and algal polyphenols, along with the nutrients manganese, zinc and vitamin B6, significantly enhanced immune function in a four-week pilot study of ten healthy adults.[40] The study participants were randomly divided into two groups: five received 100 mg daily (containing 75 mg total fucoidan), and five received 1000 mg daily delivered as four 250 mg capsules (containing a total of 750 mg fucoidan). This lower and upper range was used to determine both safety and efficacy. The extract was well tolerated with no clinically relevant changes to measurements of liver or kidney function or to the formation of blood cells.

Changes in immune cells such as T lymphocytes, helper T cells and cells of the innate immune system were measured at day 1, day 3, and day 28. Numerous measures of immune function significantly improved, including the total number of T cells. There was a continual increase over the 28 days in the activity of innate immune cells called granulocytes and monocytes. These cells attack pathogens as soon as they are encountered.

The adaptive immune system responded as well—by day 3, there were significant increases in killer T cells known as cytotoxic T cells, which recognize infected cells by the presence of antigens on their surface, and then kill them. The researchers conclude that “overall, these data suggest an immune-priming role of the nutrient seaweed complex.”

The fucoidan extract was anti-inflammatory as well. Cells in blood samples were ‘challenged’ with phytohemagglutinin (PHA-M), a protein that stimulates T-cells. After challenge, T cells produced less of an inflammatory molecule called interleukin (IL)-6 on day 28 as compared to day 1. Inappropriate levels of IL-6 have been linked to increased cardiovascular risk in the Women’s Health Study—a six-year study with 619 participants.[41] As the researchers note, “any agent capable of reducing IL-6 may confer substantive health benefits.” Finally, it may have the potential for lowering cholesterol, as there was a near-significant beneficial change in blood lipid levels by the end of the 4-week study.[42] It is notable that this small-scale study did not show a dose response effect in the efficacy outcomes between the two doses of the study preparation. Both doses were effective and well tolerated. However, the researchers point out that a larger study needs to be undertaken to determine dose responsiveness [Can you make some comment to the dosage effect of 75 mg vs 750? People will want to know this. Is the amount of effect dosage related?]

“This research set out to determine the potential activity of fucoidan and polyphenol rich seaweed extract on immune function,” explains the study’s lead researcher Stephen Myers. “Previous research had demonstrated that fucoidans have real potential as immune modifying agents and our results have added to these findings. You can never state with absolute certainty, that we’d get the same result, with a pure preparation of Fucus vesiculosus. However, I have little doubt the combination of fucoidan and polyphenols in the preparation tested were the principal active constituents.”³⁹

At the higher dosage, the same combination reduced symptoms of osteoarthritis by over fifty percent in a 2010 pilot study of twelve individuals.[43] Eleven participants completed 12 weeks and one completed 10 weeks of the study. The severity of the patients’ average comprehensive arthritis test (COAT) score was measured weekly. This test is comprised of four sub-scales: pain, stiffness, difficulty with physical activity, and overall symptom severity. The COAT score was reduced by 18% with the 100 mg treatment (75 mg fucoidan) and 52% with the 1000 mg dose (750 mg fucoidan) by the end of the study. This preparation also caused a significant increase in total antioxidant capacity (ORAC), demonstrating potential for antioxidant activity.

The algal polyphenols themselves, separate from the fucoidan, are health-promoting, anti-inflammatory and antioxidant.[44] Phlorotannins, polyphenols present in the extract studied, are metabolised and absorbed in the colon and thus are bioavailable.[45]

Fucoidan may mobilise human progenitor stem cells (HPC). Progenitor cells are critical for the maintenance and replenishment of blood cells in the bone marrow.[46] In mice and in nonhuman primates, intravenous (IV) fucoidan has a significant mobilising effect on HPC.[47] In humans, oral intake of fucoidan also mobilises HPC.[48]

Fucoidan Inhibits the Activity of Both Bacteria and Viruses

In 2005, the Nobel Prize in Physiology or Medicine was awarded to Barry Marshall and Robin Warren, his long-time collaborator, for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease.[49] H. pylori colonizes the stomach of half the world’s humans, and can cause chronic gastritis, peptic ulcer, gastric cancer and gastric MALT lymphoma.[50] Unfortunately, the efficacy of standard triple antibiotic combination therapy has declined in recent years to only 70%.[51]^,[52

Fucoidan may make a clinical difference in that antibiotic efficacy. Three fucoidan aqueous extracts were tested (from Fucus versicolus and Undaria pinnatifida), for their ability to inhibit H. pylori from adhering to the stomach lining. When human gastric epithelial cells were tested in vitro, it was found that fucoidans attach to H. pylori, potentially dislodging the bacteria from the gastric cell, or simply preventing it from adhering. In fact, analysis has shown that H. pylori carries several proteins on its outer membrane that bind to fucoidan.[53] It is possible, the researchers conclude, that fucoidan could be used as a blocking agent against pathogenic bacteria colonizing on the mucosa of the entire gastrointestinal system

Just as fucoidan inhibits bacteria from attaching to cells, it can bind to receptors that some viruses use to enter cells, including herpes viruses such as those that cause oral and genital herpes. An extract of 75% pure fucoidan was tested in vitro against 32 clinical strains of herpes simplex virus (HSV), composed of 14 strains of HSV-1 and 18 strains of HSV-2. HSV-1 tends to cause oral herpes lesions, while HSV-2 causes genital herpes lesions.[54] Many strains of herpes are now resistant to acyclovir, the most common antiviral drug used to combat infection. Fucoidan exhibited “excellent in vitro antiviral activity,” the researchers concluded, and was “significantly more active against clinical strains of HSV-2 than HSV-1.”[55] This research has been confirmed in animal studies as well; in a 2008 study, oral administration of fucoidan protected mice from infection with HSV-1, as judged from the survival rate and lesion scores.[5

Fucoidans offer a remarkable array of bioactivity, ranging for immune modulation to inhibiting infection by bacteria and viruses. This ‘food’ from the sea is truly the ocean’s great medicinal gift.

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