HK1116424A - Fucoidan compositions and methods for dietary and nutritional supplements - Google Patents

Description

Fucoidan compositions and methods for dietary and nutritional supplements

Background

The present invention relates generally to dietary supplements incorporating fucoidan derived from seaweed. More particularly, the present invention relates to dietary supplements incorporating fucoidan from seaweed such as Thogany moui and Japanese hokukombu and mozuku, and optionally comprising one or more ingredients with high Oxygen Radical Absorbance Capacity (ORAC).

Fucoidan is a sulfated polysaccharide found in many marine plants and animals, and is particularly concentrated in the cell wall of brown algae (Phaeophyceae). Fucoidan is a complex carbohydrate polymer consisting essentially of sulfated L-fucose residues. These polysaccharides are easily extracted from the cell walls of brown algae with hot water or dilute acid and can account for more than 40% of the dry weight of the isolated cell walls. Bertheau & b mulloy, sulfated fucans, recent expectations: the structural, functional and biological properties of sulfated fucans and a summary of enzymes active on such polysaccharides, 13Glycobiology29R-40R (2003). Fucoidan structures appear to be related to algae, but there is insufficient evidence to demonstrate any systematic correspondence between structure and algal order. Fucoidan derived from Ascophyllum nodosum has high content of alpha (1-3) and alpha (1-4) glycosidic bonds. The disaccharide repeating units of alternating α (1-3) and α (1-4) bonds represent the most abundant structural features of fucoidan from both a. nodosum and Fucus vesiculosus. The sulfate residue occurs predominantly at position 4. Furthermore, the increase in heterogeneity is due to the presence of acetyl groups and branches linked to oxygen atoms, which are present in all the plant fucooligosaccharides.

Fucoidan-containing seaweeds have been consumed and used medicinally for at least 3000 years in tangga and for at least 2000 years in china. A large number of studies have been documented in the modern scientific literature, of which over 500 are mentioned in PubMed search for fucoidan.

The physiological properties of fucoidan in seaweed appear to be a function in cell wall organization and may play a role in the cross-linking of alginate and cellulose and morphogenesis of algal embryos. Fucoidan also has a broad spectrum of activity in biological systems. They have anticoagulant and antithrombotic activity, act on the inflammation and immune system, have antiproliferative and antiadhesive effects on cells, and protect cells from viral infections.

In addition, fucoidan has many beneficial functions that can cure and strengthen the different systems of the body, including antiviral, anti-inflammatory, anticoagulant and antitumor properties. Usov et al, Polysaccharides of Algae: polysacchar ide Composition of partial Brown Algae from Kamchatka, 27 Russian J.Bio.chem.395-399 (2001). Fucoidan has been found to establish and promote the immune system. Studies have also shown that fucoidan reduces allergies, inhibits blood clotting, counteracts diabetes by controlling blood glucose, prevents ulcers, relieves stomach discomfort, reduces inflammation, protects the kidney by increasing blood flow to the kidney, and detoxifies the body. Fucoidan also helps to reduce and prevent cardiovascular disease by reducing high cholesterol levels and activating enzymes involved in the beta-oxidation of fatty acids.

Japanese studies have found that fucoidan enhances phagocytosis, a process by which white blood cells phagocytose, kill, digest, and eliminate dead cells, viruses, and bacteria. Studies in the united states reported that fucoidan increases the number of circulating mature white blood cells. Argentina's studies and Japanese's studies found that fucoidans inhibit viruses, such as herpes simplex type I, from adhering to, penetrating, and replicating in host cells. Swedish studies are one of many studies that show that fucoidan inhibits inflammatory progression and tissue damage that may lead to allergy. Other studies, such as those in canada, found that fucoidan blocks the complement activation process, which is thought to play an adverse role in chronic degenerative diseases, such as atherosclerosis, heart attack, and alzheimer's disease. Two U.S. studies found that fucoidan increases and mobilizes stem cells.

Researchers have also determined that fucoidan contributes to cancer resistance by reducing angiogenesis (blood vessel growth), inhibiting metastasis (spread of cancer cells to other parts of the body), and promoting death of cancer cells. Brown algae are used by some populations as part of their diet and exhibit a significantly lower incidence of cancer. For example, some residents in the okinawa area of japan enjoy the highest life expectancy, which is also exactly one of the areas with the highest per capita consumption rate of fucoidan. It is noteworthy that cancer mortality in Okinawa is the lowest in all areas of Japan.

Brown algae is found abundant in various ocean regions of the world. One of the purest places that provides some of the highest production of fucoidan is the clean water surrounding the tanga island, where the seaweed is called limu moui. In Japan, hoku kombu (kelp) (Laminaria japonica), is said to be particularly rich in fucoidan and similar to limu moui. Japanese also consumes at least two other types of brown algae-wakame and mozuku (Cladosiphon and Nemacystus).

Typically, about 4% by weight of the soup plus limu moui is fucoidan. At least three types of fucoidan multimeric molecules are found in brown algae. U-fucoidan, having about 20% glucuronic acid, plays a role in carrying out the destruction of cancer cells, among other things. F-fucoidan, a polymer of mostly sulfated fucose, and G-fucoidan all tend to induce the production of HGF cells, which helps to reconstitute and repair damaged cells. All three types of fucoidans tend to induce the production of substances that enhance the immune system.

Therefore, in order to benefit from many of the advantages described above, beverages and other compositions of edible fucoidan are needed. The method of making fucoidan can be used to promote consumption without destroying its beneficial effects.

In view of the above, it should be appreciated that it would be a significant advancement in the art to provide a nutritional supplement containing fucoidan.

Summary of The Invention

The dietary supplement according to the present invention provides a number of benefits including longevity, anti-aging and regeneration of cells and tissues, such as muscle and bone; promoting growth factors in the body; promoting vigorous energy, vitality and youth; prevention of blood clots and thrombosis; reduction and prevention of inflammation; enhancing the immune system; against viral, bacterial and other types of infections; preventing tumorigenesis and the spread of cancer; reduction of allergies; anti-diabetic by controlling blood glucose; preventing ulcer; alleviating stomach discomfort; protecting the kidney by increasing blood flow to the kidney; detoxicate the body and reduce and prevent cardiovascular diseases; and activating the stem cells.

An illustrative embodiment of a dietary supplement according to the present invention includes about 0.5 to about 70 parts by weight partially hydrolyzed fucoidan and about 30 to about 99.5 parts by weight water. During the hydrolysis reaction, the partially hydrolyzed fucoidan may or may not be sulfonated. It is believed that sulfonated fucoidan provides certain benefits to the dietary supplement, such as enhanced properties associated with: anticancer, antimicrobial, anti-inflammatory, longevity-extending, anti-aging, cell and tissue regeneration, and stem cell activation effects. Other illustrative embodiments further comprise other ingredients, which may optionally be added in any selected combination. For example, the dietary supplement may additionally contain about 0.5 to about 20 parts by weight of a nutraceutical ingredient having a high ORAC value, such as a concentrated juice of the following fruits: black grape, red grape, white grape, blueberry, acai fruit, raspberry, blackberry, strawberry, plum, orange, cherry, kiwi, blackcurrant, elderberry, redcurrant, cranberry, garcinia concentrate, noni fruit, aronia fruit (aronia), thinleaf western snow fruit, proanthocyanidins (e.g., from grape seed extract), curcuminoids, or mixtures thereof. In addition, the dietary supplement may further comprise about 0.01 to about 2 parts by weight of minerals, such as deep sea minerals. Still further, the dietary supplement may also contain about 0.001 to about 1 part by weight of pepper extract, such as black pepper or Sichuan pepper extract or mixtures thereof. Fucoidan from which partially hydrolyzed fucoidan is prepared may be derived from Thomas plus limumoui seaweed or Japanese mozuku or kombu seaweed, or mixtures of these fucoidans. The dietary supplement may additionally contain flavouring agents, preservatives and the like.

Another illustrative dietary supplement according to the present invention comprises about 0.5 to about 70 parts by weight partially hydrolyzed fucoidan, about 0.5 to about 20 parts by weight of a nutraceutical ingredient having a high ORAC value, and about 10 to about 99 parts by weight water.

Yet another illustrative dietary supplement according to the present invention comprises about 0.5 to about 70 parts by weight partially hydrolyzed fucoidan, about 0.001 to about 1 part by weight pepper extract, and about 29 to about 99.5 parts by weight water.

Another illustrative dietary supplement according to the present invention comprises about 0.5 to about 70 parts by weight of partially hydrolyzed, sulfonated fucoidan, about 0.001 to about 1 part by weight of pepper extract, about 0.5 to about 20 parts by weight of a high ORAC value nutraceutical ingredient, and about 9 to about 99 parts by weight water.

Yet another illustrative embodiment according to the present invention comprises a solid dosage form for providing a dietary supplement, the dosage form comprising partially hydrolyzed fucoidan. Such solid dosage forms include, for example, tablets, capsules or spray-dried or freeze-dried powders. The solid dosage may additionally contain any of the ingredients described above in connection with the dietary supplement in liquid form. In addition, the solid dosage form may contain pharmaceutical necessities for its preparation and formulation.

Another illustrative embodiment of the invention includes a method of making a partially hydrolyzed fucoidan composition comprising:

(a) mixing a selected amount of fucoidan-containing seaweed with water and adjusting the hydrogen ion concentration to a pH of about 2.0-4.0 to produce a mixture;

(b) heating the mixture to a temperature of about 37 ℃ to about 95 ℃ for a selected period of time while continuing to stir the mixture, thereby partially hydrolyzing fucoidan in the seaweed to produce a heated mixture;

(c) cooling the heated mixture to ambient temperature, and while cooling, continuing to mix the heated mixture to produce a cooled mixture; and

(d) incubating the cooled mixture at ambient temperature while mixing for up to about 72 hours, thereby obtaining a partially hydrolyzed fucoidan composition. The hydrogen ion concentration is generally adjusted by adding an acid according to methods well known in the art. Examples of acids include sulfuric acid, and when sulfuric acid is used, conditions can be selected so as to sulfonate available reactive groups resulting from the partial hydrolysis of fucoidan, resulting in a partially hydrolyzed, sulfonated fucoidan composition. Heating the mixture may be carried out at an increased pressure, for example, at greater than one atmosphere, to accelerate the hydrolysis reaction.

Another illustrative embodiment of the present invention includes a method of preparing a dietary supplement, the method comprising:

(a) mixing about 0.5 to about 70 parts by weight of the partially hydrolyzed fucoidan composition with about 30 to about 99.5 parts by weight of water to form a mixture;

(b) sterilizing the mixture; and

(c) the sterilized mixture is packaged in a suitable container. As mentioned above, other ingredients may be added to the mixture. The mixture may be sterilized by pasteurizing the mixture or treating the mixture with a High Temperature Short Time (HTST) process or a ultra high temperature process (UHT). Packaging the sterilized mixture may include a hot-fill process or a cold-fill process.

Detailed Description

Before the present fucoidan-containing dietary supplement and method are disclosed and described, it is to be understood that this invention is not limited to the particular arrangements, process steps, and materials disclosed herein as such arrangements, process steps, and materials may vary somewhat. It is also to be understood that the terminology used herein is used for the purpose of describing particular embodiments only and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims and equivalents thereof.

The publications and other references referred to herein are incorporated by reference for the purpose of describing the background of the invention and for the purpose of providing additional details respecting the practice thereof. The references discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention.

It should be noted that, as used in this specification and the appended claims, the singular forms: "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to a dietary supplement containing "partially hydrolyzed fucoidan" includes a mixture of two or more such partially hydrolyzed fucoidans, reference to "an acid" includes two or more such acids, and reference to "a preservative" includes a mixture of two or more such preservatives.

In describing and claiming the present invention, the following terminology will be used in accordance with the definitions set out below.

As used herein, the terms "comprising," "including," "containing," "characterized by," and grammatical equivalents thereof are inclusive or open-ended terms that do not exclude additional, unrecited elements or method steps. "comprising" should be interpreted to include the more restrictive terms "consisting of and" consisting essentially of.

As used herein, "partially hydrolyzed fucoidan" means a fucoidan that has been hydrolyzed to smaller polymers and oligomers, but not so hydrolyzed sufficiently as to be completely hydrolyzed to monosaccharides.

As used herein, "high ORAC value" or similar terms means an ORAC value of about at least 400 per 100g of fruit or vegetable. For example, the ORAC value for blueberries is about 2,400/100g, and the ORAC values per 100g of the following fruits are shown in parentheses: blackberry (2,036), cranberry (1,750), strawberry (1,540), raspberry (1,220), plum (949), orange (750), red grape (739), cherry (670), kiwi (602), and white grape (446). Other fruits known to have a high ORAC value include black grape, mangosteen, noni, aronia, thinleaf west fruit, acai, and the like. In addition, it is known that health food ingredients having a high ORAC value include proanthocyanidins, such as extracts from grape seeds and bark of the pine bark of the pinus sylvestris (e.g., pycnogenol, US4,698,360), and curcuminoids. Oligomeric Proanthocyanidins (OPC) are used as illustrative examples.

As used herein, "sterilize" and similar terms, with respect to a dietary supplement having a pH of less than 4.6 and a water activity of greater than 0.85, means that the nutritional supplement is pasteurized and stored at room temperature. By "sterilization" and similar terms, with respect to a nutritional supplement having a pH greater than 4.6 and a water activity greater than 0.85, is meant the application of heat treatment to render the nutritional supplement free of microorganisms that can propagate in the nutritional supplement under normal non-refrigerated conditions of storage and sale.

As used herein, "pasteurization" conventionally refers to a process named under the scientist pasteur lewis. By this process, every particle in the milk is heated to not less than 62.8 ℃ (i.e., 145 ° f) for not less than 30 minutes and rapidly cooled to destroy any harmful bacteria that may be present without affecting taste and nutritional value. The most common pasteurization method in the united states today is High Temperature Short Time (HTST) pasteurization, which uses a metal plate and hot water to raise the temperature to 71.7 ℃ (i.e., 161 ° f) for no less than 15 seconds, followed by rapid cooling. Ultra Pasteurization (UP) is a process similar to HTST pasteurization, but with higher temperatures and longer times. UP pasteurization results in a product with a longer shelf life, but still requires refrigerated milk, whereas acidified foods or nutritional supplements (pH < 4.6) do not require refrigeration. Another method, Ultra High Temperature (UHT) pasteurization, raises the temperature above 93.3 ℃ (i.e. 200 ° f) for a few seconds, followed by rapid cooling. The aseptically packaged UHT-pasteurized product forms a "shelf-stable" product that does not require refrigeration prior to opening it.

As used herein, "aseptic processing and packaging" and similar terms mean filling a sterilized chilled product into pre-sterilized containers, followed by aseptic sealing with a pre-sterilized closure in a microbe-free environment.

As used herein, "sealed container" and similar terms mean a container designed to ensure that entry of microorganisms is prevented and thus its contents are maintained sterile after processing.

As used herein, a "tablet" is a solid dosage form containing a dietary supplement, with or without suitable excipients or diluents, prepared by compression or molding methods known in the art. Tablets have been commonly used and continue to be marketed since the late 19 th century. Tablets remain popular as a dosage form because of the advantages they provide to the manufacturer (e.g., simplicity and economy of manufacture, stability and ease of packaging, shipping and distribution) and to the user (e.g., precise dosage, small size, portability, bland taste and ease of administration). Although tablets are most commonly discoid, they may also be circular, oval, rectangular, cylindrical or triangular. Depending on the amount of dietary supplements present and the intended method of administration, they may vary widely in size and weight. They can be divided into two general categories, (1) compressed tablets and (2) molded tablets or tablet developers. In addition to the active or therapeutic ingredient, tablets may contain a wide variety of inert substances or additives. A first group of such additives includes those which help to impart satisfactory compression characteristics to the formulation, including diluents, binders and lubricants. A second group of such additives helps to impart other desirable physical characteristics to the finished tablet, such as disintegrants, coloring agents, flavoring agents and sweeteners.

As used herein, a "diluent" is an inert substance added to increase the volume of the formulation to make the tablet a practical size for compression. Commonly used diluents include calcium phosphate, calcium sulfate, lactose, kaolin, mannitol, sodium chloride, dry starch, powdered sugar, silicon dioxide, and the like.

As used herein, a "binder" is a substance used to impart cohesiveness to a powdered material. Binders, or sometimes called "granulating agents," impart cohesiveness to the tablet formulation, which ensures that the tablet remains intact after compression, while increasing free-flowing properties by making granules of the desired hardness and size. Materials commonly used as binders include starch; gelatin; sugars, such as sucrose, glucose, dextrose, molasses and lactose; natural and synthetic gums such as gum arabic, sodium alginate, extracts of irish moss, panwar gum, ghatti gum, mucilage of isapol coat, carboxymethyl cellulose, methyl cellulose, polyvinyl pyrrolidone, Veegum, microcrystalline cellulose, microcrystalline dextrose, amylose, and larch arabinogalactan, and the like.

As used herein, a "lubricant" is a substance that performs many functions in tablet production, such as increasing the flow rate of tablet granulation, preventing tablet material from adhering to the surfaces of the die and punch, reducing inter-granular friction, and facilitating the ejection of the tablet from the die cavity. Commonly used lubricants include talc, magnesium stearate, calcium stearate, stearic acid and hydrogenated vegetable oils.

As used herein, a "disintegrant" or "disintegrant" is a substance that aids in the breaking or disintegration of a tablet after administration. Substances used as disintegrants have been classified chemically as starches, clays, celluloses, algins or gums. Other disintegrants include Veegum HV, methylcellulose, agar, bentonite, cellulose and wood products, natural sponges, cation exchange resins, alginic acid, guar gum, citrus pulp, cross-linked polyvinylpyrrolidone, carboxymethylcellulose, and the like.

As used herein, a "colorant" is a substance that imparts a more pleasing appearance to the tablet, and in addition helps the manufacturer control the product during its preparation and helps the user identify the product. Any approved water-soluble FD & C dye, mixtures thereof, or their corresponding lakes may be used to color the tablets. Lakes are a combination of dyes that are adsorbed in an oxide hydrate of a heavy metal by a water-soluble dye, resulting in an insoluble form.

As used herein, "flavors" vary widely in their chemical structures, ranging from simple esters, alcohols and aldehydes to sugars and complex volatile oils. Almost any desired type of natural and synthetic flavoring agents can be obtained.

As used herein, a "capsule" is a solid dosage form in which the dietary supplement package is enclosed in a container or shell of hard or soft (including gel caps), soluble suitable polymer, such as gelatin. Soft gelatin capsules were invented by the French pharmacist Mothes in 1833. In the next year, Dublanc patented his soft gelatin capsule. In 1848, Murdock patented a two-part hard gelatin capsule. Encapsulation of pharmaceutical agents, dietary supplements, and the like remains a popular method of administration by the oral route. The capsule is odorless, easy to take and easy to fill. Some find that capsules are easier to swallow than tablets and therefore prefer to take this form when possible. This preference has prompted manufacturers to market products in capsule form, even though such products have been produced in tablet form.

As used herein, "pharmaceutical necessity" means a substance that has little or no nutritional or therapeutic value, but is useful in the preparation and formulation of various dietary supplement formulations. These include antioxidants and preservatives; coloring, flavoring and diluting agents; emulsifying and suspending agents; a base for the ointment; drug solvents and miscellaneous agents. See, for example, a review of the pharmaceutical requirements known in the art in Remington's pharmaceutical Sciences.

As used herein, "powder" means a solid dosage form that is suspended or dissolved in water or another liquid or mixed with a soft serve prior to administration. Powders are typically prepared by spray drying or freeze drying liquid formulations. Powders have advantages due to flexibility, stability, quick action and ease of administration.

As used herein, "Brix" is a measure for measuring the sugar content of a grape, wine, or the like. Brix per degree corresponds to 1g of sugar per 100mL of liquid. Thus, an 18 degree Brix sugar solution contains 18% by weight sugar. Brix also describes the percentage of suspended solids in a liquid. Thus, for example, 95Brix means a liquid containing 95% by weight of suspended solids. Brix is measured with an optical device called a refractometer. The measurement system of Brix is known from the german inventor in the 19 th century a.f.w.brix.

The present invention advances the art by providing dietary supplements formulated with fucoidan from seaweed, such as 1imu moui, kombu or mozuku. The addition of fucoidan to the dietary supplement of the present invention serves to provide significant dietary and nutritional benefits not found in the dietary supplements of the prior art. The fucoidan-fortified dietary supplement of the present invention provides a number of beneficial functions, including providing longevity, anti-aging, and regeneration of cells and tissues, such as muscle and bone; promoting growth factors in the body; promoting vigorous energy, vitality and youth; maintaining and strengthening the immune system, reducing allergies, inhibiting blood clotting, controlling blood glucose, preventing ulcers, relieving gastric discomfort, reducing inflammation, protecting the kidneys, and detoxifying the body. The preparation of fucoidan according to the invention may also help to reduce and prevent cardiovascular diseases by lowering cholesterol levels, inhibiting smooth muscle cell proliferation and activating enzymes involved in beta-oxidation of fatty acids.

In addition, the fucoidan-fortified dietary supplement of the present invention antagonizes cancerous tumors and minimizes the visible signs of biological and environmental aging. That is, the dietary supplement may slow the aging process, help regenerate damaged cells and tissues, and promote growth factors in the body. Fucoidan is rich in antioxidants that help to combat damage to the body by free radicals that may lead to cancer. Fucoidan also provides significant benefits to the skin. Fucoidan is rich in antioxidants that help to resist free radical damage caused by sunlight and other altered environmental conditions and elements.

Brown algae are grown in many oceans, including Okinawa islands in japan, offshore waters in russia, coastal waters in tangca and elsewhere. One excellent source of fucoidan is the limu moui marine plant grown in the waters of tanga islands. This brown algae contains many vitamins, minerals and other beneficial substances and is particularly rich in fucoidan.

Typically, brown algae grow in the long angel stem region with many leaves. The fucoidan component is found in the natural composition on the algal cell wall, providing a slippery, sticky texture that protects the cell wall from sunlight.

In one embodiment, the kombu-type or mozuku-type seaweeds are harvested from offshore waters of tokaga. These seaweeds are usually collected manually by divers, including stems and leaves, and washed to remove foreign matter. The seaweed is then usually frozen in large containers and transported to processing plants.

During processing, a large number of the outer fibers must first be broken down to provide access to the fucoidan component. If frozen, the seaweed material is first thawed, and if not frozen, the seaweed material is placed in a mixing tub and shredded while being hydrolyzed with acid and water. The material may optionally be sulfonated with sulfuric acid to help break down a large number of cellular fibers. The mixture may also be buffered with citric acid and thoroughly mixed to maintain the suspension. The material may also be heated at or above atmospheric pressure while mixing. The resulting sludge was tested and maintained at a pH of about 2-4 to maintain acidity and thereby enhance preservative and stability characteristics.

The mash may be used to prepare a dietary supplement product. Alternatively, the mixture may be re-frozen in a small container for later processing.

The present invention provides dietary supplement beverages formulated with fucoidan components from seaweed, such as the limu moui seaweed plant. In selected embodiments, the fucoidan component is present in an amount of about 0.5 to about 70 weight percent based on the total weight of the composition. Other ingredients may include antioxidants such as acai fruit and blueberry with high Oxygen Radical Absorbance Capacity (ORAC). Such antioxidants are present in amounts of about 0 to about 20 weight percent. Additionally, minerals, such as deep sea minerals, are present in amounts of about 0 to about 2 weight percent to provide significant minerals.

High ORAC health food ingredient

Free radicals are very reactive and highly destructive compounds in the body. Free radicals are products of oxidative deterioration of substances such as polyunsaturated fats. Antioxidants convert free radicals into less reactive and harmless chemical forms. Antioxidants that may be used in the dietary supplement include beta-carotene, vitamin E, vitamin C, N-acetylcysteine, alpha-lipoic acid, selenium, and the like. Antioxidants with high ORAC values are particularly desirable. Illustrative high ORAC value nutraceutical antioxidants that may be used in the present invention include the following fruit juice concentrates: grapes (red, black or white), blueberries, acai fruits, raspberries, blackberries, strawberries, plums, oranges, cherries, kiwifruits, blackcurrants, elderberries, redcurrants, cranberries, mangosteen, noni fruits, aronia fruits, thinleaf western snow fruits and mixtures thereof. Other high ORAC health food ingredients include proanthocyanidins, such as oligomeric proanthocyanidins, curcuminoids, and the like.

Inorganic substance

Minerals serve a variety of basic physiological functions, ranging from structural components of body tissues to essential components of many enzymes and other important biomolecules. Minerals are classified as micronutrients or trace elements according to the amount present in the body. Seven micronutrients (calcium, potassium, sodium, magnesium, phosphorus, sulfur and chloride) are present in the body in amounts greater than 5 grams. Trace elements, including boron, copper, iron, manganese, selenium and zinc, are present in the body in amounts less than 5 grams.

Micronutrient minerals

Calcium is considered the most mineral element in the diet in the united states. If the diet is deficient in milk and dairy products, it is difficult to achieve a calcium intake of more than 300mg per day. This is well below the recommended daily food intake (RDA) for calcium (1000 mg per day for adults and children 1-10 years old, 1200mg per day for adolescents and pregnant and lactating women, which is equivalent to about 4 cups of milk per day). Indeed, it has been reported that women over the age of 12 have an average daily calcium intake of no more than 85% of the recommended daily intake. In addition, during those years of highest bone mass development (18 to 30 years), more than 66% of all american women failed to consume the recommended amount of calcium on any given day. After age 35, this percentage rises to over 75%.

Although the general public is not fully aware of the consequences of long-term mineral intake insufficiency, there is a great deal of scientific evidence that low calcium intake is one of several contributing factors to osteoporosis. In addition, the dietary ratio of calcium to phosphorus (Ca: P) is directly related to bone health. A ratio of Ca to P of 1: 1 to 2: 1 is recommended to enhance human bone multimyelination (marrowation). Such ratios are difficult to achieve in dietary supplies lacking sufficient milk and dairy products, or in supplies of calcium and other minerals to people with lactose intolerance.

Magnesium is the second most abundant cation in the intracellular fluid. It is essential for the activity of many enzyme systems and plays an important role for neurochemical transmission and muscle excitability. The deficiency is associated with a variety of structural and functional disorders. An average 70kg adult contains about 2000mEq of magnesium in his body. About 50% of magnesium is found in bone, 45% is present as intracellular cations and 5% is present in extracellular fluid. About 30% of the magnesium in bone represents an exchangeable pool present in the hydrated shell or on the crystalline surface. Mobilization of cations from this pool in bone is fairly rapid in children, but not in adults. The greater part of magnesium in bone is apparently a constituent of bone crystals.

The average adult human in the united states ingests about 20-40mEq of magnesium per day in the daily diet, and wherein about 1/3 is absorbed from the gastrointestinal tract. Evidence suggests that most absorption occurs in the upper small intestine. Absorption relies on active processes that are apparently closely linked to the transport system of calcium. The uptake of low amounts of magnesium leads to an increased absorption of calcium and vice versa.

Magnesium is a cofactor for all enzymes involved in phosphotransferase reactions that utilize Adenosine Triphosphate (ATP) and other nucleotide triphosphates as substrates. The various phosphatases and pyrophosphatases also represent enzymes on a long list that are affected by this metal ion.

Magnesium plays a crucial role in the reversible association of intracellular particles and the binding of macromolecules to subcellular organelles. For example, the binding of messenger ribonucleic acid (mRNA) to ribosomes is magnesium-dependent, as is the functional integrity of the ribosomal subunits. Some of the effects of magnesium on the nervous system are similar to those of calcium. Increased concentrations of magnesium in the extracellular fluid lead to depression of the Central Nervous System (CNS). Hypomagnesaemia leads to increased CNS excitability, disorientation and convulsions. Magnesium also has a direct inhibitory effect on skeletal muscle. Abnormally low concentrations of magnesium in the extracellular fluid result in increased acetylcholine release and increased muscle excitability, which can produce tetany.

Trace elements

The body requires trace amounts of boron for proper metabolism of calcium, magnesium and phosphorus. Boron contributes to brain function, healthy bones, and can improve alertness. Boron is also useful for those who want to strengthen muscles. Boron is known to help prevent postmenopausal osteoporosis. In addition, a lack of boron in the diet is associated with the possibility of arthritis. R.E. Newnham, 46 Journal of applied Nutrition (1994).

Chromium is an important trace element and the lack of sufficient chromium in the diet leads to a reduction in glucose utilization, however, disturbances in protein and lipid metabolism are also observed. Reduced glucose utilization occurs in many middle-aged and elderly people. In experimental studies, a large number of such people showed increased glucose utilization after treatment with chromium. Chromium is transported by transferrin in plasma and competes with iron for binding sites. Chromium may be of benefit as a dietary supplement because it enhances glucose utilization and it may promote the binding of insulin to the insulin receptor, which enhances its effect on carbohydrate and lipid metabolism. Chromium as a supplement may have benefits in atherosclerosis, diabetes, rheumatism and weight control.

Copper is another important trace element in the diet. The most common defect observed in animals deficient in copper is anemia. Other abnormalities include growth inhibition, skeletal defects, demyelination and nervous system degeneration, ataxia, pigmentation and defects in hair or fetal hair structure, reproductive failure and cardiovascular disease, including anatomical aneurysms. Several copper-containing metalloproteins have been isolated, including tyrosinase, ascorbate oxidase, laccase, cytochrome oxidase, uricase, monoamine oxidase, delta-aminolevulinic acid hydratase, and dopamine-beta-hydroxylase. Copper plays a role in the processes of iron absorption and utilization, electron transport, connective tissue metabolism, phospholipid formation, purine metabolism and development of the nervous system. Ferrous oxidase I (ceruloplasmin), a cupramminase, causes the oxidation of fe (ii) to fe (ih), a step required for mobilization of stored iron. Cuprammonucleases are thought to cause oxidative deamination of the epsilon amino group of lysine to produce desmosine and isodesmosine, i.e., a cross-linked body of elastin. In animals lacking copper, arterial elastin is weaker and dissecting aneurysms may occur.

Iodine is important for the production of thyroid hormones, which regulate cellular oxidation. The iodine deficiency disease is goiter. In young people lacking iodine, growth is retarded and sexual development is delayed, skin and hair are often rough, and hair becomes thin. In severe deficiency, dull, hypoenergetic and deaf-mute states occur. Birth failure occurs in women and fertility decline occurs in men if there is a lack of sufficient iodine in the diet.

Iron is an essential component in several important metalloproteins. These metalloproteins include hemoglobin, myoglobin and many oxidoreductases. In iron deficiency, reduced concentrations of some iron-containing enzymes may be present, such as cytochrome C in the liver, kidney and skeletal muscle, and succinate dehydrogenase in the kidney and heart.

Manganese plays a role in the synthesis of GAGs, collagen and glycoproteins, which are important components of cartilage and bone. Manganese is required for the enzymatic activity of glycosyltransferases. The family of enzymes results in the linkage of sugars into GAGs, the addition of sugars to other glycoproteins, the addition of sulfates to amino sugars, the conversion of sugars to other modified sugars, and the addition of sugars to lipids. These functions are manifested by GAG synthesis (hyaluronic acid, chondroitin sulfate, keratan sulfate, heparin sulfate, dermatan sulfate, etc.), collagen synthesis, and many other glycoprotein and glycolipid functions. GAGs and collagen are the major structural elements of all connective tissues. Their synthesis is essential for proper maintenance and repair of connective tissue.

Manganese deficiency in humans and animals leads to abnormal bone growth, swelling and enlarged joints and slipped tendons. In humans, manganese deficiency is associated with bone destruction, arthritis, and reduced glucose utilization. During manganese deficiency, levels of all GAGs in the connective tissue are reduced and chondroitin sulfate is almost depleted. When manganese is provided, manganese deficient organisms rapidly normalize GAG and collagen synthesis.

Manganese is also required for the activity of manganese superoxide dismutase (MnSOD) which is only present in mitochondria. Manganese deficiency decreases the activity of MnSOD and may lead to mitochondrial dysfunction, manifested as decreased cellular function. Manganese is required for conversion of mevalonate to squalene. Pyruvate carboxylase is a manganese metalloenzyme, which is repressed by insulin and is important in the citric acid cycle for carbohydrate, lipid and protein oxidation, and synthesis of glucose and lipids.

Molybdenum is an essential mineral found in the liver, kidneys, skin and bones at the highest concentration. The body requires this mineral for proper nitrogen metabolism. It is also an extremely important component of xanthine oxidase, which is required to convert purines to uric acid, a normal metabolic byproduct. Molybdenum also supports the body's storage of iron and other cellular functions such as growth. The lack of molybdenum is associated with oral and gingival disorders and cancer. Diets rich in refined and processed foods can result in molybdenum deficiency in animals, resulting in anemia, loss of appetite and weight loss, and impaired growth. Although these defects have not been directly observed in humans, it is known that molybdenum deficiency can lead to impotence in elderly men.

Selenium is an essential trace element that functions as a component of defense against antioxidants and enzymes involved in thyroid hormone metabolism. Among several intracellular and extracellular glutathione peroxidases and iodothyronine 5' -deiodinases, selenium is located as the active center of seleno-amino acids, namely selenocysteine (SeCYS). At least two other proteins of unknown function also contain SeCYS. Although SeCYS is an important dietary form, it cannot be incorporated directly into these specific selenoproteins; instead, its translational processing generates tRNA binding to SeCYS. In contrast, selenium is non-specifically incorporated as selenomethionine into many proteins because it competes with methionine in general protein synthesis. Thus, when both SeCYS and selenomethionine are consumed, tissues often contain specific, as well as non-specific selenoproteins, as found in many food products. Selenium is a major antioxidant nutrient and is involved in protecting cell membranes and preventing free radical production, thereby reducing the risk of cancer and heart and vascular diseases. Medical investigations have shown that increasing selenium intake reduces the risk of breast, colon, lung and prostate cancer. Selenium also maintains tissue elasticity; slowing down the aging and hardening of the tissue due to oxidation; and helps to treat and prevent dandruff. Recent studies have shown the anti-tumorigenic effect of high levels of selenium in the diet of several animal models.

Vanadium is an essential nutrient beneficial to thyroid hormone metabolism. The daily requirement necessary to prevent deficiency is about 10-20 mug per day. Vanadium deficiency can lead to growth retardation, skeletal defects and altered lipid metabolism. Vanadium plays a role similar to insulin in some respects, and a great deal of research is being conducted on vanadium and diabetes. In insulin-dependent diabetes, vanadium is found to reduce the amount of insulin required to control the disease, whereas in non-insulin-dependent diabetes, vanadium is known to completely control the condition. Studies have shown that vanadium supplementation leads to increased glucose transport into cells, which indicates that vanadium supplementation in the diet can improve glucose metabolism and can help prevent diabetes.

Zinc is known to be present in many important metalloenzymes. These metalloenzymes include carbonic anhydrase, carboxypeptidases A and B, alcohol dehydrogenase, glutamate dehydrogenase, D-glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, malate dehydrogenase, alkaline phosphatase, and aldolase. Reduced nucleic acid and protein synthesis has been observed in zinc deficiency. There is also evidence that zinc may be involved in insulin secretion and hormonal function.

According to the present invention, the inorganic substance may be provided as an inorganic compound such as chloride, sulfate, or the like. In addition, some minerals may be provided in more bioavailable forms, such as amino acid chelates, which are well known in the art. US patent US5,292,538. Examples of minerals that may be provided as amino acid chelates include calcium, magnesium, manganese, zinc, iron, boron, copper, molybdenum, and chromium. In addition, the inorganic substance may be provided as a deep sea inorganic substance.

Additional ingredients of the disclosed compositions may include fruit flavors and colorants, such as small amounts of grapes and raspberry. Sweeteners, such as bitter melon fruit, may also be included. Ingredients promoting absorption by the body, such as black pepper or Sichuan pepper extract, may be added. Preservatives, such as sodium benzoate or potassium sorbate, may also be included. Substantially pure water, such as deionized water, is also an important component of the liquid mixture.

In one embodiment, the dietary supplement may be provided in the form of a nutritional beverage or drink. The supplement may also be dried to a powder and provided in the form of a freeze-dried or spray-dried powder, capsule or tablet. An exemplary beverage supplement is now described in more detail.

Starting with the fucoidan-containing puree described above, juices or concentrates for providing a high Oxygen Radical Absorbance Capacity (ORAC) are added, such as acai fruit, grapes and blueberries. Fruit flavors and colorants, such as grapes and raspberry, can also be added to the mixture; inorganic substances, such as deep sea inorganic substances; sweeteners, such as bitter melon fruits; peppers for enhancing flavor and promoting body absorption, such as black pepper; preservatives, such as sodium benzoate or potassium sorbate; and deionized water. Next, the mixture is sterilized by pasteurization or other heating techniques. Although pasteurization (at least 87.8 ℃ or 190 ℃ F.) can effectively eliminate pathogenic microorganisms, sterilization at higher temperatures may be required to eliminate all microorganisms.

To accomplish the necessary sterilization, two different sterilization processes are typically used. Using the HTST (high temperature short time) process, the temperature of the mixture can be raised to about 85 deg.C (185 deg.F) for about 20-30 seconds. Alternatively, the Ultra High Temperature (UHT) process involves raising the temperature of the mixture to about 140.6 deg.C (285 deg.F) for about 4-6 seconds. In either process, the temperature is rapidly reduced immediately after the heating step to an ambient temperature of at least about 21.1-26.7 ℃ (70-80 ° f). Alternatively, the mixture may be cooled to about 4.4 ℃ (40 ° f).

The heating of the mixture may be achieved by direct or indirect heating. For example, the mixture may be heated by direct contact with steam or indirectly through a heat exchanger of a selected type.

The sterilized mixture may then be poured into containers using hot-fill or cold-fill methods. In the hot-fill process, the product is first heated to a temperature of pasteurization, HTST or UHT. It is then poured into the container at an elevated temperature to kill any microorganisms inside the container. Preservatives are used, for example sodium benzoate and potassium sorbate are commonly used. The pH is usually kept below 4.4, possibly with an acid such as lemon juice or vinegar. After filling, the bottles may be slowly cooled with an aerosol. Filling of the containers is performed by aseptic processing and packaging methods, which are well known in the art.

In the cold-fill process, after pasteurization or sterilization temperatures are reached, the product is immediately cooled to about room temperature using aseptic processing and packaging processes and then bottled. Immediate cooling results in reduced vitamin degradation and flavor changes that can be found in hot-fill processes. Thus, in cold-fill processing, the taste may be fresher. Preservatives are typically included to control the growth of yeast, mold and bacteria.

The cold filling process may be coupled with filling using High Density Polyethylene (HDPE) or polyethylene terephthalate bottles so as not to compromise the structural integrity of the bottles. The bottle may be a 500mL bottle, which may contain about 660g per bottle. If the recommended dose is about 22g per day, the specification may provide a beverage that is sufficient for 30 days to drink.

The solid dosage forms according to the present invention may be prepared in the form of powders, tablets and capsules according to methods well known in the art. For example, the powder can be prepared by drying the fucoidan preparation and then mixing the dried fucoidan with other dry ingredients. Alternatively, the fucoidan preparation can be mixed with other ingredients and the mixture then dried to a powder. Exemplary drying methods include spray drying and freeze drying. The powder can be ingested by suspending or dissolving the powder in a liquid and then drinking the resulting suspension or solution. Exemplary liquids that may be used for this purpose include water, juices, and the like. The powder may also be compressed into tablets or filled into capsules. Tablets or capsules are typically swallowed with water or other liquid. Liquid dietary supplements may also be encapsulated and administered in such solid dosage forms.

Examples

The following are examples of the preparation of brown algae to provide a fucoidan puree for use in a dietary supplement, and dietary supplement formulations prepared from the fucoidan puree. These examples are illustrative only and are not meant to be limiting in any way.

The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description or examples. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.

Example 1

Preparation of fucoidan puree compositions

Manually collecting soup and limu moui seaweed, cleaning to remove foreign matter, freezing, and transporting to a processing factory. According to any one set of conditions listed in table 1, at the processing plant, the frozen seaweed was thawed, weighed and placed in a stainless steel mixer with aqueous buffer and optionally sulfuric acid. These ingredients were then mixed using a medium shear mixer (impeller type) at 50-75 rpm. While mixing, the mixture is heated to 37-95 ℃ for a selected period of time (typically 5 minutes-8 hours). At this point, heating is stopped, but mixing is continued for 0.5-10 hours to dissipate the heat and micronize the shredded seaweed. The cooled mixture was then filtered to remove insoluble material, and the filtrate was then masked and mixed at room temperature for about 4-72 hours. The pH of the resulting sauce was determined to be about 2.0-4.0, and refractometry generally indicated a Brix value of 2-4. The sauce containing partially hydrolyzed fucoidan is then frozen and stored. If sulfuric acid is added during the hydrolysis, the partially hydrolyzed fucoidan is sulfonated.

TABLE 1
									Test of
I	II	III	IV	V	VI	VII
							pH		2.0-2.4	2.2-2.5	2.4-2.7	2.6-3.0	2.9-3.2	3.2-3.6	3.6-4.0
Sulfuric acid	--	0.01N	--	0.001N	0.004N	--		0.001
							Seaweed (Sargassum)		20wt％	10wt％	25wt％	40wt％	33wt％	15wt％	42wt％
Temperature of	37℃	42℃	50℃	60℃	75℃	80℃		95℃
							Time of heating		5 hours	4 hours	4 hours	3 hours	35 minutes	20 minutes	15 minutes
Filtering and mixing	24 hours, 37 deg.C	16 hours, 37 deg.C	72 hours, 22 deg.C	24 hours, 22 deg.C	48 hours, 22 deg.C	36 hours, 22 deg.C		8 hours, 22 deg.C

Example 2

Preparation of fucoidan beverage

The fucoidan paste prepared according to the procedure in example 1 was thawed and then mixed with the other ingredients of the present invention as shown in tables 2 and 3, wherein the amounts are parts by weight. The ingredients were thoroughly mixed and then sterilized according to any one of the conditions listed in table 4 and bottled by aseptic manipulation and packaging methods.

TABLE 2
								Preparation number
	1	2	3	4	5	6
							Fucoidan	20	25	30	35	40	45
Water (W)	80	75	64	64.2	54.63	45.62
							Grape			6
Blueberry						4
							acai				0.5
Fructus Rubi Corchorifolii Immaturus					2.5
							Blackberry					1.5
Strawberry					0.5
							Plum fruit
Orange
							Cherry						4
Kiwi fruit
							Black currant						1
Ramulus Sambuci Williamsii fruit
							Black currant
Cranberry
							Deep sea inorganic matter					0.5	0.2
Balsam pear				0.2	0.25	0.1
							Sodium benzoate				0.08		0.05
Potassium sorbate					0.1
							Black pepper		0.05		0.01	0.02
Sichuan pepper			0.02			0.03

TABLE 3
								Preparation number
	7	8	9	10	11	12
							Fucoidan	0.5	8	13	17	19	22
Water (W)	86.17	85.06	83.63	76.65	72.72	69.97
							Grape			2		5.7	5.5
Blueberry				4.2		1.5
							acai			0.5	0.1	0.3	0.5
Fructus Rubi Corchorifolii Immaturus					0.3	3
							Blackberry					0.1
Strawberry				1.0	0.8
							Plum fruit		3.5
Orange	10
							Cherry
Kiwi fruit	3				0.4
							Black currant
Ramulus Sambuci Williamsii fruit			0.3
							Black currant				0.5
Cranberry		2.4
							Deep sea inorganic matter		0.33	0.4	0.23	0.29	0.31
Balsam pear	0.12	0.5			0.17	0.16
							Sodium benzoate	0.12		0.15	0.18	0.16	0.06
Potassium sorbate	0.08	0.2			0.04	0.11
							Black pepper	0.005	0.01		0.14		0.01
Sichuan pepper	0.005		0.02		0.015

TABLE 4
			Conditional order	Sterilization	Bottling
I	At 62.8 ℃ for 30 minutes	Hot filling
			II	71.7 ℃ for 15 seconds	Hot filling
III	93.3 ℃ for 10 seconds	Hot filling
			IV	96.0 deg.C, 10 seconds	Hot filling
V	At 62.8 ℃ for 30 minutes	Cold filling
			VI	140.6 ℃ for 6 seconds	Cold filling

Example 3

About 70 parts by weight of the fucoidan puree prepared according to the procedure of example 1 was mixed with about 99 parts by weight of distilled water, about 20 parts by weight of the concord grape extract, about 2 parts by weight of the deep sea mineral, about 1 part by weight of momordica charantia and about 1 part by weight of the black pepper extract. The resulting mixture is spray dried to a powder and packaged for storage and sale.

Example 4

The procedure of example 3 was followed except that the powder was encapsulated in a gelatin capsule.

Example 5

The procedure of example 3 is followed except that the powder is mixed with selected amounts of diluents, binders, lubricants, disintegrants, coloring agents, flavoring agents and sweeteners and then compressed into tablets.

Claims (77)

1. A dietary supplement comprising about 0.5 to about 70 parts by weight of partially hydrolyzed fucoidan and about 30 to about 99.5 parts by weight water.

2. The dietary supplement of claim 1, further comprising about 0.5 to about 20 parts by weight of a nutraceutical ingredient having a high ORAC value.

3. The dietary supplement of claim 2, wherein the nutraceutical ingredient with a high ORAC value comprises grape juice concentrate.

4. The dietary supplement of claim 2, wherein the nutraceutical ingredient having a high ORAC value comprises blueberry concentrate.

5. The dietary supplement of claim 2, wherein the nutraceutical ingredient with a high ORAC value contains acai fruit concentrate.

6. The dietary supplement of claim 2, wherein the nutraceutical ingredient with a high ORAC value is a member selected from the group consisting of: grape juice concentrate, blueberry juice concentrate, acai fruit juice concentrate, raspberry juice concentrate, blackberry juice concentrate, strawberry juice concentrate, plum juice concentrate, orange juice concentrate, cherry juice concentrate, kiwi juice concentrate, blackcurrant juice concentrate, elderberry juice concentrate, redcurrant juice concentrate, cranberry juice concentrate, mangosteen, noni, aronia, passion fruit, anthocyanidins, curcuminoids, and mixtures thereof.

7. The dietary supplement of claim 1, wherein the partially hydrolyzed fucoidan is sulfonated.

8. The dietary supplement of claim 1, wherein the fucoidan is from Thomas plus limu moui seaweed.

9. The dietary supplement of claim 1, wherein the fucoidan is derived from mozuku or kombu seaweed, or a mixture comprising fucoidan derived from mozuku or kombu seaweed.

10. The dietary supplement of claim 1, further comprising about 0.01 to about 2 parts by weight of minerals.

11. The dietary supplement of claim 10, wherein the minerals comprise deep sea minerals.

12. The dietary supplement of claim 1, further comprising about 0.01 to about 1 parts by weight of a flavoring agent.

13. The dietary supplement of claim 1, further comprising about 0.01 to about 1 parts by weight of a preservative.

14. The dietary supplement of claim 13, wherein the preservative comprises sodium benzoate.

15. The dietary supplement of claim 1, further comprising about 0.001 to about 1 parts by weight of pepper extract.

16. The dietary supplement of claim 15, wherein the pepper extract comprises black pepper.

17. The dietary supplement of claim 15, wherein the pepper extract comprises sichuan pepper.

18. A dietary supplement comprising about 0.5 to about 70 parts by weight of partially hydrolyzed fucoidan, about 0.5 to about 20 parts by weight of a nutraceutical ingredient having a high ORAC value, and about 10 to about 99 parts by weight of water.

19. The dietary supplement of claim 18, wherein the nutraceutical ingredient having a high ORAC value comprises grape juice concentrate.

20. The dietary supplement of claim 18, wherein the nutraceutical ingredient having a high ORAC value comprises a blueberry concentrate.

21. The dietary supplement of claim 18, wherein the nutraceutical ingredient with a high ORAC value comprises acai fruit concentrate.

22. The dietary supplement of claim 18, wherein the nutraceutical ingredient with a high ORAC value is a member selected from the group consisting of: grape juice concentrate, blueberry juice concentrate, acai fruit juice concentrate, raspberry juice concentrate, blackberry juice concentrate, strawberry juice concentrate, plum juice concentrate, orange juice concentrate, cherry juice concentrate, kiwi juice concentrate, blackcurrant juice concentrate, elderberry juice concentrate, redcurrant juice concentrate, cranberry juice concentrate, mangosteen, noni, aronia, passion fruit, anthocyanidins, curcuminoids, and mixtures thereof.

23. The dietary supplement of claim 18, wherein the partially hydrolyzed fucoidan is sulfonated.

24. The dietary supplement of claim 18, wherein the fucoidan is derived from Thangogany moui seaweed, Japanese mozuku seaweed, or Japanese kombu seaweed, or a mixture comprising fucoidan derived from at least two of Thangogany moui seaweed, Japanese mozuku seaweed, and kombu seaweed.

25. The dietary supplement of claim 18, further comprising about 0.01 to about 2 parts by weight of minerals.

26. The dietary supplement of claim 25, wherein the minerals comprise deep sea minerals.

27. The dietary supplement of claim 18, further comprising about 0.01 to about 1 parts by weight of a flavoring agent.

28. The dietary supplement of claim 18, further comprising about 0.01 to about 1 parts by weight of a preservative.

29. The dietary supplement of claim 18, further comprising about 0.001 to about 1 parts by weight of pepper extract.

30. The dietary supplement of claim 29, wherein the pepper extract comprises black pepper, Sichuan pepper or a mixture thereof.

31. A dietary supplement comprising about 0.5 to about 70 parts by weight partially hydrolyzed fucoidan, about 0.001 to about 1 parts by weight pepper extract, and about 29 to about 99.5 parts by weight water.

32. The dietary supplement of claim 31, wherein the pepper extract comprises black pepper.

33. The dietary supplement of claim 31, wherein the pepper extract comprises sichuan pepper.

34. The dietary supplement of claim 31, further comprising about 0.5 to about 20 parts by weight of a nutraceutical ingredient having a high ORAC value.

35. The dietary supplement of claim 34, wherein the nutraceutical ingredient having a high ORAC value comprises grape juice concentrate.

36. The dietary supplement of claim 34, wherein the nutraceutical ingredient having a high ORAC value comprises blueberry concentrate.

37. The dietary supplement of claim 34, wherein the nutraceutical ingredient with a high ORAC value comprises acai fruit concentrate.

38. The dietary supplement of claim 34, wherein the nutraceutical ingredient with a high ORAC value is a member selected from the group consisting of: grape juice concentrate, blueberry juice concentrate, acai fruit juice concentrate, raspberry juice concentrate, blackberry juice concentrate, strawberry juice concentrate, plum juice concentrate, orange juice concentrate, cherry juice concentrate, kiwi juice concentrate, blackcurrant juice concentrate, elderberry juice concentrate, redcurrant juice concentrate, cranberry juice concentrate, mangosteen, noni, aronia, passion fruit, anthocyanidins, curcumin, and mixtures thereof.

39. The dietary supplement of claim 31, wherein the partially hydrolyzed fucoidan is sulfonated.

40. The dietary supplement of claim 31, wherein the fucoidan is derived from Thangogany moui seaweed, Japanese mozuku seaweed, or Japanese kombu seaweed, or a mixture comprising fucoidan derived from at least two of Thangogany moui seaweed, Japanese mozuku seaweed, and kombu seaweed.

41. The dietary supplement of claim 31, further comprising about 0.01 to about 2 parts by weight of minerals.

42. The dietary supplement of claim 41, wherein the minerals comprise deep sea minerals.

43. The dietary supplement of claim 31, further comprising about 0.01 to about 2 parts by weight of a flavoring agent.

44. The dietary supplement of claim 31, further comprising about 0.01 to about 1 parts by weight of a preservative.

45. A dietary supplement comprising about 0.5 to about 70 parts by weight of partially hydrolyzed, sulfonated fucoidan, about 0.001 to about 1 part by weight of pepper extract, about 0.5 to about 20 parts by weight of a nutraceutical ingredient having a high ORAC value, and about 9 to about 99.0 parts by weight of water.

46. The dietary supplement of claim 45, wherein the pepper extract comprises black pepper or Sichuan pepper.

47. The dietary supplement of claim 45, wherein the nutraceutical ingredient with a high ORAC value is a member selected from the group consisting of: grape juice concentrate, blueberry juice concentrate, acai fruit juice concentrate, raspberry juice concentrate, blackberry juice concentrate, strawberry juice concentrate, plum juice concentrate, orange juice concentrate, cherry juice concentrate, kiwi juice concentrate, blackcurrant juice concentrate, elderberry juice concentrate, redcurrant juice concentrate, cranberry juice concentrate, mangosteen, noni, aronia, passion fruit, anthocyanidins, curcuminoids, and mixtures thereof.

48. The dietary supplement of claim 45, further comprising about 0.01 to about 2 parts by weight of deep sea minerals.

49. A method of making a partially hydrolyzed fucoidan composition, the method comprising:

(a) mixing a selected amount of fucoidan-containing seaweed with water and adjusting the hydrogen ion concentration to a pH of about 2.0-4.0 to produce a mixture;

(b) heating the mixture to a temperature of about 37 ℃ to about 95 ℃ for a selected period of time while continuing to stir the mixture, thereby partially hydrolyzing fucoidan in the seaweed to produce a heated mixture;

(c) cooling the heated mixture to ambient temperature, and while cooling, continuing to mix the heated mixture to produce a cooled mixture; and

(d) incubating the cooled mixture at ambient temperature while mixing for up to about 72 hours, thereby obtaining a partially hydrolyzed fucoidan composition.

50. The method of claim 49, wherein adjusting the hydrogen ion concentration comprises adding an acid.

51. The method of claim 49 wherein the acid comprises sulfuric acid and the sulfuric acid sulfonates the available reactive groups resulting from the partial hydrolysis of fucoidan to produce a partially hydrolyzed, sulfonated fucoidan composition.

52. The method of claim 49, wherein heating the mixture is performed at greater than one atmosphere.

53. A method of preparing a dietary supplement, the method comprising:

(a) mixing about 0.5 to about 70 parts by weight of the partially hydrolyzed fucoidan composition with about 30 to about 99.5 parts by weight of water to form a mixture;

(b) sterilizing the mixture; and

(c) the sterilized mixture is packaged in a suitable container.

54. The method of claim 53, wherein the partially hydrolyzed fucoidan composition is prepared by the steps of:

(1) mixing a selected amount of fucoidan-containing seaweed with water and adjusting the hydrogen ion concentration to a pH of about 2.0-4.0 to produce a mixture;

(2) heating the mixture to a temperature of about 37 ℃ to about 95 ℃ for a selected period of time while continuing to stir the mixture, thereby partially hydrolyzing fucoidan in the seaweed to produce a heated mixture;

(3) cooling the heated mixture to ambient temperature, and while cooling, continuing to mix the heated mixture to produce a cooled mixture; and

(4) incubating the cooled mixture at ambient temperature while mixing for up to about 72 hours, thereby obtaining a partially hydrolyzed fucoidan composition.

55. The method of claim 54, wherein heating the mixture is performed at greater than one atmosphere.

56. The method of claim 53, further comprising adding about 0.5 to about 20 parts by weight of a nutraceutical ingredient having a high ORAC value to the mixture.

57. The method of claim 56, wherein the nutraceutical ingredient with a high ORAC value is a member selected from the group consisting of: grape juice concentrate, blueberry juice concentrate, acai fruit juice concentrate, raspberry juice concentrate, blackberry juice concentrate, strawberry juice concentrate, plum juice concentrate, orange juice concentrate, cherry juice concentrate, kiwi juice concentrate, blackcurrant juice concentrate, elderberry juice concentrate, redcurrant juice concentrate, cranberry juice concentrate, mangosteen, noni, aronia, passion fruit, anthocyanidins, curcuminoids, and mixtures thereof.

58. The method of claim 53, wherein the partially hydrolyzed fucoidan is sulfonated.

59. The method of claim 53, further comprising adding about 0.01 to about 2 parts by weight of a mineral to the mixture.

60. The method of claim 59, wherein the minerals comprise deep sea minerals.

61. The method of claim 53, further comprising adding about 0.001 to about 1 part by weight of pepper extract to the mixture.

62. The method of claim 61, wherein the pepper extract comprises black pepper or Sichuan pepper.

63. The method of claim 53, wherein sterilizing the mixture comprises pasteurizing the mixture.

64. The method of claim 53, wherein sterilizing the mixture comprises treating the mixture with a High Temperature Short Time (HTST) process.

65. The method of claim 53, wherein sterilizing the mixture comprises treating the mixture with an Ultra High Temperature (UHT) process.

66. The method of claim 53, wherein packaging the sterilized mixture comprises a hot-fill process.

67. The method of claim 53, wherein packaging the sterilized mixture comprises a cold fill process.

68. A solid dosage form of a dietary supplement is provided, the solid dosage form comprising partially hydrolyzed fucoidan.

69. The solid dosage form of claim 68, wherein the dosage form comprises a tablet, capsule, or powder.

70. The dosage form of claim 68 comprising at least about 0.5 parts by weight of partially hydrolyzed fucoidan and further comprising about 0.5 to about 20 parts by weight of a nutraceutical ingredient having a high ORAC value.

71. The dosage form of claim 68, wherein the nutraceutical ingredient with a high ORAC value is a member selected from the group consisting of: grape juice concentrate, blueberry juice concentrate, acai fruit juice concentrate, raspberry juice concentrate, blackberry juice concentrate, strawberry juice concentrate, plum juice concentrate, orange juice concentrate, cherry juice concentrate, kiwi juice concentrate, blackcurrant juice concentrate, elderberry juice concentrate, redcurrant juice concentrate, cranberry juice concentrate, mangosteen, noni, aronia, passion fruit, anthocyanidins, curcuminoids, and mixtures thereof.

72. The dosage form of claim 68 wherein the partially hydrolyzed fucoidan is sulfonated.

73. The dosage form of claim 68, further comprising about 0.01 to about 2 parts by weight of a mineral.

74. The dosage form of claim 73, wherein the mineral comprises a deep sea mineral.

75. The dosage form of claim 68, further comprising about 0.001 to about 1 parts by weight of pepper extract.

76. The dosage form of claim 75, wherein the pepper extract comprises black pepper or Sichuan pepper.

77. The dosage form of claim 69, wherein the dosage form comprises a powder prepared by spray drying or freeze drying.