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WO2012161572A1 - Composition comprising vitamin k2 - Google Patents

Composition comprising vitamin k2 Download PDF

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Publication number
WO2012161572A1
WO2012161572A1 PCT/NL2012/050350 NL2012050350W WO2012161572A1 WO 2012161572 A1 WO2012161572 A1 WO 2012161572A1 NL 2012050350 W NL2012050350 W NL 2012050350W WO 2012161572 A1 WO2012161572 A1 WO 2012161572A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition according
vitamin
blood
mammal
health
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/NL2012/050350
Other languages
French (fr)
Inventor
Elisabeth Gertruda Hendrika Maria Van Den Heuvel
Renate Marie Louise Zwijsen
Ioannis MANIOS
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
FrieslandCampina Nederland BV
Original Assignee
Friesland Brands BV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Friesland Brands BV filed Critical Friesland Brands BV
Priority to PH1/2013/502396A priority Critical patent/PH12013502396A1/en
Priority to RU2013156676A priority patent/RU2606767C2/en
Priority to EP12724777.3A priority patent/EP2709460A1/en
Priority to CN201280035691.8A priority patent/CN103687495A/en
Publication of WO2012161572A1 publication Critical patent/WO2012161572A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/13—Fermented milk preparations; Treatment using microorganisms or enzymes using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C13/00—Cream; Cream preparations; Making thereof
    • A23C13/12—Cream preparations
    • A23C13/16—Cream preparations containing, or treated with, microorganisms, enzymes, or antibiotics; Sour cream
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C17/00—Buttermilk; Buttermilk preparations
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C19/00—Cheese; Cheese preparations; Making thereof
    • A23C19/06—Treating cheese curd after whey separation; Products obtained thereby
    • A23C19/09—Other cheese preparations; Mixtures of cheese with other foodstuffs
    • A23C19/0921—Addition, to cheese or curd, of minerals, including organic salts thereof, trace elements, amino acids, peptides, protein hydrolysates, nucleic acids, yeast extracts or autolysate, vitamins or derivatives of these compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/13—Fermented milk preparations; Treatment using microorganisms or enzymes using additives
    • A23C9/1315—Non-milk proteins or fats; Seeds, pulses, cereals or soja; Fatty acids, phospholipids, mono- or diglycerides or derivatives therefrom; Egg products
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/13—Fermented milk preparations; Treatment using microorganisms or enzymes using additives
    • A23C9/1322—Inorganic compounds; Minerals, including organic salts thereof, oligo-elements; Amino-acids, peptides, protein-hydrolysates or derivatives; Nucleic acids or derivatives; Yeast extract or autolysate; Vitamins; Antibiotics; Bacteriocins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A23C9/1522—Inorganic additives, e.g. minerals, trace elements; Chlorination or fluoridation of milk; Organic salts or complexes of metals other than natrium or kalium; Calcium enrichment of milk
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A23C9/1528—Fatty acids; Mono- or diglycerides; Petroleum jelly; Paraffine; Phospholipids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A23C9/158—Milk preparations; Milk powder or milk powder preparations containing additives containing vitamins or antibiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23D—EDIBLE OILS OR FATS, e.g. MARGARINES, SHORTENINGS OR COOKING OILS
    • A23D7/00—Edible oil or fat compositions containing an aqueous phase, e.g. margarines
    • A23D7/001—Spread compositions
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23D—EDIBLE OILS OR FATS, e.g. MARGARINES, SHORTENINGS OR COOKING OILS
    • A23D7/00—Edible oil or fat compositions containing an aqueous phase, e.g. margarines
    • A23D7/005—Edible oil or fat compositions containing an aqueous phase, e.g. margarines characterised by ingredients other than fatty acid triglycerides
    • A23D7/0056—Spread compositions
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/19—Dairy proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/306—Foods, ingredients or supplements having a functional effect on health having an effect on bone mass, e.g. osteoporosis prevention
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/326—Foods, ingredients or supplements having a functional effect on health having effect on cardiovascular health
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/3262—Foods, ingredients or supplements having a functional effect on health having an effect on blood cholesterol
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/328—Foods, ingredients or supplements having a functional effect on health having effect on glycaemic control and diabetes
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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    • A23V2200/332—Promoters of weight control and weight loss
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/15—Inorganic Compounds
    • A23V2250/156—Mineral combination
    • A23V2250/1578—Calcium
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/15—Inorganic Compounds
    • A23V2250/156—Mineral combination
    • A23V2250/161—Magnesium
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/70—Vitamins
    • A23V2250/714—Vitamin K
    • A23V2250/7144—Vitamin K2

Definitions

  • the present invention relates to the field of nutrition, and in particular to products comprising and/or supplemented with micronutrients.
  • the invention relates to food products comprising vitamins, minerals or other micronutrients and the use of these products for promoting cardiovascular health of mammals and, in particular, for supporting and/or improving vascular elasticity.
  • Functional foods are an emerging field in food science due to their increasing popularity with health-conscious consumers.
  • Functional food is any food or food ingredient that may provide a health benefit beyond the traditional nutrients comprised in it.
  • the general category of functional foods includes processed food or foods fortified with health-promoting additives, e.g., vitamin enriched products.
  • the invention provides, in a first aspect, a composition comprising vitamin K2, calcium and magnesium, wherein the weight ratio calcium/magnesium is less than 8.
  • composition according to the present invention can effectively be used against vascular stiffness and/or to improve, support and/or maintain the flexibility and/or the strength of blood vessels. In this manner, a healthy blood circulation and/or blood flow can be improved, supported and/or maintained.
  • the present invention concerns a food composition of the type generally intended for daily consumption and particularly intended to have a positive effect on human or animal health, and/or to improve, support and/or maintain human or animal inconvenience.
  • vitamin K2 is a member of the vitamin K group which is a group of fat soluble vitamins. All members of the vitamin K group share a methylated naphthoquinone ring structure, and vary in the aliphatic side chain attached at the 3-position.
  • Phylloquinone also known as vitamin Kl
  • Menaquinones have side chains composed of a variable number of unsaturated isoprenoid residues; generally they are designated as MK-n, where n specifies the number of isoprenoids.
  • Vitamin K is essential for the carboxylation of glutamate residues in certain proteins. These vitamin K-dependent proteins require carboxylation to become biologically active. Although the coagulant factors are the most well- known vitamin K dependent proteins, there are many others with important physiologic roles. Matrix Gla Protein (MGP), osteocalcin and Growth Arrest Specific Gene 6 (Gas-6) are the three particularly important vitamin K dependent proteins. Vitamin K is commonly found in multiple vitamin supplements and in infant formula. However, it is mostly present in the form of vitamin Kl and therefore a general designation to vitamin K refers in fact to vitamin Kl, since this form is considerably less expensive to obtain and it has been generally recognised as safe in food since a long time.
  • MGP Matrix Gla Protein
  • Gas-6 Growth Arrest Specific Gene 6
  • Vitamin K2 in the present invention may be obtained from any suitable source, e.g., fermented soy product such as natto. Also synthetically prepared vitamin K2 is suitable having an advantage that the quality of such obtained vitamin K2 can easily be controlled. However, vitamin K2 obtained from a natural source, e.g., by microbial production, is preferred.
  • the content of vitamin K2 and other ingredients in the composition according to the invention is characterised in this description in amounts per daily intake, or in amounts per serving.
  • a serving is about 125 g for a viscous (spoonable) product, or about 200-250 ml for a pourable product such as milk or a yogurt drink.
  • a serving means one slice of about 30-40 g, and for a spread or butter a serving is about 3.5-7 g normally used with a one slice of bread.
  • Daily intake means the total amount of an ingredient as consumed within the product or products of the invention per day.
  • a daily intake may be consumed in one serving, but can also be divided over 2, 3, 4 or even more servings per day.
  • the daily intake can also be spread over several products, such as milk and yogurt, milk and cheese, etc.
  • a skilled person is able to find an appropriate amount of servings, or an appropriate combination of products, based on the provided information.
  • spoonable and drink yogurts are usually consumed once or twice per day, therefore the daily intake is generally one to two servings per day.
  • a daily intake usually means one slice per day, but can also be more.
  • a daily intake usually means about 4 servings, assuming that on average 4 slices of bread are consumed per day.
  • the composition according to the present invention preferably comprises at least 5 meg vitamin K2 per daily intake.
  • the upper limit for vitamin K2 in the composition is preferably less than 200 meg per daily intake. More preferably, the composition contains from 5 to 150 meg, and even more preferably from 7 to 100 meg of vitamin K2 per daily intake. Yet more preferably, the composition contains from 10 to 90 meg vitamin K2 per daily intake. More preferably the amount of vitamin K2 per day from 15 to 75 meg even more preferably from 25 to 60 meg, even more preferably from 35 to 50 meg and most preferably from 40 to 45 meg of vitamin K2 per day.
  • “meg” is meant to mean microgram.
  • vitamin K2 contains from 4 to 13 isoprenoid residues, especially 6-13 isoprenoid residues. Yet more preferably, vitamin K2 contains from 6 to 10 isoprenoid residues, in particular 6, 7, 8, 9 or 10 residues. These forms of vitamin K2, especially MK-6 and higher, have a considerably higher bioavailability than menaquinones having less isoprenoid residues.
  • composition according to the invention further contains minerals calcium and magnesium.
  • minerals calcium and magnesium any form of food grade sources of calcium and magnesium may be used. These include organic and inorganic compounds, salts, molecular complexes, chelates, such as calcium citrate, calcium carbonate, calcium gluconate, calcium lactate, calcium phosphate, magnesium oxide, magnesium citrate, etc.
  • a preferred source is magnesium citrate.
  • dairy products or dairy components, especially milk and milk parts are examples of suitable sources of calcium.
  • Calcium (Ca) is preferably present in the composition of the invention in an amount from 20 to 1600 mg, and preferably from 70 to 1000 mg, more preferably, from 80 to 800 mg per daily intake.
  • a preferred amount of calcium in the present composition is in the range of 100-600 mg per daily intake, more preferably from 150-500 mg per daily intake, more preferably from 200 to 450 mg per daily intake, even more preferably from 250-400 mg per daily intake and most preferably from 300-350 mg calcium per daily intake.
  • “mg” is mean to mean milligram.
  • the content of magnesium (Mg) is preferably from 20 to 800 mg, more preferably, from 30 to 600 mg, and even more preferably from 50 to 500 mg per daily intake, more preferably from 75 to 400 mg, even more preferably from 100 to 300 mg, even more preferably from 150 to 250 mg and most preferably from 160 to 200 mg magnesium per daily intake.
  • the composition comprises 80-800 mg calcium and 50-300 mg magnesium per daily intake or 100-600 mg calcium and 75 to 400 mg magnesium, or 150-500 mg calcium and 100 to 300 mg magnesium. If the composition according to the invention is a dairy composition, in one preferred embodiment, the dairy component is the sole source of calcium, that is, the composition is not supplemented with additional calcium.
  • the level of calcium corresponds to the level of calcium in milk, that is, from 50 to 200 mg per 100 g, or from 60 to 400 mg per serving.
  • the calcium daily intake in this case is preferably from 80 to 800 mg, more preferably, from 100 to 700 mg, even more preferably from 120 to 600 mg, and particularly preferably from 240 to 500 mg and even more preferably from 300 to 450 mg, and most preferably from 350 to 400 mg calcium.
  • the dairy composition may be supplemented with additional calcium so that the total amount of calcium present is, e.g., from 100 to 1200 mg, and preferably from 120 to 1000 mg and even more preferably from 240 to 800 mg, more preferably from 300 to 700 mg, even more preferably between 400 and 600 mg and most preferably between 450 and 550 mg per daily intake.
  • the weight ratio calcium/magnesium (Ca/Mg) is less than in cow's milk. In normal cow's milk the calcium/magnesium ratio is by nature about 10.
  • the Ca/Mg ratio is not greater than 8 and more preferably not greater than 6, such as 5 or less.
  • the Ca/Mg ratio is not greater than 3.5 and even more preferably, not greater than 3.
  • a preferred range for the Ca/Mg ratio is 0.5-2.7.
  • a low Ca/Mg ratio relates to each product or serving separately. Where the daily intake of vitamin K2 can be spread over several servings or products, the Ca/Mg ratio must be in the described range for each serving or each product.
  • the optimal Ca/Mg ratio allows lower amounts of vitamin K2 to needed in order to achieve the same health effect. In this way, less vitamin K2 is needed per serving or per daily intake. This has the advantage of a lower risk of blood clotting associated with high dosages of vitamin K2, and also allows costs be reduced, since vitamin K2 is considerably more expensive than, e.g., vitamin Kl.
  • the calcium/phosphate ratio of the composition according to the present invention is from 0.5 to 5, more preferably from 1 to 4, more preferably from 1.5 to 3.5, and most preferably from 2 to 2.5.
  • this ratio is preferably in the range 1-2.
  • the composition further comprises at least one polyunsaturated fatty acid (PUFA).
  • PUFA's are fatty acids that contain more than one double bond in the backbone. This class includes many important compounds, such as essential fatty acids, e.g., omega-3 and omega-6 fatty acids.
  • long chain polyunsaturated fatty acids are suitable, and preferably those having at least 20 carbon atoms in the molecule.
  • Such long chain omega-3 fatty acids include cis- 11, 14, 17-eicosatrienoic acid (ETE) C20:3, cis-8, 11, 14, 17-eicosatetraenoic acid (ETA) C20:4, cis-5,8, l l, 14, 17-eicosapentaenoic acid (EPA) C20:5, cis- 7, 10, 13, 16, 19-docosapentaenoic acid (DPA, Clupanodonic acid) C22:5, cis- 4, 7, 10, 13, 16, 19-docosahexaenoic acid (DHA) C22:6, cis-9, 12, 15, 18,21- tetracosapentaenoic acid C24:5; cis-6,9, 12, 15, 18,21-tetracosahexaenoic acid (N
  • Long chain omega-6 fatty acids having at least 20 carbon atoms include cis-11, 14-eicosadienoic acid C20:2, cis-8, 11, 14-eicosatrienoic acid (Dihomo-gamma-linolenic acid) (DGLA) C20:3, cis-5,8, 11, 14-eicosatetraenoic acid (Arachidonic acid) (AA) C20:4, cis-13, 16-docosadienoic acid C22:2, cis- 7, 10, 13, 16-docosatetraenoic acid (Adrenic acid) C22:4, cis-4, 7, 10, 13, 16- docosapentaenoic acid (Osbond acid) C22:5.
  • the LC-PUFAs are preferably present in the product according to the invention in an amount from 20 to 1000 mg, and preferably from 30 to 500 mg per daily intake.
  • LC-PUFAs are EPA C20:5, DHA C22:6 and a combination of these.
  • the animal sources are preferably used, in particular fish and marine oil, or algae oil.
  • the fish oil obtained from cod liver, herring, mackerel, salmon, menhaden and sardine is used as a source of LC- PUFAs.
  • the composition according to the invention preferably contains EPA, DHA or a combination of these in an amount from 10 to 500 mg per daily intake, and preferably from 30 to 350 mg.
  • Particularly preferred is a combination of EPA with DHA in an amount from 40 to 250 mg per daily intake.
  • composition according to the invention and embodiments thereof may further contain other vitamins and/or minerals, emulsifiers, colorants, preservatives, gums, thickeners.
  • PUFAs emulsifiers
  • antioxidants like vitamin C, vitamin E, selenium, polyphenols, bioflavonoids to prevent the oxidation of long chain fatty acids, which can lead to unwanted taste changes and a short shelf life of the product.
  • the composition contains further vitamin D and, preferably, vitamin D3.
  • the amount of vitamin D can range from 0.25 to 6 meg and preferably from 1 to 5 meg, more preferably from 2 to 4 meg and most preferably from 2.5 to 3.5 meg per daily intake.
  • vitamin D refers, to any of known form of vitamin D, and specifically includes vitamin D2 (ergocalciferol), vitamin D3 (cholecalciferol), vitamin D precursors, metabolites and another analogues, and combinations thereof, as well as the various active and inactive forms of vitamin D.
  • vitamin D3 may be provided in its unhydroxylated inactive form as cholecalciferol, or may be provided in its hydroxylated active form as calcitriol.
  • the composition contains vitamin B12 (various cobalamins).
  • vitamin B12 variable cobalamins
  • This vitamin contributes to energy metabolism, red blood cell formation, function of the immune system and mental health.
  • Suboptimal blood levels are quite common in human and particularly in elderly, as absorption through the gut declines with age.
  • Low vitamin B12 blood levels results in a macrocytic anemia, elevated homocysteine which increases the risk for cardiovascular diseases, peripheral neuropathy, memory loss and other cognitive deficits.
  • a preferred amount for vitamin B12 is from 0.25 to 3 meg, and preferably from 0.375 to 2 meg, more preferably from 0.45 to 1.75 meg, more preferably from 0.5 to 1.5 meg, even more preferably from 0.75 to 1.3 meg and most preferably from 0.9 to 1.2 meg per daily intake.
  • the composition according to the invention and embodiments thereof is a dairy composition, which is understood as a composition containing further at least one of the following components: milk fat, milk protein, skim milk or other milk constituents.
  • milk and products based on milk or obtained by processing of milk such as dairy cream, cheese, milk powder, sauces, yogurt, other fermented milk products are encompassed by the term dairy composition.
  • the low Ca/Mg ratio as described in this invention has a further positive effect on the taste of the product, especially on the yogurts such as fruit yogurts. The taste of a yogurt can become
  • the low Ca/Mg ratio such as lower than 8 and preferably lower than 5, however, surprisingly provides for a better taste and is capable of masking the PUFA taste in a yogurt, without the necessity to add taste improving agents. The effect is especially advantageous in fruit yogurt compositions.
  • the composition according to the present invention is a food or beverage product, or a dietary supplement. Most preferably, it is a dairy food product.
  • the composition according to the invention and embodiments thereof is a yogurt or other fermented milk product such as cheese, processed cheeses, butter milk, creme fraiche, sour cream.
  • the yogurt can be of a thick consistency (spoonable yogurt), or have a pourable consistency (drink yogurt).
  • the product is a fruit yogurt, or a milk product containing fruit juices.
  • the product is based on non-fermented milk, e.g. milk drink, milkshakes, fruit-milk drinks, chocolate milk.
  • the product is a dairy cream, whippable cream, dairy based spread, ice cream, butter, margarine, melange, cream sauce, bakery cream and the like.
  • the product according to the invention may be prepared in any convenient way, known to a person skilled in the art.
  • a preferred method known to a person skilled in the art.
  • the composition according to the invention is prepared by adding a suitable source of vitamin K2, a suitable source of magnesium and, optionally, a suitable source of calcium to a food product.
  • a suitable source such as a compound or a composition comprising the desired vitamin or element, which source is suitable for use in food products (food grade).
  • the suitable source contains the vitamin or mineral in a bioavailable form, such as in a chelated form or as an organic acid salt. Minerals from animal sources are preferred over those from plant sources.
  • the ingredients can be mixed in any conventional way known to a person skilled in the art.
  • vitamin K2 can be first dissolved in a fat phase while calcium and/or magnesium - in an aqueous phase, followed by emulsification and addition to a food product to be fortified.
  • Vitamin K2 can also be used in powder form and be added to the remaining ingredients in an aqueous phase, or directly to the product.
  • some additional amount of calcium is added to reach the needed levels, for example, when the product contains fruit juices.
  • the product according to the invention may advantageously be used for maintaining, supporting and/or promoting cardiovascular health of mammals, and particularly humans.
  • the described composition can be used for maintaining, supporting and/or promoting vascular elasticity and/or for the prevention of vascular hardening.
  • it can effectively be used for maintaining, supporting and/or improving of blood circulation and/or blood flow of micro- and/or macrovascular system; and/or for maintaining, supporting and/or improving of the transport of oxygen and nutrients to the tissues and/or of removal of waste and carbon dioxide from the tissues; and/or for maintaining, supporting and/or promoting an adequate energy level, particularly for high oxygen consuming tissues, including heart, brain, skeletal muscles, liver and kidney and/or keeping physically and mentally fit.
  • Another aspect of the invention relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve vascular health, in particular cardiovascular health.
  • the invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve vessel flexibility.
  • the invention further relates to a composition according to the invention or embodiments thereof to prevent and/or maintain and/or reduce arterial stiffness.
  • the invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve bone health.
  • the invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve normal clotting capability and/or to maintain normal platelet aggregation and/or to prevent adherence of platelets to blood vessel walls and/or fatty plaques.
  • the invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve glucose control and/or insulin secretion and/or insulin sensitivity.
  • the invention further relates to a composition according to the invention or embodiments thereof to prevent and/or maintain and/or reduce chronic inflammation and/or low grade inflammation.
  • the invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve mental health and/or cognitive performance and/or alertness, and/or mental sharpness and/or memory.
  • the invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve a healthy bodyweight, and/or a healthy body mass index (BMI), and/or a healthy triglyceride blood levels, and/or a healthy waist circumference.
  • the health status of all health parameters mentioned in this invention is preferably according to the World Health Organization guidelines (WHO guidelines for the prevention, management and care of diabetes mellitus, 2006; Global strategy on diet, physical activity and health, WHO report 2004).
  • the invention further relates to a composition according to the invention or embodiments thereof to maintain a healthy blood pressure and/or to prevent and/or reduce high blood pressure (according to WHO guidelines).
  • the invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve blood flow.
  • the invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve blood circulation, including the macrocirculation and/or the microcirculation.
  • the invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve blood perfusion.
  • This is the process of delivery of blood to a capillary bed to tissues of a mammal, such as to the brain, kidney, heart, lung, liver, limbs and to the gastrointestinal tract tissue.
  • the invention further relates to a composition according to the invention or embodiments thereof to prevent and/or maintain and/or reduce metabolic syndrome.
  • the invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of vascular disease, and/or cardiovascular disease, and/or atherosclerosis, and/or arteriosclerosis, and/or arterial stiffness and/or hypertension and/or clogged arteries and/or varicose veins and/or transient ischemic attack (TIA) and/or stroke and/or cold limbs.
  • the invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of vessel
  • the invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of thrombosis and/or stroke.
  • the invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of diabetes and/or insulin resistancy.
  • the invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of chronic inflammation and/or low grade inflammation.
  • the invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of mental decline and/or mental disease, such as dementia and/or Alzheimer disease.
  • the invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of obesity, and/or metabolic syndrome, and/or high BMI, and/or high triglyceride in blood, and/or high body weight, and/or high waist circumference.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve vascular health, and/or cardiovascular health.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve vessel flexibility
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to prevent and/or maintain and/or reduce arterial stiffness.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to maintain a healthy blood pressure and/or to prevent and/or reduce high blood pressure (according to WHO guidelines).
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve blood flow.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve blood circulation, including the macrocirculation and/or the
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to support, maintain and/or improve blood perfusion.
  • This is the process of delivery of blood to a capillary bed to tissues of a mammal, such as to the brain, kidney, heart, lung, liver, limbs and to the gastrointestinal tract tissue.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve bone health.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve normal clotting capability and/or to maintain normal platelet aggregation and/or to prevent adherence of platelets to blood vessel walls and/or fatty plaques.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve glucose control mechanism, and/or insulin secretion and/or insulin sensitivity, and/or to prevent diabetes and/or hyperglycemia.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to prevent and/or maintain and/or reduce to chronic inflammation and/or low grade inflammation.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve mental health and/or cognitive performance and/or alertness and/or memory and/or mental sharpness.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve healthy weight management and/or a healthy body mass index and/or a healthy triglyceride blood levels and/or to prevent the increase of body fat mass.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain a healthy waist circumference and/or to reduce a high waist circumference.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to prevent and/or maintain and/or reduce metabolic syndrome.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to enhance bioavailability of vitamin K and/or vitamin K2.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to increase the biological activity of vitamin K and/or vitamin K2.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to increase the level of vitamin K and/or vitamin K2 in blood of a mammal.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to reduce the level of circulating uncarboxylated MGP and/or uncarboxylated osteocalcin in blood in a mammal.
  • the invention further relates to the use of a composition according to the invention or embodiments thereof to increase the level of circulating carboxylated MGP and/or carboxylated osteocalcin in blood in a mammal.
  • the reduction of the level of circulating uncarboxylated MGP and/or uncarboxylated osteocalcin, and/or the increase of the level of circulating carboxylated MGP and/or carboxylated osteocalcin in blood in a mammal and/or the increase of the level of vitamin K and/or vitamin K2 in blood of a mammal is obtained within 12 weeks, preferably within 8 weeks, more preferably within 4 weeks.
  • the invention further relates to a method to reduce the level of circulating uncarboxylated MGP and/or uncarboxylated osteocalcin in blood of a mammal by administering to a mammal a composition according to the invention or embodiments thereof.
  • the invention further relates to a method to increase the level of circulating carboxylated MGP and/or carboxylated osteocalcin in blood of a mammal by administering to a mammal a composition according to the invention or embodiments thereof.
  • the invention further relates to a method to increase the level of vitamin K2 in blood of a mammal by administering to a mammal a
  • composition according to the invention or embodiments thereof.
  • composition according to the invention or
  • embodiments thereof in a method according to the invention or embodiments thereof is administered for a period of at least 4 weeks, preferably at least 8 weeks and most preferably at least 12 weeks.
  • the composition of the present invention and embodiments thereof is administered life-long, suitably 3, 5, 7, 10, 12, 15, 18, 20, 23, 25, 27, 30, 32, 35, 38, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or even up to 95years.
  • the intake of vitamin K and/or vitamin K2 and/or MK-7 is preferably daily, each day, so as to maintain a steady level of vitamin K, vitamin K2 in the blood.
  • the products of the present invention may easily be incorporated in a normal healthy diet, so that each day, a life long, the vitamin K, vitamin K2 level is improved.
  • Control group 2 servings of dairy (choice of milk or yogurt) containing a daily intake of 10 meg vitamin D and 800 mg calcium.
  • the Ca/Mg ratio of the daily intake varies between about 10 (only milk) and about 15 (only yogurt).
  • Vitamin Kl group 2 servings of dairy (choice of milk or yogurt) containing a daily intake of 100 meg vitamin Kl, 10 meg vitamin D and 800 mg calcium.
  • the Ca/Mg ratio of the daily intake varies between about 10 (only milk) and about 15 (only yogurt).
  • Vitamin K2 group 2 servings of dairy (choice of milk or yogurt) containing a daily intake of 100 meg vitamin K2, 10 meg vitamin D and 800 mg calcium.
  • the Ca/Mg ratio of the daily intake varies between about 10 (only milk) and about 15 (only yogurt).
  • a vitamin K enriched product has a beneficial effect on vascular elasticity.
  • a vitamin Kl enriched dairy product has only a small nonsignificant effect on the vascular health parameter. This effect is comparable with the control group which had a dairy product with added vitamin D and calcium.
  • vitamin K2 is more effective as to vascular elasticity, whereas vitamin Kl is not.
  • the use of dairy with added vitamin D and calcium has a small, non significant effect on the vascular health parameter.
  • the two treatments arms are:
  • Control group daily 2 servings of yogurt of 250 ml each. These contain no DHA or EPA, 0 meg vitamin D and have a Ca/Mg ratio of about 10.
  • Treatment group daily 2 servings of yogurt of 250 ml each, containing a daily intake of 56.5 meg vitamin K2, 3.75 meg vitamin D3, 600 mg calcium, 280 mg magnesium and fish oil containing 200 mg of DHA and EPA.
  • the Ca/Mg ratio is 2.1.
  • the LC-PUFA's (particularly EPA and DHA) have been included in the composition for safety/antithrombotic reasons to reverse the thrombotic effects of vitamin K. It is believed that the LC-PUFAs do not contribute to the vascular elasticity marker MGP. The observed effect is, hence, due to the low Ca/Mg ratio in combination with vitamin K2.

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Abstract

The present invention relates to food products supplemented with micronutrients and, in particular, to a composition comprising vitamin K2. The composition further comprises calcium and magnesium, wherein the ratio Ca/Mg is less than 8. Optionally, the composition comprises polyunsaturated fatty acids and/or vitamin D. Preferably, the composition is a dairy composition and, more preferably, a yogurt. The composition according to the invention provides health benefits and can be used, in particular, for supporting, maintaining and/or improving of vascular elasticity and for the prevention of vascular hardening. It is further effective for supporting, maintaining and/or improving blood circulation and/or blood flow of micro- and/or macrovascular system; and/or for improving blood transfusion and the transfusion of oxygen and nutrients to the tissues and for the removal of waste and carbon dioxide from the tissues; and/or for keeping an adequate energy level.

Description

Title: Composition comprising vitamin K2
The present invention relates to the field of nutrition, and in particular to products comprising and/or supplemented with micronutrients. In particular, the invention relates to food products comprising vitamins, minerals or other micronutrients and the use of these products for promoting cardiovascular health of mammals and, in particular, for supporting and/or improving vascular elasticity.
Functional foods are an emerging field in food science due to their increasing popularity with health-conscious consumers. Functional food is any food or food ingredient that may provide a health benefit beyond the traditional nutrients comprised in it. The general category of functional foods includes processed food or foods fortified with health-promoting additives, e.g., vitamin enriched products.
An advantage of a functional food over a traditional food supplement containing an active ingredient or ingredients is that the active ingredients are incorporated into a conventional food product so that no separate
administration, e.g. in the form of vitamin supplement tablets, is needed.
Although many foods fortified with food supplements are known, there is a growing need for functional foods providing specific health benefits, e.g. cardiovascular health.
However, a conventional food product supplemented with vitamins and/or minerals does not always exhibit the health benefits expected based on the micronutrients added. The micronutrients added should be compatible with each other and with other components contained in the food product. Moreover, the addition of vitamins may also have an adverse influence on the sensoric characteristics of the supplemented product, such as taste, smell, or consistency. Moreover, good keeping properties and heat-stability of the resulting product are often desired. In order to better address on or more of the foregoing desires, the invention provides, in a first aspect, a composition comprising vitamin K2, calcium and magnesium, wherein the weight ratio calcium/magnesium is less than 8.
Surprisingly, it was found that the composition according to the present invention can effectively be used against vascular stiffness and/or to improve, support and/or maintain the flexibility and/or the strength of blood vessels. In this manner, a healthy blood circulation and/or blood flow can be improved, supported and/or maintained.
The present invention concerns a food composition of the type generally intended for daily consumption and particularly intended to have a positive effect on human or animal health, and/or to improve, support and/or maintain human or animal inconvenience.
An essential ingredient of the composition according to the present invention is vitamin K2, or menaquinone. Vitamin K2 is a member of the vitamin K group which is a group of fat soluble vitamins. All members of the vitamin K group share a methylated naphthoquinone ring structure, and vary in the aliphatic side chain attached at the 3-position. Phylloquinone (also known as vitamin Kl) invariably contains in its side chain four isoprenoid residues, one of which is unsaturated. Menaquinones have side chains composed of a variable number of unsaturated isoprenoid residues; generally they are designated as MK-n, where n specifies the number of isoprenoids.
The group of vitamin K is involved in blood clotting, and in calcium metabolism. Vitamin K is essential for the carboxylation of glutamate residues in certain proteins. These vitamin K-dependent proteins require carboxylation to become biologically active. Although the coagulant factors are the most well- known vitamin K dependent proteins, there are many others with important physiologic roles. Matrix Gla Protein (MGP), osteocalcin and Growth Arrest Specific Gene 6 (Gas-6) are the three particularly important vitamin K dependent proteins. Vitamin K is commonly found in multiple vitamin supplements and in infant formula. However, it is mostly present in the form of vitamin Kl and therefore a general designation to vitamin K refers in fact to vitamin Kl, since this form is considerably less expensive to obtain and it has been generally recognised as safe in food since a long time.
Vitamin K2 in the present invention may be obtained from any suitable source, e.g., fermented soy product such as natto. Also synthetically prepared vitamin K2 is suitable having an advantage that the quality of such obtained vitamin K2 can easily be controlled. However, vitamin K2 obtained from a natural source, e.g., by microbial production, is preferred.
The content of vitamin K2 and other ingredients in the composition according to the invention is characterised in this description in amounts per daily intake, or in amounts per serving. A serving is about 125 g for a viscous (spoonable) product, or about 200-250 ml for a pourable product such as milk or a yogurt drink. For cheese, a serving means one slice of about 30-40 g, and for a spread or butter a serving is about 3.5-7 g normally used with a one slice of bread. Daily intake means the total amount of an ingredient as consumed within the product or products of the invention per day. A daily intake may be consumed in one serving, but can also be divided over 2, 3, 4 or even more servings per day. The daily intake can also be spread over several products, such as milk and yogurt, milk and cheese, etc. A skilled person is able to find an appropriate amount of servings, or an appropriate combination of products, based on the provided information. For example, spoonable and drink yogurts are usually consumed once or twice per day, therefore the daily intake is generally one to two servings per day. For cheese, a daily intake usually means one slice per day, but can also be more. For a spread or butter, a daily intake usually means about 4 servings, assuming that on average 4 slices of bread are consumed per day. However, also lower or higher amounts of servings are possible, depending on the type and content of the product and depending also on consumer's habits. The composition according to the present invention preferably comprises at least 5 meg vitamin K2 per daily intake. Since vitamin K2 promotes blood clotting, which can be undesired, the upper limit for vitamin K2 in the composition is preferably less than 200 meg per daily intake. More preferably, the composition contains from 5 to 150 meg, and even more preferably from 7 to 100 meg of vitamin K2 per daily intake. Yet more preferably, the composition contains from 10 to 90 meg vitamin K2 per daily intake. More preferably the amount of vitamin K2 per day from 15 to 75 meg even more preferably from 25 to 60 meg, even more preferably from 35 to 50 meg and most preferably from 40 to 45 meg of vitamin K2 per day. For the purpose of the present invention, "meg" is meant to mean microgram. In a preferred embodiment, vitamin K2 contains from 4 to 13 isoprenoid residues, especially 6-13 isoprenoid residues. Yet more preferably, vitamin K2 contains from 6 to 10 isoprenoid residues, in particular 6, 7, 8, 9 or 10 residues. These forms of vitamin K2, especially MK-6 and higher, have a considerably higher bioavailability than menaquinones having less isoprenoid residues.
The composition according to the invention further contains minerals calcium and magnesium. It is understood that any form of food grade sources of calcium and magnesium may be used. These include organic and inorganic compounds, salts, molecular complexes, chelates, such as calcium citrate, calcium carbonate, calcium gluconate, calcium lactate, calcium phosphate, magnesium oxide, magnesium citrate, etc. For magnesium, a preferred source is magnesium citrate. As to calcium, dairy products or dairy components, especially milk and milk parts, are examples of suitable sources of calcium.
In a preferred embodiment of the present invention and
embodiments thereof, Calcium (Ca) is preferably present in the composition of the invention in an amount from 20 to 1600 mg, and preferably from 70 to 1000 mg, more preferably, from 80 to 800 mg per daily intake. A preferred amount of calcium in the present composition is in the range of 100-600 mg per daily intake, more preferably from 150-500 mg per daily intake, more preferably from 200 to 450 mg per daily intake, even more preferably from 250-400 mg per daily intake and most preferably from 300-350 mg calcium per daily intake. For the purpose of the present invention "mg" is mean to mean milligram.
In a preferred embodiment of the present invention and
embodiments thereof, the content of magnesium (Mg) is preferably from 20 to 800 mg, more preferably, from 30 to 600 mg, and even more preferably from 50 to 500 mg per daily intake, more preferably from 75 to 400 mg, even more preferably from 100 to 300 mg, even more preferably from 150 to 250 mg and most preferably from 160 to 200 mg magnesium per daily intake. In a preferred embodiment of the present invention and embodiments thereof, the composition comprises 80-800 mg calcium and 50-300 mg magnesium per daily intake or 100-600 mg calcium and 75 to 400 mg magnesium, or 150-500 mg calcium and 100 to 300 mg magnesium. If the composition according to the invention is a dairy composition, in one preferred embodiment, the dairy component is the sole source of calcium, that is, the composition is not supplemented with additional calcium. Therefore, in this embodiment, the level of calcium corresponds to the level of calcium in milk, that is, from 50 to 200 mg per 100 g, or from 60 to 400 mg per serving. The calcium daily intake in this case is preferably from 80 to 800 mg, more preferably, from 100 to 700 mg, even more preferably from 120 to 600 mg, and particularly preferably from 240 to 500 mg and even more preferably from 300 to 450 mg, and most preferably from 350 to 400 mg calcium. In a preferred embodiment of the present invention and embodiments thereof,, however, the dairy composition may be supplemented with additional calcium so that the total amount of calcium present is, e.g., from 100 to 1200 mg, and preferably from 120 to 1000 mg and even more preferably from 240 to 800 mg, more preferably from 300 to 700 mg, even more preferably between 400 and 600 mg and most preferably between 450 and 550 mg per daily intake. It is essential for the present invention that the weight ratio calcium/magnesium (Ca/Mg) is less than in cow's milk. In normal cow's milk the calcium/magnesium ratio is by nature about 10. Preferably, the Ca/Mg ratio is not greater than 8 and more preferably not greater than 6, such as 5 or less. Yet more preferably, the Ca/Mg ratio is not greater than 3.5 and even more preferably, not greater than 3. A preferred range for the Ca/Mg ratio is 0.5-2.7. The ratio Ca/Mg in the range 1.5-2.4, for example, about 1.7 to 2.2 or 1.8 to 2 for the Ca/Mg ratio, is particularly preferred. A low Ca/Mg ratio relates to each product or serving separately. Where the daily intake of vitamin K2 can be spread over several servings or products, the Ca/Mg ratio must be in the described range for each serving or each product.
As shown in the examples, the optimal Ca/Mg ratio allows lower amounts of vitamin K2 to needed in order to achieve the same health effect. In this way, less vitamin K2 is needed per serving or per daily intake. This has the advantage of a lower risk of blood clotting associated with high dosages of vitamin K2, and also allows costs be reduced, since vitamin K2 is considerably more expensive than, e.g., vitamin Kl.
In a preferred embodiment of the present invention and
embodiments thereof,, the calcium/phosphate ratio of the composition according to the present invention is from 0.5 to 5, more preferably from 1 to 4, more preferably from 1.5 to 3.5, and most preferably from 2 to 2.5. For dairy compositions such as yogurts, this ratio is preferably in the range 1-2.
In a composition of the present invention and embodiments thereof,, the composition further comprises at least one polyunsaturated fatty acid (PUFA). PUFA's are fatty acids that contain more than one double bond in the backbone. This class includes many important compounds, such as essential fatty acids, e.g., omega-3 and omega-6 fatty acids.
In the present invention especially long chain polyunsaturated fatty acids (LC-PUFAs) are suitable, and preferably those having at least 20 carbon atoms in the molecule. Such long chain omega-3 fatty acids include cis- 11, 14, 17-eicosatrienoic acid (ETE) C20:3, cis-8, 11, 14, 17-eicosatetraenoic acid (ETA) C20:4, cis-5,8, l l, 14, 17-eicosapentaenoic acid (EPA) C20:5, cis- 7, 10, 13, 16, 19-docosapentaenoic acid (DPA, Clupanodonic acid) C22:5, cis- 4, 7, 10, 13, 16, 19-docosahexaenoic acid (DHA) C22:6, cis-9, 12, 15, 18,21- tetracosapentaenoic acid C24:5; cis-6,9, 12, 15, 18,21-tetracosahexaenoic acid (Nisinic acid) C24:6. Long chain omega-6 fatty acids having at least 20 carbon atoms include cis-11, 14-eicosadienoic acid C20:2, cis-8, 11, 14-eicosatrienoic acid (Dihomo-gamma-linolenic acid) (DGLA) C20:3, cis-5,8, 11, 14-eicosatetraenoic acid (Arachidonic acid) (AA) C20:4, cis-13, 16-docosadienoic acid C22:2, cis- 7, 10, 13, 16-docosatetraenoic acid (Adrenic acid) C22:4, cis-4, 7, 10, 13, 16- docosapentaenoic acid (Osbond acid) C22:5. The LC-PUFAs are preferably present in the product according to the invention in an amount from 20 to 1000 mg, and preferably from 30 to 500 mg per daily intake.
Particularly preferred LC-PUFAs are EPA C20:5, DHA C22:6 and a combination of these. Of all sources of PUFAs the animal sources are preferably used, in particular fish and marine oil, or algae oil. In one embodiment of the present invention, the fish oil obtained from cod liver, herring, mackerel, salmon, menhaden and sardine is used as a source of LC- PUFAs. The composition according to the invention preferably contains EPA, DHA or a combination of these in an amount from 10 to 500 mg per daily intake, and preferably from 30 to 350 mg. Particularly preferred is a combination of EPA with DHA in an amount from 40 to 250 mg per daily intake.
The composition according to the invention and embodiments thereof may further contain other vitamins and/or minerals, emulsifiers, colorants, preservatives, gums, thickeners. Where PUFAs are used in the composition, it is preferred to use antioxidants like vitamin C, vitamin E, selenium, polyphenols, bioflavonoids to prevent the oxidation of long chain fatty acids, which can lead to unwanted taste changes and a short shelf life of the product. In a preferred embodiment of the present invention and
embodiments thereof,, the composition contains further vitamin D and, preferably, vitamin D3. The amount of vitamin D can range from 0.25 to 6 meg and preferably from 1 to 5 meg, more preferably from 2 to 4 meg and most preferably from 2.5 to 3.5 meg per daily intake. As used herein, "vitamin D" refers, to any of known form of vitamin D, and specifically includes vitamin D2 (ergocalciferol), vitamin D3 (cholecalciferol), vitamin D precursors, metabolites and another analogues, and combinations thereof, as well as the various active and inactive forms of vitamin D. For example, vitamin D3 may be provided in its unhydroxylated inactive form as cholecalciferol, or may be provided in its hydroxylated active form as calcitriol.
In another preferred embodiment of the present invention and embodiments thereof,, the composition contains vitamin B12 (various cobalamins). This vitamin contributes to energy metabolism, red blood cell formation, function of the immune system and mental health. Suboptimal blood levels are quite common in human and particularly in elderly, as absorption through the gut declines with age. Low vitamin B12 blood levels results in a macrocytic anemia, elevated homocysteine which increases the risk for cardiovascular diseases, peripheral neuropathy, memory loss and other cognitive deficits. A preferred amount for vitamin B12 is from 0.25 to 3 meg, and preferably from 0.375 to 2 meg, more preferably from 0.45 to 1.75 meg, more preferably from 0.5 to 1.5 meg, even more preferably from 0.75 to 1.3 meg and most preferably from 0.9 to 1.2 meg per daily intake.
In a preferred embodiment, the composition according to the invention and embodiments thereof is a dairy composition, which is understood as a composition containing further at least one of the following components: milk fat, milk protein, skim milk or other milk constituents. Also milk and products based on milk or obtained by processing of milk such as dairy cream, cheese, milk powder, sauces, yogurt, other fermented milk products are encompassed by the term dairy composition. In dairy compositions, the low Ca/Mg ratio as described in this invention has a further positive effect on the taste of the product, especially on the yogurts such as fruit yogurts. The taste of a yogurt can become
unfavourable, e.g., due to the off- flavours caused by the nutritional
supplements and in particular by the added fatty acids, even in low amounts. Therefore, the taste of added PUFA's such as fish oil should often be masked in dairy compositions with additional taste agents. The low Ca/Mg ratio, such as lower than 8 and preferably lower than 5, however, surprisingly provides for a better taste and is capable of masking the PUFA taste in a yogurt, without the necessity to add taste improving agents. The effect is especially advantageous in fruit yogurt compositions.
Preferably, the composition according to the present invention is a food or beverage product, or a dietary supplement. Most preferably, it is a dairy food product.
In one embodiment, the composition according to the invention and embodiments thereof is a yogurt or other fermented milk product such as cheese, processed cheeses, butter milk, creme fraiche, sour cream. The yogurt can be of a thick consistency (spoonable yogurt), or have a pourable consistency (drink yogurt). In a preferred embodiment, the product is a fruit yogurt, or a milk product containing fruit juices.
In another embodiment, the product is based on non-fermented milk, e.g. milk drink, milkshakes, fruit-milk drinks, chocolate milk. In yet another embodiment of the present invention, the product is a dairy cream, whippable cream, dairy based spread, ice cream, butter, margarine, melange, cream sauce, bakery cream and the like.
The product according to the invention may be prepared in any convenient way, known to a person skilled in the art. In a preferred
embodiment, the composition according to the invention is prepared by adding a suitable source of vitamin K2, a suitable source of magnesium and, optionally, a suitable source of calcium to a food product. Under suitable source it is understood a source such as a compound or a composition comprising the desired vitamin or element, which source is suitable for use in food products (food grade). Preferably, the suitable source contains the vitamin or mineral in a bioavailable form, such as in a chelated form or as an organic acid salt. Minerals from animal sources are preferred over those from plant sources. The ingredients can be mixed in any conventional way known to a person skilled in the art. For example, vitamin K2 can be first dissolved in a fat phase while calcium and/or magnesium - in an aqueous phase, followed by emulsification and addition to a food product to be fortified. Vitamin K2 can also be used in powder form and be added to the remaining ingredients in an aqueous phase, or directly to the product.
When a dairy product is prepared, it is preferred, in one
embodiment, to only add vitamin K2 and magnesium to a product and not to add additional calcium. The desired Ca/Mg ratio is then achieved by the added magnesium due to the original presence of calcium in the dairy product.
However, in another embodiment, some additional amount of calcium is added to reach the needed levels, for example, when the product contains fruit juices.
The product according to the invention may advantageously be used for maintaining, supporting and/or promoting cardiovascular health of mammals, and particularly humans. In particular, the described composition can be used for maintaining, supporting and/or promoting vascular elasticity and/or for the prevention of vascular hardening. Further, it can effectively be used for maintaining, supporting and/or improving of blood circulation and/or blood flow of micro- and/or macrovascular system; and/or for maintaining, supporting and/or improving of the transport of oxygen and nutrients to the tissues and/or of removal of waste and carbon dioxide from the tissues; and/or for maintaining, supporting and/or promoting an adequate energy level, particularly for high oxygen consuming tissues, including heart, brain, skeletal muscles, liver and kidney and/or keeping physically and mentally fit. Another aspect of the invention relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve vascular health, in particular cardiovascular health.
The invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve vessel flexibility.
The invention further relates to a composition according to the invention or embodiments thereof to prevent and/or maintain and/or reduce arterial stiffness.
The invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve bone health.
The invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve normal clotting capability and/or to maintain normal platelet aggregation and/or to prevent adherence of platelets to blood vessel walls and/or fatty plaques.
The invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve glucose control and/or insulin secretion and/or insulin sensitivity.
The invention further relates to a composition according to the invention or embodiments thereof to prevent and/or maintain and/or reduce chronic inflammation and/or low grade inflammation.
The invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve mental health and/or cognitive performance and/or alertness, and/or mental sharpness and/or memory.
The invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve a healthy bodyweight, and/or a healthy body mass index (BMI), and/or a healthy triglyceride blood levels, and/or a healthy waist circumference. The health status of all health parameters mentioned in this invention is preferably according to the World Health Organization guidelines (WHO guidelines for the prevention, management and care of diabetes mellitus, 2006; Global strategy on diet, physical activity and health, WHO report 2004).
The invention further relates to a composition according to the invention or embodiments thereof to maintain a healthy blood pressure and/or to prevent and/or reduce high blood pressure (according to WHO guidelines).
The invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve blood flow.
The invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve blood circulation, including the macrocirculation and/or the microcirculation.
The invention further relates to a composition according to the invention or embodiments thereof to support and/or maintain and/or improve blood perfusion. This is the process of delivery of blood to a capillary bed to tissues of a mammal, such as to the brain, kidney, heart, lung, liver, limbs and to the gastrointestinal tract tissue.
The invention further relates to a composition according to the invention or embodiments thereof to prevent and/or maintain and/or reduce metabolic syndrome.
The invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of vascular disease, and/or cardiovascular disease, and/or atherosclerosis, and/or arteriosclerosis, and/or arterial stiffness and/or hypertension and/or clogged arteries and/or varicose veins and/or transient ischemic attack (TIA) and/or stroke and/or cold limbs. The invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of vessel
inflexibility.
The invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of bone
demineralisation and/or osteoporosis.
The invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of thrombosis and/or stroke.
The invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of diabetes and/or insulin resistancy.
The invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of chronic inflammation and/or low grade inflammation.
The invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of mental decline and/or mental disease, such as dementia and/or Alzheimer disease.
The invention further relates to a composition according to the invention or embodiments thereof for use in the treatment of obesity, and/or metabolic syndrome, and/or high BMI, and/or high triglyceride in blood, and/or high body weight, and/or high waist circumference.
The invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve vascular health, and/or cardiovascular health.
The invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve vessel flexibility The invention further relates to the use of a composition according to the invention or embodiments thereof to prevent and/or maintain and/or reduce arterial stiffness.
The invention further relates to the use of a composition according to the invention or embodiments thereof to maintain a healthy blood pressure and/or to prevent and/or reduce high blood pressure (according to WHO guidelines).
The invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve blood flow.
The invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve blood circulation, including the macrocirculation and/or the
microcirculation.
The invention further relates to the use of a composition according to the invention or embodiments thereof to support, maintain and/or improve blood perfusion. This is the process of delivery of blood to a capillary bed to tissues of a mammal, such as to the brain, kidney, heart, lung, liver, limbs and to the gastrointestinal tract tissue.
The invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve bone health.
The invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve normal clotting capability and/or to maintain normal platelet aggregation and/or to prevent adherence of platelets to blood vessel walls and/or fatty plaques.
The invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve glucose control mechanism, and/or insulin secretion and/or insulin sensitivity, and/or to prevent diabetes and/or hyperglycemia.
The invention further relates to the use of a composition according to the invention or embodiments thereof to prevent and/or maintain and/or reduce to chronic inflammation and/or low grade inflammation.
The invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve mental health and/or cognitive performance and/or alertness and/or memory and/or mental sharpness.
The invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain and/or improve healthy weight management and/or a healthy body mass index and/or a healthy triglyceride blood levels and/or to prevent the increase of body fat mass.
The invention further relates to the use of a composition according to the invention or embodiments thereof to support and/or maintain a healthy waist circumference and/or to reduce a high waist circumference.
The invention further relates to the use of a composition according to the invention or embodiments thereof to prevent and/or maintain and/or reduce metabolic syndrome.
The invention further relates to the use of a composition according to the invention or embodiments thereof to enhance bioavailability of vitamin K and/or vitamin K2.
The invention further relates to the use of a composition according to the invention or embodiments thereof to increase the biological activity of vitamin K and/or vitamin K2.
The invention further relates to the use of a composition according to the invention or embodiments thereof to increase the level of vitamin K and/or vitamin K2 in blood of a mammal. The invention further relates to the use of a composition according to the invention or embodiments thereof to reduce the level of circulating uncarboxylated MGP and/or uncarboxylated osteocalcin in blood in a mammal.
The invention further relates to the use of a composition according to the invention or embodiments thereof to increase the level of circulating carboxylated MGP and/or carboxylated osteocalcin in blood in a mammal.
In a preferred embodiment of the present invention and
embodiments thereof the reduction of the level of circulating uncarboxylated MGP and/or uncarboxylated osteocalcin, and/or the increase of the level of circulating carboxylated MGP and/or carboxylated osteocalcin in blood in a mammal and/or the increase of the level of vitamin K and/or vitamin K2 in blood of a mammal is obtained within 12 weeks, preferably within 8 weeks, more preferably within 4 weeks.
The invention further relates to a method to reduce the level of circulating uncarboxylated MGP and/or uncarboxylated osteocalcin in blood of a mammal by administering to a mammal a composition according to the invention or embodiments thereof.
The invention further relates to a method to increase the level of circulating carboxylated MGP and/or carboxylated osteocalcin in blood of a mammal by administering to a mammal a composition according to the invention or embodiments thereof.
The invention further relates to a method to increase the level of vitamin K2 in blood of a mammal by administering to a mammal a
composition according to the invention or embodiments thereof.
Preferably the composition according to the invention or
embodiments thereof in a method according to the invention or embodiments thereof is administered for a period of at least 4 weeks, preferably at least 8 weeks and most preferably at least 12 weeks. Preferably the composition of the present invention and embodiments thereof is administered life-long, suitably 3, 5, 7, 10, 12, 15, 18, 20, 23, 25, 27, 30, 32, 35, 38, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or even up to 95years. The intake of vitamin K and/or vitamin K2 and/or MK-7 is preferably daily, each day, so as to maintain a steady level of vitamin K, vitamin K2 in the blood. The products of the present invention may easily be incorporated in a normal healthy diet, so that each day, a life long, the vitamin K, vitamin K2 level is improved.
The invention will now further be illustrated in the following, non- limiting examples. Example 1
To study the effect of a dairy product with high levels of vitamin Kl, vitamin K2 or no vitamin K after a 1 year treatment, intervention in postmenopausal women (45-65 year) was performed during one year with 3 different treatments using a parallel design. The three treatment arms were:
Control group: 2 servings of dairy (choice of milk or yogurt) containing a daily intake of 10 meg vitamin D and 800 mg calcium. The Ca/Mg ratio of the daily intake varies between about 10 (only milk) and about 15 (only yogurt).
Vitamin Kl group: 2 servings of dairy (choice of milk or yogurt) containing a daily intake of 100 meg vitamin Kl, 10 meg vitamin D and 800 mg calcium. The Ca/Mg ratio of the daily intake varies between about 10 (only milk) and about 15 (only yogurt).
Vitamin K2 group: 2 servings of dairy (choice of milk or yogurt) containing a daily intake of 100 meg vitamin K2, 10 meg vitamin D and 800 mg calcium. The Ca/Mg ratio of the daily intake varies between about 10 (only milk) and about 15 (only yogurt).
Blood samples were taken prior and after the intervention period of 1 year. In these blood samples the carboxylation grade of MGP has been analysed in order to obtain the ratio of uncarboxylated ucMGP to MGP which is the sum of carboxylated cMGP and uncarboxylated ucMGP (ucMGP/MGP ratio). In the current state-of-the-art, this is considered to be a relevant marker for vascular health and in particular for the calcification of blood vessels. Inhibition of calcification of blood vessels in order to keep blood vessels flexible is regarded as an active regulated process by bioactive (carboxylated) MGP. The results are given in Table 1.
Table 1. Changes in ucMGP and in ucMGP/MGP percent ratio by treatment arm.
Figure imgf000019_0001
*: Statistically different from Control Group and Vit Kl Group.
†: Statistically different from Control Group.
After one year treatment, the intake of dairy product with high levels of vitamin K2 in a dairy product reduces the % ucMGP/MGP by 17 %. So, a vitamin K enriched product has a beneficial effect on vascular elasticity. Surprisingly, a vitamin Kl enriched dairy product has only a small nonsignificant effect on the vascular health parameter. This effect is comparable with the control group which had a dairy product with added vitamin D and calcium. In conclusion, vitamin K2 is more effective as to vascular elasticity, whereas vitamin Kl is not. The use of dairy with added vitamin D and calcium has a small, non significant effect on the vascular health parameter. Example 2
Effect of a dairy product with added moderate levels of vitamin K2 and Ca/Mg for 3 months.
Intervention with postmenopausal women en men (45-65 year) for 3 months and a parallel design have been performed. In this study, a dairy product with a mixture of moderate levels of vitamin K2, fish oil and a low Ca/Mg ratio was compared to a diary product with no added nutrients.
The two treatments arms are:
Control group: daily 2 servings of yogurt of 250 ml each. These contain no DHA or EPA, 0 meg vitamin D and have a Ca/Mg ratio of about 10.
Treatment group: daily 2 servings of yogurt of 250 ml each, containing a daily intake of 56.5 meg vitamin K2, 3.75 meg vitamin D3, 600 mg calcium, 280 mg magnesium and fish oil containing 200 mg of DHA and EPA. The Ca/Mg ratio is 2.1.
Blood samples have been taken prior and after 1, 2 and 3 months of the intervention. In these blood samples the carboxylation grade of MGP has been analysed in order to obtain the ratio of uncarboxylated ucMGP to MGP which is the sum of carboxylated cMGP and uncarboxylated ucMGP
(ucMGP/MGP ratio). The results are depicted in Table 2.
Table 2. Changes in cMGP, ucMGP and ucMGP to MGP percent ratio (ucMGP/MGP% ratio) by treatment arm and by treatment period
cMGP ucMGP Mean % change
(SD), pM (SD), pM ucMGP/MGP to
baseline
Control group
baseline 1817 ± 342 415 ± 157
t=l mo 1805 ± 422 391 ± 180 4.3
t= 2 mo 1884 ± 447 406 ± 201 4.8
t= 3 mo 1891 ± 414 406 ± 178 5.3
Treatment group
baseline 1953 ± 743 481 ± 211
t= 1 mo 1871 ± 534 417 ± 190* 8.1*
t= 2 mo 1906 ± 592 393 ± 169* 13.6*
t= 3 mo 1891 ± 573 371 ± 141* 17.1*
* Statistically different from baseline, p<0.01
After treatment, the intake of the dairy product with added nutrients vitamin K2 (daily 56.5 meg) reduces ucMGP/MGP significantly. This effect occurs at each test period and increases in time. The ratio ucMGP/MGP was decreased by 8, 14 and 17 % after respectively 1, 2 and 3 months.
Surprisingly, a unique mixture (moderate levels of vitamin K2 together with a low Ca/Mg ratio) was equally effective (namely 17% improvement) as a product with high vitamin K2 levels that was taken for a long time (as shown in Example 1). In addition, like in the long term intervention trial, dairy has a small, not significant effect.
The LC-PUFA's (particularly EPA and DHA) have been included in the composition for safety/antithrombotic reasons to reverse the thrombotic effects of vitamin K. It is believed that the LC-PUFAs do not contribute to the vascular elasticity marker MGP. The observed effect is, hence, due to the low Ca/Mg ratio in combination with vitamin K2.
It is, therefore, concluded that an optimal Ca/Mg ratio in combination with vitamin K2 makes the product work faster at lower levels of vitamin K2. This experiment shows that this ingredient mixture works synergistically.

Claims

Claims
1. A composition comprising vitamin K2, calcium and magnesium, wherein the weight ratio calcium/magnesium is less than 8.
2. The composition according to claim 1 wherein the Ca/Mg ratio is less than 3.5, and preferably in the range from 1.5 to 2.4.
3. The composition according to claim 1 or 2, wherein vitamin K2 is present in an amount of 5 to 200 meg per daily intake.
4. The composition according to any one of the preceding claims, wherein vitamin K2 contains from 6 to 13 isoprenoid residues.
5. The composition according to any one of the preceding claims, wherein calcium is present in an amount of 20-1600 mg per daily intake.
6. The composition according to any one of the preceding claims, wherein magnesium is present in an amount of 20-800 mg per daily intake.
7. The composition according to any one of the preceding claims, further comprising at least one long chain polyunsaturated fatty acid (LC- PUFA) having at least 20 carbon atoms.
8. The composition according to claim 7, wherein the LC-PUFA is eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or a mixture thereof.
9. The composition according to claim 8, wherein the EPA, DHA or a mixture thereof is present in an amount of 10-500 mg per daily intake.
10. The composition according to any one of claims 7-9, wherein the LC- PUFA is present in the form of fish oil.
11. The composition according to any one of the preceding claims, further comprising vitamin D in an amount 0.25 to 6 meg per daily intake.
12. The composition according to any one of the preceding claims, further comprising vitamin B12 in an amount 0.25 to 3 meg per daily intake.
13. Dairy food product comprising the composition according to any one of the preceding claims.
14. The product according to claim 13, being a spoonable yogurt, a yogurt drink, cheese, processed cheeses, butter milk, creme fraiche, sour cream, dairy based spread, margarine, melange, milk, or dairy cream.
15. The product according to claim 14, being a fruit yogurt or milk containing fruit juice.
16. A method for the preparation of the product according to any one of claims 13-15, comprising adding vitamin K2, magnesium and, optionally, calcium to a food product.
17. A composition according to any one of claims 1-12, for supporting, maintaining and/or improving vascular elasticity and/or for the prevention of vascular hardening; and/or for supporting, maintaining and/or improving blood circulation and/or blood flow of micro- and/or macrovascular system; and/or for supporting, maintaining and/or improving blood transfusion and/or the transfusion of oxygen and nutrients to the tissues and/or for the removal of waste and carbon dioxide from the tissues; and/or for keeping an adequate energy level in order to support physical and mental health.
18. A composition according to any one of claims 1-12, to support and/or maintain and/or improve a condition selected from the group comprising vascular health, cardiovascular health, blood flow, blood circulation, macrocirculation of the blood, microcirculation of the blood, blood perfusion of tissues, vessel flexibility, bone health, clotting capability, normal platelet aggregation capabilities, glucose control, insulin secretion, insulin sensitivity, mental health, cognitive performance, memory, alertness, mental sharpness, weight management, triglyceride levels in blood, blood pressure, BMI, and/or waist circumference and/or to prevent diabetes, obesity, metabolic syndrome, arterial stiffness, chronic inflammation and/or low grade inflammation.
19. A composition according to any one of claims 1-12, for use in the treatment of a condition selected from the group comprising vascular disease, cardiovascular disease, atherosclerosis, atheriosclerosis, clogged arteries, vessel inflexibility, varicose veins, arterial stiffness, transient ischemic attack, cold limbs, bone disease, bone demineralisation, osteopororis, thrombosis, stroke, diabetes, insulin resistancy, high triglyceride blood levels, metabolic syndrome, obesity, bodily fat mass accumulation, high waist circumference, hypertension, chronic inflammation, low-grade inflammation, mental disease, mental decline, dementia, and/or Alzheimer disease.
20. Use of a composition according to any one of claims 1-12, to support and/or maintain or improve a condition selected from the group comprising vascular health, cardiovascular health, blood flow, blood circulation, macrocirculation of the blood, microcirculation of the blood, blood perfusion of tissues , vessel flexibility, bone health, clotting capability, normal platelet aggregation capabilities, glucose control, insulin secretion, insulin sensitivity, mental health, cognitive performance, memory, alertness, mental sharpness, weight management, triglyceride levels in blood, blood pressure, BMI, and/or waist circumference and/or to prevent diabetes, obesity, metabolic syndrome, arterial stiffness, chronic inflammation and/or low grade inflammation..
21. Use of a composition according to any one of claims 1-12, to enhance bioavailability of vitamin K and/or vitamin K2 and/or MK-7.
22. Use of a composition according to any one of claims 1-12, to increase the biological activity of vitamin K and/or vitamin K2 and/or MK-7.
23. Use of a composition according to any one of claims 1-12, to increase the level of vitamin K and/or vitamin K2 and/or MK-7 in blood of a mammal.
24. Use of a composition according to any one of claims 1-12, to reduce the level of circulating uncarboxylated MGP and/or uncarboxylated osteocalcin in blood of a mammal.
25. Use of a composition according to any one of claims 1-12, to increase the level of circulating carboxylated MGP and/or carboxylated osteocalcin in blood of a mammal.
26. Use according to any of claim 23, 24 or 25, wherein the reduction of the level of circulating uncarboxylated MGP and/or uncarboxylated
osteocalcin, and/or the increase of the level of circulating caboxylated MGP and/or carboxylated osteocalcin in blood in a mammal, and/or the increase of the level of vitamin K in blood of a mammal is obtained within 12 weeks, preferably within 8 weeks more preferably within 4 weeks.
27. Method to reduce the level of circulating uncarboxylated MGP and/or uncarboxylated osteocalcin in blood of a mammal by administering to a mammal the composition according to any one of claims 1-12.
28 Method to increase the level of circulating carboxylated MGP and/or carboxylated osteocalcin in blood of a mammal by administering to a mammal the composition according to any one of claims 1-12.
29. Method to increase the level of vitamin K in blood in a mammal by administering to a mammal the composition according to any one of claims 1-
12.
30. Method according to anyone of claim 27, 28 and/or 29 wherein the composition according to any one of claims 1-12 is administered for a period of at least 4 weeks, preferably at least 8 weeks and most preferably at least 12 weeks.
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WO2016131993A2 (en) 2015-02-20 2016-08-25 Vitak B.V. Vitamin k and capillary function
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