EP1221868A1 - Dietary supplement - Google Patents
Dietary supplementInfo
- Publication number
- EP1221868A1 EP1221868A1 EP00969600A EP00969600A EP1221868A1 EP 1221868 A1 EP1221868 A1 EP 1221868A1 EP 00969600 A EP00969600 A EP 00969600A EP 00969600 A EP00969600 A EP 00969600A EP 1221868 A1 EP1221868 A1 EP 1221868A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- folate
- composition
- folic acid
- matter
- subject
- 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.)
- Withdrawn
Links
- 235000015872 dietary supplement Nutrition 0.000 title claims abstract description 10
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims abstract description 85
- 235000019152 folic acid Nutrition 0.000 claims abstract description 60
- 239000011724 folic acid Substances 0.000 claims abstract description 60
- 229940014144 folate Drugs 0.000 claims abstract description 35
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229960000304 folic acid Drugs 0.000 claims abstract description 25
- 239000000203 mixture Substances 0.000 claims abstract description 18
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 13
- 239000000126 substance Substances 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 12
- 235000013305 food Nutrition 0.000 claims abstract description 11
- 239000000047 product Substances 0.000 claims abstract description 11
- 235000018823 dietary intake Nutrition 0.000 claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 239000013543 active substance Substances 0.000 claims abstract description 4
- 230000002708 enhancing effect Effects 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000013589 supplement Substances 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 3
- 230000037396 body weight Effects 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 2
- 235000015173 baked goods and baking mixes Nutrition 0.000 claims description 2
- 238000005728 strengthening Methods 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 19
- 102000006996 Aryldialkylphosphatase Human genes 0.000 description 18
- 108010008184 Aryldialkylphosphatase Proteins 0.000 description 18
- 210000002966 serum Anatomy 0.000 description 15
- 108010010234 HDL Lipoproteins Proteins 0.000 description 8
- 102000015779 HDL Lipoproteins Human genes 0.000 description 7
- 210000003743 erythrocyte Anatomy 0.000 description 7
- 208000029078 coronary artery disease Diseases 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 235000013339 cereals Nutrition 0.000 description 4
- 230000009469 supplementation Effects 0.000 description 4
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- MPJKWIXIYCLVCU-UHFFFAOYSA-N Folinic acid Natural products NC1=NC2=C(N(C=O)C(CNc3ccc(cc3)C(=O)NC(CCC(=O)O)CC(=O)O)CN2)C(=O)N1 MPJKWIXIYCLVCU-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000000378 dietary effect Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- -1 folinic acid Chemical compound 0.000 description 3
- 235000008191 folinic acid Nutrition 0.000 description 3
- 239000011672 folinic acid Substances 0.000 description 3
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 3
- 229960001691 leucovorin Drugs 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 235000008429 bread Nutrition 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- WYMSBXTXOHUIGT-UHFFFAOYSA-N paraoxon Chemical compound CCOP(=O)(OCC)OC1=CC=C([N+]([O-])=O)C=C1 WYMSBXTXOHUIGT-UHFFFAOYSA-N 0.000 description 2
- 229960004623 paraoxon Drugs 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 239000004150 EU approved colour Substances 0.000 description 1
- 239000004129 EU approved improving agent Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 108010009043 arylesterase Proteins 0.000 description 1
- 102000028848 arylesterase Human genes 0.000 description 1
- 230000000778 atheroprotective effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 125000003929 folic acid group Chemical group 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000013622 meat product Nutrition 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000021067 refined food Nutrition 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular 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
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the object of the invention is the use of folic acid or folate or a functionally equivalent substance as a supplement or additive for the manufacture of a composition of matter for dietary intake with antioxidative defences enhancing effect.
- the term "effective amount” means an amount of the active agent which after administration is sufficient to enhance the serum paraoxonase activity and thus the antioxidative defences in the subject.
- folic acid and folate can be used interchangeably.
- the composition of matter can be any dietary, typically orally administered composition, preparation or product, such as a food or feed product, food supplement, a drug preparation, or a raw material for such a product.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Mycology (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
- Toxicology (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Fodder In General (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Bakery Products And Manufacturing Methods Therefor (AREA)
Abstract
The present invention concerns a method for the manufacture of a composition of matter for dietary intake, such as a food or feed product or food supplement, for strengthening the antioxidative defence system of a subject, such as a human. The method is characterized in that to the composition, folic acid or folate or a functionally equivalent substance is added as the active agent.
Description
Dietary supplement
The present invention relates to a novel use of folic acid or folate, or of a functionally equivalent substance having the biochemical activity of folic acid or folate, such as folinic acid, as a dietary supplement in or for fortification of compositions of matter, such as products for ingestion or dietary intake, for example food and feedstuff s.
Although low serum folate concentration has been established as a new risk factor for cardiovascular diseases (CVD), the mechanism underlying the risk-lowering effect is unclear. Folate is an important substrate in the remethylation of homo- cysteine (tHcy) back to methionine and it is supposed that folic acid could lower the risk of CVD through reducing plasma tHcy concentrations .
The human serum paraoxonase (PON) is an antioxidative enzyme in high density lipoproteins (HDL), which eliminates lipid soluble radicals in the circulation and protects against coronary disease . There is epidemiologic evidence showing that persons with elevated HDL cholesterol levels are at reduced risk of coronary heart disease (CHD). HDL has been shown to possess antioxidative properties, which might conceivably contribute to the protection by HDL against CHD.
Paraoxonase/ arylesterase has been suggested to account for an important part of the antioxidative property of HDL5. A lowered PON activity has been reported also in patients with myocardial infarction (MI)2"3.
The present invention is based on the finding that there is a positive correlation between circulating folate or dietary folate intake and enhanced serum PON activity. Enhanced serum PON activity improves the endogenous antioxidative capacity and defences of a subject, e.g. a human, thus reducing the risk e.g. for CHD, cancer, type II diabetes and cataract, and is also associated with the process of aging.
In its broadest sense the invention is directed to a method for enhancing the endogenous antioxidative defences of the body by dietary folic acid or folate supplementation. The term "folate" refers to the salts and esters of folic acid.
Acceptable salts include i.e. the alkali metal salts, such as the sodium salt and the methylglucamine salt. Esters of folic acid can be prepared in a manner known to the person skilled in the art.
The object of the invention is thus a method for the manufacture of a composition of matter for dietary intake with antioxidative defences enhancing effect, according to which method, in the said composition, folic acid or folate or a functionally equivalent substance is used as the active or effective agent.
According to a second aspect, the object of the invention is the use of folic acid or folate or a functionally equivalent substance as a supplement or additive for the manufacture of a composition of matter for dietary intake with antioxidative defences enhancing effect.
According to a third aspect, the object of the invention is a method for enhancing the antioxidative defences in a subject comprising administering, e.g. orally or parenterally, to said subject, an effective amount of folic acid or folate or a functionally equivalent substance.
A functionally equivalent substance of folic acid or folate is intended to mean a substance that has the biochemical activity of folic acid, for example folinic acid or a salt or ester of folinic acid.
The term "subject" means here a mammal, such as a human, or an animal, especially livestock or farm animals.
The term "effective amount" means an amount of the active agent which after administration is sufficient to enhance the serum paraoxonase activity and thus the antioxidative defences in the subject. In the following, the terms folic acid and folate can be used interchangeably.
The composition of matter can be any dietary, typically orally administered composition, preparation or product, such as a food or feed product, food supplement, a drug preparation, or a raw material for such a product.
The product to be used as the composition of matter to be supplemented or fortified by adding thereto folic acid or folate or a functionally equivalent its derivative, can in principle be any type of food or feed product. According to an exemplary embodiment of the invention, it is contemplated to add folic acid or a functionally equivalent derivative thereof to grain, and to use such supplemented grain in grain based foods or feeds, or to add it as a supplement to such foods or feeds, such as to bakery products, cereals, snack foods, beverages etc. However, it is possible to include folic acid or its derivative in any type of food or feed product, in which it can be properly included and distributed, such as processed foods, for example meat products, such as sausages, or also other ready made foods. It is also possible to fortify dairy products, such as milk, cheese, butter and youghurt, as well as other beverages, such as fruit drinks and juices, with the dietary supplement according to the invention.
A dietary supplement can also be in the form of tablets, capsules, lozenges, granules, syrups, solutions, suspensions for oral administration, wherein the folic acid or folate is suitably included together with a carrier or filler substance, such as lactose, silica, glucose, starch, glycerol, diluents and solvents. Such dosage forms may include conventional additives such as glidants, stabilizer, colouring agents, preservatives, taste improving agents as well as a matrix to slow down absorption such as methyl cellulose or microcrystalline cellulose with colloidal anhydrous silica.
The preparation of such supplements in dosage form is well known to the person skilled in the art.
The amount of folic acid or the functionally equivalent substance to be included in a composition of matter for dietary intake, can vary broadly depending on the type of product to be supplemented or fortified, as well as on its intake frequency and intake levels. Such amounts can easily be determined by the person skilled in the
art, to provide for and secure a suitable daily total intake of the dietary supplement. A typical amount for intake would be for example 15 to 1200 μg of folate per day for a subject of normal size, such as a human subject of appr. 80 kg, or a daily intake ranging from appr. 0.2 to 15 μg per kg body weight. This amount can be administered for example in bread, such as in 100 g of bread constituting a suitable single portion.
Experimental section
Serum PON enzyme activity was analyzed based on its capacity to hydrolyze paraoxon, and erythrocyte folate levels were measured by RIA. First the association between erythrocyte folate levels and serum PON activity in a population-based sample of 155 men aged 53-71 years examined in 1998-99 as a part of the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) was examined. The correlation coefficient for the association between serum PON activity and erythrocyte folate levels was 0.25 (P = 0.002). The unadjusted mean (95 % confidence interval (CI)) serum PON activity was 26.3 % lower (63.2, 47.5 to 79.0 nmol/mL/min) in the lowest fifth of erythrocyte folate concentration than in the highest fifth (85.7, 63.2 to 108.2 nmol/mL/min).
To confirm the observational finding in an experiment, the effect of oral folate supplementation on PON activity in a placebo-controlled double-blind folic acid supplementation trial was studied. In this study 39 healthy voluntary men aged 19-36 years were randomized to receive either 0.9 mg folate or placebo daily for 8 weeks. The correlation coefficient for the association between changes in erythrocyte folate concentration and PON activity during the study period was 0.36 (P = 0.025). The mean serum PON activity increased by 4.0 % (2.43 nmol/mL/min) in the folic acid group and decreased by 3.6 % (-2.87 nmol/mL/min) in the placebo group (P = 0.015 for the difference between groups). The correlation coefficient for the association between changes in erythrocyte folate concentration and plasma total homocysteine (tHcy) concentration was -0.62 (P < 0.001), and that for changes in plasma tHcy concentration and serum PON enzyme activity -0.25 (P = 0.134). In
a linear regression model strongest predictors of change in serum PON activity were the change in erythrocyte folate concentration (standardized coefficient 0.41, P = 0.010), and age (0.27, P = 0.091) (adjusted R Square for the model 0.151, P = 0.020) .
In summary, the experimental findings indicate that folate supplementation and blood folate concentration affect serum PON activity in humans.
References
1. Verhoef P, Stampfer MJ, Rimm EB. Folate and coronary heart disease. Curr. Opin. Lipid. 9, 17-22 (1998).
2. McElveen J, et al. Distribution of paraoxon hydralytic activity in the serum of patients after myocardial infarction. Clin. Chetn. 32, 671-3 (1986). 3. Ayub A, et al. Serum paraoxonase after myocardial infarction. Arteήoscler.
Thromb. Vase. Biol. 19, 331-5 (1999). 4. Salonen JT, et al. Polymorphism in high density lipoprotein paraoxonase gene and risk of acute myocardial infarction in men: prospective nested case-control study. Brit. Med. I. 319, 487-8 (1999). 5. Stein O, Stein Y. Atheroprotective mechanisms of HDL. Atherosclerosis 144,
285-301 (1999).
Claims
1. Method for the manufacture of a composition of matter for dietary intake with antioxidative defences enhancing effect, characterized in that folic acid, folate or a substance which is functionally equivalent thereto is used as the active agent in the said composition.
2. The method according to claim 1 , characterized in that the composition of matter is a food or feed product, a food supplement, a drug preparation, or a raw material therefor.
3. The method according to claim 1 or 2, characterized in that to the composition of matter an amount of active agent is added which provides for a daily dietary intake of 0.2 to 15 μg of folic acid or folate, per kg of body weight of a subject to which the composition is administered.
4. The method according to claim 1 or 2, characterized in that the composition of matter provides a daily intake of 15 to 1200 μg of folic acid or folate, for example in a bakery product.
5. Use of folic acid or folate or a substance which is functionally equivalent thereto as a supplement or additive for the manufacture of a composition of matter for dietary intake with antioxidative defences enhancing effect .
6. The use according to claim 5 wherein the composition of matter is a food or feed product, a food supplement, a drug preparation, or a raw material therefor.
7. A method for enhancing the the antioxidative defence system in a subject comprising administering to said subject an effective amount of folic acid or folate or a substance which is functionally equivalent thereto.
8. The method according to claim 7 comprising administering to the said subject 0.2 to 15 μg per kg of body weight per day of folic acid or folate or a functionally equivalent substance.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI992239 | 1999-10-18 | ||
| FI992239A FI19992239A (en) | 1999-10-18 | 1999-10-18 | nutritional Supplement |
| PCT/FI2000/000899 WO2001028365A1 (en) | 1999-10-18 | 2000-10-17 | Dietary supplement |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1221868A1 true EP1221868A1 (en) | 2002-07-17 |
Family
ID=8555463
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP00969600A Withdrawn EP1221868A1 (en) | 1999-10-18 | 2000-10-17 | Dietary supplement |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1221868A1 (en) |
| JP (1) | JP2003511097A (en) |
| AU (1) | AU7927200A (en) |
| FI (1) | FI19992239A (en) |
| WO (1) | WO2001028365A1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6420342B1 (en) | 2000-05-08 | 2002-07-16 | N.V. Nutricia | Nutritional preparation comprising ribose and medical use thereof |
| US6740746B2 (en) | 2001-03-20 | 2004-05-25 | Oy Jurilab Ltd. | DNA molecule encoding a variant paraoxonase and uses thereof |
| DE10301354A1 (en) * | 2003-01-16 | 2004-07-29 | Esa Patentverwertungsagentur Sachsen-Anhalt Gmbh | To produce raw sausages, with an accelerated ripening, folic acid and/or folates are added with the herbs/spices for an even distribution to provide micrococcus and/or lactobacillus |
| ES2302571B2 (en) * | 2005-03-18 | 2009-03-16 | Universidad Complutense De Madrid | PROCEDURE FOR OBTAINING COOKED ENRICHED ENERGIES WITH FOLIC ACID. |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06192105A (en) * | 1992-09-14 | 1994-07-12 | Vesta Medicines Pty Ltd | Medical preparation for lowering level of homocysteine |
| US5932624A (en) * | 1995-10-17 | 1999-08-03 | Herbert; Victor D. | Vitamin supplement composition |
| DE29808384U1 (en) * | 1998-05-08 | 1998-08-06 | Eckes-Granini GmbH & Co. KG, 55268 Nieder-Olm | drink |
| US6121249A (en) * | 1998-07-01 | 2000-09-19 | Donald L. Weissman | Treatment and prevention of cardiovascular diseases with help of aspirin, antioxidants, niacin, and certain B vitamins |
-
1999
- 1999-10-18 FI FI992239A patent/FI19992239A/en unknown
-
2000
- 2000-10-17 WO PCT/FI2000/000899 patent/WO2001028365A1/en not_active Application Discontinuation
- 2000-10-17 JP JP2001530969A patent/JP2003511097A/en not_active Withdrawn
- 2000-10-17 EP EP00969600A patent/EP1221868A1/en not_active Withdrawn
- 2000-10-17 AU AU79272/00A patent/AU7927200A/en not_active Abandoned
Non-Patent Citations (1)
| Title |
|---|
| See references of WO0128365A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU7927200A (en) | 2001-04-30 |
| WO2001028365A1 (en) | 2001-04-26 |
| JP2003511097A (en) | 2003-03-25 |
| FI19992239A (en) | 2001-04-19 |
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