EP1571926A1 - Verwendung von präbiotika zur vorbeugung oder behandlung von oxidationsstress - Google Patents

Verwendung von präbiotika zur vorbeugung oder behandlung von oxidationsstress

Info

Publication number
EP1571926A1
EP1571926A1 EP03813628A EP03813628A EP1571926A1 EP 1571926 A1 EP1571926 A1 EP 1571926A1 EP 03813628 A EP03813628 A EP 03813628A EP 03813628 A EP03813628 A EP 03813628A EP 1571926 A1 EP1571926 A1 EP 1571926A1
Authority
EP
European Patent Office
Prior art keywords
fructose
oligosaccharides
prebiotics
fos
approximately
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Withdrawn
Application number
EP03813628A
Other languages
English (en)
French (fr)
Inventor
Yves Rayssiguier
Jérômes BUSSEROLLES
André MAZUR
Elyett Gueux
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.)
Institut National de la Recherche Agronomique INRA
Original Assignee
Institut National de la Recherche Agronomique INRA
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 Institut National de la Recherche Agronomique INRA filed Critical Institut National de la Recherche Agronomique INRA
Publication of EP1571926A1 publication Critical patent/EP1571926A1/de
Withdrawn legal-status Critical Current

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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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • 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
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • 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
    • A61P39/06—Free radical scavengers or antioxidants
    • 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 present invention relates to the use of prebiotics for the preparation of food preparations, ahcaments, or pharmaceutical compositions intended for the prevention or treatment of oxidative stress.
  • Oxidative stress is the result of an imbalance within the body in favor of pro-oxidant species compared to antioxidant species.
  • the pro-oxidant species are generally free radicals and in particular oxygenated free radicals.
  • the presence of an unpaired electron makes these compounds extremely reactive towards the biological macromolecules of the organism; lipids, carbohydrates, proteins and nucleic acids are thus privileged targets of "these species.
  • the oxidative degradation of these macromolecules leads to numerous cellular dysfunctions.
  • the origin of these free radicals essentially takes its source in the metabolism of Most of the oxidative stress comes from energy metabolism, so the final stage of food oxidation, the mitochondrial respiratory chain, is responsible for the formation of oxygenated free radicals. during the inflammatory reaction, stimulation of phagocytic cells is also accompanied by the formation of free radicals.
  • the body's antioxidant defenses call on protein systems, such as superoxide dismutase, but also on antioxidant compounds provided by food, such as vitamins C and E, or other nutrients, like carotenoids, polyphenols or flavonoids. Dietary imbalances can be the cause of oxidative stress.
  • the inventors have in particular shown previously that a diet too rich in sugars, and in particular in sucrose (Busserolles et al, 2002a) and in fructose (Busserolles et al, 2002b), could generate significant oxidative stress. These pro-oxidant effects are all the more important as the diet is depleted in antioxidants.
  • Fructose is a monosaccharide whose consumption has greatly increased, either as such or in the form of sucrose. Due to their low cost of obtaining, syrups rich in fructose from corn are preferably used in sugary drinks.
  • fructose is naturally present in honey and in fruits where it is associated with many protective micronutrients, one can wonder about the consequences for health, an unlimited increase in this purified carbohydrate. Indeed, fructose has many properties that distinguish it from other sugars and the high intake of this carbohydrate could be responsible for undesirable metabolic effects.
  • the methods of combating oxidative stress generally involve the use of anti-free radical nutrients having a direct effect on free radicals: carotenes, ascorbic acid (vitamin C), tocopherols (vitamin E) , polyphenols (US Patent No. 6,207,702).
  • the present invention stems from the discovery by the inventors of the fact that prebiotics and more particularly fructo-oligosaccharides (FOS) make it possible to combat oxidative stress resulting from an excess of fructose in the diet.
  • FOS fructo-oligosaccharides
  • Prebiotics are complex, non-digestible carbohydrates degraded by microorganisms. the intestinal flora, and whose degradation- is responsible for beneficial effects ⁇ for the health of the host.
  • These microorganisms are generally bacteria, and in particular bifodobacteria, which are found mainly in the colon.
  • the beneficial effects caused by said microorganisms may be due to the selective stimulation of the growth of certain species of microorganisms, in particular bifodobacteria, and / or to the release of metabolites resulting from the transformation of prebiotics by microorganisms.
  • oligosaccharides As it stands, the only clearly defined pre-biotics are sugar polymers with a degree of polymerization between 2 and 12, classified among complex carbohydrates: oligosaccharides. Mention may thus be made, in addition to the fructo-oligosaccharides whose effects are the most documented, fructans, galacto-oligosaccharides, xylo-oligosaccharides, soy oligosaccharides, gentio-oligosaccharides or isomalto-oligosaccharides.
  • Fructo-oligosaccharides are obtained either by hydrolysis of inulin, or by enzymatic synthesis, by transfructosylation from saccharide precursors. They correspond to the general formula Glucosyl- (Fructosyl) n -Fructose or (Fructosyl) m -Fructose where n represents an integer from 1 to 8 and m represents an integer from 1 to 8. In most cases the preparations of FOS are not homogeneous. They include mixtures of chains of variable size.
  • the polymers correspond to the formula Glucosyl- (Fructosyl) n -Fructose (l ⁇ n ⁇ 8)
  • the FOS prepared by hydrolysis correspond to the two formulas Glucosyl- (Fructosyl) n-Fructose and / or (Fructosyl) m -Fructose (l ⁇ n ⁇ 8 and l ⁇ m ⁇ 8).
  • the FOS include in particular short-chain fructo-oligosaccharides, synthesized by transfructosylation, for which the degree of polymerization is less than 6, and in particular short chain FOS with 2, 3 or 4 fructose units such as 1-kestose, nystose and fructosyl-nystose
  • Fructans are polymers in which the fructosyl-fructose type bonds are predominant.
  • the galacto-oligosaccharides are formed from 2 to 6 hexose units, they mainly include galactose as the basic unit. They are synthesized by the action of ⁇ -galactosidase on lactose.
  • the xylo-oligosaccharides come from the hydrolysis of xylan, they are composed of xylose. Soy oligosaccharides are extracted from soy, they are mainly mixtures of oligosaccharides comprising from 1 to 4 sugar units, the main components being raffinose ⁇ and stachyose-.
  • Gentio-oligosaccharides are polymers resulting from the digestion of starch, for which the major part of the bonds is of the form ⁇ -glucopyranosyl- (1-6) -glucopyranose.
  • Isomaltosaccharides are also glucose polymers resulting from the hydrolysis of starch, they are mixtures of isomaltose, panose, isomaltotriose and other branched polymers with 4 or 5 glucose units.
  • the inventors have shown that the addition of prebiotics in the food ration, advantageously the addition of FOS, makes it possible to reduce the oxidative stress due in particular to a diet rich in sugars, and in particular in fructose.
  • the object of the invention is to provide new means of preventing or treating oxidative stress.
  • the subject of the invention is the use of prebiotics for the preparation of food preparations, ahcaments, or pharmaceutical compositions intended for the prevention or treatment of oxidative stress.
  • a more particular subject of the invention is the aforementioned use of at least one oligosaccharide chosen from:
  • the invention relates more particularly to the above-mentioned use of fructo-oligosaccharides (FOS) of general formula Glucosyl- (Fructosyl) n -Fructose or (Fructosyl) m - Fructose where n represents an integer from 1 to 8, in particular from 1 to 5, and m represents an integer from 1 to 8, in particular from 1 to 5, such as the short chain FOS 1-kestose, nystose or fructosyl-nystose.
  • FOS fructo-oligosaccharides
  • Another subject of the invention is the use of prebiotics in the context of the prevention or treatment of oxidative stress linked to the consumption of sugars.
  • the invention relates more particularly to the use of prebiotics in the context of the prevention or treatment of oxidative stress linked to the consumption of fructose.
  • the invention relates in particular to the use of prebiotics in the context of the prevention or treatment of oxidative stress due to consumption of food fruetose greater than about 50 g / day on average.
  • the invention also relates to the use of prebiotics, for which said prebiotics are administered at a daily dose of approximately 1 g to approximately 20 g, in particular from approximately 2 g to approximately 17 g, in particular from approximately 5 g to approximately 15 g.
  • the invention also relates to the use of prebiotics as compounds having an anti-free radical effect in the context of the prevention or treatment of oxidative stress.
  • the invention also relates to the use of prebiotics as compounds having an anti-aging effect linked to an effect of protection of the cells of the organism against the action of free radicals.
  • the invention also relates to any food preparation comprising simple carbohydrates in combination with prebiotics.
  • the invention relates more particularly to a food preparation comprising: at least one simple carbohydrate such as fructose or sucrose, in combination with one or more oligosaccharides chosen from:
  • the food preparation of the invention is such that the proportion of prebiotics represents by weight at least 5% of the amount of simple carbohydrates present in said preparation.
  • the invention relates in particular to a food preparation for which the proportion by weight of fructo-oligosaccharides (FOS) relative to the amount of fructose present in said preparation varies between 10% and 100% and is in particular from approximately 15% to approximately 35 % and is notably around 20%.
  • FOS fructo-oligosaccharides
  • the invention relates in particular to a food preparation comprising a mixture of fructo-oligosaccharides (FOS), as defined above, comprising 64% of Glucosyl-
  • FOS fructo-oligosaccharides
  • the invention relates more particularly to a food preparation comprising a mixture of fructo-oligosaccharides (FOS), as defined above, comprising 64% of Glucosyl- (Fructosyl) n -Fructose and 36% of (Fructosyl) m -Fructose, of average polymerization degrees 4.8, the proportion by weight of said FOS present in said preparation varying between 10% o and 100%, and being in particular from approximately 15% to approximately 35%, preferably approximately 20% o, by relative to the amount of fructose present in said preparation.
  • FOS fructo-oligosaccharides
  • the blend of FOS used corresponds to the preparation Raftilose ® of ORAFTI P 5, Thienen, Belgium.
  • the subject of the invention is also a food product containing the food preparation defined above, said food product being chosen from a group comprising pastries, confectionery, desserts, drinks, cereal bars, chocolate bars, sweet bars, breakfast cereals, dairy products and dietary supplements.
  • the inventors have shown, on an animal model, that the addition of fructo-oligosaccharides (FOS) in the food ration makes it possible to reduce the oxidative stress due to a diet enriched in fructose.
  • FOS fructo-oligosaccharides
  • the rats were placed in wire bottom cages in a temperature-controlled room (22 ° C) with 12-hour day / night cycles. The animals were treated according to the recommendations of the Ethics Committee of INRA, decree n ° 87-848.
  • the rats were first fed on a semi-purified starch-based diet for 7 days. They were then randomly divided into 4 groups of 1-0 rats: -a starch group (A), a fructose group (F), a starch group + FOS (A / FOS) and a fructose group + FOS (F / FOS ). They then followed their proper diet for 4 weeks. Food and distilled water were provided ad libitum. The composition of the food rations was as follows (in g / kg):
  • Vitamin blend (AIN-76A) 10 10 10 10 10
  • the mixtures AIN-76 and ALN-76A were supplied by I ⁇ N Biomedicals, Orsay,> France.
  • the FOS (Raftilose ® P 95 ) were obtained from ORAFTI, Thienen, Belgium. They were gradually introduced into the diet in order to avoid diarrhea which could start in response to the too rapid administration of large quantities of this compound.
  • Raftilose ® P 5 is a mixture of Glucosyl- (Fructosyl) n -Fructose (64%) and (Fructosyl) m - Fructose (36%) with an average degree of polymerization 4.8. 4 days before sacrifice, the animals were kept individually in stainless steel cages with ad libitum access to water and food.
  • Urine samples were collected 24 hours before sacrifice in 50 ml graduated tubes, volumes were precisely measured, the samples were then centrifuged and stored at -80 ° C until analysis. At the time of sacrifice, the rats were weighed, then anesthetized using sodium pentobarbital (40 mg / kg intraperitoneal injection) and killed. Blood was taken from the abdominal aorta and collected in heparinized tubes. The plasma obtained after centrifugation at low speed (2000 g, 15 min) was stored at -80 ° C for biochemical analyzes. The heart was quickly removed and then washed in an ice-cold saline solution.
  • TBARS thiobarbituric acid
  • TBARS lipid peroxidation of a sample subjected to oxidative stress.
  • the plasma TBARS levels were determined by spectrofluorometry on an LS 5 device (Perkin Elmer, Norwalk, CT, USA). A method adapted from Okhawa et al. (1979) was used as previously described (Rayssiguier et al, 1993). The level of urinary TBARS was measured as described in Lee et al. (1992) and calculated on the basis of a 24-hour urine volume. Finally, the measurement of cardiac TBARS was based on Ohkawa et al. (1979), they allow the evaluation of the susceptibility of cardiac lipids to peroxidation.
  • the cardiac tissues were homogenized on ice in a ratio of 1 g of fresh tissue to 9 ml of KC1 150 mmol / 1 using a Polytron homogenizer, these homogenates were then subjected to a lipid peroxidation induced by a FeSO 4 mixture (2 ⁇ mol 1) - ascorbate (50 ⁇ mol / 1) for 30 min in a bath at 37 ° C. in the absence of oxygen, a control 1,1,3,3-tetraethoxypropane was used; TBARS were then measured by spectrophotometry (Uvikon 941 plus series, Kontron Instruments, St Quentin en Yvelines, France).
  • TBARS u ⁇ natres 11 99 ⁇ 0.50 21.97 ⁇ 1.58 13.40 ⁇ 0.53 15.86 ⁇ 1.19 ⁇ 0.001 ⁇ 0.05 ⁇ 0.001 nmol / 24h. ,, -. - -. ,. . i * - -, -
  • results are the averages for 10 animals ⁇ standard deviation a p value for ANOVA The ANOVA results are significant for p ⁇ 0.05, NS not significant
  • the TBARS of the Fructose + FOS group are significantly lower than those of the Fructose group and are not significantly different from those of the Amidon + FOS group. FOS therefore make it possible to limit oxidative stress due to the consumption of fructose.
  • Vitamin E / plasma triglyceride ratio allows is a reflection of the oxidative stress to which an organism has been subjected. The lower the value of this ratio, the higher the level of oxidative stress.
  • Plasma triglyceride concentrations were measured using enzymatic procedures according to the supplier's recommendations (Biotrol, Paris, France).
  • a multipurpose control serum (Biotrol-33-plus) was treated in parallel with the samples in order to check the accuracy of the results of the plasma analysis.
  • Plasma vitamin E concentrations were determined by reverse-phase high performance liquid chromatography on a Kontron series 400 device (Kontron St Quentin en Yvelines, France) using a hexane extract. ⁇ -Tocopherol acetate (Sigma) was added to the samples as an internal control. The samples were extracted twice with hexane after precipitation of the proteins with ethanol.
  • the extract was dried under nitrogen, dissolved in an ethanol-methylene chloride mixture (65:35, v / v) and injected onto a C 18 column (nucleosil; 250 mm in length, di 46 mm., Particles of 5 .mu.m). Pure methanol made it possible to elute the ⁇ -tocopherol in 5 min and the tocopherol acetate in 6.3 min at a flow rate of 2 ml / min. The compounds were detected by UV (292 nm) and then quantified by internal and external calibrations using control solutions.
  • Vitamin E 9.01 ⁇ 0.54 9.74 ⁇ 0.92 7.21 ⁇ 0.35 8.74 ⁇ 0.62 NS ⁇ 0.05 NS ⁇ g / ml
  • results are the means calculated for 10 animals ⁇ standard deviation. has value of p for ANOVA. ANOVA results are significant for p ⁇ 0.05, NS, not significant
  • the high fructose diet decreases the ratio
  • Vitamin E / TG which testifies to the existence of oxidative stress.
  • FOS supplementation prevents the reduction of this ratio, in other words decreases the oxidative stress resulting from the consumption of the diet rich in fructose.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Epidemiology (AREA)
  • Nutrition Science (AREA)
  • Molecular Biology (AREA)
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  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
EP03813628A 2002-12-18 2003-12-17 Verwendung von präbiotika zur vorbeugung oder behandlung von oxidationsstress Withdrawn EP1571926A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR0216136 2002-12-18
FR0216136A FR2848783B1 (fr) 2002-12-18 2002-12-18 Utilisation de prebiotiques pour prevenir ou traiter le stress oxydant
PCT/FR2003/003770 WO2004056210A1 (fr) 2002-12-18 2003-12-17 Utilisation de prebiotiques pour prevenir ou traiter le stress oxydant

Publications (1)

Publication Number Publication Date
EP1571926A1 true EP1571926A1 (de) 2005-09-14

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EP03813628A Withdrawn EP1571926A1 (de) 2002-12-18 2003-12-17 Verwendung von präbiotika zur vorbeugung oder behandlung von oxidationsstress

Country Status (7)

Country Link
US (1) US20060252725A1 (de)
EP (1) EP1571926A1 (de)
JP (1) JP2006510703A (de)
AU (1) AU2003300651A1 (de)
CA (1) CA2510766A1 (de)
FR (1) FR2848783B1 (de)
WO (1) WO2004056210A1 (de)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2502507A1 (de) * 2011-03-21 2012-09-26 Abbott Laboratories Verfahren zur Verbesserung der Knochengesundheit bei Kleinkindern mit Präbiotika
WO2013126015A1 (en) * 2012-02-23 2013-08-29 N. V. Nutricia Composition comprising non- digestible oligosaccharides

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008108651A1 (en) * 2007-03-08 2008-09-12 Friesland Brands B.V. Infant foods with optimized amino acid composition

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0638589B1 (de) * 1993-08-10 1998-01-28 Südzucker Aktiengesellschaft Mannheim/Ochsenfurt Verfahren zur Herstellung von Inulinderivaten
EP0692252B1 (de) * 1994-06-14 2001-04-04 "Raffinerie Tirlemontoise", société anonyme: Verwendung einer Zusammensetzung enthaltend Inulin oder Oligofructose als Antikrebsmittel
JP3579128B2 (ja) * 1995-05-31 2004-10-20 明治製菓株式会社 過酸化脂質上昇抑制材
EP0879600A1 (de) * 1997-05-20 1998-11-25 Tiense Suikerraffinaderij N.V. (Raffinerie Tirlemontoise S.A.) Fruktan-haltige Zusammensetzung zur Vorbeugung und Behandlung von Dickdarmkrebs
DE19817877C2 (de) * 1998-04-22 2002-06-13 Hans Guenter Berner Energy-Drink auf Fruchtsaftbasis
EP1125507A1 (de) * 2000-02-15 2001-08-22 Tiense Suikerraffinaderij N.V. (Raffinerie Tirlemontoise S.A.) Inulinprodukte mit verbesserten Nahrungseigenschaften
US6774111B1 (en) * 2000-03-14 2004-08-10 Abbott Laboratories Carbohydrate system and a method for providing nutrition to a diabetic
EP1174118A1 (de) * 2000-06-28 2002-01-23 Cognis France S.A. Verwendung von Inulinen und Inulinderivaten
EP1175905A1 (de) * 2000-07-24 2002-01-30 Societe Des Produits Nestle S.A. Ernährungszusammensetzung
DE20106845U1 (de) * 2001-04-19 2001-11-08 Rats Apotheke Dr Wolfgang Albr Likör für Diabetiker
US20030004211A1 (en) * 2001-05-25 2003-01-02 Frank Corsini Carbohydrate modifying agent and drinks containing the modifying agent

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
WO2008108651A1 (en) * 2007-03-08 2008-09-12 Friesland Brands B.V. Infant foods with optimized amino acid composition

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO2004056210A1 *

Also Published As

Publication number Publication date
US20060252725A1 (en) 2006-11-09
FR2848783A1 (fr) 2004-06-25
FR2848783B1 (fr) 2005-05-13
JP2006510703A (ja) 2006-03-30
AU2003300651A1 (en) 2004-07-14
CA2510766A1 (fr) 2004-07-08
WO2004056210A1 (fr) 2004-07-08

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