WO2007016952A1 - Composition for reducing the risk of alcohol induced esophagenal and oropharyngolaryngeal cancer - Google Patents

Composition for reducing the risk of alcohol induced esophagenal and oropharyngolaryngeal cancer Download PDF

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Publication number
WO2007016952A1
WO2007016952A1 PCT/EP2005/009150 EP2005009150W WO2007016952A1 WO 2007016952 A1 WO2007016952 A1 WO 2007016952A1 EP 2005009150 W EP2005009150 W EP 2005009150W WO 2007016952 A1 WO2007016952 A1 WO 2007016952A1
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Prior art keywords
food composition
dietary supplementation
alcohol
dose
supplementation according
Prior art date
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PCT/EP2005/009150
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French (fr)
Inventor
Markus Graf V. Matuschka-Greiffenclau
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Matuschka-Greiffenclau Markus
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Publication date
Application filed by Matuschka-Greiffenclau Markus filed Critical Matuschka-Greiffenclau Markus
Priority to AT06762860T priority Critical patent/ATE554663T1/en
Priority to EA200800427A priority patent/EA012753B1/en
Priority to CN2006800278400A priority patent/CN101232822B/en
Priority to KR20137031344A priority patent/KR101487848B1/en
Priority to AU2006278823A priority patent/AU2006278823B2/en
Priority to PCT/EP2006/007466 priority patent/WO2007017139A1/en
Priority to ES06762860T priority patent/ES2386460T3/en
Priority to KR1020077028054A priority patent/KR101562271B1/en
Priority to EP06762860A priority patent/EP1909600B1/en
Priority to PT06762860T priority patent/PT1909600E/en
Priority to JP2008523251A priority patent/JP5371428B2/en
Priority to CA2611389A priority patent/CA2611389C/en
Priority to UAA200800602A priority patent/UA94713C2/en
Priority to US11/997,127 priority patent/US8580750B2/en
Priority to DK06762860.2T priority patent/DK1909600T3/en
Priority to PL06762860T priority patent/PL1909600T3/en
Priority to SI200631337T priority patent/SI1909600T1/en
Publication of WO2007016952A1 publication Critical patent/WO2007016952A1/en
Priority to HK08110628.1A priority patent/HK1117709A1/en
Priority to HRP20120489TT priority patent/HRP20120489T1/en
Priority to JP2013091972A priority patent/JP5785581B2/en
Priority to US14/058,388 priority patent/US9402849B2/en

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • 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
    • A23L33/155—Vitamins A or D
    • 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
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • 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
    • A23L33/30—Dietetic or nutritional methods, e.g. for losing weight
    • 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
    • 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
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/32—Alcohol-abuse
    • 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 is directed to a composition, in particular a food composition, or dietary supplementation, which is active in respect to a reduction of alcohol induced rise of esophagenal and oropharyngolarynal cancer.
  • the invention is directed to a composition affecting the moderation of alcohol degradation process within the human body.
  • an object of the present invention is to achieve solutions which provide a reduction in the toxic effects or physiological stress in connection with the consumption of alcohol, in particular for people with a predisposition towards rapid alcohol degradation and subsequent accumulation of acetaldehyde due to a genetic polymorphism of human acetaldehyde-dehydrogenase enzym.
  • the present invention particularly solves the problem of a long impact of an accumulation of acetaldehyde after rapid alcohol degradation i.e. alcohol metabolism as may occur in most people of Non-Caucasian type genetic structure.
  • the particular food composition or dietary supplementation is considered to be appropriate to reduce a peak of excess acetaldehyde entering the blood stream and is intended to lower the risk of damage to vital organs and functions of the human body, and in this connection also lowers the risk of breast cancer.
  • Ethanol taken into the body is eliminated by its oxidation.
  • Ethanol (CH3CH2OH) is first metabolised to acetaldehyde (CH3CHO) by alcohol dehydrogenase (ADH), and then acetaldehyde (CH3CHO) is further metabolised to acetic acid (CH3COOH) by aldehyde dehydrogenase (ALDH).
  • ALDH2 class 2 ALDH
  • Km affinity constant
  • ALDH2 has a genetic polymorphism and a single nucleotide change (G ⁇ A) causes the replacement of glutamic acid (GIu) at amino acid position 487 by lysine (Lys) in its mutant ALDH2*2 allele, which encodes a catalytically inactive subunit.
  • G ⁇ A single nucleotide change
  • Individuals with heterozygous ALDH2* 1/2*2 genotype should have only 6% activity compared to those with normal homozygous ALDH2* 1/2* 1 genotype.
  • ALDH2*2 allele varies by race: it is prevalent in East Asia but has not been found in Caucasians and Africans. 40-50% of East Asians have inactive ALDH2*2 allele.
  • the average peaks of blood acetaldehyde concentrations of ALDH2* 1/2*2 heterozygotes and ALDH2*2/2*2 homozygotes after drinking of small amount of ethanol (0.1 g/kg body weight) are five times and 18 times, respectively, of that found in ALDH2* 1/2*1 homozygotes after drinking of moderate amount of ethanol (0.8 g/kg body weight).
  • the amount of acetaldehyde in saliva is increased in ALDH2* 1/2*2 heterozygotes given alcohol, and its level falls when alcohol oxidation of active ALDH2* 1/2*1 homozygotes is inhibited by an ALDH inhibitor 4-methylpyrazol. Therefore, acetaldehyde oxidation is strikingly impaired in individuals with ALDH2*2 allele.
  • the supplement mix according to the invention accelerates the disappearance of alcohol and acetaldehyde after drinking in not only ALDH2* 1/2*1 homozygotes but ALDH2* 1/2*2 heterozygotes.
  • the supplement according to the invention effectively accelerates alcohol metabolism, and is expected to suppress the secretion of acetaldehyde from salivary glands. Therefore, the supplement according to the invention can be used to diminish the risk of cancer of the oral cavity, pharynx, larynx and esophagus for alcohol drinkers with ALDH2*2 allele.
  • the niacin-fraction (Vitamin B3) included in the composition functions as nicotinamide adenine dinucleotide (NAD), which is effective towards a coenzyme to alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH).
  • NAD nicotinamide adenine dinucleotide
  • ADH alcohol dehydrogenase
  • ADH alcohol dehydrogenase
  • ADH aldehyde dehydrogenase
  • the composition also includes Pantotheic acid.
  • Pantotheic acid functions as coenzyme A (CoA), which is considered necessary to metabolize acetic acid.
  • Acetic acid is activated in conjugation with CoA to form acetyl-CoA, which is metabolized in TCA cycle.
  • elimination of a product (acetic acid) is effective towards an acceleration of the metabolism of a substrate (acetaldehyde).
  • this food composition or supplements should be taken about 5 minutes prior to consumption of alcohol and in case of high alcohol consumption again whilst consuming alcohol.
  • the mass of the food composition taken by the consumer should be in the range of about 70 to 120% of the mass of the alcohol included in the consumed drinks.
  • a standard dose might include about 10. Og dextrose, 1.Og Vitamin C, 1.5g L-glutamine, 500mg cysteine, 40mg riboflavin, 100 mg succinic acid, 100 mg fumaric acid, 60mg coenzyme Ql 0, and about 10 mg Niacin (Vitamin B3).
  • the relation of the components of the composition is oriented towards the above given relation.
  • the overall dosage may be adapted to the body mass weight of the consumer.
  • the particular food composition, or dietary supplementation is intended to prevent too much acetaldehyde passing into the mitochondrial matrix and to suppress self- blockade of the enzymatic activity of ALDH and thus facilitate its the decomposition of acetaldehyde.
  • the physiological risks in connection with alcohol consumption may therefore be significantly reduced by the use of the food composition according to the present invention, as this food composition or dietary supplementation facilitates in a synergetic manner an early decrease of the level of acetaldehyde after drinking and simultaneously provides a protective effect in respect of the suppression of the generation of free radicals.
  • Said food composition or dietary supplementation is preferably in such a form, preferably as ingredients of a kind of aperitif, that it allows the food composition to be consumed within a restaurant or a bar prior to consuming alcoholic drinks.
  • a dosage for a person with a body weight of about 80 kg includes a dextrose fraction of approx. 75%, wherein the said dosage may have an overall weight of about 10 to 15, preferably 13.3g.
  • Such a dosage is to provide a considerable moderation in degrading about 18ml alcohol.
  • the food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same, includes a dextrose fraction of about 75.2 mass%, i.e. a quantity of dextrose in the range from 7.2 to 12.8g, preferably 10.0 g within a dose of 13,3g.
  • the food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a Vitamin C fraction of about 7.5 mass% i.e a quantity of Vitamin C in the range from 0.78 to 1.18 g, preferably 1.Og, within a dose of 13.3g.
  • the food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a L-glutamine fraction of about 11.27 mass%, i.e. a quantity of said L-glutamine fraction in the range from 1.23 to 1.7 g, preferably 1.5g, within a dose of 13.3g.
  • the food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a cysteine fraction of about 3.76 mass%, i.e. a quantity of said cysteine fraction in the range from 460 to 540 mg, preferably 500mg, within a dose of 13.3g.
  • the food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a riboflavin fraction of about 0.30 mass% i.e. a quantity of said riboflavin in the range from 32 to 48 mg, preferably 40mg, within a dose of 13.3g.
  • the food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a succinic acid (Bernsteinsaure) fraction of about 0.752 mass%, i.e. a quantity of said succinic acid in the range from 90 to 110 mg, preferably lOOmg, within a dose of 133g.
  • a succinic acid Boesteinsaure
  • the food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a fumaric acid (Fumarsaure) fraction of about 0.752 mass%, i.e. a quantity of said fumaric acid in the range from 90 to 110 mg, preferably lOOmg, within a dose of 13.3g.
  • a fumaric acid Frumarsaure
  • the food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a coenzyme fraction of about 0,451 mass%, i.e. a quantity of said coenzyme fraction in the range from 50 to 70 mg, preferably 60mg, within a dose of 13.3 g.
  • the food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same is in the form of tablets.
  • each tablet is so shaped and dimensioned that it allows said tablet to be easily swallowed.
  • said tablets are in such a form that one dosage includes a plurality of those tablets.
  • the tablets may be accommodated within a dosage receptacle which includes a number of those tablets. It is possible for the food composition to be in the form of small tablets or balls, and to keep same in a small tube, while the volume of the food composition taken by the consumer can be determined with respect to the volume of alcohol which is expected to be consumed.
  • the food composition or dietary supplementation may also be in a form similar to sugar-cubes, or might be in the form of cryopowder.
  • the food composition or dietary supplementation may be separated into separate subunits. It is possible to provide one unit, for example a capsule including the Vitamin C fraction, cysteine, riboflavin, succinic acid, fumaric acid and coenzyme QlO, whilst most of the dextrose fraction is kept in separate units, capsules, tablets or the like.
  • the food-composition or dietary supplementation may also be in the form of a liquid, in particular a sirup-type liquid. It is possible to provide the food composition in the appearance of a soft drink in a small bottle.
  • Glucose is rapidly oxidised in the cytosol of liver cells using the same cytosol NAD+ pool used by ethanol to be converted into acetaldehyde. Because the amount of cytosolic NAD+ is limited and can only constantly be reproduced from NADH+H much less acetaldehyde accumulates.
  • the second achievement is also believed to be achieved by the intake of a large dose of glucose.
  • Glucose augments the enzymatic activity of ADH as well as of ALDH.
  • a large glucose load occurs in the cytosol of liver cells then there is no possibility that the acetaldehyde reaches levels which could lead to inactivation of ALDH or to mitochondrial destruction.
  • Riboflavin will quickly be transformed to FMN, which together with coenzyme Qi 0 is the determining substance for the speed of the reoxidation of NADH+H + to NAD + in the mitochondrial matrix.
  • Acetaldehyde needs NAD+ when it is metabolised to acetic acid.
  • NAD + is transformed into NADH+H + .
  • NADH+H + has to be re-transformed into NAD + to serve again for acetaldehyde decomposition.
  • coenzyme Qio also makes also sense because its level decreases in the human body with progressing age.
  • the activation of the Krebs (citrate) cycle is believed to be achieved by the inclusion of succinic acid and fumaric acid. Both substances activate the second half of the citrate cycle and thereby activate the aerobic oxidation process in mitochondria.
  • L-glutamine helps to speed up the mitochondria-cytosolic malate- asparate shuttle, which plays a key role in the course of intoxication by acetaldehyde. It also speeds up the succinate oxidation process by preventing oxalic and acetic inhibition of succinate dehydrogenase.
  • cysteine Ascorbic acid and also of L-glutamine.
  • Cysteine should provide a strong anti-oxidant effect as well as ascorbic acid.
  • the human body transforms cysteine to gluthatione which specially protects against the toxic effects of acetaldehyde. To reach an optimal level of gluthatione and to avoid cysteine being transformed to cystine, it is important to combine cysteine with glutamine and give twice as much ascorbic acid as cysteine.

Abstract

The present invention is directed to a composition, in particular a food composition, or dietary supplementation which is active in respect to the support and/or the moderation of an alcohol degradation process within the human body. The present invention particularly addresses the problem of rapid alcohol degradation i.e. alcohol metabolism as may occur in most people of Non-Caucasian type genetic structure. In this regard, an object of the present invention is to achieve solutions which provide a reduction in the physiological stress in connection with the consumption of alcohol in particular for people with a predisposition towards rapid alcohol degradation. According to the present invention this object is attained by a food composition or dietary supplementation including the following substances: niacin, dextrose, Vitamin C, L-glutamine cysteine, riboflavin, succinic acid, fumaric acid, and coenzyme Q 10, all substances in physiologically relevant doses in particular as disclosed. The composition reduces alcohol induced risk of esophagenal and oropharyngolarynal cancer.

Description

COMPOSITION FOR REDUCING THE RISC OF ALCOHOL INDUCED ESOPHAGENAL AND OROPHARYNGOLARYNGEAL CANCER
The present invention is directed to a composition, in particular a food composition, or dietary supplementation, which is active in respect to a reduction of alcohol induced rise of esophagenal and oropharyngolarynal cancer. In this respect the invention is directed to a composition affecting the moderation of alcohol degradation process within the human body.
In this regard, an object of the present invention is to achieve solutions which provide a reduction in the toxic effects or physiological stress in connection with the consumption of alcohol, in particular for people with a predisposition towards rapid alcohol degradation and subsequent accumulation of acetaldehyde due to a genetic polymorphism of human acetaldehyde-dehydrogenase enzym.
According to the present invention this object is attained by a food composition, or dietary supplementation including the following substances:
dextrose, Vitamin C, L-glutamine cysteine, riboflavin, succinic acid, fumaric acid, coenzyme QlO, and niacin.
all substances in physiologically relevant doses.
With this particular food composition, or dietary supplementation it will become possible to reduce the activity, or to suppress the production of a particular alcohol dehydrogenase enzyme (ADH3), to slow down the production of acetaldehyde and the ethanol metabolism process and to reduce the alcohol induced peak load on the human organism. Further the enzymatic activity of aldehyde dehydrogenase ALDH2 will be enhanced, so that the metabolisation of acetaldehyde will be supported.
These particular effects help to reduce the peak load of critical substances on the human body, and further reduce a flushing syndrome, reduce the likelihood of headaches and also help to avoid or ease a hangover the day after.
The present invention particularly solves the problem of a long impact of an accumulation of acetaldehyde after rapid alcohol degradation i.e. alcohol metabolism as may occur in most people of Non-Caucasian type genetic structure.
The particular food composition or dietary supplementation is considered to be appropriate to reduce a peak of excess acetaldehyde entering the blood stream and is intended to lower the risk of damage to vital organs and functions of the human body, and in this connection also lowers the risk of breast cancer.
It is considered that drinking alcoholic beverages is associated with increases risk for esophagenal and oropharyngolarynal cancer. The association of alcohol consumption with increased risk for esophagenal and oropharyngolarynal cancer is considered as being evident at least implicitly from epidemiological studies indicating that alcohol itself and/or its metabolite(s) has carcinogenic potency.
Ethanol taken into the body is eliminated by its oxidation. Ethanol (CH3CH2OH) is first metabolised to acetaldehyde (CH3CHO) by alcohol dehydrogenase (ADH), and then acetaldehyde (CH3CHO) is further metabolised to acetic acid (CH3COOH) by aldehyde dehydrogenase (ALDH).
CH3CH2OH + NAD → CH3CHO + NADH + H+
CH3CHO + NAD + H2O → CH3COOH + NADH + H+ It appears that alcoholic beverages are carcinogenic to humans and causally related to cancer of the oral cavity, pharynx, larynx and esophagus. The first metabolite of orally ingested alcohol, acetaldehyde, is suspected to play a pivotal role in the development of alcohol related cancers because of its established DNA damaging effects (single-strand and double-strand breaks) and carcinogenicity in laboratory animals.
There are polymorphic isoforms of ALDH and class 2 ALDH (ALDH2), which has the lowest affinity constant (Km), is the most important enzyme for acetaldehyde oxidation. ALDH2 has a genetic polymorphism and a single nucleotide change (G→A) causes the replacement of glutamic acid (GIu) at amino acid position 487 by lysine (Lys) in its mutant ALDH2*2 allele, which encodes a catalytically inactive subunit. Individuals with heterozygous ALDH2* 1/2*2 genotype should have only 6% activity compared to those with normal homozygous ALDH2* 1/2* 1 genotype. Distribution of ALDH2*2 allele varies by race: it is prevalent in East Asia but has not been found in Caucasians and Africans. 40-50% of East Asians have inactive ALDH2*2 allele. The average peaks of blood acetaldehyde concentrations of ALDH2* 1/2*2 heterozygotes and ALDH2*2/2*2 homozygotes after drinking of small amount of ethanol (0.1 g/kg body weight) are five times and 18 times, respectively, of that found in ALDH2* 1/2*1 homozygotes after drinking of moderate amount of ethanol (0.8 g/kg body weight). The amount of acetaldehyde in saliva is increased in ALDH2* 1/2*2 heterozygotes given alcohol, and its level falls when alcohol oxidation of active ALDH2* 1/2*1 homozygotes is inhibited by an ALDH inhibitor 4-methylpyrazol. Therefore, acetaldehyde oxidation is strikingly impaired in individuals with ALDH2*2 allele.
It appears that ALDH2 deficiency is associated with increased the risk of cancer of the oral cavity, pharynx, larynx and esophagus. Epithelial cells in these upper digestive tract are attacked by acetaldehyde not only diffused from blood but also secreted from salivary glands after drinking, especially in persons with ALDH2*2 allele. The supplement mix according to the invention accelerates the disappearance of alcohol and acetaldehyde after drinking in not only ALDH2* 1/2*1 homozygotes but ALDH2* 1/2*2 heterozygotes. The supplement according to the invention effectively accelerates alcohol metabolism, and is expected to suppress the secretion of acetaldehyde from salivary glands. Therefore, the supplement according to the invention can be used to diminish the risk of cancer of the oral cavity, pharynx, larynx and esophagus for alcohol drinkers with ALDH2*2 allele.
The niacin-fraction (Vitamin B3) included in the composition functions as nicotinamide adenine dinucleotide (NAD), which is effective towards a coenzyme to alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). This vitamin is provided to accelerate ethanol metabolism.
According to a particularly preferred embodiment, the composition also includes Pantotheic acid. Pantotheic acid functions as coenzyme A (CoA), which is considered necessary to metabolize acetic acid. Acetic acid is activated in conjugation with CoA to form acetyl-CoA, which is metabolized in TCA cycle. In enzymatical point of view, elimination of a product (acetic acid) is effective towards an acceleration of the metabolism of a substrate (acetaldehyde).
Preferably this food composition or supplements should be taken about 5 minutes prior to consumption of alcohol and in case of high alcohol consumption again whilst consuming alcohol. The mass of the food composition taken by the consumer should be in the range of about 70 to 120% of the mass of the alcohol included in the consumed drinks. A standard dose might include about 10. Og dextrose, 1.Og Vitamin C, 1.5g L-glutamine, 500mg cysteine, 40mg riboflavin, 100 mg succinic acid, 100 mg fumaric acid, 60mg coenzyme Ql 0, and about 10 mg Niacin (Vitamin B3). Preferably the relation of the components of the composition is oriented towards the above given relation. The overall dosage may be adapted to the body mass weight of the consumer.
The particular food composition, or dietary supplementation is intended to prevent too much acetaldehyde passing into the mitochondrial matrix and to suppress self- blockade of the enzymatic activity of ALDH and thus facilitate its the decomposition of acetaldehyde. The physiological risks in connection with alcohol consumption may therefore be significantly reduced by the use of the food composition according to the present invention, as this food composition or dietary supplementation facilitates in a synergetic manner an early decrease of the level of acetaldehyde after drinking and simultaneously provides a protective effect in respect of the suppression of the generation of free radicals.
Said food composition or dietary supplementation is preferably in such a form, preferably as ingredients of a kind of aperitif, that it allows the food composition to be consumed within a restaurant or a bar prior to consuming alcoholic drinks. Preferably a dosage for a person with a body weight of about 80 kg includes a dextrose fraction of approx. 75%, wherein the said dosage may have an overall weight of about 10 to 15, preferably 13.3g. Such a dosage is to provide a considerable moderation in degrading about 18ml alcohol.
The food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same, includes a dextrose fraction of about 75.2 mass%, i.e. a quantity of dextrose in the range from 7.2 to 12.8g, preferably 10.0 g within a dose of 13,3g.
The food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a Vitamin C fraction of about 7.5 mass% i.e a quantity of Vitamin C in the range from 0.78 to 1.18 g, preferably 1.Og, within a dose of 13.3g.
The food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a L-glutamine fraction of about 11.27 mass%, i.e. a quantity of said L-glutamine fraction in the range from 1.23 to 1.7 g, preferably 1.5g, within a dose of 13.3g.
The food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a cysteine fraction of about 3.76 mass%, i.e. a quantity of said cysteine fraction in the range from 460 to 540 mg, preferably 500mg, within a dose of 13.3g.
The food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a riboflavin fraction of about 0.30 mass% i.e. a quantity of said riboflavin in the range from 32 to 48 mg, preferably 40mg, within a dose of 13.3g.
The food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a succinic acid (Bernsteinsaure) fraction of about 0.752 mass%, i.e. a quantity of said succinic acid in the range from 90 to 110 mg, preferably lOOmg, within a dose of 133g.
The food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a fumaric acid (Fumarsaure) fraction of about 0.752 mass%, i.e. a quantity of said fumaric acid in the range from 90 to 110 mg, preferably lOOmg, within a dose of 13.3g.
The food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same includes a coenzyme fraction of about 0,451 mass%, i.e. a quantity of said coenzyme fraction in the range from 50 to 70 mg, preferably 60mg, within a dose of 13.3 g.
The food composition or dietary supplementation is preferably constituted in a manner wherein a dosage of same is in the form of tablets. Preferably, each tablet is so shaped and dimensioned that it allows said tablet to be easily swallowed.
Preferably, said tablets are in such a form that one dosage includes a plurality of those tablets.
The tablets may be accommodated within a dosage receptacle which includes a number of those tablets. It is possible for the food composition to be in the form of small tablets or balls, and to keep same in a small tube, while the volume of the food composition taken by the consumer can be determined with respect to the volume of alcohol which is expected to be consumed.
The food composition or dietary supplementation may also be in a form similar to sugar-cubes, or might be in the form of cryopowder.
The food composition or dietary supplementation may be separated into separate subunits. It is possible to provide one unit, for example a capsule including the Vitamin C fraction, cysteine, riboflavin, succinic acid, fumaric acid and coenzyme QlO, whilst most of the dextrose fraction is kept in separate units, capsules, tablets or the like.
It is possible to add further substances such as fruit juice extracts, curcuma, tannin, a powder of Panax notoginseng, and Vinca rosea in suitable amounts. Oolong tea, aloe vera and spiral water algae might also be added.
The food-composition or dietary supplementation may also be in the form of a liquid, in particular a sirup-type liquid. It is possible to provide the food composition in the appearance of a soft drink in a small bottle.
The particular food composition or dietary supplementation is considered to provide the following achievements:
1. Reduction of ethanol metabolism by slowing down the process of ethanol oxidation into acetaldehyde, to prevent accumulation of acetaldehyde in the first place.
2. Stimulation of the activity of ALDH and avoiding any blockade of its enzymatic activity.
3. Speeding up the reaction from acetaldehyde to acetic acid and the further decomposition in the citrate cycle.
4. Improving the levels of those anti-oxidants of the alcohol consumer, which specially protect against toxic effects of acetaldehyde. The first achievement
is believed to be reached by the intake of a large dose of dextrose sugar (glucose). Glucose is rapidly oxidised in the cytosol of liver cells using the same cytosol NAD+ pool used by ethanol to be converted into acetaldehyde. Because the amount of cytosolic NAD+ is limited and can only constantly be reproduced from NADH+H much less acetaldehyde accumulates.
The second achievement is also believed to be achieved by the intake of a large dose of glucose. Glucose augments the enzymatic activity of ADH as well as of ALDH. When a large glucose load occurs in the cytosol of liver cells then there is no possibility that the acetaldehyde reaches levels which could lead to inactivation of ALDH or to mitochondrial destruction.
The third achievement
is believed to be performed by
a) Accelerating the reoxidation from NADH+H+ to NAD+ by speeding up the transport of electrons through the inner mitochondrial membrane
b) Accelerating the Krebs cycle
It is believed to be achieved by the inclusion of coenzyme Qi0 and riboflavin. Riboflavin will quickly be transformed to FMN, which together with coenzyme Qi0 is the determining substance for the speed of the reoxidation of NADH+H+ to NAD+ in the mitochondrial matrix. Acetaldehyde needs NAD+ when it is metabolised to acetic acid. Within this reaction NAD+ is transformed into NADH+H+. Because the availability of NAD+ is limited in the mitochondrial matrix NADH+H+ has to be re-transformed into NAD+ to serve again for acetaldehyde decomposition. This reaction is only possible because FMN and coenzyme Qi0 absorb the electrons of NADH+H+ and shuttle them through the mitochondrial membrane. The more FMN and coenzyme Qi0 are available, the more this process is speeded up and, because more NAD+ is available, the metabolism of acetaldehyde is accelerated.
The inclusion of coenzyme Qio also makes also sense because its level decreases in the human body with progressing age.
The activation of the Krebs (citrate) cycle is believed to be achieved by the inclusion of succinic acid and fumaric acid. Both substances activate the second half of the citrate cycle and thereby activate the aerobic oxidation process in mitochondria. L-glutamine helps to speed up the mitochondria-cytosolic malate- asparate shuttle, which plays a key role in the course of intoxication by acetaldehyde. It also speeds up the succinate oxidation process by preventing oxalic and acetic inhibition of succinate dehydrogenase.
The fourth achievement,
the elevation of anti-oxidant levels, is believed to be achieved by the inclusion of cysteine, ascorbic acid and also of L-glutamine. Cysteine should provide a strong anti-oxidant effect as well as ascorbic acid. The human body transforms cysteine to gluthatione which specially protects against the toxic effects of acetaldehyde. To reach an optimal level of gluthatione and to avoid cysteine being transformed to cystine, it is important to combine cysteine with glutamine and give twice as much ascorbic acid as cysteine.
By taking the mentioned substances, it is expected that the level of acetaldehyde after drinking alcohol will be remarkably reduced and flushing symptoms at least diminished. The other known side-effects of acetaldehyde such as headaches and hangovers should also disappear.

Claims

1. Food composition, or dietary supplementation for reducing alcohol induced rise of esophagenal and oropharyngolarynal cancer by moderating an alcohol degradation process in respect to ethanol metabolism within the human body, including the following substances in physiologically relevant amount:
niacin (Vitamin B3), dextrose,
Vitamin C,
L-glutamine, cysteine, riboflavin, succinic acid, and/or fumaric acid, coenzyme QlO.
2. Food composition or dietary supplementation according to claim 1, wherein a dose of same has a weight of about 13.8g, said dose being configured in a manner which allows same to be consumed within a restaurant or a bar prior to the consumption of alcohol.
3. Food composition or dietary supplementation according to claim 1 or 2, wherein a dose of same includes a dextrose fraction of about 75.2 mass%.
4. Food composition or dietary supplementation according to at least one of claims 1 to 3, wherein a dose of same includes a Vitamin C fraction of about 7.5 mass%.
5. Food composition or dietary supplementation according to at least one of claims 1 to 4, wherein a dose of same includes a L-glutamine fraction of about 11.28 mass%.
6. Food composition or dietary supplementation according to at least one of claims 1 to 5, wherein a dose of same includes a cysteine fraction of about 3.76 mass%.
7. Food composition or dietary supplementation according to at least one of claims 1 to 6, wherein a dose of same includes a riboflavin fraction of about 0.3 mass%.
8. Food composition or dietary supplementation according to at least one of claims 1 to 7, wherein a dose of same includes a succinic acid fraction of about 0.752 mass%.
9. Food composition or dietary supplementation according to at least one of claims 1 to 8, wherein a dose of same includes a fumaric acid fraction of about 0.752 mass%.
10. Food composition or dietary supplementation according to at least one of claims 1 to 9, wherein a dose of same includes a coenzyme fraction of about 0.451 mass%.
11. Food composition or dietary supplementation according to at least one of claims 1 to 10, wherein same is in the form of tablets.
12. Food composition or dietary supplementation according to at least one of claims 1 to 10, wherein a dose of same includes a plurality of small tablets or capsules.
13. Food composition or dietary supplementation according to at least one of claims 1 to 10, wherein said tablets or capsules are contained in a dosage receptacle.
14. Food composition or dietary supplementation according to at least one of claims 1 to 10, wherein said composition is of a sugar-cube type form.
15. Food composition or dietary supplementation according to at least one of claims 1 to 10, wherein same is in the form of cryopowder.
16. Food composition or dietary supplementation according to at least one of claims 1 to 10, wherein same is in the form of a small drink unit.
17. Food composition or dietary supplementation according to at least one of claims 1 to 10, wherein same is in the form of a sirup.
18. Food composition, or dietary supplementation for reducing alcohol induced rise of esophagenal and oropharyngolarynal cancer, said composition including niacin for affecting an alcohol degrading process in particular in respect to ethanol metabolism within the human body, and substances, in particular substances mentioned above, providing the following effects within the human body:
Reducing ethanol metabolism by slowing down the process of ethanol oxidation into acetaldehyde, to prevent accumulation of acetaldehyde in the first place;
- Stimulating the activity of ALDH and avoiding any blockade of its enzymatic activity;
Speeding up the reaction from acetaldehyde to acetic acid and further decomposition in the citrate cycle;
- Improving the levels of those anti-oxidants of the alcohol consumer which specially protect against toxic effects of acetaldehyde.
PCT/EP2005/009150 2005-07-29 2005-08-24 Composition for reducing the risk of alcohol induced esophagenal and oropharyngolaryngeal cancer WO2007016952A1 (en)

Priority Applications (21)

Application Number Priority Date Filing Date Title
PT06762860T PT1909600E (en) 2005-07-29 2006-07-27 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
CA2611389A CA2611389C (en) 2005-07-29 2006-07-27 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
EA200800427A EA012753B1 (en) 2005-07-29 2006-07-27 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
KR20137031344A KR101487848B1 (en) 2005-07-29 2006-07-27 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
AU2006278823A AU2006278823B2 (en) 2005-07-29 2006-07-27 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
PCT/EP2006/007466 WO2007017139A1 (en) 2005-07-29 2006-07-27 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
ES06762860T ES2386460T3 (en) 2005-07-29 2006-07-27 Composition to moderate alcohol metabolism and to reduce the risk of alcohol-induced diseases
KR1020077028054A KR101562271B1 (en) 2005-07-29 2006-07-27 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
UAA200800602A UA94713C2 (en) 2005-07-29 2006-07-27 Composition for moderating alcohol metabolism and for reducing risk of alcohol induced diseases
AT06762860T ATE554663T1 (en) 2005-07-29 2006-07-27 COMPOSITION FOR CONTROLLING ALCOHOL METABOLISM AND REDUCING THE RISK OF ALCOHOL-RELATED DISEASES
JP2008523251A JP5371428B2 (en) 2005-07-29 2006-07-27 Composition for reducing alcohol metabolism and reducing the risk of alcohol-induced diseases
CN2006800278400A CN101232822B (en) 2005-07-29 2006-07-27 Composition for reducing the risc of ethanol metabolism and alcohol induced neuropathy
EP06762860A EP1909600B1 (en) 2005-07-29 2006-07-27 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
US11/997,127 US8580750B2 (en) 2005-07-29 2006-07-27 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
DK06762860.2T DK1909600T3 (en) 2005-07-29 2006-07-27 Composition for moderation of alcohol metabolism and to reduce the risk of alcohol-caused diseases
PL06762860T PL1909600T3 (en) 2005-07-29 2006-07-27 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
SI200631337T SI1909600T1 (en) 2005-07-29 2006-07-27 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
HK08110628.1A HK1117709A1 (en) 2005-07-29 2008-09-24 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
HRP20120489TT HRP20120489T1 (en) 2005-07-29 2012-06-12 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
JP2013091972A JP5785581B2 (en) 2005-07-29 2013-04-25 Composition for reducing alcohol metabolism and reducing the risk of alcohol-induced diseases
US14/058,388 US9402849B2 (en) 2005-07-29 2013-10-21 Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases

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EP2583686A4 (en) * 2010-06-19 2013-11-06 Amano Enzyme Inc Agent for reducing acetaldehyde in oral cavity

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