Induced Diseases

The present invention refers to a liquid composition comprising Vitamin C, L-glutamine and/or L-glutamic acid, L-cysteine and/or L-cystine, riboflavin, succinic acid, fumaric acid, coenzyme Q 10, niacin and hydrogen carbonate, phosphate or any other buffering system, in particular for use as a food composition, dietary or food supplementation, and pharmaceutical composition, respectively. The present invention refers further to the composition according to the invention for use in the treatment and/or prophylaxis of neuropathy, neurodegenerative diseases including late-onset Alzheimer's disease, tumour metastasis and cancer, in particular of pancreatic, esophageal, oropharyngolaryngeal, liver, colorectal, lung and/or breast cancer

The present invention particularly addresses the problem of accumulation of acetaldehyde after rapid alcohol degradation i.e. alcohol metabolism as may occur in most people of Non- Caucasian type genetic structure. It is assumed that drinking alcoholic beverages is associated with an increased risk for neuropathy diseases. Ethanol induces a lot of effects on the brain and nerve system which leads to change in behaviour, motor coordination and, in the extreme case, brain damage. In particular, peripheral nerve polyneuropathy is commonly observed in alcoholic patients. One possible mediator of the alcohol effects is acetaldehyde, a highly toxic metabolite of ethanol. Acetaldehyde is a highly reactive molecule with oxidative activity and has cytotoxic effects and modifies proteins in the cells, leading to their dysfunction.

It is also assumed that drinking alcoholic beverages is associated with an increased risk for neurodegenerative diseases. These diseases are expected as being caused by the deposition of inclusion bodies in the neuronal cells, and finally disappearance of the cells. Oxidative stress and the following lipid peroxidation caused by oxidants, such as reactive oxygen species, are reported to play an important role in the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and cerebral ischemia. Acetaldehyde is thus thought to be the cause of several alcohol-induced neuronal changes. Acetaldehyde is also 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. It is also assumed that drinking alcoholic beverages is associated with an increased risk for certain kinds of cancer including pancreatic, liver, colorectal, lung, breast, esophageal and oropharyngolarynal cancer. The association of alcohol consumption with increased risk for esophageal 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.

Furthermore, increased estrogen levels in female drinkers appear to be an important mechanism for development of breast cancer. One possible mechanism for the increase of estrogen is that overproduced acetic acid after drinking is converted to steroids. The possible role of acetaldehyde for the alcohol-induced breast cancer appears to be evident.

A recent paper (Lancet Oncol 7: 149-156, 2006) discussed the relationship between alcohol consumption and the risk of colorectal cancer and lung cancer. Ethanol taken into the body is eliminated by its oxidation, mainly in the liver. Ethanol (CH ₃ CH ₂ OH) is first metabolised to acetaldehyde (CH ₃ CHO) by alcohol dehydrogenase (ADH), and then acetaldehyde (CH ₃ CHO) is further metabolised to acetic acid (CH ₃ COOH) by aldehyde dehydrogenase (ALDH), mainly by liver aldehyde dehydrogenase 2 (ALDH2). CH3CH2OH + NAD→ CHsCHO + NADH + H ⁺

CHsCHO + NAD + H2O→ CHsCOOH + NADH + H ⁺

Most of acetaldehyde generated during alcohol metabolism is promptly eliminated by ALDH2, the low Km ALDH. 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. A mutant allele, ALDH2*2, has a single point mutation (G— >A) in exon 12 of the active ALDH2*1 gene. This mutation results in a substitution of glutamic acid (Glu) at amino acid position 487 by lysine (Lys). ALDH2*2 encodes thus a catalytically inactive subunit and acts in a dominant negative fashion. 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, who have the active ALDH2*1 allele. 40-50% of East Asians have the 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 a 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. Deficiency of ALDH2 activity is associated with an increased risk of cancer and therefore acetaldehyde is regarded as a carcinogen. In fact, acetaldehyde can damage culture hepatocytes and results in secondary hyper proliferation.

It appears also evident that ALDH2 deficiency is associated with an increased risk of polyneuropathy and of late-onset Alzheimer' s disease. Moreover, sensory conduction time is significantly longer in Japanese alcoholic patients with hypoactive ALDH2*2 allele than that in active ALDH2* 1/2*1 homozygotes, indicating dysfunction of peripheral neurons of the formers. The experimental neuronal cell system, in which ALDH is genetically inactivated, becomes highly vulnerable to exogenously added aldehyde metabolite, indicating that oxidative stress caused by acetaldehyde considerably damage neuronal cells. These results collectively suggest that oxidative stress induced by acetaldehyde may damage mitochondrial energy production and modify proteins in the neuronal cells, leading to form the deposition of modified proteins. These changes further damage cellular function and finally cause cell death. Therefore, acetaldehyde may closely be involved in the pathogenesis of polyneuropathy and/or neurodegenerative diseases such as late-onset Alzheimer's disease.

It is also assumed that ALDH2 deficiency is associated with an increase of the risk of breast cancer. Acetaldehyde has a lipophilic nature and accumulates in adipose tissues. Mammary gland is enriched in fat and other lipophilic tissues. It is concluded that drinking alcoholic beverages is associated with increases risk for breast cancer. The possible role of acetaldehyde for the alcohol-induced breast cancer is thus assumed as well.

For liver cancer it is known that Hepatitis viruses (HV), especially HVB and HVC, increase the risk of liver cancer. However, epidemiological surveys are considered to support that ALDH2 deficiency is also associated with an increased risk of liver cancer for alcohol drinkers with or without hepatitis viruses. This supports the notion that acetaldehyde is closely involved in the carcinogenesis of hepatocytes in human alcohol drinkers.

Additionally, it appears to be evident that alcoholic beverages are carcinogenic to humans and causally related to cancer of the oral cavity, pharynx, larynx and esophagus. In particular, it appears that ALDH2 deficiency is also associated with an increased 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.

In Japan, alcoholic pancreatitis is the most common type (68.5%) of chronic pancreatitis in males. Chronic pancreatitis has been indicated as a risk factor for pancreatic cancer. While smoking is a well- documented risk factor for the development of pancreatic cancer, it appears that ALDH2 deficiency increases the risk of pancreatic cancer in smokers and it is assumed that alcohol increases the risk of pancreatic cancer of smokers. These data collectively suggest that alcohol, most possibly its metabolite acetaldehyde, takes part in the carcinogenesis of pancreatic cells. It appears that ALDH2 deficiency is also associated with an increase of the risk of pancreatic cancer. 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. By now only compositions in solid dosage form are available. Since the amount of composition to be administrated to a subject having a desired effect, may be relative high, e.g. about 3 g, the composition has to be administrated in form of large capsules or tablets or a plurality of tables have to be taken.

Therefore, it is an object of the present invention to provide compositions effective in reducing alcohol induced diseases in an appropriate dosage form.

The object is solved by the subject-matter as defined in the claims.

The advantage of the composition of the present invention which is provided in a liquid dosage form is that even high amounts of the composition can be administrated easily by drinking. Thus, the full effects of the composition can be achieved easily. The term "neuropathy" as used herein, refers to any disease or abnormality of the neurons of the nervous system. In particular "neuropathy" means a disorder of the peripheral nervous system, affecting nerves anywhere except brain and the spinal cord. A non-limiting example for neuropathy is alcoholic polyneuropahy which is characterized by numbness, abnormal sensations called dysesthesias and allodynias that occur either spontaneously or in reaction to external stimuli, and a characteristic form of pain, called neuropathic pain or neuralgia.

The term "neurodegenerative disease" as used herein, refers to any disease or abnormality of the nervous system caused by deterioration of neurons, which include death of neurons and functional loss of neurotransmitters. Non-limiting examples for a neurodegernative disease are Alzheimer's disease and Parkinson's disease.

The term "food composition" as used herein, refers to any kind of composition which is eatable and/or drinkable without causing toxic symptoms in the subject eating or drinking the respective composition.

The term "supplement", "dietary supplement" or "food supplement" as used herein, refers to a composition which is consumed in addition to the daily meals or in between. The term "late-onset Alzheimer's disease" as used herein, refers to the onset of Alzheimer's disease in elderly people, in particular in people being 65 years old and older.

The term "flushing syndrome" as used herein, refers to the flushing as a consequence of drinking alcohol. Flushing is associated with the erythema (reddening caused by dilation of capillaries) of the face, neck, and shoulder, after consumption of alcohol. Flushing after alcohol consumption is often associated with a range of symptoms: dizziness, nausea, headaches, an increased pulse, occasional extreme drowsiness, and occasional skin swelling and itchiness. There symptoms are collectively called "Flushing syndrome" or "Asian flush".

The term "oropharyngolaryngeal cancer" as used herein, refers to cancers derived from oral cavity, pharynx, larynx or upper esophagus. At early stage of the cancer of this area, the origin could be determined. However, very often, the cancer of this area is found at the late invasive stage and the origin cannot be determined. Therefore, cancers arising from these sources are collectively termed "oropharyngolaryngeal cancer".

The term "dosage form" as used herein, refers to an amount of medication to be taken at one time, optionally in regular intervals. According to the present invention the object is attained by a liquid composition comprising the following substances:

Vitamin C, L-glutamine and/or L-glutamic acid, L-cysteine and/or L-cystine, riboflavin, succinic acid, fumaric acid, coenzyme Q10, niacin and optionally dextrose.

The single substances of the composition according to the present invention are solved in a liquid, in particular in water. For preventing the formation of sediments hydrogen carbonate, phosphate or any other buffering system should be added. The addition of hydrogen carbonate (also called bicarbonate), phosphate or any other buffering system prevents the acidic effect of fumaric acid and succinic acid by neutralizing.

In a preferred embodiment the composition according to the present invention comprises hydrogen carbonate, phosphate or any other buffering system in a final concentration ranging from and including 0.0036 M to 4.55 M, 0.0091 M to 1.82 M, 0.0136 M to 0.45M or 0.036 M to 0.073 M.

In another preferred embodiment the composition according to the present invention comprises hydrogen carbonate, phosphate or any other buffering system in a final concentration of about 0.0036 M, 0.0055 M, 0.0073 M, 0.0091 M, 0.0136 M, 0.019 M, 0.0227 M, 0.027 M, 0.0318 M, 0.036 M, 0.055 M, 0.073 M, 0.091 M, 0.136 M, 0.18 M, 0.45 M, 0.91 M, 1.82 M or 4.55 M. In a preferred embodiment as riboflavin fraction of the composition of the present invention riboflavin phosphate sodium salt or water soluble compounds containing riboflavin is used.

In a preferred embodiment the composition according to the present invention comprising coenzyme Q10, riboflavin, L-cystine, niacin, Vitamin C, succinic acid, fumaric acid, L- glutamine and optionally dextrose.

The composition according to the present invention stimulates the activity or enhances the production of a particular alcohol dehydrogenase enzyme, namely the ADH, so that the production of acetaldehyde and the ethanol metabolism process is accelerated and the alcohol induced peak load on the human organism is reduced. Furthermore, the enzymatic activity of the aldehyde dehydrogenase ALDH2 is enhanced, so that the metabolisation of acetaldehyde is supported.

The composition of matter according to the present invention accelerates the disappearance of alcohol and acetaldehyde after drinking. The composition is active preferably in ALDH2* 1/2*1 homozygote and ALDH2* 1/2*2 heterozygote subjects. The composition according to the present invention effectively accelerates alcohol metabolism and suppresses the secretion of acetaldehyde from salivary glands. Therefore, the composition according to the present invention can be used to diminish the risk of neuropathy, neurodegenerative diseases, e.g. late-onset Alzheimer's disease, and of cancer, in particular of pancreatic, esophageal, oropharyngolarynal, colorectal, lung, liver and breast cancer.

By reducing the peak of excess acetaldehyde entering the blood stream, thereby lowering the risk of damage to vital organs and functions of the human body, the composition according to the present invention lowers the risk of several forms of cancer such as pancreatic, esophageal, oropharyngolarynal, colorectal, lung, liver and/or breast cancer.

By decreasing the concentration of blood acetaldehyde after drinking the composition according to the present invention decreases the risk of pancreatic cancer, preferably for alcohol drinkers with smoking habit, especially those who have the ALDH2*2 allele.

By eliminating acetic acid through activation of the tricarboxylic acid (TCA) cycle and electron transport system, and consequently by preventing the synthesis of steroids including estrogen the composition according to the invention reduces the risk of breast and liver cancer, preferably for alcohol drinkers, especially those who have the ALDH2*2 allele.

The composition according to the present invention contains several substances, which are often deficient in patients with alcoholic neuropathy. The composition is thus effective in reducing a flushing syndrome, reducing an alcoholic intoxication, reducing the likelihood of headaches and also helps to avoid or ease an alcohol induced hangover the day after. 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). Said niacin-fraction is provided to accelerate ethanol metabolism.

Preferably this composition should be taken prior to consumption of alcohol, e.g. about 15 to 5 minutes and in case of high alcohol consumption again whilst consuming alcohol. The mass of the 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 1.0 g Vitamin C, 1.0 g L-glutamine and/or L-glutamic acid, 500 mg L-cysteine and/or L-cystine, 40 mg riboflavin, 100 mg succinic acid or one of its salts (e.g. succinate), 100 mg fumaric acid or one of its salts (e.g. fumarate), 100 mg coenzyme Q10, 10 mg niacin (Vitamin B3) and optionally 10.0 g dextrose. Additionally 4.0 ml of 0.4 M sodium hydrogen carbonate or any other buffering system is added for solubility reasons and for neutralization of the acidic effect of fumaric acid and succinic acid. 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. In a preferred embodiment the standard dose of the composition of the present invention includes 100 mg coenzyme Q10, 40 mg riboflavin, 500 mg L-cystine, 10 mg niacin, 1000 mg Vitamin C, 100 mg succinic acid, 100 mg fumaric acid and 1000 mg L-glutamine solved in 40 ml water and 4 ml of 0.04, 0.06, 0.08, 0.1, 0,15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.6, 0.8, 1, 1.5, 2, 5, 10, 20 and/or 50 M hydrogen carbonate, phosphate or any other buffering system is added.

In another preferred embodiment the standard dose of the composition of the present invention includes 100 mg coenzyme Q10, 40 mg riboflavin, 500 mg L-cystine, 10 mg niacin, 1000 mg Vitamin C, 100 mg succinic acid, 100 mg fumaric acid and 1000 mg L- glutamine solved in 40 ml water and 4 ml of 0.4 M sodium hydrogen carbonate is added.

The composition according to the present invention 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 the decomposition of acetaldehyde.

The physiological risks in connection with alcohol consumption may therefore be significantly reduced by the use of the composition according to the present invention, as this composition 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.

If the composition is to be administered as a food composition or food or dietary supplement it is preferably in such a form, preferably as ingredients of a kind of aperitif, that it allows the food composition or food or dietary supplement to be consumed within a restaurant or a bar prior to consuming alcoholic drinks. The food composition, food or dietary supplement is preferably constituted in a manner wherein a dosage of same is in a liquid form. Preferably, the composition according to the present invention is provided as a solution, emulsion or suspension. In another preferred embodiment the compounds of the composition according to the present invention are solubilized or microparticulate active agents. The volume of the composition according to the present invention taken by the consumer can be determined with respect to the volume of alcohol which is expected to be consumed. 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 composition according to the present invention may also be in the form of a liquid, in particular a syrup-type liquid or a drink. It is possible to provide the composition in the appearance of a soft drink in a small bottle. The food composition, food or dietary supplement taken orally may supplement the diet. The food composition, food or dietary supplement may also be provided in bars, drinks, shakes and other food products. In general, a food composition, food or dietary supplement is not intended to be the sole item of a meal or diet. The food composition, food or dietary supplement may be taken before, after or simultaneously with a meal. The food composition, food or dietary supplement may be taken once or several times a day. The food composition, food or dietary supplement may be taken at any time of day.

Preferably, the composition according to the present invention comprises a niacin fraction in a quantity ranging from and including 0.01 to 2 mg/kg body weight, 0.1 to 1.5 mg/kg body weight or 0.2 to 0.75 mg/kg body weight, preferably 0.125 mg/kg body weight. Preferably, the composition according to the present invention comprises a L-cystine or L- cysteine fraction in a quantity ranging from and including 1 to 15 mg/kg body weight, 2.5 to 10 mg/kg body weight or 5 to 8 mg/kg body weight, preferably 6.25 mg/kg body weight.

Preferably, the composition according to the present invention comprises a L-glutamine and/or L-glutamic acid fraction in a quantity ranging from and including 1 to 20 mg/kg body weight, 5 to 15 mg/kg body weight or 7 to 13 mg/kg body weight, preferably 12.5 mg/kg body weight.

Preferably, the composition according to the present invention comprises a riboflavin fraction in a quantity ranging from and including 0.05 to 2 mg/kg body weight, 0.1 to 1.5 mg/kg body weight or 0.2 to 0.75 mg/kg body weight, preferably 0.5 mg/kg body weight.

Preferably, the composition according to the present invention comprises a succinic acid fraction in a quantity ranging from and including 0.1 to 10 mg/kg body weight, 0.5 to 5 mg/kg body weight or 0.75 to 2 mg/kg body weight, preferably 1.25 mg/kg body weight.

Preferably, the composition according to the present invention comprises a fumaric acid fraction in a quantity ranging from and including 0.1 to 10 mg/kg body weight, 0.5 to 5 mg/kg body weight or 0.75 to 2 mg/kg body weight, preferably 1.25 mg/kg body weight. Preferably, the composition according to the present invention comprises a coenzyme Q10 fraction in a quantity ranging from and including 0.1 to 10 mg/kg body weight, 0.5 to 5 mg/kg body weight or 0.75 to 2 mg/kg body weight, preferably 1.25 mg/kg body weight.

Preferably, the composition according to the present invention comprises a Vitamin C fraction in a quantity ranging from and including 1 to 20 mg/kg body weight, 5 to 15 mg/kg body weight or 7 to 13 mg/kg body weight, preferably 12.5 mg/kg body weight. Optionally, the composition is constituted in a manner wherein a dosage of same, comprises a dextrose fraction ranging from and including 10 to 200 mg/kg body weight, 50 to 150 mg/kg body weight or 70 to 130 mg/kg body weight, preferably 125 mg/kg body weight.

Preferably a dosage for a person with a body weight of about 80 kg includes a dextrose fraction of approx. 75%. Such a dosage is to provide a considerable moderation in degrading about 18 ml alcohol.

Preferably, the composition is constituted in a manner wherein a dosage of same includes a Vitamin C fraction of about 35 mass% i.e. a quantity of Vitamin C in the range from 0.78 to 1.18 g, preferably 1.0 g, within a dose of 2.85 g in 44 ml for a person with a body weight of about 80 kg.

Preferably, the composition is constituted in a manner wherein a dosage of same includes a L-glutamine and/or L-glutamic acid fraction of about 35 mass%, i.e. a quantity of said L- glutamine and/or L-glutamic acid fraction in the range from 0.78 to 1.18 g, preferably 1.0 g, within a dose of 2.85 g in 44 ml for a person with a body weight of about 80 kg.

Preferably, the composition is constituted in a manner wherein a dosage of same includes a L-cystine or L-cysteine fraction of about 17.6 mass%, i.e. a quantity of said L-cystine or L- cysteine fraction in the range from 460 to 540 mg, preferably 500 mg, within a dose of 2.85 g in 44 ml for a person with a body weight of about 80 kg.

Preferably, the composition is constituted in a manner wherein a dosage of same includes a riboflavin fraction, preferably riboflavin sodium phosphate or water soluble compounds containing riboflavin of about 1.41 mass% i.e. a quantity of said riboflavin in the range from 32 to 48 mg, preferably 40mg, within a dose of 2.85 g in 44 ml for a person with a body weight of about 80 kg. Preferably, the composition is constituted in a manner wherein a dosage of same includes a succinic acid fraction or one of its salts (e.g. succinate) of about 3.5 mass%, i.e. a quantity of said succinic acid in the range from 90 to 110 mg, preferably 100 mg, within a dose of 2.85 g in 44 ml for a person with a body weight of about 80 kg. Preferably, the composition is constituted in a manner wherein a dosage of same includes a fumaric acid fraction or one of its salts (e.g. fumarate) of about 3.5 mass%, i.e. a quantity of said fumaric acid in the range from 90 to 110 mg, preferably 100 mg, within a dose of 2.85 g in 44 ml for a person with a body weight of about 80 kg. Preferably, the composition is constituted in a manner wherein a dosage of same includes a coenzyme Q10 fraction of about 3.5 mass%, i.e. a quantity of said coenzyme fraction in the range from 30 to 200 mg, preferably 100 mg, within a dose of 2.85 g in 44 ml for a person with a body weight of about 80 kg. Preferably, the composition is constituted in a manner wherein a dosage of same includes a niacin fraction of about 0.35 mass%, i.e. a quantity of said coenzyme fraction in the range from 1 to 20 mg, preferably 10 mg, within a dose of 2.85 g in 44 ml for a person with a body weight of about 80 kg. Optionally, the composition is constituted in a manner wherein a dosage of same, includes a dextrose fraction of about 77.82 mass%, i.e. a quantity of dextrose in the range from 7.2 to 12.8 g, preferably 10.0 g within a dose of 12.85 g in 44 ml for a person with a body weight of about 80 kg. Preferably, the standard dose of the composition according to the invention comprises a sodium hydrogen carbonate fraction ranging from and including 0.1 to 50 mg/kg body weight, 0.5 to 25 mg/kg body weight, 1.5 to 20 mg/kg or 1 to 8 mg/kg body weight, preferably 1.68 mg/kg body weight. In another preferred embodiment the composition according to the invention is constituted in a manner wherein a dosage of same includes a sodium hydrogen carbonate fraction of about 4.5 mass%, i.e. a quantity of said sodium hydrogen carbonate fraction in the range from 1 to 200 mg, preferably 134.4 mg, within a dose of 2.9844 g for a person with a body weight of about 80 kg. More preferably each ingredient of the composition is in the range from about 0.01 to about 100 gram, preferably from about 0.05 to 50 gram.

The composition is considered to provide the following achievements: 1. Acceleration of ethanol metabolism by enhancing the process of ethanol oxidation into acetaldehyde.

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 and second achievements are believed to be performed by a) Accelerating ADH and ALDH reactions by constantly providing coenzyme NAD b) Accelerating the reoxidation from NADH+H ⁺ to NAD in the electron transport system c) Accelerating the transportation of NAD through mitochondrial membrane

NAD (nicotinamide adenine dinucleotide), active form of niacin functions as a coenzyme in both ADH (catalyzing the reaction of ethanol to acetaldehyde) and ALDH (catalyzing the reaction of acetaldehyde to acetic acid) reactions. The necessity of NAD for alcohol metabolism is well documented. However, the simple increase in the level of NAD in the cytosol does not necessary work, because NAD is easily reduced to NADH during alcohol oxidation to acetaldehyde. The amount of NAD is limited in the cell. The speed of ethanol oxidation is mainly determined by the availability of NAD. Therefore, to continue these reactions, NADH + H ⁺ should be regenerated to NAD. NADH cannot penetrate the mitochondrial membrane. Therefore, NADH has to be reoxidized to NAD via malate/aspartate shuttle. Oxaloacetate can be reduced to malate with the aid of NADH. Malate can penetrate the mitochondrial membrane and then oxidized to oxaloacetate to form NADH in the mitochondria. NADH is then oxidized to NAD in the electron transport system. In order to maintain oxaloacetate -> malate reaction in the cytosol, oxaloacetate should move to the cytosol. Due to the impermeability of the mitochondrial membrane to oxaloacetate, it must react with glutamic acid to form aspartic acid and a-ketoglutarate before transport through the mitochondrial membrane and reconstitution to oxaloacetate in the cytosol. The inappropriate operation of malate/asparate shuttle causes the reduction of pyruvate to lactate. The massive production of lactate may lead to lactic acidosis.

The composition according to the present invention contains glutamine which is easily converted to glutamic acid as well as fumaric acid and succinic acid. The latter two materials are easily metabolized to malate in the Krebs cycle. Our invention effectively supports the operation of malate/asparate shuttle to regulate NAD for ADH.

Riboflavin will quickly be transformed to FMN, which together with coenzyme Qio is the determining substance for the speed of the reoxidation of NADH+H ⁺ to NAD ⁺ in the mitochondrial electron transport system. The more FMN and coenzyme Qio are available, the more this process is speeded up and, because more NAD is available, the metabolism of acetaldehyde as well as ethanol is accelerated.

It is known that the inclusion of coenzyme Qio decreases in the human body with progressing age.

The third achievement, the activation of the Krebs (citrate) cycle is 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. They are easily converted to oxaloacetic acid, which reacts with acetyl-CoA (metabolically active form of acetic acid) for metabolism to carbon dioxide and water. Therefore, these compounds stimulate the elimination of acetic acid.

The fourth achievement, the elevation of anti-oxidant levels, is achieved by the inclusion of L-cysteine, ascorbic acid (vitamin C) and also of L-glutamine and/or L-glutamic acid. Cysteine should provide a strong anti-oxidant effect as well as ascorbic acid. The human body transforms cysteine and glutamine to glutathione (γ-glutamyl-cysteinyl-glycine), which specially protects against the toxic effects of acetaldehyde. To reach an optimal level of gluthatione, it is important to combine cysteine with glutamine and give twice as much ascorbic acid as cysteine.

By administering the mentioned substances, 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.

Thus, the present invention relates to a composition for reducing alcohol induced risk of neuropathy, neurodegenerative diseases including late-onset Alzheimer's disease and of cancer, in particular of esophageal, oropharyngolarynal, colorectal, lung, liver, breast and/or pancreatic cancer by accelerating an alcohol degradation process in respect to ethanol metabolism within the human body. The composition of the present invention includes the following substances in physiologically relevant amount: Vitamin C, L-glutamine and/or L- glutamic acid, L-cysteine and/or L-cystine, riboflavin, succinic acid, fumaric acid, coenzyme Q10, niacin and optionally dextrose. Another aspect of the invention refers to the use of the composition according to the present invention for reducing alcohol induced risk of neuropathy, neurodegenerative diseases including late-onset Alzheimer's disease and of cancer, in particular of esophageal, oropharyngolarynal, colorectal, lung, liver, breast and/or pancreatic cancer. Another aspect of the invention refers to the use of the composition according to the present invention for accelerating the alcohol degradation process within the human body.

In a further aspect of the present invention the composition according to the present invention can be used as a food composition, food or dietary supplement. Furthermore, the compositions according to the present invention can be used as a pharmaceutical. The pharmaceutical or medicament, respectively, can be used for example for the manufacture of a medicament for the treatment and/or prophylaxis of cancer. By way of non-limiting example, such cancers can be selected from breast cancer, liver cancer, pancreatic cancer, esophageal cancer, colorectal cancer, lung cancer and oropharyngolaryngeal cancer.

In a further embodiment the composition of the present invention can also be used for the manufacture of a medicament for the treatment and/or prevention of tumour metastasis in general.

In a further embodiment, the composition of the present invention can also be used for the manufacture of a medicament for the treatment and/or prophylaxis of neuropathy and treatment and/or prophylaxis of a neurodegenerative disease, in particular of late-onset Alzheimer' s disease.

In a further embodiment the composition according to the present invention can also be used for the manufacture of a medicament for the treatment and/or prophylaxis of hangover, flushing syndrome, headache and/or alcoholic intoxication.

In a further embodiment the composition according to the present invention is present in the form of a liquid. In another embodiment the composition according to the present invention is in the form of a small drink unit. In another embodiment the composition according to the present invention is in the form of a syrup. Preferably, the composition according to the present invention is a liquid, more preferably the liquid is water. Furthermore preferably, the single substances of the composition according to the present invention are solved in a liquid, in particular in water.

In a further aspect the present invention relates to a food composition, food or dietary supplementation, and pharmaceutical composition according to the present invention for reducing alcohol induced risk of neuropathy and/or neurodegenerative diseases including late-onset Alzheimer's disease, esophageal cancer, oropharyngolarynal cancer, breast cancer, liver cancer, lung cancer, colorectal cancer and/or pancreatic 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:

- Accelerating ethanol metabolism by enhancing 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.

As mentioned above, the present invention relates to a composition comprising Vitamin C, L-glutamine and/or L-glutamic acid, L-cysteine and/or L-cystine, riboflavin, succinic acid, fumaric acid, coenzyme Q10, niacin and optionally dextrose. As mentioned above there are various embodiments of this composition.

In a further aspect the present invention relates to a method of treating a disorder, disease or condition in a subject in need of treatment and/or prevention, which method comprises administering to said subject an effective amount of composition according to the present invention. In particular said method of treatment may be for the treatment and/or prevention of neuropathy, of a neurodegenerative disease, in particular of late-onset Alzheimer's disease, of hangover, flushing syndrome, headache, alcoholic intoxication, tumour metastasis and/or cancer, in particular of breast cancer, liver cancer, colorectal cancer, lung cancer, pancreatic cancer, esophageal cancer and oropharyngolaryngeal cancer. The following examples explain the present invention but are not considered to be limiting. Examples:

Example 1 : Preparation of the supplement solution

The supplement consists of the following ingredients:

Coenzyme Q10* 100 mg (CoQ10P40 250 mg)

Riboflavin phosphate sodium salt 54.8 mg (riboflavin 40 mg equivalent)

L-Cystine 500 mg

Niacin 10 mg

Ascorbic acid 1000 mg Succinic acid 100 mg

Fumaric acid 100 mg

L-Glutamine 1000 mg

Sodium hydrogen carbonate 4.0 ml of 0.4 M solution

All ingredients were dissolved in 40 ml H ₂ 0, and finally sodium hydrogen carbonate was added. Without sodium hydrogen carbonate, sediments remains.

Ingredients of the supplement except Coenzyme Q10 were purchased from Sigma Aldrich Japan (Tokyo, Japan). *CoQ10P40 (Nisshin Pharma, Tokyo Japan) was used as Coenzyme Q 10. CoQ10P40 contains 40 % weight of Coenzyme Q10 and easy soluble to water.

Example 2: Alcohol and volunteers Three healthy adult volunteers were agreed with alcohol consumption and blood sampling. Four hundred ml of red wine which contains 12.5% of ethanol was used as alcohol, and this amount is exactly same as 50 gram of ethanol. The supplement was administered orally to test subjects 20 min prior to alcohol ingestion. Example 3 : Blood sampling, and the measurement of blood ethanol

Seven ml of blood was obtained from the cubitus vein 30 min after finishing ingestion of alcohol. Two ml of blood was used for the determination of the ethanol concentration, and 5 ml for the determination of the acetaldehyde concentration. Control subjects ingested the same kind and amount of wine, but received no composition prior to the alcohol ingestion.

For the ethanol measurement, whole blood was stored at 4 °C in a heparin coated tube. Ethanol was measured by bio medical laboratories company BML, INC. (Shibuya-ku, Tokyo, Japan). Statistical analysis of the results was conducted by student-i test, and p<0.5 was defined as the level of significance. The results of this blood ethanol experiments are shown in the table 1 below. Table 1: The effects of supplement on human blood ethanol Supplement in liquid

Control

form

No.l 76 86

No.2 64 81

No.3 71 81

70.33333 82.66667

P=0.01 (student-i test)