WO2025163413A1

WO2025163413A1 - Compositions for blood alcohol reduction and liver detoxification in animal or human subjects

Info

Publication number: WO2025163413A1
Application number: PCT/IB2025/050475
Authority: WO
Inventors: Julie LAPOINTE; Michael Lapointe
Original assignee: Individual
Current assignee: Individual
Priority date: 2024-02-02
Filing date: 2025-01-16
Publication date: 2025-08-07
Anticipated expiration: 2026-08-02
Also published as: GB202401422D0

Abstract

Disclosed is a composition or medicament consisting, comprising or comprising essentially of, the ingredients (L, D or LD) methionine, vitamin C, a magnesium compound, vitamin B3 and vitamin B6, and it's use as a medicament for reducing blood alcohol concentration (BAC) as well as aiding detoxification of the liver. The compositions disclosed herein double and triple the rate at which BAC drops after intoxication.

Description

Compositions for blood alcohol reduction and liver detoxification in animal or human subjects

Field of the invention

This invention relates to compositions for detoxification of the liver, and in particular, but not exclusively, for increasing the rate at which blood alcohol is metabolised in animal or human subjects with an elevated blood alcohol concentration (BAC).

One very common and potentially fatal toxin which affects the liver is alcohol. Herein, alcohol refers principally to ethanol (ethyl alcohol) and BAC in turn refers to the alcohol composition found in blood when ethanol is absorbed into the bloodstream, for example, after consumption by drinking. Furthermore, herein, BAC is referred to in different terms, for example in percentage where 0.1 % BAC [weight/volume] equals 0.1 g/dL, which equals 100mg/dL. Breath alcohol, often measured instead of blood alcohol because it is generally recognised that breath alcohol (BrAC) is indicative of BAC. A change in BrAC is equivalent to a change in BAC. Thus, in percentage terms, for example, a 10% drop in BrAC is considered to be a 10% drop in BAC. The generally accepted ratio is 2100:1. In other words it is accepted that there is 2100 times more blood alcohol than the measured breath alcohol. However, they are not the same measure and there is a variation in that ratio. Ratios of between 1500 and 3000 have been reported. As an example, in the UK (except Scotland) the legal limit of BAC for driving a vehicle on a public road is 0.08% BAC (80mg/dL of alcohol in blood, and 0.000035% BrAC ( 35 pg/dL alcohol per dL breath= 0.035mg/dL). So, roughly there is 1/2000 the alcohol in breath, compared to the same volume of blood as far as UK driving law is concerned. Most errors in BrAC measurements seem to arise due to evaporation of ethanol that has just been ingested, rather than measuring its evaporation from the lung walls, giving rise to an apparent increase in the measured BrAC immediately after ingesting alcohol. For completeness, the urine legal driving limit is 107 mg/dL of urine.

The pleasant effects of alcohol consumption are very well documented, for example: euphoria, happiness, increased sociability, and decreased anxiety. The undesirable effects of alcohol consumption are also well known, such as: impairment of memory, cognition, motor and sensory functions, and aggressive behaviour in some cases. Some time after excessive consumption, there is a feeling of being generally unwell, known as a hangover, which has been attributed, in part to excess metabolites like acetaldehyde. Longer term health effects of continued excessive alcohol consumption are reported as: alcohol dependence, hypertension, heart disease, stroke, liver disease, increased risk of certain cancers, and compromised immune system.

Given the ubiquitous nature of alcohol, its social acceptance in most cultures and its pleasant effects, it is a very common to consume alcohol, even though the unpleasant effects and longer term health risks are generally known. This invention addresses the above mentioned problems associated with alcohol consumption by enhancing liver detoxification as measured by reducing the concentration of alcohol in a subject’s blood.

Once consumed as a beverage, alcohol passes into the blood via the stomach and upper intestinal tract quickly. From there, as reported by Samir Zakhari, Ph.D. in Alcohol Research & Health Vol 29, No 4 2006 pages 245-254 in a paper with the title ‘Overview: How is alcohol metabolised by the body by various metabolic mechanisms. The primary enzymes involved are aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH), cytochrome P450 (CYP2E1), and catalase. Variations in the genes for these enzymes have been found to influence alcohol consumption, alcohol- related tissue damage, and alcohol dependence. The consequences of alcohol metabolism include oxygen deficits (i.e., hypoxia) in the liver; interaction between alcohol metabolism by-products and other cell components, resulting in the formation of harmful compounds (i.e., adducts); formation of highly reactive oxygen-containing molecules (i.e., reactive oxygen species [ROS]) that can damage other cell components; and changes in the ratio of NADH to NAD+ (i.e., the cell’s redox state).

In Elsevier, Medical Hypotheses 140 (2020) 109638, David F. Wilson and Franz M. Matschinsky reported on ‘Ethanol metabolism: The good, the bad and the ugly’. In that paper, it is postulated that the three metabolic alcohol oxidisation systems in humans are:

1 . Alcohol dehydrogenase; ADH1 , KM = 1 .4 mM:

Ethanol + NAD+ Acetaldehyde + NADH + H+ (1)

2. Catalase; KM = 12 mM: Ethanol + H2O2 Acetaldehyde + 2 H2O (2)

3. Cytochrome P450 2E1 (CYP2E1); KM = 8-10 mM:

Ethanol + 02 + NADPH — > NADP+ + acetaldehyde + acetate

The chemistry behind these pathways is further explained in that paper.

Based on the chemistry, that paper provides an estimate for the normal rate at which BAC is metabolised of about 0.016%/hour (16mg/dL/hour) for men and about 0.018%/hour (18mg/dL/hour) for women. So, using these estimates, averaged to 0.017% BAC per hour reduction, one might expect to see about 0.000008% BrAC, as a normal metabolic reduction, using BrAC as a measure. Other reports find a 0.015% reduction in BAC.

Background

Many products are sold which are said to alleviate a hangover. For example, Figure 1 shows the numerous ingredients used in hangover treatments listed according to their popularity in products sold online via the trading platform Amazon US, as of December 2019. It is apparent that various vitamins are popular, as well as plant extracts and some metal compounds.

Some examples of such remedies are:-

Life Extension Anti-Alcohol Complex https://www.lifeextension.com/vitamins-supplements/item02240c/anti-alcohol- hepatoprotection-complex?oldltem=02140

Life Extension Anti-Alcohol Complex uses vitamin C, vitamin B1, vitamin E, selenium, zinc, benfotiamine, glutathione, and N-acetyl-L-cysteine which are claimed to reduce oxidative stress and help the body manage the toxic effects of the metabolite acetaldehyde. The formula also incorporates chlorophyllin, grapeseed extract, milk thistle extract, and trans-resveratrol to protect DNA and support healthy liver function. Clove extract is also included in the formulation to promote the body's natural detoxification process, counteract oxidative stress, and encourage a healthy inflammatory response. No clinical trial results are advertised with this product, but it is directed at improving liver function and has good sales reviews. Safety Shot https://safetyshotofficial.com/

Safety Shot has garnered much attention since, and leading up to, its launch in December 2023 by leveraging the power of social media influencer marketing. The product contains a blend of vitamins, minerals, and nootropics, which an article in Forbes states can reduce BAG by 50% in 30 minutes. Studies not available to the public have reportedly shown BAG reduction of 0.079% BAC/hour, while the control group exhibited a 0.01% BAC/hour reduction. The company has also commissioned a larger double-blinded placebo-controlled trial, but no data from the trial are currently available.

Some attempts have been made to conduct trails on other remedies (with various trade names), some of which are described below:-

Phyllpro

In Pharmaceutical Biology 2019, VOL. 57, NO. 1 , 145-153 https://doi.Org/10.1080/13880209.2019.1585460

Annie George, Jay K. lldani and Ashril Yusof reported on the Effects of Phyllanthus amarus leaves on hangover symptoms. In a small trial, an extract of the plant Phyllanthus amarus (given the trade name Phyllpro), taken orally at 750mg/day for ten days prior to alcohol intoxication, showed a slightly increased rate for metabolising blood alcohol after intoxication, i.e, BAC reduced from 0.130 to 0.00% in 11 hours for the medicated group, and from 0.140 to 0.05% in 10 hours for the unmedicated placebo group. Given that natural metabolic reduction (as reported by Wilson and Matschinsky in Elsevier mentioned above) is around 0.016% per hour, then a 0.130% reduction over 11 hours (average of 0.012% per hour) is underwhelming.

Formula RM88

In Pharmacology & Pharmacy Vol.11 No.06(2020), Article I D: 101161 , 13 pages https ://www. scirp . org/htm I/3-2501111_101161.htm

E. Russell Vickers reported that herbal and natural compounds were selected that could potentially reduce BAC, improve liver health and enhance regenerative medicine procedures. The combination formula was given the name RM88, but the constituents were not disclosed. Two small trials were conducted in which participants consumed RM88 mixed into a biscuit prior to drinking alcohol. Results showed a general increase in the rate of BAC in the test subjects, alcohol reduction either a cookie or water infused with the herbal blend. Thirteen subjects (5 males, 8 females, age range 18 to 85 years) completed 16 paired sessions of alcohol only, versus RM88 with alcohol. Subjects consumed one to three standard drinks of beer, wine, or spirits (14.7 to 29.4 gm alcohol). Measurements were made by a fuel cell breathalyser for a period of 90 minutes. Summated BAC showed a reduction in 94% (15/16) of paired test sessions (BAC reduction range 23% - 79%, mean 50.9% ± 16.5%, p = 0.0005). Data normalized to 20 gm alcohol (two standard drinks) showed a significance of p = 0.00026. One subject on prednisone and hydroxychloroquine drugs had increased BAC from RM88. The average reductions of BAC for the beverages were spirits 34% (n = 3), beer 36% (n = 3), and wine 52% (n = 10).

Red Ginseng https://doi.Org/10.1111/j.1440-1681.1987.tb01510.x

Fourteen healthy male volunteers were studied to assess the effects of Panax ginseng on blood alcohol clearance, utilizing each subject as his own control.

At 40 min after the last drink, the blood alcohol level in the test group receiving ginseng extract (3 g/65 kg body weight) along with alcohol (72 g/65 kg body weight) was about 35% lower than their control values. When the blood alcohol level was compared on individual bases, alcohol concentrations in 10 out of 14 test subjects ranged from 32- 51% lower than their control values.

Daidzin

Lin, R. C., & Li, T.-K. in The American Journal of Clinical Nutrition, 1998 Dec;68(6 Suppl):1512S-1515S. doi: 10.1093/ajcn/68.6.1512S- ‘Effects of isoflavones on alcohol pharmacokinetics and alcohol-drinking behaviour in rats, describe Daidzin as a potent antioxidant compound extracted from the edible vine, Pueraria lebata. Studies in rats have indicated that when diadzin and alcohol are administered concurrently, BAC rose more slowly and had a significantly lower peak as compared to the food-deprived controls. This is due in part to its impact on stomach emptying. Vitamin E and thiotic acid, also antioxidants, were also evaluated in the same study, demonstrating similar supressing effects on BAC. These data suggest that the effects of diadzin are also in part due to its antioxidant activity.

High-dose Fructose

Mascord D, Smith J, Starmer GA, Whitfield JB. The effect of fructose on alcohol metabolism and on the [lactate]/[pyruvate] ratio in man. Alcohol. 1991 ;26(1):53-9. PM ID: 1854373.

Ten male subjects were given alcohol by intravenous infusion and maintained at a constant blood alcohol level. The rate of alcohol metabolism was measured before and after an oral dose of fructose (100 g), as the amount of alcohol required to maintain the steady state. The mean rate of alcohol metabolism increased by 80% after fructose but there was considerable variation among the subjects, which was related to their plasma fructose concentrations. Blood lactate increased after fructose to a greater degree than blood pyruvate, resulting in a significant increase in [lactate]/[pyruvate] ratio. Since fructose increased the [lactate]/[pyruvate] ratio when it increased alcohol metabolism, the action of fructose cannot be explained by a decrease in the liver cytoplasmic [NADH]/[NAD] ratio and some other mechanism must be sought.

AB001 (key ingredient in Myrkl)

Pfutzner A, Hanna M, et al. Impact of a Single Dose of a Probiotic Nutritional Supplement (AB001) on Absorption of Ethyl alcohol: Results From a Randomized Double-Blind Crossover Study. Nutrition and Metabolic Insights. 2023; 16. doi:10.1177/11786388221141174

AB001 is a probiotic nutritional supplement developed to reduce alcohol absorption from the intestine tract. A placebo-controlled double-blind randomized study to assess the impact of a single dose of a nutritional Supplement (AB001) on alcohol absorption was conducted on 24 healthy volunteers (12 male, 12 female, age: 28.3 ± 10.8 years, BMI: 23.5 ± 5.7 kg/m²). They ingested a light breakfast together with a single dose (2 capsules) of AB001 (or placebo) and drank 2 moderate glasses of spirit (a total of 0.6 g/kg body weight). BAC was measured via breathalyser and blood draws over the course of 6 hours. A crossover experiment was conducted the subsequent week to calculate alcohol absorption rates. It was found that BAG was reduced by 10.1% (P < .001) with AB001 , when compared to placebo.

Summary of the invention

The above remedies and studies demonstrate that, in some cases, it is possible to influence the rate of metabolism of blood alcohol using various medicaments, some better than others. However, there is no common thread in the above mentioned remedies. From their investigations, the inventors have noted that metabolising alcohol can have many consequences on human health. Alcohol metabolism is an oxidative process that produces harmful by-products which can cause damage to human tissues and cells, and negatively impact other metabolic processes. In particular, the production of acetaldehyde - a toxic by-product that can cause tissue damage and the formation of damaging molecules known as reactive oxygen species (ROS). ROS can combine with molecules making them highly reactive radicals which have shown to play important roles in causing cancer, atherosclerosis, diabetes, inflammation, and even aging.

These studies and remedies noted that the effects of alcohol depend on its concentration and duration in the blood measured as BAG. BAG is influenced by factors such as the rate of alcohol consumption, the type of alcohol consumed, the presence of food in the stomach, a person’s age, weight, as well as genetic factors including sex and differences in the body’s ability to produce the enzymes that breakdown alcohol.

They noted that the liver is the main organ responsible for metabolizing alcohol, although other organs such as the stomach, the lung, and even the brain are thought to play a role. Blood alcohol concentration is reduced at a rate of about 0.015-0.018% BAG per hour, meaning a person who has consumed enough alcohol to have a BAG of 0.08% would require up to 4-6 hours to eliminate alcohol from their blood.

The inventors of the present invention realised that liver detoxification could be aided with a composition comprising a synergistic blend of selected vitamins, a mineral, and an amino acid. The combination of these ingredients created a powerful and rapid- response formula that provides a unique therapeutic effect which could be put to good use to detoxify the liver following the consumption of alcohol.

The composition of the invention was shown to reduce BAC (by measurement of BrAC) with rates more than about 0.03% per hour (around a 100% increase than normal body metabolism).

The composition of the invention includes selected vitamins, a mineral, and an amino acid to reduce the negative effects of alcohol to the human body, primarily targeting support of the liver in helping to produce antioxidants and reducing oxygen free radicals. The inclusion of magnesium replenishes the body’s balance of that mineral which is otherwise expelled at higher than normal rates because of the diuretic properties of alcohol. Deficiencies in minerals like magnesium and B vitamins have been linked to increased hangover symptoms.

The present invention relates to a composition designed to detoxify the liver and thereby achieve an increased reduction of Blood Alcohol Concentration (BAC) levels within the human body compared to reductions without the use of the composition.

The key components of the BAC-reduction composition work in concert to address the biochemical pathways associated with BAC, leading to a rapid and effective reduction in BAC levels. The selection and proportioning of each ingredient in the formulation have been optimized through research and testing.

In addition to its efficacy, the composition of the invention is characterized by its safety and minimal side effects, making it a viable option for widespread use. The formulation is based on scientifically supported principles and has undergone testing to confirm effectiveness in reducing BAC levels. All components have an excellent safety profile and history of use.

In summary, the multivitamin composition described herein represents a groundbreaking advancement in the field of nutritional supplements, BAC reduction, and alcohol-related harm reduction. Its ability to achieve up to a 0.085% reduction in BAC levels within just 90 minutes (males) provides a unique rate of liver detoxification and is suitable for administering by individuals, care-providers, healthcare practitioners, and first responders. According to a first aspect of the invention, there is provided a composition for use in a method of reducing BAC in a subject having an elevated blood alcohol content, the method comprising administering to the subject effective amounts of at least the following ingredients: a) methionine, b) vitamin C, c) magnesium, d) vitamin B3, and e) vitamin B6, before, during or after alcohol consumption.

According to another aspect, the invention includes use of a composition in a method for reducing BAC, the composition consisting, comprising or comprising essentially of: (L, D or LD) methionine at 62%, vitamin C at 22%, a magnesium compound at 6%, vitamin B3 at 5%, and vitamin B6 at 5% for example in the form of an ingestible pill.

According to another aspect, the invention there is provided a composition or medicament consisting, comprising or comprising essentially of, the ingredients (L, D or LD) methionine, vitamin C, a magnesium compound, vitamin B3 and vitamin B6.

According to another aspect, the invention there is provided a composition for use in a method of liver detoxification the method comprising providing the effective amounts of the ingredients recited in the first aspect of the invention.

According to another aspect of the invention, there is provided a package for storing the composition recited in the other aspects of the invention.

The invention extends to a method of liver detoxification or reducing blood alcohol content in a subject having an elevated BAC, the method comprising administering effective therapeutic amounts of the ingredients: a) methionine; b) vitamin C; c) magnesium; d) vitamin B3 and; e) vitamin B6.

Detailed description

The invention will now be described with reference to the drawings, wherein:

Figure 1 shows a list of ingredients sold commercially as ‘hangover’ cures.

Figure 2 shows a graph of BAG over time in response to the administering of the composition according to the invention to female human test subjects;

Figure 3 shows a similar graph to the graph of Fig 2, for male human subjects;

Figure 4 shows the results of a further trial;

Figure 5 shows the results of a yet further trial; and

Figure 6 shows an example of a storage device for the composition.

In Figure 1, anecdotally, it appears that many different vitamins, minerals, and plant extracts have been sold as treatments for hangovers, but the variance of ingredients used suggests that there has not been a definitive treatment that stands out above others, or that they actually reduce BAG. The inventors have formulated and tested a composition based on vitamins, a mineral and an amino acid, which has been shown to be very effective at detoxifying the liver, in particular detoxifying by aiding the reduction of BAG, and thereby treating the effects known as a hangover.

Example 1

A composition having the ingredients listed in the Table A below was prepared as a powder mixture and formed into pills, such that each pill contained the amount of ingredient listed, with the remainder of the pill’s weight being formed from the non- medicinal ingredients as such binders, fillers and lubricants.

Table A medicinal ingredients:

The ingredients mentioned above are of a grade and purity commensurate with their intended use as a nutritional/health product and are readily available at such a grade from numerous commercial suppliers.

In a study (Study 1), one pill, formulated as above was administered orally to 5 male (average weight 104kg) and 5 female (average weight 73kg) trial subjects, who had just finished consuming: males- 150mL (15 units); females- 100mL (10 units) of alcohol. One placebo pill was also administered to 5 males and 5 females who consumed the same amount of alcohol as the rest of the subjects. The subject’s breath alcohol (BrAC) was measured at 30, 60 and 90 minutes after taking the pill. The results of the reduction in BrAC are given in Figs 2 and 3 (estimated as BAC based on the conversion factor mentioned above), as line c.

It can be seen from the graphs that the pill formulation shown as the line c reduces BAC alcohol at an increased rate compared to both the placebo rates (line b) and the body’s normal/natural metabolism rate expected from literature (line a). More specifically, at a rate for women (Fig 2) is about [(0.075-0.025)/1.5=] 0.03% BAC per hour, compared to about 0.015% for the expected rate. And a rate for men (Fig 3) is [(0.1 -0.055)/1 .5=] 0.03% BAC per hour, with an expected literature reduction about the same as for females. In other words, the pill composition was found to reduce the rate of BAC twice as quickly would be expected naturally, or 100% more quickly.

Example 2

A similar formulation to example 1 , i.e. having the same medicinal ingredients, but in capsule form, was used for a further controlled trial (Study 2).

In the trial, the medicinal composition of example 1 was used in a double-blind, randomized, placebo-controlled clinical trial, conducted by an experienced medical doctor acting as the primary investigator. The trial was registered with the Institutional Review Board (IRB) and www.ClinicalTrials.gov and approved by National Clinical Trials (NCT). Trial subjects were trained in the use of DRUID™ app on their phones. This is a software application that has been proven to accurately measure psychomotor impairment compared to baseline scores. The subjects performed several baseline scores in the days prior to the study dates and at the time of each study. Subjects agreed to not eat or drink anything starting three hours prior to each study. The subjects were texted a reminder of this three hours before each study. Subjects agreed to not drink alcoholic beverages or consume tetrahydrocannabinol (THC) in the 24 hours prior to the studies. Subjects signed an informed consent and passed an interview for ‘inclusion’ and ‘exclusion’ criteria.

Subjects received a standardized alcoholic beverage consisting of 80-proof vodka diluted with soda (1 :1) and two ice cubes. The alcohol was administered in three parts, 10 minutes apart. In the study the subjects were given 0.62gm/kg (kg weight of the subject).

Each group of 5-7 subjects had a supervising technician and was monitored by a nurse.

The study followed a structured timeline:

• Subjects consumed their allocated drink over a 30-minute period (3 equal parts);

• 30-minute absorption period was observed after finishing the alcohol;

• 60-minute minutes after starting to drink alcohol the subjects received either the medication mentioned above as a capsule or a placebo capsule; and

• BAG measurements were taken at baseline, 60, 90, and 120 minutes after starting to drink alcohol. The 120-minute timeline then would be 60 minutes after taking the active or placebo medication.

Measurement Methods

All BAG measurements were conducted using the BACtrack S80™ advanced technology breathalyser under standardized conditions. There was at least 20 minutes of ‘rest’ before any one breathalyser was reused. New mouthpieces were used for each measurement, and each subject was instructed to rinse their mouth with water to remove any residual alcohol. The subjects had been trained and observed for correct breathalyser technique prior to starting the session.

Demographics:

• 30 subjects, predominantly in their 20-30s, 2/3rd Caucasian and the remainder a mix of African and Asian heritage;

• Age range: 22-70 years;

• 21 females and 9 males;

• Average weight: 79.2kg;

• Average height: 1.71 meters;

• Average BM I: 27.1

Results

Study 2 results data (0.62gm/kg of alcohol consumed) are given in Table B below, where:

A = active

P= Placebo

Alcohol gm/kg = total grams of liquid alcohol per kg mass of the subject’s weight consumed over a 30 minute period

BAC% is the machine estimated BAC% extrapolated from machine breath alcohol measurements, and where 60, 90 and 120 is the time in minutes from commencing drinking alcohol and 0, 30 and 60 minutes respectively from taking the active or placebo capsule. Table B

Test Alcohol BAC% 60 BAC% 90 BAC% 120 gm/kg % % % Change

A 0.62gm/kg 0.057 0.049 0.043 0.014

A 0.62gm/kg 0.080 0.068 0.063 0.017

A 0.62gm/kg 0.067 0.047 0.039 0.028

A 0.62gm/kg 0.040 0.020 0.020 0.020

A 0.62gm/kg 0.031 0.027 0.018 0.013

A 0.62gm/kg 0.054 0.040 0.037 0.017

A 0.62gm/kg 0.071 0.057 0.047 0.024

A 0.62gm/kg 0.057 0.039 0.034 0.023

A 0.62gm/kg 0.041 0.041 0.037 0.004

A 0.62gm/kg 0.057 0.040 0.029 0.028

A 0.62gm/kg 0.072 0.051 0.052 0.020

A 0.62gm/kg 0.033 0.030 0.024 0.009

A 0.62gm/kg 0.060 0.040 0.030 0.030

A 0.62gm/kg 0.057 0.055 0.043 0.014

A 0.62gm/kg 0.060 0.060 0.050 0.010

A 0.62gm/kg 0.093 0.070 0.060 0.033

A 0.62gm/kg 0.080 0.070 0.067 0.013

A 0.62gm/kg 0.064 0.050 0.040 0.024

A 0.62gm/k 0.067 0.045 0.035 0.032

A 0.62gm/kg 0.090 0.050 0.040 0.050

A 0.62gm/kg 0.060 0.060 0.020 0.040 Table B continued

Test Alcohol BAC% 60 BAC% 90 BAC% 120 gm/kg % % % Change

A 0.62gm/kg 0.068 0.054 0.043 0.025

A 0.62gm/kg 0.062 0.048 0.037 0.025

A 0.62gm/kg 0.047 0.039 0.026 0.021

P 0.62gm/kg 0.031 0.032 0.025 0.006

P 0.62gm/kg 0.034 0.037 0.035 -0.001

P 0.62gm/kg 0.063 0.063 0.057 0.006

P 0.62gm/kg 0.058 0.049 0.043 0.015

P 0.62gm/kg 0.060 0.049 0.030 0.030

P 0.62gm/kg 0.059 0.047 0.044 0.015

Conclusions for Study 2

The average BAC% for the entire group of subjects after starting to drink alcohol were:

60 Min 0.059%, 90 Min 0.048%, 120 Min: 0.039%, however from 60 to 120 minutes, the average BAC% in the ‘active’ group decreased from 0.061% to 0.039%, for a total change in BAC% of 0.022%. From 60 to 120 minutes, the average BAC% in the ‘placebo’ group decreased from 0.051 % to 0.039%, for a total change in BAC% of 0.012%. The 95% Confidence Interval for change over 60 Mins is Active: 0.026- 0.018% Placebo: 0.023-0.001%. Using Student T-Test for Independent Variables, the difference in between the active and the placebo groups are the following (p-values): P < 0.05 is statistically significant (italic font): 60 Min p=0.157; 90 Min p=0.762; 120 Min p=0.989; 60 Min Change p=0.038.

In summary study 2 showed that the medication resulted in a BAC% which was on average 1.83 times lower (183%) compared to the placebo group 60 minutes after taking the medication. Example 3

A further trial (Study 3) using the same subjects as the Study 2 and under the same conditions, was conducted. In this study the subjects were given an increased amount of alcohol.

The results of Study 3 (0.95gm/kg of alcohol consumed) are given in Table C below, having the same nomenclature as table B.

Table C

Test Alcohol BAC% 60 BAC% 90 BAC% 120 gm/kg % % % Change

A 0.95gm/kg 0.140 0.155 0.156 -0.016

A 0.95gm/kg 0.151 0.151 0.156 -0.005

A 0.95gm/kg 0.253 0.197 0.162 0.091

A 0.95gm/kg 0.104 0.101 0.097 0.007

A 0.95gm/kg 0.089 0.075 0.066 0.023

A 0.95gm/kg 0.183 0.135 0.120 0.063

A 0.95gm/kg 0.125 0.132 0.122 0.003

A 0.95gm/kg 0.113 0.104 0.090 0.023

A 0.95gm/kg 0.141 0.124 0.115 0.026

A 0.95gm/kg 0.180 0.150 0.143 0.037

A 0.95gm/kg 0.182 0.170 0.150 0.032

A 0.95gm/kg 0.157 0.135 0.115 0.042

A 0.95gm/kg 0.120 0.120 0.120 0.000

A 0.95gm/kg 0.138 0.130 0.115 0.023

A 0.95gm/kg 0.141 0.134 0.114 0.027

A 0.95gm/kg 0.114 0.100 0.087 0.027 Table C continued

Test Alcohol BAC% 60 BAC% 90 BAC% 120 gm/kg % % % Change

P 0.95gm/kg 0.085 0.090 0.117 -0.032

P 0.95gm/kg 0.160 0.153 0.131 0.029

P 0.95gm/kg 0.132 0.105 0.095 0.037

P 0.95gm/kg 0.150 0.150 0.150 0.000

P 0.95gm/kg 0.132 0.140 0.132 0.000

P 0.95gm/kg 0.150 0.140 0.118 0.032

P 0.95gm/kg 0.125 0.123 0.118 0.007

P 0.95gm/kg 0.128 0.120 0.104 0.024

P 0.95gm/kg 0.160 0.150 0.150 0.010

P 0.95gm/kg 0.068 0.054 0.043 0.025

P 0.95gm/kg 0.118 0.117 0.114 0.004

P 0.95gm/kg 0.100 0.100 0.100 0.000

P 0.95gm/kg 0.095 0.090 0.086 0.009

P 0.95gm/kg 0.141 0.136 0.137 0.004

P 0.95gm/kg 0.160 0.160 0.159 0.001

P 0.95gm/kg 0.127 0.125 0.117 0.010

Conclusions for Study 3

The average BAC% at 60, 90 and 120 minutes after starting to drink alcohol were:

60 Min 0.137%: 90 Min 0.127%: 120 MinO.119%. From 60 to 120 minutes, the average BAC% in the ‘active’ group decreased from 0.146% to 0.121%, for a total change in BAC% of 0.025%. From 60 to 120 minutes, the average BAC% in the ‘placebo’ group decreased from 0.127% to 0.118%, for a total change in BAC% of 0.009%. The 95% Confidence Interval for change over 60 Mins is: Active 0.392- 0.011%; Placebo 0.018-0.001 %. Using Student T-Test for Independent Variables, the difference between the active and the placebo groups are the following (p-values); P < 0.05 is statistically significant (italic font): 60 Min p= 0.081 ; 90 Min p=0.762; 120 Min p=0.208; 60 Min Change p=0.005.

In summary study 3 showed that the medication resulted in a BAC% which was on average 2.77 times lower (277%) compared to the placebo group 60 minutes after taking the medication.

The high dose of 0.95gm/kg resulted in a high average BAC% of 0.0137% at 60 minutes after starting to drink alcohol, which resulted in a few subjects appearing not having absorbed all of the alcohol by 60 minutes, and therefore a continued increase in the BAC%. This could have affected the measured rate of decline in both the active and placebo groups. A study with a lower dose of alcohol is expected to resolve this issue.

It should be noted that for examples 2 and 3 those studies measured breath alcohol values of a sub group of subjects who had taken the medication, with a subgroup who had been given a placebo, the whole group having consumed alcohol under the same conditions and being statistically relevant in number.

Example 4

In a further study (Study 4), the ingredients mentioned in Table D below were mixed as a 60ml drink and administered using the same regime as for Example 1. The results are again shown in Figs 2 and 3 as lines d.

It can be seen that the drink formulation, (line d) reduces BAG even quicker than the pill formulation of example 1. Here it is postulated that the body’s quicker take-up of the ingredients in liquid form.

In numerical terms- Female BAG reduction was [0.075/1.5] = 0.05% per hour, and male reduction was [(0.1 -0.0125)/1 .5=] 0.058% per hour, with an expected reduction of about 0.015% per hour. So, in the powder form, the composition acts to reduce BAG 3 to 4 times more quickly than expected by the body’s natural metabolism. Whilst drinking and driving must never be condoned or encouraged, as can be seen from Fig 3, the BAG of the male trial subjects who took the placebo pill (line b) exceeded the UK legal driving limit of 0.08% BAC for about 80 minutes after they stopped drinking, whereas for those subjects who took the drink composition (line d), were over the legal limit for only about 30 minutes after drinking the same amount of alcohol.

Table D

It should be noted that the min mg was used in Study 4, but the max mg is quoted here as the amount of ingredient which is postulated as being the upper range of what is considered to be therapeutically effective, with more being likely to simply be wasted by the body. The last two columns of table D equate to the approximate minimum and maximum of the percentage of the ingredients in a 60ml drink, but could be recalculated for, for example, a 30 to 90ml drink accordingly.

Example 5

Further studies (Study 5) were conducted with additional pills and drink/beverage formulations, keeping the ratio of therapeutic ingredients listed in examples 1 and 4 above but varying the overall dosage amounts, with the objective of enhancing or optimising the performance of the formulation.

The range of the ingredients considered beneficial for the pills is given in table E below, and for the drink ingredients, in table F below. Table E Range table for pills

Table F range for Drinks/Beverage

It will be noted that the dosage of active ingredients in Table F (drink) is the same as that of Table C (pills). However, because the ingredients were sometimes diluted in the drink the lower end of the range of percentage of ingredients is lower where the liquid content of the drink has been increased. In the studies that used drinks, the drink included the non-active ingredients:- water, citric acid, flavour, colour, sweetener, preservatives (potassium sorbate, sodium benzoate). A 60ml drink (including the non active ingredients listed) was used, but 30ml-90ml is considered to provide equal efficacy.

The results of the further studies for example 5 are reported in the graph shown in Figure 4.

In Figure 4 a bar graph is shown, which for the X axis shows various blends ( overall amounts of active ingredients used), where it can be seen that pills with a range of total dosage of active ingredients of 310mg, 400 mg, 480mg, 630 mg and 650 mg were studied. Across the Y axis are, for each bar, three different blocks, representing the amount of change in measured BAC, at 30, 60 and 90 minutes after ending alcohol consumption and taking the medication. In other words, every 30 minutes.

The same bar graph also shows the results for beverages containing 310mg, and 400mg and also their change in measured BAC over the same time periods.

Overall it can be seen that the composition is capable of reducing BAC by more than 0.08% in 1 hour (650mg pill) which is 5 times faster than the normal metabolic rate of BAC reduction. It is noted also that slightly higher total dosage seems to be better at reducing BAC, but not significantly so, and so the amounts of the ingredients listed is thought to be a reasonably wide range to provide the therapeutic effects discussed herein, as outlined in tables D and E. It is postulated that the synergistic effects of the ingredients outweigh the effects of the dosage amount to a large extent.

In both pill and drink form subjects also reported a reduction in adverse effects associated with alcohol (e.g., nausea, headaches, dizziness, fatigue, etc.) and the ‘hangover’ effects were reduced also.

For the drink composition, mentioned above, a readily usable form the composition can be encapsulated in a hermetically sealed way with a bottle top, arranged to drop the top’s contents into the bottle when the bottle is opened prior to drinking the contents of the bottle. Thereby, the ingredients of the composition are not significantly affected by oxygen or preservatives in the drink. The drink can be any combination of water, electrolytes, fruit juice, fruticose, coconut water, all thought to help in liver detoxification and rehydration.

The composition can be hermetically sealed in an inert atmosphere, e.g. enclosed in a capsule in a bottle top and the capsule is opened when the bottle is opened. The bottle may contain a beverage. Such an embodiment is illustrated in Figure 6, which shows a drinks bottle in section, whereby a PET drinks bottle 10 containing, in this example a 50/50 mix of coconut water and regular water 12 has a neck with a screw thread 14 and a modified cap 20 with a thread complementary to the bottle’s thread 14. The cap 20 seals the bottle 10 in a conventional way, by means of an annular seal 26.

In this embodiment the cap has additionally a soft waterproof membrane 22 inside the cap formed from plastics material, for example polyethylene, heat sealed to the inside of the cap to make a hermetically sealed capsule 24, having an inert atmosphere trapped in the capsule and containing the composition mentioned above.

In use, unscrewing of the cap 20 by a user brings a projecting element 16, affixed to the inside of the neck of the bottle, into contact with the membrane 22, tearing the same and allowing the composition inside the capsule 24 to drop into the drink 12. In this way a fresh dose of the composition can be administered by drinking the contents of the bottle.

Example 6

A further study (Study 6) was performed for different dosages in capsule form. The ratio of ingredients were as described in Table A, but in capsule form with different dosage rates Subjects were given alcohol, and their BAG was measured at time zero (30 minutes after stopping consuming alcohol and taking the medication), then 30 and 60 minutes after that.

The results of this study are shown in Figure 5 where capsules having dosages of 480mg to 690 mg were tested. The X axis shows the measured values of subjects’ BAG. Each participants’ BAG was recorded at the times mentioned above and plotted as lines b to f on the graph. The benchmark of expected reduction in BAG through typical metabolization (line a= -0.015 % per hour) is shown for comparison against line b, d, and f. For comparison against lines c and e the benchmark line a would need to be transposed so that its origin started at the same BAG value on the X axis as lines c and e.

In this study typical reductions in BAG are 2.3 to 3.6 times faster than the expected normal metabolic reduction rate. Overall, it is clear that the dosage has only a small effect on slope of the lines b to f and so it appears that provided a therapeutic amount has been taken, then the dosage above that level does not change the effect significantly.

Whilst administration of the compositions described herein is intended to be as a pill or capsule or a powder, for example taken with a beverage, it is possible that other delivery mechanisms could be used, for example, tablets, hard-shell capsules, soft gels, syrups, tinctures, elixirs, oral sprays, drops, intravenous infusion, transdermal patches, sublingual tablets, sublingual spray, fortified or functional foods, nasal spray, or suppositories.

In the examples L-methionine was used as the preferred form of methionine, although its isomers referred to as D and DL are considered to be usable, but less effective.

Any biologically compatible compound with magnesium may be employed, for example citrate, glycinate or malate or a combination thereof. The compound of Magnesium used in the examples was Magnesium Bisglycinate, and so the Magnesium Bisglycinate listed in Tables B to F is not a material change in the formulation compared to examples 1 . The pure magnesium content will of course be lower at about 2-32mg

Vitamin B3 in the form of niacin was used.

Vitamin B6 in the form of as pyridoxine hcl was used.

Vitamin C as ascorbic acid was used.

Whilst specific quantities of ingredients were administered in the examples, it will be appreciated that ranges of quantities could be used to provide results which the inventors expect to be about the same as the reported results or be only marginally better or worse than the doses in the examples. For example, a range of ingredients is outlined in table G below. Table G ingredient range table

NB in the outer ranges is it thought that an excess of the ingredients is likely to be wasted by the body, and so the upper limits in the outer ranges are influenced by recommended maxima for those ingredients.

The compositions of examples were taken immediately after subjects consumed alcohol, although it is thought that taking the compositions shortly before, e.g. up to 3 hours before, or during consumption of alcohol, or up to 6 hours after, would provide an effective increase in the rate at which BAG reduces in the body compared to the expected rate.

It will be appreciated that the numerous features described above and/or illustrated herein are set forth by way of example and are not intended to limit the scope of the invention. Numerous alternatives, variations, modifications, additions, and omissions, to those examples will be apparent to a skilled person in the relevant art. It is envisaged that features from different embodiments may be brought together, without adding to the scope of the invention. In addition, the order of any features in the form of method steps or sequences in the description, claims and/or drawings herein is not intended to require that order of performance unless a particular order is necessary for technical reasons. Multiple features in a single claim herein may be so combined in that claim for, for example, fiscal, not technical reasons and so such combined features are not necessarily intended to form a whole inseparable technical concept. Thereby, in the claims set forth, it is intended that claim features may be exchanged between, or extracted from, claims containing other features without broadening the scope of the invention or causing a so-called intermediate generalisation.

The original Applicant grants permission to copy, distribute and display this work in unaltered form, with attribution to the Applicant or their Assignee, to meet legal requirements regarding publication or for non-commercial purposes only. All other rights, including commercial rights, are reserved to the Applicant or their Assignee.

Claims

1. A composition for use in a method of reducing blood alcohol concentration (BAC) in a subject having an elevated BAC, the method comprising administering to the subject an effective amount of at least the following ingredients: a) (L, D or LD) methionine, b) vitamin C, c) magnesium, d) vitamin B3, and e) vitamin B6, before, during or after alcohol consumption.

2. A composition as claimed in claim 1 wherein the effective amount is: a) 100-839 mg of methionine for example as L-methionine; b) 30-300 mg of vitamin C for example as ascorbic acid; c) 9-230 mg of Magnesium, for example as a citrate, (bis)glycinate , gluconate or malate or a combination thereof; d) 8-72 mg of vitamin B3 for example as niacin; and e) 7-60 mg of vitamin B6 for example as pyridoxine hcl;

3. A composition as claimed in claim 1 or 2 wherein the effective amount is: a) 100-180 mg of methionine for example as L-methionine; b) 30-75 mg of vitamin C for example as ascorbic acid; c) 9-18 mg of Magnesium, for example as a citrate, (bis)glycinate, gluconate or malate or a combination thereof; d) 8-16 mg of vitamin B3 for example as niacin; and e) 7-13 mg of vitamin B6 for example as pyridoxine hcl;

4. A composition as claimed in claim 1,2 or 3 wherein the effective amount is about: a) 140-428 mg for example 140 mg of methionine for example as L- methionine; b) 50-152 mg for example 50 mg of vitamin C for example as ascorbic acid; c) 14-42mg for example 14mg of magnesium, for example as a citrate, glycinate, bisglycinate or malate or a combination thereof; d) 12-42mg for example 12mg of vitamin B3 for example as niacin; and e) 10-60mg for example 10mg of vitamin B6 for example as pyridoxine hcl.

5. A composition as claimed in any one of claims 1 to 4, wherein the ingredients further include one or more binders, fillers or lubricants.

6. A composition according to any one of the preceding claims wherein said ingredients and optionally said further ingredients are all administered or consumed at the same time.

7. A composition as claimed 6, wherein, said ingredients are administered in a time period of between about 3 hours prior and up to about 6 hours after of said alcoholic consumption.

8. A composition as claimed in any one of the preceding claims wherein the method provides a reduction in BAC at least twice and preferably 3 times the rate of that expected through a normal metabolic rate of BAC reduction.

9. Use of a composition for reducing BAC, the composition consisting, comprising, or comprising essentially of: (L, D or LD) methionine, vitamin C, a magnesium compound, vitamin B3 and vitamin B6.

10. Use of a composition according to claim 9, the composition consisting, comprising or comprising essentially of a) a pill, capsule formulation including:

(L, D or LD) methionine at 40% - 62%, vitamin C at 21% - 28%, a magnesium compound at 6% - 33%, vitamin B3 at 3% - 5%, and vitamin B6 at 3% - 5%; or b) a drink formulation including:

(L, D or LD) methionine at 0.16% - 62%, vitamin C at 0.084% - 28%%, a magnesium compound at 0.024% - 33%, vitamin B3 at 0.012% - 5%, and vitamin B6 at 0.012% - 4%.

11. A composition, medicament, health product or beverage consisting, comprising or comprising essentially of, the ingredients (L, D or LD) methionine, vitamin C, a magnesium compound, vitamin B3 and vitamin B6.

12. A composition or medicament as claimed in claim 11 wherein said ingredients are there listed in order of reducing % by weight (greatest first) and methionine is the majority ingredient of those listed being present in a % which is higher than the weight of the other ingredients combined.

13. A beverage containing the composition ingredients claimed in any one of claims 1 , 2, 3 or 4, and including one or more of:- water, citric acid, flavoring , coloring, sweetener, and preservatives for example potassium sorbate and/or sodium benzoate, wherein said beverage has a total volume of 30ml to 90ml, and preferably about 60ml.

14. A composition for use in a method of liver detoxification the method comprising providing the effective amounts of the ingredients a) to e) as claimed in any one of claims 1 to 4 to a subject following liver toxification.

15. A package for storing the composition claimed in claim 13; the package containing a beverage and a sealed compartment housing said composition.

16. A package for storing the composition as claimed in claim 13, wherein the compartment has an inert atmosphere and is openable by a consumer of the composition.

17. A package as claimed in claim 15 or 16 wherein the package is a drinks bottle and the compartment comprises the bottle’s cap, arranged such that the cap houses said composition in a sealed manner at least until the cap is separated from the bottle.

18. A method of reducing blood alcohol content or liver detoxification in a subject having an elevated BAC, the method comprising administering a therapeutic amount of the ingredients: a) (L, D or LD) methionine; b) vitamin C; c) magnesium; d) vitamin B3 and; e) vitamin B6. before, during or after alcohol consumption.

19. A method as claimed in claim 17, wherein the ingredients a) to e) are administered in the amounts claimed in claim 2, 3 or claim 4.

20. A method as claimed in claim 17 or 18, wherein said ingredients are selfadministered with a beverage, preferably a non-alcoholic beverage.