Alcohol drinking is prevalent at social intercourse and celebration occasions in Hong Kong and western society as well. According to The Behavioural Risk Factor Survey (April 2011) issued by the Centre for Health Protection of the Department of Health which revealed that among interviewees who had consumed at least one alcoholic beverage at the month before the survey, 20.6% of them had tried binge drinking (consumed at least 5 glasses/cans of alcohol by drinkers continuously in one occasion). Moreover, 16.6% of the interviewers reported that they had drunk excessively that they showed behaviors of alcohol intoxication. (Drunkeness) (Centre for Health Protection of the Department of Health [CHPDH], 2011)
Recently, the World Health Organiztion described ï¿½ï¿½binge drinkingï¿½ï¿½ as term of ï¿½ï¿½heavy episodic drinkersï¿½ï¿½, which defines that people who aged 15 or above, consume at least 60 grams or more of pure alcohol at least once per week. (Desai, 2010) This is equivalent to six standard alcoholic drinks which means consumption of approximate 4.5 cans of regular beer with 5% alcohol content. (ï¿½ï¿½Change4Healthï¿½ï¿½, 2011) Binge drinking is considered as a kind of acute alcohol consumption and is being common in Hong Kong especially at festival-related celebration occasion such as Charismas and Halloween.
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Meanwhile, alcohol drinking during business-related intercourse is noticeable. The survey also indicated that people who are managerial or professional workers and service workers are more likely consumed three or above glasses of alcoholic drink on the days that they drank alcohol. Therefore, either acute or excessive alcohol consumption is considerably common in our daily life.
1.2 Effects of alcohol consumption
Acute alcohol consumption may cause acute alcohol intoxication which refers to the psychological changes induced by the increased blood ethanol concentration. As the properties of alcohol are sedative and mild anesthetic, it can produce a sense of relaxation and euphoria. Alcohol also causes depressive effect on the central nervous system. The most common observed psychological changes include increasing of heart rate, impairing of balance, flushing of face, vomiting, feeling euphoria coma and muscle weakness, etc. Some serious symptoms may be unconsciousness, irritating breath rate and even death. (Alex, 2005)
1.3 Appearance of anti-alcoholic products
In order to relieve the alcohol-induced effects to our body, various commercial products or supplements have been introduced to the market. Many of them proclaimed that they have pronounced anti-alcoholic effects such as avoiding alcohol intoxication, relieving hangover symptoms, increasing the total amount of alcohol consumption as well as enhancement of ethanol metabolism inside the body. Consumers with alcohol intolerance may base on these commercial descriptions or advertisements to select the products.
However, news has been recently reported and aroused the awareness towards the misleading information of some commercial products because of their overstated anti-alcoholic effects. The Practicing Pharmacists Association of Hong Kong disclosed that some of the products only have limited effectiveness on ethanol metabolism which cannot reduce the chance of alcohol intoxication. Besides, they also emphasized that most of those commercial anti-alcoholic products are regarded as health supplements rather than medicine. (Ming Pao Daily, 2012)
In the other words, those anti-alcoholic products do not comply with a strict regulation due to the absence of specific regulatory ordinance for health supplements in Hong Kong. Therefore, the anti-alcoholic effects of the products may be exaggerated.
This thesis aims to examine protective mechanisms of several commercial products including both Eastern and Western products (AlcolOut(ï¿½sï¿½Kï¿½ï¿½), RU21 (ï¿½wï¿½é´¶ï¿½Æ¦Xï¿½ï¿½), Hythiol-C (ï¿½wï¿½Kï¿½Pï¿½Ñ°sï¿½Y), Niu-chang-chih Royal Health Supplement (ï¿½ï¿½ÌªÛºï¿½ï¿½) and Jiejiuling Koufuye(ï¿½Ñ°sï¿½Fï¿½fï¿½A) that can induce anti-alcoholic effects. Secondly, summarizes the different protective mechanisms. Finally, it critically evaluates on the effectiveness and reliability of the products upon different anti-alcoholic effects based on their corresponding protective mechanisms.
Part II. Alcohol absorption and its metabolisms
Drinking alcohol, also called ethanol, which is colorless, water-soluble, volatile and with a molecular formula CH3CH2OH, is the most well-known type of alcohol found in alcoholic beverages. Alcohol is absorbed in stomach relative slowly, while it is absorbed in small intestine more rapidly. (Alex, 2005) Theoretically, alcohol metabolism involves three main enzymatic pathways: alcohol dehydrogenase (ADH) pathway, microsomal ethanol oxidizing system (MEOS), and catalase located in peroxisomes. (Jimenez-Lopez et al., 2002).
2.1 Alcohol absorption
Alcohol is absorbed throughout the gastrointestinal (GI) tract by the process of simple diffusion. The absorption rate mainly depends on various factors. Firstly, difference in diffusion concentration gradient between the mucosa of GI tract to the adjacent blood vessels. Secondly, gastric emptiness during drinking, for example, presence of food in the stomach can lower the rate of alcohol absorption while an empty stomach can fasten the rate of alcohol absorption when drinkers consumed the same concentration of alcohol. Thirdly, types of alcoholic beverages, which means different concentration of alcohols. The absorption rate of alcohol is quicker when consuming the same volume of whisky or vodka rather than beers. Moreover, some individual factors like gender, age, nationality of consumer, body temperature etc. are also important in alteration alcohol absorption rate, while, the mobility of gastric muscles and the intestinal blood flow may also play an important role as well. (Bode & J., 1997)
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2.2 Alcohol dehydrogenase isozymes and first pass metabolism in the GI tract
Human alcohol dehydrogenase (ADH) is a zinc-containing enzyme which mainly located in the cytoplasm of cells. Human ADH exists with five classes of different molecular forms that arise from the association of eight types of subunits into active dimeric molecules. ( Lieber, 2000). ADH has broad substrate specificity that can metabolize different form of alcohol such as primary, secondary, and aromatic alcohols into their corresponding aldehydes and ketones. ADH is a key enzyme that mediates the conversion of alcohols into their corresponding aldehyde assisted by cofactor. Up to 80-90% of ADH is distributed in liver. ( Seitz, H. K., & Oneta, 1998) However, the isozymes of ADH are also found to be present in GI tract of rat by Lamboeuf, de Saint-Blanquat and Derache (1981). Gastrointestinal ADH involves in the metabolism of oral-taken alcohol into acetaldehyde. Later on Cabelleria et al. (1989) and Frezza et al. (1990) suggested that alcohol metabolism actually starts at stomach, as a results, first pass metabolism (FPM) appeared when a certain quantity of oral-taken alcohol is primary metabolized in either the GI tract or the liver before entering the circulation.
In general, the hepatic ADH has a much higher affinity to ethanol than in extrahepatic tissues. The extrahepatic ADH enzymes are almost inactive to ethanol so that their contribution to overall alcohol metabolism is negligible. Exceptionally, gastric ADH has a relatively high affinity in high alcohol concentrations. The co-expression of different combinations of class I, III and IV ADH isozymes (Seitz et al., 1998) throughout the GI tract acts as a metabolic barrier against endogenous ethanol produced via bacterial fermentation or against orally taken ethanol. Therefore, a noticeable amount of ethanol is metabolized into acetaldehyde to avoid ethanol form directly entering the circulation through digestive system. The presence of ADH in GI tract explains why the blood alcohol concentration is usually higher after intravenous administration of alcohol while it is lower after oral intake of same amount of alcohol as intravenous administration. (N Sato & T Kitamura, 1996)
2.3 Acetaldehyde dehydrogenase isozymes
Acetaldehyde dehydrogenase (ALDH) isozymes are the major family of enzymes that oxidize acetaldehyde derived from ethanol oxidation. ALDH isozymes are NAD+ dependent. and can be simply classified into cytosolic ALDH1 and mitochondrial ALDH2 according to their locations. (Greenfield& Pietruszko, 1977). However, Goedde and Agarwal(1987) reported that at least 4 isozymes of ALDH coded by various gene loci have been found in human body according to their different properties such as kinetic properties, electrophoretic mobility and their distributions. Therefore, ALDH can be classified into ALDH-I ,II, III and IV regarding to their increasing isoelectric point and decreasing anodic electrophoretic mobility. In order to avoid the confusion of the nomenclature on the ALDH, nomenclature of ALDH-I ,II, III and IV will be used in this study. Isozymes ALDH I and II are predominant in most body tissue including liver, intestine, kidney and brain, while ALDH III are mainly found in stomach. (Agarwal and Goedde, 1990a). Since liver is the most important organ for ethanol metabolism, ALDH I and II are the two prominent isozymes mediating the major oxidation of ethanol-derived acetaldehyde.
2.4 Alcohol dehydrogenase pathway
After drinking alcohol, it simply diffuses into mucosal cells and then oxidized by mucosal ADH, while the remaining portion is metabolized by hepatic ADH. The two hydrogen atoms of ethanol are split by ADH so that ethanol is converted to acetaldehyde with the reduction of NAD+ to NADH. The chemical equation is shown below:
CH3CH2OH + NAD+ ï¿½ï¿½ CH3CH=O + NADH + H+
Acetaldehyde is highly toxic and carcinogenic to our body which needs a quick removal by ALDH in liver. ALDH oxidizes acetaldehyde into acetate with the reduction of NAD+ to NADH. The chemical equation is shown below:
CH3CH=O + NAD+ ï¿½ï¿½ [CH3COO]- + NADH + H+
Acetate molecules will be further broken down into water and carbon dioxide or it can be converted to acetyl-coA for the source of Kreb cycle.
During these two biochemical reactions, a co-enzyme nicotinamide adenine dinucleotide (NAD) serves as the hydrogen acceptor to facilitate the reactions by chemically reduced itself into NADH. Besides, in the case of over drinking of alcohol, the production of NADH insides the cells (mucosa or liver cell) increases excessively during alcohol metabolism. This may lead to a rise of NAD+ to NADH ratio and subsequently alters intracellular biochemical pathways so as to promote the fatty acid synthesis.
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2.5 The microsomal ethanol oxidizing system
The microsomal ethanol oxidizing system (MEOS), which is also called cytochrome P450 pathway, is an alternative pathway of alcohol metabolism found in at liver microsome. The reaction aims to oxidize ethanol to acetaldehyde by the ethanol- inducible CYP2E1 (an enzyme belonging to cytochrome P450 family of enzymes). This enzyme system depends on nicotinamide adenine dinucleotide phosphate (NADPH) as a co-enzyme rather than NAD. In fact, the activity of MEOS increases significantly among individuals with chronic alcohol consumption; however, it only plays a minor role in ethanol oxidation in individuals without chronic alcohol consumption. This adaption response on increasing ethanol oxidation results in increasing production of acetaldehyde, which exhibits certain toxicity to the hepatic cells. Even though with the absence of alcohol, CYP2E1 is still being metabolically active that may produce reactive oxidative species (ROS) such as hydrogen peroxide and free radicals (Figure 5.). An increase in consumption of alcohol also increases the activity of MEOS as well as production of CYP2E1 inside the body. Therefore, long-term alcohol consumption significantly increases ROS generation by cytochromes, which may lead to damage to the cell membrane likes lipid peroxidation and consequent cell damage. (Doria, 1997)
2.6 Catalase mediated pathway
Catalase, which located in the peroxisomes in liver, may be involved in the alcohol metabolism. Catalase is able to oxidize various alcohols to their corresponding aldehydes with the presence of hydrogen peroxide. The chemical equation is shown below:
CH3CH2OH +H2O2 +Catalase ï¿½ï¿½ CH3CH=O + 2H2O + Catalase
Since the rate determining factor of this reaction is amount of hydrogen peroxide. Therefore, the ethanol metabolism is limited by the amount of hydrogen peroxide inside the cells. Lieber et al. pointed out that the contribution of catalase for the total alcohol oxidation is generally minimal. (Agarwal & Goedde, 1990b)
Part III. Anti-alcoholic mechanisms of the commercial products
Four types of anti-alcoholic mechanisms can be categorized for the 5 commercial products (AlcolOut, RU21, Hythiol-C, Niu-chang-chih Royal Health Supplement and Jiejiuling Koufuye). They involve in both physical mechanisms such as acting as physical barrier to prevent alcohol absorption; and biochemical mechanisms for instance reduction on: acetaldehyde level; the ethanol induced oxidative stress by maintaining glutathione level and the desire on alcohol drinking.
Figure 7. AlcolOut (ï¿½sï¿½Kï¿½ï¿½) (Source : http://www.alcolout.com/en/products.html)
Figure 8. RU21(ï¿½wï¿½é´¶ï¿½Æ¦Xï¿½ï¿½) (Source: http://www.ru21.com/index.html)
Figure 9. Hythiol-C (ï¿½wï¿½Kï¿½Pï¿½Ñ°sï¿½Y)
(Source : http://www.rabbit.com.hk/product_detail.php?id=15)
Figure 10. Niu-chang-chih Royal Health Supplement (ï¿½ï¿½ÌªÛºï¿½ï¿½)
Figure 11. Jiejiuling Koufuye(ï¿½Ñ°sï¿½Fï¿½fï¿½Aï¿½G)
3.1 Physical mechanism
3.1.1 Physical barrier
AlcolOut (ï¿½sï¿½Kï¿½ï¿½) is commercial anti-alcoholic products that exhibited in form of capsules. AlcolOut is made of the powder of Konjac glucomannan (KGM)(ï¿½ï¿½ï¿½) and the capsule is made of hydroxypropyl methylcellulose. Konjac mannan is a high molecular weight, water-soluble, nonionic glucomannan found in tubers of the Amorphophallus konjac plant (ï¿½]ï¿½ï¿½). KGM is a linear random copolymer of linked beta-D-mannose and beta-D glucose. (Figure 12.) It has mannose and glucose units at molar ratio of 1.6 : 1. (Vipul Dave, & Stephen, P. M., 1997) KGM is the most viscous soluble fiber in nature. The high viscosity contributes to the ability of absorption and retains large quantities of water and forms a viscous gel within half an hour after hydration. (Patents, 2012)
The mechanism proposed by AlcolOut is that the capsules dissolve in the stomach and then release KGM powder which will form a water-soluble fiber gel after absorption of water, KGM can swell and become bulky gel in the stomach which acts as a physical barrier to reduce the concentration of alcohol form entering the bloodstream. Since KGM is resistant to degradation by digestive enzymes, the fiber gel with alcohol will be excreted out of body through intestinal peristalsis.
3.2 Biochemical mechanisms
3.2.1Sequestration of ethanol-derived acetaldehyde
RU-21(ï¿½wï¿½é´¶ï¿½Æ¦Xï¿½ï¿½) was produced by a group of scientists under the lead of Russian scientist, Prof. Eugene Mayevsky at the Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences. RU-21 is regarded as dietary supplement as its main ingredients are amino acid and vitamins, including L-cysteine alpha lipoic acid, L-glutamiate, succinic and fumaric acids, glucose and vitamin B2, B6, C. At the same time, another anti-alcoholic product Hythiol-C (ï¿½wï¿½Kï¿½Pï¿½Ñ°sï¿½Y) manufactured by Japanese enterprise (ï¿½é¥»ï¿½Õ¨ßµP) in Japan, whose main ingredients are also L-cysteine, and vitamin C, as well as vitamin B5. In my review, cysteine is studied in the function of acetaldehyde sequestering.
Cysteine, (2R)-2-amino-3-sulfanyl-propanoic acid is a sulfur-containing, non-essential amino acid, classified as a hydrophilic amino acid (Peana et al., 2009), which can be synthesized by human body. Cysteine is considered to provide important source of sulfide for various metabolism. The high reactive thiol group of cysteine is usually involved in many enzymatic reactions. As acetaldehyde is the first metabolite of ethanol, which may mediates several ethanol-induced effects, scientists considered that sequestration of acetaldehyde may help to relieve those ethanol-induced effects. An experiment, conducted by Peana et al., revealed that a competitive inhibitor of acetaldehyde, 4-methylpyrazole (4-MP) and a selective acetaldehyde-sequestrating agent, D-penicillamine (DP) administered before the intragastric administration of ethanol reduces ethanol-induced conditioned place preference (cpp), supporting the hypothesis that motivational actions of ethanol consumption may be mediated by acetaldehyde (Font et al., 2006; Melis et al., 2007; Peana et al., 2008).
DP is a compound also contains the thiol group just similar to cysteine. Therefore, cysteine is proved that it can be acetaldehyde-sequestering agent, which is able to bind covalently with ethanol-derived acetaldehyde in vivo (Cederbaum and Rubin, 1976; Nagasawa et al., 1978, 1984). Acetaldehyde undergoes a non-enzymatic condensation reaction and consecutive ring formation with cysteine to form 2-methylthiazolidine-4-carboxylic acid (MTCA) (Reischl et al., 2012) and thus prevents ethanol-derived acetaldehyde from interacting with cellular proteins (Salaspuro et al., 2002; Sprince et al., 1974; Vasdev et al., 1995) to cause cellular damage. The mechanism of acetaldehyde sequestering is illustrated in Figure 13.
3.2.2 Maintenance of glutathione (GSH) level
Niu-chang-chih Royal Health Supplement (ï¿½ï¿½ÌªÛºï¿½ï¿½) is manufactured by GeneFerm Biotechnology Company limited in Taiwan. The active ingredients in this product are Antrodia camphorate and soybean Polyenylphosphatidylcholine (PPC). These two important ingredients contribute to maintaining of GSH level.
Antrodia camphorate, commonly named Niu-chang-chih(ï¿½ï¿½Ìªï¿½) is a unique fungus found locally in Taiwan. Niu-chang-chih has common name called ï¿½ï¿½Niu-chang-kuï¿½ï¿½ or ï¿½ï¿½chang-chihï¿½ï¿½ in China. Niu-chang-chih is precious fungus that only grows in the inner wall of the hollow of the Cinnamomum kanehirae Hayata (Lauraceae ) , ï¿½ï¿½Niu-changï¿½ï¿½ (ï¿½ï¿½ï¿½) is the Chinese common name for Cinnamomum kanehirae (Bull camphor tree)(Wu et al., 1997). Cinnamomum kanehirae is endemic tree with large evergreen broad-leave in Taiwan. (Geethangili and Tzeng, 2011) As a local species, Niu-chang-chih had been long used in Taiwanese aborigines as a traditional prescription for the discomforts caused by alcohol drinking or exhaustion. (Ao et al., 2009)
There is over 78 compounds have been identified in the crude extracts of Niu-chang-chih. (Geethangili and Tzeng, 2011) Those chemical ingredients found in Niu-chang-chih include triterpenoids, polysaccharides sesquiterpene lactones, steroids, phenol compounds, adenosine, cordycepin, ergosterol, etc. (Chang et al., 2005; Lu et al., 2006). Recently, scientists have put emphasis on investigation of hepatoprotectvie effects induced by Niu-chang-chih. Thus, either the fruiting bodies or mycelia of Antrodia camphorate have been reported to exhibit ability of ameliorating liver disease for instance, alcohol ï¿½Vinduced liver injury, fatty liver and liver fibrosis as well as inhibiting liver cancer cell growth. (Ao et al., 2009)
As mentioned, Niu-chang-chih has been used to relieve the hangover syndrome and cure the discomfort caused by excessive alcohol consumption for a long history. Recently, scientific research showed evidence on the hepatoprotectvie effects of Niu-chang-chih against liver injury caused by acute hepatotoxicity of alcohol via acute ethanol-intoxicated rats as an experimental model. Although the protective mechanism of Niu-chang-chih is not clearly known, Lu et al. proposed a mechanism related to prevention of oxidative damage induced by acute alcohol consumption based on their experimental results. (Lu et al., 2011)
They believed that Niu-chang-chih exerts its hepatoprotectvie effect by up-regulating glutathione (GSH)-dependent enzymes and inhibits ROS formation in the liver.
In liver mitochondria, GSH perform as a free radical scavenger which converts hydrogen peroxide into water by the action of glutathione peroxidase (GPx). GSH is oxidized to GSSG and then turns back to GSH by glutathione reductase (GR). It is regarded as an important antioxidant mechanism. However, excess intake of alcohol causes the elevation of alcohol-derived acetaldehyde by the increase in action of ADH with the conversion of cofactor NAD to NADH. High production of acetaldehyde leads to binding of GSH and then caused a significant depletion of GSH in mitochondrial GSH pool in the liver. Apart from this, the aforementioned study showed a decline in activities of both GPx and GR in the rats treated with acute alcohol intake compared to control group. This may be resulted from significantly drop in GSH level. Therefore, inhibition in GR leads to a decrease in reconversion of GSSH to GSH. Extract of Niu-chang-chih could normalize the above depletion of GSH level as well as enzymatic activities of both GPx and GR(Lu et al., 2011), which may be contributed to the ability of Niu-chang-chih for up-regulating hepatic GSH-dependent enzymes.(Song and Yen, 2003)
Apart from Niu-chang-chih, soybean PPC is another active ingredient from the same anti-alcoholic products which obtained from soybean extract. Since excessive alcohol consumption could cause alcoholic diseases which could be attributed to the excessive generation of free radicals which enhances oxidative stress in liver. As a consequence, hepatic GSH would be reduced. The mechanism of soybean PPC is that it has effect on remediation of the increased oxidative stress and GSH depletion by maintaining S-Adenosyl methionine (SAM) level.
Soybean PPC is a mixture containing around 95% of polyunsaturated phosphatidylcholines (PC), about half of which is dilinoleoylphosphatidylcholine. (Lieber et al. 1994) Actually, PC is a class of phospholipids that incorporate choline as a headgroup. The body cells synthesize PC by methylation of phosphatidylethanoamine (PE) in the methionine cycle for the production of extracellular fats and lipoproteins. (Figure 17.) As a result, the level of intracellular SAM is reduced as partial SAM is converted into S-Adenosyl homocysteine (SAH) under the methylation process. However, soybean PPC in the products can act as the exogenous source of PCs so that the intracellular SAM can be reserved for the synthesis of GSH through the transsulphuration.
An experiment conducted by Aleynik & Lieber , which indicated that the alcohol treated group of rats showed obvious SAM depletion when comparing to control group after 8 weeks of treatment. However, the SAM depletion was remediated by PPC treatment.
Meanwhile, the depletion of GSH in alcohol treated group of rats show an increase in the oxidative stress. Rats treated with either PPC in their diet alone or with alcohol together also showed a remediation of GSH level comparing to the alcohol treated group.
Therefore, the active ingredient PPC can minimize the utilization of SAM by providing the source of PCs and thereby SAM can be reserved for the replenishment of GSH in order to alleviate the alcohol induced oxidative stress. (Aleynik & Lieber, 2003)
3.2.3 Reduction on desire of alcohol consumption
Jiejiouling Koufuye (ï¿½Ñ°sï¿½Fï¿½fï¿½Aï¿½G), is a Chinese herbal liquid extract for direct oral intake, whose main ingredients is Radix pueraria. Radix pueraria has common name called gegeng (ï¿½ï¿½ï¿½ï¿½) in Chinese as well as kudzu root in western society. Daidzin, an isoflavone isolated from Radix puerariae whose formal name is the 7-glucoside of 4',7-dihydroxyisoflavone. Keung and Vallee found that daidzin is possible inhibitor for the mitochondrial aldehyde dehydrogenase (ALDH-I) potentially and reversibly. ( Keung and Vallee, 1993) Even though the mechanism still is not clearly known. But interestingly, daidzin does not act like disulfiram.
Disulfiram, an official medication has been approved by the United States for treating alcohol dependence. Disulfiram can increase the sensitivity to alcohol due to its irreversible inhibiting effect on ALDH. It inactivates ALDH activity by covalent alternation of amino acid residue which is important for catalysis of ALDH, in where disulfiram can promote disulfide bond linkage between Cys-302 and a vicinal sulfhydryl group, those in the enzyme active site. (Hempel, Pietruszko, Fietzek & Jornvall, 1982) Since the ALDH activities are inhibited, acetaldehyde will be accumulated in body and thereby leading wide range of uncomfortable hangover symptoms including severe vomiting and headache to occur quirkily after individual orally intake of small amount of alcohol. As a result, disulfiram can discourage drinkers to drink more alcohol due to their unpleasant feeling. (Disulfiram, 2010)
However, the chemical structure of disulfiram and daidzin are not resembled. This may explain that daidzin has different mechanism toward ALDH-I inhibition. Keung and Vallee thought that the possible reason for the action of daidzin may be attributed to its a,a -unsaturated carbonyl function, which is similar with the vinyl ketone. For an example, (Z)-hexadeca-1,11-dien-3-one is vinyl ketone can inactive ALDH by the formation of Michael addition product with the Cys-302. (Blatter, Tasayco, Prestwich and Pietruszko, 1990)
Therefore, daidzin has similarity with vinyl ketone allow it to form adduct with Cys-302. This kind of ALDH inhibition can be relieved by dilution effect of daidzin. ( Keung and Vallee, 1993) The experimental results showed that a low concentration daidzin selectively inhibited ALDH-I (cytosolic ALDH) while disulfram preferably inhibited ALDH-II (mitochondrial ALDH). (Figure 23.)
A further study demonstrated that the Syrian golden hamsters treated with daidzin (150mg/kg/d) successfully suppressed alcohol intake by almost 70%. (Keung et al.1995)
In order to investigate whether gegeng has effecitvie anti-alcoholic effect on human body, Lukas et al. demonstrated that human individuals pretreated with gegeng extracts containing three major isoflavones (puerarin, daidzin, and daidzein) and then undergone ethanol treatment. In Figure 25., it shows that individuals with gegeng pretreatment resulted in a marked reduction in the sip volume whereas an increase in total number of sips per beer, which indicated that the testing individuals took significantly more number of sips but with smaller sips volume to drink and finish each beer after receiving gegeng pretreatment. Figure 26. also shows a total reduction on drinking of subsequent beer. (Lukas et al., 2005)
Lukas et al. also reported that testing participants had showed intoxicated symptoms after consuming a standard alcohol drink. Those participants were pretreated with the same gegeng extract in their previous experiments. (Lukas et al., 2000) These results may suggest gegeng achieving the effect of reduction on alcohol drinking by prolonging or enhancing the acute effects of the first drink. This alternation in the drinking pattern may indicate that gegeng has an effect on postponement or elimination the desire of drinkers to drink subsequent beers especially in ï¿½ï¿½bingeï¿½ï¿½ drinking occasion. (Lukas et al., 2005) Even though daidzin do not similar to disulfiram, it seems that daidzin potently generate the similar effect that to cause aversion to further drinking alcohol and thus to reduce the desire alcohol consumption.
Part IV. Critical review on the effectiveness of the products
After the study of different anti-alcoholic mechanisms of five different commercial products, the next step is to evaluate the effectiveness and reliability of the products.
Firstly, AlcolOut possesses physical mechanism that mainly relying on KGM as absorbent to absorb alcohol in stomach. However, the stability for alcohol absorption by KGM has not been studied. It is no evidence that KGM can hold ethanol molecule tightly, thus it may release alcohol during intestinal peristalsis, which is still absorbed by small intestine. Therefore, AlcolOut might delay the absorption of alcohol but not reduce the amount of alcohol being absorbed. Besides, negative effect might be induced by the intake of AlcolOut. Since the gel formation inside stomach can reduce the gastric emptiness. It delays gastric emptiness time and leads to a longer exposure of ethanol to gastric ADH. It would result in increased of gastric ethanol metabolism and gastric FPM. (Oneta et al., 1998) Formation of acetaldehyde locally in mucosa of stomach would be increased which might further cause acetaldehyde-associated toxicity to mucosal layer. Thus, AlcolOut is considered as not reliable upon its proclaimed anti-alcoholic effects.
Secondly, RU21 and Hythiol-C provide amino acids and vitamins for bodyï¿½ï¿½s needs which is indirectly support ethanol metabolism. This is regarded as relatively less contribution to ethanol metabolism. However those nutrients may faster the energy replenishment after hang-over and support anti oxidative system. Especially for cysteine, apart from acetaldehyde sequestration, it is important for production of hepatic GSH. Despite importance of cysteine, it can be produced by human body and various vitamins can be absorbed from diets. Hesitation is stirred whether we need to intake of these kinds of supplements to boost up the ethanol metabolism. Thus, this makes the products less persuasive on its proclaimed effectiveness but it is theoretically reliable.
Thirdly, although the aforementioned mechanisms of isoflavones (daidzin) from gegeng of the product Jiejiouling Koufuye is not really clear, the experiment results still support daidzin possessing inhibitory effect on ALDH-I and then to reduce the desire of drinking on subsequent alcoholic beverages. However, the effectiveness of herbal extraction products mainly depend on the concentration of the active ingredients like daidzin. Lukas et al. (2005) have analyzed various commercial kudzu root preparations and discover their isoflavone concentrations are widely different, even though within the same manufacturer. The concentrations of the active ingredients extracted from natural gegeng in the most preparations are less than 1%. Therefore, we can deduce that only a trace amount of isoflavones present in the commercial products like Jiejiouling Koufuye, thus it is considered as not reliable due to the insufficient concentration of the active ingredients for reaching the effective dose or therapeutic dose regarding to human. Therefore, the effective dosage of daidzin or other isoflavones to cause inhibitory effect on human ALDH still need further studies.
Finally, the mechanism of Antrodia camphorata in the Niu-chang-chih Royal Health Supplement is not well known even though many reports showed positive effects on hepatic protection against alcoholic liver diseases and alcohol-induced oxidative stress. On the other hand, another ingredient, Soybean PPCs was found to restore the SAM level so that more SAM would be available for remediation of the depleted GSH level. Therefore, Niu-chang-chih Royal Health Supplement is considered as relatively reliable products. However, majority of the existing reports or researches used rats as testing target. Neither the human-testing research nor clinical experiment on mechanism of Antrodia camphorate is limited.
Table 2. summarizes the corresponding types of mechanisms and the reliability of anti-alcoholic effects. Among the 5 products, Niu-Chang chih is reliable; RU21 and Hythiol-C are theoretically reliable whereas AlcolOut and Jiejiouling Koufuye are considered to be not reliable respectively and relatively.
Name of products Active ingredients Types of mechanism Reliability of the effects
ï¿½sï¿½Kï¿½ï¿½ KGM Physical barrier Not reliable
ï¿½wï¿½é´¶ï¿½Æ¦Xï¿½ï¿½ L-cysteine Acetaldehyde removal Theoretically reliable
ï¿½wï¿½Kï¿½Pï¿½Ñ°sï¿½Y L-cysteine Acetaldehyde removal Theoretically reliable
Niu-chang-chih Royal Health Supplement
ï¿½ï¿½ÌªÛºï¿½ï¿½ Antrodia camphorata ,
PPCs Maintenance of GSH level Relatively reliable
ï¿½Ñ°sï¿½Fï¿½fï¿½Aï¿½G Daidzin Reduction on desire of alcohol consumption Not reliable
Part V. Further investigation
In fact, some commercial anti- alcoholic products are regarded as health supplements; there is no corresponding ordinance to monitor these types of product in Hong Kong. People may be neglect on the harmful effects caused by the over consumption of those anti-alcoholic products. Therefore, toxicity of the products, that especially containing Chinese herbal ingredients, would be a major concern when intake of the products. As mentioned, although isoflavones from Radix puerariae shows potently inhibitory effects on ALDH-I, its toxicity is not fully studied. It is considerable to determine the toxic dosage for human as the anti-alcoholic products with Radix puerariae as active ingredient are being common in not only China but also western market. (McGregor, 2007)
Furthermore, it is critical that whether toxicity would be induced by combined usage of products or drugs. For example, Radix puerariae has similar metabolic activity with drug Disulfiram, and thus it might trigger unexpected effects when these two products were consumed at the same time by drinkers. In addition, further investigation can put emphasis on testing the active ingredients alone of each product in order to determine whether the anti-alcoholic effects are induced by single active ingredients or multiple compounds through reactions and certain mechanisms. Therefore, the relationship between different chemicals in the same anti-alcoholic products can be independently studied in order to find out any effects related to anti-alcohol or toxicity toward subjects.
Apart from the toxicity, effectiveness on either short-term or long-term consumption of the products is another consideration. For example, whether individual need either short-term or long-term consumption of products containing ingredients of amino acids and vitamins to achieve effective anti-alcoholic effects.
Part VI. Conclusion
After a comprehensive literature review on different mechanisms of various anti-alcoholic supplements, some of them (Alcolout, Jiejiouling Koufuye) are considered as has low reliability on their effectiveness to meet the proclaimed pronounced anti-alcoholic effects. Even though, misleading message can be easily found on productsï¿½ï¿½ advertisement likes AlcolOut since Hong Kong lacks corresponding ordinance to regulate the health supplements. Meanwhile, the public mainly concern about efficacy and safety of products but sometime neglect the reliability of the products. RU21 and Hythiol-C are example that cannot show a relative constant reliability of their effects. However, Niu-chang-chih was proved to have certain degree of reliability on hepactic protective effect.