Christian Spirituality and Science Issues in the Contemporary World

Volume 8 Issue 1 and the Christian Faith Article 3

2010

The Biochemical and Pathophysiological Effects of Alcohol Consumption

Jodie Beecroft Avondale College

Amanda Kemp Avondale College

Sophie Lassila Avondale College

Daniel Sheedy Avondale College

Ewan Ward Avondale College

Follow this and additional works at: https://research.avondale.edu.au/css

Recommended Citation Beecroft, J., Kemp, A., Lassila, S., Sheedy, D., & Ward, E. (2010). The biochemical and pathophysiological effects of alcohol consumption. Christian Spirituality and Science, 8(1), 25-43. Retrieved from https://research.avondale.edu.au/css/vol8/iss1/3

This Article is brought to you for free and open access by the Avondale Centre for Interdisciplinary Studies in Science at ResearchOnline@Avondale. It has been accepted for inclusion in Christian Spirituality and Science by an authorized editor of ResearchOnline@Avondale. For more information, please contact [email protected]. Beecroft et al.: The Biochemical and Pathophysiological Effects of Alcohol Consump

The Biochemical and Pathophysiological Effects of Alcohol Consumption Jodie Beecroft, Amanda Kemp, Sophie Lassila, Daniel Sheedy and Ewan Ward Faculty of Science and Mathematics Avondale College

Abstract While the stance of some conservative Christian (and other) groups advocat- ing abstinence from alcohol intake may not be popular, contemporary research into alcohol and its effects on the body may lend weight to such a position. The consumption of alcohol, coupled with its addictive properties, can lead to a wide variety of societal problems that are not only costly in medical terms but also in terms of domestic violence, accidents and antisocial behaviour.

Alcohol is metabolised by the liver and this organ may be consequently damaged resulting in serious impairment of normal hepatic structure and function. Nearly all the physiological systems of the body are adversely affected by alcohol to varying degrees and the behavioural effects observed with intoxication are associated with compromised neurotransmitter functions in the brain and altered brain structure in the long term. Adverse consequences of alcohol intake may be evident in other systems including the cardiovascular, gastrointestinal, reproductive and immuno- logical systems. There is an increased risk of atherosclerosis, of the oral cavity, and immune system disturbances associated with prolonged alcohol intake. In pregnant women alcohol metabolism is reduced and as the developing foetus has lowered ability to metabolise blood alcohol compared to an adult there is an elevated risk of serious consequences associated with foetal alcohol syndrome. Despite the nearly overwhelming negative consequences of alcohol intake, the beneficial effects of drinking red wine linked to lowered heart disease despite a high (the ‘French Paradox’) may be associated with the antioxidants and other polyphenols also found in non-alcoholic red juice. Serious consideration of the effects of alcohol on the body should inform decisions on the intake of alcohol.

In troduction Conservative Christian denominations this view that range from the preven- and associated temperance groups tion of alcohol related social disrup- have often advocated total abstinence tion, increased accidents and impair- from alcohol consumption. Various ment of family life to the Christian reasons have been given in support of responsibility of honouring the body

25 Published by ResearchOnline@Avondale, 2010 1 Christian Spirituality and Science, Vol. 8 [2010], Iss. 1, Art. 3

as the temple of the Holy Spirit. Such The Role of the Liver positions have often been viewed in in Metabolism a negative sense by not only secular The human body is continuously society but also other more liberal subject to a wide variety of environ- Christian groups. There is no doubt mental chemicals2. While many of that alcohol is a significant contribut- these chemicals are of benefit, there ing factor for many problems in soci- are those that are very harmful2. The ety, a fact supported by contemporary food we eat, the air we breathe, our sociological and scientific research. occupations, the very environment that Such research may lend significant surrounds us on this planet consists of support to the arguments of temper- a massive reservoir of such chemicals. ance groups. Chemical compounds from the envi- ronment (both beneficial and harmful) In 2004, 83 percent of Australians may gain entry (deliberately or other- reported drinking alcohol, and one wise) to the body through the lungs, in five of these reported drinking at gastrointestinal tract and the skin. The levels associated with a high risk of liver is the major metabolic organ of harm at least once a month1. Con- the body not only processing nutrient sidering the contribution of alcohol molecules from the gastrointestinal consumption to a range of societal tract but also detoxifying harmful problems including serious systemic chemicals by transforming them into disease, domestic violence and road more water soluble forms so that they accidents, this behaviour appears to be may be more easily excreted from uninformed given the accumulation of the body (often through the urinary a large body of literature documenting system)2. Unfortunately the detoxifica- the harmful effects of alcohol on the tion process can result in liver damage, body. The wide range of serious medi- either directly from exposure to the cal problems associated with alcohol harmful molecules themselves or from consumption relates to the fact that subsequent metabolites formed during nearly all the body’s physiological the detoxification. systems are adversely affected. This also results in diverse psychosocial The liver is the second largest organ of problems which are of great cost the body and weighs about 1.4 kilograms to society in general, families and in an average adult. The main functional individuals specifically. This paper cell of the liver is the hepatocyte which examines some of the biochemical and is relatively large when compared to the pathophysiological effects associated average body somatic cell3. Hepatocytes with alcohol consumption beginning are metabolically very active, continu- with how the body metabolises or ously processing and storing nutrients, processes alcohol. manufacturing proteins and carrying out detoxification reactions2.

26 https://research.avondale.edu.au/css/vol8/iss1/3 2 Beecroft et al.: The Biochemical and Pathophysiological Effects of Alcohol Consump

Kupffer cells are also present in the there are two main enzymes that are sinusoids of the liver. They are ac- involved in the metabolic oxidation tive phagocytic cells and effectively of ethanol5. These reactions mostly remove pathogens or other unwanted occur within the hepatocytes of the substances from the blood filtering liver and involve the enzymes alcohol through this organ. Both of these cell dehydrogenase (ADH) and aldehyde types are affected by high concentra- dehydrogenase (ALDH). The presence tions of alcohol which can lead to of ADH is essential in dealing with a decrease in their ability to act in different types of alcohols resulting disease prevention3. from normal cellular metabolism or even the low levels occurring in Metabolism of Alcohol ripe fruit etc. Such alcohols derive Although most ingested alcohol is me- from metabolites such as lactate, hy- tabolised in the liver, between two and droxybutyrate, sorbitol, and glycerol ten percent escapes metabolic activity phosphate5. and is directly excreted through the lungs, or in the urine or perspiration4. These enzymes participate in a simple The excretion of alcohol from the two step oxidative pathway that ulti-

lungs forms the basis of breath test- mately converts (CH3CH2OH) - 5 ing for intoxication levels. In humans into acetate (CH3CO2 ) .

+ ADH + 1. CH3CH2OH + NAD CH3CHO + NADH + H

+ ALDH - + 2. CH3CHO + NAD CH3CO2 + NADH + H

Acetaldehyde (CH3CHO), produced alcoholic beverages. Acetate can also by the action of ADH on ethanol is a be a reactive molecule when present very reactive molecule being quickly in higher concentrations that may re- converted to acetate by ALDH6. sult from alcohol metabolism. It can Acetaldehyde is capable of binding depress the central nervous system to proteins forming harmful modifica- and detrimentally affect various other tions which can cause serious damage metabolic processes6. in brain and liver tissue6. Pathophysiological The final product of this two step Effects of Alcohol reaction is the much less harmful The harmful effects of alcohol on acetate, which is a naturally occurring different organs of the body are quite metabolite5. However the formation of diverse. Some of the more common excess acetate can have a damaging pathological problems associated caloric effect along with any sugar with alcohol consumption are now or other nutrient molecules added to considered.

27 Published by ResearchOnline@Avondale, 2010 3 Christian Spirituality and Science, Vol. 8 [2010], Iss. 1, Art. 3

Liver lagen, the basis of scar tissue7. Scar As the liver is the main site of al- tissue is non-functional tissue and as cohol metabolism, it is particularly it progressively replaces healthy liver susceptible to the harmful effects of tissue liver functionality is lost. alcohol. There are three main stages of alcoholic liver disease: fatty liver, The final stage of liver disease is cir- , and alcoholic cir- rhosis. This is characterised by fibrosis rhosis. of the liver to such an extent that it Fatty Liver stiffens blood vessels passing through The metabolic breakdown of alcohol to the liver, and seriously alters liver acetaldehyde is an oxidation reaction structure and function9. In cirrhotic that changes the chemical redox state livers blood flow is directed around of the hepatocyte, favouring the ac- rather than through damaged areas of cumulation of the coenzyme NADH7. hepatic tissue thereby leaving toxins This change affects several elements in the blood to affect other organs8. of liver metabolism. Gluconeogenesis In cirrhosis there is the vicious circle (the metabolic production of glucose of increased alcohol intake causing from non-carbohydrate sources) is increased liver damage but the liver prevented by the accumulation of becomes less and less able to metabo- fatty acids resulting from accelerated lise the alcohol, thus worsening and fatty acid synthesis7. This leads to fat prolonging the damaging effects of being deposited in the liver, and can alcohol. Cirrhosis has a high mortality eventually lead to the condition known rate, although death is usually from as fatty liver. This condition does not secondary causes, such as kidney fail- show clinical effects until the late ure8. It is estimated that ten to fifteen stages, and may be reversible if the percent of alcoholics will develop individual abstains from alcohol8. alcoholic cirrhosis10. The potential to prevent this condition was clearly Alcoholic Hepatitis demonstrated during the period of Pro- The next stage in liver disease is hibition in the United States when the hepatitis characterised by widespread mortality rates from cirrhosis halved hepatic inflammation and subsequent for the next twenty years11. development of necrosis and sub- sequent scar tissue formation9. The Brain and Central Nervous inflammation is a result of overpro- System duction of inflammatory mediators by The typical behaviour associated with activated Kupffer cells (liver macro- intoxication (slurred speech, impaired phages) in response to tissue damage7. reflexes and reaction times, unsteadi- Long term consumption of alcohol ness, disorientation, confusion and stimulates liver cells to produce col- emotional disturbances) is caused by

28 https://research.avondale.edu.au/css/vol8/iss1/3 4 Beecroft et al.: The Biochemical and Pathophysiological Effects of Alcohol Consump

the action of alcohol on the brain and ated with learning and memory13. central nervous system (CNS)12. Alcohol inhibits glutamate activity Neurotransmitters at NMDA receptors which can cause memory loss during intoxication Information is relayed throughout the (memory blackouts) and over time brain by electrochemical signalling reduce learning ability. It is believed processes where activated neurons that this may contribute to the memory release neurotransmitters that bind to impairing effects of alcohol12. Spatial receptors on other neurons. Electrical memory is also affected as the amount signals travelling down neurons cause of glutamate released in the hip- the release of neurotransmitters that pocampus of the brain is decreased. cross the synaptic junctions between Due to inhibited glutamate activity, nerve cells in order to carry signals chronic alcohol use can cause more through the complex neural networks NMDA receptors to form particularly of the brain. According to some neu- in the hippocampus, thalamus and the rologists there are well over 100 dif- cerebral cortex15. Following episodes ferent types of neurotransmitters and of alcohol consumption the amount hundreds of different respective target of glutamate released then increases receptors13. Any chemical interference which can lead to hyperexcitabilty, with neurotransmitters can manifest seizures, cell death and possibly ir- in motor and behavioural changes reversible alcohol-induced neuronal evident in an intoxicated individual12. damage during alcohol withdrawal14. Alcohol induces alterations in many different neurotransmitters and their Gamma-Amino- interactions with receptors. The main (GABA) System neurotransmitter systems affected are Gamma-amino-butyric acid (GABA) the glutamate, gamma-amino-butyric is a major inhibitory neurotransmitter acid (GABA), dopamine, serotonin in the CNS mediating fast synaptic and opioid peptide systems. inhibition throughout the brain12. GABA is sensitive to the effects of Glutamate System alcohol, causing enhancement of the Glutamate is a major excitatory function of GABA receptors on neurotransmitter in the brain and has A postsynaptic neurones. This means numerous different receptors in the that alcohol can bind to different nervous system14. One such target is sites on GABA receptors to that of the N-methyl-D-aspartate (NMDA) A GABA improving the efficiency of receptor and is most sensitive to alco- receptor activation12. There is uncer- hol exposure even at low doses12. tainty as to which GABAA subtypes NMDA receptors mediate enhanced are affected by alcohol because the signal transmission referred to as specific binding site has not yet been long-term potentiation (LTP) associ- identified14. However, the effects of

29 Published by ResearchOnline@Avondale, 2010 5 Christian Spirituality and Science, Vol. 8 [2010], Iss. 1, Art. 3

alcohol have been observed at very ogy. Alcohol acts on this system by low consumption levels, for example increasing dopamine release. This has the alcohol from a single drink binds a stimulating and energising effect

to GABAA receptors enhancing their and the accompanying pleasurable function13. Alcohol has the ability sensations are mostly experienced to act on presynaptic neurons which during the first twenty minutes of causes an increase in the release of alcohol exposure13. The elevation in GABA in some synaptic junctions in dopaminergic transmission increases the brain. This appears to cause some the firing rate of dopaminergic neu- of the characteristic signs of intoxica- rons thus increasing the amount of tion such as a lack of motor coordina- dopamine released in the mesolimbic tion, reduced anxiety and sedation12. system14. This appears to raise the Chronic causes alterations extracellular dopamine levels in other

to the subunits on GABAAreceptors regions of the brain connected by these which can in turn alter the effective- neurones. Altered dopamine levels in ness and timing of inhibitory synaptic other major brain structures have also transmissions. However the most been observed12. Furthermore, it is noticeable effects can occur during believed that dopamine plays a key alcohol withdrawal as the brain can role in alcohol addiction. As dopamine become hyperexcitable, triggering levels are decreased during alcohol seizures and anxiety12. withdrawal there is a reduction in neu- Dopamine ral firing causing melancholic feelings including depression and anxiety14. Dopamine is a neurotransmitter that is This can account for the typical feel- part of the brain’s mesolimbic system ing of needing to drink again to restore also known as the pleasure or reward levels of dopamine and experience the centre13. The dopaminergic (dopamine associated pleasurable feelings. activated) mesolimbic system is believed to be involved in functions Serotonin such as the brain’s mechanisms of The neurotransmitter serotonin (also reward, evaluation of environmental known as 5-hydroxytryptamine or stimuli and general behavioural activ- 5-HT) is involved in the regulation ity levels. Dopamine has a significant of mood, eating, arousal, sleep, pain effect on brain function even though it perception and perception of other is only produced by a limited number environmental stimuli14. It is a close of brain cells and only acts on specific chemical relative of dopamine. Se- brain regions12. There are at least five rotonin is produced by small distinct different types of dopamine receptors clusters of neurons located at the base and two of these classes have separate of the brain which are connected to and in some cases opposing or syn- other neurons throughout the CNS ergistic effects on neuronal physiol- including those in the cerebral cortex

30 https://research.avondale.edu.au/css/vol8/iss1/3 6 Beecroft et al.: The Biochemical and Pathophysiological Effects of Alcohol Consump

and other forebrain structures12. Effects of Alcohol on Brain Structures The consumption of alcohol acts to Alcohol not only affects chemical neu- increase the amount of serotonin that rotransmitters but also brain structure is released, even after a single drink. itself. It has been demonstrated that al- This affects behaviours such as emo- cohol can damage many regions of the tion, mood and cognitive thought brain and this damage may be either in individuals14. In the presence of temporary or permanent. The degree alcohol, each type of serotonin recep- of damage usually depends upon the tor produces different effects related age and gender of the individual, the to intoxication such as the perceived period of time in which they have rewarding effects of alcohol as well as been drinking and the level of alcohol withdrawal symptoms. Serotonin can consumption. Damage to the brain also stimulate an increase in dopamine due to alcohol intake occurs at lower production causing increased emo- consumption levels in women than tional behaviour and it may also affect men. Women may attain higher blood the GABA system influencing decision alcohol concentrations than men due making14. to their smaller body size and lower Opioid Peptide Systems concentrations of alcohol dehydro- Certain protein peptides are able to genase in the liver. Therefore they function as neurotransmitters and are reach the threshold for brain damage referred to as neuropeptides12. The at lower levels of alcohol consumption three major types of opioid peptide compared to their male counterparts17. include endorphins, dynorphins and Research has also shown that with enkephalins which contribute to the increasing age the brain becomes more regulating of pain, mood, appetite, vulnerable to the effects of alcohol reinforcement and response to stress14. consumption18. Alcohol enhances the activity of en- Brain Atrophy dogenous opioids by increasing their Brain atrophy, or shrivelling of the release in the brain, particularly from brain, is characterised by the loss of the pituitary and hypothalamus16. Al- neurons and connections between cohol also alters endogenous opioid them19. This results in impaired func- peptide receptors12. However, it is tioning of activities that the damaged not known how these effects con- regions of the brain control. Further- tribute to intoxication. On the other more, the consumption of alcohol has hand chronic alcohol use can lead to been linked with whole brain atrophy reduced endorphin levels accounting as well as atrophy of only certain for some of the negative emotional regions of the brain. For example, effects that are experienced during in males aged 60-64 years of age, withdrawal14. greater cortical atrophy in the frontal

31 Published by ResearchOnline@Avondale, 2010 7 Christian Spirituality and Science, Vol. 8 [2010], Iss. 1, Art. 3

and midtemporal lobes which is indi- amygdala activity also provides an ex- cated by larger lateral ventricles and planation for abnormal behaviour such less grey and white matter, has been as angry outbursts, emotional flatness observed17. and sensitivity22. Another contributor Neuroplasticity to this change in behaviour may be due to a reduction in the volume of the hip- Neuroplasticity refers to the brain’s pocampus observed in both alcoholic ability to change and reorganise it- men and women18. self throughout life by forming new connections between nerve cells and Prefrontal Cortex altering the activities of existing neu- The prefrontal cortex is the part of rons. This is important as it allows the the brain which decides whether an brain to compensate for injuries and to individual should take action or not23. adjust to new experiences, situations A percentage blood alcohol level of and changes in the environment. The about 0.08 has been shown to alter the plasticity of neurons is often decreased function of NMDA receptor ion chan- by the presence of alcohol in the brain nels. This inhibition affects the ability which is significant as it affects the of neurons to carry out their functions interaction between neurotransmitters and in the prefrontal cortex it results in and their receptors, damaging brain an inability to assess the consequences function16. of an individual’s reactions. This may Hippocampus and Amygdala contribute to poor decisions being made and uncontrolled behaviour by Magnetic resonance imaging (MRI) those consuming alcohol. In addition, studies indicate that alcoholics have it may be one of the reasons why decreased activation of neural cen- alcoholics have difficulty controlling tres such as the hippocampus and their drinking habits23. amygdala20. There is also reduced neuronal plasticity in these regions Cerebellum of the brain21. This appears to cause The cerebellum is one of the main emotional and cognitive abnormalities areas of the brain involved with motor which results in difficulty in detecting control and coordination. It is adverse- the emotional expressions of other ly affected by alcohol, decreasing in people21. The amygdala is involved size due to the shrinkage of large neu- in responding to facial expressions, rons in the anterior superior vermis24. while the hippocampus remembers Alcohol consumption also damages them. This has the potential to interfere the granule cells and Purkinje cells with interpersonal relationships and that make up the cerebellar cortex. can cause miscommunications which Purkinje cells are found throughout may lead to conflict or criminal be- the cerebellum and are packed tightly haviour. Diminished hippocampus and into a single celled layer2. They are the

32 https://research.avondale.edu.au/css/vol8/iss1/3 8 Beecroft et al.: The Biochemical and Pathophysiological Effects of Alcohol Consump

most abundant nerve cells found in the superior brain regions of alcoholics cerebellum and it has been found that and women display higher levels of chronic alcoholism has degenerative degradation than men24. A reduction effects on these cells. This explains in white matter of the frontal and why chronic alcoholics often ex- temporal lobes has been observed in hibit general co-ordination problems2. those who consume alcohol compared Thus, alcohol related damage to the to those who do not24. Therefore, there cerebellum results in body and lower is a clear link between alcohol con- limb motor deficits which are seen as sumption and decreased total white a lack of coordination and degraded matter volume. sense of equilibrium, slurred speech, Long term alcohol use has been shown visual problems, as well as diminished to result in changes in the morphol- higher order functions such as problem ogy, proliferation and survival of solving and memory. These effects neurons. Furthermore, many studies are irreversible after chronic alcohol have revealed that in alcoholics many consumption15. brain structures have reduced volume Grey Matter and White Matter compared to non-alcoholics. This MRI measurements have shown that has particularly been observed in the the consumption of alcohol causes a prefrontal cortex responsible for deci- reduction in cortical grey matter as sion making, the amygdala, the corpus well as grey matter in the superior callosum and the cerebellum25. Studies frontal and parietal lobes17. Alcohol have demonstrated that some of the use also decreases the grey matter structural and functional effects of volume in the cerebral cortex which alcohol on the brain may be reversed is the folded outer layer of the brain24. over time during a period of Alcohol can cause changes in white as the brain is able to regenerate some matter which are referred to as white regions, thus improving cognitive, matter hyperintensities (WHMs). sensory and motor functions. This WHMs are associated with brain at- may occur through remyelination, cel- rophy, poor physical health and with lular revoluming and neurogenesis24. cognitive, balance and gait deficits17. However, some changes are perma- A decrease in white matter volume has nent. Recovering chronic alcoholics been observed in those who consume particularly have impaired complex alcohol compared to those who do cognitive processes such as visuospa- not. This reduction in white matter tial abilities, psychomotor speed, gait, may be explained by demyelination balance and executive functions like or changes in axonal integrity caused working memory, problem solving, by alcohol17. Studies have also shown temporal ordering and response in- signs of fibre tract degradation, par- hibition24. Although the consumption ticularly of myelin in the frontal and of alcohol results in the impairment

33 Published by ResearchOnline@Avondale, 2010 9 Christian Spirituality and Science, Vol. 8 [2010], Iss. 1, Art. 3

of many functions it has been found ties have been linked to sudden death that alcoholics sometimes are still able occurring among alcoholics26. In a to achieve normal levels of perform- study of sudden death in individuals ance as the brain compensates for the between the ages of twenty and fifty, damage by using regions of the brain one remarkable autopsy finding indi- that are not usually used for the task. cated excessive fat in the liver26. This This has been termed “processing observation often normally correlates inefficiency” and although they may with high consumption of alcohol. successfully carry out the task with ac- However, these individuals did not curacy it takes a lot longer to complete have high concentrations of alcohol it than normal24. in their blood at the time of death, so while there is a definite link between Despite the negative effects of alcohol, alcohol and sudden death, the exact research suggests that a low intake of cause is more complicated than just alcohol in certain specific population arrhythmia or tachycardia caused groups has a limited positive effect on by high levels of alcohol26. Another brain health. For example it is believed potentially serious cardiovascular that one drink a day may be neuro- effect is increasing blood pressure27. protective which means that it allows Long term heavy drinking also has individuals to experience less age- negative effects on the heart muscle, related brain atrophy17. It has also been causing enlargement of the heart and suggested that low doses decrease the a loss of some contractility resulting occurrence of WMHs and reduce the in insufficient blood flow to the rest risk of cerebral infarction17. of the body28. Alcohol may also cause Other Body Systems an increase in the amount of triglyc- Affected By Alcohol erides found in the blood29. Increased In addition to compromising the triglyceride levels are associated with liver and CNS alcohol has numerous hypertension and coronary artery other detrimental systemic effects. It disease29. has serious negative effects on the Blood cardiovascular system, the immune Alcohol also has several negative system, the gastrointestinal tract, the effects on blood. It has direct toxic ef- reproductive system, the bones, the fects on bone marrow where the blood pancreas and the blood. cells are produced, the precursor cells Heart that blood cells derive from, and on the When consumed in large quantities, mature blood cells themselves30. It also alcohol can cause irregular heart- has indirect effects, through nutritional beat (arrhythmia), and even smaller deficiencies and other metabolic prob- doses of alcohol can increase heart lems30. There are also effects on blood rate (tachycardia)26. Heart irregulari- biochemistry and enzymic reactions.

34 https://research.avondale.edu.au/css/vol8/iss1/3 10 Beecroft et al.: The Biochemical and Pathophysiological Effects of Alcohol Consump

Combined, these direct and indirect processes31. Alcohol also inhibits the effects can result in decreased produc- absorption of nutrients in the small tion of red and white blood cells, as intestine possibly leading to weight well as platelets30. Alteration of the loss and also malnutrition31. structure and metabolic function of The mouth and throat are the first the red blood cells can also result30. parts of the body to come into contact In alcoholics large fluid filled vacuoles with alcohol. There is a definite link are found in cellular precursors to red between alcohol consumption and can- and white blood cells and are an indi- cers of the mouth, tongue and throat31. cator of recent heavy drinking30. The The risk of oesophageal is in- resulting appearance of macrocytes creased by damage caused by alcohol (enlarged red blood cells) is common to the mucosal lining of the oesopha- among heavy drinkers and this can be gus31. There is also a stronger cancer used as a relatively reliable method risk for individuals who both drink and for identifying people who drink to smoke, as the alcohol solubilises the excess30. also causes carcinogens found in the cigarettes and several types of anaemia by interfering increases membrane permeability thus with the production of red blood cells increasing carcinogenicity31. in such a way that they are structur- ally defective and are consequently Pancreas destroyed more rapidly than normal Alcohol has two important negative healthy cells30. Alcohol also decreases effects on the pancreas. Firstly, as the numbers of platelets in the blood liver cells break down alcohol, the decreasing the ability of the blood to breakdown products exert toxic effects stop bleeding. on pancreatic cells, and can lead to acute pancreatitis . When the pancreas Gastrointestinal Tract becomes inflamed, the digestive en- There are many different ways in zymes that it normally produces leak which alcohol can negatively affect out, and begin to digest the pancreas the gastrointestinal tract as it comes itself32. This leads to chronic pan- into contact with the alcohol in its creatitis, which causes destruction of most concentrated form. Alcohol is the pancreas that is irreversible32. The absorbed into the blood stream by major cause of chronic pancreatitis is simple diffusion through the walls of the excessive use of alcohol32. the stomach and small intestines31. Al- cohol can directly impair the function Reproductive System of the oesophageal muscles, leading There have been several studies in- to heartburn31. Alcohol increases the vestigating whether alcohol has any permeability of the walls of the small effect on fertility and the ability of intestine to toxins which can lead women to conceive. It was found that to liver damage during detoxifying among women who drank moderately

35 Published by ResearchOnline@Avondale, 2010 11 Christian Spirituality and Science, Vol. 8 [2010], Iss. 1, Art. 3

their chances of falling pregnant were use weakens the bones, making them greatly decreased by their alcohol more fragile by decreasing their den- intake33. It was also found that there sity35. Studies have also shown that was a much higher risk of menstrual there is increased risk of bone fracture disturbance, abortion and miscarriage for alcoholics28. 34 among alcoholic women . These stud- Mother-Foetal Metabolism ies would suggest that women aiming of Alcohol to fall pregnant abstain from drinking In a pregnant woman, the metabolic 33 all alcoholic beverages . breakdown of alcohol occurs a lot Immune system slower and with less efficiency when Acute bacterial infections are found compared to a woman who is not preg- to be more common among alcoholics nant28. This is due to the presence of suggesting that alcohol has a detrimen- oestrogens in the mother’s blood. Oes- tal effect on some components of the trogens (particularly oestradiol) inhibit immune system30. Normally when an the functioning of ADH and ALDH individual has a bacterial infection, resulting in a slower metabolism of the numbers of neutrophils (white alcohol by the liver. The levels of oes- blood cells) in the blood are found trogen in the blood are raised 10-100 to be increased30. In alcoholics the times in the first stages of pregnancy, numbers of neutrophils are decreased and this increases to 100-1000 times contributing to suppression of the im- in the last half of pregnancy28. mune system and the reduced ability The metabolism of alcohol in the to deal with infections effectively30. In body has no feedback mechanism, the presence of alcohol the movement thus the body is unable to increase or of neutrophils to the site of an infec- decrease the rate at which alcohol is tion is slowed quite considerably28. broken down. The rate at which the This indicates that even individuals liver breaks down alcohol is about who drink only moderately are com- 7 grams per hour28. However, as the promising their immune systems by metabolism of alcohol is less efficient doing so. in a pregnant woman’s body, this rate Bones is decreased by one and a half times28. There appears to be a well documented Therefore, it will take 1.5 times longer link between heavy drinking and oste- for the mother to completely metabo- oporosis. These effects are more pro- lise a glass of alcohol compared to a nounced in older individuals, however non-pregnant woman. A foetus has heavy drinking during the teen years very limited ability to metabolise increases the risk of osteoporosis later alcohol as the foetal liver only pro- in life28. This osteoporosis risk seems duces small amounts of ADH from the to be due to the fact that heavy alcohol middle of the third month onwards28.

36 https://research.avondale.edu.au/css/vol8/iss1/3 12 Beecroft et al.: The Biochemical and Pathophysiological Effects of Alcohol Consump

Although the production of ADH in Alcohol is also classified as a tera- the foetal liver steadily increases over togen, meaning that it is able to im- the pregnancy in a linear fashion, the pair normal development and cause amount is insignificant compared to birth defects in the offspring due to the levels produced by the mother’s exposure during pregnancy37. Tera- liver. Consequently alcohol passing togens may cause four main types of into the circulatory system of the foe- complications in offspring, including tus is largely unmetabolised. This has death, disfigurement or malformed harmful effects on the foetus as half of body parts, stunted growth, and prob- the alcohol in the mother’s blood (or lems in systemic functions. These more if she has a compromised liver) four complications are all commonly crosses the placental wall and directly associated with FAS. enters the foetal circulatory system. There is a dose-response relation- Foetal Alcohol Syndrome and ship where the alcohol dose directly Teratogenicity of Alcohol relates to effects on the offspring. Foetal alcohol syndrome (FAS) mani- With respect to FAS the more the fests as birth defects primarily affect- mother drinks during her pregnancy, ing the developing brain. The cause the more likely it is that there will be of FAS is exposure of the foetus to adverse neonatal complications and alcohol during pregnancy with the birth defects in the baby39. The tim- most dangerous period being the first ing of when the mother drinks is also 36 trimester . The effects of the FAS important, as the alcohol will only endure throughout the lifetime of the affect the tissues that are developing individual; however the effects may at that time. If the mother drinks early 37 change as the person ages . Common on in the pregnancy during embryonic characteristics of FAS include growth formation the baby will have a greatly retardation of the foetus in utero, post- increased risk of structural defects natal growth retardation, underweight and malformations37. However if the during childhood and microcephaly mother only drinks in the last trimester (smaller head than normal due to poor when the foetus is mostly growing in 38 development of brain) , mental retar- size, the baby will be born smaller than dation, hyperactivity, underdeveloped usual. Additionally, since the brain is muscles, typical facial features such developing throughout the duration of as a rounded forehead, and improper pregnancy, the brain will be affected development of other organs such as by alcohol at any stage37. The drink- 36 the heart and genitals . There are also ing pattern of the mother is also very increased risks of miscarriage, still- important in relation to how the foetus births, neonatal morbidity, neonatal develops. Occasionally death and much reduced longevity. will affect the foetus differently to regular light exposure37.

37 Published by ResearchOnline@Avondale, 2010 13 Christian Spirituality and Science, Vol. 8 [2010], Iss. 1, Art. 3

Alcohol has a direct toxic effect on the (LDL - also known as ‘bad choles- foetal brain (as in the adult brain) pro- terol’) which is associated with the moting cell death. The foetal hippoc- formation of atherosclerotic plaques ampus, cerebellum, corpus callosum on arterial walls leading to coronary (which coordinates left and right side heart disease42. These plaques contrib- activity), and cortex are specific areas ute to blockages in coronary arteries of the brain targeted by alcohol. In the and are also associated with blood developing brain alcohol also impairs clot formation. Polyphenols found the transport of amino acids and in purple grape juice act to reduce glucose and may reduce the amount adhesion of blood platelets and the of oxygen available to the foetus by subsequent clot formation associated affecting placental blood flow. Alcohol with acute coronary events such as may also impact the endocrinal and heart attacks43. Further, consumption chemical systems in the body which of purple grape juice is also associ- regulate the development of nerve ated with arterial vasodilatation44. cells in the brain37. Arterial vasodilatation leads to better Positive Effects of Alcohol? Red blood flow in coronary arteries which Wine vs Grape Juice also contributes to a lowered risk of It is observed that French population . groups have considerably lower mor- Thus evidence would suggest that tality rates related to coronary heart the health benefits of red wine intake disease despite their diet containing observed in the French Paradox are foods that are high in fat. This has be- associated with grape polyphenols and come known as the ‘French Paradox’ are independent of the alcohol content and is thought to be associated with of the red wine. The intake of purple 40 the regular consumption of red wine . grape juice has the obvious benefit It has been demonstrated that it is not of reducing cardiovascular disease only the consumption of red wine risk without the increased systemic that is associated with a reduced risk health risks associated with alcohol for cardiovascular disease, but also consumption. the consumption of and grape juice41. There is significant evidence Conclusion suggesting that such health benefits The consumption of alcohol not only are associated with the antioxidant affects physical structures of the body properties of polyphenols found in such as the liver and brain, but also grapes rather than the alcohol content physiological processes and behav- of the wine itself. iour. These effects may be permanent if alcohol consumption is continued Polyphenols help prevent the oxi- over a prolonged period of time or may dation of low-density lipoproteins be partly reversible if consumption is

38 https://research.avondale.edu.au/css/vol8/iss1/3 14 Beecroft et al.: The Biochemical and Pathophysiological Effects of Alcohol Consump

ceased. While the body does have the the individual. Possibly the most seri- capacity to metabolise alcohol through ous consequence of alcohol consump- hepatic metabolic pathways these tion is that imposed on the foetus in processes may eventually function pregnant women who decide to drink. inefficiently as the tissues involved The risk of foetal alcohol syndrome with alcohol metabolism become for the unborn is a serious matter and damaged. The consequences of short due consideration should be given to and long term interference with brain the fact that the foetus has no choice neurotransmitters and altered brain in its exposure to alcohol. The long structure argue strongly against alco- term consequences of foetal alcohol hol consumption. The Christian would syndrome need to be weighed. consider the intellect and the ability to Perhaps Christian temperance move- make intelligent and informed deci- ments may appear restrictive in terms sions a part of being created in the of free will choices. The free will image of God. Thus any chemical choices of individuals should be interference with brain structure or respected in all aspects of life, includ- neurotransmitter function would work ing the decision to consume alcohol. against this concept. Impaired immune However, any decision that has seri- system function renders the body more ous consequences for the individual susceptible to infectious disease. The and those with whom they associate development of atherosclerosis with (and especially with respect to foetal associated cardiovascular complica- development) should be as informed tions is accelerated with alcohol as possible. Given the wealth of ma- intake. With respect to cardiovascular terial now available reporting on the disease, the benefits observed in the negative effects of alcohol consump- ‘French Paradox’ appear to be associ- tion it is possible to be intelligently ated with the ingestion of antioxidants informed regarding the choice of found in red grape juice. whether to consume alcohol or not. The decision to drink alcohol should There is certainly sufficient evidence be informed by contemporary research to suggest that abstinence from al- into its short and long term effects. cohol consumption, while appearing Deciding to ingest alcohol as an indi- unpopular to some, may be an intel- vidual may have ramifications for not ligently informed and respected option only individual health and well being to alcohol consumption. but may have ramifications for others Discussion Questions: as well. Antisocial behaviour, implica- 1. Where does Christian tions for marriage and family, risk of responsibility lie with respect accident and injury should also be con- to personal decisions regarding sidered. The consequences of alcohol the use of alcohol and other consumption are rarely restricted to recreational drugs?

39 Published by ResearchOnline@Avondale, 2010 15 Christian Spirituality and Science, Vol. 8 [2010], Iss. 1, Art. 3

2. What could be done to enhance , 24: 55-78. public discussion regarding the 8. Arria, A. M., Tarter, R. E. and problems of alcohol in society? Van Thiel, D. H. (1990) Liver- 3. Discuss the unique health Brain Relations in Alcoholics. benefits associated with the Alcohol Health and Research ‘French Paradox’. What other World, 14(2): 112-7. lifestyle choices have direct 9. Maher, J. J. (1997) Exploring effects on health? Consider alcohol’s effects on liver the Mediteranean and Okinawa function. Alcohol Health and diets. Research World, 21(1): 5-6. REFERENCES 10. Mann, R.E., Smart, R. G. 1 Ministerial Council on Drug and Govoni, R., (2003) The Strategy (2006) National Alcohol of Alcoholic Liver Strategy 2006-2009. Australian Disease. Alcohol Research and Government, http://www. Health, 27(3): 209-19. alcohol.gov.au 11. Karsan, H. A., Rojter, S. E. 2. Rhoades.R, and Pflanzer.R, and Saab, S. (2004) Primary (2003) Human Physiology prevention of cirrhosis; public Fourth Edition. Thomson health strategies that can make Learning: USA a difference. Postgraduate 3. Ribeaux, M. B., (1997) Medicine, 115(1): 25-30. Overview of Liver Structure and 12. Lovinger, D., (2008) Function. Alcohol Health and Communication Networks in Research World, 21(4). the Brain: Neurons, Receptors, 4. Schuckitt, M., (2009) Alcohol- Neurotransmitters, and Alcohol. Use Disorders. The Lancet, Alcohol Research and Health, 373(9662): 492-501. 31(3): 196-214. 5. Crow, K. E., Batt, R, D., (1989) 13. Braun, S., (1996) Buzz: The Human Metabolism of Alcohol Science and Law of Alcohol and Volume II. CRC Press: USA. Caffeine. Oxford University Press: New York, USA. 6. Zakhari, S., (2006) How is Alcohol metabolised by the 14. Chastain, G., (2006) Alcohol, Body?. Alcohol Research and Neurotransmitter Systems, Health, 29(4). and Behaviour. The Journal of General Psychology, 133(4): 7. Nagy, L. E., (2004) Molecular 329-335, aspects of alcohol metabolism: Transcription Factors Involved 15. Watson, R.R. (ed.), (1992) in Early Ethanol- Induced Alcohol and Neurobiology: Liver Injury. Annual Review of Receptors, Membranes, and Channels. CRC Press: USA.

40 https://research.avondale.edu.au/css/vol8/iss1/3 16 Beecroft et al.: The Biochemical and Pathophysiological Effects of Alcohol Consump

16. Clapp, P., Bhave, S.V., and Drinking: Role of Amygdala and Hoffman, P.L., (2008) How Prefrontal Cortex. Philosophical Adaptation of the Brain to Transactions of the Royal Alcohol Leads to Dependence: Society, B 363(1507): 3169- A Pharmacological Perspective. 3179. Alcohol Research and Health, 22. Excessive Drinking can 31(4): 310-340. Damage Brain Regions Used 17. Anstey, K.J., Jorm, A.F., for Processing Facial Emotions. Reglade-Meslin, C., Maller, Science Daily. (Aug 12, 2009) J., Kumar, R., von Sanden, C., http://www.sciencedaily.com/ Windsor, T.D., Rodgers, B., releases/2009/08/090811161257. Wen, W., and Sachdev, P., (2006) htm Weekly Alcohol Consumption, 23. Alcoholism; Alcohol Alters Brain Atrophy, and White Prefrontal Cortex Activity Matter Hyperintensities in a Through Ion Channel Disruption. Community-Based Sample Aged NewsRx Health. (2008) http:// 60 to 64 Years. Psychosomatic www.newsrx.com/newsletters/ Medicine, 68: 778-785. Biotech-Week.html 18. Pfefferbaum, A., Rosenbloom, 24. Rosenbloom, M., and M., Deshmukh, A., and Sullivan, Pfefferbaum, A., (2008) E.V., (2001) Sex Differences in Magnetic Resonance Imaging the Effects of Alcohol on Brain for Brain Degeneration Among Structure. The American Journal Alcoholics and Recovery with of Psychiatry, 158(2): 188-197. Abstinence. Alcohol Research 19. National Institute of and Health, 31(4): 362-376. Neurological Disorders and 25. Gilpin, N.W., and Koob, Stroke, (2009) NINDS Cerebral G.F., (2008) Neurobiology of Atrophy Information Page. : Focus http://www.ninds.nih.gov/ on Motivational Mechanisms. disorders/cerebral_atrophy/ Alcohol Research and Health, cerebral_atrophy.htm 31(3): 185-195. 20. Excessive Drinking can 26. Friedman, H. S. (1992) Alcohol, Damage Brain Regions Used Arrhythmia and Sudden Death. for Processing Facial Emotions. Alcohol Health and Research Science Daily. (Aug 12, 2009) World, 16(1) http://www.sciencedaily.com/ releases/2009/08/090811161257. 27. Wong, D. R., Willet, W. C., and htm Rimm, E. B. (2006) America Journal of Epidemiology, 21. Stephens, D.N., and Duka, T., 165(7): 838-845. (2008) Cognitive and Emotional Consequences of Binge 28. Medical consequences of alcohol

41 Published by ResearchOnline@Avondale, 2010 17 Christian Spirituality and Science, Vol. 8 [2010], Iss. 1, Art. 3

abuse. (2000) Alcohol Research 26(4): 292-8. and Health, 24(1): 27-31. 36. Spohr, H. and Steinhausen, 29. Miller-Keane (1992) H. (eds.), (1996) Alcohol, Encyclopedia and Dictionary of Pregnancy and the Developing Medicine, Nursing, and Allied Child. Cambridge University Health. Saunders: USA Press: New York, USA. 30. Ballard, H. S. (1993) Alcohol, 37. Streissguth, A., (1997) Fetal Bone Marrow and Blood. Alcohol Syndrome. Paul H. Alcohol Health and Research Brookes Publishing Co.: World, 17(4): 310-315. Baltimore, USA. 31. Bode, C and Bode, C. J., 38. National Institute of (1997) Alcohol absorption, Neurological Disorders and metabolism and production in Stroke (2008) Microcephaly the gastrointestinal tract. Alcohol Information Page. http:// Health and Research World, www.ninds.nih.gov/disorders/ 21(1): 82-83. microcephaly/microcephaly.htm 32. Vonlaufen, A., Wilson, J. S., 39. Abel, E., (2006) Fetal Alcohol Pirola, R. C. and Apte, M. Syndrome: A Cautionary Note. V., (2007) Role of alcohol Current Pharmaceutical Design, metabolism in chronic 12(12): 1521-1529. pancreatitis. Alcohol Research 40. Tunstell-Pedoe, H., Kuulasmaa, and Health, 30(1): 48-54. K., Mahonen, M. (1999) 33. Jensen, T. K., Hjollund, N. I., Contribution of trends in Henriksen, T. B., Scheike, T., et survival and coronary-event al. (1998) Does moderate alcohol rates to changes in coronary consumption affect fertility? heart disease mortality: 10-year Follow up study among couples results from 37 WHO MONICA planning first pregnancy. British project populations: monitoring Medical Journal, 317(7157): trends in and determinants in 505-510. cardiovascular disease. Lancet. 8353: 1547-1557. 34. Grodstein, F., Goldman, M. B. and Cramer, D. W. (1994) 41. Dohadwala, M. and Vita, Infertility in Women and J. (2009) Grapes and Moderate Alcohol Use. The Cardiovascular Disease. American Journal of Public The Journal of Nutrition. Health, 84(9): 1429. 139(9):1788S-1793S. 35. Sampson, W. H., (2002) Alcohol 42. Stein, J., Keevil, J., Wiebe, D., and other factors affecting Aeschlimann, S. and Folts, osteoporosis risk in women. J. (1999) Purple Grape Juice Alcohol Research and Health, Improves the Endotheilial

42 https://research.avondale.edu.au/css/vol8/iss1/3 18 Beecroft et al.: The Biochemical and Pathophysiological Effects of Alcohol Consump

Function and Susceptibility of LDL Cholesterol to Oxidation in Patients with Coronary Heart Disease. Circulation. 100:1050- 1055. 43. Demrow, H., Slane, P. and Folts, J. (1995) Administration of Wine and Grape Juice Inhibits In Vivo Platelet Activity and Thrombosis in Stenosed Canine Coronary Arteries. Circulation. 91:1182- 1188. 44. Freedman, J., Parker, C., Li, L., Perlman, J., Frei, B., Vadim, I., Deak, L., Iafrati, M. and Folts, J. (2001) Select Flavenoids and Whole Juice from Purple Grapes Inhibit Platelet Function and Enhance Nitric Oxidase Release. Circulation. 103:2792-2798.

43 Published by ResearchOnline@Avondale, 2010 19