Alcohol & Health Benefit or Hazard?
by Ben Best
Alcohol & specifically ethanol (ethyl alcohol, EtOH,
CH3CH2OH) & is the most socially-accepted addictive
drug which can have life-threatening health hazards. Its pleasures are very
widely acknowledged and form a bond of community for the majority of adults
in Western countries. References to those pleasures form a kind of
&standing joke& & physical & mental
discoordination/disorientation are viewed with bemused affection.
Alcoholic beverages are a standard &lubricant& (anxiety-reliever)
at social gatherings, and those who refuse to consume ethanol run the risk
of being social outcasts.
Yet some people, myself included, feel concern about consuming a
substance which causes physical & mental discoordination/disorientation.
Although the effects appear to be temporary, one could easily wonder about
the physiological changes being wrought on the brain. And one could wonder
whether the temporary effects are really
desireable & even if pleasurable & and whether the brain really escapes
permanent harm. Because ethanol enters tissues in proportion to water content it
is far more prevalent in the brain than in muscle or fat.
For those who highly value
their brains/minds this should be a matter of great concern.
In the United States alcohol is responsible for about one-third
of fatal car crashes, one-third of hospital admissions,
one-third of all suicides, and half of all homicides
People who are genetically disposed to experience alcohol as tasting
bitter are the least likely to drink alcohol. As well, alcohol taste
becomes increasingly unpleasant with age, which correlates with age-related
decrease in the consumption of alcoholic
beverages&[].
Health benefits are frequently claimed for alcohol & when consumed in
moderation. Most of the claimed benefits are associated
with reducing
The incentives
for wishful thinking are very high and study designs are often poor &
conditions which can make for bad science. Between 16%
and 33% of people in Europe and North America are estimated to abstain
from drinking beverage alcohol, many of whom are former alcoholics. Ex-drinkers
have high rates of ischemic heart disease, hypertension, ulcers, diabetes,
gall bladder disease and bronchitis&[INTERNATIONAL JOURNAL OF
EPIDEMIOLOGY 17(2):307-316 (1988)]. Life-long abstainers are more often
non-conformists and are less frequently married (unmarried people have a
higher mortality rate).
People often abstain from alcohol due to interaction
with prescription drugs or other health-related reasons. The poor health of
many abstainers should not be taken as proof of the beneficial effects of
ethanol & but usually are.
In reality, studies of ethanol are usually based on self-reported
descriptions of current alcohol consumption. Like a village idiot chasing a
wallet on a string, epidemiologists typically take self-reporting at face
value and fail to distinguish between ex-drinkers and lifetime teetotalers
& calling both &abstainers&. Not surprisingly, the abstainers
(including the former alcoholics) are deemed to be less healthy than
light drinkers.
A study of nearly 4,500
former University of North Carolina students (intended to be a somewhat
uniform socio-economic group)&] sought to discover the possible
confounding lifestyle variables (masked by &proxy variables&).
Drinkers were distinguished from nondrinkers and drinkers were divided into
those who prefer wine, beer, spirits or have no preference among types of
alcoholic beverages. A tabulation of health behaviors by
sex and beverage preference included the following:
Health (hazard) practices by gender and beverage preference
NONDRINKER
PREFER WINE
PREFER BEER
PREFER SPIRITS
NO PREFERENCE
Female Smokers (%)
Male Smokers (%)
Female Exercisers (%)
Male Exercisers (%)
Wine drinkers would clearly be the healthiest subset insofar as they
smoke less and engage in more aerobic exercise. But why would non-drinkers
smoke more than wine-drinkers and exercise less than any of the other
groups? Upon further investigation, only 27% of the nondrinkers said
they had never been drinkers and 27% provided no
information about their past drinking or non-drinking habits. The vast
majority of alcoholics are smokers & who very often continue to smoke
while abstaining from alcohol. This would also be true of non-alcoholic
ex-drinkers who stopped drinking because of health problems. It would
be no surprise to find higher rates of cardiovascular disease among
nondrinkers who smoke more than light drinkers & an effect
not due to the difference in drinking behavior. Not
surprisingly, the investigators discovered that the lifelong
teetotalers among the nondrinkers had lower rates of smoking.
Additionally, even among the nondrinkers who did not have a previous
history of drinking there may have been those who did not drink because
of concern about interaction with prescription drugs.
Further investigation of the wine-drinkers revealed that they
consumed more fruit & vegetables and had higher fiber intakes
than the other groups. All these confounding influences show how
highly irrelevant epidemiological data indicating the so-called
health benefits of light drinking are to the
who does not drink ethanol, does not smoke, exercises regularly and
eats lots of fruits, vegetables & fiber & while restricting calories.
The February 1998
issue of the journal ADDICTION contains a research
report which greatly advanced the study of the relationship between
alcohol consumption and mortality. It was probably also larger than
previous studies because it pooled the results of the best
available previous studies&.
Unlike many previous studies which have a single category for
non-drinkers, this study carefully distinguished between former
drinkers and long-term abstainers. Using this distinction, the
reputed reduced mortality risk for light drinkers over long-term abstainers
was disproven for both men and women. However, a large meta-analysis of
epidemiological studies that attempted to adjust for lifetime
abstainers within the category of non-drinkers concluded that
minimum risk of coronary artery disease occurred for 1-2 drinks
per day&, although
there was no adjustment for health conditions that could reduce
alcohol consumption.
In the case of males, the confounding effect of grouping
former drinkers with long-term abstainers was particularly
illuminating. Six statistically significant differences were seen
between the two groups. Compared to long-term abstainers, former male
drinkers were more likely to be: (1) heavy smokers (2) marijuana users
(3) unemployed (4) depressed (5) less well educated and (6) have better
educated fathers. The last result is somewhat puzzling. It might be a
marker for &downward mobility& & people who are depressed &
unemployed because they failed to achieve the standards of their parents.
There have been fewer alcohol studies on women than on men, so
there is less data available, and the results are less definitive & except
to rule-out a definite conclusion that light drinkers have less mortality
than long-term abstainers OR former drinkers. Evidence was found for
demographic factors which might account for the mortality results of some
studies on women. These factors are unrelated to the physical effects of
alcohol. Both &long-term abstainers and former drinkers were more likely
to have low income, had less education, were less likely to be employed
and were less likely to be European American than light drinkers ...&
Among the females, there were 5 statistically significant differences between
former drinkers and long-term abstainers. Former drinkers tended to be: (1)
heavy smokers (2) in poorer health (3) unmarried (4) less religious (5)
better educated. A demographic study in Australia indicated that abstainers
had a higher incidence of asthma, diabetes, arthritis, thyroid
abnormalities, religiosity, lower education, and lower cognitive
No adjustment was made to account for former alcoholics being abstainers,
nor was it established whether abstension is a cause or consequence of
health problems.
is mistaken with regard to the animal fat & the French eat a great deal of fish.)
Japan has very low animal fat consumption and
less than half the per capita ethanol consumption of France. The highest
rates of coronary heart disease mortality are in Ireland & Finland,
where per capita ethanol consumption is about the same as in Japan. Ireland
has the lowest per capita fruit consumption and wine consumption of the
21 countries. Drinking patterns in Finland are very different from those
in France. Wine is often consumed with meals in France, which may reduce
alcohol absorption. By contrast, moderate daily imbibing is rare in Finland
where the principle aim of drinking is rapid intoxication once every week
or two&[INTERNATIONAL JOURNAL OF EPIDEMIOLOGY 12(2):151-155 (1983)].
An ardent defense of the benefits of red wine was written
by a group in Montpellier, France&[JOURNAL OF NUTRITION 132:
(2002)]. Using hamsters, the group demonstrated that red wine extract
significantly reduces atherosclerotic fatty streaks in the aorta and that
this effect is even greater when combined with ethanol. In contrast
to studies that have usually shown increased plasma triglycerides due to ethanol
in humans, this study showed reduced triglycerides. Most of the benefits of red
wine extract were attributed to polyphenols (compounds with multiple
hydroxylated benzene rings), also known to be very effective in preventing
. [For a good summary of grape
phenolics see ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 957:21-36 (2002)].
is a benzene ring with an alcohol&(-OH) group that
can act as an
by donating a hydrogen atom to a
A polyphenol is a molecule with many phenols and better antioxidant properties.
However, all phenolic antioxidants (including
) neutralize hydroxyl
radicals by becoming weaker pro-oxidants & in contrast to an antioxidant like
which donates electrons to hydroxyl radicals&[JOURNAL OF PINEAL
RESEARCH 32:135-142 (2002)].
(trans-3,4',5-trihydroxystilbene),
present in purple , peanuts and red wine, is known to be a modulator of
lipid and lipoprotein synthesis.
Resveratrol is also an antioxidant which can cross the
blood-brain barrier to protect against brain ischemic injury&[BRAIN RESEARCH
958:439-447 (2002)] (melatonin also crosses the blood-brain barrier). Andrew
Waterhouse (a professor of hydroxyl chemistry & author of the grape phenolics paper
cited above) has described resveratrol as &trendy and famous&, adding "it is
no better an antioxidant than the hundred or so other phenolic compounds in red wine".
But Waterhouse himself adds to the pro-alcohol hype by referring to red wine
rather than grapes or grape juice, as if children &
teetotallers are excluded from the benefits. During fermentation, alcohol draws phenolics
from grape seed & skin, resulting in a drink with 50% greater concentration of
antioxidants. But there are plenty of fruits with more antioxidant capacity than red grapes,
like blueberries, strawberries or raspberries & see
by Joseph, Nadeau &
Underwood. Concerning red wine as a source of antioxidants, THE COLOR CODE quotes cancer
expert Dr.&John D. Potter: &Drink grape juice&.
The greatest benefits of resveratrol may not be due to its antioxidant
effects. Mice fed a high-calorie diet who were supplemented with resveratrol (equivalent
to 2,000&milligrams per day in a 200&pound human & more than 300 times the
amount found in a glass of red wine) showed physiology similar to mice fed a standard
diet. Unlike mice fed a high-calorie diet who did not receive resveratrol, the
resveratrol-supplemented mice showed insulin sensitivity,
, motor function,
mitochondrial number and survival comparable to mice fed a standard
diet&[]. Because of these
results and because resveratrol
it is suggested that resveratrol mimics the effects of
& although a better suggestion might be opposing some
of the health effects of the
Modest doses of ethanol beneficially increases plasma HDL
cholesterol and reduces blood pressure while harmfully raising
plasma triglycerides, decreasing heart muscle contractility and
increasing heart rate. Heavier drinking increases blood pressure.
A six-year study of nearly three thousand men showed nearly four
times greater incidence of ischemic heart disease in abstainers as in
heavy drinkers and nearly twice the incidence in moderate drinkers over
heavy drinkers for the fifth with the highest LDL cholesterol levels. For
those in the lowest fifth no association was seen, and only a non-significant
association was seen for the middle
three-fifths&. This
might indicate that alcohol is only of benefit for those with high LDL cholesterol
(the French have high LDL cholesterol and drink heavily, hence the &French
Paradox&), but it is worth noting that the abstainers in the study were taking
more medications and were more likely to be suffering from non-insulin dependent
diabetes. For diabetics, ethanol may produce atherosclerosis at all doses in a direct
dose-dependent fashion&[DIABETES CARE 25: (2002)], although not all studies
agree on this. A meta-analysis of intervention studies concerning effects of
ethanol on plasma risk factors of heart disease concluded that alcohol significantly
increases ,
significantly decreasing &[].
Reduced clotting is another
benefit of light ethanol consumption & an effect ethanol shares with
aspirin. And as with aspirin, with less clotting there is less chance of
coronary artery disease, but a greater danger of hemorrhagic stroke.
Reduced levels of thromboxane&A2 due to ethanol reduce
blood vessel constriction and platelet aggregation [BRITISH MEDICAL
JOURNAL 293:715-718 (1986)].
The Honolulu Heart Study found a direct correlation between incidence of
hemorrhagic stroke and all levels of alcohol consumption & in contrast to
the Framingham Study which did not show this association&[STROKE
33:230-237 (2002)]. In contrast to chronic alcohol consumption, drinking
to intoxication significantly increases the risk of brain infarction
within 24 hours&[STROKE 26:40-45 (1995)].
Many studies of cardiovascular disease, have given mixed results:
&Use of ethanol has been associated with higher risk of mortality
from hypertension, hemorrhagic stroke and cardiomyopathy, but with lower
risk from CAD, occlusive stoke and nonspecific cardiovascular disease.&
Cardiomyopathy is damaged heart muscle cells unrelated to coronary artery
disease. Ethanol reacts with
to produce
[general molecular formula
CH3(CH2)nCOOCH2CH3] which
are toxic to mitochondria & leading to heart muscle cell damage.
Ethanol impairment of protein synthesis affects both skeletal and heart
muscle. In isolated heart cells ethanol reduces the number &
uniformity of fibrils (minute fibers). Heart muscle in alcoholics shows
a loss of contractile elements and/or fragmentation & disarrangement
of those elements&[THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY &
CELL BIOLOGY 33:457-473 (2001)].
In seeing claims of the benefits of light alcohol consumption
to prevent cardiovascular disease, one should always consider the possible
role of proxy variables, as cited above.
A good investigation that did not
grouped ex-drinkers with long-term abstainers under the rubric
&non-drinkers& was a very large study of over
100,000 people done in 1990&[AMERICAN JOURNAL OF CARDIOLOGY 66:].
This study established that light drinkers have no less risk of mortality
for non-cardiovascular disease than lifetime abstainers, but do have lower
coronary artery disease (CAD) mortality.
A person practicing CRAN
() and/or who exercises would probably have an excellent
HDL/LDL profile anyway, and would probably be better off without extra
calories from alcohol & or the metabolic disturbances it creates.
Epidemiological studies of Chinese have shown that for people who are lean
and active, HDL cholesterol is not lowered with ethanol.
Clotting can as
reduced by aspirin as by ethanol & or even better by the use of a
in the diet.
so-called because when the reduced form is exposed to carbon
monoxide it exhibits a spectrum Peak of 450nm).
An enzyme in the E&subfamily of the second
family of P450s (CYP2E1) normally accounts for under 10% of
ethanol metabolism, also using NAD as a co-factor. Ethanol can increase liver
concentrations of CYP2E1 up to tenfold. Induction of CYP2E1
by ethanol may be a significant contributer to alcohol-induced liver
disease&[BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
205(2): (1994)]. CYP2E1 generates many different
while depeting glutathione&(GSH).
CYP2E1 can covert many xenobiotics & such as
industrial solvents, anesthetics, isoniazid, phenylbutazone, cocaine and
acetaminophen & into highly toxic metabolites.
As a third route of ethanol metabolism, catalase in the peroxisomes of liver and
in other cells metabolizes a small amount of ethanol when sufficient hydrogen peroxide
(H2O2) is available & without requiring NAD as
a cofactor. All three of these means of metabolizing ethanol result in acetaldehyde.
Acetaldehyde is then further metabolized in mitochondria by the enzyme
acetaldehyde dehydrogenase to acetic acid
(CH3COOH) &
which can be metabolized into carbon
dioxide and water with a release of energy. Daily drinking can
increase liver metabolism of ethanol by as much as a third.
But acetaldehyde
is not always rapidly metabolized. High doses of acetaldehyde
are so unpleasant that alcoholics have been given an acetaldehyde
dehydrogenase blocking agent (disulfiram). The alcoholics
find the flushing, headache, nausea, vomiting and other side effects
to be a strong disincentive for further ethanol ingestion.
Large quantities NADH resulting from heavy drinking can lead to
triglyceride accumulation & fatty liver. High alcohol & fat consumption
along with low protein & carbohydrate consumption helps turn fatty
liver into
& a cause of death for some alcoholics. Protein
deficiency increases liver damage due to ethanol. Fat
accumulation in the liver is worsened by reduced lipoprotein biosynthesis
& secretion and impaired fatty acid oxidation. Ethanol potentiates the capacity
of Vitamin&A to cause liver damage. Ethanol also increases the
, increasing oxidative
Liver cells degenerate
& die, replaced by connective tissue, lymphocytes and leucocytes as
inflammation proceeds. Only 10-15% of alcoholics develop liver
cirrhosis, however.
Ethanol influence on mitochondrial free-radical production
High levels of NADH in mitochondria can cause an increase
in the number of superoxide&(O2.-) free
radicals leaked from oxidative phosphorylation & leading to the
formation of hydroxyl radicals&(.OH), lipid
peroxidation and damage to mitochondrial DNA&[GASTROENTEROLOGY
122: (2002)]. (For more on these subjects see
Acetaldehyde which escapes immediate conversion
to acetic acid can bind to cysteine, a constituent of the anti-oxidant
peptide glutathione&(GSH) & further compromising liver
mitochondrial function with oxidative damage. Acetaldehyde released into
the bloodstream can drift to other organs & notably the brain & where
it can damage proteins & DNA as well as cause lipid peroxidation
in membranes.
In ethanol-damaged livers there is a decrease in activity of
S-AdenosylMethionine&(SAMe) synthetase, the enzyme that synthesizes SAMe
from methionine. SAMe is the principal methylating agent in the human body &
important for the synthesis of proteins & nucleic acids. Deficiency of
SAMe results in membrane damage, which further worsens liver
damage&[ANNUAL REVIEW OF NUTRITION 20:395-430 (2000)].
SAMe provides a source of cysteine for GSH production. Ethanol also
inhibits methionine synthase, blocking the
inhibiting the capacity for methylation.
]. Even blood alcohol levels of 0.1%
markedly impair visuospatial skills (for driving, flying or
operating machinery) associated with the right parietal region of
the brain&[AVIATION, SPACE AND ENVIRONMENTAL
MEDICINE 65:7-15 (1994)].
A review of
indicated brain shrinkage and decreases in
volume for any amount of
drinking&.
The studies were likely cross-sectional rather than longitudinal, and gave
no indication of not counting former alcoholics as abstainers, or of adjusting
for health conditions that limit alcohol use & which makes this study all
the more persuasive (although longitudinal studies and better adjustments
would be preferred).
Prefrontal neuron activity in rats is decreased in a dose-dependent
fashion by ethanol&. Tissue
slices of neurons show reduced duration, amplitude, and spike activity with
increasing ethanol
concentration&.
Ethanol is a vasodilator which has been shown to increase brain blood
but ethanol impairs memory
and&. Chronic
ethanol administration to rats
deposition in neurons of the
comparable to changes seen in
Animal experiments have demonstrated that bouts of binge
drinking can produce necrotic neurodegeneration in the areas of
the brain most closely associated with the
&[ALCOHOLISM:
CLINICAL & EXPERIMENTAL RESEARCH 26(4):547-557 (2002)]. A small study of young,
non-alcoholic social drinkers indicated cognitive & neurological impairment (reduced
event-related brain potentials when sober) among the heavy drinkers&[JOURNAL OF
STUDIES ON ALCOHOL 57:125-135 (1996)]. The
produced in the brain from ethanol
are particularly damaging to the
&. Even low
to moderate consumption of alcohol was associated with brain atrophy in a study of middle-aged
By potentiation of GABA-mediated inhibition and blockage of glutamate release
in the hippocampus, ethanol can significantly reduce spatial learning and memory by
30&minutes following administration, and the effect does not fully reverse until
24&hours in rats&[BRAIN RESEARCH REVIEWS; Silvers,JM; 43:275-284 (2003)]. Ethanol
also reversibly inhibits neurogenesis in the hippocampus in
adults&[], but may lead to permanent reduction of pyramidal
hippocampal cells in a foetus subjected to binge-like alcohol bouts&[HIPPOCAMPUS; Miki,T;
14:124-134 (2004)]. The hippocampus is also the area of the brain showing the greatest
increase of
deposition
in neurons as a result of chronic alcohol consumption&[NEUROBIOLOGY OF AGING; Borges, MM;
7:347-355 (1986)].
Light drinking increases social conversation and reduces
inhibition among virtually all people who consume alcoholic
beverages on social occasions. The effects are particularly
dramatic for some people suffering from high anxiety. Light
drinking can also increase violent aggression in some people.
Yet the same doses of ethanol producing these seemingly
stimulant effects usually reduce performance on complex tasks.
In the United States the legal definition of &intoxication&
is based on Blood Alcohol Concentration (BAC) in
grams of alcohol per deciliter of blood. Legal limits of BAC vary from state
to state, typically between 0.08 and 0.10. A BAC of 0.10 usually results in
slurred speech, 0.50 is associated with coma and 0.60 can lead to respiratory
paralysis & death in adults. A BAC lower than 0.60 can kill children.
Ethanol exerts its primary effects through modulation of
action of a number of
, notably subtypes of receptors for GABA &
glutamate. Ethanol also alters the activity of the brain signaling
chemicals serotonin, acetylcholine, dopamine, noradrenaline, endorphin,
encephalin and neuropeptide&Y. Ethanol also reversibly reduces
sodium transport in neurotransmission&[NATURE 200:476 (1963)].
many of the effects of ethanol are through
. Ethanol may inhibit adenosine transport, interact directly with adenosine
receptors and increase adenosine formation & the latter as a byproduct of ethanol
metabolism&[THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
259(1):403-408 (1991)]. Caffeine can offset the effects of alcohol when the levels of
caffeine are high and the levels of alchohol are low. The reversal is best for the
effects of alcohol, but co-ordination & performance
may not improve as much & leaving a &wide-awake drunk&.
Alcohol ingestion prior to bed reduces
& especially in the first half of the night &
resulting in impaired memory for recently-learned procedural
GABA () is the major
inhibitory neurotransmitter in the brain. By increasing the
inflow of chloride&(Cl-) across neural
membranes, GABA opposes the tendency of neurons to depolarize.
Ethanol augments the influx of chlorine ions due to GABA,
which has much to do with the sedative, tranquilizing and/or
anaesthetic properties of beverage alcohol. Yet ethanol does
not have this effect on all GABA receptors, only the
GABA&A subtypes (the GABA-benzodiazepine receptors)
containing subunits that can be phosphorylated with Protein
Kinase C&(PKC) & an enzyme that normally
provides negative feedback-inhibition for receptor stimulation.
The motor incoordination due to ethanol is caused by potentiation
of GABAA-associated adenosine A2A receptors in the
striatum (caudate nucleus & putamen)&[BRAIN RESEARCH 776:235-245 (1997)].
The second brain neurotransmitter receptor most strongly
affected by ethanol is the NMDA (N-Methyl-D-Aspartate)
receptor for
. Ethanol,
especially in high doses associated with heavy drinking,
is a potent inhibitor of the NMDA receptor. NMDA function
in the hippocampus is associated with memory formation
through a process known as
Ethanol produces a dose-dependent suppression of the
magnitude of LTP&[BRAIN RESEARCH 688:27-33 (1995)].
In high doses ethanol can block LTP almost entirely. LTP blockage is the likely
explanation for the fact that after an evening of heavy drinking, 30-40%
of males in their late teens or early twenties experience a
blackout which eliminates all or part of their memory of what
occurred while drinking.
Ethanol can increase release of arachidonic acid from cell membranes and
(with increased cyclooxygenase activity) can cause oxidative stress in the brain.
Hydroxyethyl
derived directly from ethanol are nearly as damaging
as hydroxyl radicals and are more long-lived&[FREE RADICAL BIOLOGY & MEDICINE
32(4):314-318 (2002)].
induces slow-wave sleep, but
serotonin activity is reduced during Rapid Eye Movement&(REM)
sleep. Ethanol potentiates serotonin
activity, thereby suppressing REM sleep. Ethanol initially promotes
sleep (even though suppressing REM sleep), but after several hours
there will be more awakenings & an unsatisfying sleep experience.
Low doses of ethanol can enhance
's muscarinic activation of
the hippocampus (thereby opposing some of the NMDA blockage),
but higher doses depress the acetylcholine effect. Ethanol increases
release in the nucleus
accumbens, a brain &pleasure center& similarly
activated by cocaine. Ethanol also acts on voltage-gated
calcium channels and adenosine receptors.
Pharmacological disruptions in brain signalling probably
lead to erroneous thoughts & memories which accumulate and
may be hard to remove & even if there is no permanent physiological
damage. Such effects would be difficult to detect unless they were
gross, in part because no individual person has a control subject.
Ethanol is known to produce both tolerance and dependence.
Tolerance refers to the fact that an increasingly higher
dose of the drug is required to produce the same effect.
Dependence refers to the fact that withdrawal of the
drug produces unpleasant physiological effects. Ethanol
withdrawal symptoms include tremor, anxiety, aberrations
in body temperature and potentially fatal convulsions.
Alcohol tolerance & dependence can be attributed to
compensatory synaptic plasticity, particularly an adaptive
increase in NMDA receptors. Hyperexcitablility of NMDA
receptors is associated with the withdrawal convulsions
and an increase in &[PHARMACOLOGY, BIOCHEMISTRY AND BEHAVIOR
59(4):981-991 (1998)]. There is evidence, however, that blockage of
NMDA receptors by ethanol can reduce excitotoxic damage in head
injury&[JOURNAL OF NEUROSURGERY 86:876-882 (1997)].
Nutritional deficiency is certainly a factor in alcoholic
brain damage. Alcohol amnesic disorder (Korsakoff's
Disease) is usually associated to a deficiency of
Vitamin&B1 (Thiamine). Lesions are found in the
thalamus and mammillary bodies as well as in the hippocampus.
But even without nutritional deficiency, chronic alcoholics
show significant reduction of white matter and reduction of neuron
density, particularly in the prefrontal cortex, the cerebellum and the
amygdala&[JOURNAL OF NEUROPATHY AND EXPERIMENTAL NEUROLOGY 57(2):101-110
(1998)]. Even without thiamine deficiency, nearly a fifth of the neurons in
the frontal association cortex are lost
in chronic alcohol consumption&[NEUROSCIENCE 79(4):993-998 (1997)].
Reductions in cerebral blood flow & brain function
(observed when not under the immediate influence of alcohol)
have been demonstrated
in heavy drinkers with no nutritional deficiencies and
whose ethanol consumption was less than that typically seen in
alcoholics&[JOURNAL OF THE AMERICAN GERIATRIC SOCIETY
31:540-543 (1983)]. (The study corrected for the effects of
age and smoking.)
Females are more sensitive to brain damage by ethanol than are
males&[ALCOHOL & ALCOHOLISM 25(5):445-448 (1990)]. Nonetheless, although
3-5% of males are alcoholics, no more than 1% of women are.
The unborn foetus is also highly sensitive to brain damage by ethanol
& in the extreme cases leading to
(FAS), a condition characterized by
facial disfigurement, growth retardation and brain damage
(particularly to the corpus callosum, basal ganglia and cerebellum).
FAS infants show reduced overall brain size and reduced thickness of the
cerebral cortex due to fewer cells&[ALCOHOL HEALTH & RESEARCH
WORLD 18(1):17-21 (1994)].
Although clinically obvious FAS only occurs in a small percentage of
alcoholic mothers, pregnant women are well advised to abstain from
drinking ethanol.
is a trophic factor for brain development
& and serotonin is significantly decreased in a foetus exposed to
ethanol&[PHARMACOLOGICAL EFFECTS OF ETHANOL ON THE NERVOUS
SYSTEM Deitrich & Erwin, Editors, 1996, page&351]. Experiments
on neonatal rats indicate that the combination of aspirin & ethanol
results in a greater reduction of brain weight than either aspirin or
ethanol alone&[NEUROTOXICOLOGY AND TERATOLOGY 11:135-143 (1989)].
(For photographs of the effects of FAS, see
Acetaldehyde in the brain & liver forms adducts (attachments) to
DNA, thiamine (worstening Korsakoff's Disease), enzymes (inactivating
them) and tubulin. By binding the lysine of tubulin protein,
acetaldehyde prevents the polymerization necessary for microtubule
formation. Microtubules in neurons are essential for transport of
proteins, nutrients and organelles along the long axons&[ALCOHOL
& ALCOHOLISM 25(2/3):217-230 (1990)].
Binding of
(GSH) and/or cysteine by acetaldehyde causes
inhibition of GSH synthesis and
marked decreases in GSH after acute or chronic ethanol intoxication.
But increases in free-radical production with ethanol is not simply
due to reduction in GSH&[ALCOHOL & ALCOHOLISM 20(2):161-173
(1985)]. Ethanol has been shown to increase lipid peroxidation by
21.8% in the brain, but higher increases are seen in the
heart (28.8%), lung (35.9%) and testes (45.3%)&[ALCOHOL
& ALCOHOLISM 34(6):842-850 (1999)]. Isolated synaptosomes
(presynaptic membrane-containing vesicles) subjected to ethanol show
considerable oxidative damage&[JOURNAL OF NEUROCHEMISTRY
63: (1994)].
Aside from arachidonic acid release due to ethanol, hydroxyethyl
radicals derived directly from ethanol can be nearly as reactive as
hydroxyl radicals & while having a longer half-life. Polyphenols in
grapes oppose the oxidative stress due to ethanol&[FREE RADICAL BIOLOGY
& MEDICINE 32(4):314-318 (2002)] & a better justification for eating
grapes than for drinking red wine.
The amino acid
can protect the brain from alcohol-induced
oxidative damage, and can protect against alcohol impairment of
The cancer rate in alcoholics is ten times higher than that in
the general population.
Epidemiological studies find a much lower incidence
of cancer among abstaining religious groups such as Mormons and Seventh-Day
Adventists (though non-smoking and vegetarianism are certainly
influences). (As stated above, a controlled randomized, double-blind,
long-term longitudinal epidemiological study of ethanol will probably
never be done.)
Every 10&grams (10&milliliters & just under &one
drink&) per day of ethanol consumption is associated with a
9% increase in breast cancer&[EUROPEAN
JOURNAL OF CANCER 36: (2000) and JOURNAL OF THE AMERICAN
MEDICAL ASSOCIATION 279(7):535-540 (1998)] & up to 60&grams
(ie, a 9% greater risk of breast cancer with 10&grams per day
and a 54% greater risk with 60&grams per day). Users of
post-menopausal hormones who drink more than 20&grams of alcohol per
day have nearly twice the incidence of breast cancer as users who do not
drink&[ANNALS OF INTERNAL MEDICINE 137:798-804 (2002)]. An
extremely large study of nearly 60,000 women found that both smokers and
nonsmokers increased their risk of breast cancer by 7.1% for each
additional 10&grams per day of ethanol, concluding that about 4%
of breast cancer in developed countries can be attributed to
alcohol&[BRITISH JOURNAL OF CANCER 87(11): (2002)].
Four drinks (60&grams
ethanol) per day is associated with a 21% increased risk of prostate
cancer&[EPIDEMIOLOGIC REVIEWS 23(1):110-114 (2001)]. Heavy drinking
accounts for nearly 20% of all prostate cancers.
Both acute & chronic ethanol consumption increases serum
estrogen and decreases serum androgen in both men & women. Many
alcoholic men have irreversible atrophy of their testicles. Because
excess estrogen & androgen is associated with increased cancer
risk, the effect of ethanol on sex hormones explains the increase in
breast cancer, but the increase in prostate cancer with ethanol must be
due to another mechanism. Ethanol may contribute to osteoporosis at least
partially through testosterone reduction&[THE AMERICAN JOURNAL OF
MEDICINE 86:282-288 (1989)].
Animal experiments indicate that ethanol itself does not cause cancer, but
that acetaldehyde (the first metabolic product of ethanol) is toxic, mutagenic and
carcinogenic (cancer-causing). Acetaldehyde interferes with
by DNA-repair enzyme
blockage and by binding to DNA and proteins&[ALCOHOL & ALCOHOLISM; Poschl,G;
39(3):155-165 (2004)]. Alcohol induction of CYP2E1 enzyme in the liver leads to production
of many carcinogens. Nearly half of all cancers in the oral cavity, pharynx, larynx and
esophagus have been attributed to alcohol&[same reference].
The combination of ethanol & cigarette smoking seems to have a
powerful synergistic effect in oral & pharyngeal cancer. Daily
consumption of 20-39 cigarettes (for a period of over 20 years) and 2-4
drinks (30-60 milligrams ethanol) results in a
(increased probability compared to control, ie, compared
to abstainers) of 7.2 for those cancers. The relative risk rises to nearly
38 times the probability of these cancers in those who consume more than
30 cigarettes and 4 drinks daily. 75% of all oral/pharyngeal cancer
cases are attributed to the smoking/drinking combination. Both alcohol
& tobacco have been shown to reduce epithelial thickness by cell
shrinkage on human tongues&[CANCER RESEARCH 52(suppl):s
Ethanol is known to reduce T-cells (Thymus-derived lymphocytes)
& suppression of the immune system that can increase cancer incidence
and decrease resistance to infectious diseases&[IMMUNOPHARMACOLOGY
15:85-94 (1988)]. Ethanol may also suppress DNA methylation of oncogenes
(cancer-inducing genes) leading to dedifferentiation &
proliferation&[GUT 51:132-139 (2002)].
Other mechanisms suggested for increased incidence of cancer with
ethanol include effects on liver carcinogen
metabolism, generation of
depression of
reduced nutrients due to reduced absorption and reduced consumption
of food nutrients associated with obtaining calories from alcohol.
Polyphenols & resveratrol (a phytochemical synthesized by grapes
in response to fungal infections) are anti-cancer compounds found in high
quantities in red wine & and to a lesser extent in peanuts, grape juice
and cranberry juice&[JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
50:431-435 (2002)]. But there is no need
to drink red wine to get polyphenols & the polyphenols in
may well be more potent. Tablets of concentrated resveratrol
can be purchased at health food stores or online from the Life Extension
Foundation (LEF,
number 13356).
Ethanol stimulates excess levels of plasma cortisol, which can
have harmful immunosuppressant and
. Some alcoholics develop hypercortisolism
(pseudo-Cushing's syndrome)&[ENDOCRINOLOGY 124(1):518-526 (1989)].
A general review entitled &Alcohol and energy intake& can
be found in THE AMERICAN JOURNAL OF CLINICAL NUTRITION 62(suppl):S
(1995). Despite the fact that alcohol does not reduce average food
intake (evidently being a stimulant to the appetite), alcohol does not
always lead to weight gain. Part of the reason is that alcohol drinkers
reduce their consumption of food as a result of the calories they get
from alcohol. But there is also a suppression of oxidation of fat. Alcohol
damages energy-generating systems of mitochondria, while at the same time
increasing metabolism. &Liver mitochondria from
ethanol-fed rats had 55% fewer active ribosomes and 46% less
initiation of protein synthesis.&
The INTERNATIONAL JOURNAL OF OBESITY [19(Supplement 5):S44-S50 (1995)]
contains a review of the &paradox of alcohol& which ends by
speculating about the dehydrating effects of alcohol perhaps affecting weight & or
an effect on insulin. The paper concludes that further studies are
required to determine the paradoxical nature of alcohol calories.
There is evidently much individual variation to the
effects of alcohol. Alcohol appears to have no trend of making
lean individuals obese, but causes obese individuals to become
more obese. Ethanol contains 7.1&Calories (kilocalories) per gram and
it decreases total body fat metabolism by nearly 80%.
Ethanol stimulates acid-rich gastric secretions, making alcohol
consumption inadvisable for patients with peptic ulcers. Ethanol
ingestion is inadvisable for epileptics taking phenytoin (Dilantin)
due to interference with metabolic clearance. Ethanol also
interferes with the metabolism of oral hypoglycemics (such as
tolbutamide) taken by some diabetics.
Asthma is worsened by
alcoholic beverages for nearly a third of asthmatics. For Caucasians,
this effect is usually due to the non-alcohol components
(&congeners&), being more serious for wine (30%)
than beer (23%) or whisky (16%)&[CLINICAL AND
EXPERIMENTAL ALLERGY 32:186-191 (2002)].
Aspirin & ethanol are not a good combination. Taken together they
significantly worsen bleeding time (hemorrhagic stroke), gastric irritation
and foetal brain damage.
The risk of spinal osteoporosis with vertebral fractures is significantly
greater among men who drink alcoholic beverages than those who don't. The
risk increases by a factor of 1.007 for each ounce per-day-for-a-year of
cumulative ethanol exposure&[THE AMERICAN JOURNAL OF MEDICINE
75:977-983 (1983)].
Small amounts of alcohol can increase (disinhibit?) the sex drive of
men, while at the same time reducing their capacity to get an erection.
Ethanol has a reputation as an appetite stimulant. The claim is
dubious, but if true this would count against it from the point of
view of health & longevity (see ).
One of the purported benefits of ethanol is for
& associated with the legend of a St.&Bernard
dog wearing a barrel of brandy on his neck coming to the rescue of
a snow-stranded skier. But although ethanol causes a sensation of
warmth through dilation of peripheral blood vessels, the loss of heat
can be fatal. Large amounts of ethanol reduce body temperature by
depressing the temperature-regulating mechanisms in the brain.
10-15% of alcoholics experience peripheral neuropathy, causing
numbness & tingling.
Studies of all-cause mortality show a linear relationship between
alcohol consumption and death below the age of 60&[ADDICTION
90(2):471-498 (1995)].
This relationship
should not be surprising in light of the fact that
contribute
to such a large proportion of deaths below the age of 60.
Driving under the influence of alcohol is the most important cause of death
in automobile accidents. In the United States between %
of motor vehicle fatalities were due to intoxication (nearly half of the
motor vehicle fatalities in the 25-29 age group were due to intoxication).
For non-motor vehicle accidents, ethanol intoxication accounted
for 32% of fatal falls, 42% of fatal fires/burns, 34%
of fatal drownings and 29% of fatal poisonings. 32% of homicide
victims and 23% of suicide victims were intoxicated&[ANNALS OF
EMERGENCY MEDICINE 33(6):659-701 (1999)].
Ethanol is implicated in up to half of all cases of marital violence.
Small doses of alcohol can reduce
inhibition and allow personalities to become &expansive&,
while at the same time reducing manual dexterity and good judgement.
A person under the influence of only one or two drinks may be less
capable of dealing effectively with an unexpected life-threatening
emergency situation.
result from blockage of AntiDiuretic Hormone
(ADH) by alcohol, which leads to high urination and subsequent dehydration.
The most severe hangovers occur with alcoholic beverages which are high in
methanol, such as brandy & red wine, whereas less severe hangovers occur for
alcoholic beverages which are low in methanol, such as white wine, gin and vodka.
The symptoms are throbbing head (due to reduced cranial blood pressure), dry mouth,
lethargy, nausea and hypersensitivity to light & sound. Drinking large
amounts of water before, during and after a binge can prevent & treat
symptoms. Caffeine, aspirin and more alcohol can relieve hangover symptoms,
although alcohol & caffeine worsen the dehydration because both are
diuretics (increase urination).
Aspirin before or during a binge can worsen matters because aspirin
blocks alcohol dehydrogenase & elevating blood alcohol (while contributing to
Medical authorities typically suggest total abstinence from ethanol
for those who have uncontrolled high blood pressure, substantially elevated
triglycerides, liver disease, gastrointestinal ulcers and alcoholic
myopathy. Ethanol is also contraindicated for patients on many medications,
including antihistamines such as diphenhydramine&(Benadryl), tricyclic
antidepressants such as amitriptyline&(Elavil), and antianxiety drugs
such as alprazolam&(Xanax) and lorazepam&(Ativan).
concluded that because of the many
obvious health hazards of alcohol (including temporary impairment of
neurological function) and because of the availability of so many other
cardiovascular drugs [ I would add niacin, , weight loss and exercise ] and because &the
benefits of alcohol are small and ill-understood& that the recommendation
to be a light drinker is &not only meaningless but also
irresponsible&.}