The Effects of Alcohol

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THE AMERICAN JOURNAL OF GASTROENTEROLOGY
© 2000 by Am. Coll. of Gastroenterology
Published by Elsevier Science Inc.

Vol. 95, No. 12, 2000
ISSN 0002-9270/00/$20.00
PII S0002-9270(00)02140-7

The Effects of Alcohol Consumption
Upon the Gastrointestinal Tract
Luis Bujanda, M.D., Ph.D.
Department of Gastroenterology, San Eloy Hospital, Baracaldo, Spain

ABSTRACT
Regardless of the type and dose of beverage involved,
alcohol facilitates the development of gastroesophageal reflux disease by reducing the pressure of the lower esophageal sphincter and esophageal motility. Fermented and nondistilled alcoholic beverages increase gastrin levels and acid
secretion. Succinic and maleic acid contained in certain
alcoholic drinks also stimulate acid secretion. Low alcohol
doses accelerate gastric emptying, whereas high doses delay
emptying and slow bowel motility. Alcohol facilitates the
development of superficial gastritis and chronic atrophic
gastritis—though it has not been shown to cause peptic
ulcer. Alcoholic beverages, fundamentally wine, have important bactericidal effects upon Helicobacter pylori and
enteropathogenic bacteria. The main alcohol-related intestinal alterations are diarrhea and malabsorption, with recovery after restoring a normal diet. Alcohol facilitates the
development of oropharyngeal, esophageal, gastric, and colon cancer. Initial research suggests that wine may be comparatively less carcinogenic. (Am J Gastroenterol 2000;95:
3374 –3382. © 2000 by Am. Coll. of Gastroenterology)

INTRODUCTION
Excess alcohol consumption has been associated with multiple pathologies at all levels. In the digestive apparatus,
alcohol has generally been related to its toxic effects upon
the liver (1, 2) and pancreas (3)—relatively little attention
having centered on its actions within the gastrointestinal
tract. However, many studies have investigated the actions
of alcohol upon the individual organs that constitute the
gastrointestinal apparatus— esophagus, stomach, small
bowel, and colon. On the other hand, in recent years, the
effects of alcohol upon a given apparatus or system have
been found to depend on the dose and type of alcoholic
beverage involved.
Alcoholic beverages are generally divided into three
types: wines, beers, and liquors. Although alcohol is an
ingredient common to all three, some beverages also contain
many other substances that exert additional effects upon the
gastrointestinal apparatus, thereby differentiating alcoholic
beverages in terms of both composition and biological action upon the digestive tube.

EFFECTS OF ALCOHOL CONSUMPTION
UPON THE ESOPHAGUS
The most known effects of excess alcohol ingestion at
esophageal level are the development of esophageal varicosities secondary to liver damage caused by alcohol, and
the Mallory-Weiss syndrome (or tearing of the distal third of
the esophagus) due to vomiting. In the case of MalloryWeiss syndrome, 60 – 80% of patients are seen to have
consumed important amounts of alcohol in the preceding
hours (4).
The consumption of large amounts of alcohol with a
normal meal facilitates acid regurgitation by reducing the
pressure of the lower esophageal sphincter and slowing both
esophageal motility and gastric emptying (5, 6). Gastroesophageal reflux is also facilitated in chronic alcoholics
due to the existence of esophageal peristaltic dysfunction,
with an increase in amplitude of the contractions in the
middle third of the esophagus and a decrease in the lower/
middle amplitude ratio (7). Interestingly, despite the increased gastroesophageal reflux in chronic alcoholics, such
patients often present a hypertensive lower esophageal
sphincter (7). It is thought that despite this increased lower
esophageal sphincter pressure, chronic alcoholics are more
prone to experience spontaneous sphincter relaxations,
thereby accounting for the increased reflux (7). Likewise,
the decrease in salivary bicarbonate and the peripheral neuropathy affecting muscle contraction constitute additional
factors that may contribute to reduced acid clearance in the
esophagus (5). Alcohol not only causes direct damage to the
esophageal mucosa but also has noxious effects when it is
no longer in contact with the mucosa. Alcohol thus sensitizes the mucosa to damage. The pathophysiological mechanisms by which alcohol damages the epithelium include
alterations in epithelial transport, intercellular junction disorders, and impairment of the mucosal barrier—all of
which, in turn, facilitate hydrogen ion penetration into the
mucosa (8). Regardless of the type of alcoholic beverage
involved (liquors, white wine, or beer), lower alcohol doses
also have been shown to induce pressure decrements in both
the upper and lower esophageal sphincters, as well as a
decrease in esophageal motility and an enhanced risk of
gastroesophageal reflux in healthy volunteers (9, 10).

AJG – December, 2000

In 1997, Grande et al. (11) studied the effect of red wine
(350 ml) with meals in healthy subjects and its influence
upon esophageal motility and esophagogastric pH values 30
min, 90 min, 9 h and 24 h after mealtimes. The controls
received the same amount of water. During the postprandial
period, the red wine group showed an increase in the number and duration of reflux episodes. Nevertheless, the parameters recorded did not exceed the upper normality limit.
No differences were observed in the variables used to assess
reflux during the nocturnal period. Likewise, no differences
were recorded in the gastric pH values. Thus, according to
these authors, red wine in healthy subjects favors postprandial gastroesophageal reflux, though without exceeding normal limits. In addition to alcohol as such, other mechanisms
that could influence gastroesophageal reflux in patients
given red wine comprise its high titrabable acidity and low
pH. No relationship has been found between the high osmolarity of wine or beer and episodes of heartburn (12).
In sum, alcohol tends to facilitate or cause gastroesophageal reflux and esophageal mucosal damage, regardless of
the type of alcoholic beverage involved.

EFFECTS OF ALCOHOL CONSUMPTION
UPON THE STOMACH
Of the different effects of alcohol upon the stomach, its
influence on acid secretion, gastric emptying, and certain
acid-related diseases, such as gastritis and gastroduodenal
ulcer, have been the focus of research.
Effects of Alcohol Upon Acid Secretion
In 1993, Chari et al. (13) conducted a review of the effects
of alcohol and of different alcoholic beverages upon gastric
acid and gastrin secretion. Most studies found intravenous,
intragastric, or oral alcohol dosing at low concentrations (up
to 5% alcohol) to stimulate acid secretion, whereas higher
doses either exerted no effect or showed inhibitory action. In
contrast, red and white wine and beer at moderate doses
stimulated acid secretion and gastrin release (14). The
mechanism by which wine or beer increases acid secretion
was explained in terms of gastrin release and, to a lesser
degree, as a direct effect upon the gastric parietal cells.
High-grade alcoholic beverages (such as whiskey, gin, or
brandy) did not stimulate acid secretion or gastrin release.
The mechanisms proposed to explain the stimulatory effect
of low-dose alcohol upon the gastric mucosa include mediation via the cholinergic system, topical stimulation of the
parietal cells with an increase in cyclic AMP (cAMP) production, and histamine release. The reasons why pure or
higher concentration alcohol (above 5%) does not stimulate
gastric acid secretion are not known, though a number of
hypotheses have been proposed—including a direct inhibitory effect upon the G cells, parietal cell damage or inhibition, the production of gastric secretion inhibitors (somatostatin, prostaglandins), or the high osmolarity of the
solutions employed (13, 15, 16). These results have recently

Effects of Alcohol Upon the GI Tract

3375

been confirmed by Teyssen et al. (17), in a 1997 study
showing fermented and nondistilled alcoholic beverages
(i.e., beer, wine, champagne, martini, and sherry) to increase
acid secretion, mean acid output (MAO), and gastrin release
up to 5.1 times more than the control beverage (isotonic
glucose and water) in healthy individuals. When these beverages (beer, wine, and sherry) were distilled, the distillation
remnant increased acid and gastrin secretion up to 4.3-fold
versus the controls, whereas the same distilled beverages
exerted no effect. Alcoholic beverages subjected to distillation—such as whiskey, brandy, calvados, Armagnac, and
rum—were found to have no effect upon acid and gastrin
secretion versus the controls. Three important conclusions
may be drawn from this study:
1) Fermented alcoholic beverages, such as red and white
wine, beer, champagne, martini, and sherry, are potent stimulators of acid secretion and gastrin release in healthy,
nonalcoholic subjects. The effect of champagne is not dependent only upon the presence of carbon dioxide and
alcohol.
2) Fermented and distilled alcoholic beverages, such as
whiskey, brandy, rum, and other liquors, such as Armagnac,
calvados and Cointreau, have no effect upon acid secretion
or gastrin release. In this sense, the substances that increase
acid secretion probably disappear or decrease in concentration during the distillation process. Alternatively, substances
that inhibit acid secretion could be produced during distillation.
3) Distillation causes beer, wine, and sherry to lose all
their properties.
Some authors are of the opinion that the substances responsible for the stimulation of acid secretion are thermally
stable, anionic molecules with molecular weights under 700
Daltons (17). Some authors have recently found succinic
and maleic acid— both present in beer and wine—to stimulate acid secretion; this effect was not mediated by gastrin
release, however (18).
The acid secretion capacity of alcoholics is highly variable and can be increased, diminished, or similar to that
observed in healthy individuals.
Effects of Alcohol Upon Gastric Emptying
The effects of alcohol upon gastric motility and emptying
have been extensively studied—with contradictory results,
apparently dependent upon the dose and type of beverage
involved. In this context, the administration of a low alcohol
dose accelerates gastric emptying, whereas high doses delay
emptying and reduce bowel motility (8). Pfeiffer et al.
investigated gastric emptying and bowel transit following
different beverages and found wine and beer to increase
gastric emptying and intestinal motility versus physiological
saline or alcohol (19). On the other hand, ethanol has also
been seen to cause pyloric relaxation, which may facilitate
gastric emptying, though it could also favor duodenogastric
reflux (20).

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Bujanda

Relation of Alcohol to Gastritis and
Gastroduodenal Ulcer
Both superficial and chronic atrophic gastritis are common
in alcoholics: 25.8% of those enrolled in detoxification
programs presented with superficial gastritis, and 24.2% had
chronic atrophic gastritis—versus 10.7% and 3%, respectively, in healthy subjects (21). Posterior studies have observed that some of these lesions are more the result of
Helicobacter pylori (HP) action than a consequence of alcohol as such, and that many disappear upon eradicating HP,
though not on interrupting alcohol consumption (22). Acute
alcohol ingestion at concentrations of over 25% altered the
gastric mucosal barrier—an effect that was in turn intensified by nonsteroidal anti-inflammatory drugs (NSAIDs).
Although alcohol stimulates acid secretion and can cause
acute gastritis as a result of direct mucosal damage, it has
not been possible in healthy subjects to show that acute
alcohol administration alters the pH gradient across the
mucous layer, from the acidified lumen to near-neutral pH at
the mucosa (23). It has not been possible to show that
alcohol consumption produces or is associated with an increased incidence of gastroduodenal peptic ulcer (9), or to
the healing or relapse of peptic ulcer. It is important to point
out that studies of this kind should avoid the introduction of
elements or bias that could alter acid secretion, such as the
pH, volume, osmolarity, and caloric contents of the infusions or beverages employed.
Some authors (24) have studied the actions of alcohol and
the type of beverage upon the gastric and duodenal mucosa
in healthy subjects. To this effect, they administered 100 ml
of beer; white wine; whiskey; 4%, 10% or 40% alcohol
solution; or physiological saline orally to healthy individuals on a controlled, randomized and double-blind basis. The
mucosa was in turn analyzed before ingestion and 30, 60,
and 240 min, and 24 h after administration. Mucosal
changes were scored from 0 to 5, where 0 corresponded to
a normal mucosa, and 5 represented a mucosa with 10 or
more hemorrhagic lesions. The resulting gastric lesions
were observed to be alcohol-dose dependent (control, 1.5;
4% alcohol, 1.3; 10% alcohol, 1.8; 40% alcohol, 3.8), appearing within the first 30 min and peaking after 60 min.
White wine, beer, and whiskey caused lesions, though these
were less extensive than those associated with a solution
containing the same grade of alcohol. Twenty-four hours
after ingestion, only whiskey and the alcohol solutions with
concentrations of over 10% showed lesions. These authors
speculate that alcoholic beverages are likely to contain substances other than alcohol, which exert a protective effect,
and that wine and beer possess more protective substances
than other alcoholic beverages (24).
Excess alcohol consumption produces neither macroscopic nor light microscopic alterations in the duodenal
mucosa. However, on examining samples subjected to immunohistochemical staining or under the electron microscope, fibrosis of the duodenal villi is observed, associated
with the transformation of villous juxtaparenchymal cells

AJG – Vol. 95, No. 12, 2000

into active subepithelial myofibroblast-like cells capable of
producing a different extra cellular matrix (collagen I and
III) (25). Chronic alcohol consumption also stimulates the
production of gamma-glutamyl transferase (GGT) and intestinal alkaline phosphatase (IAP) in the mucosal absorptive cells of the small intestine and duodenum (26).
Quercetin, one of the polyphenols contained in wine,
inhibits the formation of gastric ulcers caused by absolute
alcohol (27). The underlying mechanism appears to involve
inhibition of leukotriene and histamine release from the
mast cells present within the gastric mucosa (28).

EFFECT OF ALCOHOL UPON
GASTROINTESTINAL INFECTIONS
In past decades, the consumption of wine with water was
advised on a daily basis with meals, to prevent diarrhea.
Likewise, during the cholera epidemics of the 19th century,
the vibrios were seen to be destroyed in water-diluted wine.
Balsams prepared with wine were in turn used to cleanse
and disinfect wounds in the past. Wine was used in times of
war to prevent dysentery. Thus, the Diary of Perey (during
the Prussian campaign of 1807) reported: “Dysentery
progresses. The army suffers from it, though weakly so:
wine is distributed among the troops for it is the best
preservative . . . ”
In 1988, Sheth et al. (29) conducted an in vitro study of
the effect of different beverages (lemonade, beer, wine, cola,
milk, and water) upon enteropathogenic bacteria (Salmonella typhimurium, Shigella sonnei, Escherichia coli). This
study was designed to define a beverage for avoiding diarrhea among travellers to countries with very poor hygienesanitary conditions. Most such cases of diarrhea are caused
by the three above-mentioned enteropathogens. These authors found neither water nor milk to reduce the number of
colonies, though wine quickly reduced their presence. The
effects of beer and the other beverages were inferior to those
of wine. Posteriorly, in 1995, Weisse et al. (30) carried out
an in vitro study of the effect of a 10% tequila solution,
white and red wine, 10% alcohol, and bismuth salicylate
upon the same bacterial species investigated by Sheth et al.
They found the bactericidal effect of white and red wine to
be superior to that of the rest of solutions upon Salmonella
enteriditis and Shigella sonnei, and similar to that afforded
by bismuth salicylate against Escherichia coli. These authors postulated a possible bactericidal effect produced by
the pH, alcohol, or nonalcohol substances contained in wine.
Our group (31) posteriorly conducted a study to elucidate
the bactericidal mechanism of wine. To this effect we carried out an in vitro analysis of the bactericidal effect upon
Salmonella enteriditis of red wine, an HCl solution at pH
3.5, a solution containing a 12% concentration of alcohol at
pH 3.5, and a control solution (water). Red wine was seen

AJG – December, 2000

to possess intense bactericidal activity, which was moreover
superior to that afforded by the solution presenting the same
concentration of alcohol and pH as wine. A large proportion
of the bactericidal effect of red wine against Salmonella was
found to be due to its acid pH and alcohol contents, though
these factors provided only a partial explanation for the
observed effects.
Bellido et al. (32), in a retrospective study of an outbreak
of Salmonella enteriditis, found the number of affected
individuals to decrease with increasing ethanol consumption. In turn, the relative risk of infection among those who
had consumed wine was 0.13 versus 1.6 for beer drinkers—
abstemious subjects serving as controls (relative risk ⫽ 1).
In 1996, Cook (33) reviewed the bactericidal action of
alcohol on enteropathogenic bacteria. Two studies (not published) suggested wine to exert a protective effect against
intestinal infections, whereas the rest of the reviewed articles (four in total) involved alcoholic beverages other than
wine. Two of these studies reported a diminished risk of
severe gastroenteritis due to Salmonella heidelberg or Shigella sonnei.
Likewise in recent years, an inverse correlation has been
established between alcohol consumption and the prevalence of HP infection, both in the general population and
among cirrhotics. We have carried out an in vitro analysis of
the bactericidal action of different solutions on HP. The
study solutions included red wine, an HCl solution at pH
3.5, a solution containing 12% alcohol, a solution containing
the same alcohol concentration at pH 3.5, and a control
solution (water). Red wine was seen to exert a marked
bactericidal effect upon HP, superior to that observed for the
other solutions. Nevertheless, not all the bactericidal effect
could be attributed to the acid pH of wine and its alcohol
concentration (34). No explanation has yet been found for
the mechanism by which wine exerts an in vitro bactericidal
effect independent of its alcohol concentration, nor have the
substances responsible been identified to date. Other in vivo
mechanisms that could contribute to the protective effect of
wine might be the rise in acid secretion and the increase in
intestinal motility. Recent epidemiological studies have also
found a high consumption of alcohol to be inversely related
to the presence of HP infection. Accordingly, the relative
risk of HP infection in individuals who consumed more than
75 g of alcohol was found to be 0.31 versus 1 among the
abstemious subjects. This effect was in turn more closely
associated with wine than with beer (35).
Clinical studies entail numerous ethical and technical
problems, such as the degree of foodstuff contamination, the
amount ingested, individual susceptibility, the alcohol consumed, the type of beverage involved, and the timing of
beverage consumption.
Other authors have reported a protective effect of alcoholic beverages against other microorganisms, such as an
outbreak of hepatitis A caused by the consumption of oysters (36) or other infections (37).

Effects of Alcohol Upon the GI Tract

3377

EFFECTS OF ALCOHOL CONSUMPTION
UPON THE INTESTINE
Alcohol has been related to alterations in the absorption of
food in the small bowel and to intestinal motility disorders.
Effects of Alcohol Upon Food Absorption
The most frequent intestinal disorders observed among alcoholics are diarrhea and malabsorption, caused by alterations in the digestion and absorption of food. These alterations, nevertheless, disappear upon returning to a normal
diet following the cessation of alcohol consumption.
The mechanism underlying diarrhea is mixed and involves a decrease in the activity of the mucosal disaccharidases and an increase in permeability that facilitates the
output of water and solutes (sodium and chloride) into the
intestinal lumen. Steatorrhea is an additional complication
that can be observed in alcoholics and is generally attributed
to pancreatic insufficiency and the alcoholic liver disease
sometimes found in such patients (3). The intestinal permeability in chronic alcoholics is increased, but returns to
normal after 1 or 2 weeks of abstinence (38). This suggests
the existence of increased endotoxemias in alcoholics,
which could contribute to or explain the development of
liver disease in some. A contributing consideration in this
sense might be the fact that the jejunum in alcoholic patients
contains an increased presence of aerobic and anaerobic
bacteria that facilitates the production of endotoxins (39).
Malnutrition in chronic alcoholism is the result of numerous alterations in the transport and absorption of most nutrients. Nevertheless, in many cases the condition is caused
by a deficient dietary provision of nutrients. Thus, many of
these nutritional disorders normalize after restoring a normal diet— even in the event of continued alcohol consumption. In fact, despite an important alcohol intake, the jejunum in alcoholics appears normal both macroscopically and
histologically when examined under a light microscope
(39). However, an electron microscope may reveal alterations affecting the mitochondria, Golgi apparatus, and endoplasmic reticulum (40).
In terms of each individual nutrient, some have been
shown to exhibit absorption disorders, whereas in other
cases, only a deficient dietary provision seems to be involved. Altered intestinal absorption may affect a number of
nutrients or substances, including the following:
1) Thiamin: The acute or intravenous administration of
alcohol diminishes thiamin absorption in one-third of
patients. This effect appears to be related to the inhibitory action of ethanol upon the ATPase in the vasolateral
membrane of the epithelial cell (41).
2) Vitamin B12: Chronic alcohol administration reduces
vitamin B12 absorption in the terminal ileum, as determined by the Schilling test. This phenomenon has also
been observed in rats, along with alcohol-induced inhibition of the secretion of intrinsic factor and active
vitamin B12 transport, and impaired bonding of the vi-

3378

3)

4)
5)
6)

7)

Bujanda

tamin B12-intrinsic factor complex to the corresponding
ileal receptors (42).
Amino acids: Alcohol inhibits the active transport of
different amino acids, such as phenylalanine, leucine,
glycine, alanine, methionine, and valine.
Calcium: The acute or chronic administration of alcohol
in rats reduces calcium transport in the duodenum (43).
Iron: Oral or intravenous ethanol slightly increases the
absorption of ferric chloride (44) in normal subjects.
Intestinal lactase: In black (but not caucasian) individuals suffering from chronic alcoholism, lactase activity is
seen to be inhibited in comparison with normal subjects
(45).
Zinc: Alcoholics present malabsorption of this ion, with
increased losses in urine (46).

No altered absorption has been demonstrated in the case
of other foods or substances when ingested in normal
amounts:
1) D-xylose: Acute ethanol ingestion does not affect Dxylose absorption, provided the dietary supply of this
substance remains normal (47).
2) Folic acid: Folate deficiency is the most common hypovitaminosis (megaloblastosis) observed in alcoholics,
though no folic acid malabsorption has been demonstrated in alcoholics with a normal diet (48).
3) Magnesium: The low magnesium levels observed in
alcoholics are due to insufficient intake and increased
losses in urine and the bowel lumen secondary to vomiting and diarrhea—not malabsorption.
Effects of Alcohol Upon Bowel Motility
The mean duration of orocecal transit as assessed by the
hydrogen breath test after administering 10 g of lactulose in
healthy, abstemious individuals has been found to be 85.5
min versus 156.3 min in alcoholics (mean consumption:
191 g of alcohol/day) and 94 min among so-called social
drinkers. The authors of this study failed to define consumption by social drinkers, however. The mechanisms by which
bowel motility is reduced in alcoholics include the toxic
action of alcohol upon the contractile proteins of the small
intestine, alterations in vagal function, and impaired neuroendocrine factors (49). Alcoholics present increased cortisol and corticotropin levels, which would act by inhibiting
the musculature of the gastrointestinal tract (50). Another
factor that increases orocecal transit time in alcoholics is the
prolonged rectosigmoid transit time, which normalizes after
10 days of alcohol abstinence (51). Other authors have
demonstrated altered small bowel motility after alcohol administration in both normal volunteers and alcoholic patients. Following the administration of ethanol by either the
oral or intravenous route, a consistent decrease was observed in the jejunum in the quiescent phase (phase I) of the
migrating motor complex, though without changes in the
regular activity phase (phase III). In contrast, the ileum

AJG – Vol. 95, No. 12, 2000

showed an increase in phase III wave motility, but no
change in phase I (52).
Effects of Alcohol Upon the Colon
One of the most characterized findings in alcoholics is the
development of hemorrhoids and colonic varicosities secondary to the presence of liver cirrhosis and portal hypertension. The rectal mucosa of chronic alcoholics has also
been shown to exhibit an increased mononuclear cell infiltrate, with more abundant mitochondria and a hypertrophic
endoplasmic reticulum, which disappear with abstinence
(53).
Other Effects of Alcohol Upon the
Gastrointestinal Apparatus
Wine mixed with blood in the gastric cavity reduces the
sensitivity of the guaiac test (54). Controversy exists over
the effects of alcohol upon the sphincter of Oddi. Although
some studies have described an alcohol-induced increase in
the pressure of the sphincter (55), others have reported
decreases in sphincter of Oddi pressure (56, 57).

EFFECTS OF ALCOHOL CONSUMPTION UPON THE
DEVELOPMENT OF GASTROINTESTINAL TUMORS
Cells generate enormous amounts of free radicals that, in
turn, oxidize proteins and other essential components, with
resulting serious alterations of their biological functions. In
an attempt to counter these actions, the body possesses
numerous intra- and extracellular protective systems. In this
context, the extracellular antioxidants include vitamin C
(ascorbic acid), vitamin E (alpha-tocopherol), urates
and—in lesser amounts— beta-carotenes, bilirubin, and glutathione. These compounds are, in turn, consumed by the
pro-oxidizing reactions. Many extracellular antioxidants are
supplied in the diet.
Effects of Alcohol Upon Carcinogenesis
Ethanol and its metabolites (acetaldehyde) promote tumor
development by generating free radicals (superoxide, peroxide, and hydroxyl) and other oxidizing agents. Moreover,
alcohol is directly cytotoxic and is able to produce aberrant
methylation of DNA, with an impairment of its self-repair
capacity. For example, alcohol shortens the ovarian cell
cycle in hamsters, as well as the cycles of other cell lines and
fibroblasts (58, 59). Other factors associated with alcohol
consumption that favor tumor development comprise (59):
1) Diminished host defenses
2) Alterations in hormonal balance
3) Nitrosamines contained in some alcoholic beverages,
including certain beers, or polycyclic hydrocarbons
4) Microtoxins present in some wines and in corn beer
5) Urethane contained in some fruit liquors
6) Inorganic arsenic
7) Pesticide traces
8) Preservatives, antifrothing agents, and other additives

AJG – December, 2000

9) The activation or induction of certain P450 isoenzymes,
such as CYP1A2, which favors the release of certain
carcinogens, such as dimethylnitrosamine
10) The depletion of vitamin deposits (e.g., vitamin A) in
the liver
Effects of Polyphenols in Alcoholic
Beverages Upon Carcinogenesis
The association of antioxidants in fruits and vegetables with
a reduced risk of tumor development has been established in
many studies (60). Flavonoid-rich foodstuffs, such as tea or
onions, have also been inversely related to tumor development (61). One of the differentiating characteristics among
alcoholic beverages is their polyphenol composition. In this
context, wine contains abundant polyphenols—more than
either beer or liquors. A number of polyphenols found in
wine have been shown to possess antioxidant and anticancer
properties. The first such polyphenols studied were quercetin and rutin (62), followed more recently by resveratrol.
Quercetin has important antidegenerative properties (63).
In a number of experimental studies, its administration to
rats has been found to diminish the development of breast
cancer (64). However, in other experimental models, quercetin at high doses has been seen to increase the development of certain tumors (benign renal neoplasms) (65). These
results have been confirmed by the observation that quercetin is able to damage DNA, favoring the appearance of
mutations (66) and incrementing lipid peroxidation in the rat
liver—particularly in the presence of iron (67). Thus, the
effect of quercetin as a pro-oxidant or antioxidant is dependent upon the corresponding redox status and prevalent
biological environment (68).
Resveratrol possesses important anti-inflammatory effects in vitro, similar to those observed for indomethacin
and phenylbutazone, and it has even been found to inhibit
carcinogenesis in animal models (69). Resveratrol induces
apoptosis, mediated by caspase activation in tumor cells in
vitro models (70). When resveratrol is administered to rats
with a rapid tumor growth factor, a very significant reduction in the number of tumor cells is observed—an effect that
appears to be due to tumor cell apoptosis (71).
The polyphenols contained in tea (72, 73), like those
found in wine, have important anticancer actions mediated
by the following:
1) Antioxidant activity. This involves three mechanisms: a)
The catechol structure is able to chelate active metals,
such as ferrous and ferric iron, from within cells—these
metals being needed for the generation of free radicals.
b) Certain catechins act by eliminating superoxide and
hydroxyl radicals, the latter being oxygen-reactive
agents that damage DNA and initiate lipidic peroxidation
processes. c) Flavonols react with peroxy radicals and
thus interrupt the lipid peroxidation chain reaction.
2) Inhibition of nitrosation reactions. These reactions are

Effects of Alcohol Upon the GI Tract

3379

important in certain tumors, such as those found in the
gastrointestinal tract.
3) Enzyme modulation of xenobiotic metabolism.
4) Inhibition of cell proliferation. Certain catechins interrupt tumor promoters and their corresponding receptors.
5) Inhibition of cyclooxygenase and lipoxygenase, which
are enzymes required in cell proliferation.
Effects of Alcohol Upon Oropharyngeal,
Esophageal, and Gastric Cancers
Alcohol consumption has been linked to an increased risk of
tumors of the oral cavity, pharynx, esophagus, stomach, and
upper airways (74, 75)—a risk that increases markedly
when associated with tobacco smoking (76, 77). A recent
epidemiological study (78) has analyzed the relation between different types of alcoholic beverages and the risk of
developing oropharyngeal and esophageal tumors, controlling for confounding factors, such as patient age and sex,
tobacco smoking, and educational level. Specifically, the
risk of developing such neoplasms was investigated in
15,117 males and 13,063 females, aged 20 to 98 yr, with a
mean duration of follow-up of 13.5 yr. In the course of this
follow-up period, 156 patients were found to present tumors. The risk of developing tumors in these locations was
seen to increase linearly with the number of alcoholic beverages consumed weekly. However, on considering the type
of beverage, the risk was seen to decrease notably among
those patients who drank wine, in all alcoholic beverage
groups. Thus, drinkers of 7–21 beers or liquors weekly
presented a relative risk of 3 of developing a tumor (the
relative risk of abstemious subjects being 1). If these same
subjects consumed more than 30% of their total alcohol
intake in the form of wine, the relative risk dropped to 0.5.
Similar findings applied to heavy drinkers. People who
consumed more than 21 beers or liquors per week exhibited
a relative risk of 5.2, whereas those subjects in this group
who included wine in their consumption presented a decrease in relative risk to 1.7. The authors concluded that
moderate wine consumption probably does not increase the
risk of esophageal and oropharyngeal cancer, whereas moderate beer or liquor consumption increases the development
of such tumors considerably (78).
Other studies have found certain alcoholic beverages,
such as wine, to protect against the development of some of
the above mentioned tumors (50). Thus, in a case-control
epidemiological survey, wine was seen to protect against the
development of esophageal and stomach cancer; in some
cases, the degree of protection reached 40%—a phenomenon not observed for either beer or liquors (79).
Effects of Alcohol Upon Colorectal Cancer
Moderate alcohol consumption (starting at 10 –15 g/alcohol/
day) has been related to an increased risk of colon cancer
and colorectal adenomas versus abstemious individuals
(80 – 82). On analyzing the type of beverage, most authors
associate this risk to liquors and beer, and less so to wine. In

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contrast, a recent Italian case-control study has reported no
association between alcohol consumption and colorectal
cancer; likewise, no association to wine consumption has
been observed (83).
The hypotheses proposed to account for the development
of colon cancer include DNA alteration with hypomethylation secondary to S-adenosylmethionine deficiency. The
latter would, in turn, be related (among other causes) to high
alcohol consumption (84).
Despite the above comments, it should be pointed out that
although many studies have been published on the effects of
alcohol upon the gastrointestinal tract, numerous biasing
factors may be implicated. Those factors include differences
in lifestyle and dietary habits related to each type of alcoholic beverage, which are very difficult to control. Caution
is thus required in attempting to draw firm conclusions.
Reprint requests and correspondence: Luis Bujanda, M.D.,
C/Ocharan Mazas, 13 Q—1° A, 39700 Castro Urdiales, Spain.
Received Mar. 30, 2000; accepted Aug. 15, 2000.

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