1

Literature review: Does chronic alcohol consumption affect protein synthesis

in adult aged rats and humans?
Jesse Owens
ID#0857892
Dr. Gen Newton
April 3rd, 2015

2
Abstract
Objective: To investigate the affects of chronic alcohol consumption on
protein synthesis in adult humans and rats.
Data sources: A systemic review was conducted using PubMed, Cochrane,
and SPORTDiscus online databases.
Study selection: For this review we looked for studies with at least one
group that had consumed ethanol chronically for a period of time and a
control group. The electronic search identified that there was 1113 studies
and 97 were removed due to duplication. In this study 30 ended up being
chosen for this review.
Results: Significant decreases in protein synthesis for the muscles that
contained majority fast-twitch muscle fiber (Gastrocnemius and psoas) and
no significant decrease in the soleus muscle which is primarily slow-twitch
muscle fiber (Lang et al, 1999). The rats that chronically consumed alcohol
had 10% lower heart weights than the control fed rats and a decrease by
25% in protein content in the heart (Vary et al, 2001). The male rats saw a
decrease in protein synthesis by 33% while the female rats did not see any
significant changes (Vary et al, 2007).
Conclusion: Overall chronic alcohol consumption affects protein synthesis
in fast-twitch and cardiac muscle for humans and rats while also no effects
on slow-twitch muscle fiber in rats. Also female rats and humans tend to be

3
less affected by chronic alcohol consumption with regards to protein
synthesis than men.

Introduction
Alcohol has been shown to have its benefits, as long as consumed in
moderation; but it can also negatively affect an individuals health
(Fernndez-Sol et al, 2000). Alcohol is easily accessible by all adults in
most countries (Preedy et al, 2001). With rising obesity levels and
cardiovascular diseases, fitness has become a large part of many adults
lives (Kumar et al, 2009). For those individuals wanting to improve their
physical fitness in muscle strength and or size, but still be able to consume
alcoholic beverages, it is important to address if chronic alcohol consumption
inhibits this anabolic effect on muscle protein synthesis.
Protein synthesis is our bodys way of making new proteins from our
DNA through two processes called transcription and translation (Kumar et al,
2009). Studies have stated that consuming alcohol over short durations of
time as well as long durations of time can inhibit protein synthesis (Vary, &
Lang, 2008). One study done by Addolorato et al (1998), has stated that
many chronic alcohol abusers may have a decreased protein synthesis as a
result of being malnourished because of the excess alcohol consumption
while not consuming the proper caloric intake needed to maintain their

4
normal protein synthesis rates. This review only included studies that made
sure that malnourishment was not a reason for decreased protein synthesis.
The differences in how chronic alcohol consumption affects protein
synthesis in males versus females in rats and human studies has started to
be well explored in recent years (Vary et al, 2007). Many studies suggest
that females in both human and rat studies are less affected by chronic
alcohol consumption than men (Vary et al, 2007, Lang et al, 1999,
Fernndez-Sol et al, 1997).
Studies in rats and humans are exploring how some different muscle
fiber types are affected more than others when it comes to chronic alcohol
consumption. The 3 main fiber types in a muscle are fast-twitch oxidative
(type llx), fast-twitch glycolytic (type llb), and slow-twitch oxidative (type l)
(Reilly et al, 2001). Which muscle fiber type is affected by alcohol has been
well studied and results show that protein synthesis in fast-twitch muscle
fiber decreases but slow-twitch muscle fibers type seems to be relatively
unaffected by any type or amount of alcohol consumption (Reilly et al, 2001,
Koo-Ng et al, 2000). As well as skeletal muscle, cardiac muscle in both
humans and rats was also explored to see if chronic alcohol consumption
affects protein synthesis in this musculature.
Eukaryotic initiation (eIF) and elongation (eEF) factors have been
explored as a possible reason for why chronic alcohol consumption decreases
muscle protein synthesis in both skeletal and cardiac muscle (Vary et al,

5
2004). Eukaryotic initiation factors are involved in eukaryotic translation
which is the process where mRNA is translated into proteins (Vary et al,
2004). Eukaryotic elongation factors is the process whereby amino acids are
added to a protein chain (Vary et al, 2004). Total RNA was also explored to
see if capacity of protein synthesis was a limiting factor. A Hunter et al
(2003), study looked at the proteins nebulin and titin to see if they were the
cause for decrease in protein synthesis. Titin contributes to passive force by
relaxed muscle fibers, and helps maintain the structure of the myofibril
during contraction (Hunter et al, 2003). Nebulin is a protein that binds to
actin and may control the length of the actin filaments (Hunter et al, 2003).
Just as moderate consumption of alcohol has been studied and shown
to be not all bad determining whether chronic alcohol consumption does not
have any positive benefits with regards to protein synthesis must be
explored. Also, whether or not we can restore protein synthesis after chronic
alcohol consumption should be looked into, as well as whether
supplementation such as with -tocopherol (ATC) would reduce muscle
damage from decreased protein synthesis during chronic ethanol
consumption in rats (Koll et al, 2003).
The purpose of this review is to look at the effects of chronic alcohol
consumption on protein synthesis in adult aged humans and rats.
Additionally in this review we will look at 1) the effects of chronic alcohol
consumption on protein synthesis in skeletal and cardiac musculature in rats
and humans. 2) The effects of chronic alcohol consumption on different

6
muscle fiber types in human and rat studies and 3) the effects of chronic
alcohol consumption on males vs females in human and rat studies and 4)
whether protein synthesis can be restored after chronic alcohol consumption.
Materials and methods
Literature Search
The following databases were used to find articles: PubMed, Cochrane, and
SPORTDiscus. Reference lists from reviews and articles were also used to
search for journal articles. Search term example 1: (((chronic ethanol) AND
protein synthesis) AND rat) AND adult produced 23 results in Pubmed.
Search term example 2: ((((chronic ethanol) AND protein synthesis) AND
female) AND male) AND rats produced 20 results in PubMed.
Eligibility Criteria
Types of studies
The studies that were included involved the effect of chronic alcohol
consumption on protein synthesis in adult rats or humans over the age of 18
years old. Participants did not have to have alcoholic myopathy before the
study began. Studies looking at specific factors affecting protein synthesis
were also included, such as proteins nebulin and titin, as well as eukaryotic
elongation and initiation factors were also examined. Protein synthesis in
skeletal muscle and cardiac muscle were included in this review. All studies
were involved whether they resulted in a decrease or increase in protein

7
synthesis so that no bias was present. Some studies also included
supplementation to improve or stop decrease in protein synthesis. Studies
with minimal amounts of human participants were included due to limited
research on humans to date. Also included in this review were studies done
on restoration of protein synthesis. Studies that were older than 15 years
were limited to those thought to be very well done or which involved human
study.
Intervention
All studies must have included one group that was chronically
consuming ethanol of some sort. Participants could be either male or female
for both rat and human groups. Chronic alcohol consumption was defined as
consuming a certain amount of alcohol every day for a number of weeks.
Rat studies involved the rats consuming alcohol for a minimum of 6 weeks to
26 weeks. Human studies lasted 5 years. Skeletal and cardiac muscle
studies were included. Studies that included binge drinking were not
excluded if the study also included chronic alcohol consumption and acute
affects were not noted in this review. Acute alcohol consumption was
defined as binge drinking. Studies that did not monitor caloric intake
between groups to be the same were also excluded to limit any malnutrition
affect. Rat studies involved the rats consuming 30-40% of their caloric
intake as ethanol. Human studies involved the humans consuming 20-194g
of alcohol per day.

8
Outcome Measures
Protein synthesis through flood dosing technique in rats was very
common while in human studies protein synthesis was measured through a
muscle biopsy. Many studies in rats measured weight of the muscle prior to
and after the study. Total RNA was also measured in many studies as well as
mRNA. Eukaryotic initiation (eIF) and elongation (eEF) factors amount and
activity was measured. Proteins nebulin and titin were measured.
Risk of bias
Since all studies included ethanol dosages, it was made sure that if
ethanol dosages were different compared to other groups tested in the study
that the study concluded that these could have caused the difference in
outcome. Malnutrition was very important to watch to make sure that the
nutrition was not the reason for the results. Studies that included women
and men in human studies generally had less women being studied which
could have affected the outcome of the results (Fernndez-Sol et al, 1997).

ity
ng
on
ed

PRISMA 2009 Flow Diagram

Full-text articles
excluded, date too
Studies included in
old, not large enough
quantitative
testing
group,
tested
Records
excluded
Studies
Full-text
included
articles
Additional
in
records identified
Records identified through
Records
Records
after
duplicates
screened
removed
synthesis
(metapigs
not
rats,
study
based off of title or
qualitative
assessed
synthesis
for through other sources
database searching
(n
(n
=
==1016)
1016)
analysis)
not long
enough
abstract
eligibility
(n
32)
(n = 0)
(n = 1113)

Results
Skeletal muscle, fast-twitch and slow-twitch muscle fiber
A Significant amount of the studies collected focused on skeletal
muscle and chronic alcohol consumption. Most common muscle used for
dissection in rats representing a fast-twitch muscle was the gastrocnemius

10
and the soleus was used to represent the slow-twitch muscle group. In
several of the studies it was stated that after chronic alcohol consumption in
rats, protein synthesis had decreased in the gastrocnemius muscle
significantly compared to the control trials (Reilly et al, 2001, Koo-Ng et al,
2000, Lang et al, 1999, Pruznak et al, 2013). Several studies also stated that
even with the same amount of ethanol consumption the soleus muscle did
not see a significant decrease in weight or protein synthesis in rats.
A study by Fernndez-Sol et al, (2000) and another study by Pacy et
al (1991), both looked at long term studies with human chronic alcohol
misusers. Fernndez-Sol et al (2000), study included 68 patients who
suffered from skeletal muscle myopathy due to chronic alcohol consumption.
Fernndez-Sol et al, (2000) study looked at chronic alcohol misusers over a
5 year period and showed that with consuming different ranges of alcohol
per day (20-60g per day, 61-99g per day, and more than 100g per day)
protein synthesis still decreased in the deltoid muscle with all 3 dosages, but
the lower the dose, the lower the decrease in protein synthesis that was
seen. Pacy et al, (1991) study looked at skeletal muscle protein synthesis in
the quadriceps muscle and whole body protein in 6 adult humans (age 42.7
9.3) who suffered from chronic alcoholism. The individuals consumed a
minimum of 100g of alcohol a day for a minimum of 10 years which showed
a decreased protein synthesis in the quadriceps but no significant decrease
in whole body protein (Pacy et al, (1991).

11
A study by Vary and Lang (2008), examined effects of chronic alcohol
consumption on fast-twitch and slow-twitch muscle fibers in male rats. The
rats were all considered mature adults and consumed ethanol for 14 weeks
(Vary and Lang, 2008). Lang et al (1999), looked at gastrocnemius, psoas,
soleus, for the skeletal muscle group in male rats. Results showed significant
decreases in protein synthesis for the muscles that contained majority fasttwitch muscle fiber (Gastrocnemius and psoas) and no significant decrease in
the soleus muscle which is primarily slow-twitch muscle fiber (Lang et al,
1999). Reilly et al (2000), analyzed whether chronic alcohol feeding in rats
affects myosin heavy chain (MYoHC) isoform in fast-twitch and slow-twitch
muscle fiber. The study included male rats (N=12) which included an
ethanol-fed group consuming 35% ethanol and control-fed group. In the
alcohol-fed group the total MyoHC were reduced in plantaris group but not
soleus with decreases in 1b, IIx and IIb isoforms (Reilly et al, 2000). MyoHC
Ib mRNA decreased in both soleus and plantaris group (Reilly et al, 2000).
A study done by Koo-Ng et al (2000), researched whether an increase
in reactive oxygen species damage to the muscles because of alcohol
consumption is caused by increased carbonyl formation. The ethanol-fed
male rats consumed 35% of their calories as ethanol. The muscles used in
the study were the plantaris, soleus, gastrocnemius, and the heart. Ethanol
feeding caused a significant reduced weight in the plantaris muscle
compared to the control group but did not significantly decrease weight in
the soleus muscle group (Koo-Ng et al, 2000). Protein carbonyl increased

12
significantly in both the soleus and plantaris muscle but the increase in the
ethanol fed rats for the soleus was significantly higher than it was for the
control group soleus (Koo-Ng et al, 2000). A study done by Rouach et al
(1997), also found that protein carbonyl increased significantly after alcohol
ingestion. Pruznak et al (2013), studies purpose was to research alcohol in
the central nervous system and whether it is capable of reducing protein
synthesis in fast-twitch and slow-twitch muscle fiber in male rats. The
soleus muscle was unaffected by the ethanol injections with regards to
protein synthesis at any point in time (Pruznak et al, 2013). The
gastrocnemius did see a decrease in protein synthesis (Pruznak et al, 2013).
A study done by Ohlendieck et al (2003), researched whether chronic
alcohol ingestion affects proteins related to calcium homeostasis. In this
study only male rats were used. Control group consumed the same amount
of energy as the ethanol-fed group. The rats were fed a diet containing 35%
ethanol for a total of 6 weeks. Ion-regulatory skeletal muscle proteins were
measured such as sarcoplasmic-endoplasmic reticulum calcium (SERCA), and
adenosine triphosphatase (ATPase) in the gastrocnemius but showed no
significant change in io-regulatory skeletal muscle proteins (Ohlendieck et al,
2003).
In a study completed Hong-Brown et al, (2001) the purpose was to see
what the effect of excessive alcohol consumption had on protein metabolism
in skeletal muscle cells in response to insulin-like growth factor and insulin.
Insulin and IGF-I are used for normal growth of skeletal muscle (Hong-Brown

13
et al 2001). In this study adult human skeletal muscle cells were used. The
cells were incubated with ethanol at different dosages. Other cells were
incubated with acetaldehyde, acetate, insulin or insulin like growth factors
(IGF) or with a combination of ethanol and insulin. The decrease in protein
synthesis plateaued at 72 hours so the anabolic agents were induced at that
mark (Hong-Brown et al 2001). Excessive alcohol consumption did impair
both insulin and IGF-I but not until the 72hr mark (Hong-Brown et al 2001).
Anh Nguyen et al (2012), researched insulin and IGF resistance and oxidative
stress to see if it causes alcoholic related myopathy. The study consisted of
adult male rats consuming 35.5% ethanol if in the alcohol-fed group. Insulin,
IGF-1, and IGF-2 receptors, IRS-1, and IRS-2 all decreased in the ethanol-fed
group as well as myofiber size in the gastrocnemius muscle (Anh Nguyen et
al, 2012).
Malnutrition in alcoholics is always a concern and could be a reason for
decreased protein synthesis (Nicols et al, 2003). A study done by Nicols et
al (2003), researched how malnutrition with ethanol intake affect skeletal
muscle and function in chronic alcoholics (N=219, adult men, 25-64 years
old). The results showed that average deltoid strength was lower in
alcoholics vs control and got worse with severity of myopathy (Nicols et al,
2003). Type ll fiber area decreased in alcoholics and got worse with
increased severity of myopathy and decreased total plasma proteins in
alcoholics (Nicols et al, 2003). Alcoholics with better nutrition had

14
significantly more muscle strength than alcoholics with malnutrition (Nicols
et al, 2003).
Cardiac muscle
Ten of the studies collected looked at chronic alcohol consumption and
how it affects protein synthesis in humans and rats. All of the rat studies
used heart weight as one of the measurement outcomes (Cite). All studies
showed a decrease in heart weight in the rats that consumed alcohol
compared to the control group. One study compared skeletal muscle protein
synthesis and cardiac protein synthesis and found that both decreased in
protein synthesis when consuming ethanol chronically but cardiac muscle
protein synthesis did not decrease as much as skeletal muscle (Vary, & Lang,
2008).
One study looked at what proteins in cardiac muscle were decreasing
after chronic alcohol consumption. The Fogle et al, (2010) study looked at
what proteins decreased in cardiac muscle after chronic ethanol consumption
in rats. The study included 4 control group male rats and 4 alcohol fed rats
(Fogle et al, 2010). The study lasted 16 weeks and the alcohol fed rats
consumed 40% of their caloric intake as ethanol in their food and water
(Fogle et al, 2010). Results showed that 18 sarcoplasmic proteins decreased
while 10 had actually increased even though there was a 25% decrease in
cardiac protein (Fogle et al, 2010). Vary and Deiter (2005), looked at
myofibrillar and non-myofibrillar fractions in the heart in male rats for 16

15
weeks. Those chosen to go into the alcohol-fed group received 40% of their
caloric intake from ethanol. Rate of protein synthesis was measured using
flooding-dose technique (Vary and Deiter, 2005). Non-myofibrillar proteins
significantly decreased by 20% and myofibrillar proteins significantly
decreased by 23% (Vary & Deiter, 2005). Vary et al (2001), looked at if
protein synthesis would be inhibited in the heart after chronic alcohol
consumption had the rats consuming 30% of their caloric intake as ethanol
for 16 weeks in male rats. Rates of protein synthesis were calculated using
flooding-doses (Vary et al, 2001). The rats that chronically consumed alcohol
had 10% lower heart weights than the control fed rats and a decrease by
25% in protein content in the heart (Vary et al, 2001). The rate of myocardial
protein synthesis was decreased by 30% (vary et al, 2001).
Vary et al (2007), studied feeding male and female rats both 40% of
their caloric intake as ethanol for either 28 weeks or 12-14 weeks or were
put in the control-fed group. Flooding-dose technique was used to calculate
the rate of protein synthesis (Vary et al, 2007). In the male rats we saw a
decrease in left ventricular stroke volume of 33% and cardiac output of 11%
(Vary et al, 2007). There were no differences in females stroke volume or
cardiac output compared to the control group (Vary et al, 2007). Male rats
that consumed the ethanol saw an 18% decrease in heart weight, 14% being
protein content while female rats saw no significant changes compared to
the control group (Vary et al, 2007). The male rats saw a decrease in protein
synthesis by 33% while the female rats did not see any significant changes

16
(Vary et al, 2007). A study done by Fernndez-Sol et al (1997), performed a
study on male and female human participants alcoholic cardiomyopathy.
This study took place over 5 years and accounted for 3,310 patients both
male and female adults but only 10 women and 26 men met all of the
requirements for the study (Fernndez-Sol et al, 1997). Women consumed
a little less alcohol on average today then the men in the study (women:
124+ 58g/day, men 194+ 56g/day) (Fernndez-Sol et al, 1997). Women
had a higher left ventricular ejection and shortening fractions than men
(Fernndez-Sol et al, 1997). The women who consumed alcohol chronically
had a significantly lower left ventricular mass index than the men
(Fernndez-Sol et al, 1997). The prevalence of alcohol cardiomyopathy in
women was 0.43% and 0.25% in men (Fernndez-Sol et al, 1997).
Eukaryotic initiation (eIF), eukaryotic elongation (eEF) factors, mRNA, mTOR
and total RNA
A study by Vary et al (2007), looked at eukaryotic initiation (eIF) and
elongation (eEF) factors in male and female rats and saw decreases in eIF4E
and eIF4G but only in the male rats. Lang et al (1999), study looked at adult
male rats and measured in the gastrocnemius, psoas, soleus, and heart
tissue as well as measuring the amount of eIF2 and eIF2B and total RNA.
The study showed that protein synthesis decreased in gastrocnemius muscle
as well as having a decrease in RNA but not significant and had a significant
decrease in eIF2B activity (Lang et al, 1999). A study done by Vary et al
(2004), also measured Eukaryotic initiation factors (eIF) as well as eukaryotic

17
elongation factors (eEF) in gastrocnemius and cardiac musculature. Results
showed chronic ethanol consumption decreased the formation of eIF and eEF
in the rats and then after the 72hr withdrawal period from alcohol the eIF
and eEF levels increased to control levels in both the gastrocnemius and
cardiac musculature (Vary et al, 2004).
A study done by Preedy et al (1997), was done to see if reduced
amounts of mRNA contributed to a reduction in protein synthesis due to
chronic ethanol ingestion. Total of 12 mature rats divided into 2 groups
(Preedy et al, 1997). The gastrocnemius muscle weighed significantly less in
the rats that consumed ethanol than the control group (Preedy et al, 1997).
Ethanol-fed rats mRNA in the gastrocnemius was also seen to decrease
significantly by 35% but was not significant enough to decrease total RNA
(Preedy et al, 1997).
A study done by Koll et al (2003), was done to see if -tocopherol (ATC)
supplementation would reduce muscle damage during chronic ethanol
consumption in male adult rats. The researchers measured changes in
protein synthesis, RNA and DNA contents to analyse whether the ATC
supplement reduced muscle damage in the plantaris muscle. The study
lasted a duration of 4 weeks. All groups including the control group saw a
decrease in protein and DNA content except the only ATC group (Koll et al,
2003). Both alcohol fed groups saw a decrease in muscle mass in the
plantaris muscle (Koll et al, 2003). Durn Castelln et al (2005), study also

18
looked a supplementation to reduce myopathy but found no significant
results with supplementation with zinc.
Two studies looked at mTOR activity with regards to chronic alcohol
consumption. Korzick et al (2013), study was to assess whether muscle
protein is more affected in aged rats (18months old) than adult rats
(3months old). Aged and adult rats both ended up consuming 36% of total
caloric intake as ethanol for 18 weeks. Adult rats had significantly reduce
LBW with increased BF% compared to the control group while aged rats had
significantly reduced LBW and increased BF% compared to both. No
difference in total protein synthesis was observed but both aged and adult
had decrease in mTOR activity (Korzick et al, 2013). Vary, Deiter and Lantry
(2008), researched if chronic alcohol consumption in male rats reduces
mTOR activity. Ethanol fed group consumed 40% of their total calories as
ethanol for 20-26 weeks. Protein synthesis significantly decreased by 35%
and phosphorylation of mTOR decreased by 30% (Vary, Deiter and Lantry,
2008). No significant difference in mTOR levels. S6K1 and eIF4G
phosphorylation also decreased (Vary, Deiter and Lantry, 2008).
Protein synthesis restoration
Two studies looked at restoration. One looked at protein synthesis after
chronic alcohol consumption (Vary et al, 2004), and the other looked at
restoring protein levels back to normal after having myopathy (Estruch et al,
1998). Study done by Vary et al (2004), looked at male rats. The study

19
showed that after rats consumed alcohol chronically for 16 weeks straight
after 72 hours of abstinence had restored their protein synthesis rates to
normal. Estruch et al (1998), study included 30 males who had a history of
alcoholism and had heart failure. 14 of the subjects had myopathy. After 5
years of abstinence, individuals who had alcoholic myopathy from chronic
alcoholism showed that 8 of the 14 subjects recovered to normal levels at
the end of the study (Estruch et al, 1998).
Male versus female
A study done by Nakahara et al, (2003), showed that female rats
chronically consuming ethanol compared to control female rats significantly
increased their c-myc mRNA levels in skeletal muscle while male rats did not.
A study done by Vary et al (2007), also looked at heart weight as an outcome
measurement and results showed that while the male rats heart weight
decreased by 18% compared to the control group the female rats heart
weight did not decrease significantly compared to the control group. Women
had a higher left ventricular ejection and shortening fractions than men
(Fernndez-Sol et al, 1997). When testing the gastrocnemius the male rats
saw a significant decrease in protein synthesis while the female rats did not
and both groups saw no significant total RNA (Vary et al, 2007). One study
by Hunter et al, (2003) looked at proteins nebulin and titin to see if chronic
alcohol consumption decreased these protein contents in both male and
female rats. In female rats it was shown that the RNA/protein ratio had a
larger reduction compared to males (Hunter et al, 2003). Also results show

20
nebulin and titin did decrease which may have affected muscle function in
both female and male rats in this study (Hunter et al, 2003). Nakahara et al
(2006), also looked at male and female rats when comparing protein
synthesis and chronic alcohol consumption. The study lasted 6-7weeks and
the ethanol-fed group consumed 35% of their caloric intake as ethanol
(Nakahara et al, 2006). HSP 27 mRNA was shown too decreased in male rats
but not in female rats, while HSP 90 mRNA did not change in males but was
shown too increase in females after ethanol consumption (Nakahara et al,
2006).

Discussion
This review shows that protein synthesis is affected by chronic alcohol
consumption in both rats and humans. Serious outcomes can come with
chronic alcohol ingestion such as alcoholic skeletal and cardiomyopathy
(Preedy et al, 2001). Chronic alcoholism has caused about 50% of all alcohol
patients to have myopathy (Preedy et al, 2001). With regards to skeletal
muscle, fast-twitch muscle fiber in both human and rat studies was shown to
decrease muscle protein synthesis (Lang et al, 1999, Fernndez-Sol et al,
2000). Slow-twitch muscle fiber in rats which was tested on the soleus
muscle was not shown to have any significant decrease in protein synthesis
(Koo-Ng et al, 2000), while in humans slow-twitch muscle fiber has not been
studied primarily on its own. This could be due to the fact that the soleus

21
muscle is a difficult muscle to take a muscle biopsy from and humans have
less of a division when it comes to a muscle being all or majority fast-twitch
muscle fiber and another being all slow-twitch like it is in rats (FernndezSol et al, 2000). Two muscles used for muscle biopsies in human studies
explored was the deltoid and the rectus femoris muscle due to them being
easily accessible and not causing much harm to the subject after the biopsy
(Fernndez-Sol et al 2000).
Many studies examined looked at how chronic alcohol ingestion affects
cardiac tissue and slow and fast-twitch muscle fibers in humans and rats.
Fernndez-Sol et al (1997), was done to show whether or not women are
more susceptible to alcoholic cardiomyopathy than men and showed that
men had lowered left ventricular ejection and shortening fraction rates but
believe in this study it was because women consumed much less alcohol on
average than the men did. This also could be due to the fact that the study
had only 10 women enrolled versus 26 men. Vary et al (2007), study after
looked at rats to see if there were any differences between male and female
rats with regards to cardiac tissue and found that the female rats seem to be
less affected when it comes to chronic alcohol consumption than male rats.
With knowing that muscle protein synthesis decreased in rats and
humans in fast-twitch muscle fibers in skeletal muscle and cardiac muscle,
studies started to examine if the reason protein synthesis decreased was due
to total RNA decreasing, which would reduce the muscles capacity to
produce protein (cite). Only rats were examined in these studies. A study by

22
Hunter et al (2003), saw in female rats it was shown that the RNA/protein
ratio had a larger reduction compared to males. Lang et al (1999),study
which lasted 14 weeks and the rats consumed 30% of their caloric intake as
ethanol, as well as Preedy et al (1997), which lasted 4 weeks and 35%
ethanol was consumed out of their total caloric intake both showed that total
RNA was not significantly decreased after the rats consuming chronic
consumption of ethanol. Both of these studies concluded that the reduced
protein synthesis in the rats was not due to the muscles capacity to produce
protein (Lang et al, 1999, Preedy et al, 1997). Preedy et al (1997), also
examined mRNA levels in male rats and found a 35% significant decrease in
the rats but was not enough to affect RNA levels which would have affected
total protein synthesis capacity.
Researchers then knew that mRNA levels significantly reduced in male
rats but did not affect total RNA, so they started to look at eIF and eEF.
Eukaryotic initiation factors are involved in eukaryotic translation which is
the process where mRNA is translated into proteins (Cite). Eukaryotic
elongation factors is the process whereby amino acids are added to a protein
chain (cite). If protein synthesis capacity was not the problem then they
started to look at these because they play a very big role in the
manufacturing of proteins (Vary et al, 2007). Male rats were proved to be
more affected by chronic alcohol consumption with regards to protein
synthesis and Vary et al (2007), research found that male rats suffered
decreases in eIF4E and eIF4G which may have been the cause for the

23
difference in protein synthesis between male and female rats. Other studies
results suggest that a decrease in protein synthesis in fast-twitch muscle
fiber due to chronic alcohol consumption in rats results from reductions in
elongation-termination and peptide chain initiation (Lang et al, 1999). Also
that impairment in translational initiation results mostly from a decrease in
eIF2B activity (Lang et al, 1999). With these results it is still unclear as to
why male and females have different mechanisms when consuming chronic
alcohol (Vary et al, 2007).
A few studies examined looked at if supplementation can reduce the
effects of chronic alcohol consumption including zinc supplementation and
ATC. Zinc study included a good number of rats (N=40) but zinc had no
effect of improving or reducing effects of myopathy. ATC supplementation
was also ineffective with reducing effects of chronic alcohol consumption on
decreasing protein synthesis. Both of these studies looked at rats.
Protein synthesis has been proven to decrease with chronic alcohol
ingestion and two studies looked at restoration of protein synthesis after
chronic alcohol consumption. Vary et al, (2004) showed that in male rats
after consuming high amounts of ethanol for 16 weeks that after 72 hours of
abstinence protein synthesis levels return to normal. Even though the
gastrocnemius and heart musculature protein synthesis restored, hepatic
proteins seemed to stay decreased showing it was more selective on the
proteins that restored after the 72 hour period (Vary et al, 2004). A human
study by Estruch et al (1998), also examined restoration of myopathy after 5

24
years of abstinence in 14 individuals. The results show that myopathy can
be restored to normal in the heart musculature in humans if the individuals
are able to stay away from alcohol entirely for the duration of 5 years, and
only 8 of the 14 were able to restore back to fully normal (Estruch et al,
1998).
The biggest problem with the research in this field of study is there are
just not enough studies done on humans and very few studies done on
humans that do not involve incredibly large amounts of alcohol. More
studies should also be examined on nutrition status and whether the effects
of chronic alcohol consumption can be reduced or not.
Conclusion
The purpose of the review was to examine the effects of chronic
alcohol consumption on protein synthesis in adult aged humans and rats.
We found that it depends on what muscle fiber type you look at since fasttwitch and cardiac musculature are affected in both humans and rats and
slow-twitch muscle fiber seems to not be affected by chronic alcohol
consumption in rats and is not well studied in humans. In both human
studies and rat studies, females seem to be less affected by chronic alcohol
consumption possibly due to eIF and eEF. Also in this review we found that
protein synthesis can be restored after 72 hours of abstinence in a rate after
chronic ethanol consumption, while in humans about 57% were able to
restore myopathy to normal after 5 years of abstinence.

25

Data Extraction Table

Citati
on

Study
Purpose

Vary
and
Deiter,
2005

Purpose
was to
research
protein
synthesis
in
myofibrilla
r and nonmyofibrilla
r fractions
in the
heart in
response
to chronic
alcohol
consumpti
on.

Vary et
al,
2007

Purpose
was to find
sex
difference
s with
regards to
regulation
of
myocardia
l protein
synthesis
after
chronic
alcohol
consumpti
on in the
heart in
rats.

Sampl
e
popul
ation
Adult
Male
Rats

Settin
g or
situati
on
Laborat
ory
setting

Adult
Male
rats

Laborat
ory
setting

Interven
tion

Measure
s

Outcome
s

Experime
ntal
design

The rats
were
either
assigned
to the
control
group or
alcohol
fed
group.
Rats
consume
d 40% of
total
calories
as
ethanol
in alcohol
fed
group.
The male
and
female
rats were
randomly
assigned
to the
ethanol
feeding
group or
the
control
group.

Rate of
protein
synthesis
was
measure
d using
floodingdose
techniqu
e.

Nonmyofibrilla
r proteins
decreased
by 20%
and
myofibrilla
r proteins
decreased
by 23%.

16 week
study. 2
groups.
Control
group and
ethanol
consuming
group
where 40%
of their
caloric
intake from
ethanol.

Floodingdose
techniqu
e was
used to
calculate
the rate
of protein
synthesis
.
Eukaryoti
c
initiation
(eIF) and
elongatio
n (eEF)
factors
were also
measure

Male rats
that
consumed
the
ethanol
saw an
18%
decrease
in heart
weight,
14% being
protein
content
while
female
rats saw
no
significant
changes.

26 week
study. 2
groups.
Control
group and
ethanol
consuming
group
where 40%
of their
caloric
intake from
ethanol.

26
d.

Fernn
dezSol et
al,
1997

Purpose of
this study
was to
show
whether or
not
women
are more
susceptibl
e to
alcoholic
cardiomyo
pathy than
men.

N=36.
10
wome
n and
26
men
where
includ
ed in
the
study.

Patient
s had a
history
of
alcoholi
sm and
had
heart
conditi
ons.

Vary et
al,
2001

The
purpose
was to see
if rats
were
chronically
fed alcohol
for 16
weeks
would
protein
synthesis
be
inhibited
in hearts
and what
the
potential
mechanis
ms are.

Adult
Male
rats

Laborat
ory
setting

Two
control
groups
were
used, one
for men
and the
other for
women
without
heart
failure
and
consume
d <20g of
alcohol a
week.
Two
groups.
Ethanol
consumin
g group
the rats
consume
d 30% of
their diet
being
ethanol.
The
control
group
were
made
sure to
intake
the same
amount
of energy
as the

Left
ventricul
ar
ejection
and
shortenin
g
fractions
were
measure
d and left
ventricul
ar mass
index.

Heart
weight
and
protein
content
was
measure
d. Rates
of protein
synthesis
were
calculate
d using
floodingdoses.
The
soleus
was also
used to
collect
protein
synthesis

male rats
saw a
decrease
in protein
synthesis
by 33%
while the
female
rats did
not see
any
significant
changes.
Women
had a
higher left
ventricular
ejection
and
shortening
fractions
than men
possible
due to
men
consuming
more
alcohol.

Rats that
chronically
consumed
alcohol
had 10%
lower
heart
weights
than the
control fed
rats
caused by
a 25%
decrease
in protein
content in
the heart.
myocardial
protein
synthesis
was
decreased

Study took
place over
5 years.
Four
groups
were used,
2 control
groups and
2 chronic
alcohol
consuming
groups.

30%
ethanol, or
control
group

27
alcohol
consumin
g rats.

Vary
and
Lang,
2008

The
purpose
was to
show that
acute and
chronic
alcohol
consumpti
on limits
protein
synthesis
in skeletal
and
cardiac
muscle in
rats.

Adult
Male
Spragu
eDawle
y rats
(225
250 g)

Laborat
ory
setting

Half of
the rats
in the
study
either
were the
control
group
and did
not
receive
any
ethanol,
or in the
alcohol
group
which did
receive
ethanol.

, mTOR
content,
and highenergy
phosphat
es. The
other half
of the
soleus
was used
to assess
the
regulatio
n of
eukaryoti
c
initiation
factor
system.
The
study
measure
d protein
synthesis
in rats
skeletal
muscle
both fast
and slow
twitch as
well as
cardiac
muscle.

by 30%.
In the
soleus no
decrease
in protein
synthesis.

When
caloric
intake is
controlled
between
both
groups the
rats that
chronically
consumed
alcohol
experience
d
decreased
rates of
protein
synthesis
in fasttwitch but
not in the
soleus
muscle.
Also had
decrease
protein
synthesis
in cardiac
muscle but
not as
much as
fast-twitch
muscle
fiber.

Control
group,
ethanol
group (75
mmol/kg)

28
Fogle
et al,
2010

The
purpose of
this study
was to
researche
d rats
cardiac
muscle
protein
expression
after
chronic
alcohol
consumpti
on
compared
to control
fed rats.

N=8,
male
adult
rats

Laborat
ory
setting

Half of
the rats
were in
the
control
group
and half
in the
alcohol
consumpt
ion
group.

Heart
weight
and 28
myocardi
al
mitochon
drial
proteins
were
measure
d in rats.

Lang
et al,
1999

The
purpose of
this study
was to
look at
whether
chronic
alcohol
consumpti
on in rats
changes
certain
steps in
the
initiation
phase of
translation
of mRNA.

N=24
male
adult
rats

Laborat
ory
setting

Half of
the rats
in the
study we
fed a
regular
diet with
energy
consumpt
ion equal
to the
rats that
consume
d 30% of
their total
diet as
alcohol.

Total RNA
and
amount
of eIF2
and
eIF2B in
the
gastrocn
emius,
psoas,
soleus,
and
heart.

Chronic
alcohol
consumpti
on caused
a lower
heart
weight and
25% loss
in cardiac
protein. 18
sarcoplas
mic
proteins
decreased
while 10
had
increased
in the rats
that
consumed
alcohol
compared
to the
control
group.
No
significant
decrease
in total
RNA.
Soleus had
no
significant
decrease.
Studies
results
suggest
that a
decrease
in protein
synthesis
in fasttwitch
muscle
fiber due
to chronic
alcohol
consumpti
on in rats
results
from
reductions

Control
group,
ethanol-fed
group
(40%)

Control
group,
ethanol-fed
group
(30%)

29

Koo-Ng
et al,
2000

The
purpose of
this study
researche
d whether
an
increase in
reactive
oxygen
speciesinduced
damage to
the
muscles
because of
alcohol
consumpti
on is
caused by
increased
carbonyl
formation.

Male
adult
rats

Laborat
ory
setting

Vary et
al,
2004

Purpose
was to test
whether
chronic
alcohol
consumpti
on has

N=20
male
rats

Laborat
ory
setting

The
ethanolfed rats
consume
d 35% of
their
calories
as
ethanol
while the
control
group
was
matched
with the
same
caloric
intake.
Rats in
the
control
and the
ethanolfed rats
were
Inhibition
of muscle
protein
synthesis
by
alcohol is
associate
d with
modulati
on of
eIF2B
and eIF4E
Controlfed group
and
ethanolfed
group.
The rats

The
muscles
used in
the study
were the
plantaris,
soleus,
gastrocn
emius,
and the
heart.
Weight of
the
muscle
was
measure
d as well
as
protein
carbonyl.

Eukaryoti
c
initiation
factors
(eIF) and
eukaryoti
c

in
elongation
terminatio
n and
peptide
chain
initiation.
Ethanol
feeding
caused a
reduced
weight in
the
plantaris
muscle
compared
to the
control
group but
did not
significantl
y decrease
weight in
the soleus
muscle
group.
Protein
carbonyl
increased
significantl
y in both
the soleus
and
plantaris
muscle but
the
increase in
the
ethanol
fed rats for
the soleus
was
significantl
y higher.
This study
shows that
after 16
weeks of
chronic
alcohol
consumpti

Control
group,
ethanol fed
group
(35%),
both

Control-fed
group and
ethanol-fed
group
(40%).

30

Pruzna
k et al,
2013

irreversibl
e effects
on protein
synthesis
which
includes
mRNA
translation
in skeletal
muscle
and
cardiac
muscle.
Purpose
was to
study
alcohol in
the central
nervous
system
and
whether it
is capable
of
reducing
protein
synthesis
in rats.

N=14,
Adult
male
rats

Laborat
ory
setting

Fernn
dezSol et
al,
2000

Purpose
was to
evaluate
the effects
of different
ethanol
dosages
on skeletal
muscle
function in
chronic
alcoholics
with
skeletal
myopathy.

N=68,
male
adults

Male
subject
s that
were
seen in
the
alcoholi
c unit
of the
hospita
l.

Nakah
ara et
al,
2003

Purpose to
assess the
long term
and short

Male
and
female
rats

Lab
setting

were
maintain
ed on an
ethanolfed diet
for 16
weeks
followed
by 72hrs
of no
alcohol.

elongatio
n factors
(eEF)
were
measure
d in both
gastrocn
emius
and
cardiac
musculat
ure.

on protein
synthesis
rates can
be
restored to
normal
levels after
72hrs with
any
alcohol
consumpti
on.

Groups 1
and 2
received
either
cerebrosp
inal fluid
or alcohol
over the
course of
10min.
Groups 3
and 4
received
alcohol
over
2min or
sterile
saline.
Muscle
biopsies
were
taken
from the
patients
from the
deltoid
muscle.

The
gastrocn
emius
and
soleus
were
used to
measure
protein
synthesis
levels.

Consumin
g alcohol it
is possible
that the
decrease
in protein
can be
affected
secondaril
y by the
central
nervous
system in
fast-twitch
not slowtwitch
muscle
fiber.
The
degree of
alcohol
consumpti
on reflects
the
severity of
skeletal
muscle
myopathy
in chronic
alcohol
misusers.

Three
studies.
Study
one

Effects of
20-60g of
alcohol
per day,
61-99g of
alcohol
per day
and more
than
100g per
day
affects
on
skeletal
muscle
myopathy
.
This
study
measure
d c-myc,

Female
rats had
an
increase in

Groups 1
and 2
received
either
cerebrospi
nal fluid or
alcohol
over the
course of
10min.
Groups 3
and 4
received
alcohol
over 2min
or sterile
saline.
For 5 years
the
subjects
either
consumed
20-60g of
alcohol per
day, 6199g of
alcohol per
day and
more than
100g per
day or
were in a
control
group.
2 control
groups,
one for
male and

31
term
effects of
alcohol on
male and
female
rats and
also to
assess the
effects of
chronic
and acute
alcohol
with
starvation
and
cyanamide
.

Preedy
et al,
1997

Purpose
was to see
if reduced
amounts
of mRNA
contribute
d to a
reduction
in protein
synthesis
due to
chronic
ethanol
ingestion.

Male
Wistar
rats

Lab

Vary et
al,
2007

This study
focused on
determinin
g if there
are any
sex
difference
s with
regards to
muscle
protein
synthesis
when

Male
and
female
adult
rats

Lab

compare
d chronic
alcohol
ingestion
in male
and
female
rats. The
second
and 3rd
studies
looked at
acute
alcohol
ingestion
exposure
to
cyanamid
e and
starvatio
n.
Half of
the rats
consume
d ethanol
in their
food
while the
control
group did
not.

Half of
the rats
consume
d ethanol
for 26
weeks
and were
randomly
assigned
to a
group.
Male and
female

p53, and
Bcl-2
mRNA in
skeletal
muscle
with rats
not
consumin
g ethanol
compare
d to rats
consumin
g
ethanol.

c-myc
mRNA
levels in
the
ethanol
fed group
compared
to the
control
group
while all
other
categories
so no
significant
changes.

one for
female, 2
alcohol-fed
groups,
male and
one
female.

Measured
changes
in
myofibrill
ary
protein
contents.
The
gastrocn
emius
was the
muscle
chosen
for the
extractio
n of the
RNA in
the rats.
The
gastrocn
emius
muscle
was used
to find
protein
synthesis
levels.
Total RNA
levels
were also
measure

mRNA did
decrease
by 35%
but it was
not
significant
enough to
affect total
RNA.

Control
group and
ethanol-fed
group
(35%)

The male
rats saw a
significant
decrease
in protein
synthesis
while the
female
rats did
not
compared
to the
decrease

Ethanolfed group
and
controlfed.

32

Koll et
al,
2003

Ohlend
ieck et
al,
2003

chronically
consuming
alcohol in
male and
female
rats.
The
purpose
was to see
if tocopherol
(ATC)
suppleme
ntation
would
reduce
muscle
damage
during
chronic
and or
acute
ethanol
consumpti
on in rats.

The
purpose
was to see
whether
chronic
alcohol
ingestion
affects
proteins
related to
calcium
homeostas
is.

rats were
separate
d into
separate
groups.

d.

in male
rats. No
differences
in total
RNA.

The
research
ers
measure
d
changes
in protein
synthesis
, RNA
and DNA
contents
to
analyse
whether
the ATC
suppleme
nt
reduced
muscle
damage.
The
plantaris
muscle
group
was used
for
testing.
Ionregulator
y skeletal
muscle
proteins
were
measure
d such as
sarcoplas
micendoplas
mic
reticulum
calcium
(SERCA),
and
adenosin
e
triphosph

Both
alcohol fed
groups
saw a
decrease
in muscle
mass in
the
plantaris
muscle.

Ethanolfed group
with ATC
supplemen
tation, just
ethanol-fed
group,
control-fed
and control
+ ATC

There
were no
changes in
the ionregulatory
skeletal
muscle
proteins
that
proved
statisticall
y
significant.

Control
and
ethanol-fed
group
(35%).

Male
rats

Lab

The
groups
were a
controlfed group
and an
ethanolfed group
and an
ethanol
and ATC
fed group
as well as
just ATC
group.

Male
Wistar
rats,
adult

Lab
setting

Control
group
consume
d the
same
amount
of energy
as the
ethanolfed
group.
The rats
were fed
a diet
containin
g 35%
ethanol.

33

Hunter
et al,
2003

The
purpose
was to
study the
effects of
alcohol on
proteins
nebulin
and titin,
as well as
difference
s between
male and
female
rats with
regards to
biochemist
ry when
consuming
alcohol.

Male
and
female
adult
rats

Lab
setting

Both half
of the
male and
female
rats
consume
d the
alcohol
fed diet
while the
other half
consume
d the
control
diet.

HongBrown
et al,
2001

Purpose
was to see
what the
effect of
excessive
alcohol
consumpti
on had on
protein
metabolis
m in
skeletal
muscle
cells in
response
to
anabolic
agents
such as
insulin-like
growth
factor and

Human
cells

Lab

The cells
were
incubate
d with
ethanol
at
different
dosages.
Other
cells
were
incubate
d with
acetaldeh
yde,
acetate,
insulin or
insulin
like
growth
factors or
with a

atase
(ATPase).
Measure
proteins
titin and
nebulin.
Also
measure
RNA/prot
ein ratio.

Protein
synthesis
and
Insulin
and IGF-I
were
measure
d.

Female
rats it was
shown that
the
RNA/protei
n ratio had
a larger
reduction
compared
to males.
Nebulin
and titin
did
decrease.
female
rats are
more
susceptibl
e to
negative
effects of
chronic
alcohol
consumpti
on than
male rats
on skeletal
muscle.
Protein
synthesis
did
decrease
before
insulin and
IGF-I were
impaired.

Four
groups
were
investigate
d: alcoholic
males,
pair-fed
males,
alcoholic
females,
pair-fed
females.

Cells were
either
incubated
with
ethanol at
different
dosages or
in a control
group.
Other cells
were
incubated
with
acetaldehy
de,
acetate,
insulin or
insulin like
growth
factors or
with a
combinatio

34
insulin.

Pacy et
al,
1991

The study
looked at
middle
aged
adults that
were
chronic
alcohol
misusers
and their
protein
metabolis
m in whole
body and
skeletal
muscle

N=12,
human
s, 6
chroni
c
alcohol
misuse
rs for
10year
s. age
44.8
10.4
years.
6
health
y
popula
tion

Patient
s were
hospita
lized
for the
study

Rouac
h et al,
1997

Determine
the effects
of ethanol
on lipid
peroxidati
on as well
as
oxidative
protein
damage.

Male
rats

Lab
Setting

combinati
on of
ethanol
and
insulin.
Leucine
levels
and
expired
air was
collected
prior to
the test
to view
baseline
levels.
Following
the
collection
of
baseline
levels
leucine
and
NaHCO3
were
infused
into the
blood for
the 8hr
study
period.
The rats
were fed
a high fat
diet as
well as
ethanol
or a from
an
isocaloric
dextrose.

n of
ethanol
and
insulin.
Muscle
protein
synthesis
in
quadrice
ps,

Protein
synthesis
levels
significantl
y
decreased
in the
quadriceps
muscle.

Control
group and
chronic
alcoholic
group

Protein
oxidation
was
evaluate
d by
protein
thiols,
protein
carbonyl
groups
and
activity
of
glutamin
e
synthetas
e.

Glutamine
synthetase
and
protein
thiols were
significantl
y
decreased
while the
protein
carbonyl
levels
significantl
y
increased
in the rats
that
consumed
ethanol
compared

Study
lasted 4
weeks, 3
groups, a
high fat
diet as well
as ethanol
or a from
an
isocaloric
dextrose
and a
control
group.

35

Nakah
ara et
al,
2006

The
purpose of
the study
was to see
if chronic
alcohol
consumpti
on alters
expression
of heat
shock
proteins in
male and
female
rats.

Male
and
female
rats

Lab
setting

Male and
female
rats were
fed either
alcohol
containin
g diet or
control
diet.

Muscle
weights,
muscle
protein
content,
atrophy
of
muscle,
and heat
shock
protein
content.

Estruc
h et al,
1998

This study
looks at
the affects
of
recovering
alcoholics
who
become
abstinent
versus
those who
relapse
over a 5
year
period

N=62,
human
patient
s, all
patient
s were
white
males

Hospita
l

Control
group
consume
d less
than 20g
of
ethanol
per week,
patients
who
consume
d more
than
100g per
day over
4 periods
were
included
in study.

Total
body
protein,
retinol
binding
protein
and lean
body
mass
were
measure
d. Force
produced
was also
measure
d.

Nicols
et al,
2003

The
purpose of
this study
was to see
how

N=219
, adult
men,
25-64
years

Alcohol
ism
Unit of
a
Hospita

Alcoholic
s
reported
197+5g
per day

In this
study
energy
intake
and

to the
control.
HSP 27
mRNA was
decreased
in male
rats but
not female
rats, while
HSP 90
mRNA did
not
decrease
in males
but
increased
in females
after
ethanol
consumpti
on.
30
became
abstinent
and 20 did
not.
Abstaining
alcoholic
patients
significantl
y
improved
strength
but were
still lower
than
control
group
after 5
years. Out
of 14
patients
that had
myopathy
8
recovered
to normal.
Average
deltoid
strength
was lower
in

The
alcohol fed
group
consumed
35% of
their diet
as alcohol
for 67weeks.

Either
control
group and
consumed
less than
20g of
ethanol a
week or
alcohol
group and
consumed
more than
100g per
day.

Three
groups,
one
malnutritio
n alcoholic

36

Korzick
et al,
2013

malnutritio
n with
ethanol
intake
affect
skeletal
muscle
and
function in
chronic
alcoholics.

old

The
purpose of
this study
was to
assess
whether
muscle
protein is
more

3
month
old
and
18mon
th old
female
rats.

l in
Barcelo
na.

for on
average
22 years.
146 men
in the
chronic
alcoholic
group
and 73
healthy
individual
s in the
control
group.

protein
intake
were
measure
d.
Deltoid
strength
and arm
muscle
are were
measure
d. Type ll
and type
l fiber
area.
Total
protein in
plasma
was also
measure
d.

Aged and
adult rats
both
ended up
consumin
g 36% of
total
caloric
intake as

Whole
body
weight,
lean
body
mass and
fat mass,
rate of
protein

alcoholics
vs control
and got
worse with
severity of
myopathy,
type ll
fiber area
decreased
in
alcoholics
and got
worse with
increased
severity of
myopathy,
type l
became
slightly
thinner,
lower
crosssectional
area of
arm and
decreased
total
plasma
proteins in
alcoholics.
Alcoholics
with better
nutrition
had
significantl
y more
muscle
strength
than
alcoholics
with
malnutritio
n.
Adult rats
had
significantl
y reduce
LBW with
increased
BF%
compared
to the

group, one
alcoholic
group with
good
nutrition,
and a
control
group.

Control
group,
aged fed
alcohol
group, and
adult fed
group,
36%
ethanol

37
affected in
aged rats
than adult
rats.

ethanol
for 18
weeks

synthesis
in
gastrocn
emius
and
soleus
and
mTOR
activity
was
measure
d.

Vary,
Deiter
and
Lantry,
2008

The
purpose
was to see
if chronic
alcohol
consumpti
on in rats
reduces
mTOR
activity

Male
rats

Study
was 2026
weeks,
rats were
fed either
a control
diet or
40%
ethanol
diet.

Protein
synthesis
and
mTOR
levels
were
measure
d in
cardiac
tissue.

Reilly
et al,
2000

The
purpose of
this study
is to
analyze
whether
chronic
alcohol
feeding in

N=12,
male
rats

Ethanolfed group
and
controlfed
group, 6
rats each,
liquid diet
with 35%

MyoHC
isoforms
Ib, IIa, IIx
and IIb
were all
measure
d in
plantaris
muscle

control
group
while aged
rats had
significantl
y reduced
LBW and
increased
BF%
compared
to both.
No
difference
in total
protein
synthesis.
Both aged
and adult
had
decrease
in mTOR
activity.
Protein
synthesis
significantl
y
decreased
by 35%.
Phosphoryl
ation of
mTOR
decreased
by 30%.
No
significant
difference
in mTOR
levels.
S6K1 and
eIF4G
phosphoryl
ation also
decreased.
In alcohol
fed total
MyoHC
were
reduced in
plantaris
group but
not soleus
with

diet fro 18
weeks.

Protein
synthesis
measured
by flooddosing
technique.
2 groups,
one
control-fed
and the
other
consumed
40%
ethanol.

Two groups
including 6
male adult
rats in
each,
alcohol-fed
group
(35%) and
control-fed

38
rats
affects
myosin
heavy
chain
isoform.

ethanol
diet for
alcoholfed rats.

Castell
n et
al,
2005

The
purpose
was to see
if zinc
suppleme
ntation
improves
alcoholic
myopathy.

N=40,
male
rats

Four
groups,
rats were
either
assigned
to one of
two
groups
with
ethanol
or one of
two
groups
without
ethanol.
All
suppleme
nted with
zinc (227
mg/l).

Anh
Nguye
n et al,
2012

The
purpose of
this study
was to see
if
insulin/IGF
resistance
and
oxidative
stress
causes
alcoholic
related
myopathy.
Purpose
was to
compare

N=21,
adult
male
rats

Rats were
either fed
control
group
diet of
35.5% of
caloric
intake as
ethanol
for 8
weeks.

Addola
roto et
al,

N=64,
18
alcohol

Catholi
c
Univers

Mean
alcohol
over

and
soleus
muscle.
Myosin
heavy
chain
mRNA
and
proteins
were
measure
d.
Measured
type lla
and llb
muscle
fiber
atrophy

Myofiber
size in
gastrocn
emius
was
measure
d and
insulin,
IGF-1,
and IGF-2
receptors
, IRS-1,
and IRS2.
Body
compositi
on and

decreases
in 1b, IIx
and IIb
isoforms.
MyoHC Ib
mRNA
decreased
in both
soleus and
plantaris
group.

for 6
weeks.

Type ll
muscle
fibers both
had
atrophy
with the
groups
consuming
alcohol
and
significantl
y
decreased
with the
low dose
protein
group.
Suppleme
ntation
with zinc
did not
decrease
atrophy
Insulin,
IGF-1, and
IGF-2
receptors,
IRS-1, and
IRS-2 al
decreased
in the
ethanolfed group
as well as
myofiber
size

Four
groups,
one control
18%
protein,
group two
2%
protein,
group
three 18%
protein
and 36%
ethanol,
group four
2% protein
and 36%
ethanol.
All
supplemen
ted with
zinc (227
mg/l).

Decreased
body
weight in

Compared
32
alcoholics

Rats were
either fed
control
group diet
(n=8) or
35.5% of
caloric
intake as
ethanol
(n=11) for
8 weeks.

39
1998

healthy
social
drinkers vs
chronic
alcoholics
on body
weight
and
energy
metabolis
m.

Doser
et al,
2009

The
purpose
was to see
if altered
acetaldeh
yde
metabolis
m affects
chronic
alcoholism
cardiomyo
pathy.

ic men
and 14
alcohol
ic
wome
n, 32
health
y
individ
uals
adults,
age
40.9+
10.7
N= 16,
Male
rats

ity in
Rome
Italy

100g per
day for 5
years had
body
comp and
energy
metabolis
m
compare
d to
healthy
individual
s.

energy
metabolis
m were
measure
d.

alcoholics,
and a
higher
resting
energy
expenditur
e rate.

body
compositio
n and
energy
metabolis
m to 32
healthy
individuals.

Aldehyde
dehydrog
enase
type 2
was
increased
in half of
the rats
and
either fed
a control
diet or
ethanolfed diet
lasting 14
weeks.

Protein
damage
was
measure
d and
apoptosis
. ASK-1,
GSK-3,
GATA4
and
cAMPresponse
element
binding
protein
also was
measure
d.

Left
ventricular
wall
thickness
increased
in alcohol
groups
and
reduced
fractional
shortening
rate in non
ALDH2
group that
consumed
ethanol
but not
ALDH2
group that
consumed
ethanol.
ADLH2
impoved
protein
carbonyl
formation,
ASK-1,
GSK-3,
GATA4 and
CREB
activation.

Aldehyde
dehydroge
nase type
2 was
increased
in half of
the rats
and either
fed a
control diet
or ethanolfed diet
containing
4% ethanol
for 14
weeks.

40

References
Addolorato G, Capristo E, Greco AV, Stefanini GF, Gasbarrini G. (1998).
Influence of chronic alcohol abuse on body weight and energy metabolism: is
excess ethanol consumption a risk factor for obesity or malnutrition? J Intern
Med. 244(5):387-95.

41
Durn Castelln MC, Gonzlez-Reimers E, Lpez-Lirola A, Martn Olivera R,
Santolaria-Fernndez F, Galindo-Martn L, Abreu-Gonzlez P, GonzlezHernndez T. (2005). Alcoholic myopathy: lack of effect of zinc
supplementation. Food Chem Toxicol. 43:13331343.
Estruch R, Sacanella E, Fernndez-Sol J, Nicols JM, Rubin E, UrbanoMrquez A. (1998). Natural history of alcoholic myopathy: a 5-year study.
Alcohol Clin Exp Res. 22(9):2023-8.
Fernndez-Sol J, Estruch R, Nicols JM, Par JC, Sacanella E, Antnez E,
Urbano-Mrquez A. (1997). Comparison of alcoholic cardiomyopathy in
women versus men. Am J Cardiol. 80:481-485.
Fernndez-Sol J, Nicols JM, Sacanella E, et al. (2000). Low-dose ethanol
consumption allows strength recovery in chronic alcoholic myopathy. QJM.
93(1):3540.
Fogle, R., Lynch, C., Palopoli, M., Deiter, G., Stanley, B., & Vary, T. (2010).
Impact of Chronic Alcohol Ingestion on Cardiac Muscle Protein
Expression. Alcoholism: Clinical and Experimental Research, 34(7).
DOI: 10.1111/j.1530-0277.2010.01200.x
Hong-Brown LQ, Frost RA, Lang CH. (2001). Alcohol impairs protein synthesis
and degradation in cultured skeletal muscle cells.
Alcohol Clin Exp Res, DOI:25:1373-1382
Hunter, R., Neagoe, C., Jrvelinen, H., Martin, C., Lindros, K., Linke, W., &
Preedy, V. (2003). Alcohol Affects the Skeletal Muscle Proteins, Titin and
Nebulin in Male and Female Rats. The American Society for Nutritional
Sciences, 133(4). Doi: 1154-1157
Nguyen VA, Le T, Tong M, Silbermann E, Gundogan F, de la Monte SM. (2012).
Impaired insulin/IGF signaling in experimental alcohol-related myopathy.
Nutrients. 4:1058-1075
Nicols JM, Garca G, Fatj F, Sacanella E, Tobas E, Bada E, Estruch R,
Fernndez-Sol J. (2003). Influence of nutritional status on alcoholic
myopathy. Am J Clin Nutr. 78(2):326-33.
Koll M, Beeso JA, Kelly FJ, Simanowski UA, Seitz HK, Petes TJ, Preedy
VR (2003). Chronic alpha-tocopherol supplementation in rats does not
ameliorate either chronic or acute alcohol-induced changes in muscle protein
metabolism. Clin Sci (Lond) 104:287294.
Koo-Ng R, Falkous G, Reilly M, Peters TJ, Mantle D, Preedy VR. (2000).
Carbonyl levels in type I and II fiber-rich muscles and their response to

42
chronic ethanol feeding in vivo and hydroxyl and superoxide radicals in
vitro. Alcohol Clin Exp Res. 24:18621868.
Korzick DH, Sharda DR, Pruznak AM, Lang CH. (2013). Aging accentuates
alcohol-induced decrease in protein synthesis in gastrocnemius. Am J Physiol
Regul Integr Comp Physiol. 304(10):R887-98. doi:
10.1152/ajpregu.00083.2013.
Kumar V., Atherton P., Smith K., Rennie M. (2009). Human muscle protein
synthesis and breakdown and after exercise. J. Appl. Physiol. 106 20262039
10.1152/japplphysiol.91481.2008
Lang, C., Wu, D., Frost, R., Jefferson, L., Kimball, S., & Vary, T. (1999).
Inhibition of muscle protein synthesis by alcohol is associated with
modulation of eIF2B and eIF4E. American Journal of Physiology,277(2). DOI:
E268-E276
Nakahara T., Hashimoto K., Hirano M., Koll M., Martin C. R., Preedy V. R.
(2003). Acute and chronic effects of alcohol exposure on skeletal muscle cmyc, p53, and Bcl-2 mRNA expression.Am. J. Physiol. Endocrinol. Metab. 285,
E1273E1281 10.1152/ajpendo.00019.2003
Nakahara T., Hunter R., Hirano M., Uchimura H., McArdle A., Broome C. S., et
al. (2006). Alcohol alters skeletal muscle heat shock protein gene expression
in rats: these effects are moderated by sex, raised endogenous
acetaldehyde, and starvation. Metabolism 55, 843851
10.1016/j.metabol.2006.02.009
Ohlendieck K, Harmon S, Koll M, Paice AG, Preedy VR (2003) Ca2+-regulatory
muscle proteins in the alcohol fed rat. Metabolism52:11021112.
Pacy, P., Preedy, V., Peters, T., Read, M., & Halliday, D. (1991). THE EFFECT OF
CHRONIC ALCOHOL INGESTION ON WHOLE BODY AND MUSCLE PROTEIN
SYNTHESIS A STABLE ISOTOPE STUDY. Alcohol and Alcoholism, 26(5).
Accessed at
http://alcalc.oxfordjournals.org.subzero.lib.uoguelph.ca/content/26/56/505.long retrieved January 20th, 2015.
Preedy VR, Adachi J, Ueno Y, Ahmed S, Mantle D, Mullatti N, Rajendram R,
Peters TJ. (2001). Alcoholic skeletal muscle myopathy: definitions, features,
contribution of neuropathy, impact and diagnosis. Eur J Neurol. 8:677687.
Preedy VR, Macallan DC, Griffin GE, Cook EB, Palmer TN, Peters TJ. (1997).
Total contractile protein contents and gene expression in skeletal muscle in
response to chronic ethanol consumption in the rat.Alcohol. 14(6):545549.

43
Pruznak AM, Nystrom J, Lang CH. (2013). Direct central nervous system effect
of alcohol alters synthesis and degradation of skeletal muscle
protein. Alcohol Alcohol. 48:138145. doi: 10.1093/alcalc/ags113.
Reilly ME, McKoy G, Mantle D, Peters TJ, Goldspink G, Preedy VR. (2000).
Protein and mRNA levels of the myosin heavy chain isoforms Ibeta, IIa, IIx
and IIb in type I and type II fibre-predominant rat skeletal muscles in
response to chronic alcohol feeding. J Muscle Res Cell Motil 21: 763773,
Rouach, H., Fataccioli, V., Gentil, M., French, S.W., Morimoto, M., and
Nordmann, R. (1997). Effect of chronic ethanol feeding on lipid peroxidation
and protein oxidation in relation to liver pathology. Hepatology, 25(2): 351
355. doi:10.1002/hep.510250216.
Vary TC, Deiter G. (2005). Long-term alcohol administration inhibits synthesis
of both myofibrillar and sarcoplasmic proteins in heart. Metabolism 54: 212
219.
Vary TC, Deiter G, Lantry R. (2008). Chronic alcohol feeding impairs
mTOR(Ser 2448) phosphorylation in rat hearts. Alcohol Clin Exp Res. 32:43
51.
Vary TC, Frost RA, Lang CH. (2008). Acute alcohol intoxication increases
atrogin-1 and MuRF1 mRNA without increasing proteolysis in skeletal muscle.
Am J Physiol Regul Integr Comp Physiol 294: R1777R1789.
Vary TC, Kimball SR, Sumner A. (2007). Sex-dependent differences in the
regulation of myocardial protein synthesis following long-term ethanol
consumption. Am J Physiol Regul Integr Comp Physiol 292: R778R787.
Vary, T, & Lang, C. (2008). Assessing Effects of Alcohol Consumption on
Protein Synthesis in Striated Muscles. Methods in Molecular Biology, 447(1).
doi: 10.1007/978-1-59745-242-7_22.
Vary TC, Lynch CJ, Lang CH. (2001) Effects of chronic alcohol consumption on
regulation of myocardial protein synthesis. Am J Physiol Heart Circ Physiol
281: H1242H1251.
Vary TC, Nairn AC, Lang CH. (2004). Restoration of protein synthesis in heart
and skeletal muscle after withdrawal of alcohol. Alcohol Clin Exp Res 28:
517525.