Muscle Mass and Weight Gain
There are numerous sports supplements available that claim to increase lean
body mass. However, for these sports supplements to exert any favorable
changes in lean body mass, they must influence those factors regulating skeletal
muscle hypertrophy (i.e., satellite cell activity, gene transcription, protein
translation). If a given sports supplement does favorably influence one of
these regulatory factors, the result is a positive net protein balance (in which
protein synthesis exceeds protein breakdown). Sports supplement categories
aimed at eliciting a positive net protein balance include anabolic hormone
enhancers, nutrient timing pre- and postexercise workout supplements, antic-
atabolic supplements, and nitric oxide boosters. Of all the sports supplements
available, only a few have been subject to multiple clinical trials with repeated
favorable outcomes relative to increasing lean body mass. This chapter focuses
on these supplements and others that have a sound theoretical rationale in
relation to increasing lean body mass.
Lean body mass
To appreciate fully how certain nutritional supplements
increase lean body mass, a thorough understanding of the struc-
tural, systemic, and molecular processes that are responsible for
such increases in lean body mass is needed. Although there is still
a lot to be determined and understood relative to how skeletal
muscle is increased, research scientists for the most part have
From: Nutritional Supplements in Sports and Exercise
Edited by: M. Greenwood, D. Kalman, J. Antonio,
DOI: 10.1007/978-1-59745-231-1_7, Ó Humana Press Inc., Totowa, NJ
agreed on several key components that are absolutely necessary
for such adaptations to occur. Some of these components are
satellite cell activity, muscle-specific gene transcription, protein
translation, and nutrient (amino acid) transport into the skeletal
muscle. In addition, growth factors/anabolic hormones including
testosterone, growth hormone, insulin-like growth factor-1
(IGF-1), and insulin are also necessary for increases in skeletal
Although some sports supplements have been repeatedly
observed to increase skeletal muscle mass, they are at best utilized
as a complement to an optimally periodized resistance training
program. In fact, the greatest stimulus for muscle hypertrophy
is mechanical stress in the form of resistance training. The main
question to ask relative to sports supplements is whether a given
supplement is able to augment the stimulus of resistance training so
muscle hypertrophy is maximized. An overview of how skeletal
muscle hypertrophy is regulated follows.
2. IMPORTANCE OF NET PROTEIN BALANCE
The functional component of skeletal muscle is comprised of
two primary proteins: actin and myosin. Of the two, myosin is
the primary protein that increases in size. Hence, when exercise
biochemists observe changes in muscle mass from a cellular frame
of reference, myosin is often the protein of interest. From a
general perspective, muscle hypertrophy can be summarized by
the status of net protein balance. Net protein balance is equal to
muscle protein synthesis minus muscle protein breakdown. For
skeletal muscle hypertrophy to occur, the net protein balance must
be positive (synthesis must exceed breakdown). At rest, in the
absence of an exercise stimulus and nutrient intake, the net protein
balance is negative (1–4). As previously stated, resistance training
is essential for creating the stimulus necessary for skeletal muscle
hypertrophy to occur. However, when resistance training is per-
formed alone, in the absence of nutritional and supplemental inter-
ventions, net protein balance still does not increase to the point of
becoming anabolic. Specific nutrients and supplements noted later
in the chapter are needed in conjunction with the resistance training
for the net protein balance to become positive.
3. ROLE OF GENES IN SKELETAL MUSCLE
As already mentioned, net protein balance has two components:
synthesis and breakdown. To understand how sports supplements
can increase protein synthesis, an understanding of the biochem-
ical process is needed. The center of all bodily functions (including
the addition of skeletal muscle) is at the level of genes. Specific to
hypertrophy, it is the genes that must be expressed as the proteins
in skeletal muscle (i.e., myosin and actin). For instance, once
muscle-specific genes are activated, they are copied into messenger
RNA (mRNA), which is specific to certain proteins in cells. Once
mRNA is transcribed, it is then translated into actual proteins.
Using myosin as an example, what must first happen is an increase
in activation of the myosin gene. Once the myosin gene is acti-
vated, is it copied into myosin mRNA. It is this myosin mRNA
that then directs the process of changing amino acids into poly-
peptides and ultimately a functional myosin protein that is added
to the existing matrix of the sarcomere. The point at which the
myosin protein is synthesized (from the addition of amino acids
under the direction of mRNA), the myosin gene is said to be
‘‘expressed.’’ The reason why all of this tedious biochemical infor-
mation is necessary is that any supplement that claims to increase
muscle mass must in some way influence one of these aforemen-
tioned variables. For instance, some supplements increase growth
hormone, which has been associated with increases in IGF-1. IGF-1,
in turn, increases the activity of certain cell-signaling pathways,
which may increase muscle-specific (i.e., myosin) gene transcrip-
tion. Other sports supplements may increase lean body mass by
increasing the rate at which amino acids are synthesized into
muscle proteins under the direction of mRNA. Yet other sports
supplements may increase the delivery of nutrients (i.e., amino
acids, glucose) to contracting skeletal muscle, which conceivably
results in greater substrate from which lean body mass is acquired.
Each of these mechanisms and the supplements that may enhance
Muscle Mass and Weight Gain Nutritional Supplements 191
these contributions to skeletal muscle hypertrophy are discussed.
Following is a discussion of one of the best and traditional sports
4. PROTEIN SUPPLEMENTS
When attempting to increase lean body mass, an essential
component equal to a sound resistance training program is protein
consumption. Not only is protein intake required for skeletal
muscle hypertrophy, protein is also needed to repair damaged
cells and tissue and for a variety of metabolic and hormonal
activities. Protein is the only macronutrient that contains nitrogen.
Given the importance of attaining a positive nitrogen balance,
it is vitally important that protein be ingested on a daily (and
meal-to-meal) basis. When discussing protein as a nutritional
supplement, two main questions arise: 1) How much protein is
required for an individual engaging in resistance training? 2) What
are the types of protein supplements and which are the best
sources of protein?
4.1. Protein Requirements
One of the most controversial subjects in the science of sports
nutrition has been protein intake. The main controversy and
divided opinions have focused on the safety and effectiveness of
protein intake currently recommended by the recommended daily
allowance (RDA). Currently, the RDA for protein in healthy
adults is 0.8 g/kg body weight per day (5). This recommendation
accounts for individual differences in protein metabolism, varia-
tions in the biological value of protein, and nitrogen losses in the
urine and feces. When determining the amount of protein that
needs to be ingested to increase lean body mass, many factors
must be considered, such as protein quality, energy intake, carbo-
hydrate intake, the amount and intensity of the resistance training
program, and the timing of the protein intake. Although 0.8 g/kg/
day may be sufficient to meet the needs of nearly all non-resistance-
trained individuals, it is likely not sufficient to provide substrate
for lean tissue accretion or for the repair of exercise-induced
muscle damage (6,7). In fact, many clinical investigations indicate
that individuals who engage in physical activity/exercise require
higher levels of protein intake than 0.8 g/kg/day regardless of the
mode of exercise (i.e., endurance, resistance) (8–12) or training state
(i.e., recreational, moderately or well trained) (13–15). So the ques-
tion that remains: How much protein is required for individuals
engaging in resistance training and wanting to increase lean body
mass? General recommendations for individuals who engage in
strength/power exercise range from 1.6 to 2.0 g/kg/day (6,13–16).
A protein intake at these levels help ensure that the net protein
balance remains positive, a prerequisite for skeletal muscle hyper-
trophy to occur.
4.2. Types of Protein Supplement
Although protein can be obtained from whole foods, many resis-
tance trained athletes supplement their diet with protein containing
supplements (e.g., protein powders, meal replacements drinks,
sports bars). Advances in food processing technology have allowed
for the isolation of high quality proteins from both animal and plant
sources. Other reasons for supplementing the diet with protein
supplements include convenience, simplicity, and the fact that pro-
tein supplements also have other benefits, such as a longer shelf life
than whole food sources in addition to being more cost-effective in
Ingesting protein at 1.6 to 2.0 g/kg/day is not the only parameter
to consider, however, because it is also important to note that not all
protein is the same. Different types of protein are composed of
varying amounts of amino acids, which serve as the building blocks
of protein. There are approximately 20 amino acids that can be used
to make proteins (Table 1). There are eight essential amino acids
that must be obtained from the diet because the body cannot
synthesize these amino acids. There are also approximately six con-
ditionally essential amino acids that the body has difficulty synthe-
sizing, and therefore individuals are primarily dependent on dietary
sources for these amino acids. The body can easily synthesize the
remaining amino acids, so they are considered nonessential. Not all
protein sources contain the same amounts of amino acids. Protein is
classified as complete or incomplete depending on whether it con-
tains adequate amounts of the essential amino acids. Animal sources
of protein contain all essential amino acids and are therefore
Muscle Mass and Weight Gain Nutritional Supplements 193
complete sources of protein, whereas plant proteins are missing
some of the essential amino acids (i.e., incomplete). Additionally,
there are varying levels of quality of protein depending on the amino
acid profile of the protein. Complete protein sources that contain
larger amounts of essential amino acids generally have higher pro-
Four of the most common types of protein found in protein
supplements are whey, casein, soy, and egg (ovalbumin) proteins.
Each of these proteins is a complete protein, and all are classified as
high quality proteins. Whey protein, derived from milk protein, is
currently the most popular source of protein used in nutritional
supplements. Whey proteins are available as whey protein concen-
trates, isolates, and hydrolysates. The primary differences among
these forms are the method of processing and small differences in fat
and lactose content, amino acid profiles, and ability to preserve
glutamine residues. In comparison to other types of protein, whey
protein is digested at a faster rate, has better mixing characteristics,
and is often perceived as a higher quality protein. Research has
indicated that the rapid increase in blood amino acid levels follow-
ing whey protein ingestion stimulates protein synthesis to a greater
degree than casein (17,18). Theoretically, individuals who consume
Classification of Amino Acids
Essential amino acids
Cysteine (cystine) Asparagine
Lysine Glutamine Aspartic acid
Methionine Histidine Glutamic acid
Phenylalanine Proline Glycine
Threonine Tyrosine Serine
Branched-chain amino acids
whey protein frequently throughout the day may optimize protein
synthesis. In fact, a study by Dangin and associates (19) repor ted
that frequent ingestion of a small amount of whey protein served to
increase protein synthesis to a greater degree than less frequent inges-
tion of various proteins. Overall, whey protein is an excellent source
of protein to supplement due to its amino acid content (including high
branched-chain amino acid content) and its ability to be rapidly
Casein, also a milk protein, is often described as a slower-acting
protein (17,19). It is considered a slower protein than whey protein
because it takes longer to digest and absorb. This is most likely due
to fact that casein has a longer transit time in the stomach (17).
Although casein stimulates protein synthesis, it does it to a much
lesser extent than whey protein (17). Unlike whey, casein helps
decrease protein breakdown (21), which has led to the status of
casein as having anticatabolic properties. Given the findings that
whey protein stimulates protein synthesis and casein helps decrease
muscle breakdown, some supplement manufacturers add both whey
and casein to their formulations. The effectiveness of combining
whey and casein proteins was illustrated in a recent investigation
conducted by Kerksick and colleagues (22). In their study, subjects
performed a split body part (training the upper body on one day and
the lower body on another) resistance training program 4 days a
week for 10 weeks. The subjects were given 48 g of carbohydrate or
40 g of whey þ 8 g of casein or 40 g of whey þ 5 g of glutamine þ 3g
of branched-chain amino acids (BCAAs). After 10 weeks, the group
supplemented with combined whey and casein had the largest
increase in lean muscle mass.
Although soy lacks the essential amino acid methionine, it has a
relatively high concentration of remaining essential amino acids and
is therefore considered a high quality protein. Soy protein is made
from soybeans using water or a water–ethanol mixture to extract
the protein (20). Soy protein is similar to whey protein in that there
is a soy protein concentrate and isolate. Soy contains compounds
called isoflavones, which appear to be strong antioxidants and
have been implicated in possibly decreasing the risk of developing
Muscle Mass and Weight Gain Nutritional Supplements 195
cardiovascular disease and cancer. In addition to isoflavones, soy
proteins contain protease inhibitors. Given these attributes of soy,
there is some evidence to suggest that soy may decrease or prevent
the exercise-induced damage to muscle seen following a workout
(23). At this point, there are few data relative to soy protein inges-
tion and accretion of lean body mass in conjunction with resistance
training; therefore, more research is needed before definitive recom-
mendations can be given.
Egg protein is also a high quality protein and has the advantage
of being a miscible protein (it mixes easily in solution) (20). How-
ever, egg protein supplements generally do not taste good and are
more expensive than other protein supplements. For these reasons,
along with the availability of other high quality proteins such as
whey, casein, and soy, egg protein supplementation is not popular
among athletes. Despite this, egg protein is still added in small
quantities to some meal replacement/protein powders (20).
Adequate protein intake consisting of high quality proteins is a
prerequisite for the accretion of lean body mass stimulated by a
proper resistance training program. Whey, casein, soy, and egg
proteins are all high quality proteins and are commonly found in
protein supplements marketed to strength-trained athletes. In addi-
tion to ingesting the proper amounts and quality of proteins, the
timing of protein intake has been a recent area of scientific investi-
gation. A discussion of the importance of this concept, known as
‘‘nutrient timing,’’ follows.
5. CARBOHYDRATE–PROTEIN COMBINATIONS
Ingestion o f a high quality protein i s essential for in creas ing lean
body mass, b ut equally important is the timing of the prot ein
intake. This category of spor ts nutrition has been categorized as
nutrient t iming , and ther e are multiple research st udies highlighting
the importance of appropriately timing certain meals throughout
is to time high glycemic carbohydrate and protein ingestion so
it encompasses the time frame in which the resistance training
bout exerts a hypertrophic stimulus on the trained skeletal muscles.
More specifically, stimulated myofibers are ‘‘primed’’ to synthesize
protein, but both insulin and amino acid substrate are required to
maximize this adaptation in the moments following an acute bout of
resistance exercise. This time period following a resistance training
session is commonly referred to as the anabolic window to emphasize
that this time frame has specific anabolic potential.
5.1. Resistance Training in the Absence of Nutritional Intake
Inherent with the term anabolic window is the concept of net
protein balance. As stated earlier, net protein balance is equal to
muscle protein synthesis minus muscle protein breakdown. For
skeletal muscle hypertrophy to occur, net protein balance must be
positive (synthesis must exceed breakdown). To improve net protein
balance, an appropriate stimulus (e.g., resistance training) must be
applied to the skeletal muscles. However, when resistance training
is performed alone, in the absence of nutritional and supplemental
(i.e., protein, carbohydrate) interventions, net protein balance
still does not increase to the point of becoming anabolic. Several
studies observing the effects of resistance training and acute changes
in net protein balance have concluded that net protein balance is
improved as a result of the resistance training bout. Although
resistance exercise improves the net balance by stimulating muscle
protein synthesis, however, nutrient intake is required for the synth-
esis to exceed the breakdown (24).
As support for this contention, Biolo and colleagues (1) assessed
rates of protein synthesis and degradation at rest and 3 hours after a
resistance training routine in fasted subjects. At 3 hours after exer-
cise, protein synthesis had increased approximately 108% and pro-
tein breakdown had increased 51%. Thus, resistance exercise
improved the net protein balance by increasing protein synthesis at
a greater rate than protein breakdown. Although the net protein
balance was improved, it is important to note that it did not improve
to the point of becoming positive (anabolic).
Phillips and coworkers (3) conducted a similar study in which
they recruited two groups of participants (resistance trained and
untrained) and had them perform an eccentric-only resistance
exercise workout in a fasted state. Rates of protein synthesis and
Muscle Mass and Weight Gain Nutritional Supplements 197
breakdown were measured within 4 hours of completing the resis-
tance training protocol. Following the resistance training bout,
muscle protein synthesis rates increased by 118% in the untrained
group and by 48% in the resistance trained group. In terms of
muscle protein breakdown, there was an increase of 37% in the
untrained group and an increase of 15% in the resistance-trained
group. Relative to the net protein balance, the resistance training
protocol significantly improved this measure in both groups (þ37%
in the untrained group and þ34% in the trained group), but the
overall net protein balance was still negative following the bout of
Using a larger time frame, this same researcher (2) assessed rates
of protein synthesis and protein breakdown at rest and at 3, 24, and
48 hours after a resistance training workout in recreationally active
(but not previously resistance trained) subjects. Unfortunately,
however, the net protein balance was not assessed in the fasted
state; rather, each participant ingested food at his own discretion.
There was an important nutritional restriction employed: The par-
ticipants were instructed to eat a meat-free diet during the study
(which limited protein intake). In addition, it appears that the
3-hour net protein balance assessment was conducted in the fasted
state. Muscle protein synthesis was significantly increased at each
time point following the resistance training bout: at 3 hours 112%;
at 24 hours 65%; at 48 hours 34%. Muscle protein breakdown was
also increased by 31% at 3 hours after exercise and by 18% at
24 hours. Muscle protein breakdown returned to resting levels by
48 hours. One of the novel findings of this study was the observation
that muscle protein synthesis was elevated (by 34%) 48 hours after
exercise, during which time muscle protein breakdown returned to
baseline levels. Despite this finding, at no time point did the net
protein balance become positive (likely due to the restrictions on
In summary, each of these aforementioned studies indicates that
resistance training alone is not enough to elicit positive changes in
net protein balance that lead to increases in lean body mass.
5.2. Insulin, Amino Acids, and Protein Synthesis
As stated in the introduction to the chapter, muscle-specific genes
must be activated to initiate the process of skeletal muscle
hypertrophy. Once these muscle-specific genes are activated, they
are copied into messenger RNA (mRNA) which serves as a template
for which muscle proteins are then manufactured (translated).
Many researchers believe that resistance training acts as the stimu-
lus for activating muscle-specific genes, but once these genes are
copied into muscle-specific mRNA transcripts still other factors
are needed to convert the muscle-specific mRNA into functional
skeletal muscle proteins. Two biological compounds have been
shown to be an integral part of this process: insulin and amino
acids. In fact, Bolster and coworkers (25) stated in a review paper
that, ‘‘Without question, investigating the singular role of amino
acids or insulin in promoting changes in skeletal muscle protein
synthesis with resistance exercise is crucial to elucidating mechan-
isms regulating muscle hypertrophy.’’
Insulin has several roles relative to improving the net protein
balance following resistance exercise, including increasing protein
synthesis (26–28), improving the transport of amino acids into
skeletal muscle (27,29,30), and decreasing protein breakdown
(30–33). Whereas insulin should never be injected (as multiple
adverse events are likely to occur) for the purposes of improving
net protein balance, insulin can be significantly increased endogen-
ously via the consumption of carbohydrate. As important as insulin
concentrations are to anabolic processes, Biolo and Wolfe (34)
stated that if high levels of insulin are not supported by an exogen-
ous amino acid supply, insulin loses its anabolic capacity in skeletal
muscle. This observation has been shared by other investigators as
Relative to protein synthesis, when essential amino acids were
ingested after a bout of resistance exercise, the net protein balance
was changed from a negative to a positive state (37). Other clinical
studies have also demonstrated that the oral ingestion of amino
acids are responsible for increasing protein synthesis rates in multi-
ple populations of participants (38,39). Given the importance of
insulin and amino acid availability relative to improving net pro-
tein balance, ingesting these nutrients simultaneously is recom-
mended. To further this recommendation, by adding a protein
source to carbohydrate ingestion it is possible to increase insulin
to levels higher than those induced by carbohydrate ingestion
Muscle Mass and Weight Gain Nutritional Supplements 199
5.3. Importance of Combined Carbohydrate–Protein
Supplements and Timing of Ingestion
Carbohydrate (to elevate insulin) and amino acids are needed to
maximize positive shifts in net protein balance, and the time course
for which they must be present should be considered. To highlight
the importance of timing, note that when 10 g of protein, 8 g of
carbohydrate, and 3 g of fat were ingested either immediately or
3 hours after exercise, protein synthesis was increased more than
threefold with the supplement ingested immediately versus ingestion
3 hours after exercise (with which there was only a 12% increase)
(40). In a study by Rasmussen and coworkers (41), subjects were
given an amino acid–carbohydrate drink or a placebo following a
resistance exercise session. Not surprisingly, the amino acid–carbo-
hydrate drink elicited an anabolic response compared to the pla-
cebo. In another study of protein breakdown, Bird and colleagues
(42) gave subjects one of four supplements after a bout of resistance
exercise: 1) carbohydrate beverage; 2) essential amino acids; 3)
combination of carbohydrate and amino acids; 4) placebo. The
result of this nutritional intervention revealed that protein degrada-
tion (as measured by urinary 3-methylhistidine) was elevated at 24
and 48 hours after exercise in the placebo group. Relative to the
carbohydrate and amino acid group, protein degradation was
unchanged at 24 hours and actually decreased 48 hours after exer-
cise. Given these findings and the data on the aforementioned
studies, properly timed carbohydrate–protein/amino acid supple-
ments not only increase protein synthesis but also seem to attenuate
protein degradation. Most of the scientific investigations have
looked at carbohydrate–protein supplements during the postresis-
tance exercise period; however, one study looked at the difference of
ingesting an amino acid–carbohydrate supplement before versus
after resistance training (43). The investigators reported that pro-
tein synthesis was greater as a result of the preresistance training
intake of the amino acid–carbohydrate supplement, most likely due
to increased delivery of amino acids to the stimulated skeletal muscle
Most studies have examined the combination of amino acid–
carbohydrate supplements in the time frame that encompasses a
resistance training session, but not many have investigated intact
protein (e.g., whey, casein) supplementation after resistance exercise
and their effects on the net protein balance. Tipton et al. (44)
studied the ingestion of casein and whey proteins and their effects
on muscle anabolism after resistance exercise. They concluded that
the ingestion of both proteins (whey and casein) after resistance
exercise resulted in similar increases in muscle protein net balance,
resulting in net muscle protein synthesis, despite different patterns of
blood amino acid responses (a quicker response of blood amino
acids for the whey protein and a more sustained response for the
casein protein). In a similar study, Tipton and coworkers (45)
questioned if ingestion of whole proteins before exercise would
stimulate a superior response to that with ingestion after exercise.
The authors reported that the net amino acid balance switched from
negative to positive following ingestion of the whey proteins at both
time points. In another study, when whey protein was added to
an amino acid–carbohydrate supplement, the authors indicated
that there seemed to be an extension of the anabolic effect compared
to that seen with amino acid–carbohydrate supplements without
additional whey protein (46).
A proper postworkout supplement designed to increase lean
body mass should contain both carbohydrates and protein and be
in a liquid form. The reason these carbohydrate–protein supple-
ments should be in liquid form is that liquid meals are more pala-
table and digestible. In addition, liquid meals have a fast absorption
profile compared to that of whole foods, which allows faster insulin
secretion and peak plasma amino acid levels—both of which are
essential to take advantage of the anabolic window created by
the resistance training session. This section has highlighted some
of the clinical investigations and the mechanisms as to how appro-
priately timed ingestion of carbohydrate–protein supplements exert
their effects. A more detailed explanation can be found by reading
Chapter 13, on dietary meal and nutrient timing.
The sports supplement creatine has been the gold standard
against which other nutritional supplements are compared. The
reason for this prominent position is that creatine improves
Muscle Mass and Weight Gain Nutritional Supplements 201
performance, increases lean body mass, and has repeatedly been
shown to be safe when recommended dosages are consumed. Con-
sequently, creatine has become one of the most popular nutritional
supplements marketed to athletes over the past decade and a half. In
fact, one of the most consistent side effects of creatine supplementa-
tion has been weight gain in the form of lean body mass. This
increase has been observed in several cohorts including males,
females, and the elderly (47–54).
In most of the studies published on creatine supplementation, the
typical dosage pattern was divided into two phases: a loading phase
and a maintenance phase. A typical loading phase consists of ingest-
ing 20 g of creatine (or 0.3 g/kg body weight) in divided doses four
times per day for 2 to 7 days, followed by a maintenance dose of 2 to
5 g daily (or 0.03 g/kg) for several weeks to months at a time (55).
Another consideration relative to creatine dosage is to base the
amount on an individual’s lean body mass. Burke and coworkers
(56) studied this aspect of creatine supplementation by having
subjects ingest creatine at a dosage of 0.1 g/kg of lean body mass
(this equates to approximately 8 g of creatine for a 200 pound indivi-
dual at 15% body fat). Hultman and colleagues (57) demonstrated
another interesting approach to creatine ingestion. They demon-
training period of at least 4 weeks the skeletal muscle creatine levels
rose more slowly, eventually reaching levels similar to those achieved
with the loading method.
In summary, a quick way to ‘‘creatine load’’ skeletal muscle
requires ingesting 20 g of creatine monohydrate daily for 6 days
and then switching to a reduced dosage of 2 g/day (57). If the
immediacy of ‘‘loading’’ is not an important consideration, supple-
menting with 3 g/day for 28 days achieves the same high levels of
intramuscular creatine (57).
6.1. Effects on Lean Body Mass
What type of weight gain (in the form of lean body mass) can be
expected with this level of creatine supplementation? Many of the
studies performed to date indicate that short-term creatine supple-
mentation increases total body mass by approximately 0.7 to 1.6 kg
(1.5–3.5 lb) (16). Longer-term creatine supplementation (6–8
weeks) in conjunction with resistance training has been shown to
increase lean body mass by approximately 2.8 to 3.2 kg (7 lb)
(58–60). Gain in lean body mass has also been observed in women
as a result of creatine supplementation. Vandenberghe et al. (47)
investigated the changes in fat-free mass in females who ingested
creatine (20 g/day for the first 4 days followed by 5 g/day for 65 days)
in combination with resistance exercise for 10 weeks. The authors
reported an increase of 5.7 lb of fat-free mass after 10 weeks of
creatine supplementation and resistance exercise. This increase was
60% greater than in the creatine supplementation group compared
to the placebo group.
6.2. Physiological Mechanisms for Increasing Lean Body Mass
The exact physiological mechanisms responsible for increasing
lean body mass as a result of creatine supplementation remain
poorly understood. Early studies investigating creatine supplemen-
tation and weight gain led many to the conclusion that increases in
body weight were due to water retention. However, several more
recent studies suggest that creatine supplementation may help build
lean tissue. Volek et al. (61) reported that during a 12 week resis-
tance training program, resistance trained males ingesting creatine
significantly increased the fat-free mass compared to those ingesting
a placebo. Furthermore, it was reported that the subjects given
creatine demonstrated significantly greater increases in types I
(35% vs. 11%), IIA (36% vs. 15%), and IIAB (35% vs. 6%) muscle
fiber cross-sectional areas (61). The percentage increases in cross-
sectional area for all fiber types in those subjects ingesting creatine
ranged from 29% to 35%—more than twice the increase observed in
placebo subjects (6%–15%) (16).
To help elucidate the physiological mechanisms further,
Willoughby and Rosene (62,63) conducted a series of studies inves-
tigating the effects of oral creatine ingestion and the factors involved
in gene expression of contractile filaments and myosin heavy-chain
protein expression. In the first of these studies, untrained male
subjects ingested creatine at 6 g/day or a placebo in conjunction
with heavy resistance training for 12 weeks. At the end of the
intervention, those ingesting creatine significantly increased their
fat-free mass (7 lb) in comparison with the placebo group
(1 lb). One of the most interesting parameters in this study was
the information that was gathered relative to what was occurring at
Muscle Mass and Weight Gain Nutritional Supplements 203
the cellular level of the skeletal muscle. Myofibrillar protein content
(a marker of the amount of intracellular protein) was found to be
significantly greater in the creatine group than in the placebo group
despite the fact that both groups performed identical resistance
training programs. More specifically, the authors reported that
there were significant increases in the content of two isoforms of
myosin heavy-chain protein (the major constituent of contractile
skeletal muscle) (62).
In their other study, Willoughby and Rosene (63) investigated
the effects of ingesting creatine (in conjunction with a resistance
training program) on myogenic regulatory factor gene expression.
Myogenic regulatory factors (which include Myo-D, myogenin,
MRF-4, and Myf5) are proteins that function as transcription acti-
vators that regulate gene expression via their binding to DNA,
ultimately activating the transcription of muscle-specific genes
such as myosin heavy chain, myosin light chain, a-actin, troponin-
I, and creatine kinase (64). After 12 weeks of resistance training, the
authors reported that the subjects ingesting creatine had signifi-
cantly greater mRNA expression for myogenin and MRF-4 than
the subjects ingesting a placebo. These findings provide an insight
into the mechanisms by which creatine supplementation exerts its
effects on increasing lean body mass. Taken together, the aforemen-
tioned studies seem to indicate that the increases in lean body mass
as a result of creatine supplementation are due to augmenting
skeletal muscle fiber hypertrophy and not solely water retention.
6.3. Satellite Cell Activity
In addition to increasing muscle fiber cross-sectional areas,
myogenic regulatory factors, and specific isoforms of myosin
heavy chain, creatine supplementation has been shown to augment
an increase in satellite cell number in human skeletal muscle
induced by strength training. In addition to muscle-specific tran-
scription and translation, activation of satellite cells is thought
to be a major contributing factor to augmenting skeletal muscle
hypertrophy. During the process of load-induced muscle hypertro-
phy, satellite cells are thought to proliferate, differentiate, and then
fuse with existing myofibers (65). The way in which satellite cells
are thought to be involved in skeletal muscle hypertrophy is sum-
marized in what is termed the myonuclear domain theory. This
theory suggests that the myonucleus controls the production of
mRNA (i.e., transcription) and proteins (i.e., translation) for a
finite volume of cytoplasm, such that increases in fiber size must
be associated with a proportional increase in myonuclei, which are
contributed from the satellite cell populations (66). If this theory
is correct, anything that increases satellite cell activity leading to
increases in myonuclei sets the stage for increased skeletal muscle
In a truly original investigation, Olsen and coworkers (67) inves-
tigated the influence of creatine and protein supplementation on
satellite cell frequency and the number of myonuclei in human
skeletal muscle during 16 weeks of resistance training. After the 16
weeks of training, all groups in the clinical trial (creatine, protein,
and placebo groups) demonstrated significant increases in the pro-
portion of satellite cells. However, only the creatine-supplemented
group demonstrated consistent significant increases of myonuclei
per fiber. This finding led the authors to conclude that ‘‘creatine
supplementation in combination with strength training amplifies the
training-induced increase in satellite cell number and myonuclei
concentration in human skeletal muscle fibers, thereby allowing an
enhanced muscle fiber growth in response to strength training’’
(67). Given this important finding relative to creatine supplementa-
tion and satellite cell activity, additional clinical trials investigating
this aspect of creatine supplementation are needed.
7. ANABOLIC HORMONE ENHANCERS
Insulin, growth hormone, testosterone, and insulin-like growth
factor-1 (IGF-1) are all considered primary anabolic hormones. We
have already discussed insulin and its role in translating muscle-
specific mRNA into skeletal muscle proteins, and the effects that
carbohydrate–amino acid supplements have on increasing insulin
levels. The other three anabolic hormones are believed to exert their
effects on the cell-signaling properties of skeletal muscle fibers, which
ultimately result in muscle-specific gene expression. IGF-1, however,
not only acts in this regard (cell signaling) but also acts similarly to
insulin in its role of translating muscle-specific mRNA transcripts
into functional skeletal muscle proteins (actin, myosin). A further
discussion of IGF-1, growth hormone, and testosterone follows.
Muscle Mass and Weight Gain Nutritional Supplements 205
7.1. Insulin-Like Growth Factor-1
There are three isoforms of IGF-1 in human muscle (68): IGF-
1Ea (similar to the type of IGF-1 synthesized in the liver); IGF-1 Eb;
and IGF-1Ec (known as mechano growth factor) (68). IGF-1 is
produced primarily by the liver as an endocrine hormone and
is stimulated by growth hormone release. One of the isoforms of
IGF-1, known as mechano growth factor, is detectable only after
mechanical stimulation (e.g., resistance training). Skeletal muscle
hypertrophy is regulated by at least three major molecular pro-
cesses: 1) satellite cell activity; 2) gene transcription; and 3) protein
translation. Interestingly, IGF-I can influence the activity of all of
these mechanisms (69). That being the case, any increases in IGF-1
could significantly increase the potential for skeletal muscle
In addition to gr owth ho rmone r elease an d mec hanic al stimu -
lation, are there any nutritional or supplemental means that
increase endogeno us levels of IGF-1? For the most part, the
answer is no, b ut two studi es have reported that suppl emen tation
with bovine colostrum resulted in increases in serum IGF-I con-
centration in athletes during training (70,71). However, owi ng to
the relatively acute duration of these studies, lean body mass
indices were not measured. Another study that did measure mus-
cle protei n balance and strength after 2 weeks of bovine colostrum
supplementation ( 72) foun d that the bovine col ost rum had no
effect on either of these variables. Given these findings, at this
point it is safe to sa y th at th ere are no sports supplements t ha t
effectively increas e endogenous IGF- 1 levels re sulting in change s
in lean body mass.
7.2. Growth Hormone
A quick survey of the literatur e on growth hormone reveals
that the hormone d oes indeed improve body composition by
simultaneously increasing lean body mass and decreasing body
fat in diseased p opulations (73–75).However,whatisoftennot
mentioned in th e marketing camp aigns of sports supplements
designed to increase growth hormone is the fact that most of
these clinical investigations introduce d growth hormone into
their subjects via su bcutaneous injection. Many sports supple-
ments designed to inc rease endogen ous levels of gr owth hormone
are based on studies showing that specific amino acids are able
(inconsistently) to increase growth hormone. The main amino acid
that has demonstrated potential to increase growth hormone is
arginine. As discussed below, arginine is often combined with
other compounds to elicit growth hormone release.
It is well documented that the infusion of arginine stimulates
growth hormone secretion from the anterior pituitary (76,77).
This increase in growth hormone secretion from arginine infusion
has been attributed to the suppression of endogenous somatostatin
secretion (76). The amounts of arginine infused to elicit the growth
hormone response ranged from 12 to 30 g. The clinical investiga-
tions observing oral consumption of arginine and its impact on
growth hormone release are equivocal. Relative to the practical
oral ingestion of arginine, several studies have shown that such
supplementation resulted in significant increases in growth hormone
One such study (78) found that oral arginine supplementation of
5 and 9 g resulted in significant growth hormone response in males.
Interestingly, 13 g of oral arginine did not increase growth hormone
levels and caused gastrointestinal distress in most of the subjects. A
common supplemental regimen that has shown promise as a growth
hormone enhancer includes the addition of lysine to arginine. Uti-
lizing this combination, Isidori and colleagues (79) provided 1.2 g
of arginine (as arginine-2-pyrrolidone-5-carboxylate) and 1.2 g of
lysine (as lysine hydrochloride) to young males. Plasma growth
hormone concentrations increased eightfold at 90 minutes after
ingestion. Similarly, Suminski and associates (80) reported that
the ingestion of arginine and lysine resulted in a 2.7-fold increase
in plasma growth hormone concentrations in resistance trained
Another compound commonly added to arginine for the purpose
of eliciting an increase in growth hormone is aspartate. Besset and
colleagues (81) gave male subjects arginine aspartate at a dose of
250 mg/kg/day (approximately 17.5 g of arginine aspartate for a
70 kg male) for 1 week. The results indicated that the sleep-related
growth hormone peak was about 60% higher after a week of argi-
nine aspartate administration than in the controls. Colombani
et al. (82) gave 20 male endurance trained athletes 15 g of arginine
aspartate (7.5 g in the morning and 7.5 g in the evening) for 14 days
Muscle Mass and Weight Gain Nutritional Supplements 207
before a marathon run. After 31 km had been completed by the
runners, plasma growth hormone levels were 40% greater in the
arginine aspartate group. At the end of the marathon, plasma growth
hormone levels were 8% greater in the supplemented group than in
the placebo group.
Not all studies investigating arginine supplementation and
growth hormone responses have been favorable. Walberg-Rankin
(83) gave resistance-trained males ingesting a hypocaloric diet argi-
nine hydrochloride 100 mg/kg/day (approximately 8 g arginine
hydrochloride) for a 10-day period. This supplementation protocol
did not result in an increase in growth hormone concentration.
Another study also reported no increase in plasma growth hormone
concentrations when elderly men ingested 3 g of arginine and 3 g
lysine for 14 days (84). In yet another study investigating arginine
and growth hormone responses, Marcell et al. (85) investigated
whether oral arginine (5 g) increases growth hormone secretion in
young and old people (male and female) at rest and during resistive
exercise. The authors concluded that oral arginine supplementation
does not increase growth hormone secretion at rest or in combina-
tion with resistive exercise.
There are several reasons for the conflicting results in terms of
arginine eliciting an increase in growth hormone production. Some
of these reasons could be the type of arginine complex, dosages, and
delivery methods used and variations in the subjects themselves. It
has also been suggested that the growth hormone response to amino
acid ingestion may be reduced in individuals who are exercise
Even if certain amino acids do increase g rowth hormone levels
(a statement not supported by all investigations), it does not
necessarily lead to the conclus ion that they inc reas e lean body
mass. In a scie ntific review on this subject, Chrom iak a nd Anto nio
(55) stated: ‘‘There is no evidence based on properly conducted,
rigorous scientific studies tha t oral suppleme ntati on of specifi c
amino acids induces growth hormone that, in conjunction with
resistance training, increases muscle mass and strength to a
greater e xtent than resistance training alone.’’ At this point, it
appears as if specific amino acids, even if they do elicit an increas e
in growth hormone, do not increase lean body mass via this
Although each of the anaboli c h ormone s (t estost erone , g rowth
hormone, ins ulin, IGF-1) i s required t o s timulate maximum levels
of skelet al muscle hypertrophy, test osterone may be the most ana-
bolic. It is important to recognize that not all of the testosterone in
the blood is bioavailable; rather, most of it is bound to proteins
such as sex hormone-binding globulin (SHBG) or other carrier
proteins. Test oster one that is not boun d is referred to as ‘‘free ’’ or
‘‘bioavailable’’ testosterone; and it is able to bind to the androgen
receptor and exert its anabolic signal ing. This is an important
distinction becaus e as one attempts to increase te stosterone levels
(via testosterone-enhan cing supplement s) in the body, it is onl y the
bioavailable testosterone that exerts anabolic actions. Another
important co nsi dera tion is the avoidance of increasing SHBG to
a greater extent than total test osterone increases, which would
result in an environment in which there is less bioavailable testos-
terone present. Therefore, when investigating sports s upplement s
designed to increase testosterone , each of these fact ors must b e
considered. Currently, there are a few sports supplements that
claim to increase testosterone levels: ZMA, Tribulus terrestris,
and aromatase inhibitors.
The primary ingredients in ZMA supplements are zinc mono-
methionine aspartate, magnesium aspartate, and vitamin B
and magnesium deficiencies as well as urine and sweat losses of these
minerals have been observed in athletes and individuals who are
physically active (86–90). Relative to testosterone, there have been
two well designed studies investigating the effects of ZMA supple-
mentation and its effects on testosterone levels, with the studies
reporting contradictory results (91,92).
The first of these studies gave collegiate football players ZMA
(30 mg zinc monomethionine aspartate þ 450 mg magnesium aspar-
tate þ10.5 mg of vitamin B
) over the course of their spring practice
season (approximately 8 weeks) (91). Total testosterone and, more
importantly, free testosterone were significantly elevated as a result
of the ZMA supplementation compared to that of the placebo
group. This study is consistently cited as proof of the effectiveness
of ZMA to elevate testosterone levels. In the other study (92),
Muscle Mass and Weight Gain Nutritional Supplements 209
researchers gave resistance trained males a ZMA supplement (main
ingredients consisting of 30 mg zinc monomethionine aspartate þ
450 mg magnesium aspartate þand 11 mg of vitamin B
) and found
no such increases in either total or free testosterone. This investiga-
tion (92) also assessed changes in the fat-free mass and several
strength and performance variables. No significant differences
were observed in relation to these variables in subjects taking
ZMA. The discrepancies concerning these two studies may be
explained by deficiencies of these minerals. Given the role that zinc
deficiency plays relative to androgen metabolism and interaction
with steroid receptors (93), when there are deficiencies of this
mineral, testosterone production may suffer. In the study showing
increases in testosterone levels (91), there were observed depletions
of both zinc and magnesium in the placebo group over the course of
the study. Therefore, the increased testosterone levels could have
been attributed to impaired nutritional status rather than a pharma-
cological effect. Obviously, more research is needed on supplemen-
tal ZMA before any concrete recommendations can be made
relative to testosterone responses.
Tribulus terrestris is often marketed as a testosterone-boosting
sports supplement. There are relatively few, if any, scientific studies
to substantiate these claims. In fact, one clinical investigation
demonstrated that Tribulus terrestris exerts no effect on increasing
testosterone levels (94). In this study, healthy men were instructed
to supplement with Tribulus terrestris for a 4-week period after
which serum levels of testosterone and luteinizing hormone were
measured at 1, 3, 10, 17, and 24 days after supplementation. Tribulus
terrestris supplementation did not increase the levels of either tes-
tosterone or luteinizing hormone. Given the unsubstantiated claims
of Tribulus terrestris relative to increasing testosterone levels, sup-
plemental Tribulus is not recommended.
Aromatase inhibitors exert their effects by inhibiting the action
of the enzyme aromatase, which converts androgens to estrogens by a
process called aromatization. Aromatase inhibitor supplements claim
to suppress estrogen levels and increase endogenous testosterone
levels. In the only published study investigating aromatase i nhi-
bitor s upplements, Willoughby and colleagues (9 5) instructed
their male subjects to ingest an aromatase inhibitor supplement
(containing hydroxya ndrost-4-ene -6,17 dioxo-3 -THP ether and
3,17-diketo-androst-1,4,6-triene) at 72 mg/day for an 8-week per-
iod. At the e nd of the 8 weeks there was a 3-week washout period.
Multiple anabolic hormones were assayed during the duration
of the study, including total testost erone and free testosterone.
In additio n, body composition was assess ed dur ing th e inves tiga-
tion in which the participants were instructed to maint ain their
normal res istance training programs. There wer e significant
increases in both total and free testosterone levels compared to
those with placebos, with the total testosterone having an average
increase of 283% and free testosterone a n average of 625%. The
aromatase inhibitor supplement had also elicited a 3.5% decrease
in fat mass in the aromatase inhibitor group at the end of the
8-week period. After the 3-week washout period, total and free
testosterone levels decreased to the presupplementati on va lues.
Finally, the aforementioned supplementation appeared to be safe
and w ell tolerated by the study participants as measured by blood
and urinary clinical safety markers. Although this study appears
to support aromatase inhibitor supplementation for the purpose
of increasing endogenous testosterone levels, additional studies
are needed to replicate the se find ings. In summary, it ap pears tha t
of all the nutritional suppl ements designed to increase testoster-
one levels aromatase inhibitor supplementation is the most scien-
tifically valid option.
8. ANTICATABOLIC SUPPLEMENTS
Because the net protein balance is equal to muscle protein synthesis
minus muscle protein breakdown, eliciting increases in lean body
mass can be achieved not only by increasing protein synthesis but
also by decreasing protein breakdown (catabolism). Hence, a number
of sports supplements are marketed for that endeavor, including
glutamine, cortisol inhibitors, b-hy droxyl-b-methylbutyrate (HMB),
and a-ketoisocaproic acid. In addition to these specific sports
supplements, insulin has been shown repeatedly to suppress protein
Muscle Mass and Weight Gain Nutritional Supplements 211
breakdown (30,31,96,97). Hence, carbohydrate (or carbohydrate þ
protein) taken after resistance exercise (a period when protein break-
down is elevated) for the purpose of increasing insulin secretion is a
recommended practice to suppress protein breakdown (42).Other
purported anticatabolic supplements are discussed below.
8.1. a-Ketoisocaproic Acid
a-Ketoisocaproic acid (KIC) is the keto acid of the BCAA
leucine. Despite many claims of KIC and its anticatabolic proper-
ties, there is only one peer-reviewed study in humans that has
investigated the inclusion of KIC (along with HMB) on a specific
marker of muscle damage (creatine kinase). When non-resistance-
trained males ingested 3 g of HMB and 0.3 g of KIC daily for
14 days prior to a resistance training session, it was reported that
the HMB–KIC supplementation attenuated the creatine kinase
response compared to that seen with the placebo (98). Although
this may be an important finding, creatine kinase is not a direct
measure of protein breakdown. Also, the extent to which HMB or
KIC alone affected this attenuation of creatine kinase cannot be
determined. Another study that is commonly cited as evidence for
KIC supplementation and its ability to prevent proteolysis was
conducted on isolated rat diaphragm skeletal muscle (99). In this
venue, one should be cautious of overextrapolating from rodent
data to the human condition. At this point, there are not enough
data to conclude that KIC supplementation alone is an effective
b-Hydroxy-b-methylbutyrate is a metabolite of the BCAA leu-
cine and is often associated with anticatabolic potential. The origi-
nal research study to highlight HMB’s anticatabolic potential was
conducted by Nissen and coworkers (100). In this study, untrained
subjects ingested one of three levels of HMB (0, 1.5, or 3.0 g/day)
and two protein levels (117 or 175 g/day) and resistance trained 3
days per week for 3 weeks. Other markers of muscle damage were
assessed, and protein breakdown was assessed by measuring urinary
3-methylhistidine (3-MH). After the first week of the resistance
training protocol, urinary 3-MH was increased by 94% in the
control group and by 85% and 50% in individuals ingesting 1.5
and 3. 0 g o f HMB per day, respe ctivel y. During the second week
of the study, 3- MH levels were still elevated by 27% in the control
group but were 4% and 15% below basal levels for the groups on
HMB 1.5 and 3.0 g/day. Int erestingly, 3-MH measures at the end
of th e third week of resistance training wer e not s ignifi cantly
different a mong the gr oups (100). Other studies demonstrating
an anticatabolic effect or suppr essing muscle damage have sup-
ported the finding of this st udy (98,101). A study conducte d by
van S omeren and coworker s (98) instructed their male subjects to
ingest 3 g of HMB in addition to 0.3 g KIC daily for 14 days prior
to performing a single bout of eccentrically biased resistance
exercise. This supplemental intervention that included HMB
resulted in a significant reduction in the plasma markers of muscle
Although HMB supplementation may suppress protein break-
down and markers of muscle damage, the main question is if this
anticatabolic effect leads to gains in lean body mass. The scientific
literature on this topic is divided. In a second arm to the study
conducted by Nissen and colleagues (100), male subjects ingested
3 g of HMB or a placebo for 7 weeks in conjunction with resistance
training 6 days per week. In this study, the fat-free mass increased in
the HMB-supplemented group at various times throughout the
investigative period but not at the conclusion of the study. Other
studies have also reported evidence for HMB supplementation
(3 g/day) relative to increasing lean body mass (102,103). In addi-
tion, a meta-analysis conducted by Nissen and Sharp (104) stated
that only HMB and one other sports supplement (creatine) were
found to increase lean body mass significantly.
Not all studies agree with the findings that HMB increases lean
body mass, however (105–107). Each of the studies showing no
effect of HMB on lean body mass accretion also supplemented their
subjects with approximately the same amount of HMB as the studies
that demonstrated increases in lean body mass. Although not con-
clusive, it appears that HMB supplementation does suppress protein
breakdown, ultimately leading to increased lean body mass in some
individuals. Following carbohydrate supplementation (for the pur-
pose of secreting insulin), HMB is the next best anticatabolic sports
Muscle Mass and Weight Gain Nutritional Supplements 213
Another sports supplement commonly marketed as an anticata-
bolic agent is the amino acid glutamine. Glutamine is the most abun-
dant free amino acid in plasma and skeletal muscle and accounts for
more than half of the total intramuscular free amino acid pool (108).
The rationale for glutamine’s anticatabolic effects is the fact that it is
one of the major fuels used by the gut, resulting in a high cellular
turnover of glutamine in the gut (intestinal mucosal cells). This high
turnover may result in the supply of amino acids (glutamine) to the
cells of the gastrointestinal tract at the expense of skeletal muscle
protein. By providing supplemental glutamine to the gut, it theoreti-
cally spares the glutamine that is available in skeletal muscle and in this
way serves as an anticatabolic agent. One clinical investigation that
gave supplemental glutamine to individuals engaging in resistance
exercise did not demonstrate an anticatabolic potential or result in
increases in lean body mass (109). Other studies that have demon-
strated anticatabolic potential for glutamine have used critically ill
subjects or subjects who underwent surgery (110, 111). Despite a valid
theoretical rationale for glutamine supplementation, at this point there
are no scientific data demonstrating that glutamine supplementation
suppresses protein breakdown in resistance trained individuals.
9. NITRIC OXIDE BOOSTERS
One of the more recent developments in sports supplements has
been the introduction of supplements intended to increase nitric oxide
production. Relative to biological processes in humans, nitric oxide is
synthesized in cells by nitric oxide synthase. One of nitric oxide’s
primary physiological functions is to relax smooth muscle, and
hence it is one of the body’s major regulators of blood flow, especially
during exercise. Kingwell (112) indicated that nitric oxide potentially
affects metabolic control during exercise via multiple mechanisms,
Elevation in skeletal muscle and cardiac blood flow and increased deliv-
ery of oxygen, substrates, and regulatory hormones (e.g., insulin)
Preservation of intracellular skeletal muscle energy stores by promoting
glucose uptake, inhibiting glycol ysis, mitochondrial respiration, and
Together, these actions of nitric oxide on blood flow and sub-
strate utilization appear to be directed toward protection from
ischemia (112). Also, if adequate amounts of oxygen and substrate
are supplied to the skeletal muscle undergoing mechanical stress, the
possibility of extending the total workload on each set of a resistance
training bout may lead to greater stimulus for muscle fiber hyper-
trophy. The aforementioned observation, in conjunction with some
earlier studies showing nitric oxide as an integral compound relative
to improving skeletal muscle’s force production and maximal power
output (113,114), has provided a rationale for investigating ways to
increase endogenous nitric oxide production.
In every sports supplement claiming to augment endogenous
nitric oxide production, the amino acid arginine is included in the
list of ingredients. This is due to the fact that arginine serves as a
precursor for the biosynthesis of nitric oxide (115). In fact, arginine
is the only endogenous nitrogen-containing substrate of nitric oxide
synthase and thus governs production of nitric oxide. To date, only
one study has investigated the effects of an arginine-containing
sports supplement aiming at augmenting endogenous nitric oxide
production (116). Although this study was well designed, it should
be noted that nitric oxide production was not assessed in the clinical
investigation. The study investigated the effects of ingesting 12 g of
arginine a-ketoglutarate in conjunction with a periodized resistance
training program over a period of 8 weeks. Although there was some
improvement in some exercise performance variables, the investiga-
tors did not observe any increases in lean body mass. Specifically,
those ingesting arginine a-ketoglutarate had a significant increase
in upper body strength (as measured by the bench press) compared
to the subjects ingesting a placebo. In f act, those ingesting the
arginine a-ketoglutarate increased their bench press by 19 lb versus
an increase of approximately 6 lb in the placebo group. Addition-
ally, the arginine a-ketoglutarate group significantly increased their
peak power output (as measured by a 30-second cycle sprint test) in
comparison to the placebo group. Whether these improvements in
exercise performance can be associated with increases in nitric oxide
production is not known, but the fact remains that there were no
increases relative to lean body mass observed in this investigation.
At this point, there is a theoretical rationale that augmenting nitric
oxide production may lead to more intense training and ultimately
Muscle Mass and Weight Gain Nutritional Supplements 215
greater skeletal muscle hypertrophy. However, because clinical
investigations have not demonstrated this, it is premature to state
emphatically that sports supplements designed to increase nitric
oxide lead to greater gains in lean body mass.
Increasing lean body mass is a goal of many athletes, recreational
weight trainers, and those who wish to improve their body composi-
tion. When choosing a dietary supplement to augment increases in
lean body mass, it is important to consider the way in which the
supplement contributes to the highly regulated process of skeletal
muscle hypertrophy. The science of sports supplements is relatively
new, although certain sports supplements (protein, creatine) have
been scientifically investigated and have repeatedly demonstrated
their ability to increase lean body mass. Other sports supplements
(e.g., anticatabolic agents, anabolic hormone enhancers, nitric oxide
boosters) require more rigorous scientific investigation before they
can be deemed effective (or not).
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