Literature Review

A Review of Issues of Dietary Protein Intake in Humans

Article· Literature Review (PDF Available)inInternational journal of sport nutrition and exercise metabolism 16(2):129-52 · April 2006with 15,047 Reads 
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DOI: 10.1123/ijsnem.16.2.129 · Source: PubMed
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Abstract
Considerable debate has taken place over the safety and validity of increased protein intakes for both weight control and muscle synthesis. The advice to consume diets high in protein by some health professionals, media and popular diet books is given despite a lack of scientific data on the safety of increasing protein consumption. The key issues are the rate at which the gastrointestinal tract can absorb amino acids from dietary proteins (1.3 to 10 g/h) and the liver's capacity to deaminate proteins and produce urea for excretion of excess nitrogen. The accepted level of protein requirement of 0.8g x kg(-1) x d(-1) is based on structural requirements and ignores the use of protein for energy metabolism. High protein diets on the other hand advocate excessive levels of protein intake on the order of 200 to 400 g/d, which can equate to levels of approximately 5 g x kg(-1) x d(-1), which may exceed the liver's capacity to convert excess nitrogen to urea. Dangers of excessive protein, defined as when protein constitutes > 35% of total energy intake, include hyperaminoacidemia, hyperammonemia, hyperinsulinemia nausea, diarrhea, and even death (the "rabbit starvation syndrome"). The three different measures of defining protein intake, which should be viewed together are: absolute intake (g/d), intake related to body weight (g x kg(-1) x d(-1)) and intake as a fraction of total energy (percent energy). A suggested maximum protein intake based on bodily needs, weight control evidence, and avoiding protein toxicity would be approximately of 25% of energy requirements at approximately 2 to 2.5 g x kg(-1) x d(-1), corresponding to 176 g protein per day for an 80 kg individual on a 12,000kJ/d diet. This is well below the theoretical maximum safe intake range for an 80 kg person (285 to 365 g/d).
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129
A Review of Issues of Dietary Protein
Intake in Humans
Shane Bilsborough and Neil Mann
Considerable debate has taken place over the safety and validity of increased
protein intakes for both weight control and muscle synthesis. The advice to con-
sume diets high in protein by some health professionals, media and popular diet
books is given despite a lack of scientific data on the safety of increasing protein
consumption. The key issues are the rate at which the gastrointestinal tract can
absorb amino acids from dietary proteins (1.3 to 10 g/h) and the liver’s capacity
to deaminate proteins and produce urea for excretion of excess nitrogen. The
accepted level of protein requirement of 0.8g kg
-1
d
-1
is based on structural
requirements and ignores the use of protein for energy metabolism. High protein
diets on the other hand advocate excessive levels of protein intake on the order
of 200 to 400 g/d, which can equate to levels of approximately 5 g kg
-1
d
-1
,
which may exceed the liver’s capacity to convert excess nitrogen to urea. Dangers
of excessive protein, defined as when protein constitutes > 35% of total energy
intake, include hyperaminoacidemia, hyperammonemia, hyperinsulinemia nausea,
diarrhea, and even death (the “rabbit starvation syndrome”). The three different
measures of defining protein intake, which should be viewed together are: absolute
intake (g/d), intake related to body weight (g ∙ kg
-1
d
-1
) and intake as a fraction
of total energy (percent energy). A suggested maximum protein intake based on
bodily needs, weight control evidence, and avoiding protein toxicity would be
approximately of 25% of energy requirements at approximately 2 to 2.5 g ∙ kg
-1
d
-1
, corresponding to 176 g protein per day for an 80 kg individual on a 12,000kJ/d
diet. This is well below the theoretical maximum safe intake range for an 80 kg
person (285 to 365 g/d).
Key Words: increased protein intake, amino acid absorption, urea synthesis,
maximum protein intake, weight loss
Historical Background
Much controversy exists over the advantages and disadvantages of various quanti-
ties of protein consumption and the metabolic fate of the amino acid content of
Bilsborough is an independent researcher with B Personal Pty Ltd. Mann is with the Dept of Food
Science, RMIT University, Melbourne, Victoria 3001, Australia.
International Journal of Sport Nutrition and Exercise Metabolism, 2006, 16, 129-152
© 2006 Human Kinetics, Inc.
Original research
130 Bilsborough and Mann
various proteins, mainly due to the limited amounts of data pertaining to protein
metabolism and amino acid kinetics in humans. Two clearly separate areas of inter-
est can be identified in regard to protein intake, the first being the current debate on
the merits of increased protein intake at the expense of carbohydrates in relation
to weight loss and diabetic glycemic control, the second being the long-standing
interest of those in the health, fitness, and body building fraternity with increased
protein intake for perceived benefits in muscle development.
A comprehensive study of dietary protein in weight loss and glucose homeo-
stasis, focusing particularly on leucine metabolism has been published recently
by Layman et al. (1).
Essentially dietary protein requirement is described as the
minimum level of protein necessary to maintain short-term nitrogen balance under
conditions of controlled energy intake and is quantified as the Recommended Daily
Allowance (RDA) in the US. This level assumes the primary use of amino acids as
substrates for synthesis of body proteins; however there is mounting evidence that
additional metabolic roles for some amino acids require plasma and intracellular
levels above minimum needs for protein synthesis (1). Recently a meta-analysis
of 235 non-athletic individuals gathered from 19 nitrogen balance studies for
estimating protein requirements in healthy adults found the median estimated
average requirement (EAR), and 97.5th percentile (RDA) to be 105 mgN kg
-1
d
-1
, and 132 mgN ∙ kg
-1
d
-1
respectively (2). This corresponds to 0.65 and 0.83 g
good quality protein kg
-1
d
-1
, or 52 g and 66.4 g per day respectively for an 80 kg
individual.
As protein foods are generally expensive and often associated with saturated
fat, protein RDA guidelines set the minimum level needed to prevent deficiency.
Combining US protein and fat recommendations (average total energy intake of
820 kcal/d) and the average US energy intake of approximately 2100 kcal/d (3), it
is possible to estimate by default the carbohydrate intake current nutrition policy
recommends at 1280 kcal/d (320 g/d), which produces a carbohydrate:protein
intake ratio of > 3.5 (1). Although no minimum RDA has been established for
carbohydrate intake, the minimum daily carbohydrate requirement for tissues,
which are obligate users of glucose for energy, can be determined at approximately
100 to 200 g glucose/d (4), giving a dietary intake ratio of approximately 1.5 for
the minimum metabolic needs for carbohydrate to protein. Thus current nutrition
recommendations suggest a balance of macronutrients with minimum levels of
protein and fat and elevated intake of carbohydrate (1). This is despite evidence that
high carbohydrate diets may increase blood triglycerides (5), reduce fat oxidation
(6), and reduce satiety (7).
Some evidence for an increased protein intake in the Western diet, however,
is the possible reliance on protein as an energy source in the diet of our ancestors
prior to the development of agriculture (8) as verified in the diet of contemporary
hunter-gatherers (9). The main aspect of this proposal is that the phenotypic char-
acteristics of modern humans evolved primarily over a 2 to 3 million year period
during which hunted game made a progressively significant contribution to total
energy intake (10). It has been estimated that the range of dietary protein energy
intake for worldwide-hunter gatherers (19 to 35%) (9) would considerably exceed
the mean intake levels found in Western diets in general (15.5%) (11)
and in the
Australian diet (17.1%) (12).
Issues of Dietary Protein Intake in Humans 131
Modern day athletes or individuals undertaking physical training regimes
are often conscious of increasing their protein intake, a characteristic of athletes
elegantly described by food patterns of those competing in the XI Olympiad in
Berlin (1936), where consumption levels of > 800 g of meat per day were reported
(13). A comprehensive review of protein needs for strength and endurance trained
athletes have been suggested at 1.4 to 1.8 g kg
-1
d
-1
and 1.2 to 1.4 g kg
-1
d
-1
respectively, corresponding to 112 to 144 and 96 to 112 grams protein per day
for
an 80 kg individual respectively (14). Evidence suggests however, that subgroups
such as gym-goers, active people, and bodybuilders have felt that their protein needs
exceed recommended levels, and are consuming in the area of 150 to 400 grams
per day (15-17). High protein diets and popular “fad-diets” that claim to be “high
protein, low carbohydrate,” recommend intakes between 71 to 162 grams of pro-
tein per day (18-20)
also fuel interest in increased consumption of protein. This is
despite the fact that no studies have evaluated the upper limit of amino acid intake
(21), and no formal risk assessment paradigm for intakes of amino acids that are in
significant excess of physiological requirements have been established (22).
This
should be a concern for any health professional advocating a high protein diet.
Protein Metabolism
Advances in understanding protein metabolism have been made in the last few
years with the advent of dual tracer methodology for assessing differences between
exogenous and endogenous amino acid contribution to the protein pool, enhancing
our comprehension of amino acid absorption kinetics. The application of radioactive
and stable isotopes for the measurement of gluconeogenesis using mass isotopomer
distribution analysis (MIDA) have also furthered our understanding the role of
amino acids play postprandialy (23). However, the role of dietary protein and amino
acids in modulating insulin and glucagon secretion are less clear, as is an under-
standing of what fraction of amino acid load contributes to structural/functional
protein needs, oxidation, gluconeogenesis, or a combination of all three.
Although protein digestibility has been established for milk, pea, whey,
casein, and free amino acids derived from enteral protein, less is known about
specific absorption rates of protein-based foods such as meat, chicken, fish, and
legumes. Secondly, there is a dearth of practical data on actual protein absorption
rates measured in g/h or g ∙ h
-1
kg
-1
. The practical implications for understanding
this information is exemplified by a novice bodybuilder who may consume 250
to 400 g of whey protein isolate on a daily basis, in the belief that it will promote
greater skeletal muscle anabolism, a debatable point at best (24, 25); however, a
more important issue is how does the human body deal with these large (> 200 g/d)
amounts of protein?
To develop a better understanding of amino acid kinetics, the initial part of this
article will examine protein metabolism, focusing on the quantification of maximal
protein consumption using available data on maximal rates of urea synthesis, and
amino acid absorption rates and suggest using this data, a possible upper limit
(measured in grams per day) for the rate of amino acid metabolism. The article
will then outline some of the complex interplay of hormonal regulation of insulin
and glucagon by specific amino acids.
132 Bilsborough and Mann
Maximal Rate of Urea Synthesis and Excretion
Amino acid catabolism must occur in a way that does not elevate blood ammonia
(26). Catabolism of amino acids occurs in the liver, which contains the urea cycle
(26), however the rate of conversion of amino acid derived ammonia to urea is
limited. Rudman et al. (27) found that the maximal rate of urea excretion (MRUE)
in healthy individuals was 55 mg urea N ∙ h
-1
∙ kg
-0.75
, which is reached at an intake
level of 0.53 g protein N/kg
-0.75
At higher protein intakes there is no further increase
in urea excretion rate, but a prolongation of the duration of MRUE, often in excess
of 24 h (27).
In a further investigation of the fate of protein nitrogen, Rudman et al. (27)
were able to quantify the temporary accumulation of urea in body water during
MRUE and the amount hydrolyzed in the gastrointestinal tract. Subsequently an
algorithm was developed to estimate the capacity of the liver to deaminate amino
acids and produce urea, termed the maximal rate of urea synthesis (MRUS). In a
study on 10 healthy subjects, the MRUS averaged 65 mg urea N ∙ h
-1
kg
-0.75
(with
a range of 55 to 76). Thus the level of dietary protein that can be deaminated and
processed through to urea by the liver in a 24-h period is dependent on body weight
and individual variation in efficiency of the process, as indicated in Table 1. An
80 kg individual, for instance, could deaminate up to 301 g protein per day, but
may be limited to 221 g protein per day, given the range in MRUS determined by
Rudman et al. (27). However, the safe intake level of protein consumption may
even be slightly higher than these figures, as not all protein is deaminated and
converted to urea. A certain amount of protein as indicated by the RDA is used
directly for structural/functional purposes, including bone and soft tissue growth,
maintenance and repair plus production of hormones, antibodies, and enzymes,
thus not requiring deamination.
The US recommended dietary
allowance (RDA) of 0.8 g kg
-1
d
-1
(28), set
this level of necessary protein intake for structural requirements to cover the needs
of 97.5% of the population. Adding this protein requirement (64 g/d for an 80 kg
individual) to the level of protein that can be converted to urea, yields a theoretical
maximal daily protein intake based on body weight and efficiency of urea synthesis
in individuals. An 80 kg individual, for example, could theoretically tolerate 325 g
protein per day (range 285 to 365 g) without showing symptoms of hyperammo-
nemia and hyperaminoacidemia. Such levels are certainly not advocated by the
authors and no practical rationale exists for such elevated protein intakes. In fact,
common sense would even dictate that we accept the lower end of the range as the
maximum safe intake levels, to allow for individuals with reduced MRUS. Hence,
for an 80 kg individual, 285 g protein per day should be viewed as an absolute
maximum. Even this amount would be equivalent to the consumption of approxi-
mately 1 kg of lean meat per day. A more realistic intake of approximately half
this amount would contribute approximately 60 g protein to structural needs and
a further approximately 80 g to bodily energy needs, either directly, through glu-
coneogenesis or as stored fat. The advantage being that this protein could displace
fat or carbohydrate from the diet, increase satiety (plus yield less energy due to its
higher rate of thermogenesis) thus helping in weight control, a controversial but
promising area of research and will be discussed later. It may be prudent to point
out, however, that the given range of MRUS determined by Rudman et al. (27),
Issues of Dietary Protein Intake in Humans 133
had significant limitations, as it consisted of a small sample size (10 normal and 34
cirrhotic subjects), excluded individual differences according to age, sex, previous
diet history, training status, and was undertaken more than 30 y ago.
The dangers of excessive protein intake should not be underestimated and
have been recognized historically through the excess consumption of lean wild
meat by early American explorers leading to a condition referred to as “rabbit
starvation syndrome,in which symptoms included nausea and diarrhea followed
by death within 2 to 3 wk (29). This syndrome was explained as the inability of
the human liver to sufficiently upregulate urea synthesis to meet “large” loads of
protein (29). Some studies have shown animals can adapt to a high protein diet
by upregulating amino acid metabolizing enzymes such as alanine and aspartate
aminotransferases, glutamate dehydrogenase, and argininosuccinate synthetase
(30), and increase mitochondrial glutamine hydrolysis in hepatocytes (31). Other
studies, however, show that when animals are faced with large protein loads, the
rate of gastric emptying is reduced as the catabolic and anabolic systems of the
body become saturated, unable to deal with an excess of dietary nitrogen under
acute conditions (32).
This reduction in rate of gastric emptying subsequent to an
elevated dietary protein intake suggests the presence of regulation at the gastric
step to ensure the catabolic capacities of the liver are not exceeded (33). This
negative feedback on stomach emptying rate and food intake could be affiliated
with chemical, biochemical, and/or physical signals translated by the vagus
nerve (34, 35). To what degree do these processes transpire in humans, and at
what threshold intake of protein is currently unknown as very little data have
been collected on humans consuming high protein diets for prolonged periods of
time. The one well known case is that of the early 20th century Arctic explorer
Vilhjalmur Stefansson, who after many years living with the Arctic Inuit and
consuming a diet estimated to be approximately 50% energy as protein, returned
to civilization and conducted a year-long experiment on himself at Bellevue
Hospital in New York. During this time, Stefansson, a fit 72.5 kg man, consumed
meat only, with a variable protein:fat ratio. During the first 3 d he became ill
with the symptoms of “rabbit starvation” at a protein intake of 264 g/d, which
was 45.3% of his energy intake (36). As the protein level was lowered slightly
and replaced with extra fat, however, on the fourth and fifth days symptoms
disappeared. This level of protein intake may have been sustainable if hepatic
enzymes were given time to upregulate (as there were several years between
Stefansson living with the Inuit and the experiment at Bellevue Hospital and any
previous upregulation of hepatic enzymes would have diminished), but the result
for this limited study (where n = 1) indicates that the values shown in Table 1 are
at least realistic, although we would speculate that individuals would tend to be
at the lower end of the range for MRUS without a lead-in time for upregulating
hepatic enzyme function.
Protein Absorption Rates in Humans
Another critical aspect of protein metabolism involves the extent and rate of intesti-
nal absorption of dietary protein. A limited number of protein studies investigating
absorption rates of amino acid from specific protein sources such as casein, whey,
milk, pea, egg, soy, and meat have been conducted. The metabolism of dietary
134 Bilsborough and Mann
Table 1 Range of Daily Protein Intakes Based on Body Weight
and the Algorithm for Maximal Rate of Urea Synthesis (MRUS)
Developed by Rudman et al. (27) and Allowing for Protein
Requirements Set by the RDA Where Deamination is Not Occurring
MRUS Body weight (kg)
mg N ∙ h
-1
∙ kg ∙
0.75
10 20 30 40 50 60 70 80 90 100 110
Daily protein maximal intakes based on MRUS (g)
55 46 78 106 131 155 178 200 221 241 261 280 lower
60 51 85 115 143 169 194 218 241 263 285 306
65 55 92 125 155 183 210 236 261 285 308 331 mean
70 59 99 135 167 197 226 254 281 307 332 357
75 63 106 144 179 212 243 272 301 329 356 382 upper
Daily protein intake based on RDA for structural use (g)
8 16 24 32 40 48 56 64 72 80 88
Maximum daily protein intake levels (g)
55 54 94 130 163 195 226 256 285 313 341 368 lower
60 59 101 139 175 209 242 274 305 335 365 394
65 63 108 149 187 223 258 292 325 357 388 419 mean
70 67 115 159 199 237 274 310 345 379 412 445
75 71 122 168 211 252 291 328 365 401 436 470 upper
protein and amino acids is influenced by the composition of the specific protein,
meal composition, timing of ingestion, and the amount or dose of the protein or
amino acids ingested (37). The speed of absorption by the gut of amino acids
derived from dietary proteins can also modulate whole body protein synthesis,
breakdown, and oxidation (38, 39). Quantifying specific absorption rates of dietary
amino acids from the gut in humans at a variety of doses is difficult due to the lack
of specific data. A comprehensive analysis of existing data is difficult as many of
the studies that provide sound methodology to study actual amino acid kinetics do
not employ sizeable doses of amino acids and further, fail to provide data on the
body mass of the subjects used. Interpreting results yields a crude but sufficient
starting point for describing amino acid absorption from the gut, in a g/h absorp-
tion rate, rather than a more accurate g ∙ h
-1
∙ kg
-1
measure.
Milk Proteins
Using [
15
N]-labeling dietary protein methodology, 25 subjects (with mean BMI of
22.4 ± 2.5 kg/m
2
) swallowed an ileal tube and ingested 30 g of [
15
N]-milk protein
(P) alone (295 mmol N), or supplemented with either milk fat (PF) (43 g of milk
fat from 36 g butter and 46 g cream) or 100 g of sucrose (PS). In the 8-h period
Issues of Dietary Protein Intake in Humans 135
after meal ingestion, the amount of dietary nitrogen recovered in the ileum via
blood sampling in the forearm vein was 279.6 ± 1.3 mmol in the (P) group, 279.2
± 1.2 mmol in (PS), and 278.1 ± 2.4 mmol in the (PF) group. This shows the true
digestibility of exogenous milk protein nitrogen to be of the order of 94.6% with
an average rate of protein absorption of 3.5 g/h (40).
Pea Protein
The gastrointestinal absorption of pea protein of 7 adults (4 males and 3 females
with mean mass of 64 kg, ranging from 46 to 77 kg) was determined by ingesting
21.45 g (195 mmol N) of [
15
N]-labeled pea protein. Total absorption was estimated
at 89.4 ± 1.1%, resulting in 19.2 g being absorbed in the 8-h postprandial period
at a rate of 2.4 g/h (41). Another study investigated the ingestion of 30 g of raw
purified pea protein either as [
15
N]-globulins, (G meal) (301 mmol N) or as a mix
of [
15
N]-globulins and [
15
N]-albumins, (GA meal) (22 g of pea globulins and 8 g
of pea albumins, 299 mmol N). The ileal digestibility was 94.0 ± 2.5% and 89.9
± 4.0% for the G and GA meals respectively yielding amino acid absorption rates
of approximately 3.5 g/h and 3.4 g/h (42).
Egg Protein
The absorption of 25 g of
13
C-,
15
N-, and
2
H-labeled egg protein, both cooked (C)
and raw (R) were evaluated. Measurements of mean
13
CO
2
exhalation rate in breath
after the ingestion continued for 6 h. The cumulative amount of administered dose
of
13
C recovered in breath over the 6-h period was 17.23 ± 0.69 g (68.92%) for (C)
and 8.20 ± 0.94 g (32.8%) for (R), giving an estimated absorption rate of 2.9 g/h
and 1.4 g/h respectively for cooked and raw egg proteins (43).
Soy Protein Isolate (SPI)
Soy protein is believed to have a high nutritional quality for humans (44). The
absorption rates of 30 g [316 mmol N) of [
15
N]- soy protein isolate (SPI)] mixed
with 100 g of sucrose and water were analyzed in subjects who had a mean body
mass of 65 ± 9 kg (45). The overall true oro-ileal digestibility of SPI was 90.9 ±
2.2%, at an absorption rate of 3.9 g/h, which is consistent with other studies of
SPI absorption (46).
Tenderloin Pork Steak
Amino acid absorption from pork steak was determined crudely by comparison
with intravenous infusions of varying amounts of mixed amino acid solution (47).
A mixed amino acid solution (MAA) was designed to mimic that of the amino
acid profile of a 200 g portion of tenderloin pork steak meal (PS), containing 36 g
of protein and 20 g fat. The postprandial plasma amino acid profile of the subjects
consuming the PS was measured and compared with the postprandial plasma amino
acid profile of the intravenous infusions of the MAA solutions, which were infused
at 6, 10, and 14 g/h on a separate day. The closest matching infusion rate of amino
acids, which matched the amino acid pattern of the pork steak was 10 g/h (r = 0.89,
P < 0.001). If pork protein is absorbed at 10 g/h then 36 g would be absorbed in
136 Bilsborough and Mann
3.6 h. Interpretations of these findings however are difficult, as the study does not
incorporate dual tracer methodology, allowing discrimination between endogenous
and exogenous amino acid rate appearances.
Casein and Whey Protein
Absorption rates of “fast” and “slow” dietary proteins, whey (WP), and casein
(CAS) respectively, provide an interesting contrast in protein absorption kinetics.
In a study by Boirie et al. (38), subjects were fed 30 g (336 mmol N) of labeled
whey protein (
13
C-WP), or 43 g (479 mmol N) of labeled casein protein (
13
C-CAS),
with the same amount of dietary leucine (380 µmol/kg), where postprandial leucine
balance is used as an index of protein deposition (39, 48). The rapid absorption of
WP in the first 3 to 4 h accounted for the vast majority of amino acid absorption in
the order of 8 to10 g/h and ~ 6.1 g/h for CAS. A second study involved the repeated
consumption of 2.3 g of whey protein every 20 min (RPT-WP), (a rate of ~ 7g/h),
to mimic slowly absorbed amino acids. This was compared to a 30 g protein meal
of amino acids (AA). Estimated absorption rates were ~ 8 g/h and 6 g/h for AA
and RPT-WP, respectively (39).
Maximum Absorption Rates of Amino Acids
Absorption rates of amino acids estimated in this review (summarized in
Table 2) are crude, yet serve as sufficient approximates given the absence of
direct data pertaining specifically to amino acid absorption (i.e., grams per hour
per kilogram of body weight). The absorption rate (measured as g/h), of free
amino acids (AA), casein isolate (CAS), and whey protein isolate (WP) were
greater than that of raw and
cooked egg white, pea flour,
and slightly greater than milk
protein. Free amino acids with
the same amino acid profile
as casein protein elicits a fast
transient peak of plasma amino
acids, while casein releases
amino acids slowly over many
hours after consumption. This
is consistent with other stud-
ies that show free amino acid
mixtures induce a more rapid
absorption than intact proteins
(49, 50). The two milk pro-
tein fractions, micellar casein
and the soluble whey protein
have been synonymous with
the concept of slow,” and
“fast” digestibility of protein.
A detailed discussion of these
two milk protein fractions is
Table 2 Approximations of Amino
Acid Absorption from Different
Protein Sources
Protein source
Absorption
rate (g/h) Reference
Egg protein raw 1.3 43
Pea flour 2.4 41
Egg protein cooked 2.8 43
Pea flour: globulins
& albumins
3.4 42
Milk protein 3.5 40
Soy protein isolate 3.9 46
Free AA 4.3 39
Casein isolate 6.1 38
Free AA (same
profile as casein)
7-7.5 39
Whey isolate 8-10 38
Issues of Dietary Protein Intake in Humans 137
beyond the scope of this article and provided elsewhere (51). It is however worth
mentioning that WP is soluble, allowing faster gastric emptying, whereas casein
clots in the stomach delaying gastric emptying, resulting in a slower release of
amino acids (52).
An important question then must be posed: “Does a more rapidly absorbable
protein result in greater in vivo protein synthesis?” This is a central issue of large
protein consumption with fitness enthusiasts, athletes, and bodybuilders.
Early findings suggest that rapidly absorbed proteins such as free amino acids
and WP, transiently and moderately inhibit protein breakdown (39, 53), yet stimu-
late protein synthesis by 68% [using nonoxidative leucine disposal (NOLD) as an
index of protein synthesis] (54). Casein protein has been shown to inhibit protein
breakdown by 30% for a 7-h postprandial period, and only slightly increase pro-
tein synthesis (38, 54). Rapidly absorbed amino acids despite stimulating greater
protein synthesis, also stimulate greater amino acid oxidation, and hence results
in a lower net protein gain, than slowly absorbed protein (54). Leucine balance,
a measurable endpoint for protein balance, is indicated in Figure 1, which shows
slowly absorbed amino acids (~ 6 to 7 g/h), such as CAS and 2.3 g of WP repeat-
edly taken orally every 20 min (RPT-WP), provide significantly better protein
balance than rapidly absorbed amino acids (39, 54).
Figure 1—Leucine balance (a measurable endpoint for protein balance) as determined
from rapidly absorbed protein; amino acids (AA) and whey protein (WP), compared to
slowly digestible proteins; casein (CAS), and small doses of whey protein (RPT-WP 6.9 g/h)
(adapted from 39). The misconception in the fitness and sports industries is that rapidly
absorbed protein, such as WP and AA promote better protein anabolism. As the graph shows,
slowly absorbed protein such as CAS and small amounts of WP (RPT-WP) provide four
and nine times more protein synthesis than WP.
LEUCINE BALANCE(umo l.kg -1)
1 0
3 9
9 0
- 1 2 . 5
- 2 0 0 2 0 4 0 6 0 8 0 1 0 0
A A
W P
C A S
R P T - W P
L E U C I N E B A L A N C E ( u m o l /k g )
138 Bilsborough and Mann
This “slow” and “fast” protein concept provides some clearer evidence that
although human physiology may allow for rapid and increased absorption rate of
amino acids, as in the case of WP (8 to 10 g/h), this fast absorption is not strongly
correlated with a “maximal protein balance,as incorrectly interpreted by fitness
enthusiasts, athletes, and bodybuilders. Using the findings of amino acid absorption
rates shown in Table 2 (using leucine balance as a measurable endpoint for protein
balance), a maximal amino acid intake measured by the inhibition of proteolysis
and increase in postprandial protein gain, may only be ~ 6 to 7 g/h (as described
by RPT-WP, and casein) (38), which corresponds to a maximal protein intake of
144 to 168 g/d.
The rate of amino acid absorption from protein is quite slow (~ 5 to 8 g/h,
from Table 2) when compared to that of other macronutrients, with fatty acids at
~ 0.175 g kg
-1
h
-1
(~ 14 g/h) (55) and glucose 60 to 100 g/h (0.8 to 1.2 g car-
bohydrate kg
-1
h
-1
) for an 80 kg individual (56). From our earlier calculations
elucidating the maximal amounts of protein intake from MRUS, an 80 kg subject
could theoretically tolerate up to 301 to 365 g of protein per day, but this would
require an absorption rate of 12.5 to 15 g/h, an unlikely level given the results of
the studies reported above. However, some support for this level of absorption of
amino acids is found when amino acids are infused intravenously at 50, 100, 150
and 250 mg kg
-1
h
-1
(57). This protocol investigated the relationship between
the rate of infusion of amino acids and the muscle protein synthetic rate, which
peaked at 150 mg ∙ kg
-1
h
-1
, corresponding to an absorption rate of 12 g/h for an
80 kg individual (57).
Amino Acid Regulation of Endocrine Hormones
Protein meals with their associated amino acid loads are known to stimulate the
release of the pancreatic hormones glucagon and insulin into the circulatory system
(47, 58).
Glucagon
Studies evaluating the response of glucagon to real foods have shown that a 200 g
pork steak containing 36 g of protein stimulated a glucagon release, raising plasma
levels from 180 ± 24 to 960 ± 115 ng/L after 120 min (47). Following binding
to hepatic receptors, glucagon stimulates the enzyme adenylate cyclase on the
membranes inner surface which catalyses the production of cyclic AMP (cAMP)
(59), which in turn sets off a cascade of reactions resulting in the breakdown of
glycogen to glucose (59). The major purpose of this aminogenic glucagon release
is to stimulate hepatic glucose release in a bid to avert hypoglycemia resulting from
the concomitant secretion of insulin (60).
The level of glucagon release depends on the ratio of protein:carbohydrate
content of a meal (61), (resulting in stimulation when the ratio is high, and suppres-
sion when the ratio is low) and the predominance of specific amino acids in a meal.
Predominately glucagon-stimulating amino acids are serine, aspartate, glycine,
asparagines, and phenylalanine (47). In one of the long-term studies (6 months)
of elevated protein intakes, using whole food, subjects consuming 1.87 ± 0.26 g ∙
Issues of Dietary Protein Intake in Humans 139
kg
-1
d
-1
of dietary protein, had a fasting plasma glucagon 34% higher than subjects
consuming 0.74 ± 0.08 g ∙ kg
-1
d
-1
(62). Although not fully understood, glucagon
is also involved in the disposal of amino acids after protein ingestion (63), par-
ticularly the increased hepatic uptake of glucongenic amino acids presumably for
gluconeogenesis (60).
Insulin
The role of insulin in amino acid kinetics has not been fully elucidated and has
been described as “the puzzling role of insulin” (64). It has been reported in the
scientific literature however for well over 30 y that ingestion of carbohydrate-free
protein meals such as beef and casein can promote a prompt and substantial rise
in plasma insulin (65). In a study by Linn et al. (62) subjects fed a relatively high
protein diet of 1.87 ± 0.26 g kg
-1
d
-1
over a 6-month period, consistently had
elevated plasma insulin levels 8 h after the last protein meal.
In a study by Calbert et al. (24) pea protein hydrolysate (PPH), milk protein
solution (MP), and whey protein hydrolysates (WP) were co-ingested with 15 g of
glucose and compared to the hormonal pattern of 15 g of glucose solution alone.
Despite similar glucose contents, peak insulin concentrations (occurring at the
20th minute) were two and four times higher after ingestion of both PPH and WP
than after MP and glucose solutions respectively (24).
Similar results supporting
the insulinotropic properties of amino acids when added to carbohydrate have been
obtained when comparing milk solutions with milk and sucrose together (40), while
others have observed increased plasma insulin by as much as 100% above basal
when using various combinations of insulinotrophic amino acids (56, 66-68).
Recently an insulin index of foods has been established which unexpectedly
demonstrates that 1000 kJ of fish protein (~ 60 g) elicits a greater peak insulin level
than 1000 kJ of white pasta (~ 60 g) (69). As previously mentioned in this review,
amino acids, through stimulation of glucagon, release hepatic glucose. The hepatic
glucose to insulin ratio of common foods, as shown in Figure 2, indicates either a
significant insulin response to relatively small hepatic glucose release for meat and
fish, (69)
or a direct stimulatory effect of some amino acids on insulin release. The
amino acids from beef augment an insulin response 1583 times that of its simultane-
ous hepatic glucose release via glucagon. Amino acids derived from fish result in a
surge of insulin 775 times the magnitude of glucose stimulated release (69).
Not all studies however show the same large stimulatory effects of insulin
by amino acids (40). It appears that before any elevation in plasma insulin can be
detected, the plasma concentrations of amino acids must attain an as yet unidentified
threshold level (24). For example, repeated doses of rapidly absorbed whey protein
administered orally at 2.3 g every 20 min (6.9 g/h), stimulated mild hyperaminoaci-
demia, with no detectable rise in plasma insulin, while WP administered as a 30 g
doses resulted in moderate increases in plasma insulin concentrations (39). Other
factors also affect the degree of insulin release and need to be considered such as
the amino acid make up of the ingested protein. Arginine, lysine, phenylalanine,
ornithine, alanine, leucine, isoleucine, stimulate insulin, (56, 66)
while the quantity
of branched chain amino acid content in a meal, which are metabolized in muscle,
also warrants consideration (70).
140 Bilsborough and Mann
Although the study of the glucose/insulin relationship has been widely inves-
tigated, little data exists on the relationship between amino acids and insulin, and
its relevance to the etiology of diabetes, disease, and health.
The Fate of Postprandial Amino Acids
Gluconeogenesis
The major fate of dietary amino acids in the Western diet appears to be gluco-
neogenesis (26, 71)
and has been recently estimated to account for up to 60% of
endogenous glucose production (23), while others estimate 47 to 60% (72-74). In
one study a relatively high protein diet, (1.87 ± 0.26 g kg
-1
d
-1
), was shown to
elevate gluconeogenesis by 40% (62). Thus gluconeogenesis should be viewed as
a normal prandial process, not one limited to fasting periods (71), the alternative
being the diversion of amino acid carbon to triglyceride production, a process which
likely outcompetes gluconeogenesis only when carbohydrate intake is high (75).
Amino acids make up the major source of fuel for the liver and their oxidative
conversion to glucose makes up approximately half of the daily oxygen consump-
tion of the liver (71). The advantage of oxidizing most amino acids in the liver to
glucose is that only the liver need expend the energy needed to synthesize the entire
complex array of enzymes involved in amino acid oxidation. In this way all parts
of the body can use energy derived from protein without the need for amino acid
catabolizing enzymes (71). Complete oxidation of amino acids to CO
2
by the liver
A M O U N T S O F I N S U L I N C O M P A R E D T O G L U C O S E P R O D U C E D B Y
P R O T E I N F O O D S
1 3 5
1 5 8 3
3 0 7
7 7 5
0 2 0 0 4 0 0 6 0 0 8 0 0 1 0 0 0 1 2 0 0 1 4 0 0 1 6 0 0 1 8 0 0
E g g s
C h e e s e
B e e f
L e n t i l s
F i s h
B a k e d b e a n s
I N S U L I N /G L U C O S E
Figure 2—Insulin to glucose stimulated by protein based foods [adapted from (69)].
Issues of Dietary Protein Intake in Humans 141
does not occur as the ATP produced would be far more than the liver could use and
the oxygen consumption greater than that available. Hepatic O
2
consumption has
been estimated at 3000 mmoles/d (76).
An intake of 110 g of animal protein per
day contains ~ 1000 mmoles of amino acids, of which 10% is metabolized in extra-
hepatic tissues, resulting in ~ 900 mmoles to be dealt with by the liver on a daily
basis. To completely metabolize 900 mmoles of amino acid (~ 100 g of protein) to
CO
2
the liver requires 3700 mmoles of oxygen, which accordingly is a physiological
impossibility as the liver has to metabolize numerous other substances. However
only 1420 mmoles of oxygen are needed to convert this amount of amino acids to
glucose (70, 71), which can then be circulated for use in other body cells.
If diets relatively high in protein are to be tolerated it is likely that an evolu-
tionary mechanism exists to metabolize some amino acids in peripheral tissues.
Branched chain amino acids (BCAA) such as leucine, valine, and isoleucine, which
yield high levels of ATP relative to their yield of glucose, are excellent candidates
for this and are known to be oxidized in muscle tissue (71).
Degradation of BCAA
in muscle tissue is linked to the production of alanine and glutamine and the main-
tenance of glucose homeostasis (77). It has also been suggested that the glucose-
alanine cycle accounts for > 40% of endogenous glucose production during exercise
(77). Interestingly, as pointed out by Layman et al. (1), increased concentrations of
leucine have the potential to stimulate muscle synthesis during catabolic conditions
associated with food restriction (78) or exhaustive exercise (79).
Anaplerosis, Cataplerosis, and Amino Acid
Metabolism in the Athlete
The consumption of large amounts of protein by athletes and bodybuilders is not
a new practice (13). Recent evidence suggests that increased protein intakes for
endurance and strength-trained athletes can increase strength and recovery from
exercise (14, 80, 81). In healthy adult men consuming small frequent meals pro-
viding protein at 2.5 g kg
-1
d
-1
, there was a decreased protein breakdown, and
increased protein synthesis of up to 63%, compared with intakes of 1g ∙ kg
-1
d
-1
(16). Subjects receiving 1g kg
-1
d
-1
underwent muscle protein breakdown with
less evident changes in muscle protein synthesis. Some evidence suggests, however,
that a high protein diet increases leucine oxidation (82, 83), while other data dem-
onstrate that the slower digestion rate of protein (38, 54), and the timing of protein
ingestion (with resistance training) (84) promote muscle protein synthesis.
One important role of dietary carbohydrate (through pyruvate) is in anaple-
rosis, the replenishing of Krebs cycle intermediates, (or tricarboxylic acid cycle
intermediates—TCAI). The primary role of this cycle is to generate reduced forms
of the enzymes NADH and FADH
2
, transferring high energy electrons to the mito-
chondrial electron transport chain for use in the resynthesis of ATP (85). Five of
the intermediates of Krebs cycle are involved in additional reactions which involve
amino acids and will be limited if insufficient carbohydrate is available. Oxalo-
acetate and α-ketoglutarate are used in the synthesis of several amino acids such
as phosphoenolpyruvate. Heme synthesis uses succinyl CoA, glutamine synthesis
draws upon α-ketoglutarate, and citrate is the source of acetyl-CoA in the cystol
and is used for the synthesis of lipids and amino acids (59, 70). Adequate dietary
142 Bilsborough and Mann
carbohydrate during exercise is thus critical, because its availability is inversely
related to the rate of exercise protein catabolism (86), hence adequate carbohydrate
can prevent cataplerosis, the reverse of anaplerosis, which takes place in the absence
of sufficient pyruvate (from carbohydrate). Gluconeogenesis can be considered
cataplerotic and can result in a “drain” of Krebs cycle intermediates (70), which
may result in a decreased production of ATP, and an increased muscle protein
breakdown. There may be a critical minimum intake of carbohydrate to provide a
sufficient flux of pyruvate to maintain anaplerosis (87), and prevent muscle protein
breakdown via gluconeogenesis.
This has practical significance to fitness enthusiasts, athletes, and bodybuild-
ers where 150 to 400 g of protein can be consumed per day (15-17), especially if
consumed at the expense of sufficient carbohydrate. In elite athletes it has been
clearly established that low glycogen availability for exercising skeletal muscles
leads to fatigue more rapidly in prolonged exercise (88, 89). Other studies show
the time until the onset of fatigue during high-intensity exercise in untrained indi-
viduals consuming diets deficient in carbohydrate is shortened (90-93), however
similar results are not found in trained individuals (94). In high-intensity resistance
training, fatigue may also be associated with carbohydrate depletion (95).
While
high protein diets have focused on protein and its value in building lean muscle
and preventing protein breakdown, it is vitally important for athletes to understand
that high protein consumption at the expense of sufficient amounts of carbohydrate
can be potentially detrimental to lean muscle.
Dietary Advantages of Increased Protein Intake
As protein has a greater thermic effect than either fat or carbohydrate (96, 97) and
a greater satiety value than fat or carbohydrate (98) there is strong circumstantial
evidence for increased dietary protein as an effective weight loss strategy (99).
Some clinical trials have shown that energy restricted elevated protein diets are
more effective than high carbohydrate energy restricted diets for weight loss in
overweight subjects (100, 101). Recently, low energy, isoenergetic diets (7100 kJ)
containing either 1.6 g ∙ kg
-1
∙ d
-1
protein, carbohydrate < 40% of energy (HP), or
0.8 g kg
-1
d
-1
protein and carbohydrates > 55% of energy (HC), yielded significant
weight loss of 7.53 ± 1.44 kg and 6.96 ± 1.36 kg, respectively. The protein group
however, lost more body fat and less lean body mass than the carbohydrate group
(102). Suggestions made by Layman et al. (102) for these changes were 1) the lower
energy efficiency of the protein diet, 2) lower insulin response with reduced carbo-
hydrate, and 3) muscle protein sparing effect, of the protein or leucine specifically.
Another study investigating the protein to carbohydrate ratio on body composition
analyzed a high protein diet (HP) consisting of 27% protein, 44% carbohydrate,
29% fat as energy, and a standard protein diet (SP) consisting of 16% protein, 57%
carbohydrate, 27% fat (103). Although weight loss (7.9 ± 0.5 kg) and total fat loss
(6.9 ± 0.4 kg) did not differ between diet groups, total lean mass was significantly
better preserved with the HP diet in women. Further, when a high protein diet (HP)
consisting of 28% protein, 42% carbohydrate, 28% fat as energy was compared to
a low protein diet (LP) 16% protein, 55% carbohydrate, 26% fat, overall weight
loss was 5.2 ± 1.8 kg independent of diet composition (104). Women on the HP
Issues of Dietary Protein Intake in Humans 143
diet, however, lost significantly more total (5.3 vs. 2.8 kg) and abdominal (1.3 vs.
0.7 kg) fat compared to woman on the LP diet. Collectively this data describes
how elevating dietary protein intake may have a positive effect on preserving lean
muscle, while lowering body fat content.
Defining Protein Intake
A confusing point in discussing dietary protein intake is the manner in which it is
defined. What seems to be a high protein intake by one definition can appear quite
moderate when represented in an alternative manner. There are three principal
ways in which protein intake can be quoted: 1) as the absolute amount consumed
in grams per day, 2) as a percentage contribution to daily energy intake based
on its energy content of 17 kJ/g, and 3) as the amount consumed per kilogram
of body weight per day (Table 3). An individual consuming a diet containing
35% energy as protein appears to be consuming a dangerously excessive level of
protein. However, if total dietary energy intake is 8000 kJ/d, this equates to 165
g protein per day. For an 80 kg person this would be equivalent to (2.1 g kg
-1
d
-1
), well below the maximal level. Even for a 60 kg individual (2.7 g kg
-1
d
-1
)
it is below the maximal safe level. Care should be taken however at this level of
protein intake as other nutrient-rich foods may be displaced from the diet, leading
to micronutrient deficiencies. Any such diet with an elevated protein intake, should
also contain a wide range of whole grain cereals, fresh vegetables, and fruits, rich in
micronutrients and potassium alkali salts needed to reduce the potential renal acid
load and subsequent urinary calcium loss, that can occur due to the acidic nature
of protein-rich diets. A more manageable and practical approach, which may still
provide beneficial outcomes is a 25% protein energy diet, which would provide
118 g protein on an 8000 kJ/d diet at 1.5 g ∙ kg
-1
∙ d
-1
for an 80 kg individual. This
is clearly distinguishable from modern day popular purported “high protein diets,
that are actually low in carbohydrate (25 to 90 g/d) and contain large amounts of
total fat (50 to 60%), and saturated animal fat (30 to 50 g/d) (105, 106). These
fad diets should not be mistakenly compared with the recommendations of this
article, nor to the studies cited in this article which are neither high in fat nor low
in carbohydrate (100-104), especially in light of recent minimum carbohydrate
recommendations of 130 g/d (107).
Numerous studies have also shown improvements in blood lipid profiles on
diets with increased protein intakes. O’Dea et al. (108) showed a marked improve-
ment in carbohydrate and lipid metabolism in diabetic Australian Aborigines after
temporary reversion to a traditional hunter-gather lifestyle, where energy derived
from protein reached 54% (109). As the energy intake was relatively low (5040 kJ)
the estimated daily protein intake in absolute terms was only 154 g/d (99) which
equates to approximately 1.9 g kg
-1
d
-1
for an 80 kg individual. Other studies
have shown that isoenergetic substitution of protein for carbohydrate can reduce
total, LDL, and VLDL cholesterol and triacyclglycerides while increasing HDL
cholesterol (5, 110).
Improvements in insulin sensitivity and maintenance of muscle mass have also
been shown in obese women on hypo-energetic, elevated protein diets compared
with hypo-energetic high carbohydrate diets (111). Recent epidemiological evidence
144 Bilsborough and Mann
Table 3 Comparison of the Three Methods of Reporting Protein
Consumption Levels, Absolute Amount in Grams/Day, Relative
Amount As Percentage of Total Energy Consumed, and As the Daily
Quantity Relative to Body Weight (g ∙ kg
-1
∙ d
-1
)
Daily energy
intake
(kJ/d)
% Energy
as
protein
Protein
intake
(g/d)
Body weight (kg)
40 50 60 70 80 90 100 110
Protein intake (g ∙ kg
-1
∙ d
-1
)
6000 15 53 1.3 1.1 0.9 0.8 0.7 0.6 0.5 0.5
25 88 2.2 1.8 1.5 1.3 1.1 1.0 0.9 0.8
35 124 3.1 2.5 2.1 1.8 1.5 1.4 1.2 1.1
8000 15 71 1.8 1.4 1.2 1.0 0.9 0.8 0.7 0.6
25 118 2.9 2.4 2.0 1.7 1.5 1.3 1.2 1.1
35 165 4.1 3.3 2.7 2.4 2.1 1.8 1.6 1.5
10,000 15 88 2.2 1.8 1.5 1.3 1.1 1.0 0.9 0.8
25 147 3.7 2.9 2.5 2.1 1.8 1.6 1.5 1.3
35 206 5.1 4.1 3.4 2.9 2.6 2.3 2.1 1.9
12,000 15 106 2.6 2.1 1.8 1.5 1.3 1.2 1.1 1.0
25 176 4.4 3.5 2.9 2.5 2.2 2.0 1.8 1.6
35 247 6.2 4.9 4.1 3.5 3.1 2.7 2.5 2.2
14,000 15 124 3.1 2.5 2.1 1.8 1.5 1.4 1.2 1.1
25 206 5.1 4.1 3.4 2.9 2.6 2.3 2.1 1.9
35 288 7.2 5.8 4.8 4.1 3.6 3.2 2.9 2.6
also shows an inverse correlation between protein intake and cardiovascular disease
(CVD) in a cohort of 80,082 women (112).
Dietary animal protein intake has been
shown to be associated with lower plasma levels of the CVD risk factor, homocys-
teine (113), possibly through concomitant vitamin B-12 intake. Increased protein
intake has also been associated with lower blood pressure in numerous population
studies (114). A recent Japanese population study has also shown an inverse rela-
tionship between the level of protein consumption and stroke mortality (115).
The role of increased protein intake in the development and progression of renal
dysfunction is a hotly debated issue. Numerous case studies show a clear increase
in the rate of progression in renal dysfunction with increased protein ingestion.
Certainly in cases of impaired renal function, reduced levels of protein intake can
slow the progression to renal failure, however there is no link between increased
protein intake (1.2 to 2.0 g ∙ kg
-1
∙ d
-1
) and development of renal insufficiency (17,
116), and renal clearance is still highly efficient at protein intakes of up to 3.0 g
kg
-1
d
-1
(27). A recent clinical trial, for instance, has also shown that a diet with an
elevated protein intake (26% of energy) has no adverse effects upon renal function
in subjects with no pre-existing kidney disease (100).
Issues of Dietary Protein Intake in Humans 145
Summary and Recommendations
Absorption rates of amino acids from the gut can vary from 1.4 g/h for raw egg
white to 8 to 10 g/h for whey protein isolate. Slowly absorbed amino acids such
as casein (~ 6 g/h) and repeated small doses of whey protein (2.9 g per 20 min,
totaling ~ 7 g/h) promote leucine balance, a marker of protein balance, superior to
that of a single dose of 30 g of whey protein or free amino acids which are both
rapidly absorbed (8 to 10 g/h), and enhance amino acid oxidation. This gives us
an initial understanding that although higher protein intakes are physiologically
possible, and tolerable by the human body, they may not be functionally optimal
in terms of building and preserving body protein. The general, although incorrect
consensus among athletes and bodybuilders, is that rapid protein absorption corre-
sponds to greater muscle building. Less is understood about protein and amino acid
absorption from real whole foods, such as meat, chicken, fish, and vegetable-based
proteins. Future studies should focus in this area as the majority of the population
consume whole foods distinct from hydrolyzed proteins. It should be noted here,
however, that the study of maximal rates of urea synthesis conducted by Rudman
et al. (27) although comprehensive, were carried out on a limited sample size over
30 y ago, and future studies need to be carried out to safely verify these early
findings. From the limited data available on amino acid absorption rates, and the
physiological parameters of urea synthesis, the maximal safe protein intakes for
humans have been estimated at ~ 285 g/d for an 80 kg male. It is not the intention
of this article, however, to promote the consumption of large amounts of protein,
but rather to prompt an investigation into what are the parameters of human amino
acid kinetics. In the face of the rising tide of obesity in the Western world where
energy consumption overrides energy expenditure, a more prudent and practical
approach, which may still provide favorable outcomes, is a 25% protein energy
diet, which would provide 118 g protein on an 8000 kJ/d diet at 1.5 g ∙ kg
-1
∙ d
-1
for
an 80 kg individual (Table 2).
In terms of people who participate in physical activity, retaining and building
muscle is a primary goal. Diminished reserves of TCAI through restricted carbo-
hydrate intake could potentially bring about an early onset of fatigue, decrease
exercise performance, and promote muscle catabolism. As protein absorption of
real foods is approximately 1 to 4 g/h, and fat is absorbed at approximately 14 to
18 g/h, the need for adequate glucose to prevent muscle gluconeogenesis and hence
preserve lean muscle is important and further supports the need for a minimum
carbohydrate intake, especially for active people. A carbohydrate intake of 120 to
150 g/d could be sufficient with active people consuming > 150 g/d from a large
variety of cereals, whole grains, fresh fruit, and vegetables. Little data exists on the
comprehensive metabolic effects of large amounts of dietary protein in the order of
300 to 400 g/d. Intakes of this magnitude would result in some degree of prolonged
hyperaminoacidemia, hyperammonemia, hyperinsulinemia, and hyperglucagone-
mia, and some conversion to fat, but the metabolic and physiological consequences
of such states are currently unknown. The upper limit of protein intake is widely
debated, with many experts advocating levels up to 2.0 g kg
-1
d
-1
being quite
safe (102, 117, 118)
and that renal considerations are not an issue at this level in
individuals with normal renal function. Based upon the current limited evidence
available, the authors would speculate that 25% energy as protein is a safe and
146 Bilsborough and Mann
viable level for the general public and athletes to both assist with weight control
and maintain (or improve) lean body mass. However, the energy content of the diet
and individual body weight must be considered. A maximum intake rate of 2.5 g
kg
-1
d
-1
combined with the daily energy intake considerations shown in Table
2 would ensure absolute protein intakes well below potentially dangerous levels.
For example, an 80 kg individual on a 25% protein energy intake would consume
176 g protein per day (2.2 g ∙ kg
-1
d
-1
) on a 12,000 kJ/d diet. A 60 kg individual
would consume 118 g at 2.0 g ∙ kg
-1
d
-1
on a 8000 kJ/d diet and 147 g protein at
2.5 g ∙ kg
-1
∙ d
-1
on a 10000 kJ/d diet. However, apart from pure quantitative issues,
protein composition should be considered, as the importance of branched chain
amino acids such as leucine may have important roles in metabolic regulation such
as glucose homeostasis and muscle protein synthesis.
In conclusion, it is pertinent to include a quote from “The Second Workshop
on the Assessment of Adequate Intake of Dietary Amino Acids” held in Honolulu,
Hawaii, October 31 to November 1, 2002:
The amounts of protein and, therefore, of amino acids consumed by humans
vary over a wide range. When dietary nitrogen and essential amino acid intakes
are above the requirement levels, healthy individuals appear to adapt well to
highly variable dietary protein intakes, because frank signs or symptoms of
amino acid excess are observed rarely, if at all, under usual dietary conditions.
Thus, definition of tolerable ranges of amino acid intake in healthy people will
require approaches that identify deviations from normal physiological and
biochemical adaptive processes at the subclinical level. Further, the studies
necessary to do so must conform to the strictest safety standards because of
the ethical concerns of studying normal people (21).
References
1. Layman, D.K., H. Shiue, C. Sather, D. Erickson, and J. Baum. Increased dietary protein
modifies glucose and insulin homeostasis in adult woman during weight loss. J. Nutr.
133:405-410, 2003.
2. Rand, W.M., P.L. Pellett, and V.R. Young. Meta-analysis of nitrogen balance studies
for estimating protein requirements in healthy adults. Am. J. Clin. Nutr. 77:109-27,
2003.
3. FASEB Life Sciences Research Office. Third Report on Nutrition Monitoring in the
United States 1995, US Govt Printing Office, Washington, DC.
4. Flatt, J.P. Use and storage of carbohydrate and fat.
Am. J. Clin. Nutr. 61(suppl):952S-
959S, 1995.
5. Wolfe, B.M., and P.M. Giovannetti. Short term effects of substituting protein for car
-
bohydrate in diets of moderately hypercholesterolemic human subjects. Metabolism.
40:338-343, 1991.
6. Wolfe, R.R. Metabolic interactions between glucose and fatty acids in humans.
Am. J.
Clin. Nutr. 67(Suppl):519S-526S, 1998.
7. Ludwig, D.S., J.A. Majzoub, A. Al-Zahrani, G.E. Dallal, I. Blanco, and S.B. Roberts.
High Glycemic Index foods, overeating and obesity. Pediatrics. 103:E261-E266,
1999.
8. Eaton, S.B., S.B.(3rd) Eaton, and M.J. Konner. Paleolithic nutrition revisited: A
twelve year retrospective on its nature and implications. Eur. J. Clin. Nutr. 1:207-216,
1997.
Issues of Dietary Protein Intake in Humans 147
9. Cordain, L., J. Brand-Miller, S. Eaton, N. Mann, H.A. Holt, and J.D. Speth. World
wide hunter gatherer (Plant:Animal) subsistence ratios: relevance for present day
macronutrient recommendations. Am. J. Clin. Nutr. 71:682-692, 2000.
10. Mann, N. Dietary lean red meat and human evolution.
Eur. J. Nutr. 39:71-79, 2000.
11. McDowell, M., R. Briefel, and K. Alaimo. Energy and macronutrient intakes of per
-
sons ages 2 months and over in the United States: Third National Health and Nutrition
Examination Survey, Phase 1, Adv Data. 1994; 1988-91.
12. National Nutrition Survey 1995, Nutrient Intakes and Physical Measurements. Australian
Bureau of Statistics 1998, Canberra, Australia.
13. Schenk, P. Die Verpflegung von 4700 wettkampfern aus 42 Nationen im Olympischen
Dorf wahrend der XI. Olympischen Spiele 1936 zu Berlin. Muench. Med. Wochenschr.
83:1535-1539, 1936.
14. Lemon, P.W. Do athletes need more dietary protein and amino acids.
Int. J. Sport. Nutr.
5:S39-S61, 1995.
15. Lemon, P.W. Beyond the zone: protein needs of active individuals.
J. Am. Coll. Nutr.
19:513S-521S, 2000.
16. Forslund, A.H., A.E. El-Khoury, R.M. Olsson, A.M. Sjodin, L. Hambraeus, and V.R.
Young. Effect of protein intake and physical activity on 24-h pattern and rate of mac-
ronutrient utilization. Am. J. Physiol. 276:E964-E976, 1999.
17. Poortmans, J.R., and O. Dellalieux. Do regular high protein diets have potential health
risks on kidney functions in athletes? Int. J. Sport. Nutr. Exerc. Metab.10: 39-50, 2000.
18. Atkins, R. Dr. Atkins’ New diet revolution. Vintage/Ebury Books, 1993.
19. Eades, M., R. Eades, and M. Dan.
Protein power. New York: Bantam Books, 1992.
20. Heller, R., and R. Heller.
The carbohydrate addicts diet. New York: Plume Books,
1997.
21. Bier, D.M. Amino acid pharmacokinetics and safety assessment.
J. Nutr. 133:2034S-
2039S, 2003.
22. Young, V.R. Introduction to the 2nd amino acid assessment workshop.
J. Nutr.
133:2015S-2020S, 2003.
23. Ackermans, M.T., A.M. Pereira Arias, P.H. Bisschop, E. Endert, H.P. Sauerwein, and
J.A. Romijn. The quantification of gluconeogenesis in healthy men by
2
H
2
O and [2-
13
C]
yields different results: Rate of gluconeogenesis in healthy men measured with
2
H
2
O
are higher than those measured with [2-
13
C] glycerol. J. Clin. Endocrinol. Metab.
86:2220-2226, 2001.
24. Calbet, J.A., and D.A. Maclean. Plasma Glucagon and insulin response depend on the
rate of appearance of amino acids after ingestion of different solutions in humans. J.
Nutr. 132:2174-2182, 2002.
25. Volpi, E., B. Mittendorfer, S.E. Wolf, and R.R. Wolfe. Oral amino acids stimulate muscle
protein anabolism in the elderly despite higher first-pass splanchnic extraction. Am. J.
Physiol. 277:E513-E520, 1999.
26. Brosnan, J.T. Interorgan amino acid transport and its regulation.
J. Nutr.133:2068S-
2072S, 2003.
27. Rudman, D, T.J. DiFulco, J.T. Galambos, R.B. 3rd Smith, A.A. Salam, and W.D. Warren.
Maximal rates of excretion and synthesis of urea in normal and cirrhotic subjects. J.
Clin. Invest. 52:2241-2249, 1973.
28. 2002 Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cho
-
lesterol, protein, and amino acids (macronutrients). Washington: National Academies
Press (http://books.nap.edu/catalog/10490.html).
29. Lieb, C. The effect on human beings of a twelve months exclusive meat diet.
JAMA.
93:20-22, 1929.
30. Colombo, J.P., H. Cervantes, M. Kokorovic, U. Pfister, and R. Perritaz. Effect of dif
-
ferent protein diets on the distribution of amino acids in plasma, liver and brain in the
rat. Ann. Nutr. Metab. 36:23-33, 1992.
148 Bilsborough and Mann
31. Remesy, C., C. Morand, C. Demigne, and P. Fafournoux. Control of hepatic utilization
of glutamine by transport processes or cellular metabolism in rats fed a high protein
diet. J. Nutr. 118:569-578, 1988.
32. Morens, C., C. Gaudichon, G. Fromentin, A. Marsset-Baglieri, A. Bensaid, C. Larue-
Achagiotis, C. Luengo, and D. Tome. Daily delivery of dietary nitrogen to the periphery
is stable in rats adapted to increased protein intake. Am. J. Physiol. Endocrinol. Metab.
281:E826-E836, 2001.
33. Morens, C., C. Gaudichon, C. Meteges, G. Fromentin, A. Baglieri, P.C. Even, J. Huneau
and D. Tome. A high-protein meal exceeds anabolic and catabolic capacities in rats
adapted to a normal protein diet. J. Nutr. 130: 2312-2321, 2000.
34. Phillips, R.J., and T.L. Powley. Gastric volume rather than nutrients content inhibits
food intake. Am. J. Physiol. 271:R766-R769, 1996.
35. Phillips, R.J., and T.L. Powley. Gastric volume detection after selective vagotomines
in rats. Am. J. Physiol. 274:R1626-R1638, 1998.
36. McClelland, W., and E. DuBois. Prolonged meat diets with a study of kidney function
and ketosis. J. Biochem. 87:651-680, 1930.
37. Wolfe, R.R., and S.L. Miller. Protein metabolism in response to ingestion pattern and
composition of proteins. J. Nutr. 132:3207S, 2002.
38. Boirie, Y., M. Dangin, P. Gachon, M.P. Vasson, J.L. Maubois, and B. Beaufrere. Slow
and fast dietary proteins differently modulate postprandial accretion. Proc. Natl. Acad.
Sci. 94: 14930-14935, 1997.
39. Dangin, M., Y. Boirie, C. Garcia-Rodenas, P. Gachon, J. Fauquant, P. Callier, O. Bal
-
levre, and B. Beaufrere. The digestion rate of protein is an independent regulating factor
of postprandial protein retention. Am. J. Physiol. Endcrinol. Metab. 280: E340-E348,
2001.
40. Gaudichon, C., S. Mahe, R. Benemouzig, C. Luengo, H. Fouillet, S. Dare, M. Van
Oycke, F. Ferriere, J. Rautureau, and D.Tome. Net postprandial utilization of [
15
N]-
labeled milk protein nitrogen is influenced by diet composition in humans. J. Nutr.
129:890-895, 1999.
41. Gausseres, N., S. Mahe, R. Benemouzig, C. Luengo, F. Ferriere, J. Rautureau, and D.
Tome. [
15
N]-labeled pea flour nitrogen exhibits good ileal digestibility and postprandial
retention in humans. J. Nutr. 127:1160-1165, 1997.
42. Mariotti, F., M.E. Pueyo, D. Tome, S. Berot, R. Benamouzig, and S. Mahe. The influ
-
ence of the Albumin fraction on the bioavailability and utilization of pea protein given
selectively to humans. J. Nutr. 131:1706-1713, 2001.
43. Evenepoel, P., D. Claus, B. Geypens, M. Hiele, K. Geboes, P. Rutgeerts, and Y. Ghoos.
Amount and fate of egg protein escaping assimilation in the small intestine of humans.
Am. J. Physiol. 277:G935-G943, 1999.
44. Erdman, J.W., and E.J. Fordyce. Soy products and the human diet.
Am. J. Clin. Nutr.
49:725-737, 1989.
45. Mariotti, F., S. Mahe, R. Benamouzig, C. Luengo, S. Dare, C. Gaudichon, and D.
Tome. Nutritional value of
15
N-soy protein isolate assessed from ileal digestibility and
postprandial utilization in humans. J. Nutr.129:1992-1997, 1999.
46. Scrimshaw, N., A. Wayler, E. Murray, F. Steinke, W. Rand, and V.R. Young. Nitrogen
balance response in young men given one of two isolated soy proteins or milk proteins.
J. Nutr. 113:2492-2497, 1983.
47. Schmid, R., E. Schulte-Frohlinde, V. Schusdziarra, J. Neubauer, M. Stegman, V.
Maier, and M. Classen. Contribution of postprandial amino acid levels to stimulation
of insulin, glucagon, and pancreatic polypeptide in humans. Pancreas. 7(6):698-707,
1992.
48. Fouillet, H., C. Bos, C. Gaudichon, and D. Tome. Approaches to quantifying protein
metabolism in response to nutrient ingestion. J. Nutr. 132:3208S-3218S, 2002.
Issues of Dietary Protein Intake in Humans 149
49. Gropper, S.S., and P.B. Acosta. Effect of simultaneous ingestion of L-Amino acids and
whole protein on plasma amino acid and urea nitrogen concentrations in humans. J.
Parenter. Enteral. Nutr. 15:48-53, 1991.
50. Metges, C.C., A.E. el-Khoury, A.B. Selvaraj, R.H. Tsay, A. Atkinson, M.M. Regan,
B.J. Bequette, and V.R. Young. Kinetics of L-[1-13C]leucine when ingested with free
amino acids, unlabelled or intrinsically labeled casein. Am. J. Physiol. Endocrinol.
Metab. 278:E1000-E1009, 2000.
51. Bos, C., C. Gaudichon, and D. Tome. Nutritional and physiological criteria in the assess
-
ment of milk protein quality for humans. J. Am. Coll. Nutr. 19:191S-205S, 2000.
52. Mahe, S., N. Roos, R. Benamouzig, L. Davin, C. Luengo, L. Gagnon, N. Gausseres, J.
Rautureau, and D. Tome. Gastrojejunal kinetics and the digestion of [15N]beta-lacto-
globulin and casein in humans: the influence of the nature and quantity of the protein.
Am. J. Clin. Nutr. 63:546-552, 1996.
53. Giordano, M., P. Castellino, and R.A. deFonzo . Differential responsiveness of protein
synthesis and degradation to amino acid availability in humans. Diabetes. 45:393-399,
1996.
54. Dangin, M., Y. Boirie, C. Guillet, and B. Beaufrere. Influence of protein digestion rate
on protein turnover in young and elderly subjects. J. Nutr. 132:3228S-3233S, 2002.
55. Mansbach, C.M., and R. Dowell. Effect of increasing lipid loads on the ability of
the endoplasmic reticulum to transport lipid to the Golgi. J. Lipid Res. 41:605-612,
2000.
56. van Loon, L.J., W.H. Saris, M. Kruijshoop, and A.J. Wagenmakers. Maximizing post-
exercise muscle glycogen synthesis: carbohydrate supplementation and the application
of amino acid or protein hydrolysate mixtures. Am. J. Clin. Nutr. 72:106-111, 2000.
57. Rennie, M.J. Control of muscle protein synthesis as a result of contractile activity and
amino acid availability: implications for protein requirements. Int. J. Sport Nutr. Exerc.
Metab.11:S170-S176, 2001.
58. Schmid, R., V. Schusdziarra, E. Schulte-Frohlinde, V. Maier, and M. Classen. Role
of amino acids in the stimulation of postprandial insulin, glucagon and pancreatic
polypeptide in humans. Pancreas. 4(3):305-314, 1989.
59. Zubay, G. Glycolysis, gluconeogenesis and the pentose pathway, and the tricarboxylic
acid cycle. In Biochemistry 4th Ed. Dubuque, IA: Wm.C. Brown Publishers, pp. 294-
343, 1999.
60. Charlton, M.R., D.B. Adey, and K.S. Nair. Evidence for a catabolic role of glucagon
during an amino acid load. J. Clin. Invest. 98:90-99, 1996.
61. Ahmed, M., F.Q. Nuttall F, M.C. Gannon, and R.F. Lamusga. Plasma glucagon and
alpha-amino acid nitrogen response to various diets in normal humans. Am. J. Clin.
Nutr. 33:1917-1924, 1980.
62. Linn, T., B. Santosa, D. Gronemeyer, S. Aygen, N. Scholz, M. Busch, and R.G. Bretzel.
Effects of long term dietary protein intake on glucose metabolism in humans. Diabe-
tologia. 243:1257-1265, 2000.
63. Assan, R., M. Marre, M. Gormley, and P. Lefebvre. The amino acid induced secretion
of glucagon. In Glucagon II. Berlin: Springer-Verlag, pp. 19-41, 1983.
64. Rennie, M.J., J. Bohe, and R.R. Wolfe. Latency, duration and dose response relationships
of amino acid effects on human muscle protein synthesis. J. Nutr. 132:3225S-3227S,
2002.
65. Ohneda, A., E. Parada, A. Eisentraut, and R. Unger. Characterization of the responses
of circulating glucagon to intraduodenal and intravenous administration of amino acids.
J. Clin. Invest. 47:2305-2322, 1968.
66. van Loon, L.J., W.H. Saris, H. Verhagen, and A.J. Wagenmakers. Plasma insulin
responses after ingestion of different amino acids or protein mixtures with carbohydrate.
Am. J. Clin. Nutr. 72:96-105, 2000.
150 Bilsborough and Mann
67. van Loon, L.J., M. Kruijshoop, H. Verhagen, W.H. Saris, and A.J. Wagenmakers. Inges-
tion of protein hydrolysate and amino acid-carbohydrate mixtures increases postexercise
plasma insulin responses in men. J. Nutr. 130:2508-2513, 2000.
68. Jentjens, R.L., L.J. van Loon, C.H. Mann, A.J. Wagenmakers, and A.E. Jeukendrup.
Addition of protein and amino acids to carbohydrates does not enhance postexercise
muscle glycogen synthesis. J. Appl. Physiol. 91:839-846, 2001.
69. Holt, S.H., J.C. Miller, and P. Petocz. An insulin index of foods: the insulin demand
generated by 1000-kJ portions of common foods. Am. J. Clin. Nutr. 66:1264-1276,
1997.
70. Brosnan, J.T. Comments on metabolic needs for glucose and the role of gluconeogenesis.
Eur. J. Clin. Nutr. 53: S107-S111, 1999.
71. Jungas, R.L, M.L. Halperin, and J.T. Brosnan. Qualitative analysis of amino acid
oxidation and related gluconeogenesis in humans. Physiol. Rev. 72:419-448, 1992.
72. Landau, B.R., J. Wahren, V. Chandramouli, W.C. Schumann, K. Ekberg, and S.C.
Kalhan. Contributions of gluconeogenesis to glucose production in the fasted state. J.
Clin. Invest. 98:378-385, 1996.
73. Petersen, K.F., M. Krssak, V. Navarro, V. Chandramouli, R. Hundal, W.C. Schumann,
B.R. Landau, and G.I. Shulman. Contributions of net hepatic glycogenolysis and gluco-
neogenesis to glucose production in cirrhosis. Am. J. Physiol. 276(3 Pt 1):E529-E535,
1999.
74. Chandramouli, V., K. Ekberg, W.C. Schumann, S.C. Kalhan, J. Wahren, and B.R.
Landau. Quantifying gluconeogenesis during fasting. Am. J. Physiol. 273:E1209-E1215,
1997.
75. Acheson, K.J., Y. Shutz, T. Bessard, K. Anantharaman, J.P. Flatt, and E. Jequier. Glyco
-
gen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding
in man. Am. J. Clin. Nutr. 48:240-247, 1988.
76. Hagenfeldt, L., S. Erikson, and J. Wahren. Influence of leucine on arterial concentrations
and regional exchange of amino acids in healthy subjects. Clin. Sci. Lond. 59:173-181,
1980.
77. Ahlborg, G., P. Felig, L. Hagenfeldt, R. Hendler, and J. Wahren. Substrate turnover
during prolonged exercise in man. J. Clin. Invest. 53:1080-1090, 1974.
78. Fulks, R.M., J.B. Li, and A.L. Goldberg. Effects of insulin, glucose, and amino acids
on protein turnover in rat diaphragm. J. Biol. Chem. 250:290-298, 1975.
79. Anthony, J.C., T.G. Anthony, and D.K. Layman. Leucine supplementation enhances
skeletal muscle recovery in rats following exercise. J. Nutr. 129:1102-1106, 1999.
80. Wolfe, R.R. Regulation of muscle protein by amino acids.
J. Nutr.132:3219S-3224S,
2002.
81. Tipton, K., and R.R. Wolfe. Exercise, protein metabolism and muscle growth.
Int. J.
Sport Nutr. Exerc. Metab.11: 109-132, 2001.
82. Pacy, P., G. Price, D. Halliday, M. Quevedo, and D. Millward. Nitrogen homeostatis in
man: the diurnal responses of protein synthesis and degradation and amino acid oxida-
tion to diets with increasing protein intakes. Clin. Sci (Colch) 86:103-118, 1994.
83. Bowtell, J.L., G.P. Leese, K. Smith, P.W. Watt, A. Nevill, O. Rooyackers, A.J. Wagen
-
makers, and M.J. Rennie. Modulation of whole body protein metabolism, during and
after exercise by variation of dietary protein. J. Appl. Physiol. 85:1744-1752, 1998.
84. Tipton, K.D., B.B. Rasmussen, S.L. Miller, S.E. Wolf, S.K. Owens-Stovall, B.E. Petrini,
and R.R. Wolfe. Timing of amino acid-carbohydrate ingestion alters anabolic response
of muscle to resistance exercise. Am. J. Physiol. Endocrinol. Metab. 281:E197-E206,
2001.
85. Gibala, M.J. Regulation of skeletal muscle amino acid metabolism during exercise.
Int. J. Sport Nutr. Exerc. Metab. 11: 87-108, 2001.
86. Lemon, P.W., and J.P. Mullin. Effect of initial muscle glycogen levels on protein
catabolism during exercise. J. Appl. Physiol. 48:624-629, 1980.
Issues of Dietary Protein Intake in Humans 151
87. Gibala, M.J., M. Lozej, M.A. Tarnopolsky, C. McLean, and T.E. Graham. Low glycogen
and branch-chain amino acid ingestion do not impair anaplerosis during exercise in
humans. J. Appl. Physiol. 87(5):1662-1667, 1999.
88. Costill, D.L., and M Hargreaves. Carbohydrate nutrition and fatigue.
Sports Med.
13:86-92, 1992.
89. Hawley, J.A., E.J. Schabort, T.D. Noakes, and S.C. Dennis. Carbohydrate-loading and
exercise performance: an update. Sports Med. 24:73-81, 1997.
90. Greenhaff, P.L., M. Gleeson, P.H. Whiting, and R.J. Maughan. Dietary composition
and acid base status: Limiting factors in the performance of maximal exercise in man?
Eur. J. Appl. Physiol. Occup. Physiol. 56:444-450, 1987b.
91. Greenhaff, P.L., M. Gleeson, and R.J. Maughan. Diet induced metabolic acidosis and
the performance of high intensity exercise in man. Eur. J. Appl. Physiol. Occup. Physiol.
57:583-590, 1988.
92. Maughan, R.J. and D.C. Poole. The effect of a glycogen-loading regime on the capac
-
ity to perform anaerobic exercise. Eur. J. Appl. Physiol. Occup. Physiol. 46:211-219,
1981.
93. Balsom, P.D., G.C. Gaitanos, K. Soderlund, and B. Ekblom. High-intensity exercise and
muscle glycogen availability in humans. Acta. Physiol. Scand. 165:337-345, 1999.
94. Hargreaves, M., J.P. Finn, R.T. Withers, J.A. Halbert, G.C. Scroop, M. Mackay, R.J.
Snow, and M.F. Carey. Effect of muscle glycogen availability on maximal exercise
performance. Eur. J. Appl. Physiol. Occup. Physiol. 75:188-192, 1997.
95. Lambert, C.P., and M.G. Flyn. Fatigue during high intensity intermittent exercise:
application to bodybuilding. Sports Med. 32:511-522, 2002.
96. Crovetti, R., M. Porrini, A. Santangelo, and G. Testolin. The influence of thermic effect
of food on satiety. Eur. J. Clin. Nutr. 52:482-488, 1998.
97. Johnston, C., C. Day, and P. Swan. Postprandial thermogenesis is increased 100% on
a high protein, low-fat diet versus a high carbohydrate, low-fat diet in healthy young
woman. J. Am. Coll. Nutr. 21:55-61, 2002.
98. Stubbs, R.J. Nutrition Society Medal Lecture. Appetite, feeding behaviour and energy
balance in human subjects. Proc. Nutr. Soc. 57:341-356, 1998.
99. Cordain, L., S.B. Eaton, J.B. Miller, N. Mann, and K. Hill. The paradoxical nature of
hunter-gatherer diets: meat based yet non-atherogenic. Eur. J. Clin. Nutr. 56:S42-S52,
2002.
100. Skov, A.R., S. Toubro, B. Ronn, L. Holm, and A. Astrup. Randomized trial on protein
vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity. Int. J. Obes.
Relat. Metab. Disord. 23:528-536, 1999.
101. Baba, N.H., S. Sawaya, N. Norbay, Z. Habbal, S. Azar, and S.A. Hashim. High protein
vs high carbohydrate hypoenergetic diet for the treatment of obese hyperinsulinemic
subjects. . Int. J. Obes. Relat. Metab. Disord. 23:1202-1206, 1999.
102. Layman, D.K., H. Shiue, C. Sather, D.J. Erickson, and J. Baum. Increased dietary
protein modifies glucose and insulin homeostasis in adult woman during weight loss.
J. Nutr. 133:405-410, 2003.
103. Farnsworth, E., N. Luscombe, M. Noakes, G. Wittert, E. Argyiou, and P. Clifton. Effect
of a high-protein, energy-restricted diet on body composition, glycemic control and
lipid concentrations in overweight and obese hyperinsulinemic men and woman. Am.
J. Clin. Nutr. 78:31-39, 2003.
104. Parker, B., M. Noakes, N. Luscombe, and P. Clifton. Effect of a high protein high
monounsaturated fat weight loss diet on glycemic control and lipid levels in type 2
diabetes. Diabetes Care. 25:425-430, 2002.
105. Bilsborough, S.A., and Crowe TC. Low-carbohydrate diets: What are the potential
short and long-term health implications? Asia Pac. J. Clin. Nutr. 12:396-404, 2003.
106. Freedman, M.R., J. King, and E. Kennedy. Popular diets: a scientific review.
Obes. Res.
9:1S-40S, 2001.
152 Bilsborough and Mann
107. The National Academy of Sciences. Dietary Reference Intake for Energy, Carbohydrate,
Fiber, Fat, Protein, and Amino Acids (Macronutrients) 2002.
108. O’Dea, K. Marked improvements in carbohydrate and lipid metabolism in diabetic
Australian aborigines after temporary reversion to traditional lifestyle. Diabetes.
33:596-603, 1984.
109. Naughton, J.M., K. O’Dea, and A.J. Sinclair. Animal foods in traditional Australian
aboriginal diets: polyunsaturated and low in fat. Lipids. 21:684-690, 1986.
110. Wolfe, B.M., and L.A. Piche. Replacement of carbohydrate by protein in a conventional-
fat diet reduces cholesterol and triglyceride concentrations in healthy normolipidemic
subjects. Clin. Invest. Med. 22:140-148, 1999.
111. Piatti, P., F. Monti, I. Fermo, L. Baruffaldi, R. Nasser, G. Santambrogio, M. Librenti,
M. Galli-Kienle, A. Pontiroli, and G. Pozza. Hypercaloric high protein diets improve
glucose oxidation and spares lean body mass: comparison to hypocaloric high carbo-
hydrate diet. Metabolism. 43:1481-1487, 1994.
112. Hu, F.B., M.J. Stampfer, J.E. Manson, A.A. Ascherio, G.A. Colditz, F.E. Speizer, C.H.
Hennekens, and W.C. Willett. Dietary saturated fats and their food sources in relation to
the risk of coronary heart disease in woman. Am. J. Clin. Nutr. 70:1001-1008, 1999.
113. Mann, N.J., D. Li, A.J. Sinclair, N.P. Dudman, X.W. Guo, G.R. Elsworth, F.D. Kelly,
and A.K. Wilson. The effects of diet on plasma homocysteine concentrations in healthy
male subjects. Eur. J. Clin. Nutr. 53:895-899, 1999.
114. Obarzanek, E., P.A. Velletri, and J.A. Cutler. Dietary protein and blood pressure.
JAMA.
275:1598-1603, 1996.
115. Kinjo, Y., V. Beral, S. Akiba, T. Key, S. Mizuno, P. Appleby, N. Yamaguchi, S. Watan
-
able, and R. Doll. Possible protective effect of milk, meat and fish for cerebrovascular
disease mortality in Japan. J. Epidemiol. 9:268-274, 1999.
116. Brenner, B.M., T.W. Meyer, and T.H. Hostetter. Dietary protein intake and the progres
-
sive nature of kidney disease. N. Engl. J. Med. 307:652-659, 1982.
117. Hutson, S.M., and R.A. Harris. Leucine as a nutritional signal.
J. Nutr. 131:839S-840S,
2001.
118. el-Khoury, A.E., N.K. Kukagawa, M. Sanchez, R.H. Tsay, R.E. Gleason, T.E. Chap
-
man, and V.R. Young. The 24-h pattern and rate of leucine oxidation, with particular
reference to tracer estimates of leucine requirements in healthy adults. Am. J. Clin.
Nutr. 59:1012-1020, 1994.
  • ... Excessivo consumo proteico, ultrapassando a capacidade do fígado em desaminar as proteínas e converter o azoto em ureia, pode levar à deplecção de cálcio e a situações de desidratação. Excessiva ingestão de proteínas pode levar a hiperaminoacidemia, hiperamonemia, hiperinsulinemia, náusea e diarreia [38]. Embora a ingestão proteica do maratonista deste estudo exceda as recomendações, pensamos, que por si só, esse excesso não será problemático já que está, segundo Bilsborough e Mann [38], abaixo do limite de toxicidade proteica (25% do aporte energético total). ...
    ... Excessiva ingestão de proteínas pode levar a hiperaminoacidemia, hiperamonemia, hiperinsulinemia, náusea e diarreia [38]. Embora a ingestão proteica do maratonista deste estudo exceda as recomendações, pensamos, que por si só, esse excesso não será problemático já que está, segundo Bilsborough e Mann [38], abaixo do limite de toxicidade proteica (25% do aporte energético total). As preocupações derivam do facto de o excessivo aporte de proteínas ser feito à custa do reduzido aporte de carboidratos, o que pode provocar problemas metabólicos e afectar negativamente o rendimento atlético. ...
    Article
    Objectivo: Défices ou excessos nutricionais podem impedir o máximo rendimento de um desportista. Assim, estudamos a ingestão nutricional de um maratonista de elite, analisando o grau de adequação às exigências de treino e competição. Material e métodos: Maratonista de elite (32 anos, 1,69m, 55 kg), 4º lugar no Campeonato do Mundo de Atletismo, (2h09’28” - melhor marca pessoal). Realiza 12 a 14 treinos por semana. Os dados nutricionais foram obtidos por registo de sete dias. A conversão dos alimentos em nutrientes foi realizada pelo programa informático The Food Processor Plus 7.0. Estatística: Utilizaram-se as medidas descritivas, média, desvio-padrão e valores máximo e mínimo dos sete dias. Resultados: Aporte diários médios: calorias - 2296 ± 639 Kcal; carbohidratos – 40,6 ± 10,2% (4,42 ± 1,98 g/kg/dia); proteínas - 22,9 ± 6,7% (2,1 ± 0,3 g/kg/dia); gorduras – 36,5 ± 6,3%; colesterol – 488,1 ± 102,3 mg; fibras – 8,1 ± 2,8 g; vitamina C – 24,9 ± 12,5 mg; vitamina A – 211,0 ± 130,5 μg ER; Betacaroteno – 163,4 ± 265,5 μg; vitamina D – 3,7 ± 4,1 μg; vitamina E – 7,02 ± 3,4 mg ET. Reduzido aporte de cálcio (387,4 ± 154,5 mg), magnésio (222,6 ± 22,3 mg), molibdénio (2,46 ± 3,42 μg) e iodo (58,6 μg). Conclusão: Este maratonista apresenta um perfil nutricional incompatível com as elevadas exigências do treino e competição, caracterizado pelo reduzido aporte de energia, carboidratos, vitaminas antioxidantes e fibras, com excessivo consumo de colesterol. Este maratonista deve alterar o seu perfil de ingestão nutricional.Palavras-chave: perfil nutricional, esportes, provas de rendimento.
  • ... The amino acid arginine is a collagen precursor, it also stimulates insulin and growth hormone secretion and can enhance collagen accumulation. Bilsborough and Mann (2006) state the maximum protein intake based on bodily needs, weight control evidence, and avoiding protein toxicity would be approximately 25% of energy requirements at approximately 2-2.5 g x kg(-1) x d(-1), which is a lot higher than the current UK recommendation as it corresponds to 176 g protein per day for an 80 kg individual on a 12,000 kJ/d diet. They define a maximum safe intake range for an 80 kg person as 285-365 g/d (Bilsborough and Mann, 2006). ...
    ... Bilsborough and Mann (2006) state the maximum protein intake based on bodily needs, weight control evidence, and avoiding protein toxicity would be approximately 25% of energy requirements at approximately 2-2.5 g x kg(-1) x d(-1), which is a lot higher than the current UK recommendation as it corresponds to 176 g protein per day for an 80 kg individual on a 12,000 kJ/d diet. They define a maximum safe intake range for an 80 kg person as 285-365 g/d (Bilsborough and Mann, 2006). ...
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    The aim of this review is to synthesise literature on food, nutritional status and wound healing to help inform those working in wound care. A literature search was performed on PubMed, Scopus and EMBASE databases. Studies were critically appraised and the findings were analysed by narrative synthesis. Nutritional assessment is important in practice as nutritional status can impact on wound healing in several ways (including affecting both healing time and susceptibility to infection). There is widespread recognition of the importance of nutritional assessment tools, however, completion can sometimes be overlooked in practice. Healthcare professionals also need to be aware that obesity may be accompanied by micronutrient deficiency causing low micronutrient levels, however, nutritional assessment tools using body mass index (BMI) and weight loss may not identify this. Although there are intervention studies using nutritional formulations, such as amino acids, to support wound healing, the results of this review suggest that future research around using food as therapy and specific nutritional supplementation is needed.
  • ... Embora os consumos médios de proteínas no PE estejam abaixo do limiar que Bilsborough & Mann [31] consideram de toxicidade proteica (25% do CET), aconselha-se a redução do aporte proteico e aumento do consumo de carbohidratos. Relativizando o consumo proteico ao peso corpo-ral, encontramos valores eventualmente excessivos para desportistas (2,4 ± 0,8 g/kg/dia) e muito mais elevados que os verificados por Heaney et al. [18] em atletas australianas de várias modalidades (1.6 g/kg/dia). ...
    ... Relativizando o consumo proteico ao peso corpo-ral, encontramos valores eventualmente excessivos para desportistas (2,4 ± 0,8 g/kg/dia) e muito mais elevados que os verificados por Heaney et al. [18] em atletas australianas de várias modalidades (1.6 g/kg/dia). o elevado consumo de proteínas está relacionado com a elevação sanguínea de insulina e amónia [31] e o aumento do trabalho hepático de desaminação que pode conduzir a situações de desidratação e depleção de cálcio. Acresce que o consumo excessivo de proteínas, principalmente de origem animal, está relacionado com o aumento de risco de vários tipos de cancro. ...
    Article
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    Introdução: A corrida de endurance impõe um estresse sistémico que obriga a especiais cuidados no processo de treino/recuperação. A nutrição é um dos fatores que mais condiciona o rendimento atlético e deve ser objeto de especiais cuidados por parte dos atletas. Objetivo: Este estudo pretendeu avaliar a ingestão nutricional de corredoras de meio-fundo, verificando se está adequada às exigências energéticas e nutricionais dessas atletas. Métodos: A amostra foi constituída por 25 atletas do sexo feminino que participam com regularidade em competições atléticas de meio-fundo e fundo (800 m a 10.000 m), com as seguintes características: 20,6 ± 4,7 anos de idade; 52,3 ± 3,6 kg de peso corporal; 163,4 ± 4,7 cm de altura; 6,3 ± 2,8 anos de prática de atletismo; 7,4 ± 2,1 treinos/semana; 78 ± 28 km/semana de corrida. Os dados nutricionais foram obtidos por inquérito semi-quantitativo de frequência alimentar elaborado pelo Departamento de Epidemiologia Nutricional da Faculdade de Medicina da Universidade do Porto, Portugal. A conversão dos alimentos em nutrientes foi realizada pelo programa informático Food Processor Plus, versão SQL. Resultados: Verificou-se um aporte calórico médio diário de 2854 ± 868 kcal (1482-4297), correspondendo aos seguintes consumos relativos: carbohidratos 52.9 ± 6.3% (7,2 ± 2,4 g.kg-1.dia-1), gorduras 29,8 ± 5,1% (1,8 ± 0,7g.kg-1.dia-1) e proteínas 17,3 ± 3,0% (2,4 ± 0,7 g.kg-1.dia-1). Verificaram-se consumos das vitaminas D e biotina abaixo e da vitamina A muito acima das recomendações. Os consumos de macrominerais e microminerais ultrapassaram as recomendações. Conclusão: As corredoras do presente estudo apresentam um consumo médio reduzido de carbohidratos para atletas de esforços de endurance. O aporte de gorduras está adequado enquanto o de proteínas excede as recomendações. Com exceção das vitaminas D ebiotina por defeito e da vitamina A por excesso, o aporte vitamínico e mineral é adequado. As atletas do presente estudo devem aumentar o contributo relativo dos carbohidratos em detrimento das proteínas.Palavras-chave: nutrição, macronutrientes, vitaminas, minerais, consumo energético.
  • ... This could be because the familiarity in taste, flavour and colour. This will provide the required protein and energy level will provide basic nutrient for the day"s work and eventually ameliorate the problem of malnutrition (Bilsborough, 2006). ...
    Article
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    O. and Abayomi, H.T. (2013) Nutrient composition, functional and organoleptic properties of complementary food formulated from sorghum, walnut and ginger. Journal of Agricultural Technology 9(2):321-333. In developing countries, particularly sub-Saharan Africa, infant complementary foods are grossly inadequate, complementary foods were formulated. Sorghum, walnut and ginger were processed into flour separately and were then blended in ratios 100:0:0(SWG1); 80:15:5(SWG2); 70:25:5(SWG3); 60:35:5(SWG4) and 50:45:5(SWG5). The proximate, functional and sensory properties of processed flour were determined. The result indicates that the protein content increases as walnut proportion of the samples increased. The protein content of the resulting flour increased significantly from 6.52 to 10.21%, with a corresponding decrease in the carbohydrate content from 85.23 to 77.22%; the moisture content(flour) ranged from 6.30 to 9.01%; fat content from 1.67 to 2.28%; ash content from 0.05 to 0.11%; crude fibre from 0.27 to 0.3%; carbohydrate from 85.23 to 77.22%. The levels of the antinutrients were lower in the complementary foods than the control samples. The water absorption capacity, bulk density and swelling index were lower in fermented complementary blends than the control samples. There exists significant difference (P < 0.005) among the samples analyzed. Sensory evaluation conducted on the porridge showed a significant difference (p < 0.05) in color and odour. Sample blend SWG 3(70:25:5) was most generally accepted among the samples. The nutritional and textural qualities of sorghum flour were improved with the addition of walnut and ginger flour. A sample with 25% walnut and 5% ginger is more acceptable. Processing of sorghum into flour and porridge will encourage the use and utilization of the sorghum in other forms. Fortification of sorghum with walnut and ginger flour makes the food more nutritious thereby alleviating the problem of malnutrition especially in children.
  • ... Aunque se ha comprobado en muchas investigaciones que la suplementación proteica (dentro de unos límites tolerables) es segura y no tiene efectos perjudiciales, todavía existen algunas dudas razonables sobre las implicaciones clínicas que tiene el consumo excesivo de proteínas, en especial sobre los riñones y el hígado, pero hasta el momento no existen datos concluyentes en cuanto a cuáles son los límites superiores seguros de su consumo 108 . ...
  • ... Fish farming in Honduras has had a significant boom in recent years, settling in third place within Latin American countries with the highest export level of tilapia fillets [1]. The efficient use of resources becomes necessary due to competition and knowing when to harvest is critical. ...
  • ... Recommended daily protein intake for healthy adults is 0.8-1.0 grams per kilogram of body weight (23). Sometimes conventional wisdom is that an adult needs a daily amount of more than 1 gram per kilogram of body weight, referring to the organisms in an intense growth and development, and persons who are engaged in intense physical or intellectual work (24). ...
    Article
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    Taking responsibility for your life, among other factors, means also considering what to eat and which nutrition pattern to follow. Everyone needs to think about what they put on the plate and which ingredients should be avoided. Food, as such, will never be a drug or medication, like a painkilling tablet relieving pain in a short amount of time, for example. However, proper nutrition is our ally in the prevention of diseases, maintaining balance in our body and our mind. By following the main principles of a healthy diet, the physiological homeostasis can be managed, as well as faster recovery from disease achieved. This review is aimed at summarizing basic principles of nutrition recommendations and at empowering stakeholders (pharmacists, medical biochemists, physicians) to be able to communicate to their patients and customers healthy and sustainable nutrition choices through the personalized advice.
  • Chapter
    The global rise in the incidence of obesity and associated non-communicable chronic diseases has far outstripped the ability to understand and manage the causes. We introduce a field from the natural sciences, called nutritional ecology, which we believe can contribute toward unraveling the causes of and identifying key control points for managing the growing epidemic of chronic disease. We begin by clarifying how we use the term “nutritional ecology” to place it in the context of related terms, emphasizing that ours is a biologically inspired approach that can help to structure nutrition research by introducing into nutrition science theory and methods from ecological and evolutionary sciences. We then discuss some biological insights from nutritional ecology that we suggest can make a significant contribution to nutrition research and clinical practice and thereafter introduce a geometric framework for implementing this theory. We end with examples showing that the implementation of biological thinking via nutritional geometry can provide a concrete step toward understanding how human biology interacts with our radically altered industrialized food environments to generate health and disease.
  • Article
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    Whey nowadays considered as nutritional power house of future. Presently, whey mainly used as energy base drinks for sportsman and for therapeutic application in many countries. The two primary sources of protein in milk are the caseins and whey. After processing occurs, the caseins are the proteins responsible for making curds, while whey remains in an aqueous environment. Whey protein is a reliable source of amino acids and biologically active proteins which act as a nutritional supplement. The components of whey include beta lactoglobulin, alpha lactoalbumin, bovine serum albumin, lactoferrin, immunoglobluins, lactoperoxidase enzymes, glycomacropeptides, lactose, and minerals. Whey proteins have a high amount of branched chain amino acids such as leucine, isoleucine, and valine. These are also rich in the sulfur-containing amino acids cysteine and methionine, which enhance immune functions through their intracellular conversion to glutathione. The present review paper gives information about the potential beneficial properties of whey protein and focuses on using whey protein supplementation as an immuno-modulator, antioxidant, anti-inflammatory, anti-diabetic, anti-cancer. In this context, the current review presented that whey protein supplementation is shown to maintain a high concentration of cellular antioxidants and boost immune defenses that promote carcinogen detoxification. Due to the positive findings, whey protein supplementation is starting to be viewed as a non-pharmaceutical adjunct therapy in the treatment of cancer. Also, whey protein provides an abundant supply of essential amino acids to organs and tissues, which stimulate tissue regenerative mechanisms and help minimize immune suppression. J Pharm Care 2019; 7(4): 112-117.
  • Article
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    Objectivo: Os défices nutricionais de desportistas adolescentes podem afectar negativamente quer o seu rendimento desportivo quer o seu desenvolvimento e maturação. Assim, este estudo pretendeu caracterizar os hábitos de ingestão nutricional de jovens futebolistas portugueses. Avaliamos também o perfil de composição corporal da amostra. Material e métodos: A amostra foi constituída por 60 jogadores de futebol, do sexo masculino (14-16 anos de idade), pertencentes a seis equipas participantes no Campeonato Nacional de Juvenis: Braga, Chaves, Repesenses, Belenenses, Juventude de Évora e Louletano. Os dados nutricionais foram obtidos por registo de três dias consecutivos de consumo alimentar. A conversão dos alimentos em nutrientes foi realizada pelo programa informático Food Processor Plus, versão SQL. A determinação do perfil antropométrico e a composição corporal foram obtidos a partir da mensuração do peso, altura e pregas de adiposidade subcutânea tricipital e subescapular. Estatística: média, desvio-padrão e valores mínimo e máximo e amplitude. Resultados: Verificou-se um aporte calórico médio diário de 2575 ± 470 kcal (1699-3689), correspondendo aos seguintes consumos: hidratos de carbono 45,4 ± 4,1% (4,5 ± 1,1 g.kg-1.dia-1), gorduras 36,7 ± ,3% (1,6 ± 0,4 g.kg-1.dia-1) e proteínas 18 ± 2,5% (1,8 ± 0,4 g.kg-1.dia-1). Conclusão: Os jovens futebolistas do presente estudo apresentam uma nutrição incompatível com as necessidades energéticas do desporto que praticam. Além de terem um aporte calórico total diário insuficiente, a distribuição qualitativa pelos macronutrientes é desequilibrada, com um baixo consumo de hidratos de carbono, e um elevado consumo de gorduras e proteínas.Palavras-chave: nutrição, macronutrientes, composição corporal, jovens futebolistas.
Literature Review
  • Conference Paper
    Interorgan amino acid transport is a highly active and regulated process that provides amino acids to all tissues of the body, both for protein synthesis and to enable amino acids to be used for specific metabolic functions. It is also an important component of plasma amino acid homeostasis. Net movement of amino acids depends on the physiological and nutritional state. For example, in the fed state the dominant flux is from the intestine to the other tissues. In starvation the dominant flux is from muscle to the liver and kidney. A number of general principles underlie many amino acid fluxes: i) The body does not have a store for amino acids. This means that dietary amino acids, in excess of those required for protein synthesis, are rapidly catabolized; ii) Amino acid catabolism must occur in a manner that does not elevate blood ammonia. Thus, extrasplanchnic amino acid metabolism often involves an innocuous means of transporting nitrogen to the liver; iii) Because most amino acids are glucogenic, there will be a considerable flux of amino acids to the gluconeogenic organs when there is a need to produce glucose. In addition to these bulk flows, fluxes of many specific amino acids underlie specific organ function. These include intestinal oxidation of enteral amino acids, the intestinal/renal axis for arginine production, the brain uptake of neurotransmitter precursors and renal glutamine metabolism. There is no single means of regulating amino acid fluxes; rather, such varied mechanisms as substrate supply, enzyme activity, transporter activity and competitive inhibition of transport are all found. J. Nutr. 133: 2068S-2072S, 2003.
  • Conference Paper
    Objective: The recent literature suggests that high-protein, low-fat diets promote a greater degree of weight loss compared to high-carbohydrate, low-fat diets, but the mechanism of this enhanced weight loss is unclear. This study compared the acute, energy-cost of meal-induced thermogenesis on a high-protein, low-fat diet versus a high-carbohydrate, low-fat diet. Methods: Ten healthy, normal weight, non-smoking female volunteers aged 19-22 years were recruited from a campus population. Using a randomized, cross-over design, subjects consumed the high-protein and the high-carbohydrate diets for one day each, and testing was separated by a 28- or 56-day interval. Control diets were consumed for two days prior to each test day. On test day, the resting energy expenditure, the non-protein respiratory quotient and body temperature were measured following a 10-hour fast and at 2.5-hour post breakfast, lunch and dinner. Fasting blood samples were collected test day and the next morning, and complete 24-hour urine samples were collected the day of testing. Results: Postprandial thermogenesis at 2.5 hours post-meal averaged about twofold higher on the high protein diet versus the high carbohydrate diet, and differences were significant after the breakfast and the dinner meals (p < 0.05). Body temperature was slightly higher on the high protein diet (p = 0.08 after the dinner meal). Changes in the respiratory quotient post-meals did not differ by diet, and there was no difference in 24-hour glomerular filtration rates by diet. Nitrogen balance was significantly greater on the high-protein diet compared to the high-carbohydrate diet (7.6 +/- 0.9 and -0.4 +/- 0.5 gN/day, p < 0.05), and at 24-hour post-intervention, fasting plasma urea nitrogen concentrations were raised on the high protein diet versus the high-carbohydrate diet (13.9 +/- 0.9 and 11.2 +/- 1.0 mgJdL respectively, p < 0.05). Conclusions: These data indicate an added energy-cost associated with high-protein, low-fat diets and may help explain the efficacy of such diets for weight loss.
  • Conference Paper
    In vivo energy production results largely from the oxidative metabolism of either glucose or fatty acids. Under diverse physiologic and nutritional conditions, the oxidation of either glucose or fatty acids may predominate. The nature of the control of the availability and oxidation of each substrate has been studied extensively for greater than or equal to 30 y. The most popular and enduring hypothesis was proposed by Randle et al in 1963 and is termed the glucose-fatty acid cycle. This proposal places great significance on the regulation of lipolysis as a factor controlling substrate metabolism. Our work has led to an opposite perspective, which could be called the glucose-fatty acid cycle reversed. According to our hypothesis, the rate of glycolysis, determined by the intracellular availability of glucose-6-phosphate, is the predominant factor determining the rate of glucose oxidation. Whereas the rate of lipolysis may have some effect on the availability of glucose, both via a fatty acid-mediated inhibition of plasma glucose uptake and also by supplying glycerol for gluconeogenesis, there is little evidence for a direct inhibitory effect of fatty acid oxidation on the intracellular oxidation of glucose. In contrast, increased glucose oxidation limits oxidation of long-chain fatty acids directly by inhibiting their transport into the mitochondria. Consequently, whereas there is a close coupling between glucose availability and oxidation, fatty acids are generally available in greater quantities than are required for oxidation. We propose that fatty acid oxidation is largely controlled at the site of oxidation, which is in turn determined by the availability of glucose, rather than by its availability via lipolysis.
  • Article
    Objective. —To review published and presented data on the relationship between dietary protein and blood pressure in humans and animals. Data Sources. —Bibliographies from review articles and books on diet and blood pressure that had references to dietary protein. The bibliographies were supplemented with computerized MEDLINE search restricted to English language and abstracts presented at epidemiologic meetings. Study Selection. —Observational and intervention studies in humans and experimental studies in animals. Data Extraction. —In human studies, systolic or diastolic blood pressure were outcome measures, and dietary protein was measured by dietary assessment methods or by urine collections. In animal studies, blood pressure and related physiological effects were outcome measures, and experimental treatment included protein or amino acids. Data Synthesis. —Historically, dietary protein has been thought to raise blood pressure; however, studies conducted in Japan raised the possibility of an inverse relationship. Data analyses from subsequent observational studies in the United States and elsewhere have provided evidence of an inverse relationship between protein and blood pressure. However, intervention studies have mostly found no significant effects of protein on blood pressure. Few animal studies have specifically examined the effects of increased dietary protein on blood pressure. Conclusions. —Because of insufficient data and limitations in previous investigations, better controlled and adequately powered human studies are needed to assess the effect of dietary protein on blood pressure. In addition, more research using animal models, in which experimental conditions are highly controlled and detailed mechanistic studies can be performed, is needed to help provide experimental support for or against the protein—blood pressure hypothesis.(JAMA. 1996;275:1598-1603)
  • Article
    Background: Protein induces an increase in insulin concentrations when ingested in combination with carbohydrate. Increases in plasma insulin concentrations have been observed after the infusion of free amino acids. However, the insulinotropic properties of different amino acids or protein (hydrolysates) when co-ingested with carbohydrate have not been investigated. Objective: The aim of this study was to define an amino acid and protein (hydrolysate) mixture with a maximal insulinotropic effect when co-ingested with carbohydrate. Design: Eight healthy, nonobese male subjects visited our laboratory, after an overnight fast, on 10 occasions on which different beverage compositions were tested for 2 h. During those trials the subjects ingested 0.8 g*kg(-)(1)*h(-)(1) carbohydrate and 0.4 g*kg(-)(1)*h(-)(1) of an amino acid and protein (hydrolysate) mixture. Results: A strong initial increase in plasma glucose and insulin concentrations was observed in all trials, after which large differences in insulin response between drinks became apparent. After we expressed the insulin response as area under the curve during the second hour, ingestion of the drinks containing free leucine, phenylalanine, and arginine and the drinks with free leucine, phenylalanine, and wheat protein hydrolysate were followed by the largest insulin response (101% and 103% greater, respectively, than with the carbohydrate-only drink; P < 0.05). Conclusions: Insulin responses are positively correlated with plasma leucine, phenylalanine, and tyrosine concentrations. A mixture of wheat protein hydrolysate, free leucine, phenylalanine, and carbohydrate can be applied as a nutritional supplement to strongly elevate insulin concentrations.
  • Article
    Full-text available
    Weight loss is a major concern for the US population. Surveys consistently show that most adults are trying to lose or maintain weight (1). Nevertheless, the prevalence of overweight and obesity has increased steadily over the past 30 years. Currently, 50% of all adult Americans are con- sidered overweight or obese (2,3). These numbers have serious public health implications. Excess weight is associ- ated with increased mortality (4) and morbidity (5). It is associated with cardiovascular disease, type 2 diabetes, hypertension, stroke, gallbladder disease, osteoarthritis, sleep apnea and respiratory problems, and some types of cancer (6,7). Most people who are trying to lose weight are not using the recommended combination of reducing caloric intake and increasing physical activity (1). Although over 70% of persons reported using each of the following strategies at least once in 4 years, increased exercise (82.2%), decreased fat intake (78.7%), reduced food amount (78.2%,) and re- duced calories (73.2%), the duration of any one of these behaviors was brief. Even the most common behaviors were used only 20% of the time (8). Obesity-related conditions are significantly improved with modest weight loss of 5% to 10%, even when many patients remain considerably overweight (6). The Institute of Medicine (9) defined successful long-term weight loss as a 5% reduction in initial body weight (IBW) that is main- tained for at least 1 year. Yet data suggest that such losses are not consistent with patients’ goals and expectations. Foster (10) reported that in obese women (mean body mass index [BMI] of 36.3 􏰃 4.3) goal weights targeted, on average, a 32% reduction in IBW, implying expectations that are unrealistic for even the best available treatments. Interestingly, the most important factors that influenced the Address correspondence to Dr. Janet King, U.S. Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, University of California, 1 Shield Avenue, Building Surge IV, Room 213, Davis, CA 95616. E-mail: jking@ whnrc.usda.gov Copyright © 2001 NAASO selection of goal weights were appearance and physical comfort rather than change in medical condition or weight suggested by a doctor or health care professional. Is it any wonder that overweight individuals are willing to try any new diet that promises quick, dramatic results more in line with their desired goals and expectations than with what good science supports? The proliferation of diet books is nothing short of phe- nomenal. A search of books on Amazon.com using the key words “weight loss” revealed 1214 matches. Of the top 50 best-selling diet books, 58% were published in 1999 or 2000 and 88% were published since 1997. Many of the top 20 best sellers at Amazon.com promote some form of carbo- hydrate (CHO) restriction (e.g., Dr. Atkins’ New Diet Rev- olution, The Carbohydrate Addict’s Diet, Protein Power, Lauri’s Low-Carb Cookbook). This dietary advice is counter to that promulgated by governmental agencies (US Department of Agriculture [USDA]/Department of Health and Human Services, National Institutes of Health) and nongovernmental organizations (American Dietetic Associ- ation, American Heart Association, American Diabetes Association, American Cancer Society, and Shape Up America!). What is really known about popular diets? Is the in- formation scientifically sound? Are popular diets effec- tive for weight loss and/or weight maintenance? What is the effect, if any, on composition of weight loss (fat vs. lean body mass), micronutrient (vitamin and mineral) status, metabolic parameters (e.g., blood glucose, insulin sensitivity, blood pressure, lipid levels, uric acid, and ketone bodies)? Do they affect hunger and appetite, psy- chological well-being, and reduction of risk for chronic disease (e.g., coronary heart disease, diabetes, and osteo- porosis)? What are the effects of these diets on insulin and leptin, long-term hormonal regulators of energy in- take and expenditure? The objective of this article is to review the scientific literature on various types of popular diets based on their macronutrient composition in an attempt to answer these questions (see Appendix for diet summaries).
  • Article
    This study tests the hypothesis that hyperinsulinemic (HI) obese subjects respond differently from normoinsulinemics (NI) to changes in composition of hypoenergetic diets. Twenty-seven obese male subjects, 13 HI and 14 NI, were fed for 4 weeks either a high protein (HP) or a high carbohydrate (HC) hypoenergetic diet providing 80% of their resting energy expenditure (REE). On the HP diet weight loss was significantly higher in HI as compared to NI group. Alternatively, the HI group lost less weight than NI group on the HC diet. The HC diets resulted in a considerable and similar reduction in REE in both HI and NI groups as opposed to the HP diet, which maintained REE in both HI and NI. A higher decrease and normalization of fasting insulin levels was observed in the HI group on the HP as compared to HC diet. In conclusion, hyperinsulinemic, in contrast to normoinsulinemic obese subjects, seem to achieve better weight reduction, less decline in energy expenditure, and normalization of insulin levels on HP than isocaloric HC diet.
  • Article
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    The quantification of gluconeogenesis (GNG) by 2H2O and (2-13C)glycerol and the mass isotopomer dilution analysis of glucose does not involve assumptions regarding the enrichment of the ox- aloacetate precursor pool. To compare these two methods we mea- sured GNG in six healthy postabsorptive males under identical, strictly standardized, eucaloric conditions, once after oral adminis- tration of 2H2O and once during a primed continuous infusion of (2-13C)glycerol. Endogenous glucose production (EGP) was measured by infusion of (6,6-2H2)glucose. EGP was not different after 2 H2O administration or during (2-13C)glycerol infusion (12.2 6 0.7 vs. 11.7 6 0.3 mmol/kgzmin). However, GNG measured after 2H2O ad- ministration was significantly higher than that during (2-13C)glycerol infusion (7.4 6 0.7 vs. 4.9 6 0.6 mmol/kgzmin; P 5 0.03), representing approximately 60% and 41% of EGP, respectively. The 2H2O study was repeated during primed continuous infusion of unlabeled glyc- erol, showing that infusion of glycerol at the rate used in the (2-13C)- glycerol method does not affect the measurement of GNG with 2H2O, viz. 7.4 6 0.7 without glycerol vs. 7.6 6 0.9 mmol/kgzmin with glycerol, representing approximately 60% vs. 62% of EGP. In conclusion, GNG measured by 2H2O yields higher results than those measured by (2-13C)glycerol. This discrepancy is not merely caused by infusion of glycerol per se. Rather, the discrepancy between both methods prob- ably relates to conceptual problems in underlying assumptions in one or both methods. (J Clin Endocrinol Metab 86: 2220 -2226, 2001)
  • Article
    Full-text available
    The speed of absorption of dietary amino acids by the gut varies according to the type of ingested dietary protein. This could affect postprandial protein synthesis, breakdown, and deposition. To test this hypothesis, two intrinsically 13C-leucine-labeled milk proteins, casein (CAS) and whey protein (WP), of different physicochemical properties were ingested as one single meal by healthy adults. Postprandial whole body leucine kinetics were assessed by using a dual tracer methodology. WP induced a dramatic but short increase of plasma amino acids. CAS induced a prolonged plateau of moderate hyperaminoacidemia, probably because of a slow gastric emptying. Whole body protein breakdown was inhibited by 34% after CAS ingestion but not after WP ingestion. Postprandial protein synthesis was stimulated by 68% with the WP meal and to a lesser extent (+31%) with the CAS meal. Postprandial whole body leucine oxidation over 7 h was lower with CAS (272 ± 91 μmol⋅kg−1) than with WP (373 ± 56 μmol⋅kg−1). Leucine intake was identical in both meals (380 μmol⋅kg−1). Therefore, net leucine balance over the 7 h after the meal was more positive with CAS than with WP (P < 0.05, WP vs. CAS). In conclusion, the speed of protein digestion and amino acid absorption from the gut has a major effect on whole body protein anabolism after one single meal. By analogy with carbohydrate metabolism, slow and fast proteins modulate the postprandial metabolic response, a concept to be applied to wasting situations.