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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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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
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
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
) 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
, 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
, and 132 mgN ∙ kg
respectively (2). This corresponds to 0.65 and 0.83 g
good quality protein kg
, or 52 g and 66.4 g per day respectively for an 80 kg
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
and 1.2 to 1.4 g kg
respectively, corresponding to 112 to 144 and 96 to 112 grams protein per day
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).
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
. 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
∙ kg
, which is reached at an intake
level of 0.53 g protein N/kg
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
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
(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
∙ kg ∙
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
∙ kg
Milk Proteins
Using [
N]-labeling dietary protein methodology, 25 subjects (with mean BMI of
22.4 ± 2.5 kg/m
) swallowed an ileal tube and ingested 30 g of [
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 [
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 [
N]-globulins, (G meal) (301 mmol N) or as a mix
of [
N]-globulins and [
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
N-, and
H-labeled egg protein, both cooked (C)
and raw (R) were evaluated. Measurements of mean
exhalation rate in breath
after the ingestion continued for 6 h. The cumulative amount of administered dose
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 [
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 (
C-WP), or 43 g (479 mmol N) of labeled casein protein (
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
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.
1 0
3 9
9 0
- 1 2 . 5
- 2 0 0 2 0 4 0 6 0 8 0 1 0 0
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
(~ 14 g/h) (55) and glucose 60 to 100 g/h (0.8 to 1.2 g car-
bohydrate kg
) 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
(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
, 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).
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
of dietary protein, had a fasting plasma glucagon 34% higher than subjects
consuming 0.74 ± 0.08 g ∙ kg
(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).
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
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
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
), 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
by the liver
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
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
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
, there was a decreased protein breakdown, and
increased protein synthesis of up to 63%, compared with intakes of 1g ∙ kg
(16). Subjects receiving 1g kg
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
, 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).
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
∙ d
protein, carbohydrate < 40% of energy (HP), or
0.8 g kg
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
), well below the maximal level. Even for a 60 kg individual (2.7 g kg
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
∙ d
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
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
∙ d
Daily energy
% Energy
Body weight (kg)
40 50 60 70 80 90 100 110
Protein intake (g ∙ kg
∙ d
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
∙ d
) and development of renal insufficiency (17,
116), and renal clearance is still highly efficient at protein intakes of up to 3.0 g
(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
∙ d
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
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
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
) on a 12,000 kJ/d diet. A 60 kg individual
would consume 118 g at 2.0 g ∙ kg
on a 8000 kJ/d diet and 147 g protein at
2.5 g ∙ kg
∙ d
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).
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... In all proposed diet combinations, proteins are generally in excess, mostly due to the high availability of meat in the first two periods of the ASRS from the presumed slaughter of most farmed animals due to lack of feed. The MRAI upper limit was set to 140 g per WHO recommendations [34]; however, Bilsborough and Mann reported that obtaining over 35% of the energy intake as proteins (184 g for 2100 kcal) is 'dangerously excessive' while 25% (131 g) is safe [63], hence, while this does not appear to be risk-free, it is likely tolerable for a certain amount of time, especially during a catastrophe. ...
... On top of many subgroups not being taken into account, other considerations were not included in the scope. There are three different kinds of recommendations that should be considered simultaneously: absolute intake (g/day), intake related to body weight (g/kg/day), and intake as a fraction of total energy (% energy) [63]. Selecting one energy intake and body weight couple-namely 2100 kcal and 62 kg-simplified the analysis, but this omission should be dealt with in future work. ...
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Abrupt sunlight reduction scenarios (ASRS) following catastrophic events, such as a nuclear war, a large volcanic eruption or an asteroid strike, could prompt global agricultural collapse. There are low-cost foods that could be made available in an ASRS: resilient foods. Nutritionally adequate combinations of these resilient foods are investigated for different stages of a scenario with an effective response, based on existing technology. While macro- and micronutrient requirements were overall met, some—potentially chronic—deficiencies were identified (e.g., vitamins D, E and K). Resilient sources of micronutrients for mitigating these and other potential deficiencies are presented. The results of this analysis suggest that no life-threatening micronutrient deficiencies or excesses would necessarily be present given preparation to deploy resilient foods and an effective response. Careful preparedness and planning—such as stock management and resilient food production ramp-up—is indispensable for an effective response that not only allows for fulfilling people’s energy requirements, but also prevents severe malnutrition.
... For context, mean TT for a comparably aged population (27 years) is 14 nmol/L (Kelsey et al., 2014), thus −5.23 nmol/L represents a 37% decrease. Protein intakes ≥35% may outstrip the urea cycle's capacity to convert nitrogen derived from amino acid catabolism into urea, leading to hyperammonaemia and its toxic effects (Bilsborough and Mann, 2006). T has been shown to suppress the urea cycle (Lam et al., 2017), whilst glucocorticoids upregulate the urea cycle (Okun et al., 2015). ...
... In practise, most free-living LC diets will fall below the urea cycle capacity threshold (≤35% protein), as population protein intakes are stable at 15-17% (Cohen et al., 2015), likely due to a protein-specific appetite mechanism (Leidy et al., 2015). However, one can find articles online advocating protein intakes ≤35%, which if followed precisely, may lead to adverse endocrine effects, particularly in individuals with lower rates of maximal urea synthesis (Bilsborough and Mann, 2006). ...
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Background: Low-carbohydrate diets may have endocrine effects, although individual studies are conflicting. Therefore, a review was conducted on the effects of low- versus high-carbohydrate diets on men's testosterone and cortisol. Methods: The review was registered on PROSPERO (CRD42021255957). The inclusion criteria were: intervention study, healthy adult males, and low-carbohydrate diet: ≤35% carbohydrate. Eight databases were searched from conception to May 2021. Cochrane's risk of bias tool was used for quality assessment. Random-effects, meta-analyses using standardized mean differences and 95% confidence intervals, were performed with Review Manager. Subgroup analyses were conducted for diet duration, protein intake, and exercise duration. Results: Twenty-seven studies were included, with a total of 309 participants. Short-term (<3 weeks), low- versus high-carbohydrate diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01). Whereas, long-term (≥3 weeks), low-carbohydrate diets had no consistent effect on resting cortisol. Low- versus high-carbohydrate diets resulted in much higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01). Moderate-protein (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (−1.08 [−1.67, −0.48], p < 0.01) and post-exercise total testosterone (−1.01 [−2, −0.01] p = 0.05). Conclusions: Resting and post-exercise cortisol increase during the first 3 weeks of a low-carbohydrate diet. Afterwards, resting cortisol appears to return to baseline, whilst post-exercise cortisol remains elevated. High-protein diets cause a large decrease in resting total testosterone (∼5.23 nmol/L).
... According to the WHO, the daily requirement of BCAA is leucine: 10 mg/kg body weight; Valine FR: 10 mg/kg body weight; Isoleucine: 10 mg/kg body weight. Leucine activates various motor signalling pathways to regulate protein synthesis, energy detectors, and nutrient sensor and amino acids availability (leucine) (149) . The motor pathway activates during higher ATP levels and is vitally important for the hypertrophy of skeletal muscles (148) . ...
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ABSTRACTSarcopenia is a societal health issue owing to population density shifts and characterized by musclemass and muscle function loss due to age. Despite many efforts to develop treatment strategies forsarcopenia, exceptionally restricted therapies are still available for clinical use. Mostpharmacological drugs studied too far have been hormonal and targeting myostatin signaling.Alternatively, dietary supplements help to improve sarcopenia and recover muscular function. Asubstantial body of scientific and clinical data supports a positive outlook for the use of naturaltherapy and chemicals to manage or treat diseases. It is possible to take nutritional supplements insuch a way that will provide sufficient vital nutrients for human requirements. The purpose of thisstudy is to provide an overview of current information about the nutritional characteristics, helpfuland nutritious substances, and their application in the management and treatment of sarcopenia. KEYWORDS: Sarcopenia, muscle mass, ageing, giant muscle, musculoskeletal system
... Regarding dietary proteins, two main research areas have been developed. The first deals with the effect of protein intake on weight loss and glycemic control and the second deals with the long-standing interest of the preservation of muscle mass [98]. Indeed, dietary proteins provide amino acids that are essential for the synthesis of muscle protein [66,75] and glucose control and which result in reduced fasting glucose [66], triglycerides [66], and improved insulin responses [76], independently of age [93,94]. ...
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Medical and technology development have drastically the improved quality of life and, consequently, life expectancy. Nevertheless, the more people who enter the third-age, the more geriatric syndromes expand in the elderly. Sarcopenia and Type 2 diabetes mellitus (T2DM) are common diseases among the elderly and the literature has extensively studied these two diseases separately. Recent evidence, however, revealed that there is a bidirectional relationship between sarcopenia and T2DM. The aims of the present review were: (1) to present diet and exercise interventions for the management of sarcopenia and T2DM and (2) identify which diet and exercise interventions can be used simultaneously in order to effectively deal with these two disorders. Exercise and a balanced diet are used as effective countermeasures for combating sarcopenia and T2DM in older adults based on their bidirectional relationship. Lifestyle changes such as exercise and a balanced diet seem to play an important role in the remission of the diseases. Results showed that chronic exercise can help towards glycemic regulation as well as decrease the incidence rate of muscle degradation, while diet interventions which focus on protein or amino acids seem to successfully treat both disorders. Despite the fact that there are limited studies that deal with both disorders, it seems that a combined exercise regime (aerobic and resistance) along with protein intake > 1gr/kg/d is the safest strategy to follow in order to manage sarcopenia and T2DM concurrently.
... The resilience of the USO resource would have been an important driver in early hunter-gatherer patterns since humans would have relied on USOs for a source of carbohydratesdeemed an essential part of a hunter-gatherer's diet (Noli & Avery, 1988;Speth, 1987Speth, , 1989Speth & Spielmann, 1983;Tushingham, Barton & Bettinger, 2021). There is a maximal constraint on the intake of protein by humans, necessitating a diet that incorporates carbohydrates, fat and protein; referred to as "rabbit starvation"-a diet based solely on lean meat can lead to starvation or protein poisoning (Bilsborough & Mann, 2006). Nitrogen metabolized from dietary protein is toxic and must be converted to urea and excreted by the liver, which can only metabolize urea at an approximately fixed rate. ...
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Current ecological understanding of plants with underground storage organs (USOs) suggests they have, in general, low rates of recruitment and thus as a resource it should be rapidly exhausted, which likely had implications for hunter-gatherer mobility patterns. We focus on the resilience (defined here as the ability of species to persist after being harvested) of USOs to human foraging. Human foragers harvested all visible USO material from 19 plots spread across six Cape south coast (South Africa) vegetation types for three consecutive years (2015–2017) during the period of peak USO apparency (September–October). We expected the plots to be depleted after the first year of harvesting since the entire storage organ of the USO is removed during foraging, i.e . immediate and substantial declines from the first to the second harvest. However, over 50% of the total weight harvested in 2015 was harvested in 2016 and 2017; only after two consecutive years of harvesting, was there evidence of significantly lower yield ( p = 0.034) than the first (2015) harvest. Novel emergence of new species and new individuals in year two and three buffered the decline of harvested USOs. We use our findings to make predictions on hunter-gatherer mobility patterns in this region compared to the Hadza in East Africa and the Alyawara in North Australia.
... On structural needs, a casein intake of 0.8g/kg/day is advised. High-protein diets (protein consumption of 200 to 400 g/day, or roughly 5 g/kg/day), on the other hand, may exceed the liver's ability to convert more nitrogen to urea (Bilsborough and Mann, 2006). Dietary AA levels peaked at 2.5 h in the soy group and 3.9 h in the milk group. ...
... We did find tissue compositions of animals changed consistently with body size (Fig. 8;Calder 1996); this likely has greater nutritional consequences with larger animals typically containing more fat and less organ tissue. This increase in fat in larger species occurs in both fat tissue deposits and bone marrow (Speth 1989;Thompson et al. 2019) such that eating exclusively animals with insufficient fat, often smaller species, can cause repeated nausea and diarrhea, or "rabbit starvation syndrome", with potentially lethal consequences (Speth and Spielmann 1983;Bilsborough and Mann 2006). Yet many contaminants, including mercury ( Fig. 9), DDT, and PCB, (Supplementary Material 5, Fig. S4) also tended to increase in concentration with body size, suggesting the adequacy of nutritionally desirable larger species could be reduced due to contamination. ...
Traditional food systems based on harvest from the local environment are fundamental to the well-being of many communities, but their security is challenged by rapid socio-ecological change. We synthesized literature and data describing how a fundamental form of biodiversity, animal body size, contributes to the security of traditional food systems through relationships with species availability, accessibility, adequacy, and use. We found larger vertebrate species were more available, accessible, and used on a per kilogram basis, particularly for mammals. Conversely, larger species were no more or less adequate from a combined nutritional, health, and cultural perspective. Larger species represented more biomass, and this biomass required less time to harvest, with greater but more variable mean caloric returns over time. Smaller species provided more consistent caloric returns and were harvested during documented shortages of prey. This reliance on species with a range of body sizes is consistent with optimal foraging theory and the evolutionary value of flexibility, and highlights the importance of a biodiverse pool of species for traditional food security in times of change. Our synthesis of published literature and data highlights the many socio-ecological correlates of species size and how these relate to the security of traditional food systems.
Whey protein (WP) can increase insulin secretion, produce an incretin effect, delay gastric emptying, and regulate appetite, resulting in improved glycemic control. We hypothesized that WP supplementation is associated with postprandial glycemia regulation in persons with type 2 diabetes mellitus (T2DM) and conducted a quantitative meta-analysis of randomized controlled trials (RCTs) to test this hypothesis. We searched PubMed, Embase, Cochrane Library, Scopus databases, and the registry for relevant RCTs published before March 2022. We assessed the pooled effects using a random-effects model on glucose and insulin levels at 60 and 120 min, total glucagon-like peptide-1 (tGLP-1) at 30 and 60 min, and the incremental area under the curve (iAUC) of glucose, insulin, tGLP-1, and glucose-dependent insulinotropic polypeptide. Five RCTs involving 134 persons were included. Postprandial glycemia was significantly lower at 60 min (weighted mean difference: −2.67 mmol/L, 95% confidence interval: 3.62 to 1.72 mmol/L) and 120 min (−1.59 mmol/L, −2.91 to −0.28 mmol/L) in WP group than in placebo group. The iAUC of insulin was significantly higher in WP group (24.66 nmol/L × min, 1.65 to 47.66 nmol/L × min) than in placebo group. Although other results favored the WP group, differences between the groups were not statistically significant. The present study showed that premeal WP supplementation is beneficial for postprandial glycemia in persons with mild or well-controlled T2DM without substantial adverse effects. However, the level of certainty of current evidence is not high enough. Further larger and well-designed clinical trials are warranted for evaluating optimal dose and long-term effects of WP supplementation.
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Based on my interest in environmental and social justice issues, combined with my practical experience as a senior volunteer with an environmental charity, I decided to write a book addressing the key issues. The Occupy Movement was another motivating factor, because it was clear that while many of the protestors passionately sensed that something is very wrong with the current socio-political system, they could not articulate exactly what the problems were. With my capacity to research and amalgamate disparate data, it seemed like a useful contribution. Although I was familiar with many of the issues, it was a profound learning experience, confirming that we are at a tipping point pertaining to several environmental and social justice issues. Solutions fostering true hope are provided. The book was designed for a general public (trade) audience, but several of the chapters are quite academic in regards to covering key aspects of the literature, such as the Research Bias and Obesity chapters. Of significance, despite it being published several years ago, the problems plus coverage and solutions still do apply. A pdf of the full book is provided! SYNOPSIS: Collectively we are engaging in self-destructive behavior, compromising our present and jeopardizing our future bringing us to a tipping point. Rampant greed, irregular regulation, unrestrained urban and resource development, out of control global warming, biased pharmaceutical and biotechnology research, and lethal levels of obesity, are all severely damaging us. Dr. Bowins drills down exposing these forms of self-destruction, and shows why we might be setting ourselves up for widespread revolution and devastation due to their impact on environmental and social justice. Also revealed is how our psychological defenses ironically perpetuate major forms of self-destructive behavior. We have reached the tipping point, but the solutions proposed can save us from self-destruction, if we each take action.
Previous studies have indicated high-protein diet (HPD) promotes weight loss and improves metabolic parameters, but most of these studies have focused on the impact of short-term, long-term effects remain unclear. In this study, male Wistar rats were fed two diets for 88 weeks: normal control diet (NCD, 20.5% of energy as protein) or HPD (30.5% of energy as protein). At 88 weeks intervention, compared to NCD rats, HPD rats had lower fat tissue and higher skeletal muscle to body weight ratio, but there were no significantly differences in body weight and food intake. To explore the mechanism underlying metabolism and diet, we further collected rat urine samples at 16, 40, 64 and 88 weeks diet treatment and analyzed metabolomics profiles using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Partial least squares-discriminant analysis (PLS-DA) scores plots from ESI- or ESI+ model revealed a perfect separation between two diets at four time points. We identified 11 dramatically different metabolites (with VIP cut-off value >1) in HPD, including 3 up-regulated and 8 down-regulated. And these 11 metabolites were identified as effective biomarkers, which were significantly related to HPD-induced metabolism related outcomes (fat tissue and skeletal muscle to body weight ratio). Our results provided vital information regarding metabolism in long-term HPD and more importantly, a few potentially promising metabolites were firstly identified which may related to metabolic responses.
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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@ 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 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 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).
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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)
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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.
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.
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)
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.
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.