Post by EBA84 on May 14, 2007 15:47:35 GMT -5
This is long but I found it pretty interesting.
Sports Nutrition Review Journal. 1(1):45-51, 2004. (www.sportsnutritionsociety.org)
HIGH-PROTEIN WEIGHT LOSS DIETS AND
PURPORTED ADVERSE EFFECTS: WHERE IS THE
EVIDENCE?
Anssi H. Manninen
Department of Physiology, Faculty of Medicine, University of Oulu, Finland. Sports Nutrition
Review Journal. 1(1):45-51, 2004. Address correspondence to anssi.manninen@oulu.fi.
Received March 1, 2004/Accepted May 9, 2004/Published (online):
ABSTRACT
Results of several recent studies show that high-protein, low-carbohydrate weight loss diets indeed
have their benefits. However, agencies such as the American Heart Association (AHA) have some
concerns about possible health risks. The purpose of this review is to evaluate the scientific validity
of AHA Nutrition Committee´s statement on dietary protein and weight reduction (St. Jeor ST et al.
Circulation 2001;104:1869-1874), which states: “Individuals who follow these [high-protein] diets
are risk for… potential cardiac, renal, bone, and liver abnormalities overall. Simply stated, there is
no scientific evidence whatsoever that high-protein intake has adverse effects on liver function.
Relative to renal function, there are no data in the scientific literature demonstrating that healthy
kidneys are damaged by the increased demands of protein consumed in quantities 2-3 times above
the Recommended Dietary Allowance (RDA). In contrast with the earlier hypothesis that high-
protein intake promotes osteoporosis, some epidemiological studies found a positive association
between protein intake and bone mineral density. Further, recent studies studies suggest, at least in
the short term, that RDA for protein (0.8 g/kg) does not support normal calcium homeostasis.
Finally, a negative correlation has been shown between protein intake and systolic and diastolic
blood pressures in several epidemiological surveys. In conclusion, there is little if any scientific
evidence supporting above mentioned statement. Certainly, such public warnings should be based
on a thorough analysis of the scientific literature, not unsubstantiated fears and misrepresentations.
For individuals with normal renal function, the risks are minimal and must be balanced against the
real and established risk of continued obesity. Sports Nutrition Review Journal. 1(1):45-51, 2004
Key Words: high-protein diets, adverse effects, American Heart Association
INTRODUCTION our ancient ancestors. The typical Paleolithic diet
compared with the average modern American
Certainly, living organisms thrive best in the diet contained 3 to 4 times more protein.40
milieu and on the diet to which they were
evolutionarily adopted. From all indications, It is implausible that an animal that adapted to a
Homo sapiens sapiens (anatomically modern high protein diet for 5 million years suddenly in
humans) has remained biologically 10,000 years becomes a predominant
unchanged during at least the last 50,000 carbohydrate burner. Indeed, counter to the
years.39 It was not until some 10,000 years current U.S. Dietary Guidelines which promotes
ago that the transition from a roaming hunter diet high in complex carbohydrates, recent
and gatherer to a stationary farmer began. clinical investigations support the efficacy of
Consequently, our diet has become high-protein diets for weight loss/fat loss, as well
progressively more divergent from those of as for improved insulin sensitivity and blood
Sports Nutrition Review Journal©. A National Library of Congress Indexed Journal. ISSN # 1550-2783
Sports Nutrition Review Journal. 1(1):45-51, 2004. (www.sportsnutritionsociety.org)
lipid profiles. Thus, the popularity of high-
protein diets for weigh loss is unquestionable.
However, there are always some concerns
about high-protein diets.
In 2001, the American Heart Association
(AHA) Nutrition Committee published
statement on dietary protein and weight
reduction.2 According to this statement,
“Individuals who follow these [high-protein]
diets are risk for… potential cardiac, renal,
bone, and liver abnormalities overall.
However, it should be noted that there is little
if any evidence supporting these contentions.
Thus, this review deals with the relationship
between protein intake and renal function,
bone health, blood pressure, heart disease and
liver function. Also, effects of very-low
carbohydrate diet on lean body mass loss are
discussed.
PROTEIN INTAKE AND RENAL
FUNCTION
Healthy individuals. Despite its role in
nitrogen excretion, there are presently no data
in the scientific literature demonstrating the
healthy kidney will be damaged by the
increased demands of protein consumed in
quantities above the Recommended Dietary
Allowance (RDA). Furthermore, real world
examples support this contention since kidney
problems are nonexistent in the bodybuilding
community in which high-protein intake has
been the norm for over half a century.3
Recently, Walser published comprehensive
review on protein intake and renal function,
which states: “it is clear that protein
restriction does not prevent decline in renal
function with age, and, in fact, is the major
cause of that decline. A better way to prevent
the decline would be to increase protein
intake... there is no reason to restrict protein
intake in healthy individuals in order to
protect the kidney.” 4
The study by Poortmans and Dellalieux
investigated body-builders and other well-
trained athletes with high- and medium-
protein intake, respectively.5 The athletes
underwent a 7-day nutrition record analysis as
well as blood sample and urine collection to
determine the potential renal consequences of a
high protein intake. The data revealed that
despite higher plasma concentration of uric acid
and calcium, bodybuilders had renal clearances
of creatinine, urea, and albumin that were within
the normal range. To conclude, it appears, at
least in the short term, that protein intake under
2.8 g/kg does not impair renal function in well-
trained athletes.
More recently, Knight et al. determined whether
protein intake influences the rate of renal
function change in women over an 11-year
period.32 1624 women enrolled in the Nurses’
Health Study who were 42 to 68 years of age in
1989 and gave blood samples in 1989 and 2000.
Ninety-eight percent of women were white, and
1% were African American. In multivariate
linear regression analyses, high protein intake
was not significantly associated with change in
estimated glomerular filtration rate (GFR) in
women with normal renal function (defined as an
estimated GFR 80 mL/min per 1.73 m2). Thus,
the authors concluded that high protein intake
does not seem to be associated with renal
function decline in women with normal renal
function. As pointed out by Lentine and
Wrone33, the generalizability of these findings is
limited by sampling characteristics to white mid-
adulthood, but this limitation is overshadowed
by strong internal validity grounded in a large
sample size, prospective outcomes
ascertainment, and adjustment for multiple
covariates.
Chronic Renal Failure. Historically, dietary
protein restriction has been recommend as a
therapeutic approach for delaying the
progression of chronic renal failure (CRF).
However, as pointed out by Ikizler,6 it is
important to reassess the applicability of this
approach. Indeed, the results of the largest
randomised clinical trial, The Modification of
Diet in Renal Disease (MDRD), did not
demonstrate a benefit of dietary protein
restriction on progression of renal disease.7
Further, CRF patients have been shown to
require a protein intake of 1.4 g/kg/day to
Sports Nutrition Review Journal. 1(1):45-51, 2004. (www.sportsnutritionsociety.org)
maintain a positive or neutral nitrogen
balance during nondialysis days, and even this
intake may not be adequate for dialysis days.6
Diabetics. According to American Diabetes
Association (ADA), there is no evidence to
suggest that usual protein intake (15-20% of
total calories) should be modified if renal
function is normal.8 The long-term effects of
consuming > 20% of energy as protein on the
development of nephropathy has not been
determined, and therefore ADA nutritionists
felt it may be prudent to avoid protein intakes
> 20% of total daily energy.8 More recently,
the metabolic effects of a high-protein diet
were compared with those of the prototypical
healthy (control) diet, which is currently
recommended to persons with type 2
diabetes.31 The ratio of protein to
carbohydrate to fat was 30:40:30 in the high-
protein diet and 15:55:30 in the control diet.
The high-protein diet resulted in a 40%
decrease in the mean 24-h integrated glucose
area response. Further, glycated hemoglobin
decreased 0.8% and 0.3% after 5 weeks of the
high-protein and control diets, respectively.
Finally, fasting triacylglycerol was
significantly lower after the high-protein diet
than after the control diet. The authors
concluded that a high-protein diet lowers
blood glucose postprandially in persons with
type 2 diabetes and improves overall glucose
control. Cleary, longer-term studies are
necessary to determine the total magnitude of
response and possible adverse effects.
PROTEIN INTAKE AND BONE
HEALTH
Increasing dietary protein increases urine
calcium excretion such that for each 50 g
increment of protein consumed, and extra 60
mg of urinary calcium is excreted. It follows
that the higher the protein intake, the more
urine calcium is lost and the more negative
calcium balance becomes. Since 99% of the
body´s calcium is found in bone, one would
hypothesize that high protein induced
hypercalciuria would results in high bone
resorption and increased prevalence of
osteopenia or osteoporotic-related fractures.
However, the epidemiological and clinical data
addressing this hypothesis are controversial. In
fact, some epidemiological studies found a
positive association between protein intake and
bone mineral density (BMD).9,37,38 Further, there
is growing evidence that a low protein diet has a
detrimental effect on bone. For example,
Kerstetter et al. reported that in healthy young
women, acute intakes of a low-protein diet (0.7 g
protein/kg) decreased urinary calcium excretion
with accompanied secondary
hyperparathyroidism.10 The etiology of the
secondary hyperparathyroidism is due, in part, to
a significant reduction in intestinal calcium
absorption during a low protein diet.
In a recent short-term intervention trial,
Kerstetter et al. evaluated the effects of graded
levels of dietary protein (0.7, 0.8, 0.9, and 1.0 g
protein/kg) on calcium homeostasis.11 Secondary
hyperparathyroidism developed by day 4 of the
0.7 and 0.8 g protein/kg diets (due to the
decreased intestinal calcium absorption), but not
during the 0.9 or 1.0 g protein/kg diets in eight
young women. There were no significant
differences in mean urinary calcium excretion
over the relatively narrow range of dietary
protein intakes studied, although the mean value
with the 0.7-g/kg intake was lower than that with
the 1.0 g/kg intake by 0.25 mmol (10 mg).
According to authors of this study, the lack of
change may be due to the small sample and the
inherent variability in urinary calcium excretion.
Similarly, when Giannini et al. restricted dietary
protein to 0.8 g protein/kg, they observed an
acute rise in serum parathyroid hormone (PTH)
in 18 middle-aged hypercalciuric adults.12 Taken
together, both of studies suggest, at least in the
short term, that the RDA for protein (0.8 g/kg)
does not support normal calcium homeostasis.
Furthermore, dietary protein increases
circulating IGF-1, a growth factor that is thought
to play an important role in bone formation.
Indeed, several studies have examined the
impact of protein supplementation in patients
with recent hip fractures. For example, Schurch
Sports Nutrition Review Journal. 1(1):45-51, 2004. (www.sportsnutritionsociety.org)
et al. reported that supplementation with 20 g
protein/day for 6 months increased blood
IGF-levels and reduced the rate of bone loss
in the contralateral hip during the year after
the fracture.28 More recently, the Cochrane-
review assessed the effects of nutritional
interventions in elderly people recovering
from hip fracture.41 Seventeen randomised
trials involving 1266 participants were
included. According to reviewers, the
strongest evidence for the effectiveness of
nutritional supplementation exists for oral
protein and energy feeds, but the evidence is
still weak.
Moreover, many of these early studies that
demonstrated the calciuric effects of protein
were limited by low subject numbers,
methodological errors and the use of high
doses of purified forms of protein.35 Indeed,
the recent study Dawson-Hughes et al. did not
confirm the perception that increased dietary
protein results in urinary calcium loss.36
According to Dawson-Hughes et al., “The
constellation of findings that meat
supplements containing 55 g/d protein, when
exchanged for carbohydrate did not
significantly increase urinary calcium
excretion and were associated with higher
levels of serum IGF-I and lower levels of the
bone resorption marker, N-telopeptide,
together with a lack of significant correlation
of urinary N-telopeptide with urinary calcium
excretion in the high protein group (in
contrast to the low protein) point to the
possibility that higher meat intake may
potentially improve bone mass in many older
men and women.”
Finally, the cross-cultural and population
studies that showed a positive association
between animal-protein intake and hip
fracture risk did not consider other lifestyle or
dietary factors that may protect or increase the
risk of fracture.35 It is of some interest that the
author of the most cited paper favoring the
earlier hypothesis that high-protein intake
promotes osteoporosis no longer believes that
protein is harmful to bone.34 In fact, he
concluded that the balance of the evidence seems
to indicate the opposite.34
PROTEIN INTAKE AND BLOOD
PRESSURE
The AHA Nutrition Committee suggests that
high-protein intake may increase blood pressure.
However, there is no scientific evidence
supporting this contention. In fact, a negative
correlation has been shown between protein
intake and systolic and diastolic blood pressures
in several epidemiological surveys analyzed by
Obarzanek et al.13 For example,
• Honolulu Heart Study. In this study of 6,406
Japanese-American men, a negative
relationship was observed between systolic
and diastolic blood pressures and the amount
protein consumed.14
• Chinese Study. In this investigation of 2,672
adults men and women, a negative
relationship was found between systolic
pressure and the amount of animal protein
consumed.15
• MRFIT Study. Based on 11,342 adult men,
investigators observed a negative relationship
between systolic blood pressure and the
amount of total protein consumed.16
In both normotensive and hypertensive rats,
increasing the dietary protein level enhances
both urine and the amount of sodium excreted,
although the mechanism behind these effects is
unknown and still speculative.17 Interestingly,
one study in human volunteers with a family
history of hypertension has shown that a high-
protein diet may counteract the adverse effects of
excessive salt intake.18 For more information on
protein intake and blood pressure, see the recent
review by Debry.17
PROTEIN INTAKE AND HEART DISEASE
Recent findings by Hu et al. suggests that
replacing carbohydrates with protein may be
associated with a lower risk of ischemic heart
disease.25 This result is consistent with evidence
from metabolic studies that replacement of
dietary carbohydrate with protein has favorable
Sports Nutrition Review Journal. 1(1):45-51, 2004. (www.sportsnutritionsociety.org)
effect on plasma lipoprotein and lipid
concentrations. However, because an increase
in protein intake from animal products such as
meats, dairy products, and eggs is often
accompanied by increases in intakes of
saturated fat and cholesterol, dietary advice to
improve public health based on these findings
should be made with caution.25
Recent novel approaches have shown that
glucose and lipid intake may induce an
increase in the generation of reactive oxygen
species (ROS) and oxidative stress. For
example, Mohanty et al. produced evidence
that all three major macronutrients induce an
increase in ROS generation.26 However, their
data also show that different nutrients produce
distinct patterns of stimulation of ROS
generation after their intake. Of the three
nutrients, glucose induced the greatest ROS
generation, followed in decreasing order by
fat (cream) and by protein (casein). The
detriment of oxidative stress is that it may
damage proteins and lipids, the latter through
lipid peroxidation. Lipid peroxidation of
LDL-C particles is an essential step in the
development of atherosclerosis.27
PROTEIN INTAKE AND LIVER
FUNCTION
AHA Nutrition Committee suggests that high-
protein intake may have detrimental effects
on liver function. However, there is no
scientific evidence whatsoever supporting this
contention. Protein is needed not only to
promote liver tissue repair, but also to provide
lipotropic agents such as methionine and
choline for the conversion of fats to
lipoprotein for removal from the liver, thus
preventing fatty infiltration.20
Rodents fed very high protein intakes have
been found to exhibit morphological changes
in the liver mitochondria, which could be
pathological. However, Jorda et al. reported
that the liver responds to the high-protein diet
by a proliferation of normally functioning
mitochondria.24 Further, the branched-chain
amino acids to aromatic amino acids ratio was
also increased, indicating the absence of hepatic
failure in these animals. The authors concluded
that “the increased protein content of diet
induced rapid increases in several
characteristics of hepatocytes… The results
presented here constitute a good example of how
the hepatocyte adapts to a continuing metabolic
stress.”
Further, protein catabolism is increased in liver
disease and may be exacerbated by inadequate
protein in the diet.19 Unless there is
encephalopathy (vide infra), the diet should
provide high-quality protein in the amount of 1.5
to 2 g/kg.19 In alcoholic liver disease, a high-
calorie, high-protein diet has been shown to
improve hepatic function and reduce mortality.
In one study, this was achieved by providing a
regular diet plus supplements of 60 g/day of
protein and 1600 kcal/day for the first 30 days
and followed by supplements of 45 g/day of
protein and 1200 kcal/day for the next 60 days.21
Finally, the role of protein restriction in patients
with chronic hepatic encephalopathy (HE) has
been questioned recently as the efficacy of
protein withdrawal in patients with HE has never
been subjected to a controlled trial.29 According
to Srivastava et al., “the emphasis in the
nutritional management of patients with HE
[hepatic encephalopathy] should not be on the
reduction of protein intake. Instead, the goal
should be to promote synthesis by making
available ample amounts of amino acids, while
instituting other measures to reverse the ongoing
catabolism.”29
EFFECTS OF VERY-LOWCARBOHYDRATE DIET ON LEAN BODY
MASS
According to the AHA Nutrition Committee,
“Some popular high-protein/low-carbohydrate
diets limit carbohydrates to 10 to 20 g/d, which
is one fifth of the minimum 100 g/day that is
necessary to prevent loss of lean muscle tissue.”
Clearly, this is an incorrect statement since
catabolism of lean body mass is reduced by
ketones, which probably explains the
Sports Nutrition Review Journal. 1(1):45-51, 2004. (www.sportsnutritionsociety.org)
preservation of lean tissue observed during Oddly, the AHA Nutrition Committee ignores
very-low-carbohydrate diets. the fact that energy restriction increases protein
requirements. It has been know for about a half
For example, Volek et al. examined the century that inadequate energy intake leads to
effects of 6-week carbohydrate-restricted diet increased protein needs, presumably because
on total and regional body composition and some of the protein normally used to synthesize
the relationships with fasting hormones.22 both functional (enzymatic) and structural
Twelve healthy normal-weight men switched (tissue) protein is utilized for energy under these
from their habitual diet (48% carbohydrate) to conditions.1 For example, Butterfield has shown
a carbohydrate-restricted diet (8% that feeding as much as 2 g protein/kg/day to
carbohydrate) for 6 weeks and 8 men served men running 5 or 10 miles per day at 65% to
as controls, consuming their normal diet. 75% of their VO2max is insufficient to maintain
Subjects were encouraged to consume nitrogen balance when energy intake is
adequate dietary energy to maintain body inadequate by as little as 100 kcal/day.30 Thus,
mass during intervention. when trying to lose weight, it is important to
keep protein levels moderately high. The
Fat mass was significantly decreased (-3.4 kg) reduction in calories needed to lose weight
and lean body mass significantly increased should be at the expense of saturated fats and
(+1.1 kg) at week 6. However, there were no carbohydrates, not protein.
significant changes in composition in the
control group. The Authors concluded that a CONCLUSION
carbohydrate-restricted diet resulted in a
significant reduction in fat mass and a It is clear that the American Heart Association
concomitant increase in lean body mass in Nutrition Committee´s statement on dietary
normal-weight men. They hypothesized that protein and weight reduction contains misleading
elevated ß-hydroxybutyrate concentrations and incorrect information. Certainly, such public
may have played a minor role in preventing warnings should be based on a thorough analysis
catabolism of lean tissue but other anabolic of the scientific literature, not unsubstantiated
hormones were likely involved (e.g., growth fears and misrepresentations. For individuals
hormone). with normal renal function, the risks are minimal
and must be balanced against the real and
established risk of continued obesity.23
Sports Nutrition Review Journal. 1(1):45-51, 2004. (www.sportsnutritionsociety.org)
HIGH-PROTEIN WEIGHT LOSS DIETS AND
PURPORTED ADVERSE EFFECTS: WHERE IS THE
EVIDENCE?
Anssi H. Manninen
Department of Physiology, Faculty of Medicine, University of Oulu, Finland. Sports Nutrition
Review Journal. 1(1):45-51, 2004. Address correspondence to anssi.manninen@oulu.fi.
Received March 1, 2004/Accepted May 9, 2004/Published (online):
ABSTRACT
Results of several recent studies show that high-protein, low-carbohydrate weight loss diets indeed
have their benefits. However, agencies such as the American Heart Association (AHA) have some
concerns about possible health risks. The purpose of this review is to evaluate the scientific validity
of AHA Nutrition Committee´s statement on dietary protein and weight reduction (St. Jeor ST et al.
Circulation 2001;104:1869-1874), which states: “Individuals who follow these [high-protein] diets
are risk for… potential cardiac, renal, bone, and liver abnormalities overall. Simply stated, there is
no scientific evidence whatsoever that high-protein intake has adverse effects on liver function.
Relative to renal function, there are no data in the scientific literature demonstrating that healthy
kidneys are damaged by the increased demands of protein consumed in quantities 2-3 times above
the Recommended Dietary Allowance (RDA). In contrast with the earlier hypothesis that high-
protein intake promotes osteoporosis, some epidemiological studies found a positive association
between protein intake and bone mineral density. Further, recent studies studies suggest, at least in
the short term, that RDA for protein (0.8 g/kg) does not support normal calcium homeostasis.
Finally, a negative correlation has been shown between protein intake and systolic and diastolic
blood pressures in several epidemiological surveys. In conclusion, there is little if any scientific
evidence supporting above mentioned statement. Certainly, such public warnings should be based
on a thorough analysis of the scientific literature, not unsubstantiated fears and misrepresentations.
For individuals with normal renal function, the risks are minimal and must be balanced against the
real and established risk of continued obesity. Sports Nutrition Review Journal. 1(1):45-51, 2004
Key Words: high-protein diets, adverse effects, American Heart Association
INTRODUCTION our ancient ancestors. The typical Paleolithic diet
compared with the average modern American
Certainly, living organisms thrive best in the diet contained 3 to 4 times more protein.40
milieu and on the diet to which they were
evolutionarily adopted. From all indications, It is implausible that an animal that adapted to a
Homo sapiens sapiens (anatomically modern high protein diet for 5 million years suddenly in
humans) has remained biologically 10,000 years becomes a predominant
unchanged during at least the last 50,000 carbohydrate burner. Indeed, counter to the
years.39 It was not until some 10,000 years current U.S. Dietary Guidelines which promotes
ago that the transition from a roaming hunter diet high in complex carbohydrates, recent
and gatherer to a stationary farmer began. clinical investigations support the efficacy of
Consequently, our diet has become high-protein diets for weight loss/fat loss, as well
progressively more divergent from those of as for improved insulin sensitivity and blood
Sports Nutrition Review Journal©. A National Library of Congress Indexed Journal. ISSN # 1550-2783
Sports Nutrition Review Journal. 1(1):45-51, 2004. (www.sportsnutritionsociety.org)
lipid profiles. Thus, the popularity of high-
protein diets for weigh loss is unquestionable.
However, there are always some concerns
about high-protein diets.
In 2001, the American Heart Association
(AHA) Nutrition Committee published
statement on dietary protein and weight
reduction.2 According to this statement,
“Individuals who follow these [high-protein]
diets are risk for… potential cardiac, renal,
bone, and liver abnormalities overall.
However, it should be noted that there is little
if any evidence supporting these contentions.
Thus, this review deals with the relationship
between protein intake and renal function,
bone health, blood pressure, heart disease and
liver function. Also, effects of very-low
carbohydrate diet on lean body mass loss are
discussed.
PROTEIN INTAKE AND RENAL
FUNCTION
Healthy individuals. Despite its role in
nitrogen excretion, there are presently no data
in the scientific literature demonstrating the
healthy kidney will be damaged by the
increased demands of protein consumed in
quantities above the Recommended Dietary
Allowance (RDA). Furthermore, real world
examples support this contention since kidney
problems are nonexistent in the bodybuilding
community in which high-protein intake has
been the norm for over half a century.3
Recently, Walser published comprehensive
review on protein intake and renal function,
which states: “it is clear that protein
restriction does not prevent decline in renal
function with age, and, in fact, is the major
cause of that decline. A better way to prevent
the decline would be to increase protein
intake... there is no reason to restrict protein
intake in healthy individuals in order to
protect the kidney.” 4
The study by Poortmans and Dellalieux
investigated body-builders and other well-
trained athletes with high- and medium-
protein intake, respectively.5 The athletes
underwent a 7-day nutrition record analysis as
well as blood sample and urine collection to
determine the potential renal consequences of a
high protein intake. The data revealed that
despite higher plasma concentration of uric acid
and calcium, bodybuilders had renal clearances
of creatinine, urea, and albumin that were within
the normal range. To conclude, it appears, at
least in the short term, that protein intake under
2.8 g/kg does not impair renal function in well-
trained athletes.
More recently, Knight et al. determined whether
protein intake influences the rate of renal
function change in women over an 11-year
period.32 1624 women enrolled in the Nurses’
Health Study who were 42 to 68 years of age in
1989 and gave blood samples in 1989 and 2000.
Ninety-eight percent of women were white, and
1% were African American. In multivariate
linear regression analyses, high protein intake
was not significantly associated with change in
estimated glomerular filtration rate (GFR) in
women with normal renal function (defined as an
estimated GFR 80 mL/min per 1.73 m2). Thus,
the authors concluded that high protein intake
does not seem to be associated with renal
function decline in women with normal renal
function. As pointed out by Lentine and
Wrone33, the generalizability of these findings is
limited by sampling characteristics to white mid-
adulthood, but this limitation is overshadowed
by strong internal validity grounded in a large
sample size, prospective outcomes
ascertainment, and adjustment for multiple
covariates.
Chronic Renal Failure. Historically, dietary
protein restriction has been recommend as a
therapeutic approach for delaying the
progression of chronic renal failure (CRF).
However, as pointed out by Ikizler,6 it is
important to reassess the applicability of this
approach. Indeed, the results of the largest
randomised clinical trial, The Modification of
Diet in Renal Disease (MDRD), did not
demonstrate a benefit of dietary protein
restriction on progression of renal disease.7
Further, CRF patients have been shown to
require a protein intake of 1.4 g/kg/day to
Sports Nutrition Review Journal. 1(1):45-51, 2004. (www.sportsnutritionsociety.org)
maintain a positive or neutral nitrogen
balance during nondialysis days, and even this
intake may not be adequate for dialysis days.6
Diabetics. According to American Diabetes
Association (ADA), there is no evidence to
suggest that usual protein intake (15-20% of
total calories) should be modified if renal
function is normal.8 The long-term effects of
consuming > 20% of energy as protein on the
development of nephropathy has not been
determined, and therefore ADA nutritionists
felt it may be prudent to avoid protein intakes
> 20% of total daily energy.8 More recently,
the metabolic effects of a high-protein diet
were compared with those of the prototypical
healthy (control) diet, which is currently
recommended to persons with type 2
diabetes.31 The ratio of protein to
carbohydrate to fat was 30:40:30 in the high-
protein diet and 15:55:30 in the control diet.
The high-protein diet resulted in a 40%
decrease in the mean 24-h integrated glucose
area response. Further, glycated hemoglobin
decreased 0.8% and 0.3% after 5 weeks of the
high-protein and control diets, respectively.
Finally, fasting triacylglycerol was
significantly lower after the high-protein diet
than after the control diet. The authors
concluded that a high-protein diet lowers
blood glucose postprandially in persons with
type 2 diabetes and improves overall glucose
control. Cleary, longer-term studies are
necessary to determine the total magnitude of
response and possible adverse effects.
PROTEIN INTAKE AND BONE
HEALTH
Increasing dietary protein increases urine
calcium excretion such that for each 50 g
increment of protein consumed, and extra 60
mg of urinary calcium is excreted. It follows
that the higher the protein intake, the more
urine calcium is lost and the more negative
calcium balance becomes. Since 99% of the
body´s calcium is found in bone, one would
hypothesize that high protein induced
hypercalciuria would results in high bone
resorption and increased prevalence of
osteopenia or osteoporotic-related fractures.
However, the epidemiological and clinical data
addressing this hypothesis are controversial. In
fact, some epidemiological studies found a
positive association between protein intake and
bone mineral density (BMD).9,37,38 Further, there
is growing evidence that a low protein diet has a
detrimental effect on bone. For example,
Kerstetter et al. reported that in healthy young
women, acute intakes of a low-protein diet (0.7 g
protein/kg) decreased urinary calcium excretion
with accompanied secondary
hyperparathyroidism.10 The etiology of the
secondary hyperparathyroidism is due, in part, to
a significant reduction in intestinal calcium
absorption during a low protein diet.
In a recent short-term intervention trial,
Kerstetter et al. evaluated the effects of graded
levels of dietary protein (0.7, 0.8, 0.9, and 1.0 g
protein/kg) on calcium homeostasis.11 Secondary
hyperparathyroidism developed by day 4 of the
0.7 and 0.8 g protein/kg diets (due to the
decreased intestinal calcium absorption), but not
during the 0.9 or 1.0 g protein/kg diets in eight
young women. There were no significant
differences in mean urinary calcium excretion
over the relatively narrow range of dietary
protein intakes studied, although the mean value
with the 0.7-g/kg intake was lower than that with
the 1.0 g/kg intake by 0.25 mmol (10 mg).
According to authors of this study, the lack of
change may be due to the small sample and the
inherent variability in urinary calcium excretion.
Similarly, when Giannini et al. restricted dietary
protein to 0.8 g protein/kg, they observed an
acute rise in serum parathyroid hormone (PTH)
in 18 middle-aged hypercalciuric adults.12 Taken
together, both of studies suggest, at least in the
short term, that the RDA for protein (0.8 g/kg)
does not support normal calcium homeostasis.
Furthermore, dietary protein increases
circulating IGF-1, a growth factor that is thought
to play an important role in bone formation.
Indeed, several studies have examined the
impact of protein supplementation in patients
with recent hip fractures. For example, Schurch
Sports Nutrition Review Journal. 1(1):45-51, 2004. (www.sportsnutritionsociety.org)
et al. reported that supplementation with 20 g
protein/day for 6 months increased blood
IGF-levels and reduced the rate of bone loss
in the contralateral hip during the year after
the fracture.28 More recently, the Cochrane-
review assessed the effects of nutritional
interventions in elderly people recovering
from hip fracture.41 Seventeen randomised
trials involving 1266 participants were
included. According to reviewers, the
strongest evidence for the effectiveness of
nutritional supplementation exists for oral
protein and energy feeds, but the evidence is
still weak.
Moreover, many of these early studies that
demonstrated the calciuric effects of protein
were limited by low subject numbers,
methodological errors and the use of high
doses of purified forms of protein.35 Indeed,
the recent study Dawson-Hughes et al. did not
confirm the perception that increased dietary
protein results in urinary calcium loss.36
According to Dawson-Hughes et al., “The
constellation of findings that meat
supplements containing 55 g/d protein, when
exchanged for carbohydrate did not
significantly increase urinary calcium
excretion and were associated with higher
levels of serum IGF-I and lower levels of the
bone resorption marker, N-telopeptide,
together with a lack of significant correlation
of urinary N-telopeptide with urinary calcium
excretion in the high protein group (in
contrast to the low protein) point to the
possibility that higher meat intake may
potentially improve bone mass in many older
men and women.”
Finally, the cross-cultural and population
studies that showed a positive association
between animal-protein intake and hip
fracture risk did not consider other lifestyle or
dietary factors that may protect or increase the
risk of fracture.35 It is of some interest that the
author of the most cited paper favoring the
earlier hypothesis that high-protein intake
promotes osteoporosis no longer believes that
protein is harmful to bone.34 In fact, he
concluded that the balance of the evidence seems
to indicate the opposite.34
PROTEIN INTAKE AND BLOOD
PRESSURE
The AHA Nutrition Committee suggests that
high-protein intake may increase blood pressure.
However, there is no scientific evidence
supporting this contention. In fact, a negative
correlation has been shown between protein
intake and systolic and diastolic blood pressures
in several epidemiological surveys analyzed by
Obarzanek et al.13 For example,
• Honolulu Heart Study. In this study of 6,406
Japanese-American men, a negative
relationship was observed between systolic
and diastolic blood pressures and the amount
protein consumed.14
• Chinese Study. In this investigation of 2,672
adults men and women, a negative
relationship was found between systolic
pressure and the amount of animal protein
consumed.15
• MRFIT Study. Based on 11,342 adult men,
investigators observed a negative relationship
between systolic blood pressure and the
amount of total protein consumed.16
In both normotensive and hypertensive rats,
increasing the dietary protein level enhances
both urine and the amount of sodium excreted,
although the mechanism behind these effects is
unknown and still speculative.17 Interestingly,
one study in human volunteers with a family
history of hypertension has shown that a high-
protein diet may counteract the adverse effects of
excessive salt intake.18 For more information on
protein intake and blood pressure, see the recent
review by Debry.17
PROTEIN INTAKE AND HEART DISEASE
Recent findings by Hu et al. suggests that
replacing carbohydrates with protein may be
associated with a lower risk of ischemic heart
disease.25 This result is consistent with evidence
from metabolic studies that replacement of
dietary carbohydrate with protein has favorable
Sports Nutrition Review Journal. 1(1):45-51, 2004. (www.sportsnutritionsociety.org)
effect on plasma lipoprotein and lipid
concentrations. However, because an increase
in protein intake from animal products such as
meats, dairy products, and eggs is often
accompanied by increases in intakes of
saturated fat and cholesterol, dietary advice to
improve public health based on these findings
should be made with caution.25
Recent novel approaches have shown that
glucose and lipid intake may induce an
increase in the generation of reactive oxygen
species (ROS) and oxidative stress. For
example, Mohanty et al. produced evidence
that all three major macronutrients induce an
increase in ROS generation.26 However, their
data also show that different nutrients produce
distinct patterns of stimulation of ROS
generation after their intake. Of the three
nutrients, glucose induced the greatest ROS
generation, followed in decreasing order by
fat (cream) and by protein (casein). The
detriment of oxidative stress is that it may
damage proteins and lipids, the latter through
lipid peroxidation. Lipid peroxidation of
LDL-C particles is an essential step in the
development of atherosclerosis.27
PROTEIN INTAKE AND LIVER
FUNCTION
AHA Nutrition Committee suggests that high-
protein intake may have detrimental effects
on liver function. However, there is no
scientific evidence whatsoever supporting this
contention. Protein is needed not only to
promote liver tissue repair, but also to provide
lipotropic agents such as methionine and
choline for the conversion of fats to
lipoprotein for removal from the liver, thus
preventing fatty infiltration.20
Rodents fed very high protein intakes have
been found to exhibit morphological changes
in the liver mitochondria, which could be
pathological. However, Jorda et al. reported
that the liver responds to the high-protein diet
by a proliferation of normally functioning
mitochondria.24 Further, the branched-chain
amino acids to aromatic amino acids ratio was
also increased, indicating the absence of hepatic
failure in these animals. The authors concluded
that “the increased protein content of diet
induced rapid increases in several
characteristics of hepatocytes… The results
presented here constitute a good example of how
the hepatocyte adapts to a continuing metabolic
stress.”
Further, protein catabolism is increased in liver
disease and may be exacerbated by inadequate
protein in the diet.19 Unless there is
encephalopathy (vide infra), the diet should
provide high-quality protein in the amount of 1.5
to 2 g/kg.19 In alcoholic liver disease, a high-
calorie, high-protein diet has been shown to
improve hepatic function and reduce mortality.
In one study, this was achieved by providing a
regular diet plus supplements of 60 g/day of
protein and 1600 kcal/day for the first 30 days
and followed by supplements of 45 g/day of
protein and 1200 kcal/day for the next 60 days.21
Finally, the role of protein restriction in patients
with chronic hepatic encephalopathy (HE) has
been questioned recently as the efficacy of
protein withdrawal in patients with HE has never
been subjected to a controlled trial.29 According
to Srivastava et al., “the emphasis in the
nutritional management of patients with HE
[hepatic encephalopathy] should not be on the
reduction of protein intake. Instead, the goal
should be to promote synthesis by making
available ample amounts of amino acids, while
instituting other measures to reverse the ongoing
catabolism.”29
EFFECTS OF VERY-LOWCARBOHYDRATE DIET ON LEAN BODY
MASS
According to the AHA Nutrition Committee,
“Some popular high-protein/low-carbohydrate
diets limit carbohydrates to 10 to 20 g/d, which
is one fifth of the minimum 100 g/day that is
necessary to prevent loss of lean muscle tissue.”
Clearly, this is an incorrect statement since
catabolism of lean body mass is reduced by
ketones, which probably explains the
Sports Nutrition Review Journal. 1(1):45-51, 2004. (www.sportsnutritionsociety.org)
preservation of lean tissue observed during Oddly, the AHA Nutrition Committee ignores
very-low-carbohydrate diets. the fact that energy restriction increases protein
requirements. It has been know for about a half
For example, Volek et al. examined the century that inadequate energy intake leads to
effects of 6-week carbohydrate-restricted diet increased protein needs, presumably because
on total and regional body composition and some of the protein normally used to synthesize
the relationships with fasting hormones.22 both functional (enzymatic) and structural
Twelve healthy normal-weight men switched (tissue) protein is utilized for energy under these
from their habitual diet (48% carbohydrate) to conditions.1 For example, Butterfield has shown
a carbohydrate-restricted diet (8% that feeding as much as 2 g protein/kg/day to
carbohydrate) for 6 weeks and 8 men served men running 5 or 10 miles per day at 65% to
as controls, consuming their normal diet. 75% of their VO2max is insufficient to maintain
Subjects were encouraged to consume nitrogen balance when energy intake is
adequate dietary energy to maintain body inadequate by as little as 100 kcal/day.30 Thus,
mass during intervention. when trying to lose weight, it is important to
keep protein levels moderately high. The
Fat mass was significantly decreased (-3.4 kg) reduction in calories needed to lose weight
and lean body mass significantly increased should be at the expense of saturated fats and
(+1.1 kg) at week 6. However, there were no carbohydrates, not protein.
significant changes in composition in the
control group. The Authors concluded that a CONCLUSION
carbohydrate-restricted diet resulted in a
significant reduction in fat mass and a It is clear that the American Heart Association
concomitant increase in lean body mass in Nutrition Committee´s statement on dietary
normal-weight men. They hypothesized that protein and weight reduction contains misleading
elevated ß-hydroxybutyrate concentrations and incorrect information. Certainly, such public
may have played a minor role in preventing warnings should be based on a thorough analysis
catabolism of lean tissue but other anabolic of the scientific literature, not unsubstantiated
hormones were likely involved (e.g., growth fears and misrepresentations. For individuals
hormone). with normal renal function, the risks are minimal
and must be balanced against the real and
established risk of continued obesity.23