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SYSTEMATIC REVIEW
Protein intake, calcium balance and health
consequences
J Calvez
1
, N Poupin
1
, C Chesneau
2
, C Lassale
3
and D Tome
´
1
1
AgroParisTech, CRNH-IdF, UMR914 Nutrition Physiology and Ingestive Behavior, Paris, France;
2
Bongrain SA, 42 rue Rieussec,
Viroflay, France and
3
Unite
´de Recherche en Epide
´miologie Nutritionnelle, UMR U557 Inserm/U1125 Inra/Cnam/Paris 13,
CRNH IdF, SMBH Paris 13, Bobigny Cedex, France
High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on
the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The
combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of
the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In
contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data
support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In
addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip
fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for
kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in
either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting
metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be
complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.
European Journal of Clinical Nutrition (2012) 66, 281 –295; doi:10.1038/ejcn.2011.196; published online 30 November 2011
Keywords: dietary protein; calcium intake; calcium excretion; bone; kidney; acid–base balance
Introduction
The ingestion of protein-rich diets has been associated with
modifications of urinary calcium and acid excretions
suspected to reflect a state of slight acidosis inducing an
environment favorable for demineralization of the skeleton
and development of kidney stones. The metabolism of
dietary proteins contributes to endogenous acid production,
mainly through oxidation of sulfur amino acids and
phosphoproteins. However, different results also support a
positive relation between protein intake and bone health. In
this review, we attempted to summarize the effects of high-
protein (HP) diets on bone health and renal function, also
considering the relationships between dietary protein intake,
acid–base status and calcium metabolism. To identify the
related literature, searches were conducted in the MEDLINE
database through PubMed using the following keywords:
high-protein diets, dietary proteins, protein intake, meat
intake, acid–base balance, renal net acid excretion, hyper-
calciuria, calcium balance, urinary calcium, calcium excre-
tion, calcium absorption, bone health, bone mass and
fractures. Reference lists were reviewed for supplemental
relevant studies. An attempt was also made to interpret the
differences in the reported effects with regard to variations in
dietary intakes.
Protein intake, urinary calcium and acid excretions
and calcium balance
Dietary protein and urinary calcium and acid excretions
Controlled feeding studies showed a hypercalciuric effect
of HP diets when supplemental proteins were added in
the form of purified proteins (casein, lactalbumin, wheat
gluten, dried white eggs), with urinary calcium excretion being
increased by 0.7–2.2 mg/g of supplemental ingested protein,
at constant levels of calcium intake (Johnson et al., 1970;
Anand and Linkswiler, 1974; Kim and Linkswiler, 1979;
Schuette et al., 1980; Hegsted and Linkswiler, 1981; Hegsted
Received 27 April 2011; revised 10 August 2011; accepted 11 August 2011;
published online 30 November 2011
Correspondence: Professor D Tome
´, Life Sciences and Health, AgroParisTech,
16 rue Claude Bernard, 75005 Paris, France.
E-mail: tome@agroparistech.fr
European Journal of Clinical Nutrition (2012) 66, 281–295
&
2012 Macmillan Publishers Limited All rights reserved 0954-3007/12
www.nature.com/ejcn
et al., 1981; Zemel et al., 1981; Schuette and Linkswiler, 1982;
Lutz, 1984; Trilok and Draper, 1989; Pannemans et al., 1997;
Wagner et al., 2007) (Table 1). Increased urinary calcium
excretion was also observed in omnivorous than in vegetar-
ian women (Ball and Maughan, 1997) or in subjects
following an Atkins diet (Reddy et al., 2002). However, other
studies reported no change in the level of urinary calcium
with the consumption of high-meat diets compared with
low-meat diets (Spencer et al., 1978, 1983, 1988). The
hypercalciuric effect of HP diets certainly depends on the
nature of the dietary protein, and food with HP contents,
such as meat or dairy products, also contain compo-
nents that limit urinary calcium excretion. For instance,
phosphorus exerts a hypocalciuretic effect that counteracts
the hypercalciuretic effect of protein intake. When protein
and calcium intakes are held constant, an increase in
phosphorus intake causes a decrease in urinary calcium
between 40 and 65% depending on the level of protein
intake (Hegsted et al., 1981).
HP diets were also associated with a higher acid excre-
tion, as reflected by a decrease in urine pH and an increase
in total renal net acid excretion. In controlled feeding
studies, comparing diets with low and high levels of
proteins, urinar y pH was reduced by 0.3–0.8 Units when
protein intake was increased by 40–60 g/day (Lutz, 1984;
Trilok and Draper, 1989; Reddy et al., 2002; Roughead et al.,
Table 1 Main reported effects of HP diets on urinary acid excretion in association with increased calcium urinary excretion, depending on the type and
amount of dietary proteins
Author Changes
in urine
pH
a
Changes
in RNAE
(mEquiv./day)
a
Changes in
urinary TA
(mEquiv./day)
a
Changes in
urinary Ca
excretion
a
Type of
supplemental P in
HP diet compared
with LP diet
Changes
in protein
intake (g/day)
b
Study design n
Lutz (1984) k(0.8) m(þ40) m(þ10) m(þ94%) Purified P
(C, LA, WG)
þ58 (44 vs 102) CF-CO 6
Trilok and
Draper (1989)
km(þ15) m(þ5) m(þ50–70%) Purified P
(C, LA, WG, WE)
þ60 (50 vs 110) CF-CO 8
Schuette et al.
(1980)
m(þ15) m(þ10) m(þ84%) Purified P
(LA, WG)
þ65 (45 vs 110) CF-CO 11
Hegsted and
Linkswiler
(1981)
m(þ43) m(þ11) m(þ88%) Purified P
(C, LA, WG, WE)
þ77 (46 vs 123) CF-CO with
1st diet period ¼60days
2nd diet period ¼15 days
6
Schuette and
Linkswiler
(1982)
m(þ86) m(þ32) m(þ53%) Purified P
(C, LA, WG, WE)
þ90 (55 vs 145) CF-CO 8
Roughead
et al. (2003)
k(0.1) m(þ4) ¼Meat þ50 (68 vs 117) CF-CO 15
Reddy et al.
(2002)
k(0.5) m(þ56%) Meat (Atkins diet
vs usual diet)
þ73 (91 vs 164) 1 week ad libitum with FR
and 1 week with CF-CO
10
Schuette et al.
(1982)
m(þ40) m(þ12) m(þ28%) Meat þ90 (55 vs 145) CF-CO 8
Hunt et al.
(2009)
k(0.3) m(þ10) m(þ11%) Meat and milk þ55 (58 vs 113) CF-CO, diets with
two levels of Ca
27
Hunt et al.
(2009)
k(0.4) m(þ13) m(þ18%) Meat and milk þ55 (58 vs 113) CF-CO, diets with
two levels of Ca
27
Remer and
Manz (1994)
k(1.2) m(þ112) m(þ126%) Animal P þ71 (49 vs 120) CF-CO 6
Schuette et al.
(1982)
m(þ48) m(þ19) m(þ71%) Meat and dairy
products
þ90 (55 vs 145) CF-CO 8
Kerstetter
et al. (2006)
m(þ18) m(þ47%) Meat, fish and
dairy products
þ90 (45 vs 135) CF-CO 20
Frank et al.
(2009)
k(0.7) Animal P þ93 (88 vs 181) FE with recommendations
to achieve the dietary
intervention goals and
daily FR-CO
24
Wagner et al.
(2007)
k(0.8 to 0.4) m(þ100%) Meat and
dairy products
þ1.5g/kg per day CF-CO 24
Kerstetter
et al. (2006)
m(þ28) m(þ26%) Soy P þ90 (45 vs 135) CF-CO 20
Abbreviations: C, casein; CF, controlled feeding study (all the food was provided to the subjects); CO, cross-over design (either randomized or not randomized);
FE, free eating; FR, food records; G, gelatin; HP, high protein; LA, lactalbumin; LP, low protein; RNAE, renal net acid excretion; TA, titratable acids; WE, dried white
eggs; WG, wheat gluten.
a
Changes in parameters values under HP diet compared with LP diet: mindicates an increase in the parameter values, kindicates a decrease in the parameter values,
¼indicates no significant changes in the parameter values.
b
Difference in the amount of proteins in the HP diet compared with the LP diet (amount of proteins in the LP diet vs amount of proteins in the HP diet).
HP diet and calcium balance
J Calvez et al
282
European Journal of Clinical Nutrition
2003). Increases in renal net acid excretion ranging from 0.4
to 1 mEquiv. were reported for ingestion of 1 g supplemental
proteins (Schuette et al., 1980; Hegsted and Linkswiler, 1981;
Schuette and Linkswiler, 1982; Lutz, 1984; Reddy et al.,
2002). The level of supplemental acid excretion induced by
higher protein intakes may depend on the nature of the
ingested proteins. For instance, renal net acid excretion was
shown to be positively correlated with non-dairy (Hu et al.,
1993) and total (Frassetto et al., 1998) animal protein intake
but not with plant protein intake (Frassetto et al., 1998).
However, the increased renal acid load under HP diets is
not necessarily associated with modifications of the systemic
acid load. Plasma pH and bicarbonate concentration remain
within normal ranges when increasing the protein intake up
to 164 g/day (Reddy et al., 2002) or 2 g/kg (Wagner et al.,
2007). The preservation of the systemic acid–base equili-
brium suggests that protein-induced acid loads can be
adequately handled by the kidney through excretion of
excess produced acid and by activation of buffer systems.
Protein intake and calcium balance
Calcium balance is defined as calcium intake minus the sum
of urinary and fecal calcium excretions. Although there is a
large consensus over the increase in urinary calcium
excretion with increase in protein intake, the effect of HP
diets on whole-body calcium is less clear (Table 2). In some
studies, HP diets, associated with increased levels of urinary
calcium, resulted in lower and negative calcium balances
compared with low protein (LP) diets (Johnson et al., 1970;
Anand and Linkswiler, 1974; Kim and Linkswiler, 1979; Allen
et al., 1979b; Hegsted et al., 1981; Schuette and Linkswiler,
1982; Lutz, 1984), with a decrease in daily calcium balance
ranging from 1 to 1.6 mg/g of supplemental ingested proteins.
Other studies reported no changes in calcium balance with
HP diets, either with no changes in urinary calcium excretion
and calcium absorption when proteins were given as meat
(Spencer et al., 1983; Draper et al., 1991) or with a decrease in
fecal calcium excretion, which compensates for the increase
in urinary calcium when supplemental proteins were added
to the diet as purified proteins (Cummings et al., 1979;
Pannemans et al., 1997).
The discrepancies among the reported effects of HP diets
on calcium balance may be partly explained by the
difficulties in measuring whole-body calcium balance. First,
fecal calcium losses which need to be measured over a 5–10-
day period to be representative of the diet, are up to 10 times
greater than urinary calcium losses, and an error in fecal
calcium determination can strongly skew the estimation of
calcium balance. In addition, dietary factors, such as calcium
and phosphorus intakes, also modulate calcium balance. At
high levels of protein intake, an increase in phosphorus
intake causes the calcium balance to change from negative to
positive (Hegsted and Linkswiler, 1981). A HP and high
phosphorus intake was associated with a positive calcium
balance with high calcium intakes but with a negative
balance with low calcium intake (Schuette and Linkswiler,
1982). These effects are of particular importance as an
increase in protein intake from ordinary food is generally
accompanied by an increase in phosphorus intake, as meat
and dairy products are also rich in phosphorus, and it may
explain why smaller changes in calcium balance are usually
observed in studies in which HP intakes consist in high-meat
or high-dairy products instead of purified proteins.
Protein intake and modulations of calcium metabolism
Modulation of calcium renal handling
The hypercalciuric effect of dietary proteins likely results
from an alteration of calcium renal handling (Table 3). A
two- or three-fold increase in protein intake causes a 6–20%
increase in glomerular filtration rate (Kim and Linkswiler,
1979; Allen et al., 1979b; Schuette et al., 1980; Hegsted and
Linkswiler, 1981; Hegsted et al., 1981; Zemel et al., 1981),
thus resulting in an increased filtered load of calcium. In
parallel, the fractional tubular reabsorption is decreased by
0.9–2% when the protein intake is increased by 100–200%
(Kim and Linkswiler, 1979; Hegsted and Linkswiler, 1981;
Hegsted et al., 1981; Zemel et al., 1981). These modulations
of the renal function seem to be due to a direct effect of
proteins on renal cells, as the circulating level of the major
regulatory hormone of calcium metabolism, namely the
parathyroid hormone, does not vary with the increase in
protein intake (Kim and Linkswiler, 1979; Allen et al., 1979b;
Schuette et al., 1980).
Alterations of calcium renal handling could also be caused
by the increased acid excretion associated with HP intakes.
Urinary calcium excretion was reported to be higher by
B100 mg/day under an acid-forming diet compared with a
base-forming diet (Buclin et al., 2001). Meta-analysis of
studies in which the acid–base intake was manipulated
through changes in food intake or supplementation shows a
positive correlation between urinary net acid excretion and
urinary calcium, with a 0.9–1.4mg increase in urinary
calcium for a 1mEquiv. increase in acid excretion (Fenton
et al., 2008, 2009). The relationship between acid and
calcium excretion is further supported by the fact that
addition of base to the diet in the form of sodium
bicarbonate partially negates the hypercalciuretic effect of
the HP diet (Lutz, 1984). More specifically, increased urinary
calcium excretion under HP diet is often attributed, at least
partially, to the increase in urine excretion of sulfate which
results from the increased metabolism of sulfur amino acids
(Schuette et al., 1980). However, sulfur amino acids added to
a LP diet, with amounts similar to that present in a HP diet,
cause an increase in urinary calcium that account for only
44% of the increase caused by the HP diet (Zemel et al.,
1981), suggesting that other factors, such as ammonia
excretion, are involved in protein-induced hypercalciuria.
Hormones such as insulin, growth hormones and gluco-
corticoids, which affect calcium excretion, may also be
HP diet and calcium balance
J Calvez et al
283
European Journal of Clinical Nutrition
Table 2 Main reported effects of diets with different levels of protein on calcium balance, calcium intestinal absorption and calcium urinary excretion
Changes reported in HP diets
compared with LP diets
Method used
for measure of
Ca intestinal
absorption
Dietary intakes Study characteristics
Urinary Ca
excretion
(mg/g added P)
Intestinal Ca
absorption
(mg/day)
Ca balance
(mg/day)
a
Proteins in
LP vs HP
diets (g/day)
b
Type of
supplemental P in
HP diet compared
with LP diet
Calcium
(mg/day)
c
Phosphorus
(mg/day)
c
Design
d
nDuration Particularities
Increase in urinary calcium excretion
Trilock et al.
(1989)
þ1 50–110 Purified P
(C, LA, WG, WE)
¼(800) ¼(800) CF-CO 8 7 days
Zemel et al.
(1981)
þ2 70–120 Purified P
(C, LA, WG, WE)
¼(500) ¼(1100) CF-CO 8 12 days
Licata (1981) þ0.9 28–115 Complex P
(meat)
¼(800) ¼(1500) CF-CO 6 7 days
Ball and
Maughan (1997)
þ1.7 55–70 Complex P
(vegetarian vs
omnivorous diets)
¼(1000) ¼(1250) 33 Evaluation of protein
intake by food reports
Remer et al.
(1994)
þ1.4 49–120 Complex P
(animal)
? ? CF-CO 6 5 days
Wagner et al.
(2007)
þ0.7 35–140 Complex P
(meat)
? ? CF-CO 24 7 days
Increase in urinary calcium excretion with no change in intestinal calcium absorption and decrease in calcium balance (mainly observed under supplementation with purified proteins)
Anand and
Linkswiler (1974)
þ1.4 NS 151 (o0) Balance 47–142 Purified P
(C, LA, WG, G)
¼(500) ¼(800) CF-CO 9 15 days
Lutz et al. (1984) þ1.6 NS 76 (o0) Balance 44–102 Purified P
(C, LA, WG)
¼(500) ¼(900) CF-CO 6 15 days Postmenopausal
women
Hegsted and
Linkswiler (1981)
þ1.3 NS 107 (o0) Balance 46–123 Purified P
(C, LA, WG, WE)
¼(500) ¼(900) CF-CO 6 15–60 days
Kim and
Linkswiler (1979)
þ1.6 NS 141 (o0) Balance 47–142 Purified P
(C, LA, WG)
¼(500) ¼(1110) CF-CO 6 10 days
Hegsted et al.
(1981)
d
þ1.8 NS 140 (o0) Balance 50–150 Purified P
(C, LA, WG, WE)
¼(500) ¼(1010) CF-CO 8 12 days
Schuette et al.
(1980)
þ1.3 NS 70 (o0) Balance 45–110 Purified P
(C, LA)
¼(750) ¼(1100) CF-CO 11 12 days Older subjects
(445 years)
Walker and
Linkswiler (1972)
þ2.2 NS 97 (o0) Balance 47–142 Purified P
(C, LA, WG, G)
¼(800) ¼(1000) CF-CO 9 14 days
Johnson et al.
(1970)
þ1.7 NS 94 (o0) Balance 47–142 Purified P
(C, LA, WG, G)
¼(1400) ¼(1400) CF-CO 6 45 days
Allen et al.
(1979b)
þ0.6 NS 100 (o0) Balance 100–260 Purified P
(soy P isolate)
¼(1400) ¼(2300) CF-CO 6 47 days
Schuette et al.
(1982)
e
þ0.9 NS 78 (o0) Balance 55–146 Purified P
(C, LA, WG, WE)
¼(600) 4(1660) CF-CO 8 10–15 days
Reddy et al.
(2002)
þ1.2 NS 130 (o0) Dual tracer
stable isotope
91–164 Complex proteins
(meat)
¼(850) 4(2000) CF-CO 10 14 days
Increase in urinary calcium excretion with no change in intestinal calcium absorption or in calcium balance: increases in urinary excretion are smaller and these effects are mainly observed when higher protein levels
are reached by addition of food rich in proteins (meat, dairy products yas opposed to purified proteins) with a concomitant increase in phosphorus intake, suggesting a compensating effect of dietary phosphorus
in the diet
Hegsted et al.
(1981)
d
þ0.3 NS NS ( ¼0) Balance 50–150 Purified P
(C, LA, WG, WE)
¼(500) ¼(2525) CF-CO 8 12 days
Ceglia et al.
(2009)
þ0.6 NS ? Dual tracer
stable isotope
30–100 Complex P
(meat)
¼(600) 4(1125) CF-CO 23 10 days Older subjects
(450 years)
HP diet and calcium balance
J Calvez et al
284
European Journal of Clinical Nutrition
Table 2 Continued
Changes reported in HP diets
compared with LP diets
Method used
for measure of
Ca intestinal
absorption
Dietary intakes Study characteristics
Urinary Ca
excretion
(mg/g added P)
Intestinal Ca
absorption
(mg/day)
Ca balance
(mg/day)
a
Proteins in
LP vs HP
diets (g/day)
b
Type of
supplemental P in
HP diet compared
with LP diet
Calcium
(mg/day)
c
Phosphorus
(mg/day)
c
Design
d
nDuration Particularities
Kerstetter et al.
(2006)
f
þ0.7 NS ? Dual tracer
stable isotope
45–135 Complex P
(animal)
¼(800) 4(1290) CF-CO 20 4 d Eight postmenopausal
women
Kerstetter et al.
(2006)
f
þ0.4 NS ? Dual tracer
stable isotope
45–135 Complex P
(vegetal)
¼(800) 4(1520) CF-CO 20 4 d Eight postmenopausal
women
Schuette et al.
(1982)
e
þ0.5 NS NS ( ¼0) Balance 55–146 Complex P
(meat)
¼(600) 4(1660) CF-CO 8 10–15 d
Hunt et al.
(2009)
g
þ0.4 NS NS Radiotracer 58–113 Complex P
(meat þmilk)
¼(1510) 4(1960) CF-CO 27 7 wks
Increase in urinary calcium excretion with increase in intestinal calcium absorption and no change in calcium balance: the increase in calcium absorption compensates for the increase in calcium urinary excretion
Lutz (1981) þ1.4 NS (o0) Balance 50–110 Purified P
(LA, WG)
¼(710) ¼(1080) CF-CO 8 15 days Postmenopausa l
women
Pannemans et al.
(1997)
þ0.7 NS ( ¼0) Balance 80–140 Purified P
(C, WG, soyabean)
4(1200) 4(1800) CF-CO 28 3 weeks Two groups of subjects
differing in age
Kerstetter et al.
(2005)
þ1þ1.3 NS (o0) Dual tracer
stable isotope
67–136 Complex P
(animal and vegetal)
¼(800) ¼(2200) CF-CO 10 10 days
Kerstetter et al.
(1998)
þ1þ0.9 NS Dual tracer
stable isotope
46–135 Complex P
(meat þdairy
products)
¼(800) 4(1170) CF-CO 7 5 days
Hunt et al.
(2009)
g
þ0.4 þ0.3 NS Balance 58–113 Complex P
(meat þmilk)
¼(675) 4(1780) CF-CO 27 7 weeks
Cummings et al.
(1979)
þ0.7 þ0.6 NS (40) Balance 63–136 Complex P
(meat)
¼(980) ? CF-CO 4 3 weeks
Schuette et al.
(1982)
e
þ1.2 þ2.1 NS ( ¼0) Balance Complex P
(meat þdairy products)
4(1370) 4(2060) CF-CO 8 10–15 days
No change in calcium homeostasis
Draper et al.
(1991)
NS NS NS (o0) Balance 55–146 Complex P
(meat)
¼(650) 4CF 8 15 days Postmenopausa l
women
Hunt et al.
(1995)
NS NS NS (40) Balance 55–110 Complex P
(meat)
¼(750) 4(1700) CF-CO 14 7 weeks Postmenopausal
women
Spencer et al.
(1983)
NS NS NS ( ¼0) Radiotracer 76–142 Complex P
(meat)
¼(800) 4(1300) CF-CO 7 18–130 days
Roughead et al.
(2003)
NS NS Radiotracer 68–117 Complex P
(meat)
¼(600) 4(1700) CF-CO 15 8 weeks Postmenopausal
women
Abbreviations: C, casein; CF, controlled feeding study (all the food was provided to the subjects); CO, cross-over design (either randomized or not randomized); G, gelatin; HP, high protein;
LA, lactalbumin; LP, low protein; NS, no significant changes in Ca balance; WE, dried white eggs; WG, wheat gluten; ? indicates that information was not provided in the article.
a
Estimated as Ca balance under HP diet Ca balance under LP diet; o0 indicates negative Ca balance under the HP diet.
b
¼indicates that the level of calcium or phosphorus intake was held constant across protein levels by supplementation; ‘4‘ indicates higher level of calcium or phosphorus intake with the HP diet.
c
The lowest and the highest levels of protein intake are reported if 42 levels of protein intake were investigated.
d
Results from the same study, under two different levels of phosphorus intake.
e
Results from the same study, with different type of supplemental proteins.
f
Results from the same study, with two different types of supplemental proteins (animal vs vegetal).
g
Results from the same study, under two different levels of Ca intake.
HP diet and calcium balance
J Calvez et al
285
European Journal of Clinical Nutrition
involved in the hypercalciuretic effect of proteins (Allen
et al., 1981; Zemel et al., 1981).
Modulations of intestinal dietary calcium absorption
The oldest hypothesis for the increased urinary calcium
induced by HP diet was that dietary proteins enhanced
calcium intestinal absorption. However, the effect of HP diet
on calcium intestinal absorption is unclear (Table 2).
McCance et al. (1942) first observed that subjects consum-
ing a LP diet (o70 g/day) had a 20% decrease of intestinal
calcium absorption compared with those consuming a HP
diet (4145 g/day). These first findings were confirmed by
Table 3 Main reported effects of HP diets on renal handling of calcium
Changes
in GFR
a
Changes
in FTR
a
Changes in
urinary Ca
a
Dietary intakes Study
design
Subjects Duration
of diet
Changes
in protein
intake (g/day)
a
Type of added
P in HP diet
compared with
LP diet
Calcium
(mg/day)
b
nSex Age
Increase in GFR
c
Allen et al.
(1979b)
þ14% þ47% þ160 Soy P ¼(1400) CF-CO 6 #47 days
Kerstetter et al.
(2006)
þ10% þ47% þ90 Soy P ¼(800) CF-CO 20 ~12 young (30 years)
and 8 older (60 years)
4 days
Kerstetter et al.
(2006)
þ14% þ26% þ90 Animal P ¼(800) CF-CO 20 ~12 young (30 years)
and 8 older (60 years)
4 days
Kerstetter et al.
(1998)
þ15% þ64% þ89 Animal P ¼(800) CF-CO 7 ~Young (25 years) 5 days
Wagner et al.
(2007)
þ3% þ100% þ1.5 g/kg
per day
Animal P ? CF-CO 24 ~/#Young (25–40 years)
and older (55–70 years)
1 week
Frank et al.
(2009)
þ13% þ93 Animal P ? FE-CO 24 #Young (20–30 years) 7 days
Increase in GFR and decrease in FTR associated with an increase in urinary calcium
Schuette et al.
(1980)
þ20% 0.9% þ84% þ65 Purified P
d
¼(750) CF-CO 11 ~/#44–86 years 12 days
Hegsted and
Linkswiler
(1981)
þ12% 0.9% þ88% þ77 Purified P
d
¼(500) CF-CO 6 ~Young 60 or
15 days
Kim et al.
(1979)
þ10% 1% þ100% þ95 Purified P
d
¼(515) CF 6 #Young 10 days
Zemel et al.
(1981)
þ6% 2% þ100% þ100 Purified P
d
¼(500) CF-Fact. 8 #Young 12 days
Hegsted et al.
(1981)
þ16% 1.7% þ114% þ100 Purified P
d
¼(500) CF-CO 8 #12 days
Hegsted et al.
(1981)
þ8% 1% þ29% þ100 Purified P
d
¼(500) CF-CO 8 #12 days
No change in GFR
Kerstetter et al.
(2005)
NS þ47% þ69 Animal and
vegetal P
¼(800) CF-CO 10 ~Young (20–40 years) 10 days
Modulations of renal function in the postprandial phase, after a HP meal challenge
Burodom
(2010)
þ64% þ0.8g/kg Animal P
(chicken)
11 ~/#
Burodom
(2010)
þ58% þ0.8g/kg Animal P
(egg white)
11 ~/#
Allen et al.
(1979a)
NS þ36g Animal P
(dairy P)
¼(400) 9 ~/#
Allen et al.
(1981)
NS þ30g ¼(400) 11 ~/#
Abbreviations: CF, controlled feeding study (all the food was provided to the subjects); CO, cross-over design (either randomized or not randomized); fact., factorial
design; FTR, fractional tubular reabsorption; GFR, glomerular filtration rate; HP, high protein; LP, low protein; NS, no significant changes; ? indicates that information
was not provided in the article.
a
Changes in HP compared with LP diets (values in HP dietvalues in LP diet).
b
¼indicates that the level of calcium intake was held constant across protein levels by supplementation; ‘4‘ indicates higher level of calcium or phosphorus intake
with the HP diet.
c
Results from studies without assessment of FTR.
d
Casein, lactalbumin, wheat gluten, dried white eggs added in the HP diet to reach the high level of protein intake.
HP diet and calcium balance
J Calvez et al
286
European Journal of Clinical Nutrition
some intervention studies (Lutz and Linkswiler, 1981;
Schuette and Linkswiler, 1982), whereas others studies
were unable to demonstrate any effect of dietary protein
on intestinal calcium absorption (Schuette et al., 1980;
Hegsted and Linkswiler, 1981; Hegsted et al., 1981). However,
in these studies, calcium absorption was estimated using
the balance method, that is, by measuring the difference
between calcium intake and fecal calcium losses. As quan-
tifying fecal calcium losses is technically difficult and
small changes in absorption may go undetected by this
method, the results should be interpreted with caution.
Moreover, true absorption might be underestimated as
it is impossible to dissociate endogenous fecal calcium
excretion from dietary calcium.
More recently, methods using calcium isotopes, such as
the actual gold-standard double-tracer method (Heaney,
2000) or the radiotracer method, offer a more reliable way
to assess intestinal calcium absorption, but results about the
effect of dietary proteins on calcium absorption are still
contradictory. Under comparable experimental conditions,
some inter vention studies found that a HP diet (1.5–2 g/kg
compared with 0.5–1 g/kg proteins consumed each day)
induced an increase in calcium absorption associated with
an increased calcium excretion in premenopausal and
postmenopausal women (Kerstetter et al., 1998, 2005; Hunt
et al., 2009), whereas other studies found no effect of HP
intake on calcium absorption, despite an increased calcium
excretion (Kerstetter et al., 2006; Ceglia et al., 2009).
A longitudinal observational study and interventions
studies, using the radiotracer method to assess calcium
balance, also did not find any effect of a HP diet on calcium
intestinal absorption; but in these studies, no effect of the
dietary protein was found on calcium excretion (Spencer
et al., 1983; Dawson-Hughes and Harris, 2002; Roughead
et al., 2003). The level of dietary calcium might modulate the
effect of protein intake on calcium absorption and
contribute to explain the conflicting results. Indeed, Hunt
et al. (2009) showed that HP compared with LP intakes
increased calcium absorption with low (700 mg/day) but not
with high (1500 mg/day) dietary calcium intakes.
The possible mechanism for enhanced intestinal calcium
absorption in response to dietary protein is unclear. Calcium
absorption occurs primarily in the duodenum where gastric
acid secretion permits to obtain a pH o6.0 necessary for the
solubilization of calcium salts from ingested food (Goss et al.,
2007). Gastric acid production is not only stimulated by the
parasympathetic nervous system but also by chemical
signals, nutrients, including Ca
2þ
(Hade and Spiro, 1992;
Geibel and Wagner, 2006) and some amino acids (Konturek
et al., 1978; Strunz et al., 1978). Thus, the dietary protein
might increase calcium solubility by stimulating gastric acid
production (DelValle and Yamada, 1990; Schulte-Frohlinde
et al., 1993). Furthermore, some products of protein diges-
tion, such as casein, seem to enhance calcium intestinal
absorption through direct interactions with calcium (Ferrar-
etto et al., 2001; Erba et al., 2002).
Data on variations of calcium intestinal absorption are of
particular importance to determine changes in calcium
balance under HP diets. Indeed, although urinary calcium
is often reported as a marker of calcium metabolism, it is not
an exact indicator of whole-body calcium loss as there may
also be differences in calcium intestinal absorption that
compensate for changes in calcium excretion.
Mobilization of bone calcium and net calcium retention
According to the acid-ash hypothesis, HP diets causes an
excess acid load, which would be neutralized by the release
of bicarbonate ions from the bone matrix, a mechanism that
is accompanied by a loss of Na
þ
,K
þ
and a small amount of
Ca
2þ
(Green and Kleeman, 1991), and consequently, the
increase in bone resorption is reflected by the increase in
urinary calcium excretion (Barzel and Massey, 1998; Remer,
2000; Frassetto et al., 2001; New, 2003) (Table 4). The acid
load would also decrease osteoblastic activity and increase
osteoclastic activity, resulting in net bone resorption with
mobilization of calcium (Bushinsky, 1989; Krieger et al.,
1992; Alpern and Sakhaee, 1997). However, no convincing
experimental data support this theory. Results on changes in
urinary hydroxyproline, a marker of collagen metabolism, in
response to HP diets are controversial, with some studies
reporting elevation of urinary excretion of hydroxyproline
with HP diets (Kim and Linkswiler, 1979; Schuette and
Linkswiler, 1982), whereas other did not observe any change
(Allen et al., 1979b; Hunt et al., 1995).
Protein intake and bone health
No clinical support for detrimental effects of protein intake on
bone health
Protein intake was shown to be positively correlated with
bone mass in several skeletal sites in every category of the
population, from children to elderly men and women
(Hirota et al., 1992; Geinoz et al., 1993; Devine et al., 1995;
Cooper et al., 1996; Feskanich et al., 1996; Teegarden et al.,
1998; Hannan et al., 2000; Sellmeyer et al., 2001; Whiting
et al., 2002; Ilich et al., 2003; Alexy et al., 2005; Budek et al.,
2007; Chen et al., 2007; Chevalley et al., 2008; Thorpe et al.,
2008). In their systematical review, Darling et al. (2009)
noted that a large majority of the cross-sectional surveys or
cohort studies reviewed reported either no association or a
beneficial association between proteins and bone mineral
density (BMD), and only one survey found a negative
correlation between proteins and body mineral content.
They conclude that dietary proteins, if not significantly
favorable, are at least not detrimental to bone density. In
addition, a recent longitudinal study including 540 pre-
menopausal women found no adverse effect of increased
protein intakes (from 5 to 25% of the energy intake) on BMD
(Beasley et al., 2010).
Studies frequently cited to support the deleterious effect of
HP diet on bone health are retrospective analyses of hip
HP diet and calcium balance
J Calvez et al
287
European Journal of Clinical Nutrition
fracture incidence in postmenopausal women of different
countries (Abelow et al., 1992; Frassetto et al., 2000), which
found that the highest rate of hip fractures occurred in
industrialized Western countries, which have the highest
animal protein intake. However, there are several obvious
limitations to these studies as noted by Bonjour (2005). First,
countries with the highest incidence of hip fractures are also
those with the longest life expectancy, which is an important
determinant of the risk of osteoporotic fracture (Kannus
et al., 1996). The protein intake was then estimated from the
whole population but not for the specific studied group.
Finally, interethnic differences in risk of osteoporotic
Table 4 Controversial results about the effects of HP diets on calcium metabolism and bone resorption
Changes in
markers of
bone resorption
(in urine)
a
Changes in
markers of
bone formation
(in serum)
a
Changes in
regulators of
Ca metabolism
(in serum)
a
Changes in
urinary Ca
Diet Study
design
Subjects Duration
of the diet
PTH 1.25-
(OH)
2
-D
IGF-1 Changes in
protein intake
(g/day)
b
Calcium
intake
(mg/day)
c
nSex Age
(years)
Decrease in markers of bone resorption under HP diets -despite their calciuretic effect, HP diets decrease bone catabolism
Heaney
et al. (1999)
kin NTX ¼b-ALP k(9%) km(10%) mþ20
(dairy P)
4(1500) FE—PR 101 455 12 weeks
Hunt et al.
(2009)
kin DPD ¼b-ALP;
¼OC
¼¼m(23%) m(18%) þ55 ¼(675) CF-CO 27 ~60 7 weeks
Hunt et al.
(2009)
kin DPD ¼b-ALP;
¼OC
¼¼m(35%) m(11%) þ55 ¼(1510) CF-CO 27 ~60 7 weeks
Ince et al.
(2004)
min NTX k(8%) ¼m(47%) 20 (P
restriction)
¼(820) FE and
CF—CT
42 ~20–40 1 week
No change in markers of bone resorption -HP diets increase urinary calcium excretion but do not seem to alter calcium metabolism
Schurch
et al. (1998)
¼DPD ¼OC ¼¼m(84%) þ20 ¼(650) FE—PR 33 460 6 months
Ceglia et al.
(2009)
¼NTX ¼OC k(15%) m(25%) m(38%) þ70 ¼(600) CF-CO 23 ~/#450 10 days
Kerstetter
et al. (2006)
¼NTX k(60%) m(47%) þ90
(animal P)
¼(800) CF-CO 20 ~30
and 60
4 days
Kerstetter
et al. (2006)
¼NTX k(63%) m(26%) þ90
(soy P)
¼(800) CF-CO 20 ~30
and 60
4 days
Reddy et al.
(2002)
¼NTX;
¼DPD
kin OC;
¼b-ALP
¼m(56%) þ73 ¼(850) FE and
CF—CO
10 2 weeks
Allen et al.
(1979b)
¼HYP ¼m(47%) þ160 ¼(1400) CF-CO 6 #23–30 47 days
Roughead
et al. (2003)
¼NTX ¼b-ALP;
¼OC
¼¼¼ ¼ þ50 ¼(600) CF-CO 15 ~450 8 weeks
Hunt et al.
(1995)
¼HYP kin b-ALP;
¼OC
¼¼ ¼ ¼(750) CF-CO 14 ~63 7 weeks
Increase in markers of bone resorption -increase in HP intake (by addition of purified P) may increase bone resorption.
Kim et al.
(1979)
min HYP ¼m(100%) þ95
(purified P)
¼(515) CF 6 #21–29 10 days
Effects on regulators of Ca homeostasis (without evaluation of changes in markers of bone resorption)
Kerstetter
et al. (1998)
k(33%) k(18%) m(64%) þ89 ¼(800) CF-CO 7 ~25 5 days
Licata et al.
(1981)
k(37%) m(84%) þ87 ¼(800) CF-CO 6 ~/#41 7 days
Lutz et al.
(1981)
¼¼ m(91%) þ60 ¼(710) CF-CO 8 ~450 15 days
Schuette
et al. (1980)
¼¼ m(84%) þ65 ¼(750) CF-CO 11 ~/#44–86 12 days
Kerstetter
et al. (2005)
¼m(47%) þ69 ¼(800) CF-CO 10 ~20–40 10 days
Abbreviations: b-ALP, bone-specific alkaline phosphatase; CF, controlled feeding study (all the food was provided to the subjects); CO, cross-over design;
CT, controlled trial; DPD, deoxypyridinoline; FE, free eating; HP, high protein; HYP, hydroxyproline; LP, low protein; IGF-1, insulin-like growth factor-1; NTX, N-
terminal telopeptide; PR, parallel randomized design; PTH, parathyroid hormone; OC, osteocalcin; 1.25-(OH)
2
-D, 1.25-Dihydroxycholecalciferol.
a
Changes in parameters values under HP diet compared with LP diet: mindicates an increase in the parameter values, kindicates a decrease in the parameter values,
¼indicates no significant changes in the parameter values.
b
Changes in HP compared with LP diets (values in HP diet-values in LP diet).
c
¼indicates that the level of calcium intake was held constant across protein levels by supplementation; ‘4‘ indicates higher level of calcium or phosphorus intake
with the HP diet.
HP diet and calcium balance
J Calvez et al
288
European Journal of Clinical Nutrition
fracture are well known and may be attributable to many
factors such as bone structure, genotype or lifestyle (Nelson
and Megyesi, 2004; Lei et al., 2006). Other epidemiological
data provide some weak evidence that fracture incidence was
related to higher protein intake. In the 12-year Nurses’
Health Study carried out in the United States, women who
consumed 495 g protein/day had an increased risk of
forearm fracture but not of hip fracture (Feskanich et al.,
1996). In a retrospective Norwegian survey, an elevated risk
of hip fracture was associated with high non-dairy protein
intake only when calcium intake was low (Meyer et al.,
1997). A major limitation of both studies was the use of a
mailed food frequency questionnaire at a limited number of
occasions and limited evaluation of other lifestyle and
dietary factors that may have contributed to fracture risk.
On the contrary, many other prospective studies have found
a clear negative association between protein intake and risk
of hip fracture in the elderly (Huang et al., 1996; Munger
et al., 1999; Wengreen et al., 2004; Misra et al., 2010). In a
meta-analysis of cohort studies, Darling et al. (2009) found
no association between protein intake and risk fracture. In
addition, in intervention studies, oral protein supplementa-
tions significantly improved clinical outcomes after hip
fractures in the elderly (Delmi et al., 1990; Tkatch et al.,
1992; Schurch et al., 1998).
Impact of calcium intake on the relationship between protein
intake and bone health
There is some evidence that the beneficial effect of protein
intake on bone mineral mass is better expressed when supplies
of both calcium and vitamin D are adequate (Heaney, 2001,
2002; Dawson-Hughes, 2003). In Norwegian women, protein
intake was not correlated with the risk of hip fractures, except
when the protein intake was the highest and the calcium
intake the lowest (Meyer et al., 1997). In a 3-year intervention
study in men and women older than 65 years, no relation was
found between protein intake and BMD in the placebo group
(which had a normal calcium intake), whereas HP diets had a
beneficial effect on BMD in the calcium-supplemented group
(Dawson-Hughes and Harris, 2002).
Taken together, the studies regarding protein intake and
bone health suggest that high-dietary protein intake pro-
motes bone growth and retards bone loss and that LP diet is
associated with higher risk of hip fractures. The positive
effects of dietary protein intake on bone health seem to be
dependent, at least in part, on calcium intake. Furthermore,
maintenance of adequate bone strength and density with
aging is highly dependent on the maintenance of adequate
muscle mass and muscle mass is in turn dependent on
adequate intake of high-quality protein (Wolfe, 2006;
Heaney and Layman, 2008).
Mechanisms supporting the beneficial effect of protein on bone
health
Mechanisms by which the protein positively affects bone
health mainly implied insulin-like growth factor-1 (IGF-1).
Intake of proteins induces production and action of IGF-1 in
both animal and human studies (Schurch et al., 1998;
Heaney et al., 1999; Arjmandi et al., 2003; Dawson-Hughes,
2003; Ceglia et al., 2009). IGF-1 is a major regulator of bone
metabolism that can act as a systemic and local regulator of
osteoblastic function (Mohan et al., 1992; Langdahl et al.,
1998) and as a coupling factor in bone remodeling by
activating both bone resorption and bone formation (Rubin
et al., 2002). As reviewed by Bonjour et al. (1997) and Thissen
et al. (1994), the impact of dietary protein on IGF-1 and the
impact, in turn, of IGF-1 on bone health has a key role in the
prevention of osteoporosis. In adult rats, a LP diet was shown
to decrease plasma IGF-1 level and to induce negative bone
balance with a decreased formation and an increased
resorption (Ammann et al., 2000; Bourrin et al., 2000a, b).
This effect was reversed by amino-acid supplementation
(Ammann et al., 2000).
Protein intake, kidney function and kidney stone
formation
The potentially harmful effects of dietary proteins on renal
function are believed to be due to the ‘overwork’ induced by
such diets on the kidneys. Indeed, as shown previously, HP
diets cause elevation of glomerular filtration rate and
hyperfiltration (Kim and Linkswiler, 1979; Schuette et al.,
1980; Hegsted and Linkswiler, 1981; Hegsted et al., 1981;
Zemel et al., 1981; Brenner et al., 1982; Bilo et al., 1989;
Metges and Barth, 2000; Tuttle et al., 2002; Frank et al., 2009;
Burodom, 2010). In animal models, HP diets induce a renal
hypertrophy (Addis, 1926; Wilson, 1933; Hammond and
Janes, 1998) but not systematically (Robertson et al., 1986;
Collins et al., 1990; Lacroix et al., 2004), and to our
knowledge, the link between protein-induced renal hyper-
trophy or hyperfiltration and the initiation of renal disease
in healthy individuals has not been clearly shown. Only one
recent study showed in pigs that a long-term HP diet (4 or 8
months) resulted in enlarged kidneys and increased evidence
of renal damages (Jia et al., 2010). In their review, Martin
et al. (2005), concluded that there is no significant evidence
of an association between HP intakes and the initiation or
progression of renal disease in healthy individuals. For
instance, in an observational study, high animal protein
intake was correlated with a decline in renal function in
women with preexisting renal disease, but not in women
with normal renal function (Knight et al., 2003). In long
interventional studies, including overweight or obese
healthy subjects, without preexisting renal dysfunction, the
HP diet did not adversely affect renal function, whether it
increased glomerular filtration rate and kidney size (Skov
et al., 1999) or whether it did not (Brinkworth et al., 2010).
However, HP diets have been shown to accelerate renal
deterioration in patients with kidney dysfunction, and
protein restriction is a common strategy to postpone the
progression of renal diseases (Klahr, 1989; Pedrini et al.,
HP diet and calcium balance
J Calvez et al
289
European Journal of Clinical Nutrition
1996; Robertson et al., 2007). Martin et al. (2005) suggest that
in healthy people, renal hypertrophy increased glomerular
filtration rate, and hyperfiltration induced by HP intakes
might be normal physiological adaptations to the increased
demand on kidney due to its role as an acid buffer. Taken
together, these results suggest that HP diets might not have
an adverse effect on healthy people but may accelerate renal
diseases in people with renal dysfunction.
Another potentially harmful effect of HP consumption,
especially animal proteins, concerns its relation with kidney
stone formation. HP intake induces an increase in calcium
and acid excretion, which are considered as potentially
lithogenic substances (Robertson et al., 1979; Wasserstein
et al., 1987). Prospective studies found an elevated risk of
stone formation with high animal protein intakes in men or
women with no history of kidney stones (Curhan et al., 1993,
1997), whereas others reported an unchanged or reduced risk
(Hirvonen et al., 1999; Curhan et al., 2004). High intakes of
animal protein (meat) were shown to adversely affect
markers of stone formation in male recurrent stone formers,
whereas no changes were observed in healthy individuals
(Nguyen et al., 2001). It is possible that, as for renal disease,
proteins are harmful only in patients with a preexisting
dysfunction (Jaeger et al., 1983; Hess, 2002). Furthermore,
although calcium from supplementation may be associated
with an increase risk of stone formation (Curhan et al.,
1997), a higher intake of dietary calcium has been shown to
decrease the risk of kidney stone formation in healthy
subjects (Curhan et al., 1993, 1997, 2004). As high calcium
intakes reduced the absorption of oxalate, another impor-
Table 5 Main effect of high fruit and vegetable intake and potassium on calcium and acid–base balance and on bone and renal health
Effect of a diet rich in fruits and vegetables
On bone health
KPositive association between fruit and vegetable intake and BMD and bone mass New et al. (1997); Tucker et al. (1999); New et al. (2000);
Tucker et al. (2001); New (2003); Hardcastle et al. (2011)
KInhibitory activity of vegetable on bone resorption
-Not mediated by base excess: pharmacologically active compounds?
Effect of K per se?
Muhlbauer et al. (2002)
On renal health
KPositive correlation between diets with high intake of fruits, vegetables,
whole grains, nuts and dairy products and low intake of red and processed
meat (that is, low PRAL index) and higher excretion of urinary citrate
Trinchieri et al. (2006); Taylor et al. (2010)
-Reduction of stone risk
-Beneficial effect of fruits and vegetables on bone and renal health: effect of base excess and/or of nutrients composition (K)
Effect of potassium
On calcium balance
KReduction of urinary Ca excretion and positive Ca balance with short-term
administration of KHCO
3
in healthy adults
Lemann et al. (1989); Lemann et al. (1993);
Sebastian et al. (1994); Whiting et al. (1997)
KNo systematic effect of short-term administration of NaHCO
3
on urinary
Ca excretion
-Possible effect of K per se and not only of bicarbonate Lutz (1984); Lemann et al. (1989)
KDietary K is associated with urinary Ca excretion, but without any effect
on Ca balance as Ca intestinal absorption is also reduced
-Possible different effects depending of the source of K Rafferty et al. (2005)
On bone health
KPositive association between high intake of K and BMD and bone mass New et al. (1997); Tucker et al. (1999);
New et al. (2000); Tucker et al. (2001)
On renal health
KPrevention of calcium oxalate stones by potassium-magnesium citrate
supplementation in at-risk patients
Ettinger et al. (1997); Zerwekh et al. (2007)
Possible mechanisms of K
KEffect on calcium balance
-Stimulation of renal phosphate reabsorption capacity, leading to lower
serum 1.25-dihydroxycholecalciferol concentration and consequent
decrease intestinal Ca absorption
Jaeger et al. (1983); Rafferty and Heaney (2008)
KEffect on acid–base balance
-Neutralization of excess sulfate ions providing by sulfur amino acid Markovich et al. (1999)
-Modulation of various processes activated by acidosis Caudarella et al. (2003); Tosukhowong et al. (2005)
KEffect on stone formation
-Positive effector of citrate excretion Marangella et al. (2004); Demigne et al. (2004)
-Modulation of various processes activated by acidosis Caudarella et al. (2003); Tosukhowong et al. (2005)
Abbreviations: BMD, bone mineral density; PRAL, potential renal acid load.
HP diet and calcium balance
J Calvez et al
290
European Journal of Clinical Nutrition
tant risk factor for kidney stone formation, increasing
calcium intake could decrease urinary oxalate excretion
and thus offset the stone-promoting effect of the increase in
urinary calcium (Heaney, 2006). This result suggests that
dairy products might be beneficial for preventing kidney
stone formation in healthy subjects.
Impact of other dietary factors on bone health and
kidney function
The effect of proteins also depends on the presence of other
nutrients in the diet (Table 5). High intakes of fruits and
vegetables are associated with bone health in adult and
elderly men and women (New et al., 1997, 2000; Tucker et al.,
1999, 2001; New, 2002, 2003; Hardcastle et al., 2011) and
with a reduced risk of stone formation in high-risk patients
(Trinchieri et al., 2006; Taylor et al., 2010). This beneficial
effect of fruits and vegetables is probably due to their high
content in potassium and magnesium.
In healthy adults, potassium bicarbonate has been shown
to be hypocalciuric (Lemann et al., 1993; Sebastian et al.,
1994; Whiting et al., 1997) and positively associated with
bone health (New et al., 1997; Tucker et al., 1999). However,
it is not known whether the effect of potassium salts on
calcium excretion, bone and kidney is due to the alkaliniza-
tion effect of bicarbonate or due to the effect of potassium
per se. Administration of KHCO
3
reduced urinary calcium
excretion, but administration of other salts bicarbonate
(NaHCO
3
) did not have a systematic effect on calcium
balance in healthy subjects (Lutz, 1984; Lemann et al., 1989).
In rats, administration of various vegetable extracts was
shown to induce an inhibition of bone resorption in vivo,
independently of their base content (Muhlbauer et al., 2002).
These data suggest a possible role of potassium per se.Ina
cohort study of B650 premenopausal and postmenopausal
women, an inverse relation between dietary potassium and
urinary calcium was found without any effect on calcium
balance as reduced calciuria was offset by a reduction in
intestinal calcium absorption (Rafferty et al., 2005). In
addition, potassium was identified as a major stimulator of
urinary excretion of citrate, which is an inhibitor of calcium
stone formation (Demigne et al., 2004; Marangella et al.,
2004) (Crystallization y). Ingestion of alkali as potassium
and magnesium citrate reduced the risk of renal stone
formation during a 3-year period in a randomized controlled
trial (Ettinger et al., 1997) or during a 5-week bed rest at risk
period (Zerwekh et al., 2007). The alkalinic content and
potassium richness of fruits and vegetables are positively
linked to reduced calcium excretion, bone health and
reduced kidney stones formation in high-risk patients.
Conclusions
Although HP diets induce an increase in net acid and urinary
calcium excretion, they do not seem to be linked to impaired
calcium balance and no clinical data support the hypothesis
of a detrimental effect of HP diet on bone health, except in
the context of inadequate calcium supply. Thus, it is more
likely that excess urinary calcium excretion with HP diets
does not originate from bone calcium loss but from an
increased intestinal absorption. The increase of acid and
calcium excretion due to HP diets is also accused of
constituting a favorable environment for kidney stones and
renal diseases, but no damaging effect of HP diets on kidney
has been found in healthy subjects and HP diets might be
deleterious only in patients with a preexisting metabolic
renal dysfunction. However, HP diets often contain low
amounts of fruits and vegetables, which yet appear to be
beneficial to bone health and kidney function. Conse-
quently, to assess effects of dietary intakes on calcium
balance, bone health and kidney function, nutrients but
also possible deficiencies have to be taken into account.
Conflict of interest
The authors declare no conflict of interest.
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