Category Archives: Protein

Review: Protein Benefits for Bone may Require Calcium


Dietary protein is beneficial to bone health under conditions of adequate calcium intake: an update on clinical research.

To underscore recent clinical studies, which evaluate the association between dietary protein and bone health.
Epidemiologic studies show greater protein intake to be beneficial to bone health in adults. In addition, randomized controlled trials show that protein’s positive effect on bone health is augmented by increased calcium intake. The relation between dietary protein and fracture risk is unclear. Dietary protein may positively impact bone health by increasing muscle mass, increasing calcium absorption, suppressing parathyroid hormone, and augmenting insulin-like growth factor 1 production; but the effects of other factors that contribute to this association, such as dietary protein dose and timing response, require further research.
The positive effects of protein intake on bone health may only be beneficial under conditions of adequate calcium intake. Dietary protein’s relation with fracture risk requires further investigation.

Mangano KM, Sahni S, Kerstetter JE
Curr Opin Clin Nutr Metab Care Jan 2014
PMID: 24316688

Review: Protein has a Small Benefit on Bone Health


Dietary protein and bone health: a systematic review and meta-analysis.

There has been a resurgence of interest in the controversial relation between dietary protein and bone health.
This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults.
The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded.
In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD.
A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.

Darling AL, Millward DJ, Torgerson DJ, Hewitt CE…
Am. J. Clin. Nutr. Dec 2009
PMID: 19889822 | Free Full Text

Review: Protein Restriction Potentially Dangerous for Bone Health


Dietary protein and skeletal health: a review of recent human research.

Both dietary calcium and vitamin D are undoubtedly beneficial to skeletal health. In contrast, despite intense investigation, the impact of dietary protein on calcium metabolism and bone balance remains controversial. A widely held view is that high intakes of animal protein result in increased bone resorption, reduced bone mineral density, and increased fractures because of its ability to generate a high fixed metabolic acid load. The purpose of this review is to present the recent or most important epidemiological and clinical trials in humans that evaluated dietary protein’s impact on skeletal health. Many epidemiological studies have found a significant positive relationship between protein intake and bone mass or density. Similarly, isotopic studies in humans have also demonstrated greater calcium retention and absorption by individuals consuming high-protein diets, particularly when the calcium content of the diet was limiting. High-protein intake may positively impact bone health by several mechanisms, including calcium absorption, stimulation of the secretion of insulin-like growth factor-1, and enhancement of lean body mass. The concept that an increase in dietary protein induces a large enough shift in systemic pH to increase osteoclastic bone resorption seems untenable.
Recent epidemiological, isotopic and meta-analysis studies suggest that dietary protein works synergistically with calcium to improve calcium retention and bone metabolism. The recommendation to intentionally restrict dietary protein to improve bone health is unwarranted, and potentially even dangerous to those individuals who consume inadequate protein.

Kerstetter JE, Kenny AM, Insogna KL
Curr. Opin. Lipidol. Feb 2011
PMID: 21102327

High-Protein Meat Diet has No Adverse Effects on Bone in Postmenopausal Women


A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting markers of bone resorption or formation in postmenopausal women.

Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants’ serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.

Cao JJ, Johnson LK, Hunt JR
J. Nutr. Mar 2011
PMID: 21248199 | Free Full Text

The present study detected no change in potential biomarkers of osteoclast activity, such as blood TRAP, CTX, and sRANKL and urinary DPD, or biomarkers of osteoblast activity, such as blood OPG and OC. The observed changes in IGF-I and PTH were apparently insufficient to elicit detectable changes in biomarkers of osteoclast or osteoblast activity.

Many epidemiological observations have shown that long-term protein intakes are positively associated with bone mineral density (9, 11, 13, 53). Several recent meta-analyses have concluded that protein is beneficial to bone health (54) and protein-induced acid load does not promote skeletal bone mineral loss or contribute to the development of osteoporosis (55, 56). The results from this study are in agreement with those findings.

In conclusion, in postmenopausal women, a diet high in both protein and PRAL increased Ca absorption, at least partially compensating for an increase in urinary excretion. No change in either bone resorption or formation biomarkers was observed, indicating that a high-protein diet is not detrimental. However, the increased serum IGF-I combined with decreased serum PTH concentrations suggest that a high-protein diet could be beneficial to bone health.

Review: Animal Protein Not Inferior or Superior to Vegetable Protein


The interaction between dietary protein and bone health.

The role of dietary protein in bone health has been controversial. On the one hand, a plentiful supply of dietary amino acids has been considered important to support bone remodeling while on the other hand there have been concerns that the dietary acid load associated with protein consumption promotes hypercalciuria and loss of bone calcium stores. This article reviews the effect of dietary protein on bone mass and bone density, and the effect on markers of bone resorption and formation and also on fracture risk, looking at both cross-sectional and longitudinal studies and examining both meat and vegetable protein including soy and milk basic protein. The results are not entirely consistent and suggest that the interaction between dietary protein and other components in a mixed diet, such as calcium intake and vegetables and fruit to neutralize acid, are important and may determine whether high-protein diets are beneficial to bone health. Overall the results suggest that dietary protein has a modest beneficial effect on bone markers and bone density. This effect has yet to be consistently linked to reduced fracture risk, probably because of the role of other etiological factors such as the risk of falls. There is not enough evidence currently to suggest that animal protein is superior or inferior to vegetable protein, or that milk or soy protein, respectively, is more favorable than other protein sources.

Jesudason D, Clifton P
J. Bone Miner. Metab. Jan 2011
PMID: 20972896

High-Protein Diets are Not Detrimental to Bone in the Short Term in Women


The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women.

Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.

Kerstetter JE, O’Brien KO, Caseria DM, Wall DE…
J. Clin. Endocrinol. Metab. Jan 2005
PMID: 15546911

Review: Low Protein Intake and Bones – 2003


Low protein intake: the impact on calcium and bone homeostasis in humans.

Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.

Kerstetter JE, O’Brien KO, Insogna KL
J. Nutr. Mar 2003
PMID: 12612169 | Free Full Text

The subject is complicated with a lot of conflicting data. The full article is great.

When BMD is the primary outcome, most (39–48), but not all (49–53), epidemiological studies show a positive relationship between protein intake and BMD. Stated another way, most of the epidemiological evidence shows that when other known dietary factors are controlled, those individuals who consume low protein diets have lower BMD. Using the National Health and Nutrition Examination Survey (NHANES) III database, we found that in 1882 non-Hispanic white women 50 y old and older, after adjusting for age and body weight, a low protein intake was associated with a significantly lower hip bone mineral density (Fig. 5) (47). Consistent with these data, Hannan and colleagues (46) studied 615 participants in the Framingham Osteoporosis Study over a 4-y period and found that lower levels of protein intake were associated with significantly higher rates of bone loss at the hip and spine. These findings confirm the earlier work of Freudenheim et al. (39), who reported that a low protein intake was associated with greater loss in bone density from the wrist in 35- to 65-y-old women. Most recently, Promislow et al. (48) found a positive association between total dietary protein intake and BMD in elderly men and women participating in the Rancho Bernardino study. Therefore, there is substantial agreement in those studies in which BMD is the primary outcome. Munger et al. (59), reporting data from the Iowa Women’s Health Study, found an increased risk of hip fracture in 55- to 69-y-old women consuming the lowest amounts of protein.

Adequate dietary protein may also help in fracture healing and in preventing bone loss after fracture. Bonjour and colleagues (73) studied the effects of 6 mo of protein supplementation, after osteoporotic hip fracture, in a group of elderly subjects. These patients had self-selected protein intakes that were very low (∼40 g). The administration of additional protein (+20 g) was associated with significant attenuation of proximal femur bone loss in the fractured hip such that, at 1 y, bone loss rates were 50% lower in the protein-supplemented individuals. The correction of poor protein nutrition also improved serum prealbumin and insulin-like growth factor 1 (IGF-1) concentrations and decreased the length of rehabilitation (73).

There is agreement that diets moderate in protein (in the approximate range of 1.0 to 1.5 g protein/kg) are associated with normal calcium metabolism and presumably do not alter skeletal homeostasis. Approximately 30–50% of adults in the United States consume dietary protein that could be considered moderate. At low protein intakes, intestinal calcium absorption is reduced, resulting in increases in serum PTH and calcitriol that persist for at least 2–4 wk. The long-term implications of these findings are unknown; however, recent epidemiological data suggest increased rates of bone loss in individuals consuming such diets. Individuals consuming high protein intakes, particularly from omnivorous sources, develop hypercalciuria that is attributable for the most part to an increase in intestinal calcium absorption. Whether high protein diets result in an increase in bone resorption and higher fracture rates remains uncertain.


Whey Acidic Protein Fractions Increases Bone Density and Elasticity in Ovariectomised Rat


The effect of whey acidic protein fractions on bone loss in the ovariectomised rat.

Bovine milk has been shown to contain bioactive components with bone-protective properties. Earlier studies on bovine milk whey protein showed that it suppressed bone resorption in the female ovariectomised rat. A new osteotropic component was subsequently identified in the whey basic protein fraction, but bone bioactivity may also be associated with other whey fractions. In the present study, we investigated whether acidic protein fractions isolated from bovine milk whey could prevent bone loss in mature ovariectomised female rats. Six-month-old female rats were ovariectomised (OVX) or left intact (sham). The OVX rats were randomised into four groups. One group remained the control (OVX), whereas three groups were fed various whey acidic protein fractions from milk whey as 3 g/kg diet for 4 months. Outcomes were bone mineral density, bone biomechanics and markers of bone turnover. Bone mineral density of the femurs indicated that one of the whey AF over time caused a recovery of bone lost from OVX. Plasma C-telopeptide of type I collagen decreased significantly in all groups except OVX control over time, indicating an anti-resorptive effect of whey acidic protein. Biomechanical data showed that the AF may affect bone architecture as elasticity was increased by one of the whey AF. The femurs of AF-supplemented rats all showed an increase in organic matter. This is the first report of an acidic whey protein fraction isolated from milk whey that may support the recovery of bone loss in vivo.

Kruger MC, Plimmer GG, Schollum LM, Haggarty N…
Br. J. Nutr. Aug 2005
PMID: 16115359

Review: Alkaline Diets and the Acid Load Theory are Bunk – 2013


Nutritional disturbance in acid-base balance and osteoporosis: a hypothesis that disregards the essential homeostatic role of the kidney.

The nutritional acid load hypothesis of osteoporosis is reviewed from its historical origin to most recent studies with particular attention to the essential but overlooked role of the kidney in acid-base homeostasis. This hypothesis posits that foods associated with an increased urinary acid excretion are deleterious for the skeleton, leading to osteoporosis and enhanced fragility fracture risk. Conversely, foods generating neutral or alkaline urine would favour bone growth and Ca balance, prevent bone loss and reduce osteoporotic fracture risk. This theory currently influences nutrition research, dietary recommendations and the marketing of alkaline salt products or medications meant to optimise bone health and prevent osteoporosis. It stemmed from classic investigations in patients suffering from chronic kidney diseases (CKD) conducted in the 1960s. Accordingly, in CKD, bone mineral mobilisation would serve as a buffer system to acid accumulation. This interpretation was later questioned on both theoretical and experimental grounds. Notwithstanding this questionable role of bone mineral in systemic acid-base equilibrium, not only in CKD but even more in the absence of renal impairment, it is postulated that, in healthy individuals, foods, particularly those containing animal protein, would induce ‘latent’ acidosis and result, in the long run, in osteoporosis. Thus, a questionable interpretation of data from patients with CKD and the subsequent extrapolation to healthy subjects converted a hypothesis into nutritional recommendations for the prevention of osteoporosis. In a historical perspective, the present review dissects out speculation from experimental facts and emphasises the essential role of the renal tubule in systemic acid-base and Ca homeostasis.

Bonjour JP
Br. J. Nutr. Oct 2013
PMID: 23551968 | Free Full Text

…experiments carried out among patients suffering from severe metabolic acidosis caused by renal insufficiency, or among healthy subjects made acidotic by administering NH4Cl, suggested the involvement of bone tissue in maintaining the acid–base balance. This hypothesis was later refuted on the basis of both theoretical and experimental arguments. Despite this rebuttal, the hypothesis was put forward that bone could play a buffering role, with the consideration that nutrients, particularly animal proteins with their acid load, could be a major cause of osteoporosis. Several recent human studies have shown that there is no relationship between nutritionally induced variations of urinary acid excretion and Ca balance, bone metabolism and the risk of osteoporotic fractures. Variations in human diets across a plausible range of intakes have been shown to have no effect on blood pH. Consistent with this lack of a mechanistic basis, long-term studies of alkalinising diets have shown no effect on the age-related change in bone fragility. Consequently, advocating the consumption of alkalinising foods or supplements and/or removing animal protein from the human diet is not justified by the evidence accumulated over the last several decades.

High Protein + Low Calcium Increases Fracture – 2008


Proteins, dietary acid load, and calcium and risk of postmenopausal fractures in the E3N French women prospective study.

Excess dietary proteins and “acid ash” diets have been suspected to increase the risk of osteoporosis, but experimental and epidemiological evidence is mixed. We aimed to determine whether the association between protein intake and the overall acid-base equilibrium of the diet (as renal net acid excretion [RNAE] estimate) and fracture risk vary according to calcium intake. During an average of 8.37 +/- 1.73 yr of follow-up, 2408 women reported a fracture (excluding high-impact trauma) among 36,217 postmenopausal women from the E3N prospective study. We used Cox regression models to study the interaction between calcium and, respectively, proteins and RNAE, from the 1993 dietary questionnaire for fracture risk determination, adjusting for potential confounders. There was no overall association between fracture risk and total protein or RNAE. However, in the lowest quartile of calcium (<400 mg/1000 kcal), high protein intake was associated with a significant increased fracture risk (RR = 1.51 for highest versus lowest quartile; 95% CI, 1.17-1.94). An increasing fracture risk with increasing animal protein intake was also observed (trend, p < 0.0001). A similar pattern of interaction for fracture risk was observed between RNAE and calcium. In this Western population of postmenopausal women with normal to high protein intake and fairly high calcium intake, there was no overall association between total protein or RNAE and fracture risk. However, there was some evidence that high protein-high acid ash diets were associated with an increased risk of fracture when calcium intake was low (<400 mg/1000 kcal).

Dargent-Molina P, Sabia S, Touvier M, Kesse E…
J. Bone Miner. Res. Dec 2008
PMID: 18665794