Tag Archives: abstract

Review: Protein Benefits for Bone may Require Calcium

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.

 

Potassium Bicarbonate Decreases Resorption and Increases Bone Formation in Postmenopausal Women

Abstract

Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate.

In normal subjects, a low level of metabolic acidosis and positive acid balance (the production of more acid than is excreted) are typically present and correlate in degree with the amount of endogenous acid produced by the metabolism of foods in ordinary diets abundant in protein. Over a lifetime, the counteraction of retained endogenous acid by base mobilized from the skeleton may contribute to the decrease in bone mass that occurs normally with aging.
To test that possibility, we administered potassium bicarbonate to 18 postmenopausal women who were given a constant diet (652 mg [16 mmol] of calcium and 96 g of protein per 60 kg of body weight). The potassium bicarbonate was given orally for 18 days in doses (60 to 120 mmol per day) that nearly completely neutralized the endogenous acid.
During the administration of potassium bicarbonate, the calcium and phosphorus balance became less negative or more positive–that is, less was excreted in comparison with the amount ingested (mean [+/- SD] change in calcium balance, +56 +/- 76 mg [1.4 +/- 1.9 mmol] per day per 60 kg; P = 0.009; change in phosphorus balance, +47 +/- 64 mg [1.5 +/- 2.1 mmol] per day per 60 kg; P = 0.007) because of reductions in urinary calcium and phosphorus excretion. The changes in calcium and phosphorus balance were positively correlated (P < 0.001). Serum osteocalcin concentrations increased from 5.5 +/- 2.8 to 6.1 +/- 2.8 ng per milliliter (P < 0.001), and urinary hydroxyproline excretion decreased from 28.9 +/- 12.3 to 26.7 +/- 10.8 mg per day (220 +/- 94 to 204 +/- 82 mumol per day; P = 0.05). Net renal acid excretion decreased from 70.9 +/- 10.1 to 12.8 +/- 21.8 mmol per day, indicating nearly complete neutralization of endogenous acid.
In postmenopausal women, the oral administration of potassium bicarbonate at a dose sufficient to neutralize endogenous acid improves calcium and phosphorus balance, reduces bone resorption, and increases the rate of bone formation.

Sebastian A, Harris ST, Ottaway JH, Todd KM…
N. Engl. J. Med. Jun 1994
PMID: 8190153 | Free Full Text

Potassium Citrate, but not Chloride, Increases Bone Density in Postmenopausal Women

Abstract

Partial neutralization of the acidogenic Western diet with potassium citrate increases bone mass in postmenopausal women with osteopenia.

Chronic acid loads are an obligate consequence of the high animal/grain protein content of the Western diet. The effect of this diet-induced metabolic acidosis on bone mass is controversial. In a randomized, prospective, controlled, double-blind trial, 161 postmenopausal women (age 58.6 +/- 4.8 yr) with low bone mass (T score -1 to -4) were randomly assigned to 30 mEq of oral potassium (K) citrate (Kcitrate) or 30 mEq of K chloride (KCl) daily. The primary end point was the intergroup difference in mean percentage change in bone mineral density (BMD) at lumbar spine (L2 through L4) after 12 mo. Compared with the women who received KCl, women who received Kcitrate exhibited an intergroup increase in BMD (+/-SE) of 1.87 +/- 0.50% at L2 through L4 (P < 0.001), of 1.39 +/- 0.48% (P < 0.001) at femoral neck, and of 1.98 +/- 0.51% (P < 0.001) at total hip. Significant secondary end point intragroup changes also were found: Kcitrate increased L2 through L4 BMD significantly from baseline at months 3, 9, and 12 and reached a month 12 increase of 0.89 +/- 0.30% (P < 0.05), whereas the KCl arm showed a decreased L2 through L4 BMD by -0.98 +/- 0.38% (P < 0.05), significant only at month 12. Intergroup differences for distal radius and total body were NS. The Kcitrate-treated group demonstrated a sustained and significant reduction in urinary calcium excretion and a significant increase in urinary citrate excretion, with increased citrate excretion indicative of sustained systemic alkalization. Urinary bone resorption marker excretion rates were significantly reduced by Kcitrate, and for deoxypyridinoline, the intergroup difference was significant. Urinary net acid excretion correlated inversely and significantly with the change in BMD in a subset of patients. Large and significant reductions in BP were observed for both K supplements during the entire 12 mo. Bone mass can be increased significantly in postmenopausal women with osteopenia by increasing their daily alkali intake as citrate, and the effect is independent of reported skeletal effects of K.

Jehle S, Zanetti A, Muser J, Hulter HN…
J. Am. Soc. Nephrol. Nov 2006
PMID: 17035614 | Free Full Text

Despite more than 70 yr of sustained interest in the possibility that chronic metabolic acidosis might decrease bone mass, central questions regarding the effect of acid-base alterations on human bone physiology and pathophysiology remain unanswered (4,27,28). First, does chronic metabolic acidosis of any magnitude decrease bone mass? Second, does the low-grade chronic metabolic acidosis that is induced by the acidogenic Western diet result in osteoporosis? Third, can neutralization of dietary acid result in increased bone mass in normal humans or those with osteopenia?

Indirect support for a possible role of chronic metabolic acidosis to reduce bone mass comes from small, uncontrolled studies in humans with nonazotemic renal disease (distal renal tubular acidosis [29,30]). Chronic dietary acid loads were shown to result in significant and reversible negative calcium balance (6), and experimental increases in animal protein intake or its chief acidogenic constituent, methionine, within the range that is characteristic of the Western diet were shown to cause both negative calcium balance and increased systemic acid load (31,32). Compatible with and strongly supportive of these observations, short-term neutralization of endogenous acid production by oral ingestion of bicarbonate for 7 to 18 d in both postmenopausal women and young healthy adults resulted in calcium retention and—on the basis of analysis of bone markers—in inhibition of bone resorption (13,14).

[…]

This study establishes that bone mass can be increased significantly in postmenopausal women with osteopenia by increasing their daily alkali intake as Kcitrate and that this effect is independent of reported in vitro skeletal effects of co-administered K. The magnitude of the effect is large, and the safety profile was found to be excellent, albeit based on a limited sample size. The results strongly support the thesis that neutralization of the modern Western diet will promote skeletal health. The associated BP effects of the K supplement provide additional incentive to move forward with controlled outcome trials using long-term Kcitrate treatment.

Potassium Citrate or Fruits + Veggies, No Benefit Over 2 Years

Abstract

Effect of potassium citrate supplementation or increased fruit and vegetable intake on bone metabolism in healthy postmenopausal women: a randomized controlled trial.

Alkali provision may explain why fruit and vegetables benefit bone health.
We aimed to determine the effects of alkali-providing potassium citrate (double-blind) and fruit and vegetable intake (single-blind) on bone turnover over 2 y.
We conducted a randomized placebo-controlled trial in 276 postmenopausal women (aged 55-65 y). Women were randomly assigned to 4 groups: high-dose potassium citrate (55.5 mEq/d), low-dose potassium citrate (18.5 mEq/d), placebo, and 300 g additional fruit and vegetables/d (equivalent of 18.5 mEq alkali). Serum and fasted urine for bone markers were collected at baseline and at 3, 6, 12, 18, and 24 mo. An additional urine sample was collected at 4-6 wk. Bone mineral density (BMD) was measured at baseline and 2 y.
Repeated-measures ANOVA showed no difference between groups for urinary free deoxypyridinoline cross-links relative to creatinine (fDPD/Cr), serum N-terminal propeptide of type 1 collagen, or beta C-terminal telopeptide, although, at 4-6 wk, fDPD/Cr was lower in the high-dose potassium citrate group (P = 0.04). Mean +/- SD spine BMD loss in the placebo group (1.8 +/- 3.9%) did not differ significantly from that in the treatment groups (2.1 +/- 3.2%; P = 0.88). Hip BMD loss in the placebo and low-dose potassium citrate groups was 1.3 +/- 2.3% and 2.2 +/- 2.3%, respectively (P = 0.14).
Two-year potassium citrate supplementation does not reduce bone turnover or increase BMD in healthy postmenopausal women, which suggests that alkali provision does not explain any long-term benefit of fruit and vegetable intake on bone.

Macdonald HM, Black AJ, Aucott L, Duthie G…
Am. J. Clin. Nutr. Aug 2008
PMID: 18689384 | Free Full Text

In summary, neither potassium citrate at 18.5 or 55.6 mEq/d nor 300 g self-selected fruit and vegetables/d influenced bone turnover or prevented BMD loss over 2 y in healthy postmenopausal women. Further work is required to investigate whether particular fruit and vegetables are important and how much of each is optimal for bone health.