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

PURPOSE OF REVIEW: To underscore recent clinical studies, which evaluate the association between dietary protein and bone health. RECENT FINDINGS: 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. SUMMARY: 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.

Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women.

Increasing dietary protein within a physiologic range stimulates intestinal calcium absorption, but it is not known if specific amino acids or dietary protein as a whole are responsible for this effect. Therefore, we selectively supplemented a low-protein (0.7 g/kg) diet with either the calcium-sensing receptor-activating amino acids (CaSR-AAAs) L-tryptophan, L-phenylalanine, and L-histidine, or the dibasic amino acids (DAAs) L-arginine and L-lysine, to achieve intakes comparable to the content of a high-protein diet (2.1 g/kg) and measured intestinal calcium absorption. Fourteen young women took part in a placebo-controlled, double-blind, crossover feeding trial in which each participant ingested a 6-d low-protein diet supplemented with CaSR-AAAs, DAAs, or methylcellulose capsules (control) after an 11-d adjustment period. All participants ingested all 3 diets in random order. Intestinal calcium absorption was measured between days 5 and 6 using dual-stable calcium isotopes ((42)Ca, (43)Ca, and (44)Ca). There was no difference in calcium absorption between the diet supplemented with CaSR-AAAs (22.9 ± 2.0%) and the control diet (22.3 ± 1.4%) (P = 0.64). However, calcium absorption tended to be greater during the DAA supplementation period (25.2 ± 1.4%) compared with the control diet period (22.3 ± 1.4%) (P < 0.10). Larger and longer clinical trials are needed to clarify the possible benefit of arginine and lysine on calcium absorption.

Increasing dietary protein acutely augments intestinal iron transporter expression and significantly increases iron absorption in rats.

Iron (Fe) deficiency is endemic worldwide. Little data are available regarding acute effects of dietary protein on intestinal Fe absorption. The current study evaluated the short-term effects of increasing dietary protein on Fe absorption and expression of genes involved in Fe homeostasis. Sprague Dawley rats (24, female) were randomly assigned to custom-formulated isocaloric diets containing 40, 20 (control), or 5% protein (as percentage of total kilocalories) for 7 d. Whole-body Fe balance studies demonstrated that Fe retention was greater in the 40% group than in the 5% group (30.8 vs. 7.3%; P<0.01). In a separate study utilizing stable iron isotopes, the 40% group absorbed 30% of ingested Fe, while the 20% group absorbed 18% (P=0.005). Whole-genome profiling revealed that increasing dietary protein from 5 to 40% increased duodenal transcript expression of divalent metal transporter 1 (DMT1) 3.2-fold, duodenal cytochrome b (Dcytb) 1.8-fold, and transferrin receptor (TfR) 1.8-fold. Consistent with these findings, DMT1 transcript expression was 4-fold higher in RNA prepared from duodenal mucosa in the 40% group compared to the 20% group (P<0.001). These data suggest that increasing dietary protein increases intestinal Fe absorption in part by up-regulating DMT1, Dcytb, and TfR.

Polyunsaturated fatty acids and their relation with bone and muscle health in adults.

Age-related bone and muscle loss are major public health problems. Investigational therapies to reduce these losses include anti-inflammatory dietary supplementations, such as polyunsaturated fatty acids (PUFA). Surprisingly, this topic has received little attention in the osteoporosis community. Recent research highlights the role of PUFA in inflammatory regulation of bone remodeling via cellular pathways. Emerging research suggests significant roles for PUFA in reducing bone and muscle loss with aging; however, findings are conflicted for PUFA and fracture risk. Limited studies suggest a relation between higher omega-3 FA and better muscle/bone in older adults. This review highlights new research since 2008 and synthesizes our current understanding of PUFA in relation to bone and muscle. Across study designs, evidence indicates that PUFA has positive effects upon bone. As data are sparse, future clinical trials and prospective studies are important to determine the long term benefits of PUFA supplementation upon bone and muscle outcomes.

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

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

Proton pump-inhibiting drugs, calcium homeostasis, and bone health.

Proton pump inhibitors (PPIs) are commonly used drugs, several of which are available without a prescription. Two recent studies have demonstrated increased hip fracture rates associated with PPI use. Theoretically, PPIs could impair intestinal calcium absorption resulting in increased rates of bone loss and a greater risk of fragility fracture.

Determination of calcium salt solubility with changes in pH and P(CO(2)), simulating varying gastrointestinal environments.

The amount of calcium available for absorption is dependent, in part, on its sustained solubility in the gastrointestinal (GI) tract. Many calcium salts, which are the calcium sources in supplements and food, have pH-dependent solubility and may have limited availability in the small intestine, the major site of absorption. The equilibrium solubility of four calcium salts (calcium oxalate hydrate, calcium citrate tetrahydrate, calcium phosphate, calcium glycerophosphate) were determined at controlled pH values (7.5, 6.0, 4.5 and < or = 3.0) and in distilled water. The solubility of calcium carbonate was also measured at pH 7.5, 6.0 and 4.5 with two CO(2) environments (0.3 and 152 mmHg) above the solution. The precipitation profile of CaCO(3) was calculated using in-vivo data for bicarbonate and pH from literature and equilibrium calculations. As pH increased, the solubility of each calcium salt increased. However, in distilled water each salt produced a different pH, affecting its solubility value. Although calcium citrate does have a higher solubility than CaCO(3) in water, there is little difference when the pH is controlled at pH 7.5. The partial pressure of CO(2) also played a role in calcium carbonate solubility, depressing the solubility at pH 7.5. The calculations of soluble calcium resulted in profiles of available calcium, which agreed with previously published in-vivo data on absorbed calcium. The experimental data illustrate the impact of pH and CO(2) on the solubility of many calcium salts in the presence of bicarbonate secretions in the intestine. Calculated profiles using in-vivo calcium and bicarbonate concentrations demonstrate that large calcium doses may not further increase intestinal calcium absorption once the calcium carbonate solubility product has been reached.

The Effect of Dietary Glycemic Properties on Markers of Inflammation, Insulin Resistance, and Body Composition in Postmenopausal American Women: An Ancillary Study from a Multicenter Protein Supplementation Trial.

Controversy exists as to whether high glycemic index/glycemic load (GI/GL) diets increase the risk of chronic inflammation, which has been postulated as a pathogenic intermediary between such diets and age-related alterations in body composition and insulin resistance. We conducted an ancillary study to a randomized, double-blind trial comparing the effects of a whey protein supplement (PRO, n = 38) and a maltodextrin supplement (CHO, n = 46) on bone density to evaluate the impact of a calibrated increase in GI/GL on inflammation, insulin resistance, and body composition in a healthy aging population. Markers of inflammation, HOMA, body composition, and GI/GL (estimated from 3-day food records) were assessed at baseline and 18 months. By 18 months, the GL in the CHO group increased by 34%, 88.4 ± 5.2 → 118.5 ± 4.9 and did not change in the PRO group, 86.5 ± 4.1 → 82.0 ± 3.6 (p < 0.0001). Despite this change there were no differences in serum CRP, IL-6, or HOMA at 18 months between the two groups, nor were there significant associations between GL and inflammatory markers. However, trunk lean mass (p = 0.0375) and total lean mass (p = 0.038) were higher in the PRO group compared to the CHO group at 18 months There were also significant associations for GL and change in total fat mass (r = 0.3, p = 0.01), change in BMI (r = 0.3, p = 0.005), and change in the lean-to-fat mass ratio (r = -0.3, p = 0.002). Our data suggest that as dietary GL increases within the moderate range, there is no detectable change in markers of inflammation or insulin resistance, despite which there is a negative effect on body composition.

Adherence to a Mediterranean-Style Diet and Its Influence on Cardiovascular Risk Factors in Postmenopausal Women.

BACKGROUND: A Mediterranean-style diet (MedSD) is associated with positive health outcomes, particularly reduced risk of cardiovascular disease. It is of interest to assess the feasibility of adherence to a MedSD in a subset of older adults in the United States. OBJECTIVE: To assess the efficacy of implementing a MedSD intervention in a subset of postmenopausal women living in the United States, and to detect the influence of this dietary pattern on blood lipid levels. DESIGN: A partial feeding, nutrition counseling, pilot study with a one-group longitudinal design. PARTICIPANTS: Sixteen healthy, postmenopausal, American women living in suburban communities in Farmington, CT, with a mean±standard deviation age of 77±6.8 years and a body mass index of 26.1±3.1. INTERVENTION: Participants were counseled by a registered dietitian nutritionist on how to follow a MedSD, which included increased sources of n-3 polyunsaturated fatty acids, fruits, and vegetables, and decreased saturated fat, n-6 polyunsaturated fatty acids, and simple sugars for 12 weeks. To maintain isocaloric conditions, participants were asked to substitute sources of saturated fat and refined carbohydrates for extra virgin olive oil (3 T/day), walnuts (1.5 oz/day), and fatty fish (3 to 5 servings/wk), which were provided at 3-week intervals. MAIN OUTCOME MEASURES: Dietary adherence measures included the Mediterranean Diet Score, 3-day diet records, and serum fatty acid and lipid profiles. STATISTICAL ANALYSES: Mixed model longitudinal analyses were conducted to assess changes over time (Weeks 0, 12, and 24) in the outcome variables. RESULTS: Mediterranean Diet Score increased by 8.9 points (P<0.001) after the MedSD phase. Dietary sugar decreased by 10.8 g (P<0.05), total dietary n-3 increased by 1.6 g (P<0.01), total dietary n-6 increased by 5.5 g (P<0.01), and dietary n-6:n3 ratio decreased by 3.6 units (P<0.01). In serum, 22:6 (n-3), 20:5 (n-3), and 18:3 (n-3) increased (P<0.001, P<0.01, and P<0.001, respectively), and 14:0, 16:0, 17:0, 20:4 (n-6), 22:4 (n-6) declined after the intervention (P<0.01, P<0.001, P<0.01, P<0.01, and P<0.001, respectively), which support a change in dietary intake toward a MedSD. Serum high-density lipoprotein cholesterol levels increased by 3.8 mg/dL (0.098 mmol/L) (P<0.05) and serum triglyceride levels decreased by 11.6 mg/dL (0.131 mmol/L) (P<0.10). CONCLUSIONS: A pilot study of a 12-week MedSD intervention with counseling from a registered dietitian nutritionist can favorably influence the dietary pattern and lipid profile of postmenopausal women living in the United States.

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.

Dietary Protein and Vitamin D Intake and Risk of Falls: A Secondary Analysis of Postmenopausal Women from the Study of Osteoporotic Fractures.

More than 90% of hip fractures in older Americans result from a fall. Inadequate intake of dietary protein and vitamin D are common in older adults, and diets in low these could contribute to loss of muscle mass and strength or coordination, in turn increasing the risk of falling. The objective of the study was to evaluate the relationship between protein and vitamin D intake with the occurrence of falls in older women in the Study of Osteoporotic Fracture, a prospective cohort of more than 4000 postmenopausal women participating from January 1997 to September 1998. Incident falls were ascertained for one year. Protein and vitamin D intake was assessed by a food frequency questionnaire; associations with a reported fall were estimated with logistic regression, adjusted for fall-related covariates and energy. Protein and vitamin D were modeled separately because of high correlation (rho = 0.55, P < 0.001). A total of 1429 women reported a fall within one year. In separate, unadjusted models dietary protein (per 1 g/kg increase) and vitamin D (per 100 International Unit (IU) increase) significantly increased the odds ratio (OR) of falling (OR 1.35 95% CI 1.15-1.59, OR 1.11 95% CI 1.03-1.19, respectively). Once fall-related covariates were added to each model, dietary protein and vitamin D were noncontributory to falls. While we could find no direct association between vitamin D and protein intake and fall prevention, adequate intake of these two nutrients are critical for musculoskeletal health in older adults.

The Effect of a Whey Protein Supplement on Bone Mass in Older Caucasian Adults.

CONTEXT: It has been assumed that the increase in urine calcium (Ca) that accompanies an increase in dietary protein was due to increased bone resorption. However, studies using stable Ca isotopes have found that dietary protein increases Ca absorption without increasing bone resorption. OBJECTIVE: The objective of the study was to investigate the impact of a moderately high protein diet on bone mineral density (BMD). DESIGN: This was a randomized, double-blind, placebo-controlled trial of protein supplementation daily for 18 months. SETTING: The study was conducted at two institutional research centers. PARTICIPANTS: Two hundred eight older women and men with a body mass index between 19 and 32 kg/m(2) and a self-reported protein intake between 0.6 and 1.0 g/kg participated in the study. INTERVENTION: Subjects were asked to incorporate either a 45-g whey protein or isocaloric maltodextrin supplement into their usual diet for 18 months. MAIN OUTCOME MEASURE: BMD by dual-energy x-ray absorptiometry, body composition, and markers of skeletal and mineral metabolism were measured at baseline and at 9 and 18 months. RESULTS: There were no significant differences between groups for changes in L-spine BMD (primary outcome) or the other skeletal sites of interest. Truncal lean mass was significantly higher in the protein group at 18 months (P = .048). C-terminal telopeptide (P = .0414), IGF-1 (P = .0054), and urinary urea (P < .001) were also higher in the protein group at the end of the study period. There was no difference in estimated glomerular filtration rate at 18 months. CONCLUSION: Our data suggest that protein supplementation above the recommended dietary allowance (0.8 g/kg) may preserve fat-free mass without adversely affecting skeletal health or renal function in healthy older adults.

Dietary protein, calcium metabolism, and skeletal homeostasis revisited.

High dietary protein intakes are known to increase urinary calcium excretion and, if maintained, will result in sustained hypercalciuria. To date, the majority of calcium balance studies in humans have not detected an effect of dietary protein on intestinal calcium absorption or serum parathyroid hormone. Therefore, it is commonly concluded that the source of the excess urinary calcium is increased bone resorption. Recent studies from our laboratory indicate that alterations in dietary protein can, in fact, profoundly affect intestinal calcium absorption. In short-term dietary trials in healthy adults, we fixed calcium intake at 20 mmol/d while dietary protein was increased from 0.7 to 2.1 g/kg. Increasing dietary protein induced hypercalciuria in 20 women [from 3.4 +/- 0.3 ( +/- SE) during the low-protein to 5.4 +/- 0.4 mmol/d during the high-protein diet]. The increased dietary protein was accompanied by a significant increase in intestinal calcium absorption from 18.4 +/- 1.3% to 26.3 +/- 1.5% (as determined by dual stable isotopic methodology). Dietary protein intakes at and below 0.8 g/kg were associated with a probable reduction in intestinal calcium absorption sufficient to cause secondary hyperparathyroidism. The long-term consequences of these low-protein diet-induced changes in mineral metabolism are not known, but the diet could be detrimental to skeletal health. Of concern are several recent epidemiologic studies that demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low-protein diets. Studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation, or both.

Dietary acid load is associated with lower bone mineral density in men with low intake of dietary calcium.

High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: (1) evaluate the cross-sectional relation between DAL and BMD; and (2) determine whether calcium intake modifies this association. Men (n = 1218) and women (n = 907) aged ≥60 years were included from the National Health and Nutrition Examination Survey 2005-2008. Nutrient intake from 2, 24-hour recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet ) and diet + supplemental calcium (PRALtotal ). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy-adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3 years. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend = 0.04). No associations were observed with PRALtotal at any BMD site (p range, 0.38-0.82). Among men, no significant associations were observed between BMD and NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p = 0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men with <800 mg/d dietary calcium (p = 0.02); no associations were found among men with ≥800 mg/d (p = 0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intake in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake.

Claudins, dietary milk proteins, and intestinal barrier regulation.

The family of claudin proteins plays an important role in regulating the intestinal barrier by modulating the permeability of tight junctions. The impact of dietary protein on claudin biology has not been studied extensively. Whey proteins have been reported to improve intestinal barrier function, but their mechanism of action is not clear. Recent studies, however, have demonstrated increased intestinal claudin expression in response to milk protein components. Reviewed here are new findings suggesting that whey-protein-derived transforming growth factor ß transcriptionally upregulates claudin-4 expression via a Smad-4-dependent pathway. These and other data, including limited clinical studies, are summarized below and, in the aggregate, suggest a therapeutic role for whey protein in diseases of intestinal barrier dysfunction, perhaps, in part, by regulating claudin expression.

Dietary protein-induced increases in urinary calcium are accompanied by similar increases in urinary nitrogen and urinary urea: a controlled clinical trial.

To determine the usefulness of urinary urea as an index of dietary protein intake, 10 postmenopausal women were enrolled in and completed a randomized, double-blind, cross-over feeding trial from September 2008 to May 2010 that compared 10 days of a 45-g whey supplement with 10 days of a 45-g maltodextrin control. Urinary nitrogen, urinary calcium, urinary urea, and bone turnover markers were measured at days 0, 7, and 10. Paired sample t tests, Pearson's correlation statistic, and simple linear regression were used to assess differences between treatments and associations among urinary metabolites. Urinary nitrogen/urinary creatinine rose from 12.3±1.7 g/g (99.6±13.8 mmol/mmol) to 16.8±2.2 g/g (135.5±17.8 mmol/mmol) with whey supplementation, but did not change with maltodextrin. Whey supplementation caused urinary calcium to rise by 4.76±1.84 mg (1.19±0.46 mmol) without a change in bone turnover markers. Because our goal was to estimate protein intake from urinary nitrogen/urinary creatinine, we used our data to develop the following equation: protein intake (g/day)=71.221+1.719×(urinary nitrogen, g)/creatinine, g) (R=0.46, R(2)=0.21). As a more rapid and less costly alternative to urinary nitrogen/urinary creatinine, we next determined whether urinary urea could predict protein intake and found that protein intake (g/day)=63.844+1.11×(urinary urea, g/creatinine, g) (R=0.58, R(2)=0.34). These data indicate that urinary urea/urinary creatinine is at least as good a marker of dietary protein intake as urinary nitrogen and is easier to quantitate in nutrition intervention trials.

Soy proteins and isoflavones reduce interleukin-6 but not serum lipids in older women: a randomized controlled trial.

Soy foods contain several components, notably, isoflavones and amino acids, that may improve cardiovascular health. We evaluated the long-term effect of soy protein and/or soy isoflavones supplementation on serum lipids and inflammatory markers using a 1-year randomized, double-blind, placebo-control, clinical trial in 131 healthy ambulatory women older than 60 years. We hypothesized that soy protein, in combination with isoflavones, would have the largest positive effect on coronary heart disease risk factors (serum lipids and inflammatory markers) compared with either intervention alone and that, within groups receiving isoflavones, equol producers would have more positive effects on coronary heart disease risk factors than nonequol producers. After a 1-month baseline period, participants were randomized into 1 of 4 intervention groups: soy protein (18 g/d) and isoflavone tablets (105 mg/d isoflavone aglycone equivalents), soy protein and placebo tablets, control protein and isoflavone tablets, or control protein and placebo tablets. T Tests were used to assess differences between equol and nonequol producers. Ninety-seven women completed the trial. Consumption of protein powder and isoflavone tablets did not differ among groups, and compliance with study powder and tablets was 79% and 90%, respectively. After 1 year, in the entire population, there were either no or little effects on serum lipids and inflammatory markers, regardless of treatment group. Equol producers, when analyzed separately, had significant improvements in total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios (-5.9%, P = .02; -7.2%, P = .04 respectively). Soy protein and isoflavone (either alone or together) did not impact serum lipids or inflammatory markers. Therefore, they should not be considered an effective intervention to prevent cardiovascular disease because of lipid modification in healthy late postmenopausal women lacking the ability to produce equol.

Calcium intake in the United States from dietary and supplemental sources across adult age groups: new estimates from the National Health and Nutrition Examination Survey 2003-2006.

BACKGROUND: Adequate lifelong calcium intake is essential in optimizing bone health. Recent National Health and Nutrition Examination Survey data were used to quantify variation in calcium intake across adult age groups and to relate age-associated changes in calcium intake with energy intake. Additional goals were to assess differences in dietary calcium intake between supplemental calcium users and nonusers and to evaluate associations between age and calcium density in the diet. DESIGN: This cross-sectional analysis determined calcium and energy intake for National Health and Nutrition Examination Survey respondents during 2003-2006. Diet was assessed with 24-hour recall and supplement use via questionnaire. Trends in median intakes for dietary calcium, total calcium, and energy across age categories were assessed using survey analysis methods. Nutrient density was represented using calcium to energy intake ratios. RESULTS: The analyses included data from 9,475 adults. When compared to the 19- to 30-year age group, median dietary calcium intake was lower in the ≥81-year age group by 23% in men (P<0.001) and by 14% in women (P=0.003). These reductions coincided with 35% and 28% decreases, respectively, in median energy intake (P<0.001 for each sex). In contrast, the frequency of calcium supplement use increased (P<0.001) with age in both men and women. Yet, among female supplement users, the decline in median dietary calcium intake was greater than in nonusers (P=0.02). Calcium density in the diet significantly increased relative to age in men and women (P<0.001 for each sex); however, dietary and total calcium to energy ratios were insufficient to meet target ratios inferred by adequate intake standards after age 50 years. CONCLUSIONS: Although supplemental calcium use and calcium density were highest in older age groups, they were not sufficient in meeting recommended levels. New approaches to increasing the frequency and level of calcium supplement use to enhance calcium density in diets may be necessary to reduce osteoporosis risk among older Americans.

Optimizing bone health in older adults: the importance of dietary protein.

Age-related bone loss is progressive and can lead to osteoporosis. While it is accepted that both dietary calcium and vitamin D are important and beneficial for skeletal health, the impact of dietary protein on calcium metabolism and bone balance remains controversial. Contrary to the hypothesis that increasing dietary protein contributes to bone loss, research supports the notion that protein may play a pivotal role in maintenance of bone health by several mechanisms; for example, increasing dietary protein increases IGF-1, calcium absorption, muscle strength and mass, all of which could potentially benefit the skeleton. A moderate increase in dietary protein recommendations for the aging population (above the recommended dietary allowance of 0.8 g/kg) may be beneficial to bone health, while still falling within the safe and acceptable range for protein intake (as defined by the dietary reference intakes).

The effect of dietary protein on intestinal calcium absorption in rats.

Increasing dietary protein intake in humans acutely increases urinary calcium. Isotopic absorption studies have indicated that, at least in the short term, this is primarily due to increased intestinal Ca absorption. To explore the mechanisms underlying dietary protein's effect on intestinal Ca absorption, female Sprague Dawley rats were fed a control (20%), low (5%), or high (40%) protein diet for 7 d, and Ca balance was measured during d 4-7. On d 7, duodenal mucosa was harvested and brush border membrane vesicles (BBMVs) were prepared to evaluate Ca uptake. By d 7, urinary calcium was more than 2-fold higher in the 40% protein group compared with control (4.2 mg/d vs. 1.7 mg/d; P < 0.05). Rats consuming the 40% protein diet both absorbed and retained more Ca compared with the 5% protein group (absorption: 48.5% vs. 34.1% and retention: 45.8% vs. 33.7%, respectively; P < 0.01). Ca uptake was increased in BBMVs prepared from rats consuming the high-protein diet. Maximum velocity (V(max)) was higher in the BBMVs prepared from the high-protein group compared with those from the low-protein group (90 vs. 36 nmol Ca/mg protein x min, P < 0.001; 95% CI: 46-2486 and 14-55, respectively). The Michaelis Menten constant (K(m)) was unchanged (2.2 mm vs. 1.8 mm, respectively; P = 0.19). We conclude that in rats, as in humans, acute increases in protein intake result in hypercalciuria due to augmented intestinal Ca absorption. BBMV Ca uptake studies suggest that higher protein intake improves Ca absorption, at least in part, by increasing transcellular Ca uptake.