Monthly Archives: September 2013

Milk Basic Protein Inhibits Resorption in Ovariectomized Rats


Milk basic protein: a novel protective function of milk against osteoporosis.

Milk is recommended as an excellent calcium source for bone health. Moreover, milk is considered to contain other components effective for bone health. In our previous studies, using an unfractionated bone cell culture system, we found that milk whey protein, especially its basic fraction (milk basic protein [MBP]), suppressed bone resorption. In this present study, we investigated whether MBP could prevent bone loss in aged ovariectomized rats. Twenty-one 51-week-old female Sprague-Dawley rats were ovariectomized (ovx), and another seven rats received a sham operation (sham). After a 4-week recovery period, the ovx rats were separated into three groups, and they were then fed a control diet, a 0.01% MBP diet (0. 01% casein of the control diet replaced with MBP), or a 0.1% MBP diet for 17 weeks. The sham rats were fed the control diet. Bone mineral density (BMD) of the femur was measured by dual-energy X-ray absorptiometry in vivo. The BMD in the ovx-control group noticeably decreased during the experimental period in comparison with that in the sham group. However, the BMD in the OVX-0.1% MBP group was significantly higher than that in ovx-control group at weeks 12 and 16 (p < 0.05). After the 17-week feeding period, the breaking energy of the excised femur of all groups was determined by use of a three-point bending rheolometer. The breaking energy in the ovx-control group was significantly lower than that in the sham group (p < 0.05). However, the breaking energy in the ovx-0.1% MBP group was significantly higher than that of the ovx-control group (p < 0.05). Urinary deoxypyridinoline (D-Pyr) level of the ovx-control group was higher than that of the sham group, whereas the level of D-Pyr excretion in the ovx-0.01% MBP and ovx-0.1% MBP groups was significantly lower than that of the ovx-control group (p < 0.05). These results suggest that MBP suppresses the osteoclast-mediated bone resorption and prevents bone loss caused by ovariectomy. Moreover, we performed an in vitro study using isolated osteoclasts from rabbit bone to investigate the possible mechanism. MBP dose-dependently suppressed the number of pits formed by these osteoclasts. This result indicates that MBP suppresses bone resorption by its direct effects on osteoclasts. To our knowledge, this study provides the first evidence that MBP directly suppresses osteoclast-mediated bone resorption, resulting in the prevention of the bone loss that occurs in ovx rats.

Toba Y, Takada Y, Yamamura J, Tanaka M…
Bone Sep 2000
PMID: 10962352

Hypothesis: Animal Protein Associated with Hip Fracture – 1992


Cross-cultural association between dietary animal protein and hip fracture: a hypothesis.

Age-adjusted female hip fracture incidence has been noted to be higher in industrialized countries than in nonindustrialized countries. A possible explanation that has received little attention is that elevated metabolic acid production associated with a high animal protein diet might lead to chronic bone buffering and bone dissolution. In an attempt to examine this hypothesis, cross-cultural variations in animal protein consumption and hip fracture incidence were examined. When female fracture rates derived from 34 published studies in 16 countries were regressed against estimates of dietary animal protein, a strong, positive association was found. This association could not plausibly be explained by either dietary calcium or total caloric intake. Recent studies suggest that the animal protein-hip fracture association could have a biologically tenable basis. We conclude that further study of the metabolic acid-osteoporosis hypothesis is warranted.

Abelow BJ, Holford TR, Insogna KL
Calcif. Tissue Int. Jan 1992
PMID: 1739864

This study from 1992 was one of the earlier proposals that animal protein may cause osteoporosis. The hypothesis has since been discredited.

Protein Associated with Reduced Fractures – June 2012


Protein intake and fracture risk in elderly people: a case-control study.

We investigated whether protein intake (PI) is related to osteoporotic fractures (OP) in the elderly by analyzing vegetable protein intake (VPI), animal protein intake (API), and animal/vegetable protein intake ratio (AVR) and by calcium intake (CaI).
A 1:1 matched by age and sex case-control study with 167 cases was carried out at the Hospital of Jaen (Spain). Cases were patients aged ≥65 years with a low-energy fracture. Controls were people without previous fractures. Diet was assessed by a food frequency questionnaire. Multivariable analyses were fitted using analysis of covariance (for comparison of adjusted means) and conditional logistic regression (estimating adjusted odds ratios [ORs]).
The control-group showed a higher API (p = 0.046) even when CaI was <800 mg/day (p = 0.041). ORs for AVR were 0.68 (0.38-1.19) and 0.38 (0.15-0.98), respectively with a p for trend = 0.046. A PI<15% of the total energy intake showed an OR of 2.86 (1.10-7.43).
Patients with fracture history have lower API suggesting that high API reduce the occurrence of OP in elderly even if CaI is <800 mg/day. A PI<15% of total calories were associated with an increased risk of OP in elderly.

Martínez-Ramírez MJ, Delgado-Martínez AD, Ruiz-Bailén M, de la Fuente C…
Clin Nutr Jun 2012
PMID: 22182947

Review: Protein, Calcium, Vitamins D, C, K, and Fruits and Veggies in Osteoporosis


The role of diet in osteoporosis prevention and management.

Diet, a modifiable osteoporosis risk factor, plays an important role in the acquisition and maintenance of bone mass. The influence of diet on bone begins in childhood; even maternal diet can influence bone mass in the offspring. A good general nutritional status and adequate dietary protein, calcium, vitamin D, fruits, and vegetables have a positive influence on bone health, while a high caloric diet and heavy alcohol consumption have been associated with lower bone mass and higher rates of fracture. The evidence for a role of other minerals and vitamins in skeletal health is not as strong, but recent evidence suggests that vitamins C and K might also have an effect on bone.

Levis S, Lagari VS
Curr Osteoporos Rep Dec 2012
PMID: 23001895

Low Protein Increases Bone Loss in Vitamin D Deficiency or Ovariectomy in Rats


Low protein intake magnifies detrimental effects of ovariectomy and vitamin D on bone.

Protein-induced changes in bone and calcium homeostasis could potentially be greater in the elderly and in women at risk for osteoporosis. We hypothesize that a low protein intake would magnify the negative changes in bone metabolism seen in vitamin D (vitD) insufficiency and/or estrogen deficiency. The present study was undertaken to better understand how a low protein diet along with vitD insufficiency could affect bone metabolism using a rodent ovariectomized (OVX) model. Rats (n = 60) underwent ovariectomy (OVX) or sham operation. The first 15 days after surgery, all rats were fed a standard rodent diet. Thereafter, rats (n = 10/group) were fed a low protein diet (LP; 2.5 %) or a control diet (NP; 12.5 %) with 100 IU% vitD (+D; cholecalciferol) or without vitD (-D) for 45 days. The groups were as follows: SHAM + NP + D (control); SHAM + LP + D; SHAM + LP – D; OVX + NP + D; OVX + LP + D; OVX + LP – D. Body weight (BW) of control and OVX + NP + D groups increased while those feeding the LP diet, independently of vitD feedings, decreased (p < 0.05). The OVX + LP – D group presented the lowest serum Ca, phosphorus and osteocalcin levels and the highest CTX levels (p < 0.05). At the end of the study, total skeleton bone mineral content, proximal tibia bone mineral density, bone volume and trabecular number levels decreased as follows: SHAM + NP + D (controls) > SHAM + LP + D > OVX + NP + D > SHAM + LP – D > OVX + LP + D > OVX + LP – D (p < 0.05). A low protein diet negatively affected bone mass and magnified the detrimental effects of vitD and/or estrogen deficiencies.

Marotte C, Gonzales Chaves MM, Pellegrini GG, Friedman SM…
Calcif. Tissue Int. Aug 2013
PMID: 23708885

Protein Lowers Fracture in 50-59 Year Olds, not 70-89 Year Olds


Dietary protein intake and risk of osteoporotic hip fracture in elderly residents of Utah.

The role of protein intake in osteoporosis is unclear. In a case-control study in Utah (n = 2501), increasing level of protein intake was associated with a decreased risk of hip fracture in men and women 50-69 years of age but not in those 70-89 years of age. Protein intake may be important for optimal bone health.
Protein is an important component of bone, but the role of dietary protein intake in osteoporosis and fracture risk remains controversial.
The role of dietary protein intake in osteoporotic hip fracture was evaluated in a statewide case-control study in Utah. Patients, 50-89 years of age, with hip fracture (cases) were ascertained through surveillance of 18 Utah hospitals during 1997-2001. Age- and gender-matched controls were randomly selected. Participants were interviewed in their place of residence, and diet was assessed using a picture-sort food frequency questionnaire previously reported to give a useful measure of usual dietary intake in the elderly Utah population. The association between protein intake and risk of hip fracture was examined across quartiles of protein intake and stratified by age group for 1167 cases (831 women, 336 men) and 1334 controls (885 women, 449 men).
In logistic regression analyses that controlled for gender, body mass index, smoking status, alcohol use, calcium, vitamin D, potassium, physical activity, and estrogen use in women, the odds ratios (OR) of hip fracture decreased across increasing quartiles of total protein intake for participants 50-69 years of age (OR: 1.0 [reference]; 0.51 [95% CI: 0.30-0.87]; 0.53 [0.31-0.89]; 0.35 [0.21-0.59]; p < 0.001). No similar associations were observed among participants 70-89 years of age. Results from analyses stratified by low and high calcium and potassium intake did not differ appreciably from the results presented above.
Higher total protein intake was associated with a reduced risk of hip fracture in men and women 50-69 years of age but not in men and women 70-89 years of age. The association between dietary protein intake and risk of hip fracture may be modified by age. Our study supports the hypothesis that adequate dietary protein is important for optimal bone health in the elderly 50-69 years of age.

Wengreen HJ, Munger RG, West NA, Cutler DR…
J. Bone Miner. Res. Apr 2004
PMID: 15005839

Protein Supplement in Hip Rehabilitation Not Significant


Provision of high-protein supplement for patients recovering from hip fracture.

We compared clinical outcomes with a standard (Ensure) or a high-protein (Boost HP) liquid nutritional supplement for older adults recovering from hip fracture surgery in a rehabilitation hospital. This randomized, double-blind, parallel-group study compared the clinical effectiveness of a standard (Ensure) with a high-protein (Boost HP) liquid nutritional supplement among patients (n = 46) 60 y or older who recently underwent surgical repair of a hip fracture. Patients were encouraged to drink at least two 8-oz cans (17.8 g/d protein for Ensure versus 30 g/d protein for Boost HP) per day for 28 d. Study measurements included change in Functional Independence Measure between rehabilitation admission and discharge, length of rehabilitation stay, laboratory measures (i.e., serum albumin, prealbumin, and C-reactive protein), physical activity energy expenditure by 7-d triaxial accelerometry, and dietary intake by three random, telephonic, 24-h dietary recalls.
There were no significant group differences with respect to age, sex, acute hospital days, hip fracture assessment parameters, or surgical treatment. Consumption of supplement (260 oz/28 d of Ensure versus 239 oz/28 d of Boost HP) was comparable. There were no differences in complication or adverse event rates during the study. The Boost HP group consumed more protein than the Ensure group (63 versus 50 g, P < 0.048) and had a greater improvement in serum albumin over the 28-d supplementation period (+0.7 versus +0.2 g/dL, P < 0.019). The Boost HP group also consumed more fiber (12 versus 8 g), calcium (821 versus 639 mg), vitamin K (66 versus 45 microg), and phosphorus (1035 versus 833 mg) than did the Ensure group. Rehabilitation length of stay was shorter in the Boost HP than in the Ensure group, although this trend did not reach statistical significance (23 versus 28 d, P = 0.27). Outcome differences were not detected in the Functional Independence Measure.
Supplementation was well tolerated in this population and contributed significantly to total dietary intake. Consumption of a high-protein liquid nutritional supplement may offer some benefits by improving visceral protein status.

Neumann M, Friedmann J, Roy MA, Jensen GL
Nutrition May 2004
PMID: 15105027

Protein Consumption Predicts Lower Limb Bone Mass in Elderly Women


Protein consumption is an important predictor of lower limb bone mass in elderly women.

The effect of protein intake on bone density is uncertain, and evidence exists for beneficial effects of both low and high protein intakes. The objective was to study the relation between protein consumption and bone mass in elderly women with allowance for other lifestyle factors affecting bone metabolism. We conducted a cross-sectional and longitudinal study of a population-based sample of 1077 women aged 75 +/- 3 y. At baseline, protein consumption was measured with a food-frequency questionnaire, and bone mass and structure were measured by using quantitative ultrasound of the heel. One year later, hip bone mineral density (BMD) was measured by using dual-energy X-ray absorptiometry.
Subjects consumed a mean (+/-SD) of 80.5 +/- 27.8 g protein/d (1.19 +/- 0.44 g protein/kg body wt). Regression analysis showed a positive correlation between protein intake and qualitative ultrasound of the heel and BMD after adjustment for age, body mass index, and other nutrients. The dose-response effect was best characterized by protein consumption expressed in tertiles, such that subjects in the lowest tertile (<66 g protein/d) had significantly lower qualitative ultrasound of the heel (1.3%) and hip BMD (2.6%) than did the subjects in the higher tertiles (>87 g protein/d).
These data suggest that protein intakes for elderly women above current recommendations may be necessary to optimize bone mass.

Devine A, Dick IM, Islam AF, Dhaliwal SS…
Am. J. Clin. Nutr. Jun 2005
PMID: 15941897 | Free Full Text

Protein + Exercise Improves Bone Markers in Young Adults


Effect of protein supplementation during a 6-mo strength and conditioning program on insulin-like growth factor I and markers of bone turnover in young adults.

Exercise is beneficial for bone when adequate nutrition is provided. The role of protein consumption in bone health, however, is controversial. The objective was to ascertain the effect of high protein intake on insulin-like growth factor I (IGF-I) and markers of bone turnover during 6 mo of exercise training. Fifty-one subjects aged 18-25 y (28 men, 23 women) received a protein supplement (42 g protein, 24 g carbohydrate, 2 g fat) or a carbohydrate supplement (70 g carbohydrate) twice daily. Exercise consisted of alternating resistance training and running 5 times/wk. Plasma concentrations of IGF-I, insulin-like growth factor-binding protein 3, serum bone alkaline phosphatase, and urinary N-telopeptide collagen crosslink (NTx) concentrations were measured at 0, 3, and 6 mo after 24 h without exercise and a 12-h fast.Three-day diet records indicated no difference in energy intake between the groups. Average protein intakes after supplementation began in the protein and carbohydrate groups were 2.2 +/- 0.1 and 1.1 +/- 0.1 g/kg, respectively (P < 0.001). The increase in plasma IGF-I was greater in the protein group than in the carbohydrate group (time x supplement interaction, P = 0.01). There were no significant changes over time or significant differences by supplement in plasma insulin-like growth factor-binding protein 3 (44 and 40 kDa). Serum bone alkaline phosphatase increased significantly over time (P = 0.04) and tended to be higher in the protein group than in the carbohydrate group (P = 0.06). NTx concentrations changed over time (time and time squared; P < 0.01 for both) and were greater in the protein group than in the carbohydrate group (P = 0.04). Men had higher NTx concentrations than did women (74.6 +/- 3.4 and 60.0 +/- 3.8 nmol/mmol creatinine; P = 0.005). Protein supplementation during a strength and conditioning program resulted in changes in IGF-I concentrations.

Ballard TL, Clapper JA, Specker BL, Binkley TL…
Am. J. Clin. Nutr. Jun 2005
PMID: 15941900 | Free Full Text

Review: Protein RDA May be Too Low


Protein intake and bone health.

Adequate nutrition plays an important role in the development and maintenance of bone structures resistant to usual mechanical stresses. In addition to calcium in the presence of an adequate supply of vitamin D, dietary proteins represent key nutrients for bone health and thereby function in the prevention of osteoporosis. Several studies point to a positive effect of high protein intake on bone mineral density or content. This fact is associated with a significant reduction in hip fracture incidence, as recorded in a large prospective study carried out in a homogeneous cohort of postmenopausal women. Low protein intake (< 0.8 g/kg body weight/day) is often observed in patients with hip fractures and an intervention study indicates that following orthopedic management, protein supplementation attenuates post-fracture bone loss, tends to increase muscle strength, and reduces medical complications and rehabilitation hospital stay. There is no evidence that high protein intake per se would be detrimental for bone mass and strength. Nevertheless, it appears reasonable to avoid very high protein diets (i. e. more than 2.0 g/kg body weight/day) when associated with low calcium intake (i. e. less than 600 mg/day). In the elderly, taking into account the attenuated anabolic response to dietary protein with ageing, there is concern that the current dietary protein recommended allowance (RDA), as set at 0.8 g/kg body weight/day, might be too low for the primary and secondary prevention of fragility fractures.

Bonjour JP
Int J Vitam Nutr Res Mar 2011
PMID: 22139564