Category Archives: Protein

Fish or Fish Oil No Association With Fracture – 2010

Abstract

Fish consumption, bone mineral density, and risk of hip fracture among older adults: the cardiovascular health study.

Marine n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be beneficial for bone health, but few studies have investigated the association with fish consumption. Our aim was to study associations of fish and EPA + DHA consumption with bone mineral density (BMD) and hip fracture risk and determine whether high linoleic acid (LA) intake, the major dietary n-6 PUFA, modifies the associations. The study population consisted of 5045 participants aged 65 years and older from the Cardiovascular Health Study. Data on BMD were available for 1305 participants. Food-frequency questionnaire was used to assess dietary intake, and hip fracture incidence was assessed prospectively by review of hospitalization records. After multivariable adjustment, femoral neck BMD was 0.01 g/cm(2) lower in the highest versus lowest tuna/other-fish intake category (p = .05 for trend). EPA + DHA intake (higher versus lower median of 0.32 g/day) was associated with lower femoral neck BMD (0.66 versus 0.71 g/cm(2), p < .001) among those with LA intake greater than the median 12.1 g/day (p = .03 for interaction). No significant associations were found with total-hip BMD. During mean follow-up of 11.1 years, 505 hip fractures occurred. Fish or EPA + DHA consumption was not significantly associated with fracture incidence [hazard ratio (HR) for extreme categories: HR = 1.23, 95% confidence interval (CI) 0.83-1.84 for tuna/other fish; HR = 1.16, 95% CI 0.91-1.49 for fried fish; and HR = 0.98, 95% CI 0.71-1.36 for EPA + DHA]. High LA intake did not modify these associations. In this large prospective cohort of older adults, fish consumption was associated with very small differences in BMD and had no association with hip fracture risk.

Virtanen JK, Mozaffarian D, Cauley JA, Mukamal KJ…
J. Bone Miner. Res. Sep 2010
PMID: 20572022 | Free Full Text

Protein + Calcium Protects Against Fractures in the Framingham Study – 2010

Abstract

Protective effect of high protein and calcium intake on the risk of hip fracture in the Framingham offspring cohort.

The effect of protein on bone is controversial, and calcium intake may modify protein’s effect on bone. We evaluated associations of energy-adjusted tertiles of protein intake (ie, total, animal, plant, animal/plant ratio) with incident hip fracture and whether total calcium intake modified these associations in the Framingham Offspring Study. A total of 1752 men and 1972 women completed a baseline food frequency questionnaire (1991-1995 or 1995-1998) and were followed for hip fracture until 2005. Hazard ratios (HRs) were estimated using Cox proportional hazards regression adjusting for confounders. Baseline mean age was 55 years (SD 9.9 years, range 26 to 86 years). Forty-four hip fractures occurred over 12 years of follow-up. Owing to significant interaction between protein (total, animal, animal/plant ratio) and calcium intake (p interaction range = .03 to .04), stratified results are presented. Among those with calcium intakes less than 800 mg/day, the highest tertile (T3) of animal protein intake had 2.8 times the risk of hip fracture [HR = 2.84, 95% confidence interval (CI) 1.20-6.74, p = .02] versus the lowest tertile (T1, p trend = .02). In the 800 mg/day or more group, T3 of animal protein had an 85% reduced hip fracture risk (HR = 0.15, 95% CI 0.02-0.92, p = .04) versus T1 (p trend = .04). Total protein intake and the animal/plant ratio were not significantly associated with hip fracture (p range = .12 to .65). Our results from middle-aged men and women show that higher animal protein intake coupled with calcium intake of 800 mg/day or more may protect against hip fracture, whereas the effect appears reversed for those with lower calcium intake. Calcium intake modifies the association of protein intake and the risk of hip fracture in this cohort and may explain the lack of concordance seen in previous studies.

Sahni S, Cupples LA, McLean RR, Tucker KL…
J. Bone Miner. Res. Dec 2010
PMID: 20662074 | Free Full Text

Fish May Protect Bone in Older Adults – 2011

Abstract

Protective effects of fish intake and interactive effects of long-chain polyunsaturated fatty acid intakes on hip bone mineral density in older adults: the Framingham Osteoporosis Study.

Polyunsaturated fatty acids and fish may influence bone health.
We aimed to examine associations between dietary polyunsaturated fatty acid and fish intakes and hip bone mineral density (BMD) at baseline (1988-1989; n = 854) and changes 4 y later in adults (n = 623) with a mean age of 75 y in the Framingham Osteoporosis Study.

BMD measures were regressed on energy-adjusted quartiles of fatty acid intakes [n-3 (omega-3): α-linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and EPA+ DHA; n-6 (omega-6): linoleic acid (LA) and arachidonic acid (AA); and n-6:n-3 ratio] and on categorized fish intakes, with adjustment for covariates. Effect modification by EPA+DHA intake was tested for n-6 exposures.
High intakes (≥3 servings/wk) of fish relative to lower intakes were associated with maintenance of femoral neck BMD (FN-BMD) in men (dark fish + tuna, dark fish, and tuna) and in women (dark fish) (P < 0.05). Significant interactions between AA and EPA+DHA intakes were observed cross-sectionally in women and longitudinally in men. In women with EPA+DHA intakes at or above the median, those with the highest AA intakes had a higher mean baseline FN-BMD than did those with the lowest intakes (quartile 4 compared with quartile 1: P = 0.03, P for trend = 0.02). In men with the lowest EPA+DHA intakes (quartile 1), those with the highest intakes of AA (quartile 4) lost more FN-BMD than did men with the lowest intakes of AA (quartile 1; P = 0.04). LA intake tended to be associated with FN-BMD loss in women (P for trend < 0.06).
Fish consumption may protect against bone loss. The protective effects of a high AA intake may be dependent on the amount of EPA+DHA intake.

Farina EK, Kiel DP, Roubenoff R, Schaefer EJ…
Am. J. Clin. Nutr. May 2011
PMID: 21367955 | Free Full Text

Fish Consumption Helps Maintain Bone in Spanish Women – 2013

Abstract

Dietary habits, nutrients and bone mass in Spanish premenopausal women: the contribution of fish to better bone health.

The moderate consumption of fish is recommended for a healthy diet and is also a feature of the Mediterranean diet. Fish is a major food group in diets throughout the world, and studies show that fish consumption is associated with a lower risk of a number of conditions. Spain has one of the highest annual per capita consumptions of fish worldwide. As fish is a source of high quality protein; n-3 polyunsaturated fatty acids; vitamins, such as A and D; and minerals, such as selenium, calcium, iodine, magnesium, copper and zinc, nutrients that have positive effects on bone characteristics, it has been proposed that its consumption could improve bone health. In this cross-sectional study, we have investigated the relationship between dietary habits and nutrient intake of 151 Spanish premenopausal women and analyzed the association of fish consumption on bone mass measured by quantitative ultrasound of the phalanges. A higher (P < 0.05) bone mass and vitamin D intake (P < 0.05) was observed in the group with a fish intake of 5-7 servings/week. We conclude that increased fish consumption is helpful in maintaining an adequate bone mass in Spanish premenopausal women.

Calderon-Garcia JF, Moran JM, Roncero-Martin R, Rey-Sanchez P…
Nutrients Jan 2013
PMID: 23271510 | Free Full Text

Review: Protein and bones – 2003

Abstract

Dietary protein and bone health.

The effects of dietary protein on bone health are paradoxical and need to be considered in context of the age, health status and usual diet of the population. Over the last 80 years numerous studies have demonstrated that a high protein intake increases urinary Ca excretion and that on average 1 mg Ca is lost in urine for every 1 g rise in dietary protein. This relationship is primarily attributable to metabolism of S amino acids present in animal and some vegetable proteins, resulting in a greater acid load and buffering response by the skeleton. However, many of these early studies that demonstrated the calciuric effects of protein were limited by low subject numbers, methodological errors and the use of high doses of purified forms of protein. Furthermore, the cross-cultural and population studies that showed a positive association between animal-protein intake and hip fracture risk did not consider other lifestyle or dietary factors that may protect or increase the risk of fracture. The effects of protein on bone appear to be biphasic and may also depend on intake of Ca- and alkali-rich foods, such as fruit and vegetables. At low protein intakes insulin-like growth factor production is reduced, which in turn has a negative effect on Ca and phosphate metabolism, bone formation and muscle cell synthesis. Although growth and skeletal development is impaired at very low protein intakes, it is not known whether variations in protein quality affect the achievement of optimal peak bone mass in adolescents and young adults. Prospective studies in the elderly in the USA have shown that the greatest bone losses occur in elderly men and women with an average protein intake of 16-50 g/d. Although a low protein intake may be indicative of a generally poorer diet and state of health, there is a need to evaluate whether there is a lower threshold for protein intake in the elderly in Europe that may result in increased bone loss and risk of osteoporotic fracture.

Ginty F
Proc Nutr Soc Nov 2003
PMID: 15018487

Animal Protein Associated with Decreased Ultrasound Bone Measurement in Women – 2005

Abstract

The relation between dietary protein, calcium and bone health in women: results from the EPIC-Potsdam cohort.

The role of dietary protein in bone health is controversial. The objective of the present study was to examine the association between protein intake, dietary calcium, and bone structure measured by broadband ultrasound attenuation (BUA).
Our analysis includes 8,178 female study participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) Potsdam Study. Ultrasound bone measurements were performed on the right os calcis, and BUA was determined. Dietary intake was assessed by a standardized food frequency questionnaire. We applied linear regression models to estimate the association between dietary protein and BUA.
After multivariate adjustment, high intake of animal protein was associated with decreased BUA values (beta = -0.03; p = 0.010) whereas high vegetable protein intake was related to an increased BUA (beta = 0.11; p = 0.007). The effect of dietary animal protein on BUA was modified by calcium intake.
High consumption of protein from animal origin may be unfavourable, whereas a higher vegetable protein intake may be beneficial for bone health. Our results strengthen the hypothesis that high calcium intake combined with adequate protein intake based on a high ratio of vegetable to animal protein may be protective against osteoporosis.

Weikert C, Walter D, Hoffmann K, Kroke A…
Ann. Nutr. Metab. Sep-Oct 2005
PMID: 16088096 | Free Full Text

Protein Sulfur Associated with Lower Bone Density in Postmenopausal Women – 2008

Abstract

A positive association of lumbar spine bone mineral density with dietary protein is suppressed by a negative association with protein sulfur.

Dietary protein is theorized to hold both anabolic effects on bone and demineralizing effects mediated by the diet acid load of sulfate derived from methionine and cysteine. The relative importance of these effects is unknown but relevant to osteoporosis prevention. Postmenopausal women (n = 161, 67.9 +/- 6.0 y) were assessed for areal bone mineral density (aBMD) of lumbar spine (LS) and total hip (TH) using dual X-ray absorptiometry, and dietary intakes of protein, sulfur-containing amino acids, and minerals using a USDA multiple-pass 24-h recall. The acidifying influence of the diet was estimated using the ratio of protein:potassium intake, the potential renal acid load (PRAL), and intake of sulfate equivalents from protein. aBMD was regressed onto protein intake then protein was controlled for estimated dietary acid load. A step-down procedure assessed potential confounding influences (weight, age, physical activity, and calcium and vitamin D intakes). Protein alone did not predict LS aBMD (P = 0.81); however, after accounting for a negative effect of sulfate (beta = -0.28; P < 0.01), the direct effect of protein intake was positive (beta = 0.22; P = 0.04). At the TH, protein intake predicted aBMD (beta = 0.18; P = 0.03), but R2 did not improve with adjustment for sulfate (P = 0.83). PRAL and the protein:potassium ratio were not significant predictors of aBMD. Results suggest that protein intake is positively associated with aBMD, but benefit at the LS is offset by a negative impact of the protein sulfur acid load. If validated experimentally, these findings harmonize conflicting theories on the role of dietary protein in bone health.

Thorpe M, Mojtahedi MC, Chapman-Novakofski K, McAuley E…
J. Nutr. Jan 2008
PMID: 18156408 | Free Full Text

Animal Protein Increases Bone Loss and Fracture in Postmenopausal Women – 2001

Abstract

A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. Study of Osteoporotic Fractures Research Group.

Different sources of dietary protein may have different effects on bone metabolism. Animal foods provide predominantly acid precursors, whereas protein in vegetable foods is accompanied by base precursors not found in animal foods. Imbalance between dietary acid and base precursors leads to a chronic net dietary acid load that may have adverse consequences on bone. We wanted to test the hypothesis that a high dietary ratio of animal to vegetable foods, quantified by protein content, increases bone loss and the risk of fracture. This was a prospective cohort study with a mean (+/-SD) of 7.0+/-1.5 y of follow-up of 1035 community-dwelling white women aged >65 y. Protein intake was measured by using a food-frequency questionnaire and bone mineral density was measured by dual-energy X-ray absorptiometry. Bone mineral density was not significantly associated with the ratio of animal to vegetable protein intake. Women with a high ratio had a higher rate of bone loss at the femoral neck than did those with a low ratio (P = 0.02) and a greater risk of hip fracture (relative risk = 3.7, P = 0.04). These associations were unaffected by adjustment for age, weight, estrogen use, tobacco use, exercise, total calcium intake, and total protein intake. Elderly women with a high dietary ratio of animal to vegetable protein intake have more rapid femoral neck bone loss and a greater risk of hip fracture than do those with a low ratio. This suggests that an increase in vegetable protein intake and a decrease in animal protein intake may decrease bone loss and the risk of hip fracture. This possibility should be confirmed in other prospective studies and tested in a randomized trial.

Sellmeyer DE, Stone KL, Sebastian A, Cummings SR
Am. J. Clin. Nutr. Jan 2001
PMID: 11124760 | Free Full Text


More recent studies and randomized trials have discredited the conclusions of this study.

There are two published comments on this study. The full text is available for both.

Protein intake and bone health: the influence of belief systems on the conduct of nutritional science.
Heaney RP
PMID: 11124741 | Free Full Text

Dietary ratio of animal to vegetable protein and rate of bone loss and risk of fracture in postmenopausal women.
Sebastian A, Sellmeyer DE, Stone KL, Cummings SR
Am. J. Clin. Nutr. Sep 2001
PMID: 11522569 | Free Full Text

Milk Basic Protein Inhibits Resorption in Ovariectomized Rats

Abstract

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

Abstract

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.