Thorpe, M., Mojtahedi, M. C., Chapman-Novakofski, K., McAuley, E., & Evans, E. M. (2008). A positive association of lumbar spine bone mineral density with dietary protein is suppressed by a negative association with protein sulfur. The Journal of Nutrition, 138, 180-185.
The authors acknowledge that recent literature reflects a discordant view on the role of dietary protein in bone health. Dietary protein is theorized to hold an anabolic influence on bone, mediated by bone-active hormones, particularly insulin-like growth factors, and may increase calcium absorption. Conversely, sulfate equivalents derived from methionine and cysteine metabolism are exchanged by the kidney for acid equivalents; such a dietary acid load has been demonstrated to cause bone demineralization in animals and is associated with reduced bone mineral mass in humans.
In their literature review, the authors propose that bone demineralization is promoted by a mild but chronic dietary acid load characteristic of the Western diet. This acid load can be characterized by nutrient intake as the estimated NEAP, calculated using a ratio of protein to potassium intake, or using a function of protein, calcium, potassium, magnesium, and phosphorus intake known as the potential renal acid load (PRAL). These methods assume that the sulfur content of protein is a fixed ratio. However, it is known that the measurement of actual sulfur intakes improved estimates of dietary acid load, because actual methionine and cysteine contents vary according to protein source. Currently, nutrient databases are available that account for variation in sulfur-containing amino acids.
The primary aim of this study was to explain the role of dietary protein in bone health status as estimated by dual-energy x-ray absorptiometry (DXA) measures of areal bone mineral density (aBMD). Diet record analysis was used to estimate intakes of total protein and sulfate from amino acids for calculation of the dietary acid load. The authors anticipated that although dietary protein would be positively related to aBMD, this relationship would be suppressed by a negative association of aBMD, with the dietary acid load related to protein intake.
The sample consisted of 161 postmenopausal women (67.9 +/- 6.0 years) from Champaign County, Illinois. Subjects were recruited by using local media advertising, churches, senior citizens' centers, and healthcare facilities. Women with neurologic, orthopaedic, or cognitive limitations were excluded from the study.
Bone measurement was done by DXA of the lumbar spine and hips. Dietary intake and estimation of acid load was assessed by using the U.S. Department of Agriculture multiple-pass 24-hr dietary recall method. Participants completed an interview with researchers to screen for missed foods, portion-size clarification, and recall completeness. Diet records were analyzed for total energy, protein, methionine, cysteine, and micronutritients of interest for calculation of estimated NEAP.
Among the participants, 128 (80%) were taking supplemental calcium of at least 100 mg daily, 34 (20%) were taking a prescribed osteoporosis medication, 50 (31%) were taking hormone replacement therapy, and an additional 64 (40%) had undergone hormone replacement therapy in the past. One individual had the lumbar scan but not the hip scan and was dropped from the study. Thus, the study population was reduced to 160 participants.
Nutrient analysis was performed using Nutritionist Pro, Version 2.3.1 (First Data Bank). Protein sulfur load was calculated as mEq/day using intakes of methionine and cystine divided by their molecular weights, as described by Frassetto, Todd, Morris, and Sebastian (1998).
The PRAL of the diet was estimated according to the method of Remer, Dimitriou, and Manz (2003).
PRAL = 0.49 x protein (g) + 0.037 x P (mg) - 0.021 x K (mg) - 0.02 x Mg (mg) - 0.013 x Ca (mg).
The protein-to-potassium ratio estimation of NEAP was calculated according to the method of Frassetto et al. (1998).
Distributions were assessed for normality and outliers using the Shapiro-Wilk statistic in conjunction with box plot outlier labeling. Correlations for energy intake, protein, protein sulfur, minerals of interest, vitamin D, aBMD, and body composition (weight, fat mass, and lean mass) were calculated for descriptive purposes. A step-down procedure was used to assess potential confounding influences (weight, age, physical activity, and calcium and vitamin D intakes).
The results showed that protein alone did not predict lumbar spine scan aBMD (p = .81): however, after accounting for a negative effect of sulfate ([beta] = -2.28; p < .01), the direct effect of protein intake was positive ([beta] = .22; p = .04). For the hip scan, protein intake predicted aBMD ([beta] = .18; p = .03), and R2 did not improve with adjustment for sulfate (p = .83). PRAL and the protein-to-potassium ratio were not significant predictors of aBMD.
The results of this study suggest that protein intake is positively associated with aBMD, but benefit at the lumbar spine is offset by a negative impact of the protein sulfur acid load. If validated experimentally, these findings reconcile conflicting theories on the role of dietary protein in bone health. These results also highlight the need to evaluate the actual sulfur content of varying dietary protein sources rather than assuming a fixed sulfur-to-protein ratio.
There are a number of limitations to this study: (1) the size of the study population is of only 160 persons, (2) diet is measured on the basis of recall at just one point, and (3) the study is best interpreted as a rationale for additional investigation. Future research should evaluate the role of dietary protein and its components in preserving bone health in populations at higher risk for fracture such as the elderly.
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