9/26/2016. The Impact of Dietary Protein on the Musculoskeletal System. Research in dietary protein, musculoskeletal health and calcium economy

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Agnes Henderson
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1 The Impact of Dietary Protein on the Musculoskeletal System Outline A. The musculoskeletal system and associated disorders Jessica D Bihuniak, PhD, RD Assistant Professor of Clinical Nutrition Department of Nutrition and Food Studies B. Research exploring the impact of dietary protein/ amino acids on calcium economy, mineral density and body composition 1. Bad for hypothesis C. Optimal protein intake for musculoskeletal health in older adults D. Clinical/ research tools for assessing skeletal health E. Summary/ future directions The Musculoskeletal System Bones, Muscles, Tendons, Ligaments, Nerves, Cartilages Musculoskeletal disorders are the most common causes of severe long term pain and physical disability Musculoskeletal disorders include: Osteoporosis & associated fractures Sarcopenia Research in dietary protein, musculoskeletal health and calcium economy Lifestyle factors influence the musculoskeletal system/ disorders Dietary protein Urinary Ca, mg/d studies in >275 adults r = 0.7 p < What is the source of the additional urinary calcium? (Kerstetter et al. J Nutr Mar;133(3):855S 861S. ) Dietary Protein, g/d 1

2 Three Potential Sources for Additional Urinary Calcium Dietary Ca controlled. Epidemiologic data are mixed. Two large, randomized, protein supplementation trials showed no detrimental effect of higher protein diets on BMD. Dual stable Ca isotopes showed an increase in Ca absorption with higher protein intakes. We next were interested in beginning to elucidate the mechanism by which dietary protein augments intestinal Ca absorption and thus, began to explore different groups of amino acids that could be responsible for this effect. Kerstetter et al. J Nutr Zhu et al. J Bone Miner Res Kerstetter et al. JCEM Kerstetter et al. AJCN Kerstetter et al. JCEM Amino Acid Supplementation Trial Design Randomized double blind, placebo controlled, crossover study. Three 6 day, Low Protein, Study Diets (0.7 g/kg) N=14 N=14 N=14 Placebo Phenylalanine Tryptophan Arginine Lysine Histidine CaSR AAA DAA Food provided by Yale Center for Clinical Investigation metabolic kitchen. 24-h Urine Metabolites Control CaSR-AAA DAA Day 1 Day 5 Day 1 Day 5 Day 1 Day 5 Sodium (mmol) 90.8 ± ± ± ± ± ± 9.7 Calcium (mmol) 4.6 ± ± ± ± ± ± 0.5 Phosphorus (mmol) 18.4 ± ± ± ± ± ± 1.3 Data presented as mean ±SEM. *P < 0.05 indicated statistical significance. * * * * * Bihuniak et al. J Nutr. 2014;144(3): Intestinal Calcium absorption on day 5 of the three study diets Control CaSR AAA Effect Size Day 5 Day 5 Ca absorption (%) ± ± ± 0.09 Control DAA Effect Size Day 5 Day 5 Ca absorption (%) ± ± ± 0.1 If the source of urinary Ca is the skeleton due to the effect of sulfur containing AA, then non-sulfur containing amino acids should have no effect on urinary Ca. Data presented as mean ±SEM. P > 0.05 but < 0.10 indicated a trend. Bihuniak et al. J Nutr. 2014;144(3):

Revisiting the Bad for Bone Hypothesis High protein diets Sulfur containing amino acids Fixed metabolic acid load How does dietary protein/ specific amino acids increase calcium absorption?

3 Revisiting the Bad for Bone Hypothesis High protein diets Sulfur containing amino acids Fixed metabolic acid load How does dietary protein/ specific amino acids increase calcium absorption? Osteoclast mediated resorption Increased Urinary Calcium Dietary protein/ Arg+Lys?? Do findings from our calcium absorption studies translate into improvements in BMD? Supplemental Protein to Outsmart Osteoporosis Now 18-month, randomized, double-blind, placebocontrolled, multi-centered trial in older adults Kerstetter*, Bihuniak* et al. JCEM 2015 Jun;100(6): *contributed equally to this work. SPOON Intervention Maltodextrin Maltrin M100 Grain Processing Corporation Whey Protein Provon 290 Glambia Nutritionals Kcal/ 45 g powder Sodium (mg) Potassium (mg) Phosphorus (mg) Calcium (mg) All subjects (n=208; average age 70 yo) received a daily multivitamin containing 400 IU of vitamin D. Multivitamin, Ca carbonate supplement and Ca containing foods were used to ensure a minimum Ca intake of 1200 mg/d. 3

4 Primary Results: We observed no changes in BMD by DXA and QCT at 18 months. We observed minor changes in BTMs, likely not clinically relevant. No significant change in GFR. We observed no changes in handgrip strength. Urinary urea was significantly higher in the protein group compared to the carb group at 18 months. DXA: dual energy xray absorptiometry; QCT: quantitative computed tomography Changes in Body Composition, BMI and Weight Carbohydrate n=102 Protein n=105 Between Group Differences at 18 months Least square mean (95% CI) Baseline 18 Mo Baseline 18 Mo Total Lean Body Mass (Kg) 42.0 ± ± ± ± (-1.1 to 0.04) Trunk Lean Body Mass (Kg) 20.9 ± ± ± ± (-0.7 to ) Total Fat Mass (Kg) 26.3 ± ± ± ± (-0.5 to 1.3) BMI (Kg/m 2 ) 26.3 ± ± ± ± (-0.4 to 0.3) Weight (Kg) 70.3 ± ± ± ± (-1.2 to 0.8) Data are presented as Least Square Mean ± SEM or Least Square Mean (95% CI). Within and Between group differences were adjusted for baseline. Statistically significant differences are shown in bold. SPOON Summary Protein supplementation in older men and women with adequate dietary protein intakes had no detrimental or positive effect on BMD (average: 1.3 g pro/kg). Total lean body mass was preserved and truncal fat free mass was significantly higher in the protein supplemented participants. As expected protein supplementation resulted in an increase in urinary urea. Estimated GFR remained within normal limits. There were no changes in physical activity, tobacco use or alcohol consumption that could have influenced these findings. What happens when we restrict dietary protein? Low Protein Study 9.5 week feeding study with one group design (n=11). Food provided by Yale s Center for Clinical Investigation Metabolic Kitchen. 3 weeks 6.5 weeks Moderate Protein Adjustment Diet 1.2 g pro/kg/d Low Protein Intervention 0.7 g pro/kg/d Low Protein Study Summary Employed stable Ca isotopes to evaluate the long term response to a moderate protein restriction on Ca metabolism and skeletal turnover. Consistency in urinary Na reflects good dietary compliance. Low protein consumption resulted in Baseline Ca absorption & Kinetics 6 blood urine collections draws Ca absorption & Kinetics assessed at week 1 & 6 4

5 Low Protein Study Summary Summary of Protein and Amino Acid Trials Ca Lower protein diet? Short term increases in dietary protein enhances Ca absorption in young and older women. Ca Ca UCa Calcium Absorption Compromised skeletal health Bone Resorption Bone Turnover Dibasic amino acids appear to be partly responsible for this increase. The addition of the milk protein, whey, to a moderate protein diet does not appear to be detrimental to and preserves lean mass in older men and postmenopausal women. Restricting dietary protein in young women reduces Ca absorption and results in unfavorable skeletal effects. Protein intakes above the RDA appear to be beneficial in preserving and muscle mass in older adults Increased dietary protein Reference Outcome Amount Campbell et al. J Gerontol A Nitrogen balance 1.0 to 1.3 g/kg/d Biol Sci Med Sci 200;156A:M373 M380. Wolfe et al. Am J Clin Nutr 2006;84: Kerstetter et al. JCEM 2015 Jun;100(6): Kerstetter et al. JCEM 2015 Jun;100(6): Muscle anabolism & maintenance of muscle tissue Total & truncal lean mass BMD 1.6 to 1.8 g/kg/d 1.3 g/kg/d 1.0 to 1.3 g/kg/d Increasing the RDA to 1.0 to 1.2 g/kg/d would maintain normal calcium metabolism and nitrogen balance without affecting renal function (Gaffney Stomberg et al. J Am Geriatr Soc 57: , 2009). Increased growth hormone Increased IGF-1 Stimulation of formation Improved intestinal Ca absorption Suppression of PTH Decreased skeletal turnover Improved synthesis of collagen & noncollagen matrix proteins Improved density, strength Decreased fractures Improved muscle mass, strength Increased anabolic stress on Decreased falls Methods for Assessing Nutritional Impact on Calcium Economy, Bone and Body Composition Clinical/ research tools for assessing skeletal health Stable isotopes Biochemical Markers Calcium absorption Calcium kinetics Turnover Whole skeleton Sensitive, safe, expensive Variable, cheaper indirect Dual energy x-ray absorptiometry Quantitative Computed Tomography Spine, hip, whole skeleton BMD Body composition Cortical and trabecular Volumetric measure Long term intervention Long term intervention 5

Markers of Bone Turnover & Protein Status P1NP Osteocalcin CTX Isoforms IGF-1 Indicator of type 1 collagen deposition Used to assess formation in dialysis patients & pagets disease Accounts for

C-terminal cross-linking telopeptide of type I collagen Alterations in configuration of type 1 collagen possibly involved in a decline in strength, linked to osteoporosis, pagets disease & renal

material to resist indentation. Inserted in the skin of the tibia until it reaches the surface and indents it. Provides an assessment of quality material strength.

6 Markers of Bone Turnover & Protein Status P1NP Osteocalcin CTX Isoforms IGF-1 Indicator of type 1 collagen deposition Used to assess formation in dialysis patients & pagets disease Accounts for 10-20% of noncollagenous protein in Can be elevated in postmenopausal osteoporosis due to increased turnover or depressed second to a decline in formation Insight into changes that take place at the C-terminal cross-linking telopeptide of type I collagen Alterations in configuration of type 1 collagen possibly involved in a decline in strength, linked to osteoporosis, pagets disease & renal osteodystrophy Peptide hormone with insulin-like activity & induces cell proliferation Synthesis & secretion influenced by dietary proteins Osteoprobe New assessment tool for Measures the ability of material to resist indentation. Inserted in the skin of the tibia until it reaches the surface and indents it. Provides an assessment of quality material strength. Novel marker of formation Known maker of formation Novel marker of resorption Anabolic to Summary/ Future Directions Current research suggests that dietary protein positively impacts the musculoskeletal system. Evaluated the relationship between material strength (BMS) and fracture in patients with low mass. BMS values were lower in patients with a fragility fracture compared with nonfracture patients despite similar BMD. Additional studies required to predict fracture risk from BMS. RDA for protein may not support optimal musculoskeletal health. Protein data for the elderly are sparse and more data are needed. Dietary protein intervention studies should examine quality and include BMS as an outcome variable. Thank You! 6

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

ORIGINAL ARTICLE The Effect of a Whey Protein Supplement on Bone Mass in Older Caucasian Adults Jane E. Kerstetter,* Jessica D. Bihuniak,* Jennifer Brindisi, Rebecca R. Sullivan, Kelsey M. Mangano, Sarah