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.

Effects of varenicline, nicotine or placebo on depressive symptoms in postmenopausal smokers.

BACKGROUND: Varenicline carries a black box warning for neuropsychiatric adverse events. OBJECTIVE: We examined varenicline use and past history of major depressive disorder (MDD) on depressive symptoms during smoking cessation. METHOD: This is a secondary analysis of two smoking cessation studies in 152 postmenopausal women who received placebo or nicotine patch, or 78 women who received varenicline with relaxation. Lifetime history of MDD (LH-MDD) was assessed at baseline and women with current MDD were excluded. Center for Epidemiologic Study Depression scale (CESD) measured depressive symptoms at baseline, 6 and 12 weeks. RESULTS: Baseline CESD scores were 5.3 + 4.4. Those with a LH-MDD reported higher CESD scores (p > .001). Those taking varenicline reported lower scores over all time periods compared to nicotine or placebo (p < .01). The differences between varenicline and the other treatments remained when controlling for LH-MDD, indicating an independent effect. CESD scores were associated with concurrent smoking status (p < .001), and with withdrawal symptoms (p < .001). CONCLUSION: CESD score were lower in those receiving varenicline, whether this is due to an anti-depressant effect, subject selection, use of relaxation or another cause is unknown. Varenicline does not increase depressive symptoms during smoking cessation in postmenopausal women without current MDD. Subjects with a LH-MDD are susceptible to developing depressive symptoms during smoking cessation, regardless of pharmacologic aid. SCIENTIFIC SIGNIFICANCE: Pharmacologic aids did not increase depression symptoms in this select population of postmenopausal women without current depression. Smoking cessation does increase depressive symptoms in those with LH-MDD, though the degree of increase was not clinically meaningful.

Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation on Bone Turnover in Older Women.

Animal and human studies indicate that omega (n)-3 polyunsaturated fatty acids (PUFA) can influence bone health. We conducted a randomized, double-blind, placebo-controlled trial of the effects of n-3 long chain (LC) PUFA supplementation (N-3 LCPUFA) on red blood cell (RBC) fatty acid levels and bone turnover markers in older postmenopausal women. One hundred and twenty-six postmenopausal women (mean age 75±7 years) were treated with n-3 LCPUFA (1.2 g eicosapentaenoic acid [EPA]/docosahexaenoic acid [DHA]/day, n=85) or placebo (olive oil, n=41) for 6 months. All women received 315 mg calcium citrate and 1000 IU cholecalciferol. RBC DHA (weight %) increased in the n-3 LCPUFA group, compared to no change in the placebo group (P<0.001). The ratio of DHA+EPA:arachidonic acid (AA) increased by 42 % in the n-3 LCPUFA group and by 5% in the placebo group (P<0.001). Bone-specific alkaline phosphatase and osteocalcin decreased in the n-3 LCPUFA group (P<0.05) with no between-group difference. Short-term n-3 LCPUFA supplementation increased RBC concentrations of DHA and n-3:n-6 ratios. Bone turnover decreased with n-3 LCPUF, but not statistically compared to placebo. The results point to the need for investigations with greater dosages of n-3 LCPUFA for a longer duration to understand the contribution to bone metabolism in postmenopausal women.

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.

Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older women.

OBJECTIVES: To investigate the effects of dehydroepiandrosterone (DHEA) combined with exercise on bone mass, strength, and physical function in older, frail women. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: A major medical institution. PARTICIPANTS: Ninety-nine women (mean age 76.6 ± 6.0) with low sulfated DHEA (DHEAS) levels, low bone mass, and frailty. INTERVENTION: Participants received 50 mg/d DHEA or placebo for 6 months; all received calcium and cholecalciferol. Women participated in 90-minute twice-weekly exercise regimens. MEASUREMENTS: Hormone levels, bone mineral density (BMD), bone turnover markers, body composition, upper and lower extremity strength, physical performance. RESULTS: Eighty-seven women (88%) completed 6 months. There were no significant changes in BMD or bone turnover markers. DHEA supplementation resulted in gains in lower extremity strength (from 459 ± 121 N to 484 ± 147 N; P=.01). There was also improvement in Short Physical Performance Battery score, a composite score that focuses on lower extremity function, in those taking DHEA (from 10.1 ± 1.8 to 10.7 ± 1.9; P=.02). There were significant changes in all hormone levels, including DHEAS, estradiol, estrone, and testosterone, and a decline in sex hormone-binding globulin levels in those taking DHEA. CONCLUSION: DHEA supplementation improved lower extremity strength and function in older, frail women involved in a gentle exercise program of chair aerobics or yoga. No changes were found in BMD either due to small sample size, short duration of study or no effect. The physical function findings are promising and require further evaluation as frail women are at high risk for falls and fracture.

Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty.

OBJECTIVES: To investigate the effects of testosterone supplementation on bone, body composition, muscle, physical function, and safety in older men. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: A major medical institution. PARTICIPANTS: One hundred thirty-one men (mean age 77.1 +/- 7.6) with low testosterone, history of fracture, or bone mineral density (BMD) T-score less than -2.0 and frailty. INTERVENTION: Participants received 5 mg/d of testosterone or placebo for 12 to 24 months; all received calcium (1500 mg/d diet and supplement) and cholecalciferol (1,000 IU/d). MEASUREMENTS: BMD of hip, lumbar spine, and mid-radius; body composition; sex hormones, calcium-regulating hormones; bone turnover markers; strength; physical performance; and safety parameters. RESULTS: Ninety-nine men (75.6%) completed 12 months, and 62 (47.3%) completed end therapy (mean 23 months; range 16-24 months for 62 who completed therapy). Study adherence was 54%, with 40% of subjects maintaining 70% or greater adherence. Testosterone and bioavailable testosterone levels at 12 months were 583 ng/dL and 157 ng/dL, respectively, in the treatment group. BMD on testosterone increased 1.4% at the femoral neck and 3.2% at the lumbar spine (P=.005) and decreased 1.3% at the mid-radius (P<.001). There was an increase in lean mass and a decrease in fat mass in the testosterone group but no differences in strength or physical performance. There were no differences in safety parameters. CONCLUSION: Older, frail men receiving testosterone replacement increased testosterone levels and had favorable changes in body composition, modest changes in axial BMD, and no substantial changes in physical function.

Comparison of the effects of calcium loading with calcium citrate or calcium carbonate on bone turnover in postmenopausal women.

Calcium supplementation is known to increase bone mineral density and decrease fractures, but the relative efficacy of different forms of calcium supplementation is not established. We compared the effects of calcium carbonate and calcium citrate on markers of bone resorption in older postmenopausal women in an open-labeled crossover study. Forty women were randomized to receive 1000 mg/day of either calcium citrate or calcium carbonate for 12 weeks, followed by a 2-week washout without calcium supplements and 12 weeks treatment with the alternate calcium supplement. All women received vitamin D (900 IU/day). Thirty-four women (25 Caucasian, nine Hispanic) completed the study. No significant differences in the decrease in parathyroid hormone (PTH) or bone specific alkaline phosphatase or the increase in urinary calcium/creatinine were detected between the two treatments. However, calcium citrate supplementation decreased the collagen cross-link resorption markers, urinary N-telopeptide (-30%), C-telopeptide (-31%), free deoxypyridinoline (19%) and serum N-telopeptide (-8%), compared to no significant change following calcium carbonate supplementation (+2%, +3%, +2% and +2%, respectively; P<0.05). Calcium citrate decreased markers of bone resorption significantly more than calcium carbonate in postmenopausal women, although no differences in their effects in calcium excretion or PTH were detected.