Carmen Castaneda-Sceppa

Physical Activity and Public Health in Older Adults Recommendation From the American College of Sports Medicine and the American Heart Association

OBJECTIVE To issue a recommendation on the types and amounts of physical activity needed to improve and maintain health in older adults. PARTICIPANTS A panel of scientists with expertise in public health, behavioral science, epidemiology, exercise science, medicine, and gerontology. EVIDENCE The expert panel reviewed existing consensus statements and relevant evidence from primary research articles and reviews of the literature. PROCESS After drafting a recommendation for the older adult population and reviewing drafts of the Updated Recommendation from the American College of Sports Medicine (ACSM) and the American Heart Association (AHA) for Adults, the panel issued a final recommendation on physical activity for older adults. SUMMARY The recommendation for older adults is similar to the updated ACSM/AHA recommendation for adults, but has several important differences including: the recommended intensity of aerobic activity takes into account the older adults aerobic fitness; activities that maintain or increase flexibility are recommended; and balance exercises are recommended for older adults at risk of falls. In addition, older adults should have an activity plan for achieving recommended physical activity that integrates preventive and therapeutic recommendations. The promotion of physical activity in older adults should emphasize moderate-intensity aerobic activity, muscle-strengthening activity, reducing sedentary behavior, and risk management.

Testosterone and Growth Hormone Improve Body Composition and Muscle Performance in Older Men

CONTEXT Impairments in the pituitary-gonadal axis with aging are associated with loss of muscle mass and function and accumulation of upper body fat. OBJECTIVES We tested the hypothesis that physiological supplementation with testosterone and GH together improves body composition and muscle performance in older men. DESIGN, SETTING, AND PARTICIPANTS One hundred twenty-two community-dwelling men 70.8 +/- 4.2 yr of age with body mass index of 27.4 +/- 3.4 kg/m2, testosterone of 550 ng/dl or less, and IGF-I in lower adult tertile (< or =167 ng/dl) were randomized to receive transdermal testosterone (5 or 10 g/d) during a Leydig cell clamp plus GH (0, 3, or 5 microg/kg . d) for 16 wk. MAIN OUTCOME MEASURES Body composition by dual-energy x-ray absorptiometry, muscle performance, and safety tests were conducted. RESULTS Total lean body mass increased (1.0 +/- 1.7 to 3.0 +/- 2.2 kg) as did appendicular lean tissue (0.4 +/- 1.4 to 1.5 +/- 1.3 kg), whereas total fat mass decreased by 0.4 +/- 0.9 to 2.3 +/- 1.7 kg as did trunk fat (0.5 +/- 0.9 to 1.5 +/- 1.0 kg) across the six treatment groups and by dose levels for each parameter (P < or = 0.0004 for linear trend). Composite maximum voluntary strength of upper and lower body muscles increased by 14 +/- 34 to 35 +/- 31% (P < 0.003 in the three highest dose groups) that correlated with changes in appendicular lean mass. Aerobic endurance increased in all six groups (average 96 +/- 137 sec longer). Systolic and diastolic blood pressure increased similarly in each group with mean increases of 12 +/- 14 and 8 +/- 8 mm Hg, respectively. Other predictable adverse events were modest and reversible. CONCLUSIONS Supplemental testosterone produced significant gains in total and appendicular lean mass, muscle strength, and aerobic endurance with significant reductions in whole-body and trunk fat. Outcomes appeared to be further enhanced with GH supplementation.

Treatment with Potassium Bicarbonate Lowers Calcium Excretion and Bone Resorption in Older Men and Women

CONTEXT Bicarbonate has been implicated in bone health in older subjects on acid-producing diets in short-term studies. OBJECTIVE The objective of this study was to determine the effects of potassium bicarbonate and its components on changes in bone resorption and calcium excretion over 3 months in older men and women. DESIGN, PARTICIPANTS, AND INTERVENTION In this double-blind, controlled trial, 171 men and women age 50 and older were randomized to receive placebo or 67.5 mmol/d of potassium bicarbonate, sodium bicarbonate, or potassium chloride for 3 months. All subjects received calcium (600 mg of calcium as triphosphate) and 525 IU of vitamin D(3) daily. MAIN OUTCOME MEASURES Twenty-four-hour urinary N-telopeptide and calcium were measured at entry and after 3 months. Changes in these measures were compared across treatment groups in the 162 participants included in the analyses. RESULTS Bicarbonate affected the study outcomes, whereas potassium did not; the two bicarbonate groups and the two no bicarbonate groups were therefore combined. Subjects taking bicarbonate had significant reductions in urinary N-telopeptide and calcium excretion, when compared with subjects taking no bicarbonate (both before and after adjustment for baseline laboratory value, sex, and changes in urinary sodium and potassium; P = 0.001 for both, adjusted). Potassium supplementation did not significantly affect N-telopeptide or calcium excretion. CONCLUSIONS Bicarbonate, but not potassium, had a favorable effect on bone resorption and calcium excretion. This suggests that increasing the alkali content of the diet may attenuate bone loss in healthy older adults.

Effect of intra-dialytic, low-intensity strength training on functional capacity in adult haemodialysis patients: a randomized pilot trial

BACKGROUND Kidney failure is associated with muscle wasting and physical impairment. Moderate- to high-intensity strength training improves physical performance, nutritional status and quality of life in people with chronic kidney disease and in dialysis patients. However, the effect of low-intensity strength training has not been well documented, thus representing the objective of this pilot study. METHODS Fifty participants (mean +/- SD, age 69 +/- 13 years) receiving long-term haemodialysis (3.7 +/- 4.2 years) were randomized to intra-dialytic low-intensity strength training or stretching (attention-control) exercises twice weekly for a total of 48 exercise sessions. The primary study outcome was physical performance assessed by the Short Physical Performance Battery score (SPPB) after 36 sessions, if available, or carried forward from 24 sessions. Secondary outcomes included lower body strength, body composition and quality of life. Measurements were obtained at baseline and at completion of 24 (mid), 36 (post) and 48 (final) exercise sessions. RESULTS Baseline median (IQR) SPPB score was 6.0 (5.0), with 57% of the participants having SPPB scores below 7. Exercise adherence was 89 +/- 15%. The primary outcome could be computed in 44 participants. SPPB improved in the strength training group compared to the attention-control group [21.1% (43.1%) vs. 0.2% (38.4%), respectively, P = 0.03]. Similarly, strength training participants exhibited significant improvements from baseline compared to the control group in knee extensor strength, leisure-time physical activity and self-reported physical function and activities of daily living (ADL) disability; all P < 0.02. Adverse events were common but not related to study participation. CONCLUSIONS Intra-dialytic, low-intensity progressive strength training was safe and effective among maintenance dialysis patients. Further studies are needed to establish the generalizability of this strength training program in dialysis patients.

Resistance training and timed essential amino acids protect against the loss of muscle mass and strength during 28 days of bed rest and energy deficit

Spaceflight and bed rest (BR) result in losses of muscle mass and strength. Resistance training (RT) and amino acid (AA) supplementation are potential countermeasures to minimize these losses. However, it is unknown if timing of supplementation with exercise can optimize benefits, particularly with energy deficit. We examined the effect of these countermeasures on body composition, strength, and insulin levels in 31 men (ages 31-55 yr) during BR (28 days) followed by active recovery (14 days). Subjects were randomly assigned to essential AA supplementation (AA group, n = 7); RT with AA given 3 h after training (RT group, n = 12); or RT with AA given 5 min before training (AART group, n = 12). Energy intake was reduced by 8 +/- 6%. Midthigh muscle area declined with BR for the AA > RT > AART groups: -11%, -3%, -4% (P = 0.05). Similarly, greatest losses in lower body muscle strength were seen in the AA group (-22%). These were attenuated in the exercising groups [RT (-8%) and AART (-6%; P < 0.05)]. Fat mass and midthigh intramuscular fat increased after BR in the AA group (+3% and +14%, respectively), and decreased in the RT (-5% and -4%) and AART groups (-1 and -5%; P = 0.05). Muscle mass and strength returned toward baseline after recovery, but the AA group showed the lowest regains. Combined resistance training with AA supplementation pre- or postexercise attenuated the losses in muscle mass and strength by approximately two-thirds compared with AA supplement alone during BR and energy deficit. These data support the efficacy of combined AA and RT as a countermeasure against muscle wasting due to low gravity.

Site-specific concentrations of carotenoids in adipose tissue: relations with dietary and serum carotenoid concentrations in healthy adults

BACKGROUND Dietary carotenoids are related to a decreased risk of certain diseases. Serum and adipose tissue carotenoid concentrations are used as biomarkers of intake. OBJECTIVES The objectives of this study were to evaluate site-specific concentrations of carotenoids in adipose tissue and to examine relations between carotenoid concentrations in the diet, serum, and adipose tissue. DESIGN Healthy adults (12 women and 13 men) participated in this cross-sectional study. Dietary carotenoids over the past year were assessed with a food-frequency questionnaire. Serum and adipose tissue biopsy samples were collected from the abdomen, buttock, and inner thigh for the measurement of carotenoids by HPLC. RESULTS Many adipose carotenoids were inversely related to percentage body fat, although lycopene was the only carotenoid inversely correlated with all 3 sites. Most of the carotenoids were significantly higher in the abdominal adipose tissue than in the thigh (P < 0.05). Concentrations of alpha-carotene, beta-carotene, 5-cis-lycopene, and total carotenoids were significantly higher in the buttocks than in the thigh (P < 0.05). Concentrations of alpha-carotene, cis-lycopene, and lutein (with or without zeaxanthin) were significantly higher in the abdomen than in the buttocks (P < 0.05). Dietary intake was significantly correlated with serum concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, and total carotenoids. Carotenoid intake was significantly correlated with adipose tissue concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, cis-lycopene, and total carotenoids (P < 0.05) but varied by site. Of all the adipose tissue sites evaluated, the abdomen showed the strongest correlation with long-term dietary carotenoid intakes and with serum (indicator of short-term intake) for most carotenoids. CONCLUSIONS Body fat may influence the tissue distribution of carotenoids. Abdominal adipose tissue carotenoid concentrations may be a useful indicator of carotenoid status.

Resistance Training Increases Muscle Mitochondrial Biogenesis in Patients with Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Muscle wasting, a common complication in chronic kidney disease (CKD), contributes to poor outcomes. Mitochondrial biogenesis is critical for the maintenance of skeletal muscle function and structural integrity. The present study--a secondary analysis from a published randomized controlled trial--examined the effect of resistance exercise training on skeletal muscle mitochondrial (mt)DNA copy number and determined its association with skeletal muscle phenotype (muscle mass and strength). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Twenty-three patients with moderate-to-severe CKD were randomized to resistance training (n = 13) or an attention-control (n = 10) group for 12 weeks. After a run-in period of a low-protein diet that continued during the intervention, mtDNA copy number in the vastus lateralis muscle was estimated by quantitative real-time PCR at baseline and 12 weeks. RESULTS Participants mean age was 64 +/- 10 (SD) years and median (interquartile range, IQR) GFR 27.5 (37.0) ml/min. There were no differences between groups at baseline. Median (IQR) mtDNA copy number was 13,713 (10,618). There was a significant increase in muscle mtDNA with exercise compared with controls (1306 [13306] versus -3747 [15467], P = 0.01). The change in muscle mtDNA copy number was positively correlated with previously reported changes in types I and II muscle fiber cross-sectional area. CONCLUSIONS In this pilot study, resistance training was highly effective in enhancing mitochondrial content in patients with moderate-to-severe CKD. This finding suggests that the mitochondrial dysfunction observed with chronic disease could potentially be restored with this exercise modality and should be investigated further.

Increased protein maintains nitrogen balance during exercise-induced energy deficit.

PURPOSE This study examined how a high-protein diet affected nitrogen balance and protein turnover during an exercise-induced energy deficit. METHODS Twenty-two men completed a 4-d (D1-4) baseline period (BL) of an energy balance diet while maintaining usual physical activity level, followed by 7 d (D5-11) of 1000 kcal.d increased energy expenditure via exercise (50-65% V O2peak). One group consumed 0.9 g of protein per kilogram per day and maintained energy balance throughout the 11-d intervention (BAL, N = 8). The other two groups consumed their BL energy intake throughout the 11 days, resulting in a 7-d, 1000-kcal.d energy deficit. These groups consumed either 0.9 g of protein per kilogram per day (DEF, N = 7) or 1.8 g of protein per kilogram per day (DEF-HP, N = 7). Mean nitrogen balance (NB), calculated per kilogram of fat-free mass (FFM), was determined for BL, days 5-8 (EX1), and days 9-11 (EX2). Whole-body protein turnover was derived from phenylalanine and tyrosine kinetics assessed while fasting at rest on days 4, 7, and 12, using a priming dose of L-[ring-N]tyrosine and a 4-h, primed, continuous infusion of L-[N]phenylalanine and L-[ring-H4]tyrosine. RESULTS DEF experienced a decrease in NB from BL to EX 1 that was maintained in EX 2. No changes in NB occurred for BAL or DEF-HP over time. No within- or between-group differences were found over time for Phe flux (Qp), conversion rate of Phe to Tyr (Qpt), or the derived protein synthesis value (Sp). CONCLUSION Increased dietary protein maintained NB during exercise-induced energy deficit, but this did not impact resting whole-body protein turnover.

Testosterone Threshold Levels and Lean Tissue Mass Targets Needed to Enhance Skeletal Muscle Strength and Function: The HORMA Trial

BACKGROUND In the HORMA (Hormonal Regulators of Muscle and Metabolism in Aging) Trial, supplemental testosterone and recombinant human growth hormone (rhGH) enhanced lean body mass, appendicular skeletal muscle mass, muscle performance, and physical function, but there was substantial interindividual variability in outcomes. METHODS One hundred and twelve men aged 65-90 years received testosterone gel (5 g/d vs 10 g/d via Leydig cell clamp) and rhGH (0 vs 3 vs 5 μg/kg/d) in a double-masked 2 × 3 factorial design for 16 weeks. Outcomes included lean tissue mass by dual energy x-ray absorptiometry, one-repetition maximum strength, Margaria stair power, and activity questionnaires. We used pathway analysis to determine the relationship between changes in hormone levels, muscle mass, strength, and function. RESULTS Increases in total testosterone of 1046 ng/dL (95% confidence interval = 1040-1051) and 898 ng/dL (95% confidence interval = 892-904) were necessary to achieve median increases in lean body mass of 1.5 kg and appendicular skeletal muscle mass of 0.8 kg, respectively, which were required to significantly enhance one-repetition maximum strength (≥ 30%). Co-treatment with rhGH lowered the testosterone levels (quantified using liquid chromatography-tandem mass spectrometry) necessary to reach these lean mass thresholds. Changes in one-repetition maximum strength were associated with increases in stair climbing power (r = .26, p = .01). Pathway analysis supported the model that changes in testosterone and insulin-like growth factor 1 levels are related to changes in lean body mass needed to enhance muscle performance and physical function. Testosterones effects on physical activity were mediated through a different pathway because testosterone directly affected Physical Activity Score of the Elderly. CONCLUSIONS To enhance muscle strength and physical function, threshold improvements in lean body mass and appendicular skeletal muscle mass are necessary and these can be achieved by targeting changes in testosterone levels. rhGH augments the effects of testosterone. To maximize functional improvements, the doses of anabolic hormones should be titrated to achieve target blood levels.

N-Terminal Propeptide of Type III Procollagen as a Biomarker of Anabolic Response to Recombinant Human GH and Testosterone

CONTEXT Biomarkers that predict musculoskeletal response to anabolic therapies should expedite drug development. During collagen synthesis in soft lean tissue, N-terminal propeptide of type III procollagen (P3NP) is released into circulation. We investigated P3NP as a biomarker of lean body mass (LBM) and muscle strength gains in response to testosterone and GH. DESIGN Community-dwelling older men received GnRH agonist plus 5 or 10 g testosterone gel plus 0, 3, or 5 microg recombinant human GH daily. P3NP levels were measured at baseline and wk 4, 8, 12, and 16. LBM and appendicular skeletal muscle mass (ASM) were measured by dual-energy x-ray absorptiometry. RESULTS One hundred twelve men completed treatment; 106 underwent serum P3NP measurements. P3NP levels were higher at wk 4 than baseline (6.61 +/- 2.14 vs. 4.51 +/- 1.05, P < 0.0001) and reached plateau by wk 4 in men receiving testosterone alone. However, wk 8 P3NP levels were higher than wk 4 levels in men receiving testosterone plus recombinant human GH. Increases in P3NP from baseline to wk 4 and 16 were significantly associated with gains in LBM (r = 0.26, P = 0.007; r = 0.53, P < 0.001) and ASM (r = 0.17, P = 0.07; r = 0.40, P < 0.0001). Importantly, for participants receiving only testosterone, P3NP increases at wk 4 and 16 were related to muscle strength gains (r = 0.20, P = 0.056 and r = 0.36, P = 0.04). In stepwise regression, change in P3NP explained 28 and 30% of the change in ASM and LBM, respectively, whereas change in testosterone but not IGF-I and age provided only small improvements in the models. CONCLUSION Early changes in serum P3NP levels are associated with subsequent changes in LBM and ASM during testosterone and GH administration. Serum P3NP may be a useful early predictive biomarker of anabolic response to GH and testosterone.