Development of a Novel Six-Month Nutrition Intervention for a Randomized Trial in Older Men with Mobility Limitations.

OBJECTIVES: Nutrition impacts the development of sarcopenia and protein intake is an important modulator of skeletal muscle mass loss in older people. The Optimizing Protein Intake in Older Men with Mobility Limitation (OPTIMEN) Trial was designed to assess the independent and combined effects of higher protein intake and a promyogenic agent, testosterone, on lean body mass, muscle strength and physical function in older men with mobility disability. The purpose of this paper is to describe the experimental design and nutrition intervention, including techniques used by research dietitians to develop and deliver energy and protein-specific meals to the homes of community-dwelling participants. Strategies to enhance long-term dietary compliance are detailed. DESIGN: Randomized, double-blind, placebo-controlled six-month intervention trial. SETTING: Participants were recruited from Boston MA USA and surrounding communities. PARTICIPANTS: Older men who were mobility-limited (Short Physical Performance Battery (SPPB) 3-10) and consuming less protein (<0.83 g/kg/day) were recruited for this study. INTERVENTION: Here we report the successful implementation of a double-blind, placebo-controlled, parallel group, randomized controlled trial with a 6-month intervention period among community-living men, age 65 years and older with a mobility limitation. A controlled feeding plan was used to deliver required energy intakes and prescribed protein quantities of 0.8 or 1.3 grams/kilogram/day (g/kg/d) in three meals plus snacks and supplements. A 2x2 factorial design was used to assess the effects of protein level alone and in combination with testosterone (vs. placebo) on changes in lean body mass (primary outcome), muscle strength, and physical function. RESULTS: A total of 154 men met the eligibility criteria; 112 completed a 2-week run-in period designed to evaluate compliance with the nutrition intervention. Of these, 92 subjects met compliance eligibility criteria and agreed to be randomized; 85% completed the full trial. The study successfully delivered three meals per day to subjects, with a high degree of compliance and subject satisfaction. Overall self-reported compliance rates were 80% and 93% for the meals and supplements, respectively. Details of compliance strategies are discussed. CONCLUSION: This community-based study design may serve as a model for longer-term nutritional interventions requiring monitoring of dietary compliance in a home-based feeding and supplementation trial.

In vivo effects of dietary quercetin and quercetin-rich red onion extract on skeletal muscle mitochondria, metabolism, and insulin sensitivity.

Red onions and low doses of the flavonoid, quercetin, increase insulin sensitivity and improve glucose tolerance. We hypothesized that dietary supplementation with red onion extract (RO) would attenuate high fat diet (HFD)-induced obesity and insulin resistance similar to quercetin supplementation by increasing energy expenditure through a mechanism involving skeletal muscle mitochondrial adaptations. To test this hypothesis, C57BL/6J mice were randomized into four groups and fed either a low fat diet (LF), HFD (HF), HFD + quercetin (HF + Q), or HFD + RO (HF + RO) for 9 weeks. Food consumption and body weight and composition were measured weekly. Insulin sensitivity was assessed by insulin and glucose tolerance tests. Energy expenditure and physical activity were measured by indirect calorimetry. Skeletal muscle incomplete beta oxidation, mitochondrial number, and mtDNA-encoded gene expression were measured. Quercetin and RO supplementation decreased HFD-induced fat mass accumulation and insulin resistance (measured by insulin tolerance test) and increased energy expenditure; however, only HF + Q showed an increase in physical activity levels. Although quercetin and RO similarly increased skeletal muscle mitochondrial number and decreased incomplete beta oxidation, establishing mitochondrial function similar to that seen in LF, only HF + Q exhibited consistently lower mRNA levels of mtDNA-encoded genes necessary for complexes IV and V compared to LF. Quercetin- and RO-induced improvements in adiposity, insulin resistance, and energy expenditure occur through differential mechanisms, with quercetin-but not RO-induced energy expenditure being related to increases in physical activity. While both treatments improved skeletal muscle mitochondrial number and function, mtDNA-encoded transcript levels suggest that the antiobesogenic, insulin-sensitizing effects of purified quercetin aglycone, and RO may occur through differential mechanisms.

Age attenuates leucine oxidation after eccentric exercise.

Aging may alter protein metabolism during periods of metabolic and physiologic challenge. The purpose of this study was to assess the effects of age on whole-body amino acid turnover in response to eccentric exercise and hyperglycemia-induced hyperinsulinemia. 16 healthy men were divided into young (N=8) and older (N=8) groups. Protein metabolism was assessed using a [1-13C]-leucine isotopic tracer approach. Measures were obtained under fasted basal conditions and during 3-h hyperglycemic clamps that were performed without (control) and 48 h after eccentric exercise. Exercise reduced leucine oxidation in the younger men (P<0.05), but not in older men. Insulin sensitivity was inversely correlated with leucine oxidation (P<0.05), and was lower in older men (P<0.05). Healthy aging is associated with an impaired capacity to adjust protein oxidation in response to eccentric exercise. The decreased efficiency of protein utilization in older men may contribute to impaired maintenance, growth, and repair of body tissues with advancing age.

Effects of fruit and vegetable, consumed in solid vs beverage forms, on acute and chronic appetitive responses in lean and obese adults.

BACKGROUND: The effects of fruits and vegetables in solid vs beverage forms on human appetite and food intake, acutely and chronically, are unclear. METHODS: This 21-week, randomized, crossover study assessed appetitive ratings following the inclusion of fruits and vegetables, in solid and beverage form, into the habitual diet of healthy lean (n=15) and overweight/obese (n=19) adults with low customary consumption. The primary acute outcomes were satiation (amount of challenge meal consumed), satiety (latency of subsequent eating event) and dietary compensation after a 400 kcal fruit preload. Ratings of appetite were also obtained before and after 8 weeks of required increased fruit and vegetable consumption (20% estimated energy requirement). RESULTS: Acutely, overweight/obese participants reported smaller reductions of hunger after consuming the fruit preload in beverage compared with solid form (preload × form × body mass index effects, P=0.03). Participants also consumed significantly less of a challenge meal (in both gram and energy) after the ingestion of the solid fruit preload (P<0.005). However, the subsequent meal latency was not significantly different between the solid and the beverage fruit preloads. Total daily energy intake was significantly higher when the obese participants consumed the beverage fruit preload compared with the solid (P<0.001). Daily energy intake was markedly, but not significantly, higher among the lean with the beverage vs solid food form. Hunger and fullness ratings remained stable when participants consumed fruits and vegetables in solid or beverage form for 8 weeks each. CONCLUSION: Acute post-ingestive appetitive responses were weaker following consumption of fruits in beverage vs solid food forms. Consumption of beverage or solid fruit and vegetable food loads for 8 weeks did not chronically alter appetitive responses.

Effects of acute pinitol supplementation on plasma pinitol concentration, whole body glucose tolerance, and activation of the skeletal muscle insulin receptor in older humans.

Limited research with rodents and humans suggests that oral ingestion of pinitol (3- O-methyl- D- CHIRO-inositol) might positively influence glucose tolerance. This double-blinded, placebo-controlled, and cross-over study assessed the effects of acute pinitol supplementation on plasma pinitol concentration, glucose tolerance, insulin sensitivity, and activation of the skeletal muscle insulin receptor. Fifteen older, nondiabetic subjects (62+/-1 years, mean+/-SEM) completed four, 1-day trials. Subjects consumed a non-nutritive beverage with nothing (placebo) or 1,000 mg pinitol. Sixty minutes later, the subjects consumed beverages that were either energy- and carbohydrate-free (Sham) or contained 75 g glucose (OGTT). Blood samples were collected frequently over the 240-min testing period. For the OGTT trials only, vastus lateralis samples were obtained before the placebo and pinitol supplementation and 60 min after consuming the 75 g glucose beverage. Plasma pinitol concentration increased and was maintained for 240 min. Pinitol did not influence the fasting state and 180-min area under the curves for plasma glucose and insulin during the Sham and OGTT trials or hepatic (placebo 0.83+/-0.08; pinitol 0.80+/-0.08) and whole-body (placebo 6.10+/-0.54; pinitol 6.22+/-0.52) insulin sensitivities. Activation of the muscle insulin receptor was increased by 140% with glucose ingestion (Pre 0.62+/-0.12; Post 1.49+/-0.35), but pinitol did not influence this response. These results show that the pinitol supplement was quickly absorbed, but did not acutely influence indices of whole-body glucose tolerance and insulin sensitivity, or the activation of the skeletal muscle insulin receptor in older, nondiabetic humans.

Moderately increased protein intake predominately from egg sources does not influence whole body, regional, or muscle composition responses to resistance training in older people.

UNLABELLED: The effects of increased dietary protein on resistance training (RT)-induced changes in body composition and skeletal muscle fiber size are uncertain in older people. OBJECTIVES: We hypothesized that the ingestion of more animal-based foods, especially eggs, to achieve a higher protein intake would enhance RT-induced changes in body composition. SETTING: West Lafayette, IN. PARTICIPANTS: 36 older people (age 61 +/- 1 y; mean +/- SEM). INTERVENTION: Subjects completed RT three d/wk for 12 weeks, and consumed omnivorous diets that contained either 0.9 +/- 0.1 (lower protein) or 1.2 +/- 0.0 (higher protein) g protein x kg(-1) x d(-1) (12 +/- 3 and 17 +/- 5% of energy intakes, respectively), with the higher protein intake achieved by consuming more eggs, meats, and dairy foods. The lower and higher protein diets contained 213 +/- 21 and 610 +/- 105 mg cholesterol/d, respectively. MEASUREMENTS: Strength, body composition, serum lipid-lipoprotein profile, urinary creatinine, skeletal muscle fiber type and size. RESULTS: Among all subjects, over time (i.e. with RT) body weight was unchanged, lean mass (1.1 +/- 0.2 kg) increased, and fat mass (-1.4 +/- 0.2 kg) decreased (all changes P < 0.05). Regional (i.e. trunk, legs, arms) lean mass increased and fat mass decreased. Whole body muscle mass (24-h urinary creatinine excretion) increased, but skeletal muscle (vastus lateralis) type 1, type 2a, and type 2x fiber cross-sectional areas did not change from baseline. Serum total and LDL cholesterol decreased (P < 0.05) and HDL cholesterol and triacylglycerol were unchanged. Dietary protein and cholesterol intakes did not influence these responses to RT. CONCLUSION: Consumption of diets that contained moderately higher protein and variable amounts of cholesterol did not differentially affect body composition, skeletal muscle fiber size, or serum lipid-lipoprotein profile responses to resistance training in older people.

Effects of food form on appetite and energy intake in lean and obese young adults.

OBJECTIVE: To investigate the independent effect of food form on appetite and energy intake in lean and obese adults using high carbohydrate, fat or protein food stimuli. DESIGN: Crossover dietary challenge with matched beverage and solid food forms: high carbohydrate (watermelon and watermelon juice); high protein (cheese and milk); high fat (coconut meat and coconut milk). A total of 120 lean (18-23 kg/m(2); N=60) and obese (30-35 kg/m(2); N=60) adults (18-50 years old) with stable body weight. Forty different participants (N=20 lean and 20 obese) were tested with each of the food systems. MEASUREMENTS: Appetitive sensations, food palatability and dietary intake. RESULTS: Regardless of the predominant energy source, the beverage food form elicited a weaker compensatory dietary response than the matched solid food form. Thus, total daily energy intake was significantly higher by 12.4, 19 and 15% on days the beverage forms of the high-carbohydrate, -fat and -protein foods were ingested, respectively. This was due more to a weak effect on satiety than satiation. The obese participants had higher energy intake at the lunch, including the beverage high-protein load, but overall differences between lean and obese participants were small and not systematic. CONCLUSION: Food rheology exerts an independent effect on energy intake. Dietary compensation for beverages is weaker than for solid food forms of comparable nutrient content. Thus, they pose a greater risk for promoting positive energy balance.

Effects of solid versus liquid meal-replacement products of similar energy content on hunger, satiety, and appetite-regulating hormones in older adults.

OBJECTIVE: To examine whether solid versus liquid meal-replacement products differentially affect appetite and appetite-regulating hormones in older adults. METHODS: On two occasions, 9 subjects (age: 61+/-3 years; BMI: 25.6+/-1.3 kg/m (2)) consumed 25% of daily energy needs as solid or liquid meal-replacements of similar energy contents. Blood and appetite ratings were collected over 4 hours. RESULTS: The post-prandial hunger composite (area under the curve) was lower following the solid versus liquid meal-replacement (p<0.005) and remained below baseline over 4 hours (p<0.05). Similar responses were observed with the desire to eat. The insulin and ghrelin composites were lower following the solid trial compared to the liquid [insulin: 5825 (range: 4676-11639) VS. 7170 (4472-14169) uIU/l x 240 min, p<0.01; ghrelin: -92798 (range: -269130-47528) VS. -56152 (range: -390855-30840) pg/ml x 240 min, p<0.05]. Ghrelin also remained below baseline over 4 hours (p<0.05). No differences in cholecystokinin and leptin were observed between products. CONCLUSION: The consumption of comparable meal-replacement products in solid versus liquid versions with similar energy contents led to differential appetitive responses and should not be viewed as dietary equivalents in older adults.

Measurement of body composition changes with weight loss in postmenopausal women: comparison of methods.

BACKGROUND: The accurate measurement of body composition changes is important when evaluating the efficacy of medical nutrition therapy and weight management programs, yet is not well documented in older women. OBJECTIVE: We compared methods of estimating energy-restriction-induced body composition changes in postmenopausal women. DESIGN: 27 women (59 +/- 8 y; BMI 29.0 +/- 2.9 kg/m2; mean +/- SD) completed a 9-wk energy restriction period (5233 kJ/d, (1250 kcal/d)). Changes in % body fat (delta%BF), fat mass (deltaFM), and fatfree mass (deltaFFM) were measured by hydrostatic weighing (HW), air-displacement plethysmography (ADP), dual-energy x-ray absorptiometry (DXA), and deuterium oxide dilution (D2O). The Baumgartner et al. (Am J Clin Nutr 53:1345-1353, 1991) four-compartment (4C) model with body volume from HW was the criterion method. The 4C model with body volume from ADP was also compared. Regression equations were developed based on 4CHW (dependent variable) utilizing results of change (POST-PRE) for each method. RESULTS: The women lost 6.8 +/- 3.2 kg; 9% of baseline weight. Based on 4CHW, the body composition changes were -2.4 +/- 4.5 delta%BF, -4.7 +/- 3.3 kg deltaFM, and -2.6 +/- 4.4 kg deltaFFM. No differences were detected by ANOVA for delta%BF, deltaFM, and deltaFFM among 4CHW, HW, ADP, DXA, D2O, and 4CADP. Bland-Altman limits of agreement showed differences between methods that ranged from 14.5 to -14.1 delta%BF, 7.8 to -8.1 kg deltaFM, and 7.5 to -8.4 kg deltaFFM for individuals. A bias was shown with 4CADP overestimating delta%BF (1.4 %) and FM (0.6 kg) and underestimating deltaFFM (-1.2 kg) compared to 4CHW. The regression model was acceptable for %BF (4CADP, 2CHW, and 2CD2O); FM and FFM (4CADP, 3CDXA, 2CHW, and 2CD2O), but not for other estimates of %BF, FM, FFM. CONCLUSIONS: These body composition assessment methods may be used interchangeably to quantify changes in % body fat, fat mass, and fat-free mass with weight loss in groups of postmenopausal women. 4CADP overestimates delta%BF and underestimates deltaFFM. When utilizing one of these comparison methods (4CADP, 3CDXA, 2CHW, 2CD2O) to quantify changes in fat mass and fat-free mass for an individual postmenopausal woman, regression equations may be used to relate the data to 4CHW.

Modafinil for treatment of fatigue in post-polio syndrome: a randomized controlled trial.

OBJECTIVE: To determine if modafinil can improve fatigue in patients with post-polio syndrome. METHODS: We used a randomized, placebo-controlled crossover trial. Intervention with modafinil (400 mg/day) and placebo occurred over 6-week periods. Primary endpoint (fatigue) was assessed using the Fatigue Severity Scale as the main outcome measure. Other measures included the Visual Analog Scale for Fatigue and the Fatigue Impact Scale. Secondary endpoint (health-related quality of life) was assessed using the 36-Item Short-Form. Analysis of variance for repeated measures was applied to assess treatment, period, and carryover effects. RESULTS: Thirty-six patients were randomized, 33 of whom (mean age: 61 years) completed required interventions. Treatment with modafinil was safe and well-tolerated. After adjusting for periods and order effects, no difference was observed between treatments. CONCLUSION: Based on the utilized measures of outcome modafinil was not superior to placebo in alleviating fatigue or improving quality of life in the studied post-polio syndrome population.

Adult Hallervorden-Spatz syndrome simulating amyotrophic lateral sclerosis.

Hallervorden-Spatz syndrome (HSS) is a neurodegenerative disorder characterized by progressive dementia, dystonia, ataxia, and rigidity. An atypical form of adult-onset HSS was observed in a 36-year-old man presenting with progressive dysarthria. Markedly dysarthric speech and a weak atrophic tongue associated with a neurogenic pattern of motor unit recruitment in bulbar-supplied muscles on electromyography led to an initial impression of bulbar amyotrophic lateral sclerosis (ALS). Lack of expected progression of symptoms, however, prompted reinvestigation. Repeat brain magnetic resonance imaging demonstrated an "eye-of-the-tiger" pattern in the basal ganglia, characteristic of HSS, thus requiring genetic studies. DNA analyses of the pantothenate kinase gene (PANK2) was conducted and revealed two novel, disease-causing exon 3 missense mutations (Cys231Ser and Tyr251Cys). This case broadens the genotypic and phenotypic spectrum of HSS to include a late-onset syndrome resembling bulbar-onset ALS.

Protein requirement of elderly women: nitrogen balance responses to three levels of protein intake.

BACKGROUND: For elderly women, insufficient data exist to assess the accuracy of the assumed mean protein requirement of 0.6 g of protein x kg(-1) x day(-1), and the adequacy of the current Recommended Dietary Allowance (RDA) of 0.8 g of protein x kg(-1) x day(-1). The aims of this study were to assess the mean protein requirement and suggested safe and adequate protein intake (protein allowance) of elderly women using a shorter-term nitrogen balance protocol. METHODS: During three separate 18-day trials, 11 elderly women (age range, 70-81 years) were randomly fed eucaloric diets designed to provide either 0.50, 0.75, or 1.00 g of protein x kg(-1) x day(-1). Nitrogen balance was determined at Weeks 2 and 3 (Days 7-10 and 14-17, respectively) of each trial using data from total nitrogen analyses of duplicate food composites, 24-hour urine collections, and stool collections. The mean protein requirement was calculated using linear regression of individual women's data from all three trials and inverse prediction. RESULTS: At protein intakes of 0.53 +/- 0.02, 0.76 +/- 0.02, or 1.06 +/- 0.05 g of protein x kg(-1) x day(-1), net nitrogen balances during Week 2 were -14.5 +/- 3.1, 3.8 +/- 2.5 and 23.4 +/- 3.3 mg of nitrogen x kg(-1) x day(-1), respectively, for these body weight- and body composition-stable women. At Week 3, the net nitrogen balances were -0.1 +/- 2.7, 8.5 +/- 3.6 and 42.0 +/- 3.0 mg of nitrogen x kg(-1) x day(-1). From Week 2 to Week 3, shifts to more positive nitrogen balances occurred due to decreases in urinary nitrogen excretion. The mean protein requirement at Week 2 was calculated to be 0.70 +/- 0.09 g of protein. kg(-1) x day(-1) (coefficient of variation [CV] = 13%) and at Week 3 was calculated to be 0.56 +/- 0.09 g of protein x kg(-1) x day(-1) (CV = 17%). From these data, an adequate protein allowance was estimated to be greater than the RDA at Week 2 (0.90 g of protein x kg(-1) x day [d](-1)), and not different than the RDA at Week 3 (0.76 g of protein x kg(-1) x d(-1)). CONCLUSIONS: The decrease over time in urinary nitrogen excretion from Week 2 to Week 3 suggests that these elderly women did not achieve a metabolic steady state during this shorter-term nitrogen balance study. Collectively, these data suggest that the total protein needs of elderly women are at or above the current RDA for protein. However, the results of this study indicate that shorter-term nitrogen balance protocols are insufficient to firmly establish the RDA for protein of elderly women, and further research is required using alternative criteria measures.

Short-term moderate weight loss and resistance training do not affect insulin-stimulated glucose disposal in postmenopausal women.

OBJECTIVES: Moderate weight loss and exercise have been proposed as important tools in the treatment and prevention of type 2 diabetes. Therefore, we tested the hypothesis that short-term (4 weeks) moderate energy restriction (-750 kcal/day) would result in a significant increase in insulin-stimulated glucose disposal (40 mU x m(-2) x min(-1) hyperinsulinemic-euglycemic clamp) in moderately overweight postmenopausal women and that when combined with resistance training (RT) an even greater effect would be seen. RESEARCH DESIGN AND METHODS: Older women were randomly assigned to energy restriction (WLoss group; n = 9) or energy restriction plus RT (RT + WLoss group; n = 10). RESULTS: For the WLoss versus the RT + WLoss groups, changes in body weight (-3.0 +/- 0.2 kg vs. -3.2 +/- 0.3 kg), fat mass (FM) (-3.0 +/- 0.3 kg vs. -3.2 +/- 0.3 kg), and percent body fat (BF) (-2.1 +/- 0.4 vs. -2.4 +/- 0.3%) were not different between groups. Muscle mass (group-by-time interaction, P = 0.04) was preserved in RT + WLoss (0.40 +/- 0.40 kg) and reduced in WLoss (-0.64 +/- 0.18 kg). There were no changes in fat-free mass (FFM) and waist-to-hip ratio in either group. Whole body glucose disposal (WLoss 6.14 +/- 0.57 vs. 6.03 +/- 0.53, RT + WLoss 5.85 +/- 0.60 vs. 6.09 +/- 0.56 mg/kg of FFM/min) did not change in either group. CONCLUSIONS: The results of this study demonstrate that short-term energy restriction resulting in moderate decreases in body weight (4.0 +/- 0.3%) and FM (8.2 +/- 0.7%) did not improve insulin-stimulated glucose disposal. The addition of RT to the hypoenergetic diet preserved muscle mass but provided no synergistic effect on insulin action. These results suggest that a greater change in body weight or FM may be necessary to observe a significant improvement in insulin action.

Resistance training affects iron status in older men and women.

OBJECTIVE: To examine the effects of resistance training on hematological and selected indices of iron status in 17 women aged 54-71 years and 18 men aged 56-69 years. DESIGN: Tests and evaluations were done before and after all subjects participated in a resistance-training program twice weekly for 12 weeks. RESULTS: The resistance training was effective as evidenced by increases in skeletal muscle strength of 20 +/- 9% and 23 +/- 13% for the men and women, respectively. Hematological parameters and serum iron concentrations were within normal clinical ranges and were unchanged by resistance training for both the men and the women. Total iron binding capacity (TIBC) and transferrin saturation were also unaffected by resistance training in the women but were significantly affected in the men. The men showed a decreased TIBC (p < .0001) and an increased transferrin saturation (p = .050). Serum ferritin concentrations decreased significantly in the women (p = .041) but were unchanged in the men. Transferrin receptor concentrations were unaffected by resistance training in the women but increased significantly in the men (p = .030). CONCLUSIONS: With resistance training, iron status of older men and women changes in a sex specific way.

Effects of a moderate glycemic meal on exercise duration and substrate utilization.

PURPOSE: To determine whether eating a breakfast cereal with a moderate glycemic index could alter substrate utilization and improve exercise duration. METHODS: Six active women (age, 24 +/- 2 yr; weight, 62.2 +/- 2.6 kg; VO(2peak), 46.6 +/- 3.8 mL x kg(-1) x min(-1)) ate 75 g of available carbohydrate in the form of regular whole grain rolled oats (RO) mixed with 300 mL of water or water alone (CON). The trials were performed in random order and the meal or water was ingested 45 min before performing cycling exercise to exhaustion (60% of VO(2peak)). Blood samples were drawn for glucose, glucose kinetics, free fatty acids (FFA), glycerol, insulin, epinephrine (EPI), and norepinephrine (NE) determination. A muscle biopsy was obtained from the vastus lateralis muscle before the trial and immediately after exercise for glycogen determination. Glucose kinetics (Ra) were determined using a [6,6-(2)H] glucose tracer. RESULTS: Compared with CON, plasma FFA and glycerol levels were suppressed (P < 0.05) during the first 120 min of exercise for the RO trial. Respiratory exchange ratios (RER) were also higher (P < 0.05) for the first 120 min of exercise for the RO trial. At exhaustion, glucose, insulin, FFA, glycerol, EPI, NE, RER, and muscle glycogen were not different between trials. Glucose Ra was greater (P < 0.05) during the RO trial compared with CON (2.36 +/- 0.22 and 1.92 +/- 0.27 mg x kg(-1) x min(-1), respectively). Exercise duration was 5% longer during RO, but the mean times were not significantly different (253.6 +/- 6 and 242.0 +/- 15 min, respectively). CONCLUSIONS: Increased hepatic glucose output before fatigue provides some evidence of glucose sparing after the breakfast cereal trial. However, exercise duration was not significantly altered, possibly because of the sustained suppression of lipid metabolism and increased carbohydrate utilization throughout much of the exercise period.

Effects of moderate and high glycemic index meals on metabolism and exercise performance.

The purpose of this study was to determine whether pre-exercise ingestion of meals with moderate and high glycemic indexes (GI) affects glucose availability during exercise and exercise performance time. Six male volunteers (22 +/- 1 years; 80.4 +/- 3.7 kg; VO(2peak), 54.3 +/- 1.2 ml. kg(-1). min(-1)) ingested 75 g of carbohydrate in the form of 2 different breakfast cereals, rolled oats (moderate GI, approximately 61; MOD-GI) or puffed rice (high GI, approximately 82; HI-GI), combined with 300 mL of water; or water alone (control). The trials were randomized, and the meals were ingested 45 minutes before the subjects performed cycling exercise (60% VO(2peak)) to exhaustion. Venous blood samples were drawn to measure glucose, free fatty acids (FFAs), glycerol, insulin (INS), epinephrine (EPI) and norepinephrine (NE) concentrations. A muscle biopsy specimen was obtained from the vastus lateralis before the meal and immediately after exercise for glycogen determination. Before exercise, both test meals elicited significant (P <.05) hyperglycemia and hyperinsulinemia compared with control. The glycemic response was higher (P <.05) at the start of exercise after the HI-GI meal than after the control. During exercise, plasma glucose levels were higher (P <.05) at 60 (5.2 +/- 0.1, 4.2 +/- 0.2, and 4.6 +/- 0.1 mmol. L(-1)) and 90 (4.8 +/- 0.1, 4.1 +/- 0.1, and 4.3 +/- 0.1 mmol. L(-1)) minutes after the MOD-GI meal than after either the HI-GI or control. Total carbohydrate oxidation was greater (P <.05) during the MOD-GI trial than in control and was directly correlated with exercise performance time (r =.95, P <.0001). Pre-exercise plasma FFA levels were suppressed (P <.05) 30 and 45 minutes after ingestion of the HI-GI meal and 45 minutes after the MOD-GI meal compared with control. At 30, 60, and 120 minutes of exercise, FFAs remained suppressed (P <.05) for both test meals compared with control. At exhaustion, plasma glucose, INS, FFA, glycerol, EPI, and NE levels and muscle glycogen use were not different for all trials. Exercise time was prolonged (P <.05) after the MOD-GI meal compared with control, but the HI-GI trial was not different from control (MOD-GI, 165 +/- 11; HI-GI, 141 +/- 8; control, 134 +/- 13 minutes). Thus, in contrast to the HI-GI meal or control, the MOD-GI breakfast cereal ingested 45 minutes before exercise enhanced performance time, maintained euglycemia for a longer period during exercise, and resulted in greater total carbohydrate oxidation during the exercise bout. We conclude that a MOD-GI meal provides a significant performance and metabolic advantage when consumed 45 minutes before exercise.

The recommended dietary allowance for protein may not be adequate for older people to maintain skeletal muscle.

BACKGROUND: Inadequate dietary protein intake results in loss of skeletal muscle mass. Some shorter-term nitrogen balance studies suggest that the Recommended Dietary Allowance (RDA) of protein may not be adequate for older people. The aim of this study was to assess the adequacy of the RDA of protein for older people by examining longer-term responses in urinary nitrogen excretion, whole-body protein metabolism, whole-body composition, and mid-thigh muscle area. METHODS: This was a 14-week precisely controlled diet study. Ten healthy, ambulatory men and women, aged 55 to 77 years, were provided eucaloric diets that contained 0.8 g protein.kg(-1).day(-1). The study was conducted at a General Clinical Research Center using an outpatient setting for 11 weeks and an inpatient setting for 3 weeks. The main outcome measures included urinary nitrogen excretion, postabsorptive and postprandial whole-body leucine kinetics via infusion of L-[1-(13)C]-leucine, whole-body density via hydrostatic weighing, total body water via deuterium oxide dilution, and mid-thigh muscle area via computed tomography scans. RESULTS: Mean urinary nitrogen excretion decreased over time from Weeks 2 to 8 to 14 (p =.025). At Week 14, compared with Week 2, there were no changes in postabsorptive or postprandial leucine kinetics (turnover, oxidation, incorporation into protein via synthesis, release via breakdown, or balance). Whole-body composition (% body fat, fat-free mass, and protein + mineral mass) did not change over time in these weight-stable subjects. Mid-thigh muscle area was decreased by -1.7 +/- 0.6 cm(2) (p =.019) at Week 14 compared with Week 2. The loss of mid-thigh muscle area was associated with the decrease in urinary nitrogen excretion (Spearman r =.83, p =.010). CONCLUSIONS: The maintenance of whole-body leucine metabolism and whole-body composition is generally consistent with a successful adaptation to the RDA for protein. However, the decrease in mid-thigh muscle area and the association with decreased urinary nitrogen excretion are consistent with a metabolic accommodation. These results suggest that the RDA for protein may not be adequate to completely meet the metabolic and physiological needs of virtually all older people.

Relationships of plasma C-peptide and gender to the urinary excretion of inositols in older people.

PURPOSE: The urinary excretions of myo-inositol and D-chiro-inositol are elevated in diabetes, and have been suggested as possible markers or effectors of insulin action. The aim of the present study was to measure the urinary excretion of these compounds, and to assess possible relationships with the metabolic control of glucose, in older, non-diabetic men and women. SUBJECTS: 32 older (age range 54-71 yrs), moderately overweight (body mass index 29.1 +/- 0.4 kg/m2, mean +/- SEM), non-diabetic men (n = 17) and women (n = 15). METHODS: 75 g oral glucose tolerance testing was done the day after all subjects had consumed nutrient-defined menus for five days. Plasma samples were analyzed for the concentrations of glucose, insulin, and C-peptide, and the 180-minute area under the curve (AUC) for each of these compounds was calculated. Samples from 24-hour urine collections were analyzed for the concentrations of myo-inositol, D-chiro-inositol, L-chiro-inositol, and pinitol. RESULTS: The fasting glucose, insulin, and C-peptide, and the AUC for glucose and insulin, were not different between men and women. C-peptide AUC was greater in the men versus the women (p < 0.001). The median urinary excretions (micromol/g creatinine) of myo-inositol (p < 0.001), D-chiro-inositol (p < 0.001), L-chiro-inositol (p < 0.05), and pinitol (p < 0.001) were higher, and the myo-inositol:D-chiro-inositol ratio was lower (p < 0.001), in the men versus women. For all subjects combined, C-peptide AUC was positively correlated with the urinary excretion of each of the measured inositols, as well as the myo-inositol:D-chiro-inositol ratio. The correlations between C-peptide AUC and these inositols were strongly influenced by the co-linear relationship between C-peptide AUC and gender. CONCLUSIONS: Collectively, these data show that older, moderately overweight, non-diabetic men and women with gender-related differences in glucose-stimulated C-peptide AUC, an indirect indicator of insulin secretion, also display differences in the urinary excretion of myo-inositol, D-chiro-inositol, L-chiro-inositol, and pinitol. The gender-related difference in the myo-inositol:D-chiro-inositol ratio suggests that, while the urinary excretion of all of the inositols measured were higher in the men than the women, the difference was more pronounced for D-chiro-inositol.

Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: To determine the efficacy of IV immunoglobulin (IVIg) given patients with untreated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: A randomized, double-blind, multicenter, investigator-initiated study compared IVIg (Aventis Behring LLC, King of Prussia, PA) with placebo (5% albumin). On days 1, 2, and 21, IVIg (1 g/kg) or placebo was given. The primary outcome measure was the change in muscle strength from baseline to day 42, using the average muscle score (AMS). Secondary outcome measures included change from baseline AMS at days 10 and 21, the Hughes' functional disability scale, forced vital capacity (FVC), and nerve conduction studies (NCS) of four motor nerves (median, ulnar, peroneal, and tibial). RESULTS: The patients (n = 33) were randomized. Of these, 30 (14 women, 16 men, aged 54 +/- 20 years, range 13 to 82) received IVIg and 23 were given placebo (12 women, 11 men, aged 50 +/- 18 years, range 23 to 73). Baseline AMS values of the groups were similar (IVIg 7.06 +/- 1.31 versus placebo 7.28 +/- 1.18, p = 0.53). There were two dropouts in placebo group and one in the IVIg group. Mean AMS improved at day 42 comparing IVIg with placebo (0.63 versus -0.1, p = 0.006). Improved strength was seen by day 10. The placebo group lost strength over this same interval. In the IVIg, 11 subjects improved by the functional disability scale; none worsened. This differed (p = 0.019) from those in the placebo-treated group (two improved, two got worse, remainder unchanged). Forced vital capacity did not improve with IVIg treatment. IVIg improved ulnar motor distal latency (p = 0.005), tibial distal compound muscle amplitude (p = 0.003), and peroneal nerve conduction velocity (p = 0.03). CONCLUSIONS: IVIg improves strength in patients with untreated CIDP by day 10 with continued benefit through day 42; more than one third improve by at least a functional grade on a disability scale. This study provides data supporting IVIg as the initial treatment for CIDP.

Molecular characteristics of aged muscle reflect an altered ability to respond to exercise.

Studies have been performed in humans to identify changes in gene expression that may account for the relatively weak and variable response of aged muscle to resistance exercise. The gene expression profile of skeletal muscle from elderly (62-75 years old) compared to younger (20-30 years old) men demonstrated elevated expression of genes typical of a stress or damage response. The expression of the majority of these genes was unaffected by a single bout of high-intensity resistance exercise in elderly subjects but was altered acutely by exercise in younger subjects so as to approach the pre-exercise levels observed in older subjects. The inability of muscle from elderly subjects to respond to resistance exercise was also apparent in the expression of inflammatory response genes, which increased within 24 hours of the exercise bout only in younger subjects. Othergenes with potentially important roles in the adaptation of muscle to exercise, showed a similar or even more robust response in older compared to younger subjects. Taken together, these results may help to explain the variable hypertrophic response of muscle from older individuals to resistance training.