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John O. Holloszy, as perhaps the world’s preeminent exercise biochemist/physiologist, published >400 papers over his 50+ year career, and they have been cited >41,000 times. In 1965 Holloszy showed for the first time that exercise training in rodents resulted in a doubling of skeletal muscle mitochondria, ushering in a very active era of skeletal muscle plasticity research. He subsequently went on to describe the consequences of and the mechanisms underlying these adaptations. Holloszy was first to show that muscle contractions increase muscle glucose transport independent of insulin, and he studied the mechanisms underlying this response throughout his career. He published important papers assessing the impact of training on glucose and insulin metabolism in healthy and diseased humans. Holloszy was at the forefront of rodent studies of caloric restriction and longevity in the 1980s, following these studies with important cross-sectional and longitudinal caloric restriction studies in humans. Holloszy was influential in the discipline of cardiovascular physiology, showing that older healthy and diseased populations could still elicit beneficial cardiovascular adaptations with exercise training. Holloszy and his group made important contributions to exercise physiology on the effects of training on numerous metabolic, hormonal, and cardiovascular adaptations. Holloszy’s outstanding productivity was made possible by his mentoring of ~100 postdoctoral fellows and substantial NIH grant funding over his entire career. Many of these fellows have also played critical roles in the exercise physiology/biochemistry discipline. Thus it is clear that exercise biochemistry and physiology will be influenced by John Holloszy for numerous years to come.

Objective Studies of dehydroepiandrosterone (DHEA) therapy in older adults suggest sex-specific effects on bone mineral density (BMD) and body composition, but the ability of a single study to reach this conclusion was limited. We evaluated the effects of DHEA on sex hormones, BMD, fat mass and fat-free mass in older women and men enrolled in four similar clinical trials. Design Pooled analyses of data from four double-blinded, randomized controlled trials. Participants Women (n = 295) and men (n = 290) aged 55 years or older who took DHEA or placebo tablet daily for 12 months. Measurements Twelve-month changes in BMD, fat mass, fat-free mass and serum DHEA sulphate (DHEAS), (17)estradiol, testosterone and insulin-like growth factor-1 (IGF-1). Results Women on DHEA had increases (mean ± SD; all P Conclusions Dehydroepiandrosterone therapy may be an effective approach for preserving bone and muscle mass in women. Key questions are (a) the extent to which longer duration DHEA can attenuate the loss of bone and muscle in women, and (b) whether DHEA has a more favourable benefit-to-risk profile for women than oestrogen therapy.

The purpose of this study was to evaluate the hypothesis that a novel high-repetition, low-resistance back squat training protocol, designed to stimulate high-intensity interval training, improves 5-km run performance. Fifteen runners [4 male, 11 female; 150 + minutes of endurance exercise/week; age = 22.7 ± 2.0 y; 21.5 ± 2.2 kg/m(2) BMI] in this single-group test-retest design completed two weeks of back squats consisting of three sets of 15–24 repetitions at 60% of estimated one-repetition max (1RM), three times per week (1–2 days of rest between sessions). Outcome tests included a 5-km outdoor timed run, laboratory indirect calorimetry to quantify substrate oxidation rates during steady-state submaximal exercise (60% and 70% heart rate max (HRmax)), and estimated 1RM for back squats. Back squat estimated 1RM increased by 20% (58.3 ± 18.5 to 70.2 ± 16.7 kg, P < 0.001). However, 5-km run times due to the back squat protocol did not significantly change (Pre-Squats: 23.9 ± 5.0 vs. Post-Squats: 23.7 ± 4.3 minutes, P = 0.71). Likewise, the squat training program did not significantly alter carbohydrate or lipid oxidation rates during steady-state submaximal exercise at 60% or 70% of HRmax (P values ranged from 0.36 – 0.99). Short term high-repetition back squat training does not appear to impact 5-km run performance or substrate utilization during submaximal exercise.

Substance use disorders (SUDs) are maladaptive patterns of substance use that are associated with psychiatric comorbidity, unhealthy lifestyle choices, and high rates of relapse. Exercise is associated with a wide range of acute and long-term benefits for both mental and physical health and is presently being investigated as a promising adjunctive treatment for SUD. Despite positive effects of regular physical activity on treatment outcomes and risk factors for relapse, low adherence and high attrition rates limit the benefits derived from exercise interventions. Lack of motivation is one of many perceived barriers to initiating exercise that contributes to poor adherence to interventions. In the present article, we describe the protocol for a novel, integrated exercise intervention that combines motivational interviewing (MI), a client-centered approach designed to enhance intrinsic motivation and resolve ambivalence toward change, and contingency management (CM), a behavioral treatment that provides monetary incentives for the completion of target behaviors. The protocol seeks to address the challenges surrounding initiation and maintenance of an exercise program at a level consistent with public health guidelines, particularly for sedentary patients. We conclude with considerations for the implementation of the intervention in SUD specific clinics.

We appreciate the views expressed by Dr. Masten regarding our recently published study, which demonstrated that a short-term Mediterranean diet improves 5-kilometer run times as a measure of endura...

BACKGROUND Low-carbohydrate, ketogenic diets cause mild, subclinical systemic acidosis. Anaerobic exercise performance is limited by acidosis. Therefore, we evaluated the hypothesis that a low-carbohydrate, ketogenic diet impairs anaerobic exercise performance, as compared to a high-carbohydrate diet. METHODS Sixteen men and women (BMI, 23±1 kg/m2, age 23±1 years) participated in a randomized-sequence, counterbalanced crossover study in which they underwent exercise testing after 4 days of either a low-carbohydrate, ketogenic diet (LC

Objective: Healthful dietary patterns have constituents that are known to improve exercise performance, such as antioxidants, nitrates, and alkalizing effects. However, ergogenic effects of such di...

Background Cognitive functioning refers to storage and manipulation of information and includes executive functioning (EF) and attention (ATT). While physical activity (PA) improves cognitive functioning, decrements are associated with frequent substance use. This study examined PA on cognitive functioning within the context of past-year substance use. Methods Using NESARC–III data (N = 36,309), cross-sectional analysis examined interactions between self-reported past-year PA and substance use in relation to cognitive functioning. Results As hypothesized, light-to-moderate, vigorous, and total PA conditional main effects were positively associated with both facets of cognition, while frequent substance use conditional main effects were negatively associated with ATT and EF. The positive association between PA and cognition was diminished by substance use. Frequent binge drinking, marijuana, cocaine, and opioid use weakened the impact of light-to-moderate PA on EF, and only frequent cocaine use lessened the relationship between vigorous PA on EF. When PA intensities were combined, frequent binge drinking and cocaine use weakened the PA and EF association. Infrequent stimulant use reduced the association between all levels of PA and ATT, while infrequent marijuana use unexpectedly enhanced the relation between vigorous PA and ATT. Conclusions Overall, PA enhanced two facets of cognitive functioning across six substances. However, these benefits are reduced in the context of frequency of substance use. The positive association between light-to-moderate PA and EF appears to be more sensitive in the context of frequent substance use than vigorous PA. Implications for public health messaging and PA as cognitive remediation treatment for substance use disorders are discussed.

Objective The role of metabolic condition and diet in regulating circulating levels of adropin, a peptide hormone linked to cardiometabolic control, is not well understood. In this study, weight loss and diet effects on plasma adropin concentrations were examined. Methods This report includes data from (1) a weight loss trial, (2) an evaluation of acute exercise effects on mixed-meal (60% kcal from carbohydrates) tolerance test responses, and (3) a meta-analysis to determine normal fasting adropin concentrations. Results Distribution of plasma adropin concentrations exhibited positive skew and kurtosis. The effect of weight loss on plasma adropin concentrations was dependent on baseline plasma adropin concentrations, with an inverse association between baseline and a decline in concentrations after weight loss (Spearman's ρ = −0.575; P < 0.001). When ranked by baseline plasma adropin concentrations, only values in the upper quartile declined with weight loss. Plasma adropin concentrations under the main area of the bell curve correlated negatively with habitual carbohydrate intake and plasma lipids. There was a negative correlation between baseline values and a transient decline in plasma adropin during the mixed-meal tolerance test. Conclusions Plasma adropin concentrations in humans are sensitive to dietary macronutrients, perhaps due to habitual consumption of carbohydrate-rich diets suppressing circulating levels. Very high adropin levels may indicate cardiometabolic conditions sensitive to weight loss.

The omega-3 fatty acid docosahexaenoic acid (DHA) has anti-inflammatory and anti-nociceptive (pain inhibiting) effects. Because strenuous exercise often results in local inflammation and pain, we hypothesized that DHA supplementation attenuates the rise in markers of local muscle inflammation and delayed onset muscle soreness (DOMS) that occur after eccentric strength exercise. Twenty-seven, healthy women (33 ± 2 y, BMI 23.1±1.0 kg·m-2) were randomized to receive 9d of 3000 mg/d DHA or placebo in a double-blind fashion. On day 7 of the supplementation period, the participants performed 4 sets of maximal-effort eccentric biceps curl exercise. Before and 48h after the eccentric exercise, markers of inflammation were measured including measures of muscle soreness (10-point visual analog pain scale, VAS), swelling (arm circumference), muscle stiffness (active and passive elbow extension), skin temperature, and salivary C-reactive protein (CRP) concentrations. As expected, muscle soreness and arm circumference increased while active and passive elbow extension decreased. The increase in soreness was 23% less in the DHA group (48h increase in VAS soreness ratings: 4.380.4 vs. 5.600.5, p=0.02). Furthermore, the number of subjects who were able to achieve full active elbow extension 48h after eccentric exercise was greater in the DHA group (71% vs. 15%, p = 0.006), indicating significantly less muscle stiffness. No between-group differences were observed for passive elbow extension (p = 0.78) or arm swelling (p = 0.75). Skin temperature and salivary CRP concentrations did not change from baseline to 48h after exercise in either group. These findings indicate that short-term DHA supplementation reduces exercise-induced muscle soreness and stiffness. Therefore, in addition to other health benefits that n-3 fatty acids have been associated with, DHA supplementation could be beneficial for improving tolerance to new and/or strenuous exercise programs and thereby might facilitate better training adaptations and exercise adherence.

It is conceivable that lean patients (body mass index 18.5-24.9 kg/m(2)) with heart failure (HF) have low body weight due to low food consumption and that this may contribute to micronutrient deficiencies and to their poorer prognosis compared with overweight/obese patients. We hypothesized that lean patients have a greater number of inadequate micronutrient intakes (50% of recommendations) than overweight/obese patients and that this also depends on age.Lean (n = 15) and overweight/obese (n = 49) patients underwent 24-hour diet and physical activity recall interviews. Inadequate essential micronutrient intakes were ubiquitous (intakes of 13 ± 1 of 27 micronutrients were inadequate) and did not depend on race, status, or access to supermarkets. Younger (40-64 y) lean patients had inadequate intakes of 20 ± 2 micronutrients, which was more than the other weight/age subgroups (all P.01). Physical activity levels did not differ across weight and age groups.Patients with HF may be at risk of malnutrition due to numerous inadequate micronutrient intakes; younger lean patients may have an especially high risk. Future studies are needed to confirm these preliminary findings and to investigate the possibility that incorporating a micronutrient-dense meal plan will improve patient outcomes.

Objective Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function. Methods Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models. Results In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = 401). Analysis of hepatic Enho expression in male mice suggests control by the biological clock. Expression is rhythmic, peaking during maximal food consumption in the dark correlating with transcriptional activation by RORα/γ. The nadir in the light phase coincides with the rest phase and repression by Rev-erb. Plasma adropin concentrations in nonhuman primates (rhesus monkeys) also exhibit peaks coinciding with feeding times (07:00 h, 15:00 h). The ROR inverse agonists SR1001 and the 7-oxygenated sterols 7-β-hydroxysterol and 7-ketocholesterol, or the Rev-erb agonist SR9009, suppress ENHO expression in cultured human HepG2 cells. Consumption of high-cholesterol diets suppress expression of the adropin transcript in mouse liver. However, adropin over expression does not prevent hypercholesterolemia resulting from a high cholesterol diet and/or LDL receptor mutations. Conclusions In humans, associations between plasma adropin concentrations and LDL-C suggest a link with hepatic lipid metabolism. Mouse studies suggest that the relationship between adropin and cholesterol metabolism is unidirectional, and predominantly involves suppression of adropin expression by cholesterol and 7-oxygenated sterols. Sensing of fatty acids, cholesterol and oxysterols by the RORα/γ ligand-binding domain suggests a plausible functional link between adropin expression and cellular lipid metabolism. Furthermore, the nuclear receptors RORα/γ and Rev-erb may couple adropin synthesis with circadian rhythms in carbohydrate and lipid metabolism., Graphical abstract, Highlights • In male humans, plasma adropin concentrations are inversely related to low-density circulating cholesterol (LDL-C) levels. • Adropin expression is regulated by core elements of the biological clock (RORA/G, Rev-Erb). • Sterol-sensing by the ROR ligand-binding domain provides a plausible link between adropin expression and lipid metabolism. • In mouse liver, adropin expression is rhythmic and suppressed by exogenous (dietary) cholesterol.

Dietary acid load, quantified as the potential renal acid load (PRAL) of the diet, affects systemic pH and acid-base regulation. In a previous cross-sectional study, we reported that a low dietary PRAL (i.e. alkaline promoting diet) is associated with higher respiratory exchange ratio (RER) values during maximal exercise. The purpose of the present study was to confirm the previous findings with a short-term dietary intervention study. Additionally, we sought to determine if changes in PRAL affects submaximal exercise RER (as a reflection of substrate utilization) and anaerobic exercise performance. Subjects underwent a graded treadmill exercise test (GXT) to exhaustion and an anaerobic exercise performance test on two occasions, once after following a low-PRAL diet and on a separate occasion, after a high-PRAL diet. The diets were continued as long as needed to achieve an alkaline or acid fasted morning urine pH, respectively, with all being 4-9 days in duration. RER was measured during the GXT with indirect calorimetry. The anaerobic performance test was a running time-to-exhaustion test lasting 1-4 min. Maximal exercise RER was lower in the low-PRAL trial compared to the high-PRAL trial (1.10 ± 0.02 vs. 1.20 ± 0.05, p = 0.037). The low-PRAL diet also resulted in a 21% greater time to exhaustion during anaerobic exercise (2.56 ± 0.36 vs. 2.11 ± 0.31 sec, p = 0.044) and a strong tendency for lower RER values during submaximal exercise at 70% VO2max (0.88 ± 0.02 vs. 0.96 ± 0.04, p = 0.060). Contrary to our expectations, a short-term low-PRAL (alkaline promoting) diet resulted in lower RER values during maximal-intensity exercise. However, the low-PRAL diet also increased anaerobic exercise time to exhaustion and appears to have shifted submaximal exercise substrate utilization to favor lipid oxidation and spare carbohydrate, both of which would be considered favorable effects in the context of exercise performance.

Guidelines recommend the consumption of sodium during exercise to replace losses in sweat; however, the effects of sodium on thermoregulation are less clear. To determine the effects of high-dose sodium supplementation on indices of thermoregulation and related outcomes, 11 endurance athletes participated in a double-blind, randomized-sequence, crossover study in which they underwent 2-hrs of endurance exercise at 60% heart rate reserve with 1800 mg of sodium supplementation (SS) during one trial and placebo (PL) during the other trial. A progressive intensity time-to-exhaustion test was performed after the 2-hr steady state exercise as an assessment of exercise performance. Sweat rate was calculated from changes in body weight, accounting for fluid intake and urinary losses. Ratings of perceived exertion (RPE) and heat stress were assessed using verbal numeric scales. Cardiovascular drift was determined from the rise in HR during the 2-hr steady state exercise test. Skin temperature was measured with an infrared thermometer. Dehydration occurred in both SS and PL trials, as evidenced by substantial weight loss (2.03 ± 0.43% and 2.27 ± 0.70%, respectively; p = 0.261 between trials). Sweat rate was 1015.53 ± 239.10 ml·hr-1 during the SS trial and 1053.60±278.24 ml/hr during the PL trial, with no difference between trials (p = 0.459). Heat stress ratings indicated moderate heat stress (“warm/hot” ratings) but were not different between trials (p = 0.825). Time to exhaustion during the SS trial was 6.88 ± 3.88 minutes and during the PL trial averaged 6.96 ± 3.61 minutes, but did not differ between trials (p = 0.919). Cardiovascular drift, skin temperature, and RPE did not differ between trials (all p > 0.05). High-dose sodium supplementation does not appear to impact thermoregulation, cardiovascular drift, or physical performance in trained, endurance athletes. However, in light of the possibility that high sodium intakes might have other adverse effects, such as hypertension, it is our recommendation that athletes interpret professional recommendations for sodium needs during exercise with caution.

Current evidence has shown that exercise can reduce symptoms of Parkinson's disease (PD). However, previous studies indicated mixed results, possibly because of variability in terms of the nature of the exercise interventions. The purpose of this study was to perform a metaanalysis of current evidence from endurance exercise intervention studies for effects on the United Parkinson's Disease Rating Scale (UPDRS) in individuals with PD. A systematic literature search in six electronic databases was performed and two independent reviewers screened the title and abstract of 1106 records captured by the initial search. Inclusion criteria for full-text review were (A) peer-reviewed English-language publications, (B) randomized controlled trials that compared an endurance exercise intervention group to a non-exercising control group, and (C) an outcome measure which included the UPDRS total score or section III (motor) subscore. From the title/abstract screening, the same independent reviewers assessed 245 full-text articles for eligibility. Of the fulltext articles reviewed 7 articles were included in our meta-analysis, 238 were excluded for the following reasons: 147 did not meet endurance exercise criteria, 53 were review/systematic reviews, 34 were conference abstracts or posters, 2 were editorial or commentary, 1 was a study protocol, and 1 was unpublished. The d index was used to calculate the difference between means of different groups within individual studies, and a weighting factor or w was used to calculate the effect size across studies. Overall, d index was found to be -0.32 with 95% confidence interval, CI (-0.09, -0.56) found to be statistically significant indicating a positive effect of endurance exercise in UPDRS scores. In conclusion, this meta-analysis supports integrating endurance exercise training, as defined by ACSM, into treatment of PD.

After food ingestion, the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are secreted by the intestines into circulation where they act on the pancreas to promote insulin secretion. We evaluated the hypothesis that low postprandial plasma insulin levels in lean exercise-trained individuals are associated with low concentrations of incretin hormones.A cross-sectional study was performed to compare postprandial incretin hormone levels in lean endurance exercise-trained individuals (EX; n = 14, ≥40 yr) and age- and sex-matched, nonobese, sedentary control subjects (CON, n = 14). The main outcome measures were GLP-1, GIP, insulin, and glucose incremental areas under the curve (AUC) as measured in plasma samples collected during a 2-h,75-g oral glucose tolerance test (OGTT).The EX group had lower body fat percentage (14.6% ± 1.1% vs 23.3% ± 1.7%, P = 0.0002) and higher maximal oxygen uptake (53 ± 2 vs 34 ± 2, P0.0001) than CON. Glucose AUC did not differ between groups (P = 0.20). Insulin AUC was lower in EX (2.5 ± 0.5 vs 4.2 ± 1.2 μU·mL·1000 min, P = 0.02). No differences were observed between groups (EX and CON, respectively) for GLP-1 AUC (3.5 ± 0.7 vs 4.1 ± 1.1 pmol·min·100 L, P = 0.61) or GIP AUC (19.2 ± 1.4 vs 18.0 ± 1.4 pg·min·1000 mL; P = 0.56). In CON, insulin AUC was correlated with AUC for GLP-1 (r = 0.53, P = 0.05) and GIP (r = 0.71, P = 0.004), but no such correlations were observed in EX (both P ≥ 0.67).Low postprandial insulin levels in lean exercise-trained individuals are not attributable to lower incretin hormone concentrations. However, exercise may decrease the dependency of postprandial insulin levels on incretin hormones.

Summary In the United States, life expectancy has markedly increased during the past century, and population ageing is expected to double within the next 25 years. The process of ageing in a population is associated with the development of chronic diseases, such as type 2 diabetes mellitus, that can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. The evidence to date, consolidated by the numerous epidemiological studies and clinical trials conducted, suggests that caloric restriction is an effective nutritional intervention for preventing most of these age-related conditions. At a metabolic level, caloric restriction with adequate nutrition has been shown to improve insulin sensitivity, reduce fasting glucose and insulin concentration and prevent obesity, type 2 diabetes, hypertension and chronic inflammation. The purpose of this article is to review current knowledge of the metabolic and clinical implications of caloric restriction with adequate nutrition for the prevention of type 2 diabetes and cardiovascular disease. Copyright © 2013 John Wiley & Sons, Ltd.

Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m(2)) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals.

This study aimed to evaluate the hypothesis that exercise attenuates the reductions in lean mass, muscle strength, bone mineral density, and V˙O2max that accompany modest weight loss induced by calorie restriction (CR).Overweight, sedentary women and men (n = 52, 45-65 yr) were randomized to 6%-8% weight loss by using CR, endurance exercise training (EX), or both (CREX). The CR and the CREX groups underwent counseling to reduce energy intake by 20% and 10%, respectively. The EX and the CREX groups exercised 7.4 ± 0.5 and 4.4 ± 0.5 h·wk, respectively. Before and after 16.8 ± 1.1 wk of weight loss, lean mass and bone mineral density were measured with dual-energy x-ray absorptiometry, strength was measured with dynamometry, and aerobic capacity (V˙O2max) was measured with indirect calorimetry during maximal-intensity treadmill exercise.Weight loss was ~7% in all groups. Decreases in whole-body (~2%, P = 0.003) and lower extremity (~4%, P0.0001) lean mass occurred in the CR group (both P0.05). Despite similar weight loss, these reductions were attenuated in the CREX group (~1%, P = 0.44 and ~2%, P = 0.05, respectively) and absent in the EX group. Absolute aerobic capacity decreased ~6% in the CR group (P = 0.04), was unchanged in the CREX group (P = 0.28), and increased ~15% in the EX group (P0.0001). No changes in muscle strength or bone were observed.Modest weight loss (~7%) induced by 20% CR in overweight women and men decreases lean mass and reduces absolute V˙O2max. Exercise protects against these effects. Although the CR-induced changes might be considered physiologically appropriate for a reduced body weight, exercise preserves and/or improves these parameters during weight loss, which likely improves physical function. These findings support the notion of using exercise as an important component of weight loss programs.

The purpose of this study determined if oral supplementation of Protandim® (a nutraceutical) for 90 days improved 5-km running performance and reduced serum thiobarbituric acid-reacting substances (TBARS) at rest, an indicator of oxidative stress. Secondary objectives were to measure whole blood superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GPX), at rest and 10 minutes after completion of the race before and after supplementation as well as quality of life. In a double-blind, randomized, placebo controlled trial, 38 runners [mean (SD) = 34 (7) yrs; BMI = 22 (2) kg/m2] received either 90 days of Protandim® [1 pill a day, n = 19)] or placebo (n = 19). Randomization was done in blocks of two controlling for sex and 5-km baseline performance. A 5-km race was performed at baseline and after 90 days of supplementation, with blood samples taken before and 10-min after each race. Fasting blood samples were acquired at baseline, after 30, 60, and 90 days of supplementation. TBARS, SOD, GPX, and GSH were assayed in an out-of-state accredited lab. Running performance was not altered by Protandim® or placebo [20.3 (2.1) minutes, with an -8 (33) seconds change in 5-km time regardless of group]. There was no change in TBARS, SOD, or GPX (at rest) after three months of Protandim® supplementation compared to placebo. However, in a subgroup ≥ 35 years of age, there was a 2-fold higher increase in SOD in those taking Protandim® for three months compared to those on placebo (p = 0.038). The mean post-race change in TBARS (compared to pre-race) increased by about 20% in half of the subjects, but was not altered between groups, even after three months of supplementation. Quality of life was also not different between the two conditions. In conclusion, Protandim® did not (1) alter 5-km running time, (2) lower TBARS at rest (3) raise antioxidant enzyme concentrations compared to placebo (with exception of SOD in those ≥ 35 years old) or, (4) affect quality of life compared to placebo. Trial Registration: ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02172625","term_id":"NCT02172625"}}NCT02172625

Weight loss from calorie restriction (CR) and/or endurance exercise training (EX) is cardioprotective. However CR and EX also have weight loss-independent benefits.We tested the hypothesis that weight loss from calorie restriction and exercise combined (CREX) improves cardiovascular disease (CVD) risk factors more so than similar weight loss from CR or EX alone.Overweight, sedentary men and women (n = 52; aged 45-65 y) were randomly assigned to undergo 6-8% weight loss by using CR, EX, or CREX. Outcomes were measured before and after weight loss and included maximal oxygen consumption (VO2max), resting blood pressure, fasting plasma lipids, glucose, C-reactive protein, and arterial stiffness [carotid-femoral pulse wave velocity (PWV) and carotid augmentation index (AI)]. Values are means ± SEs.Reductions in body weight (∼7%) were similar in all groups. VO2max changed in proportion to the amount of exercise performed (CR, -1% ± 3%; EX, +22% ± 3%; and CREX, +11% ± 3%). None of the changes in CVD risk factors differed between groups. For all groups combined, decreases were observed for systolic and diastolic blood pressure (-5 ± 1 and -4 ± 1 mm Hg, respectively; both P0.0008), total cholesterol (-17 ± 4 mg/dL; P0.0001), non-HDL cholesterol (-16 ± 3 mg/dL; P0.0001), triglycerides (-18 ± 8 mg/dL; P = 0.03), and glucose (-3 ± 1 mg/dL; P = 0.0003). No changes were observed for HDL cholesterol (P = 0.30), C-reactive protein (P = 0.10), PWV (P = 0.30), or AI (P = 0.84). These changes would be expected to decrease the lifetime risk of CVD from 46% to 36%.Matched weight losses from CR, EX, and CREX have substantial beneficial effects on CVD risk factors. However, the effects are not additive when weight loss is matched. This trial was registered at clinicaltrials.gov as NCT00777621.

Dietary calorie restriction and exercise promote weight loss and may have additive effects for improving insulin sensitivity, independent of weight loss. It is not known if these effects are attributable to changes in circulating cytokines. We evaluated the hypothesis that modest, matched weight loss induced by calorie restriction and exercise have additive effects on circulating cytokines and these changes correlate with improvements in insulin sensitivity. Overweight and sedentary women and men (n = 52, 45–65 years) were randomized to undergo 7 % weight loss by using 3–6 months of calorie restriction, exercise, or a combination of both calorie restriction and exercise. Concentrations of cytokines and hormones were measured in fasting and oral glucose tolerance test blood samples. Insulin sensitivity was estimated based on oral glucose tolerance test for glucose and insulin. With all groups combined, fasting leptin (p

Serum dehydroepiandrosterone (DHEA) concentrations decrease approximately 80% between ages 25 and 75 year. Aging also results in an increase in arterial stiffness, which is an independent predictor of cardiovascular disease (CVD) risk and mortality. Therefore, it is conceivable that DHEA replacement in older adults could reduce arterial stiffness. We sought to determine whether DHEA replacement therapy in older adults reduces carotid augmentation index (AI) and carotid-femoral pulse wave velocity (PWV) as indices of arterial stiffness. A randomized, double-blind trial was conducted to study the effects of 50 mg day(-1) DHEA replacement on AI (n = 92) and PWV (n = 51) in women and men aged 65-75 year. Inflammatory cytokines and sex hormones were measured in fasting serum. AI decreased in the DHEA group, but not in the placebo group (difference between groups, -6 ± 2 AI units, P = 0.002). Pulse wave velocity also decreased (difference between groups, -3.5 ± 1.0 m s(-1), P = 0.001); however, after adjusting for baseline values, the between-group comparison became nonsignificant (P = 0.20). The reductions in AI and PWV were accompanied by decreases in inflammatory cytokines (tumor necrosis factor α and IL-6, P < 0.05) and correlated with increases in serum DHEAS (r = -0.31 and -0.37, respectively, P < 0.05). The reductions in AI also correlated with free testosterone index (r = -0.23, P = 0.03). In conclusion, DHEA replacement in elderly men and women improves indices of arterial stiffness. Arterial stiffness increases with age and is an independent risk factor for CVD. Therefore, the improvements observed in this study suggest that DHEA replacement might partly reverse arterial aging and reduce CVD risk.

Nitrate ingestion improves exercise performance; however, it has also been linked to adverse health effects, except when consumed in the form of vegetables. The purpose of this study was to determine, in a double-blind crossover study, whether whole beetroot consumption, as a means for increasing nitrate intake, improves endurance exercise performance. Eleven recreationally fit men and women were studied in a double-blind placebo controlled crossover trial performed in 2010. Participants underwent two 5-km treadmill time trials in random sequence, once 75 minutes after consuming baked beetroot (200 g with ≥500 mg nitrate) and once 75 minutes after consuming cranberry relish as a eucaloric placebo. Based on paired t tests, mean running velocity during the 5-km run tended to be faster after beetroot consumption (12.3±2.7 vs 11.9±2.6 km/hour; P=0.06). During the last 1.1 miles (1.8 km) of the 5-km run, running velocity was 5% faster (12.7±3.0 vs 12.1±2.8 km/hour; P=0.02) in the beetroot trial, with no differences in velocity (P≥0.25) in the earlier portions of the 5-km run. No differences in exercise heart rate were observed between trials; however, at 1.8 km into the 5-km run, rating of perceived exertion was lower with beetroot (13.0±2.1 vs 13.7±1.9; P=0.04). Consumption of nitrate-rich, whole beetroot improves running performance in healthy adults. Because whole vegetables have been shown to have health benefits, whereas nitrates from other sources may have detrimental health effects, it would be prudent for individuals seeking performance benefits to obtain nitrates from whole vegetables, such as beetroot.

Insulin-like growth factor binding protein-1 (IGFBP-1) has metabolic effects throughout the body, and its expression is regulated in part by insulin. Circulating IGFBP-1 predicts development of cardiometabolic diseases in longitudinal studies, and low IGFBP-1 concentrations are associated with insulin resistance and consumption of a high-fat diet. Because of the favorable metabolic effects of regular aerobic exercise, we hypothesized that aerobic exercise training would increase plasma IGFBP-1 concentrations and attenuate the reduction in IGFBP-1 after a high-fat meal. Ten overweight (body mass index = 28.7 ± 0.9 kg/m(2)), older (61 ± 2 years) men and women underwent high-fat feeding and oral glucose tolerance tests at baseline and after 6 months of aerobic exercise training. In response to aerobic exercise training, subjects increased cardiorespiratory fitness by 13% (P < .05) and insulin sensitivity index by 28% (P < .05). Basal plasma concentrations of IGFBP-1 increased by 41% after aerobic exercise training (P < .05). The insulin response to an oral glucose tolerance test was a significant predictor of fasting plasma IGFBP-1 concentrations at baseline and after exercise training (P = .02). In response to the high-fat meal at baseline, plasma IGFBP-1 concentrations decreased by 58% (P < .001); a 61% decrease to similar postprandial concentrations was observed after exercise training (P < .001). Plasma insulin response to the high-fat meal was inversely associated with postprandial IGFBP-1 concentrations at baseline and after exercise training (P = .06 and P < .05, respectively). Although aerobic exercise training did not attenuate the response to a high-fat meal, the increase in IGFBP-1 concentrations after exercise training may be one mechanism by which exercise reduces risk for cardiometabolic diseases in older adults.

The omega-3 fatty acid docosahexaenoic acid (DHA) has anti-inflammatory and anti-nociceptive (pain inhibiting) effects. Because strenuous exercise often results in local inflammation and pain, we hypothesized that DHA supplementation attenuates the rise in markers of local muscle inflammation and delayed onset muscle soreness (DOMS) that occur after eccentric strength exercise. Twenty-seven, healthy women (33 ± 2 y, BMI 23.1±1.0 kg·m(-2)) were randomized to receive 9d of 3000 mg/d DHA or placebo in a double-blind fashion. On day 7 of the supplementation period, the participants performed 4 sets of maximal-effort eccentric biceps curl exercise. Before and 48h after the eccentric exercise, markers of inflammation were measured including measures of muscle soreness (10-point visual analog pain scale, VAS), swelling (arm circumference), muscle stiffness (active and passive elbow extension), skin temperature, and salivary C-reactive protein (CRP) concentrations. As expected, muscle soreness and arm circumference increased while active and passive elbow extension decreased. The increase in soreness was 23% less in the DHA group (48h increase in VAS soreness ratings: 4.380.4 vs. 5.600.5, p=0.02). Furthermore, the number of subjects who were able to achieve full active elbow extension 48h after eccentric exercise was greater in the DHA group (71% vs. 15%, p = 0.006), indicating significantly less muscle stiffness. No between-group differences were observed for passive elbow extension (p = 0.78) or arm swelling (p = 0.75). Skin temperature and salivary CRP concentrations did not change from baseline to 48h after exercise in either group. These findings indicate that short-term DHA supplementation reduces exercise-induced muscle soreness and stiffness. Therefore, in addition to other health benefits that n-3 fatty acids have been associated with, DHA supplementation could be beneficial for improving tolerance to new and/or strenuous exercise programs and thereby might facilitate better training adaptations and exercise adherence. Key pointsSeven days of 3000 mg/day supplementation with algae-derived docosahexaenoic acid (DHA) attenuates the delayed onset muscle soreness and stiffness, and protects against the loss of joint range of motion that is caused by strenuous eccentric exercise.This benefit was observed in women, and supports the findings from other studies that were conducted on men or a combination of men and womenThe benefits from algae-derived DHA appear to be similar to those reported in other studies that used a combination of DHA and eicosapentaenoic acid (EPA) derived from fish oilThe findings of better recovery from strenuous exercise with DHA supplementation, paired with other research which demonstrated that DHA and EPA protect against chronic diseases suggest that DHA is an attractive optionThese findings have relevance to athletic populations, in that DHA would be expected to facilitate recovery and allow for better performance during training and competition. However, DHA supplementation might also benefit non-athletic populations, such as individuals starting new exercise programs and patient populations that are prone to muscle soreness (e.g. physical therapy patients).

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Research has shown that the majority of the cardiometabolic alterations associated with an increased risk of CVD (e.g., insulin resistance/type 2 diabetes, abdominal obesity, dyslipidemia, hypertension, and inflammation) can be prevented, and even reversed, with the implementation of healthier diets and regular exercise. Data from animal and human studies indicate that more drastic interventions, i.e., calorie restriction with adequate nutrition (CR), may have additional beneficial effects on several metabolic and molecular factors that are modulating cardiovascular aging itself (e.g., cardiac and arterial stiffness and heart rate variability). The purpose of this article is to review the current knowledge on the effects of CR on the aging of the cardiovascular system and CVD risk in rodents, monkeys, and humans. Taken together, research shows that CR has numerous beneficial effects on the aging cardiovascular system, some of which are likely related to reductions in inflammation and oxidative stress. In the vasculature, CR appears to protect against endothelial dysfunction and arterial stiffness and attenuates atherogenesis by improving several cardiometabolic risk factors. In the heart, CR attenuates age-related changes in the myocardium (i.e., CR protects against fibrosis, reduces cardiomyocyte apoptosis, prevents myosin isoform shifts, etc.) and preserves or improves left ventricular diastolic function. These effects, in combination with other benefits of CR, such as protection against obesity, diabetes, hypertension, and cancer, suggest that CR may have a major beneficial effect on health span, life span, and quality of life in humans.

Omega-3 fatty acids (omega-3) have anti-inflammatory properties. However, it is not known if omega-3 supplementation attenuates exercise-induced inflammation. We tested the hypothesis that omega-3 supplementation reduces inflammation that is induced by eccentric arm curl exercise. Healthy adult men and women (n=11; 35 ± 10 y) performed eccentric biceps curls on two occasions, once after 14d of dietary omega-3 restriction (control trial) and again after 7d of 3,000 mg/d omega-3 supplementation (omega-3 trial). Before and 48 h after eccentric exercise, signs of inflammation was assessed by measuring soreness ratings, swelling (arm circumference and arm volume), and temperature (infrared skin sensor). Arm soreness increased (p < 0.0001) in response to eccentric exercise; the magnitude of increase in soreness was 15% less in the omega-3 trial (p = 0.004). Arm circumference increased after eccentric exercise in the control trial (p = 0.01) but not in the omega-3 trial (p = 0.15). However, there was no difference between trials (p = 0.45). Arm volume and skin temperature did not change in response to eccentric exercise in either trial. These findings suggest that omega-3 supplementation decreases soreness, as a marker of inflammation, after eccentric exercise. Based on these findings, omega-3 supplementation could provide benefits by minimizing post-exercise soreness and thereby facilitate exercise training in individuals ranging from athletes undergoing heavy conditioning to sedentary subjects or patients who are starting exercise programs or medical treatments such as physical therapy or cardiac rehabilitation

Plasma dehydroepiandrosterone (DHEA) decreases ~80% between ages 25 and 75 yr. In a preliminary study, we found that 6 mo of DHEA replacement improved insulin action in elderly individuals. The purpose of the present larger, randomized double-blind study was to determine whether a longer period of DHEA replacement improves glucose tolerance. Fifty-seven men an d 68 women aged 65 to 75 yr were randomly assigned to 50 mg DHEA or placebo once daily. Year one was a randomized, double blind trial. Year 2 was an open label continuation. DHEA replacement improved glucose tolerance in participants who had abnormal GT initially, reduced plasma triglycerides, and the infla mmatory cytokines IL6 and TNFα. This trial was registered at clinicaltrials.gov as NCT00182975.

The objective of this study was to evaluate the influence of calorie restriction (CR) on free-living physical activity levels among humans. Data were from three CALERIE phase I site-specific protocols. Participants were nonobese (body mass index = 23.5–29.9 kg/m2) adults randomly assigned to 25% CR, low-calorie diet (LCD, 890 kcal/day supplement diet until 15% weight loss, then weight maintenance), or control at Pennington Biomedical Research Center (PBRC); 30% or 10% CR at Tufts University; and 20% CR or control at Washington University School of Medicine (WUSM). Activity was measured at months 0, 3, and 6 (PBRC) and at months 0, 3, 6, 9, and 12 (WUSM and Tufts). Total daily energy expenditure (TEE) by doubly labeled water and resting metabolic rate (RMR) were used to compute activity energy expenditure: AEE = TEE − RMR − 0.1 * TEE. Accelerometry and 7-day recall categorized activities by intensity. At Tufts, the 10% and 30% CR groups experienced significant decreases in AEE at months 6, 9, and 12. At month 6, a larger decrease in AEE was observed in the CR than the control group at WUSM. At months 3 and 6, larger decreases in AEE were observed in the CR and LCD groups than the control group at PBRC. Accelerometry and 7-day PAR did not consistently detect changes in activity categories. CR-associated changes in AEE were variable but, generally, reduced the energy deficit, which would reduce the expected rate of weight loss. Accelerometry and recall did not consistently explain reduced AEE, suggesting that increased muscle efficiency and/or decreased fidgeting accounted for decreased AEE. Inaccuracy of accelerometry and recall also likely negatively affected sensitivity.

The intent of this research was to explore the influence of physical activity on the appetite of older adults in long-term care. Given the impact of the anorexia of aging and the increasing numbers of older adults, this could have significant health implications. Residents (N = 93) of a long-term care, assisted living, and rehabilitation facility were surveyed using the "Appetite & Activity Questionnaire." There was no relationship found between physical activity and appetite regardless of the participants' sex or age. BMI appeared to correlate well with the amount of activity that was performed. The most salient finding was the near absence of physical activity, even in the presence of facilities, support personnel, and available time.

To determine how the frequency, timing and magnitude of hyperglycemia are associated with large-for-gestational-age (LGA) infants in pregnancies complicated by type 1 diabetes.Charts from pregnant women with type 1 diabetes (n = 70) were reviewed. Indices of maternal glycemic control were determined for seven gestational periods (weeks 7-10, 11-15, 16-19, 20-24, 25-28, 29-32 and 33-38) and compared between women who delivered LGA infants and appropriate-for-gestational-age (AGA) infants.Of the 70 pregnancies, 57% of the infants were LGA (4.3 +/- 0.4 kg) and 43% were AGA (3.2 +/- 0.4 kg). Total maternal weight gain and rate of weight gain were significantly higher in mothers with LGA infants. The glycemic variables associated with an LGA infant were percentage of preprandial values above target for weeks 11-15, 25-28 and 29-32, and percentage of all values above target for weeks 33-38. For the entire pregnancy, the strongest predictors of an LGA infant were percentage of preprandial blood glucose values above target during weeks 29-32 and maternal weight gain.In pregnant women with type 1 diabetes, frequent episodes of preprandial hyperglycemia in the third trimester significantly impact the development of LGA infants.

Excessive adiposity is associated with increased oxidative stress and accelerated aging. Weight loss induced by negative energy balance reduces markers of oxidation in experimental animals and humans. The long-term effects of weight loss induced by calorie restriction or increased energy expenditure induced by exercise on measures of oxidative stress and damage have not been studied in humans. The objective of the present study was to compare the effects of 20% caloric restriction or 20% exercise alone over 1 year on oxidative damage to DNA and RNA, as assessed through white blood cell and urine analyses. Eighteen men and women aged 50 to 60 years with a body mass index (BMI) between 23.5 to 29.9 kg/m2 were assigned to one of two conditions — 20% CR (n = 9) or 20% EX (n = 9) — which was designed to produce an identical energy deficit through increased energy expenditure. Compared to baseline, both interventions significantly reduced oxidative damage to both DNA (48.5% and 49.6% reduction for the CR and EX groups, respectively) and RNA (35.7% and 52.1% reduction for the CR and EX groups, respectively) measured in white blood cells. However, urinary levels of DNA and RNA oxidation products did not differ from baseline values following either 12-month intervention program. Data from the present study provide evidence that negative energy balances induced through either CR or EX result in substantial and similar improvements in markers of DNA and RNA damage to white blood cells, potentially by reducing systemic oxidative stress.

Objective: To compare the inter-rater and intra-rater reliability and analysis time of two methods for quantifying visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes from magnetic resonance (MR) images. Research Methods and Procedures: Ten subjects (BMI, 27.0 ± 2.1 kg/m2; 56 years of age ± 4 years) underwent MR imaging of the abdomen. Ten transverse T1-weighted images were selected from each scan and analyzed using two software packages that differ in principle. The first method, ANALYZE version 5.0, represents the manual threshold method, and the second, HIPPO version 1.3, is based on the fuzzy clustering approach. Inter-rater reliability for each method was assessed by comparing the intra-class correlation coefficients (ICCs) for VAT and SAT results from two evaluators, and intra-rater reliability for each method was assessed by comparing ICCs for VAT and SAT analyses performed 1 week apart by the same evaluator. The total time for analysis also was compared between methods. Results: The inter-rater reliability for VAT was greater with HIPPO than with ANALYZE (ICC = 0.996 vs. 0.828), whereas inter-rater reliability for SAT did not differ between methods (ICC = 0.975 and 0.987). The intra-rater reliability was equally high with HIPPO and ANALYZE for both VAT (ICC = 0.998 vs. 0.992) and SAT (ICC = 0.996 vs. 0.992). HIPPO required less than one-half as much analysis time as ANALYZE (15.9 ± 4.4 vs. 36.5 ± 8.2 minutes, p < 0.0001). Discussion: HIPPO software appears advantageous for the quantification of VAT from multislice MR images because inter-rater results are more reliable, and it is more time-efficient than less automated methods.

Increases in exercise energy expenditure without compensatory changes in food intake (EX) and restriction of calorie intake (CR) both decrease body weight and fat mass, which, in turn, improve glucoregulatory function. However, EX may provide greater benefits than can be provided through CR. Therefore, our study hypothesis was that weight loss through EX reduces visceral abdominal fat and improves glucoregulation to a greater extent than does similar weight loss through CR. Forty-eight sedentary 50- to 60-y-old men and women, most of whom were overweight, underwent 12 mo of EX, CR, or a healthy lifestyle control period. Body composition was assessed by dual-energy x-ray absorptiometry and by magnetic resonance imaging. Indices of glucoregulatory function were determined by oral glucose tolerance test and were measured ≥48 h after the last exercise bout in the EX group. Body weight, total fat mass, and visceral fat volume decreased similarly in the EX and CR groups but did not change in the HL group. Likewise, insulin sensitivity index and the oral glucose tolerance test glucose and insulin areas under the curve improved similarly in the EX and CR groups and remained unchanged in the HL group. In conclusion, weight losses induced by exercise and by CR are effective means for improving glucose tolerance and insulin action in nonobese, healthy, middle-aged men and women; however, it does not appear that exercise training-induced weight loss results in greater improvements than those that result from CR.

Background : A common functional missense mutation [Ala54Thr of the fatty acid-binding protein 2 gene (FABP2)] has previously been studied for associations with glucoregulation, postprandial lipemia, and lipid oxidation rates. However, most of those studies have not accounted for the interactive and potentially confounding effects of habitual physical activity and diet. Objective : We tested the hypothesis that, in sedentary nondiabetic subjects following a low-fat diet, Thr54 FABP2 carriers have lower glucoregulatory function, greater postprandial lipemia, and greater lipid oxidation rates than do their Ala54 FABP2-homozygous counterparts. Design : Men and women (n = 122) aged 50-75 y who were following a low-fat diet were genotyped and underwent oral-glucose-tolerance tests. A subgroup (n = 36) also underwent postprandial lipemia tests with lipid oxidation rate measurements. Results : Thr54 carriers were less likely to have normal glucose tolerance (P = 0.05) and had higher fasting glucose concentrations (P = 0.003) than did Ala54 homozygotes. In Thr54 carriers, the insulin sensitivity index was lower (P = 0.02), and the fasting insulin and the oral-glucose-tolerance test insulin area under the curve were higher (P = 0.05 and 0.03, respectively) than in Ala54 homozygotes. FABP2 genotype was not associated with fasting or postprandial lipemia test triacylglycerol or free fatty acids (P ≥0.22 for all), but postprandial lipid oxidation rates were higher (P = 0.01), which suggests that fat absorption is higher in Thr54 carriers than in Ala54 homozygotes. Conclusions : In sedentary nondiabetic persons following a low-fat diet, FABP2 Thr54 carriers have lower glucose tolerance and lower insulin action than do Ala54-homozygous persons. Furthermore, FABP Thr54 carriers have higher lipid oxidation rates, which may be the mechanism of glucoregulatory dysfunction.

We investigated the hemodynamic determinants of the age-associated decline in maximal oxygen uptake (V̇o2 max) and the influence of gender on the decline in V̇o2 max and its determinants in old and very old men and women. Sedentary, 60- to 92-yr-old women ( n = 71) and men ( n = 29), with no evidence of cardiovascular disease, underwent maximal treadmill exercise tests during which V̇o2 max and maximal cardiac output (Q̇max) were determined. V̇o2 max and age were inversely related in both women (−23 ± 2 ml·min−1·yr−1; P < 0.0001) and men (−57 ± 5 ml·min−1·yr−1; P < 0.0001). The absolute slope of the V̇o2 max vs. age relationship was twofold steeper in men than in women ( P < 0.0001). Q̇max was also inversely related to age in a gender-specific manner (women = −87 ± 25 ml·min−1·yr−1, P = 0.0009; men = −215 ± 50 ml·min−1·yr−1, P = 0.0002; P = 0.01 women vs. men). Age-related changes in maximal exercise arteriovenous oxygen content difference (a-vDo2) were marginally different ( P = 0.08) between women (−0.12 ± 0.03 ml·dl−1·yr−1, P = 0.0003) and men (−0.22 ± 0.04 ml·dl−1·yr−1, P < 0.0001). Age-associated decreases in Q̇max and a-vDo2 contributed equally to the declines in V̇o2 max in both men and women. In the later stages of life, V̇o2 max, Q̇max, and a-vDo2 decrease with age more rapidly in older men than they do in older women. As a result, the gender differences dissipate in the later decades of life. Declines in Q̇max and a-vDo2 contribute equally to the age-related decrease in V̇o2 max in men and women.

OBJECTIVE—Physical inactivity and increased adiposity contribute to insulin resistance; less is known, however, about the relative contributions of these factors in older adults. The aim of this study was to determine whether cardiovascular fitness, whole-body adiposity, or abdominal adiposity is the strongest predictor of insulin resistance into old age. RESEARCH DESIGN AND METHODS—Subjects included 407 men and women aged 50–95 years (means ± SD 69 ± 11 years). Insulin resistance was estimated using the insulin sensitivity index (ISI) of Matsuda and DeFronzo [ISI = 10,000/square root of (fasting glucose × fasting insulin) × (mean glucose × mean insulin during an oral glucose tolerance test); lower ISI = greater insulin resistance]. Fitness was determined with a treadmill maximal oxygen consumption (Vo2max) test. Whole-body adiposity measures included BMI and percent fat by dual-energy X-ray absorptiometry or hydrodensitometry; abdominal adiposity was estimated by waist circumference. RESULTS—Waist circumference was the strongest independent correlate of ISI (r = −0.52, P < 0.0001), explaining 28% of the variance when controlling for sex, BMI, percent fat, and Vo2max. BMI (r = −0.45), percent fat (r = −0.40), and Vo2max (r = 0.22) independently predicted ISI (all P < 0.0001); however, after controlling for waist circumference, only Vo2max remained significant (r = 0.13, P = 0.009). CONCLUSIONS—Adiposity and fitness continue to be significant predictors of insulin sensitivity into old age, with abdominal obesity being the most important single factor. These findings support the measurement of waist circumference to assess health risk among older adults.

OBJECTIVE It is not known whether calorie restriction (CR) has additive benefits to those from exercise (EX)-induced weight loss. We hypothesized that weight loss from CR and EX (CREX) improves insulin sensitivity more than matched weight loss induced by EX or CR alone and that the incretin system may be involved in adaptations to CR. RESEARCH DESIGN AND METHODS Sedentary, overweight men and women (n = 52, 45–65 years of age) were randomized to undergo 6–8% weight loss by using CR, EX, or CREX. Glucose, insulin, C-peptide, insulin sensitivity, and incretin hormones (glucagon-like peptide 1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) were measured during frequently sampled oral glucose tolerance tests (FSOGTTs). Incretin effects on insulin secretion were measured by comparing insulin secretion rates from the FSOGTTs to those from a glycemia-matched glucose infusion. RESULTS Despite similar weight losses in all groups, insulin sensitivity index values increased twofold more in the CREX group (2.09 ± 0.35 μM/kg/pM × 100) than in the CR (0.89 ± 0.39 μM/kg/pM × 100) and EX (1.04 ± 0.39 μM/kg/pM × 100) groups. Postprandial GLP-1 concentrations decreased only in the CR group (P = 0.04); GIP concentrations decreased in all groups. Incretin effects on insulin secretion were unchanged. CONCLUSIONS CR and EX have additive beneficial effects on glucoregulation. Furthermore, the adaptations to CR may involve reductions in postprandial GLP-1 concentrations. These findings underscore the importance of promoting both CR and EX for optimal health. However, because data from participants who withdrew from the study and from those who did not adhere to the intervention were excluded, the results may be limited to individuals who are capable of adhering to a healthy lifestyle intervention.

Dietary acid load, quantified as the potential renal acid load (PRAL) of the diet, affects systemic pH and acid-base regulation. In a previous cross-sectional study, we reported that a low dietary PRAL (i.e. alkaline promoting diet) is associated with higher respiratory exchange ratio (RER) values during maximal exercise. The purpose of the present study was to confirm the previous findings with a short-term dietary intervention study. Additionally, we sought to determine if changes in PRAL affects submaximal exercise RER (as a reflection of substrate utilization) and anaerobic exercise performance. Subjects underwent a graded treadmill exercise test (GXT) to exhaustion and an anaerobic exercise performance test on two occasions, once after following a low-PRAL diet and on a separate occasion, after a high-PRAL diet. The diets were continued as long as needed to achieve an alkaline or acid fasted morning urine pH, respectively, with all being 4-9 days in duration. RER was measured during the GXT with indirect calorimetry. The anaerobic performance test was a running time-to-exhaustion test lasting 1-4 min. Maximal exercise RER was lower in the low-PRAL trial compared to the high-PRAL trial (1.10 ± 0.02 vs. 1.20 ± 0.05, p = 0.037). The low-PRAL diet also resulted in a 21% greater time to exhaustion during anaerobic exercise (2.56 ± 0.36 vs. 2.11 ± 0.31 sec, p = 0.044) and a strong tendency for lower RER values during submaximal exercise at 70% VO2max (0.88 ± 0.02 vs. 0.96 ± 0.04, p = 0.060). Contrary to our expectations, a short-term low-PRAL (alkaline promoting) diet resulted in lower RER values during maximal-intensity exercise. However, the low-PRAL diet also increased anaerobic exercise time to exhaustion and appears to have shifted submaximal exercise substrate utilization to favor lipid oxidation and spare carbohydrate, both of which would be considered favorable effects in the context of exercise performance. Key pointsShort-term (4-9 days) changes in the acid or alkaline promoting qualities of the diet, quantified as potential renal acid load (PRAL), alter systemic pH, as evidenced in the present study by changes in fasted morning urine pH. Low-PRAL (alkaline promoting) diets are characterized by high intakes of vegetables and fruits with limited consumption of meats, cheeses, and grains while high-PRAL diets are characterized by the opposite dietary pattern.An alkaline promoting (low-PRAL) diet increases anaerobic exercise performance, as evidenced by greater time-to-exhaustion during high-intensity treadmill running.Preliminary evidence suggests that an alkaline promoting (low-PRAL) diet increases lipid oxidation and may have a carbohydrate-sparing effect during submaximal endurance exercise, although further studies are needed.In contrast to what has been observed in response to habitual/long-term dietary patterns, a short-term low-PRAL diet does not increase maximal exercise respiratory exchange ratio and even appears to lower it. This suggests that short-term and long-term alterations in PRAL have different physiologic effects on this parameter.

A polymorphism in the IL-6 gene, a G-to-C substitution 176 bp upstream of the ATG translation initiation site, has been associated with diabetes prevalence and insulin resistance. Interventions including exercise training are frequently used to modify cardiovascular disease risk factors. Consequently, this project examined associations between the IL-6 −174 genotype and oral glucose tolerance test outcomes in 50- to 75-yr-old sedentary men and postmenopausal women before and after aerobic exercise training. Among the 87 individuals who started the study, 56 were retested after 6 mo of aerobic exercise training. Subject characteristics at baseline did not differ between the IL-6 genotype groups with the exception of fasting glucose, which was higher ( P = 0.02, covariates age, gender, and ethnicity) in the CC genotype group. The training-induced change in glucose area under the curve during the oral glucose tolerance test varied between the IL-6 −174 genotype groups ( P = 0.05, covariates age, gender, ethnicity, baseline glucose area under the curve, and percent body fat change) with a significant decrease occurring only in the GG genotype group. Insulin outcomes did not differ among the groups at baseline or after training. Training-induced changes in weight, percent body fat, maximal oxygen consumption, fasting glucose, and an insulin sensitivity index also changed similarly among the genotype groups. In conclusion, fasting glucose and the extent to which glucose tolerance changes with exercise training may be influenced by the IL-6 −174 gene polymorphism.