Impact on Cardiovascular Health of Using Phentermine/Topiramate in Combination With Laparoscopic Sleeve Gastrectomy in Super Obesity.

INTRODUCTION: Management of patients with BMI≥50 kg/m2 is challenging. In previous work, pre and postoperative pharmacotherapy with phentermine/topiramate plus laparoscopic sleeve gastrectomy (PT + SG) promoted greater weight loss than sleeve gastrectomy (SG) alone at 24 mo postoperatively. This current secondary analysis studied the impact of PT + SG on blood pressure (BP), heart rate, and antihypertensive usage. METHODS: Patients with BMI≥50 kg/m2 planning to have SG (n = 13) were recruited from 2014 to 2016, at an academic medical center in Winston-Salem, North Carolina, for this open-label trial. Participants took phentermine/topiramate (PT; 7.5/46-15/92 mg/d) for ≥3 mo preoperatively and 24 mo postoperatively. The control group (n = 40) underwent SG during the same time frame. We used mixed models for BP and heart rate to compare PT + SG versus SG alone over time, adjusted for age, sex, and initial BP. RESULTS: By 24 mo postoperatively the model adjusted changes in systolic blood pressure/diastolic blood pressure (SBP/DBP) (mm Hg) were -24.44 (-34.46,-14.43)/-28.60 (-40.74,-16.46) in the PT + SG group versus -11.81 (-17.58,-6.05)/-13.89 (-21.32,-6.46) in the control group (SBP P = 0.02; DBP P = 0.03). At baseline 8 (61.5%) participants in the PT + SG arm and 22 (55.0%) in the control group used antihypertensives. Excluding patients lost to follow-up (n = 3), by 24 mo postoperatively, none of the PT + SG participants were on antihypertensives compared to 14 (41.2%) in the control group (P = 0.01). CONCLUSIONS: Patients with BMI≥50 kg/m2 treated with PT + SG had greater improvement in BP with no use of antihypertensive medication at 24 mo postoperatively versus SG alone, where 41% continued medication use. Larger trials are required to evaluate this.

Effect of Diet and Exercise on Knee Pain in Patients With Osteoarthritis and Overweight or Obesity: A Randomized Clinical Trial.

Importance: Some weight loss and exercise programs that have been successful in academic center-based trials have not been evaluated in community settings. Objective: To determine whether adaptation of a diet and exercise intervention to community settings resulted in a statistically significant reduction in pain, compared with an attention control group, at 18-month follow-up. Design, Setting, and Participants: Assessor-blinded randomized clinical trial conducted in community settings in urban and rural counties in North Carolina. Patients were men and women aged 50 years or older with knee osteoarthritis and overweight or obesity (body mass index ≥27). Enrollment (N = 823) occurred between May 2016 and August 2019, with follow-up ending in April 2021. Interventions: Patients were randomly assigned to either a diet and exercise intervention (n = 414) or an attention control (n = 409) group for 18 months. Main Outcomes and Measures: The primary outcome was the between-group difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain score (range, 0 [none] to 20 [severe]; minimum clinically important difference, 1.6) over 18 months, tested using a repeated-measures mixed linear model with adjustments for covariates. There were 7 secondary outcomes including body weight. Results: Among the 823 randomized patients (mean age, 64.6 years; 637 [77%] women), 658 (80%) completed the trial. At 18-month follow-up, the adjusted mean WOMAC pain score was 5.0 in the diet and exercise group (n = 329) compared with 5.5 in the attention control group (n = 316) (adjusted difference, -0.6; 95% CI, -1.0 to -0.1; P = .02). Of 7 secondary outcomes, 5 were significantly better in the intervention group compared with control. The mean change in unadjusted 18-month body weight for patients with available data was -7.7 kg (8%) in the diet and exercise group (n = 289) and -1.7 kg (2%) in the attention control group (n = 273) (mean difference, -6.0 kg; 95% CI, -7.3 kg to -4.7 kg). There were 169 serious adverse events; none were definitely related to the study. There were 729 adverse events; 32 (4%) were definitely related to the study, including 10 body injuries (9 in diet and exercise; 1 in attention control), 7 muscle strains (6 in diet and exercise; 1 in attention control), and 6 trip/fall events (all 6 in diet and exercise). Conclusions and Relevance: Among patients with knee osteoarthritis and overweight or obesity, diet and exercise compared with an attention control led to a statistically significant but small difference in knee pain over 18 months. The magnitude of the difference in pain between groups is of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT02577549.

Evidence of Pathogen-Induced Immunogenetic Selection across the Large Geographic Range of a Wild Seabird.

Over evolutionary time, pathogen challenge shapes the immune phenotype of the host to better respond to an incipient threat. The extent and direction of this selection pressure depend on the local pathogen composition, which is in turn determined by biotic and abiotic features of the environment. However, little is known about adaptation to local pathogen threats in wild animals. The Gentoo penguin (Pygoscelis papua) is a species complex that lends itself to the study of immune adaptation because of its circumpolar distribution over a large latitudinal range, with little or no admixture between different clades. In this study, we examine the diversity in a key family of innate immune genes-the Toll-like receptors (TLRs)-across the range of the Gentoo penguin. The three TLRs that we investigated present varying levels of diversity, with TLR4 and TLR5 greatly exceeding the diversity of TLR7. We present evidence of positive selection in TLR4 and TLR5, which points to pathogen-driven adaptation to the local pathogen milieu. Finally, we demonstrate that two positively selected cosegregating sites in TLR5 are sufficient to alter the responsiveness of the receptor to its bacterial ligand, flagellin. Taken together, these results suggest that Gentoo penguins have experienced distinct pathogen-driven selection pressures in different environments, which may be important given the role of the Gentoo penguin as a sentinel species in some of the world's most rapidly changing environments.

A randomized pilot study of nitrate supplementation with beetroot juice in acute respiratory failure.

Nitrate rich beetroot juice (BRJ) can enhance nitric oxide signaling, leading to improved physical function in healthy and diseased populations, but its safety and biologic efficacy have not been evaluated in a critically ill population. We randomized 22 previously functional acute respiratory failure patients to either BRJ or placebo daily until day 14 or discharge. We measured blood nitrate and nitrite levels and quantified strength and physical function at intensive care unit (ICU) and hospital discharge. Participants were predominantly male (54%), aged 68.5 years with an APACHE III score of 62. BRJ increased plasma nitrate (mean 219.2 µM increase, p = 0.002) and nitrite levels (mean 0.144 µM increase, p = 0.02). We identified no adverse events. The unadjusted and adjusted effect sizes of the intervention on the short physical performance battery were small (d = 0.12 and d = 0.17, respectively). In this pilot trial, administration of BRJ was feasible and safe, increased blood nitrate and nitrate levels, but had a small effect on physical function. Future studies could evaluate the clinical efficacy of BRJ as a therapy to improve physical function in survivors of critical illness.

Comparative population genomics reveals key barriers to dispersal in Southern Ocean penguins.

The mechanisms that determine patterns of species dispersal are important factors in the production and maintenance of biodiversity. Understanding these mechanisms helps to forecast the responses of species to environmental change. Here, we used a comparative framework and genomewide data obtained through RAD-Seq to compare the patterns of connectivity among breeding colonies for five penguin species with shared ancestry, overlapping distributions and differing ecological niches, allowing an examination of the intrinsic and extrinsic barriers governing dispersal patterns. Our findings show that at-sea range and oceanography underlie patterns of dispersal in these penguins. The pelagic niche of emperor (Aptenodytes forsteri), king (A. patagonicus), Adélie (Pygoscelis adeliae) and chinstrap (P. antarctica) penguins facilitates gene flow over thousands of kilometres. In contrast, the coastal niche of gentoo penguins (P. papua) limits dispersal, resulting in population divergences. Oceanographic fronts also act as dispersal barriers to some extent. We recommend that forecasts of extinction risk incorporate dispersal and that management units are defined by at-sea range and oceanography in species lacking genetic data.

Impact of Diet and/or Exercise Intervention on Infrapatellar Fat Pad Morphology: Secondary Analysis from the Intensive Diet and Exercise for Arthritis (IDEA) Trial.

OBJECTIVES: The infrapatellar fat pad (IPFP) represents intra-articular adipose tissue that may contribute to intra-articular inflammation and pain by secretion of proinflammatory cytokines. Here we examined the impact of weight loss by diet and/or exercise interventions on the IPFP volume. METHODS: Intensive Diet and Exercise for Arthritis (IDEA) was a single-blinded, single-center, 18-month, prospective, randomized controlled trial that enrolled 454 overweight and obese older adults with knee pain and radiographic osteoarthritis. Participants were randomized to 1 of 3 groups: exercise-only control (E), diet-induced weight loss (D), and diet-induced weight loss + exercise (D+E). In a subsample (n = 106; E: n = 36, D: n = 35, and D+E: n = 35), magnetic resonance images were acquired at baseline and at the 18-month follow-up, from which we analyzed IPFP volume, surface areas, and thickness in this secondary analysis. RESULTS: The average weight loss amounted to 1.0% in the E group, 10.5% in the D group, and 13.0% in the D+E group. A significant (p < 0.01) reduction in IPFP volume was observed in the E (2.1%), D (4.0%), and D+E (5.2%) groups. The IPFP volume loss in the D+E group was significantly greater than that in the E group (p < 0.05) when not adjusting for parallel comparisons. Across intervention groups, there were significant correlations between IPFP volume change, individual weight loss (r = 0.40), and change in total body fat mass (dual-energy X-ray absorptiometry; r = 0.44, n = 88) and in subcutaneous thigh fat area (computed tomography; r = 0.32, n = 82). CONCLUSIONS: As a potential link between obesity and knee osteoarthritis, the IPFP was sensitive to intervention by diet and/or exercise, and its reduction was correlated with changes in weight and body fat.

Effects of supervised exercise and dietary nitrate in older adults with controlled hypertension and/or heart failure with preserved ejection fraction.

Aerobic exercise training is an effective therapy to improve peak aerobic power (peak VO2) in individuals with hypertension (HTN, AHA/ACC class A) and heart failure patients with preserved ejection fraction (HFpEF). High nitrate containing beetroot juice (BRJ) also improves sub-maximal endurance and decreases blood pressure in both HTN and HFpEF. We hypothesized that combining an aerobic exercise and dietary nitrate intervention would result in additive or even synergistic positive effects on exercise tolerance and blood pressure in HTN or HFpEF. We report results from two pilot studies examining the effects of supervised aerobic exercise combined with dietary nitrate in patients with controlled HTN (n = 26, average age 65 ± 5 years) and in patients with HFpEF (n = 20, average age 69 ± 7 years). All patients underwent an aerobic exercise training regimen; half were randomly assigned to consume a high nitrate-containing beet juice beverage (BRJ containing 6.1 mmol nitrate for the HFpEF study consumed three times a week and 8 mmol nitrate for the HTN study consumed daily) while the other half consumed a beet juice beverage with the nitrate removed (placebo). The main result was that there was no added benefit observed for any outcomes when comparing BRJ to placebo in either HTN or HFpEF patients undergoing exercise training (p ≥ 0.14). There were within-group benefits. In the pilot study in patients with HFpEF, aerobic endurance (primary outcome), defined as the exercise time to volitional exhaustion during submaximal cycling at 75% of maximal power output, improved during exercise training within each group from baseline to end of study, 369 ± 149 s vs 520 ± 257 s (p = 0.04) for the placebo group and 384 ± 129 s vs 483 ± 258 s for the BRJ group (p = 0.15). Resting systolic blood pressure in patients with HFpEF also improved during exercise training in both groups, 136 ± 16 mm Hg vs 122 ± 3 mm Hg for the placebo group (p < 0.05) and 132 ± 12 mm Hg vs 119 ± 9 mm Hg for the BRJ group (p < 0.05). In the HTN pilot study, during a treadmill graded exercise test, peak oxygen consumption (primary outcome) did not change significantly, but time to exhaustion (also a primary outcome) improved in both groups, 504 ± 32 s vs 601 ± 38 s (p < 0.05) for the placebo group and 690 ± 38 s vs 772 ± 95 s for the BRJ group (p < 0.05) which was associated with a reduction in supine resting systolic blood pressure in BRJ group. Arterial compliance also improved during aerobic exercise training in both the HFpEF and the HTN patients for both BRJ and placebo groups. Future work is needed to determine if larger nitrate doses would provide an added benefit to supervised aerobic exercise in HTN and HFpEF patients.

Weight-loss and exercise for communities with arthritis in North Carolina (we-can): design and rationale of a pragmatic, assessor-blinded, randomized controlled trial.

BACKGROUND: Recently, we determined that in a rigorously monitored environment an intensive diet-induced weight loss of 10% combined with exercise was significantly more effective at reducing pain in men and women with symptomatic knee osteoarthritis (OA) than either intervention alone. Compared to previous long-term weight loss and exercise trials of knee OA, our intensive diet-induced weight loss and exercise intervention was twice as effective at reducing pain intensity. Whether these results can be generalized to less intensively monitored cohorts is unknown. Thus, the policy relevant and clinically important question is: Can we adapt this successful solution to a pervasive public health problem in real-world clinical and community settings? This study aims to develop a systematic, practical, cost-effective diet-induced weight loss and exercise intervention implemented in community settings and to determine its effectiveness in reducing pain and improving other clinical outcomes in persons with knee OA. METHODS/DESIGN: This is a Phase III, pragmatic, assessor-blinded, randomized controlled trial. Participants will include 820 ambulatory, community-dwelling, overweight and obese (BMI ≥ 27 kg/m2) men and women aged ≥ 50 years who meet the American College of Rheumatology clinical criteria for knee OA. The primary aim is to determine whether a community-based 18-month diet-induced weight loss and exercise intervention based on social cognitive theory and implemented in three North Carolina counties with diverse residential (from urban to rural) and socioeconomic composition significantly decreases knee pain in overweight and obese adults with knee OA relative to a nutrition and health attention control group. Secondary aims will determine whether this intervention improves self-reported function, health-related quality of life, mobility, and is cost-effective. DISCUSSION: Many physicians who treat people with knee OA have no practical means to implement weight loss and exercise treatments as recommended by numerous OA treatment guidelines. This study will establish the effectiveness of a community program that will serve as a blueprint and exemplar for clinicians and public health officials in urban and rural communities to implement a diet-induced weight loss and exercise program designed to reduce knee pain and improve other clinical outcomes in overweight and obese adults with knee OA. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02577549 October 12, 2015.

Dispersal in the sub-Antarctic: king penguins show remarkably little population genetic differentiation across their range.

BACKGROUND: Seabirds are important components of marine ecosystems, both as predators and as indicators of ecological change, being conspicuous and sensitive to changes in prey abundance. To determine whether fluctuations in population sizes are localised or indicative of large-scale ecosystem change, we must first understand population structure and dispersal. King penguins are long-lived seabirds that occupy a niche across the sub-Antarctic zone close to the Polar Front. Colonies have very different histories of exploitation, population recovery, and expansion. RESULTS: We investigated the genetic population structure and patterns of colonisation of king penguins across their current range using a dataset of 5154 unlinked, high-coverage single nucleotide polymorphisms generated via restriction site associated DNA sequencing (RADSeq). Despite breeding at a small number of discrete, geographically separate sites, we find only very slight genetic differentiation among colonies separated by thousands of kilometers of open-ocean, suggesting migration among islands and archipelagos may be common. Our results show that the South Georgia population is slightly differentiated from all other colonies and suggest that the recently founded Falkland Island colony is likely to have been established by migrants from the distant Crozet Islands rather than nearby colonies on South Georgia, possibly as a result of density-dependent processes. CONCLUSIONS: The observed subtle differentiation among king penguin colonies must be considered in future conservation planning and monitoring of the species, and demographic models that attempt to forecast extinction risk in response to large-scale climate change must take into account migration. It is possible that migration could buffer king penguins against some of the impacts of climate change where colonies appear panmictic, although it is unlikely to protect them completely given the widespread physical changes projected for their Southern Ocean foraging grounds. Overall, large-scale population genetic studies of marine predators across the Southern Ocean are revealing more interconnection and migration than previously supposed.

Dietary nitrate supplementation improves exercise performance and decreases blood pressure in COPD patients.

Dietary nitrate (NO3(-)) supplementation via beetroot juice has been shown to increase the exercise capacity of younger and older adults. The purpose of this study was to investigate the effects of acute NO3(-) ingestion on the submaximal constant work rate exercise capacity of COPD patients. Fifteen patients were assigned in a randomized, single-blind, crossover design to receive one of two treatments (beetroot juice then placebo or placebo then beetroot juice). Submaximal constant work rate exercise time at 75% of the patient's maximal work capacity was the primary outcome. Secondary outcomes included plasma NO3(-) and nitrite (NO2(-)) levels, blood pressure, heart rate, oxygen consumption (VO2), dynamic hyperinflation, dyspnea and leg discomfort. Relative to placebo, beetroot ingestion increased plasma NO3(-) by 938% and NO2(-) by 379%. Median (+interquartile range) exercise time was significantly longer (p = 0.031) following the ingestion of beetroot versus placebo (375.0 + 257.0 vs. 346.2 + 148.0 s, respectively). Compared with placebo, beetroot ingestion significantly reduced iso-time (p = 0.001) and end exercise (p = 0.008) diastolic blood pressures by 6.4 and 5.6 mmHg, respectively. Resting systolic blood pressure was significantly reduced (p = 0.019) by 8.2 mmHg for the beetroot versus the placebo trial. No other variables were significantly different between the beetroot and placebo trials. These results indicate that acute dietary NO3(-) supplementation can elevate plasma NO3(-) and NO2(-) concentrations, improve exercise performance, and reduce blood pressure in COPD patients.

Cost-Effectiveness of Community-Based Diet and Exercise for Patients with Knee Osteoarthritis and Obesity or Overweight.

OBJECTIVE: Obesity exacerbates pain and functional limitation in persons with knee osteoarthritis (OA). In the Weight Loss and Exercise for Communities with Arthritis in North Carolina (WE-CAN) study, a community-based diet and exercise (D + E) intervention led to an additional 6 kg weight loss and 20% greater pain relief in persons with knee OA and body mass index (BMI) >27 kg/m2 relative to a group-based health education (HE) intervention. We sought to determine the incremental cost-effectiveness of the usual care (UC), UC + HE, and UC + (D + E) programs, comparing each strategy with the "next-best" strategy ranked by increasing lifetime cost. METHODS: We used the Osteoarthritis Policy Model to project long-term clinical and economic benefits of the WE-CAN interventions. We considered three strategies: UC, UC + HE, and UC + (D + E). We derived cohort characteristics, weight, and pain reduction from the WE-CAN trial. Our outcomes included quality-adjusted life years (QALYs), cost, and incremental cost-effectiveness ratios (ICERs). RESULTS: In a cohort with mean age 65 years, BMI 37 kg/m2, and Western Ontario and McMaster Universities Osteoarthritis Index pain score 38 (scale 0-100, 100 = worst), UC leads to 9.36 QALYs/person, compared with 9.44 QALYs for UC + HE and 9.49 QALYS for UC + (D + E). The corresponding lifetime costs are $147,102, $148,139, and $151,478. From the societal perspective, UC + HE leads to an ICER of $12,700/QALY; adding D + E to UC leads to an ICER of $61,700/QALY. CONCLUSION: The community-based D + E program for persons with knee OA and BMI >27kg/m2 could be cost-effective for willingness-to-pay thresholds greater than $62,000/QALY. These findings suggest that incorporation of community-based D + E programs into OA care may be beneficial for public health.

Clinical, Health-Related Quality of Life, and Gait Differences Among Obesity Classes in Adults With Knee Osteoarthritis.

OBJECTIVE: The purpose of this study was to determine whether clinical, health-related quality of life (HRQL), and gait characteristics in adults with knee osteoarthritis (OA) differed by obesity category. METHODS: This cross-sectional analysis of 823 older adults (mean age 64.6 years, SD 7.8 years) with knee OA and overweight or obesity compared clinical, HRQL, and gait outcomes among obesity classifications (overweight or class I, body mass index [BMI] 27.0-34.9; class II, BMI 35.0-39.9; class III BMI ≥40.0). RESULTS: Patients with class III obesity had worse Western Ontario McMasters Universities Arthritis Index knee pain (0-20) than the overweight or class I (mean 8.6 vs 7.0; difference 1.5; 95% confidence interval [CI] 1.0-2.1; P < 0.0001) and class II (mean 8.6 vs 7.4; difference 1.1; 95% CI 0.6-1.7; P = 0.0002) obesity groups. The Short Form 36 physical HRQL measure was lower in the class III obesity group compared to the overweight or class I (mean 31.0 vs 37.3; difference -6.2; 95% CI -7.8 to -4.7; P < 0.0001) and class II (mean 31.0 vs 35.0; difference -3.9; 95% CI -5.6 to -2.2; P < 0.0001) obesity groups. The class III obesity group had a base of support (cm) during gait that was wider than that for the overweight or class I (mean 14.0 vs 11.6; difference 3.3; 95% CI 2.6-4.0; P < 0.0001) and class II (mean 14.0 vs 11.6; difference 2.4; 95% CI 1.6-3.2; P < 0.0001) obesity groups. CONCLUSION: Among adults with knee OA, those with class III obesity had significantly higher pain levels and worse physical HRQL and gait characteristics compared to adults with overweight or class I or class II obesity.

The osteoarthritis prevention study (TOPS) - A randomized controlled trial of diet and exercise to prevent Knee Osteoarthritis: Design and rationale.

Background: Osteoarthritis (OA), the leading cause of disability among adults, has no cure and is associated with significant comorbidities. The premise of this randomized clinical trial is that, in a population at risk, a 48-month program of dietary weight loss and exercise will result in less incident structural knee OA compared to control. Methods/design: The Osteoarthritis Prevention Study (TOPS) is a Phase III, assessor-blinded, 48-month, parallel 2 arm, multicenter randomized clinical trial designed to reduce the incidence of structural knee OA. The study objective is to assess the effects of a dietary weight loss, exercise, and weight-loss maintenance program in preventing the development of structural knee OA in females at risk for the disease. TOPS will recruit 1230 ambulatory, community dwelling females with obesity (Body Mass Index (BMI) â€‹≥ â€‹30 â€‹kg/m2) and aged ≥50 years with no radiographic (Kellgren-Lawrence grade ≤1) and no magnetic resonance imaging (MRI) evidence of OA in the eligible knee, with no or infrequent knee pain. Incident structural knee OA (defined as tibiofemoral and/or patellofemoral OA on MRI) assessed at 48-months from intervention initiation using the MRI Osteoarthritis Knee Score (MOAKS) is the primary outcome. Secondary outcomes include knee pain, 6-min walk distance, health-related quality of life, knee joint loading during gait, inflammatory biomarkers, and self-efficacy. Cost effectiveness and budgetary impact analyses will determine the value and affordability of this intervention. Discussion: This study will assess the efficacy and cost effectiveness of a dietary weight loss, exercise, and weight-loss maintenance program designed to reduce incident knee OA. Trial registration: ClinicalTrials.gov Identifier: NCT05946044.

Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial.

IMPORTANCE: Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity. OBJECTIVE: To determine whether a ≥10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone. DESIGN, SETTING, AND PARTICIPANTS: Single-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥55 years with body mass index of 27-41) with pain and radiographic knee OA. INTERVENTIONS: Intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise. MAIN OUTCOMES AND MEASURES: Mechanistic primary outcomes: knee joint compressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0-20), function (range, 0-68), mobility, and health-related quality of life (range, 0-100). RESULTS: Three hundred ninety-nine participants (88%) completed the study. Mean weight loss for diet + exercise participants was 10.6 kg (11.4%); for the diet group, 8.9 kg (9.5%); and for the exercise group, 1.8 kg (2.0%). After 18 months, knee compressive forces were lower in diet participants (mean, 2487 N; 95% CI, 2393 to 2581) compared with exercise participants (2687 N; 95% CI, 2590 to 2784, pairwise difference [Δ](exercise vs diet )= 200 N; 95% CI, 55 to 345; P = .007). Concentrations of IL-6 were lower in diet + exercise (2.7 pg/mL; 95% CI, 2.5 to 3.0) and diet participants (2.7 pg/mL; 95% CI, 2.4 to 3.0) compared with exercise participants (3.1 pg/mL; 95% CI, 2.9 to 3.4; Δ(exercise vs diet + exercise) = 0.39 pg/mL; 95% CI, -0.03 to 0.81; P = .007; Δ(exercise vs diet )= 0.43 pg/mL; 95% CI, 0.01 to 0.85, P = .006). The diet + exercise group had less pain (3.6; 95% CI, 3.2 to 4.1) and better function (14.1; 95% CI, 12.6 to 15.6) than both the diet group (4.8; 95% CI, 4.3 to 5.2) and exercise group (4.7; 95% CI, 4.2 to 5.1, Δ(exercise vs diet + exercise) = 1.02; 95% CI, 0.33 to 1.71; P(pain) = .004; 18.4; 95% CI, 16.9 to 19.9; Δ(exercise vs diet + exercise), 4.29; 95% CI, 2.07 to 6.50; P(function )< .001). The diet + exercise group (44.7; 95% CI, 43.4 to 46.0) also had better physical health-related quality of life scores than the exercise group (41.9; 95% CI, 40.5 to 43.2; Δ(exercise vs diet + exercise) = -2.81; 95% CI, -4.76 to -0.86; P = .005). CONCLUSIONS AND RELEVANCE: Among overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00381290.

Efficacy and Variability in Plasma Nitrite Levels during Long-Term Supplementation with Nitrate Containing Beetroot Juice.

Long-term consumption of beetroot juice on efficacy of converting dietary nitrate to plasma nitrate and nitrite was investigated. Adults were randomized to consume either beetroot juice with 380 mg of nitrate (BR) or a beetroot juice placebo (PL) for 12-weeks. Plasma nitrate and nitrite were measured before and 90-minutes after consuming their intervention beverage. Percent change in nitrite across the 90 min was greater in BR (273.2 ± 39.9%) vs. PL (4.9 ± 36.9%). Long-term consumption of nitrate containing beetroot juice increased fasting nitrate and nitrite plasma levels compared to baseline.

Effect of Vitamin C and Protein Supplementation on Plasma Nitrate and Nitrite Response following Consumption of Beetroot Juice.

Beetroot juice is a food high in nitrate and is associated with cardiometabolic health benefits and enhanced exercise performance through the production of nitric oxide in the nitrate−nitrite−nitric oxide pathway. Since various food components influence this pathway, the aim of this trial was to study the effect of beetroot juice alone and in conjunction with vitamin C or protein on the acute response to plasma nitrate and nitrite levels in healthy middle- to older-aged adults. In this cross-over trial, each participant received, in a randomized order, a single dose of Beet It Sport® alone; Beet It Sport®, plus a 200 mg vitamin C supplement; and Beet It Sport® plus 15 g of whey protein. Plasma levels of nitrate and nitrite were determined prior to and at 1 and 3 h after intervention. Log plasma nitrate and nitrite was calculated to obtain data that were normally distributed, and these data were analyzed using two-way within-factors ANOVA, with time and treatment as the independent factors. There were no statistically significant differences for log plasma nitrate (p = 0.308) or log plasma nitrite (p = 0.391) values across treatments. Log plasma nitrate increased significantly from pre-consumption levels after 1 h (p < 0.001) and 3 h (p < 0.001), but plasma nitrate was lower at 3 h than 1 h (p < 0.001). Log plasma nitrite increased from pre to 1 h (p < 0.001) and 3 h (p < 0.001) with log values at 3 h higher than at 1 h (p = 0.003). In this cohort, we observed no differences in log plasma nitrate and nitrite at 1 h and 3 h after co-ingesting beetroot juice with vitamin C or a whey protein supplement compared to beetroot juice alone. Further research needs to be undertaken to expand the blood-sampling time-frame and to examine factors that may influence the kinetics of the plasma nitrate to nitrite efficacy, such as differences in fluid volume and osmolarity between treatments employed.

The Effects of Graded Protein Intake in Conjunction with Progressive Resistance Training on Skeletal Muscle Outcomes in Older Adults: A Preliminary Trial.

Many studies have evaluated the effects of resistance training (RT) and protein intake to attenuate the age-related loss of skeletal muscle. However, the effects of graded protein intake with conjunctive RT in older adults are unclear. Older adults (n = 18) performed 10 weeks of whole-body RT with progressions to intensity and volume while consuming either a constant protein (CP) diet (0.8−1.0 g/kg/d) with no protein supplement or a graded protein (GP) diet progressing from 0.8 g/kg/d at week 1 to 2.2 g/kg/d at week 10 with a whey protein supplement. Data were collected prior to commencement of the RT protocol (PRE), after week 5 (MID), and after week 10 (POST). Dual Energy X-ray Absorptiometry derived lean/soft tissue mass, ultrasonography derived muscle thickness, and a proxy of muscle quality were taken at PRE and POST, while isokinetic dynamometry derived peak torque were taken at PRE, MID, and POST. This study demonstrated the feasibility of the RT protocol (attendance = 96%), and protein intake protocol (CP in range all weeks; GP deviation from prescribed = 7%). Peak torque, muscle quality scores, and appendicular lean/soft tissue mass demonstrated the main effects of time (p < 0.05) while no other main effects of time or group * time interactions were seen for any measure. In conclusion, RT improved appendicular lean/soft tissue mass, peak torque, and muscle quality, with no differential effects of graded or constant protein intake.

Changes in Body Weight and Knee Pain in Adults With Knee Osteoarthritis Three-and-a-Half Years After Completing Diet and Exercise Interventions: Follow-Up Study for a Single-Blind, Single-Center, Randomized Controlled Trial.

OBJECTIVE: To determine whether long-term diet (D) and exercise (E) interventions, alone or in combination (D+E), have beneficial effects for older adults with knee osteoarthritis (OA) 3.5 years after the interventions end. METHODS: This is a secondary analysis of a subset (n = 94) of the first 184 participants who had successfully completed the Intensive Diet and Exercise in Arthritis (IDEA) trial (n = 399) and who consented to follow-up testing. Participants were older (age ≥55 years), overweight, and obese adults with radiographic and symptomatic knee OA in at least 1 knee who completed 1.5-year D+E (n = 27), D (n = 35), or E (n = 32) interventions and returned for 5-year follow-up testing an average of 3.5 years later. RESULTS: During the 3.5-years following the interventions, weight regain in D+E and D was 5.9 kg (7%) and 3.1 kg (4%), respectively, with a 1-kg (1%) weight loss in E. Compared to baseline, weight (D+E -3.7 kg [P = 0.0007], D -5.8 kg [P < 0.0001], E -2.9 kg [P = 0.003]) and Western Ontario and McMaster Universities Osteoarthritis Index pain subscale scores (D+E -1.2 [P = 0.03], D -1.5 [P = 0.001], E -1.6 [P = 0.0008]) were lower in each group at the 5-year follow-up. The effect of group assignment at the 5-year follow-up was significant for body weight, with D being less than E (-3.5 kg; P = 0.04). CONCLUSION: Older adults with knee OA who completed 1.5-year D or D+E interventions experienced partial weight regain 3.5 years later; yet, relative to baseline, they preserved statistically significant changes in weight loss and reductions in knee pain.

Acute effect of a high nitrate diet on brain perfusion in older adults.

AIMS: Poor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults. METHODS AND RESULTS: In this investigation we administered a high vs. low nitrate diet to older adults (74.7±6.9 years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex. CONCLUSION: These results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning.

State craving, food availability, and reactivity to preferred snack foods.

The startle response has been shown to be useful in studying reactivity to food cues. Following 6h of food deprivation and exposure to neutral and food cues, we examined the role of state craving combined with both a short and long delay of consumption on affect and startle reflex. Participants completed the PANAS, consumed a controlled early morning meal, and experienced 6h of food deprivation. They then reported back to the laboratory, completed a second baseline PANAS, and had their baseline eyeblink EMG startle responses to 100 dB(A) startle probe assessed. Prior to and following the presentation of cues, startle probes were presented and responses were recorded. The PANAS and state craving were also assessed after each cue. Food cues provoked higher levels of state craving than neutral cues and startle responses failed to habituate as quickly to food cues as they did to neutral cues. In addition, cue exposure created the highest NA among high state cravers in the long delay of consumption group. Startle responses differed from NA in that with long delay startle was high irrespective of state craving scores; in the short delay of consumption condition, startle increased linearly with state craving. These results illustrate that state craving and expectations of food availability are important variables in understanding food-related cue reactivity.