Amy C. Ellis

Respiratory quotient predicts fat mass gain in premenopausal women.

High respiratory quotient (RQ) has been associated with fat mass (FM) gain in some, but not all studies. Variability among results may reflect differences in the RQ variable measured (fasting vs. 24‐h) or may be due to differences in control for factors that affect RQ, such as diet, energy balance, circulating insulin, and insulin sensitivity. The objective of this study was to determine whether different RQ values (fasting, sleeping, nonsleeping, and 24‐h) would predict change in FM over 2 years in obesity‐prone women, controlling for diet and adjusting for energy balance, circulating insulin, and insulin sensitivity. Participants were 33 previously overweight premenopausal women. Fasting, sleeping, nonsleeping, and 24‐h RQ values were measured during controlled‐diet conditions by respiratory chamber calorimetry. Intravenous glucose tolerance tests were also performed to adjust for fasting insulin, acute insulin response to glucose, and insulin sensitivity. Over the following 2 years, changes in FM were tracked annually by dual energy X‐ray absorptiometry. High nonsleeping RQ (NSRQ) predicted 2‐year change in FM independently of energy balance, circulating insulin, and insulin sensitivity. This observation suggests that low postprandial fat oxidation may uniquely predispose obesity‐prone individuals to accrual of adipose tissue.

The Role of Creatine in the Management of Amyotrophic Lateral Sclerosis and Other Neurodegenerative Disorders

Creatine is consumed in the diet and endogenously synthesised in the body. Over the past decade, the ergogenic benefits of synthetic creatine monohydrate have made it a popular dietary supplement, particularly among athletes. The anabolic properties of creatine also offer hope for the treatment of diseases characterised by weakness and muscle atrophy. Moreover, because of its cellular mechanisms of action, creatine offers potential benefits for diseases involving mitochondrial dysfunction. Recent data also support the hypothesis that creatine may have a neuroprotective effect.Amyotrophic lateral sclerosis (ALS) is characterised by progressive degeneration of motor neurons, resulting in weakening and atrophy of skeletal muscles. In patients with this condition, creatine offers potential benefits in terms of facilitating residual muscle contractility as well as improving neuronal function. It may also help stabilise mitochondrial dysfunction, which plays a key role in the pathogenesis of ALS. Indeed, the likely multifactorial aetiology of ALS means the combined pharmacodynamic properties of creatine offer promise for the treatment of this condition.Evidence from available animal models of ALS supports the utility of treatment with creatine in this setting. Limited data available in other neuromuscular and neurodegenerative diseases further support the potential benefit of creatine monohydrate in ALS. However, few randomised, controlled trials have been conducted. To date, two clinical trials of creatine monohydrate in ALS have been completed without demonstration of significant improvements in overall survival or a composite measure of muscle strength. These trials have also posed unanswered questions about the optimal dosage of creatine and its beneficial effects on muscle fatigue, a measure distinct from muscle strength. A large, multicentre, clinical trial is currently underway to further investigate the efficacy of creatine monohydrate in ALS and address these unresolved issues. Evidence to date shows that creatine supplementation has a good safety profile and is well tolerated by ALS patients.The purpose of this article is to provide a short, balanced review of the literature concerning creatine monohydrate in the treatment of ALS and related neurodegenerative diseases. The pharmacokinetics and rationale for the use of creatine are described along with available evidence from animal models and clinical trials for ALS and related neurodegenerative or neuromuscular diseases.

Effects of diet macronutrient composition on body composition and fat distribution during weight maintenance and weight loss

Qualitative aspects of diet may affect body composition and propensity for weight gain or loss. We tested the hypothesis that consumption of a relatively low glycemic load (GL) diet would reduce total and visceral adipose tissue under both eucaloric and hypocaloric conditions.

Nutrition and Dietary Supplements in Motor Neuron Disease

Compromised nutrition leading to weight loss is a common and significant problem in the amyotrophic lateral sclerosis (ALS) patient population. The benefit of aggressive and early nutritional therapy can profoundly influence the disease course, quality of life, and survival. This article reviews the role of nutrition, both as sustenance and treatment for patients who have ALS. Self-medication with dietary supplements has become increasingly popular within this patient population. Despite their popularity, the efficacy of these compounds has been largely unsupported by formal clinical trials. Available data will be highlighted to provide a basis upon which to advise patients requesting guidance.

Ethnic differences in glucose disposal, hepatic insulin sensitivity, and endogenous glucose production among African American and European American women

Intravenous glucose tolerance tests have demonstrated lower whole-body insulin sensitivity (S(I)) among African Americans (AA) compared with European Americans (EA). Whole-body S(I) represents both insulin-stimulated glucose disposal, primarily by skeletal muscle, and insulins suppression of endogenous glucose production (EGP) by liver. A mathematical model was recently introduced that allows for distinction between disposal and hepatic S(I). The purpose of this study was to examine specific indexes of S(I) among AA and EA women to determine whether lower whole-body S(I) in AA may be attributed to insulin action at muscle, liver, or both. Participants were 53 nondiabetic, premenopausal AA and EA women. Profiles of EGP and indexes of Disposal S(I) and Hepatic S(I) were calculated by mathematical modeling and incorporation of a stable isotope tracer ([6,6-(2)H(2)]glucose) into the intravenous glucose tolerance test. Body composition was assessed by dual-energy x-ray absorptiometry. After adjustment for percentage fat, both Disposal S(I) and Hepatic S(I) were lower among AA (P = .009 for both). Time profiles for serum insulin and EGP revealed higher peak insulin response and corresponding lower EGP among AA women compared with EA. Indexes from a recently introduced mathematical model suggest that lower whole-body S(I) among nondiabetic AA women is due to both hepatic and peripheral components. Despite lower Hepatic S(I), AA displayed lower EGP, resulting from higher postchallenge insulin levels. Future research is needed to determine the physiological basis of lower insulin sensitivity among AA and its implications for type 2 diabetes mellitus risk.

A higher-carbohydrate, lower-fat diet reduces fasting glucose concentration and improves β-cell function in individuals with impaired fasting glucose.

The objective was to examine the effects of diet macronutrient composition on insulin sensitivity, fasting glucose, and β-cell response to glucose. Participants were 42 normal glucose-tolerant (NGT; fasting glucose <100 mg/dL) and 27 impaired fasting glucose (IFG), healthy, overweight/obese (body mass index, 32.5 ± 4.2 kg/m(2)) men and women. For 8 weeks, participants were provided with eucaloric diets, either higher carbohydrate/lower fat (55% carbohydrate, 18% protein, 27% fat) or lower carbohydrate/higher fat (43:18:39). Insulin sensitivity and β-cell response to glucose (basal, dynamic [PhiD], and static) were calculated by mathematical modeling using glucose, insulin, and C-peptide data obtained during a liquid meal tolerance test. After 8 weeks, NGT on the higher-carbohydrate/lower-fat diet had higher insulin sensitivity than NGT on the lower-carbohydrate/higher fat diet; this pattern was not observed among IFG. After 8 weeks, IFG on the higher-carbohydrate/lower-fat diet had lower fasting glucose and higher PhiD than IFG on the lower-carbohydrate/higher-fat diet; this pattern was not observed among NGT. Within IFG, fasting glucose at baseline and the change in fasting glucose over the intervention were inversely associated with baseline PhiD (-0.40, P < .05) and the change in PhiD (-0.42, P < .05), respectively. Eight weeks of a higher-carbohydrate/lower-fat diet resulted in higher insulin sensitivity in healthy, NGT, overweight/obese individuals, and lower fasting glucose and greater glucose-stimulated insulin secretion in individuals with IFG. If confirmed, these results may have an impact on dietary recommendations for overweight individuals with and without IFG.

Which Equation Best Predicts Energy Expenditure in Amyotrophic Lateral Sclerosis

OBJECTIVE The purpose of this study was to compare measured resting energy expenditure (REE) with estimates from three common prediction equations with the goal of determining which equation best estimates REE in amyotrophic lateral sclerosis (ALS). DESIGN Cross-sectional measurements of REE from indirect calorimetry were compared to calculations from the Harris Benedict, Mifflin-St Jeor, and Ireton-Jones equations. Additional measurements to identify predictors of REE included pulmonary function tests, fat-free mass by bioelectrical impedance, and anthropometrics. SUBJECTS/SETTING Participants were 56 men and women with ALS. For comparison, subjects were categorized by disease progression into three groups. STATISTICAL ANALYSES Pearson correlations and paired t tests were used to compare measured REE with predicted REE from each equation, and the accuracy of each equation was quantified by the root mean squared prediction error and the percentage of REE estimates within 10% of measured values. Bias for each equation was calculated as the mean percentage difference between calculated and measured REE. Multiple linear regression was used to determine the best predictor variables for REE. RESULTS Across the disease spectrum, the Harris Benedict and Mifflin-St Jeor equations provided clinically acceptable estimates of REE, whereas the Ireton-Jones equations consistently overestimated REE. The best predictors of REE among this cohort were fat-free mass, sex, and age. CONCLUSIONS When estimating energy requirements for patients with ALS, clinicians should choose prediction equations that incorporate sex and age as predictor variables, such as the Harris Benedict and Mifflin-St Jeor equations.

A theoretically based Behavioral Nutrition Intervention for Community Elders at high risk: the B-NICE randomized controlled clinical trial.

We conducted a study designed to evaluate the efficacy and feasibility of a multilevel self-management intervention to improve nutritional intake in a group of older adults receiving Medicare home health services who were at especially high risk for experiencing undernutrition. The Behavioral Nutrition Intervention for Community Elders (B-NICE) trial used a prospective randomized controlled design to determine whether individually tailored counseling focused on social and behavioral aspects of eating resulted in increased caloric intake and improved nutrition-related health outcomes in a high-risk population of older adults. The study was guided by the theoretical approaches of the Ecological Model and Social Cognitive Theory. The development and implementation of the B-NICE protocol, including the theoretical framework, methodology, specific elements of the behavioral intervention, and assurances of the treatment fidelity, as well as the health policy implications of the trial results, are presented in this article.

Dietary macronutrient composition affects β cell responsiveness but not insulin sensitivity

BACKGROUND Altering dietary carbohydrate or fat content may have chronic effects on insulin secretion and sensitivity, which may vary with individual metabolic phenotype. OBJECTIVE The objective was to evaluate the contribution of tightly controlled diets differing in carbohydrate and fat content for 8 wk to insulin sensitivity and β cell responsiveness and whether effects of diet would vary with race, free-living diet, or insulin response. DESIGN Healthy overweight men and women (36 European Americans, 33 African Americans) were provided with food for 8 wk and received either a eucaloric standard diet (55% carbohydrate, 27% fat) or a eucaloric reduced-carbohydrate (RedCHO)/higher-fat diet (43% carbohydrate, 39% fat). Insulin sensitivity and β cell responsiveness were assessed at baseline and 8 wk by using a liquid meal tolerance test. RESULTS Insulin sensitivity did not change with diet (P = 0.1601). Static β cell response to glucose (ФS) was 28.5% lower after the RedCHO/higher-fat diet. Subgroup analyses indicated that lower ФS with the RedCHO/higher-fat diet occurred primarily among African Americans. A significant inverse association was observed for change in glucose area under the curve compared with change in ФS. CONCLUSIONS Consumption of a eucaloric 43% carbohydrate/39% fat diet for 8 wk resulted in down-regulation of β cell responsiveness, which was influenced by baseline phenotypic characteristics. Further study is needed to probe the potential cause-and-effect relation between change in ФS and change in glucose tolerance. This trial is registered at clinicaltrials.gov as NCT00726908.

Race Differences in the Association of Oxidative Stress With Insulin Sensitivity in African- and European-American Women

Excessive metabolism of glucose and/or fatty acids may impair insulin signaling by increasing oxidative stress. The objective of this study was to examine the association between insulin sensitivity and protein carbonyls, a systemic marker of oxidative stress, in healthy, nondiabetic women, and to determine if the relationship differed with race. Subjects were 25 African‐Americans (AA, BMI 28.4 ± 6.2 kg/m2, range 18.8–42.6 kg/m2; age 33.1 ± 13.5 years, range 18–58 years) and 28 European‐Americans (EA, BMI 26.2 ± 5.9 kg/m2, range 18.7–48.4 kg/m2; age 31.6 ± 12.4 years, range 19–58 years). Insulin sensitivity was determined using an intravenous glucose tolerance test incorporating [6,6‐2H2]‐glucose, and a two‐compartment mathematical model. Multiple linear regression results indicated that insulin sensitivity was inversely associated with protein carbonyls in AA (standardized regression coefficient −0.47, P < 0.05) but not EA (0.01, P = 0.945), after adjusting for %body fat. In contrast, %body fat was significantly and positively associated with insulin sensitivity in EA (−0.54, P < 0.01) but not AA (−0.24, P = 0.196). Protein carbonyls were associated with free fatty acids (FFA) in AA (r = 0.58, P < 0.01) but not EA (r = −0.11, P = 0.59). When subjects were divided based on median levels of fasting glucose and FFA, those with higher glucose/FFA concentrations had a significantly greater concentration of circulating protein carbonyls compared to those with lower glucose/FFA concentrations (P < 0.05). These results suggest that oxidative stress independently contributes to insulin sensitivity among AA women. Further, this association in AA may be mediated by circulating FFA and/or glucose.