Jane Hubbard

Assessment of macronutrient and micronutrient intake in women with anorexia nervosa

OBJECTIVE The purpose of this study is to evaluate the accuracy of diet history compared to observed food intake in the nutritional assessment of women with anorexia nervosa (AN) and healthy age-matched controls. METHOD One-month diet history was compared to 1-day observed food intake in 30 women with AN and 28 control subjects. RESULTS Reported intake by diet history was similar to observed intake for macronutrient composition and fat intake for patients with AN. Reported energy intake was higher than observed intake (1,602 +/- 200 kcal vs. 1,289 +/- 150 kcal, p <.05), but was in agreement with predicted energy expenditure by the Harris-Benedict equation (1,594 +/- 18 kcal, p =.97) in patients with AN. Micronutrient intake by diet history was highly correlated with observed intake in patients with AN. More than one half of the patients with AN failed to meet the recommended dietary allowance (RDA) for vitamin D, calcium, folate, vitamin B12, zinc, magnesium, and copper when assessed by diet history. In contrast to patients with AN, diet history did not correlate with observed intake of energy, macronutrients, or most micronutrients among the controls. DISCUSSION Diet history is an accurate tool to assess fat intake and macronutrient composition in patients with AN and demonstrates significant micronutrient deficiencies in this population. The agreement between total energy intake and predicted energy expenditure supports the overall utility of the diet history in the nutritional assessment of patients with AN.

Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled phase 2 trial

BACKGROUND Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in patients with the disease, and calorie-dense diets increased survival in a mouse model. We aimed to assess the safety and tolerability of two hypercaloric diets in patients with amyotrophic lateral sclerosis receiving enteral nutrition. METHODS In this double-blind, placebo-controlled, randomised phase 2 clinical trial, we enrolled adults with amyotrophic lateral sclerosis from participating centres in the USA. Eligible participants were aged 18 years or older with no history of diabetes or liver or cardiovascular disease, and who were already receiving percutaneous enteral nutrition. We randomly assigned participants (1:1:1) using a computer-generated list of random numbers to one of three dietary interventions: replacement calories using an isocaloric tube-fed diet (control), a high-carbohydrate hypercaloric tube-fed diet (HC/HC), or a high-fat hypercaloric tube-fed diet (HF/HC). Participants received the intervention diets for 4 months and were followed up for 5 months. The primary outcomes were safety and tolerability, analysed in all patients who began their study diet. This trial is registered with ClinicalTrials.gov, number NCT00983983. FINDINGS Between Dec 14, 2009, and Nov 2, 2012, we enrolled 24 participants, of whom 20 started their study diet (six in the control group, eight in the HC/HC group, and six in the HF/HC group). One patient in the control group, one in the HC/HC group, and two in the HF/HC group withdrew consent before receiving the intervention. Participants who received the HC/HC diet had a smaller total number of adverse events than did those in the other groups (23 in the HC/HC group vs 42 in the control group vs 48 in the HF/HC group; overall, p=0.06; HC/HC vs control, p=0.06) and significantly fewer serious adverse events than did those on the control diet (none vs nine; p=0.0005). Fewer patients in the HC/HC group discontinued their study diet due to adverse events (none [0%] of eight in the HC/HC group vs three [50%] of six in the control group). During the 5 month follow-up, no deaths occurred in the nine patients assigned to the HC/HC diet compared with three deaths (43%) in the seven patients assigned to the control diet (log-rank p=0.03). Adverse events, tolerability, deaths, and disease progression did not differ significantly between the HF/HC group and the control group. INTERPRETATION Our results provide preliminary evidence that hypercaloric enteral nutrition is safe and tolerable in patients with amyotrophic lateral sclerosis, and support the study of nutritional interventions in larger randomised controlled trials at earlier stages of the disease. FUNDING Muscular Dystrophy Association, National Center for Research Resources, National Institutes of Health, and Harvard NeuroDiscovery Center.

Effects of a lifestyle modification program in HIV- infected patients with the metabolic syndrome

Objectives:A large percentage of HIV-infected patients receiving HAART develop the metabolic syndrome. In this study, we sought to determine whether lifestyle modification improves metabolic syndrome criteria, including waist circumference, blood pressure, fasting blood sugar, triglycerides, and HDL-cholesterol among HIV-infected patients with the metabolic syndrome. Design:We conducted a randomized, 6-month study in HIV-infected patients with metabolic syndrome as defined by the National Cholesterol Education Program. Subjects were randomly assigned to an intensive lifestyle modification program, which included weekly one-on-one counseling sessions with a registered dietician, or observation (control group). Methods:Metabolic syndrome criteria and cardiovascular parameters, including blood pressure, body composition, submaximal stress testing, lipids and other biochemical parameters were determined. Results:Thirty-four patients were randomly assigned and 28 subjects completed the study. Compared with the control group, subjects randomly assigned to the lifestyle modification program demonstrated significant decreases in waist circumference (−2.6 ± 1.1 versus 1.2 ± 1.0 cm, P = 0.022), systolic blood pressure (−13 ± 4 versus 4 ± 4 mmHg, P = 0.008), hemaglobin A1C (−0.1 ± 0.1 versus 0.2 ± 0.1%, P = 0.017), lipodystrophy score (−1.2 ± 0.3 versus 0.9 ± 0.6, P = 0.006) and increased activity (17.7 ± 14.3 versus −33.1 ± 12.7 metabolic equivalents, P = 0.014) as measured by the Modifiable Activity Questionnaire, but lipid levels did not improve. Conclusion:These data demonstrate that intensive lifestyle modification significantly improved important cardiovascular risk indices in HIV-infected patients with the metabolic syndrome. Lifestyle modification may be a useful strategy to decrease cardiovascular risk in this population.

Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis

BACKGROUND Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in patients with the disease, and calorie-dense diets increased survival in a mouse model. We aimed to assess the safety and tolerability of two hypercaloric diets in patients with amyotrophic lateral sclerosis receiving enteral nutrition. METHODS In this double-blind, placebo-controlled, randomised phase 2 clinical trial, we enrolled adults with amyotrophic lateral sclerosis from participating centres in the USA. Eligible participants were aged 18 years or older with no history of diabetes or liver or cardiovascular disease, and who were already receiving percutaneous enteral nutrition. We randomly assigned participants (1:1:1) using a computer-generated list of random numbers to one of three dietary interventions: replacement calories using an isocaloric tube-fed diet (control), a high-carbohydrate hypercaloric tube-fed diet (HC/HC), or a high-fat hypercaloric tube-fed diet (HF/HC). Participants received the intervention diets for 4 months and were followed up for 5 months. The primary outcomes were safety and tolerability, analysed in all patients who began their study diet. This trial is registered with ClinicalTrials.gov, number NCT00983983. FINDINGS Between Dec 14, 2009, and Nov 2, 2012, we enrolled 24 participants, of whom 20 started their study diet (six in the control group, eight in the HC/HC group, and six in the HF/HC group). One patient in the control group, one in the HC/HC group, and two in the HF/HC group withdrew consent before receiving the intervention. Participants who received the HC/HC diet had a smaller total number of adverse events than did those in the other groups (23 in the HC/HC group vs 42 in the control group vs 48 in the HF/HC group; overall, p=0.06; HC/HC vs control, p=0.06) and significantly fewer serious adverse events than did those on the control diet (none vs nine; p=0.0005). Fewer patients in the HC/HC group discontinued their study diet due to adverse events (none [0%] of eight in the HC/HC group vs three [50%] of six in the control group). During the 5 month follow-up, no deaths occurred in the nine patients assigned to the HC/HC diet compared with three deaths (43%) in the seven patients assigned to the control diet (log-rank p=0.03). Adverse events, tolerability, deaths, and disease progression did not differ significantly between the HF/HC group and the control group. INTERPRETATION Our results provide preliminary evidence that hypercaloric enteral nutrition is safe and tolerable in patients with amyotrophic lateral sclerosis, and support the study of nutritional interventions in larger randomised controlled trials at earlier stages of the disease. FUNDING Muscular Dystrophy Association, National Center for Research Resources, National Institutes of Health, and Harvard NeuroDiscovery Center.

Practical guide to measuring physical activity.

R ESEARCH HAS DEMONSTRATED THE BENEFITS OF physical activity and the negative consequences of sedentary behavior for physical and mental wellbeing. Thus, physical activity has become increasingly prominent as an intervention tool; however, research is often hindered by the challenge of employing a valid, reliable measure that also adequately satisfies the research question or design. The doubly labeled water method (DLW) remains the gold standard for assessing total energy expenditure; however, it is not often used for research studies because it is expensive, has high subject burden, is timeintensive, and cannot capture qualitative data. The aim of our commentary is to summarize the main methods of measuring physical activity as well as offer examples of their uses in research trials.

Dietary fat intake and relationship to serum lipid levels in HIV-infected patients with metabolic abnormalities in the HAART era.

Objective:To evaluate dietary intake and its relationship to lipid parameters in HIV-infected patients with metabolic abnormalities. Method:We prospectively determined dietary intake (4-day food records or 24-h recall) in 356 HIV-infected patients and 162 community-derived HIV-negative controls evaluated for metabolic studies between 1998–2005. Differences in dietary intake between HIV-infected patients and non-HIV-infected controls, in relation to the established 2005 USDA (United States Department of Agriculture) Recommended Dietary Guidelines, were determined. The relationship between dietary fat intake and serum lipid levels among HIV-infected individuals was also evaluated. Results:Assessment of dietary intake in this group of HIV-infected patients demonstrated increased intake of total dietary fat (P < 0.05), saturated fat (P = 0.006), and cholesterol (P = 0.006) as well as a greater percentage of calories from saturated fat (P = 0.002) and from trans fat (P = 0.02), despite similar caloric intake to the control individuals. A significantly higher percentage of HIV-infected patients were above the 2005 USDA Recommended Dietary Guidelines for saturated fat (> 10%/day) (76.0% HIV vs. 60.9% controls, P = 0.003), and cholesterol (> 300 mg/day) (49.7% HIV vs. 37.9% controls, P = 0.04). Saturated fat intake was strongly associated with triglyceride level [triglyceride level increased 8.7 mg/dl (parameter estimate) per gram of increased saturated fat intake, P = 0.005] whereas total fat was inversely associated with triglyceride level [triglyceride level decreased 3.0 mg/dl (parameter estimate) per gram of increased total fat intake, P = 0.02] among HIV-infected individuals. Conclusions:Increased intake of saturated fat is seen and contributes to hypertriglyceridemia among HIV-infected patients who have developed metabolic abnormalities. Increased saturated fat intake should be targeted for dietary modification in this population.

Validation of a Food Frequency Questionnaire for Determining Calcium and Vitamin D Intake by Adolescent Girls with Anorexia Nervosa

Assessing calcium and vitamin D intake becomes important in conditions associated with low bone density such as anorexia nervosa. Food records that assess intake over a representative time period are used in research and sometimes clinical settings. However, compliance in adolescents can be suboptimal. This study was undertaken to determine the validity of a food frequency questionnaire (FFQ) for assessing calcium and vitamin D intake in adolescent girls with anorexia nervosa and healthy girls compared to validated food records assessing intake during a 4-day period, the hypothesis being that intake would be adequately predicted by the FFQ. Thirty-six girls with anorexia nervosa and 39 healthy girls aged 12 to 18 years completed both the food record and the FFQ. An additional 31 subjects (20 with anorexia nervosa, 11 controls) completed the FFQ, but not the food record, and one girl with anorexia nervosa completed the food record, but not the FFQ. Subjects demonstrated greater compliance with the FFQ (99%) than the food record (71%). Daily calcium and vitamin D intake calculated using the food record and FFQ did not differ, although the FFQ tended to under-report vitamin D intake corrected for energy intake. Using quartile analysis, no gross misclassification was noted of calcium or vitamin D intake calculated using the food record or FFQ in girls with anorexia nervosa. Strong correlations were observed for daily vitamin D intake derived from the FFQ vs the food record, particularly in girls with anorexia nervosa (r=0.78, P<0.0001). Less robust correlations were observed for calcium intake (r=0.65, P<0.0001). The FFQ used in this study can be effectively used to assess daily calcium and vitamin D intake in adolescent girls with anorexia nervosa.

Sustained Anabolic Effects of Long-Term Androgen Administration in Men with AIDS Wasting

Fifty-one human immunodeficiency virus-positive men with hypogonadism and wasting were randomized to receive testosterone enanthate, 300 mg i.m. every 3 weeks, or placebo for 6 months, followed by open-label testosterone administration for 6 months. Subjects initially randomized to placebo gained lean body mass (LBM) only after crossover to testosterone administration (mean change +/- standard error of the mean, -0.6 +/- 0.7 kg [months 0-6] vs. 1.9 +/- 0.7 kg [months 6-12]; P = .03). In contrast, subjects initially randomized to testosterone continued to gain LBM during open-label administration (2.0 +/- 0.7 kg [months 0-6] vs. 1.6 +/- 0.6 kg [months 6-12]; P = .62) and had gained more LBM at 1 year than did subjects receiving testosterone for only the final 6 months of the study (3.7 +/- 0.8 kg vs. 1.0 +/- 1.0 kg; P = .05). Testosterone administration results in sustained increases in LBM during 1 year of therapy in hypogonadal men with AIDS wasting.

Decreased respiratory quotient in relation to resting energy expenditure in HIV-infected and noninfected subjects.

The purpose of this study was to evaluate the relationship of respiratory quotient (RQ), a surrogate marker of substrate oxidation, as well as body composition and dietary intake to resting energy expenditure (REE) among HIV-infected patients in the current era of highly active antiretroviral therapy and among non-HIV-infected control subjects. Resting energy expenditure is increased in HIV-infected patients; but little is known regarding the potential contribution of altered substrate metabolism, body composition, and dietary intake to increased energy expenditure in this population. Respiratory quotient, REE, body composition, and dietary intake parameters were assessed in 283 HIV-infected patients and 146 community-derived HIV-negative controls who were evaluated for metabolic studies between 1998 and 2005. Respiratory quotient was lower (0.83 +/- 0.00 vs 0.85 +/- 0.01, P = .005), whereas REE adjusted for fat-free mass (FFM) was higher (31.8 +/- 0.3 vs 29.8 +/- 0.3 kcal/[d kg], P < or = .0001), in HIV-infected compared with control subjects. In multivariate modeling among HIV-infected patients, including age, sex, and parameters of immune function, FFM (beta = 24.811334, P < .0001), visceral adiposity (beta = .7182746, P = .008), and total body fat (beta = 8.0506839, P = .041) were positively associated with REE, whereas RQ was negatively associated with REE (beta = -528.4808, P = .024). Overall r(2) was equal to 0.705 and P was less than .0001 for the model. In control subjects, by contrast, only visceral adiposity (beta = 1.0612073, P = .004), total body fat (beta = 15.805547, P = .010), and FFM (beta = 22.613005, P < .0001) were significant predictors of REE; and there was no relationship with RQ. Overall r(2) was equal to 0.825 and P was less than .0001 for the model. These data suggest that alterations in substrate metabolism may contribute to increased REE in HIV-infected patients compared with control subjects.

Macronutrient intake associated with weight gain in adolescent girls with anorexia nervosa

OBJECTIVE Adolescents and women with anorexia nervosa (AN) are known to severely restrict total calorie and fat intake. However, data are limited regarding specific macronutrient intake associated with weight gain in AN. OBJECTIVE To prospectively investigate dietary macronutrient composition associated with weight gain in adolescent girls with AN. METHOD A prospective naturalistic study of 90 girls 12-18 years old; 45 with AN and 45 healthy normal-weight-controls over a 6-12-month period. Participants completed four-day food diaries and underwent body composition assessment using dual energy X-ray absorptiometry. Weight gain was defined as a ≥10% increase in body mass index (BMI) from baseline. RESULTS Baseline clinical characteristics did not differ between girls with AN who did not gain weight (AN-0) versus those who did (AN-1) over the following 6-12 month period except for percentage of calories from proteins (p = 0.046). At 6-12 month follow-up, AN-1 consumed a lower percentage of total calories from protein (p = .001), and a higher percentage of total calories from fat (p = .02) compared to AN-0. AN-1 had a significant increase in the percentage of total calories obtained from and poly-unsaturated-fatty acids (PUFA) (p = 0.006) compared to AN-0, between baseline and follow-up. Within the AN group, BMI at follow-up was associated positively with percentage of total calories obtained from fat, MUFA, and PUFA (p < .05) at 6/12 months, and inversely with the percentage of total calories obtained from carbohydrates and proteins (p = .03). DISCUSSION Consuming a greater proportion of total calories from fat is associated with weight gain in adolescent girls with AN.