Nonprescribed physical activity energy expenditure is maintained with structured exercise and implicates a compensatory increase in energy intake

James E Turner, Daniella Markovitch, James A Betts and Dylan Thompson

Background: Exercise interventions elicit only modest weight loss, which might reflect a compensatory reduction in nonprescribed physical activity energy expenditure (PAEE).

Objective: The objective was to investigate whether there is a reduction in nonprescribed PAEE as a result of participation in a 6-mo structured exercise intervention in middle-aged men.

Desing: Sedentary male participants [age: 54 ± 5 y; body mass index (in kg/m2): 28 ± 3] were randomly assigned to a 6-mo progressive exercise (EX) or control (CON) group. Energy expenditure during structured exercise (prescribed PAEE) and nonprescribed PAEE were determined with the use of synchronized accelerometry and heart rate before the intervention, during the intervention (2, 9, and 18 wk), and within a 2-wk period of detraining after the intervention.

Results: Structured prescribed exercise increased total PAEE and had no detrimental effect on nonprescribed PAEE. Indeed, there was a trend for greater nonprescribed PAEE in the EX group (P = 0.09). Weight loss in the EX group (–1.8 ± 2.2 kg compared with +0.2 ± 2.2 kg in the CON group, P < 0.02) reflected only 40% of the 300–373 kcal/kg body mass potential energy deficit from prescribed exercise. Serum leptin concentration decreased by 24% in the EX group (compared with 3% in the CON group, P < 0.03), and we estimate that this was accompanied by a compensatory increase in energy intake of 100 kcal/d.

Conclusions: The adoption of regular structured exercise in previously sedentary, middle-aged, and overweight men does not result in a negative compensatory reduction in nonprescribed physical activity. The less-than-predicted weight loss is likely to reflect a compensatory increase in energy intake in response to a perceived state of relative energy insufficiency.

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Dairy calcium intake, serum vitamin D, and successful weight loss

Danit R Shahar, Dan Schwarzfuchs, Drora Fraser, Hillel Vardi, Joachim Thiery, Georg Martin Fiedler, Matthias Blüher, Michael Stumvoll, Meir J Stampfer, Iris Shai and for the DIRECT Group

Background: The role of dairy calcium intake and serum vitamin D concentrations in weight loss is controversial.

Objective: The objective was to assess the association of dairy calcium intake and serum vitamin D with weight loss.

Desing: We analyzed data from participants in the 2-y Dietary Intervention Randomized Controlled Trial (DIRECT) [n = 322; mean body mass index (BMI; in kg/m2): 31; mean age: 52 y]. A representative sample (n = 126) was followed for 6 mo for serum vitamin D changes.

Results: Baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations decreased significantly across the tertiles of baseline BMI (25.6 ± 8.0, 24.1 ± 8.9, and 22.9 ± 6.8 ng/mL, respectively; P for trend = 0.02). Baseline concentrations of vitamin D and dairy calcium intake were not associated with subsequent weight loss. However, in repeated-measures models adjusted for age, sex, baseline BMI, total fat intake, and diet group assignment, higher 6-mo tertile levels of dairy calcium intake (median for tertiles: 156.5, 358.0, and 582.9 mg/d, respectively) and serum 25(OH)D (14.5, 21.2, and 30.2 ng/mL, respectively) were associated with increased weight loss across the 2-y intervention (–3.3, –3.5, and –5.3 kg, respectively, for dairy calcium; P = 0.043; –3.1, –3.8, and –5.6 kg, respectively, for vitamin D; P = 0.013). In a multivariate logistic regression adjusted simultaneously for age, sex, baseline BMI, total fat intake, diet group, vitamin D concentration, and dairy calcium, an increase of 1 SD in dairy calcium intake increased the likelihood of weight loss of >4.5 kg in the preceding 6 mo [odds ratio (OR): 1.45; P = 0.046]. A similar increase was seen for serum 25(OH)D at the 6-mo point (OR: 1.7; P = 0.009).

Conclusions: Our study suggests that both higher dairy calcium intake and increased serum vitamin D are related to greater diet-induced weight loss. This trial was registered at clinicaltrials.gov as NCT00160108.

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Effect of mother's weight on infant's microbiota acquisition, composition, and activity during early infancy: a prospective follow-up study initiated in early pregnancy

Maria Carmen Collado, Erika Isolauri, Kirsi Laitinen and Seppo Salminen

Background: It has been reported that deviations in gut microbiota composition may predispose toward obesity, and specific groups of commensal gut bacteria may harvest energy from food more efficiently than others. Alterations in microbiota compositions of mothers may be transferred to infants and lead to an increased risk of overweight.

Objective: We analyzed the fecal microbiota composition of infants of overweight and normal-weight mothers and assessed the relations of weight and excessive weight gain of mothers during pregnancy on the microbiota of infants.

Desing: Mothers (n = 16) whose prepregnancy body mass index (BMI; in kg/m2) was 25 were selected with their infants from a prospective follow-up study of 256 women. Women with a BMI <25 (n = 26) and their infants served as control subjects. At the ages of 1 and 6 mo, infant stool samples were available for the analysis of microbiota composition by fluorescence in situ hybridization combined with flow cytometry and quantitative real-time polymerase chain reaction.

Results: Infants’ fecal microbial composition was related to the weight and weight gain of their mothers during pregnancy. Fecal Bacteroides and Staphylococcus concentrations were significantly higher in infants of overweight mothers during the first 6 mo. Higher weights and BMIs of mothers were related to higher concentrations of Bacteroides, Clostridium, and Staphylococcus and lower concentrations of the Bifidobacterium group. Prevalences of Akkermansia muciniphila, Staphylococcus, and Clostridium difficile groups were lower in infants of normal-weight mothers and of mothers with normal weight gains during pregnancy.

Conclusions: The composition and development of infant gut microbiota are influenced by BMI, weight, and weight gain of mothers during pregnancy.

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Dietary intake and status of n–3 polyunsaturated fatty acids in a population of fish-eating and non-fish-eating meat-eaters, vegetarians, and vegans and the precursor-product ratio of -linolenic acid to long-chain n–3 polyunsaturated fatty acids: results from the EPIC-Norfolk cohort

Ailsa A Welch, Subodha Shakya-Shrestha, Marleen AH Lentjes, Nicholas J Wareham and Kay-Tee Khaw

Background: Intakes of n–3 (omega-3) polyunsaturated fatty acids (PUFAs) are important for health. Because fish is the major source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), non-fish-eaters may have suboptimal n–3 PUFA status, although the importance of the conversion of plant-derived -linolenic acid (ALA) to EPA and DHA is debated.

Objective: The objective was to determine intakes, food sources, and status of n–3 PUFAs according to dietary habit (fish-eaters and non-fish-eating meat-eaters, vegetarians, or vegans) and estimated conversion between dietary ALA and circulating long-chain n–3 PUFAs.

Desing: This study included 14,422 men and women aged 39–78 y from the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk cohort with 7-d diary data and a substudy in 4902 individuals with plasma phospholipid fatty acid measures. Intakes and status of n–3 PUFAs were measured, and the precursor-product ratio of ALA to circulating n–3 PUFAs was calculated.

Results: Most of the dietary intake of EPA and DHA was supplied by fish; however, meat was the major source in meat-eaters, and spreading fats, soups, and sauces were the major sources in vegetarians. Total n–3 PUFA intakes were 57–80% lower in non-fish-eaters than in fish-eaters, but status differences were considerably smaller. The estimated precursor-product ratio was greater in women than in men and greater in non-fish-eaters than in fish-eaters.

Conclusions: Substantial differences in intakes and in sources of n–3 PUFAs existed between the dietary-habit groups, but the differences in status were smaller than expected, possibly because the precursor-product ratio was greater in non-fish-eaters than in fish-eaters, potentially indicating increased estimated conversion of ALA. If intervention studies were to confirm these findings, it could have implications for fish requirements.

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Nutrition in infancy and long-term risk of obesity: evidence from 2 randomized controlled trials

Atul Singhal, Kathy Kennedy, Julie Lanigan, Mary Fewtrell, Tim J Cole, Terence Stephenson, Alun Elias-Jones, Lawrence T Weaver, Samuel Ibhanesebhor, Peter D MacDonald, Jacques Bindels and Alan Lucas

Background: Growth acceleration as a consequence of relative overnutrition in infancy has been suggested to increase the risk of later obesity. However, few studies have investigated this association by using an experimental study design.

Objective: We investigated the effect of early growth promotion on later body composition in 2 studies of infants born small for gestational age (weight <10th percentile in study 1 and <20th percentile in study 2).

Desing: We reviewed a subset of children (n = 153 of 299 in study 1 and 90 of 246 in study 2) randomly assigned at birth to receive either a control formula or a nutrient-enriched formula (which contained 28–43% more protein and 6–12% more energy than the control formula) at 5–8 y of age. Fat mass was measured by using bioelectric impedance analysis in study 1 and deuterium dilution in study 2.

Results: Fat mass was lower in children assigned to receive the control formula than in children assigned to receive the nutrient-enriched formula in both trials [mean (95% CI) difference for fat mass after adjustment for sex: study 1: –38% (–67%, –10%), P = 0.009; study 2: –18% (–36%, –0.3%), P = 0.04]. In nonrandomized analyses, faster weight gain in infancy was associated with greater fat mass in childhood.

Conclusions: In 2 prospective randomized trials, we showed that a nutrient-enriched diet in infancy increased fat mass later in childhood. These experimental data support a causal link between faster early weight gain and a later risk of obesity, have important implications for the management of infants born small for gestational age, and suggest that the primary prevention of obesity could begin in infancy.

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Perioperative arginine-supplemented nutrition in malnourished patients with head and neck cancer improves long-term survival

Nikki Buijs, Marian AE van Bokhorst-de van der Schueren, Jacqueline AE Langius, C Rene Leemans, Dirk J Kuik, Mechteld AR Vermeulen and Paul AM van Leeuwen

Background: Plasma arginine concentrations are lower in patients with cancer, which indicates that arginine metabolism may be disturbed in these patients. Arginine supplementation has been associated with positive effects on antitumor mechanisms and has been shown to reduce tumor growth and to prolong survival. Furthermore, the prognosis of patients with head and neck cancer remains disappointing. Insufficient intake frequently leads to malnutrition, which contributes to high morbidity and mortality rates.

Objective: The aim of this study was to assess the long-term effects of perioperative arginine supplementation in severely malnourished patients with head and neck cancer.

Desing: In this double-blind, randomized, controlled trial, we randomly assigned 32 severely malnourished patients with head and neck cancer to receive 1) standard perioperative enteral nutrition (n = 15) or 2) arginine-supplemented perioperative enteral nutrition (n = 17). The primary outcome was long-term ( 10 y) survival. Secondary outcomes included the long-term appearance of locoregional recurrence, distant metastases, and second primary tumors.

Results: No significant differences in baseline characteristics were observed between groups. The group receiving arginine-enriched nutrition had a significantly better overall survival (P = 0.019) and better disease-specific survival (P = 0.022). Furthermore, the arginine-supplemented group had a significantly better locoregional recurrence-free survival (P = 0.027). No significant difference in the occurrence of distant metastases or occurrence of a second primary tumor was observed between the groups.

Conclusions: Perioperative arginine-enriched enteral nutrition significantly improved the long-term overall survival and long-term disease-specific survival in malnourished patients with head and neck cancer.

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Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis

Francesco Sofi, Rosanna Abbate, Gian Franco Gensini and Alessandro Casini

Background: The Mediterranean diet has long been reported to be protective against the occurrence of several different health outcomes.

Objective: We aimed to update our previous meta-analysis of published cohort prospective studies that investigated the effects of adherence to the Mediterranean diet on health status.

Desing: We conducted a comprehensive literature search through electronic databases up to June 2010.

Results: The updated review process showed 7 prospective studies published in the past 2 y that were not included in the previous meta-analysis (1 study for overall mortality, 3 studies for cardiovascular incidence or mortality, 1 study for cancer incidence or mortality, and 2 studies for neurodegenerative diseases). These recent studies included 2 health outcomes not previously investigated (ie, mild cognitive impairment and stroke). The meta-analysis for all studies with a random-effects model that was conducted after the inclusion of these recent studies showed that a 2-point increase in adherence to the Mediterranean diet was associated with a significant reduction of overall mortality [relative risk (RR) = 0.92; 95% CI: 0.90, 0.94], cardiovascular incidence or mortality (RR = 0.90; 95% CI: 0.87, 0.93), cancer incidence or mortality (RR = 0.94; 95% CI: 0.92, 0.96), and neurodegenerative diseases (RR = 0.87; 95% CI: 0.81, 0.94). The meta-regression analysis showed that sample size was the most significant contributor to the model because it significantly influenced the estimate of the association for overall mortality.

Conclusions: This updated meta-analysis confirms, in a larger number of subjects and studies, the significant and consistent protection provided by adherence to the Mediterranean diet in relation to the occurrence of major chronic degenerative diseases.

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Skipping breakfast: longitudinal associations with cardiometabolic risk factors in the Childhood Determinants of Adult Health Study

Kylie J Smith, Seana L Gall, Sarah A McNaughton, Leigh Blizzard, Terence Dwyer, and Alison J Venn

Background: The long-term effects of skipping breakfast on cardiometabolic health are not well understood.

Objective: The objective was to examine longitudinal associations of breakfast skipping in childhood and adulthood with cardiometabolic risk factors in adulthood.

Desing: In 1985, a national sample of 9–15-y-old Australian children reported whether they usually ate breakfast before school. During follow-up in 2004–2006, 2184 participants (26–36 y of age) completed a meal-frequency chart for the previous day. Skipping breakfast was defined as not eating between 0600 and 0900. Participants were classified into 4 groups: skipped breakfast in neither childhood nor adulthood (n = 1359), skipped breakfast only in childhood (n = 224), skipped breakfast only in adulthood (n = 515), and skipped breakfast in both childhood and adulthood (n = 86). Diet quality was assessed, waist circumference was measured, and blood samples were taken after a 12-h fast (n = 1730). Differences in mean waist circumference and blood glucose, insulin, and lipid concentrations were calculated by linear regression.

Results: After adjustment for age, sex, and sociodemographic and lifestyle factors, participants who skipped breakfast in both childhood and adulthood had a larger waist circumference (mean difference: 4.63 cm; 95% CI: 1.72, 7.53 cm) and higher fasting insulin (mean difference: 2.02 mU/L; 95% CI: 0.75, 3.29 mU/L), total cholesterol (mean difference: 0.40 mmol/L; 95% CI: 0.13, 0.68 mmol/L), and LDL cholesterol (mean difference: 0.40 mmol/L; 95% CI: 0.16, 0.64 mmol/L) concentrations than did those who ate breakfast at both time points. Additional adjustments for diet quality and waist circumference attenuated the associations with cardiometabolic variables, but the differences remained significant.

Conclusions: Skipping breakfast over a long period may have detrimental effects on cardiometabolic health. Promoting the benefits of eating breakfast could be a simple and important public health message.

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Serum 25-hydroxyvitamin D and parathyroid hormone are independent determinants of whole-body insulin sensitivity in women and may contribute to lower insulin sensitivity in African Americans

Jessica A Alvarez, Ambika P Ashraf, Gary R Hunter, and Barbara A Gower

Background: Circulating 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) concentrations have been shown to be associated with insulin sensitivity; however, adiposity may confound this relation. Furthermore, African Americans (AAs) have lower insulin sensitivity and 25(OH)D concentrations than do European Americans (EAs); whether these differences are associated in a cause-and-effect manner has not been determined.

Objectives: The objectives of this study were to examine the relation of 25(OH)D and PTH concentrations with whole-body insulin sensitivity and to determine whether lower 25(OH)D concentrations in AAs compared with EAs contribute to the lower insulin sensitivity of AAs relative to that of EAs.

Desing: This was a cross-sectional study of 25 AA and 25 EA women. We determined the whole-body insulin sensitivity index (SI) with an intravenous glucose tolerance test and minimal modeling. Percentage body fat was determined with dual-energy X-ray absorptiometry, and intraabdominal adipose tissue (IAAT) was determined with computed tomography.

Results: Multiple linear regression analysis indicated that 25(OH)D and PTH concentrations were independent determinants of SI [standardized β = 0.24 (P = 0.04) and −0.36 (P = 0.002), respectively] after adjustment for age, race, and IAAT. The mean ethnic difference in SI decreased from 2.70 [• 10−4 • min−1/(μIU/mL)] after adjustment for IAAT and percentage body fat to 1.80 [• 10−4 • min−1/(μIU/mL)] after further adjustment for 25(OH)D and PTH concentrations.

Conclusions: 25(OH)D and PTH concentrations were independently associated with whole-body insulin sensitivity in a cohort of healthy women, which suggested that these variables may influence insulin sensitivity through independent mechanisms. Furthermore, ethnic differences in 25(OH)D concentrations may contribute to ethnic differences in insulin sensitivity.

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Circulating palmitoleic acid and risk of metabolic abnormalities and new-onset diabetes

Dariush Mozaffarian, Haiming Cao, Irena B King, Rozenn N Lemaitre, Xiaoling Song, David S Siscovick, and Gökhan S Hotamisligil

Background: Animal experiments suggest that circulating palmitoleic acid (cis-16:1n–7) from adipocyte de novo fatty acid synthesis may directly regulate insulin resistance and metabolic dysregulation.

Objective: We investigated the independent determinants of circulating palmitoleate in free-living humans and whether palmitoleate is related to lower metabolic risk and the incidence of diabetes.

Desing: In a prospective cohort of 3630 US men and women in the Cardiovascular Health Study, plasma phospholipid fatty acids, anthropometric variables, blood lipids, inflammatory markers, and glucose and insulin concentrations were measured between 1992 and 2006 by using standardized methods. Independent determinants of plasma phospholipid palmitoleate and relations of palmitoleate with metabolic risk factors were investigated by using multivariable-adjusted linear regression. Relations with incident diabetes (296 incident cases) were investigated by using Cox proportional hazards.

Results: The mean (±SD) palmitoleate value was 0.49 ± 0.20% (range: 0.11–2.55%) of total fatty acids. Greater body mass index, carbohydrate intake, protein intake, and alcohol use were each independent lifestyle correlates of higher palmitoleate concentrations. In multivariable analyses that adjusted for these factors and other potential confounders, higher palmitoleate concentrations were independently associated with lower LDL cholesterol (P < 0.001), higher HDL cholesterol (P < 0.001), lower total:HDL-cholesterol ratio (P = 0.04), and lower fibrinogen (P < 0.001). However, palmitoleate was also associated with higher triglycerides (P < 0.001) and (in men only) with greater insulin resistance (P < 0.001). Palmitoleate was not significantly associated with incident diabetes.

Conclusions: Adiposity (energy imbalance), carbohydrate consumption, and alcohol use—even within typical ranges—are associated with higher circulating palmitoleate concentrations. Circulating palmitoleate is robustly associated with multiple metabolic risk factors but in mixed directions, perhaps related to divergent lifestyle determinants or endogenous sources (liver, adipose tissue) of fatty acid synthesis.

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Fatty acid consumption and risk of fracture in the Women's Health Initiative

Tonya S Orchard, Jane A Cauley, Gail C Frank, Marian L Neuhouser, Jennifer G Robinson, Linda Snetselaar, Fran Tylavsky, Jean Wactawski-Wende, Alicia M Young, Bo Lu, and Rebecca D Jackson

Background: Fatty acids (FAs) may be important dietary components that modulate osteoporotic fracture risk.

Objective: The objective was to examine FA intake in relation to osteoporotic fractures.

Desing: The participants were postmenopausal women enrolled in the Women's Health Initiative (n = 137,486). Total fractures were identified by self-report; hip fractures were confirmed by medical record review. FA intake was estimated from baseline food-frequency questionnaires and standardized to total caloric intake. No data on omega-3 (n−3) FA supplements were available. Cox proportional hazard models were constructed to estimate risk of fracture.

Results: Higher saturated FA consumption was associated with higher hip fracture risk [quartile 4 multivariate-adjusted hazard ratio (HR): 1.31; 95% CI: 1.11, 1.55; P for trend = 0.001]. Lower total fracture risk was associated with a higher monounsaturated FA intake (quartile 3 HR: 0.94; 95% CI: 0.89, 0.98; P for trend = 0.050) and polyunsaturated FA intake (quartile 4 HR: 0.95; 95% CI: 0.90, 0.99; P for trend = 0.019). Unexpectedly, higher consumption of marine n−3 FAs was associated with greater total fracture risk (quartile 4 HR: 1.07; 95% CI: 1.02, 1.12; P for trend = 0.010), whereas a higher n−6 FA intake was associated with a lower total fracture risk (quartile 4 HR: 0.94; 95% CI: 0.89, 0.98; P for trend 0.009).

Conclusions: These results suggest that saturated FA intake may significantly increase hip fracture risk, whereas monounsaturated and polyunsaturated FA intakes may decrease total fracture risk. In postmenopausal women with a low intake of marine n−3 FAs, a higher intake of n−6 FAs may modestly decrease total fracture risk. This trial was registered at clinicaltrials.gov as NCT00000611.

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Adherence to a Mediterranean diet and plasma concentrations of lipid peroxidation in premenopausal women

Audrey J Gaskins, Alisha J Rovner, Sunni L Mumford, Edwina Yeung, Richard W Browne, Maurizio Trevisan, Neil J Perkins, Jean Wactawski-Wende, Enrique F Schisterman, and for the BioCycle Study Group

Background: A Mediterranean diet has been associated with a reduced risk of cardiovascular disease and mortality. A possible mechanism is through a decrease in lipid peroxidation (LPO); however, evidence linking the Mediterranean diet with lower LPO in premenopausal women is sparse.

Objective: We investigated whether adherence to a Mediterranean diet was associated with lower LPO concentrations in premenopausal women.

Desing: Two hundred fifty-nine healthy women aged 18–44 y were followed for ≤2 menstrual cycles. Plasma concentrations of F2-isoprostane (8-iso-PGF2α), 9-hydroxyoctadecadieneoic acid (9-HODE), and thiobarbituric acid reactive substances (TBARS) were measured ≤8 times per cycle at visits scheduled by using fertility monitors. Diet was assessed ≤4 times per cycle by using 24-h dietary recalls. The alternate Mediterranean Diet Score (aMED) (range: 0–9) was calculated on the basis of intake of vegetables, legumes, fruit, nuts, whole grains, red and processed meat, fish, and alcohol and the ratio of monounsaturated to saturated fat.

Results: A 1-unit increase in aMED was associated with a 4.50% decrease in 8-iso-PGF2α concentrations (95% CI: −6.32%, −2.65%) and a 14.01% decrease in 9-HODE concentrations (95% CI: −17.88%, −9.96%) after adjustment for energy intake, age, race, body mass index, plasma ascorbic acid, and serum cholesterol. No significant association was observed between aMED and TBARS. A 1-unit increase in aMED was associated with a 1.39% increase (95% CI: 0.07%, 2.72%) in plasma ascorbic acid concentrations.

Conclusions: Adherence to a Mediterranean diet is associated with lower LPO and higher ascorbic acid concentrations. These results confirm that decreased LPO is a plausible mechanism linking a Mediterranean diet to reduced cardiovascular disease risk.

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Adherence to the Mediterranean diet, long-term weight change, and incident overweight or obesity: the Seguimiento Universidad de Navarra (SUN) cohort

Juan-José Beunza, Estefanía Toledo, Frank B Hu, Maira Bes-Rastrollo, Manuel Serrano-Martínez, Almudena Sánchez-Villegas, J Alfredo Martínez, and Miguel A Martínez-González

Background: The Mediterranean dietary pattern might be a potential tool for the prevention of obesity.

Objectives: We studied the association between adherence to 6 previously published scores used to assess the adherence to the Mediterranean diet and weight change. We also assessed the risk of relevant weight gain (≥5 kg) or the risk of developing overweight or obesity.

Desing: The study population included 10,376 Spanish men and women who were university graduates (mean age = 38 y) and were followed up for a mean (±SD) of 5.7 ± 2.2 y. Diet was assessed at baseline with a 136-item, previously validated food-frequency questionnaire. Weight was assessed at baseline and biennially during follow-up.

Results: Participants with the lowest adherence (≤3 points) to the Mediterranean dietary score (MDS) proposed by Trichopoulou et al (range: 0–9; N Engl J Med 2003;348:2599–608) exhibited the highest average yearly weight gain, whereas participants with the highest (≥6 points) adherence exhibited the lowest weight gain (adjusted difference: −0.059 kg/y; 95% CI: −0.111, −0.008 kg/y; P for trend = 0.02). This inverse association was extended to other a priori–defined MDSs. The group with the highest adherence to the MDS also showed the lowest risk of relevant weight gain (≥5 kg) during the first 4 y of follow-up (odds ratio: 0.76; 95% CI: 0.64, 0.90).

Conclusions: Adherence to the Mediterranean dietary pattern is significantly associated with reduced weight gain. This dietary pattern can be recommended to slow down age-related weight gain.

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Effects of meals rich in either monounsaturated or saturated fat on lipid concentrations and on insulin secretion and action in subjects with high fasting triglyceride concentrations

Sergio Lopez, Beatriz Bermudez, Almudena Ortega, Lourdes M Varela, Yolanda M Pacheco, Jose Villar, Rocio Abia, and Francisco JG Muriana

Background: The nature of dietary fats and fasting concentrations of triglycerides affect postprandial hypertriglyceridemia and glucose homeostasis.

Objectives: The objectives were to examine the effects of meals enriched in monounsaturated fatty acids (MUFAs) or saturated fatty acids (SFAs) on postprandial lipid, glucose, and insulin concentrations and to examine the extent of β cell function and insulin sensitivity in subjects with high fasting triglyceride concentrations.

Desing: Fourteen men with fasting hypertriglyceridemia and normal glucose tolerance were given meals (≈10 kcal/kg body weight) containing MUFAs, SFAs, or no fat. Blood samples were collected at baseline and hourly over 8 h for analysis.

Results: The high-fat meals significantly increased postprandial concentrations of triglycerides, nonesterified fatty acids, and insulin and postprandial indexes of β cell function. However, postprandial indexes of insulin sensitivity decreased significantly. These effects were significantly attenuated with MUFAs relative to SFAs.

Conclusions: Adherence to the Mediterranean dietary pattern is significantly associated with reduced weight gain. This dietary pattern can be recommended to slow down age-related weight gain. MUFAs postprandially buffered β cell hyperactivity and insulin intolerance relative to SFAs in subjects with high fasting triglyceride concentrations. These data suggest that, in contrast with SFAs, MUFA-based strategies may provide cardiovascular benefits to persons at risk by limiting lipid and insulin excursions and may contribute to optimal glycemic control after meal challenges.

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Endothelial function is impaired after a high-salt meal in healthy subjects

Kacie M Dickinson, Peter M Clifton, and Jennifer B Keogh

Background: Dietary salt is related to blood pressure (BP), and cardiovascular disease and increased sodium intakes have been shown to impair vascular function. The effect of salt on endothelial function postprandially is unknown.

Objectives: The aim was to investigate the postprandial effect of dietary salt on endothelial function as measured by flow-mediated dilatation (FMD) and peripheral arterial tonometry in healthy subjects.

Desing: Sixteen healthy, normotensive subjects received a meal with added salt (HSM; 65 mmol Na) and a control low-salt meal (LSM; 5 mmol Na) on 2 separate occasions in a randomized order. Endothelial function was measured while fasting and postprandially at 30, 60, 90, and 120 min by using FMD and reactive hyperemia peripheral arterial tonometry. BP was also measured.

Results: Baseline FMD, reactive hyperemia index (RHI), and BP values were similar across interventions. Overall FMD was reduced 2 h postprandially. FMD was significantly more impaired after the HSM than after the LSM at 30 min [HSM (mean ± SD): 3.39 ± 2.44%; LSM: 6.05 ± 3.21%; P < 0.01] and at 60 min (HSM: 2.20 ± 2.77%; LSM: 4.64 ± 2.48%; P < 0.01). No significant differences in BP or RHI were observed between meals.

Conclusions: An HSM, which reflects the typical amount of salt consumed in a commonly eaten meal, can significantly suppress brachial artery FMD within 30 min. These results suggest that high salt intakes have acute adverse effects on vascular dilatation in the postprandial state. This trial was registered at www.anzctr.org.au/trial_view.aspx?ID=335115 as ACTRN12610000124033.

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Protein choices targeting thermogenesis and metabolism

Kevin J Acheson, Anny Blondel-Lubrano, Sylviane Oguey-Araymon, Maurice Beaumont, Shahram Emady-Azar, Corinne Ammon-Zufferey, Irina Monnard, Stéphane Pinaud, Corine Nielsen-Moennoz, and Lionel Bovetto

Background: Dietary proteins stimulate thermogenesis and satiety more than does carbohydrate or fat; however, less is known about the differences between protein sources.

Objectives: The objective was to determine the differential effects of 3 proteins on energy metabolism, satiety, and glucose control.

Desing: Energy metabolism, satiety, and glucose control were measured in 23 lean, healthy subjects on separate occasions, before and 5.5 h after consumption of 4 isocaloric test meals in a randomized, double-blind, crossover design. Three meals consisting of 50% protein (whey, casein, or soy), 40% carbohydrate, and 10% fat and a fourth meal consisting of 95.5% carbohydrate were compared with a glucose meal that provided the same glucose load as the protein meals.

Results: The thermic effect was greater after the whey (14.4 ± 0.5%) than after the casein (12.0 ± 0.6%; P = 0.002) and soy (11.6 ± 0.5%; P = 0.0001) meals and was greater after the whey, casein, and soy meals than after the high-carbohydrate meal (6.6 ± 0.5%; P < 0.0001). Cumulative fat oxidation tended to be greater after the whey meal (16.2 ± 1.1 g) than after the soy meal (13.7 ± 1.0 g; P = 0.097) and was greater after the whey and soy meals than after the high-carbohydrate meal (10.9 ± 0.9 g; P < 0.05). The glycemic response to glucose was attenuated 32% by the proteins (P < 0.001) at the expense of a greater insulin response after whey than after glucose (154%; P = 0.02), casein (143%; P = 0.07), and soy (151%; P = 0.03). Subjective appetite sensations indicated that casein and soy were more satiating than whey (P < 0.01), but whey was more “liked” compared with casein and soy (P = 0.025 and P = 0.09, respectively).

Conclusions: The results suggest that different protein sources could be used to modulate metabolism and subsequently energy balance.

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Unexplained chronic cough and vitamin B-12 deficiency

Caterina B Bucca, Beatrice Culla, Giuseppe Guida, Savino Sciascia, Graziella Bellone, Antonella Moretto, Enrico Heffler, Massimiliano Bugiani, Giovanni Rolla, and Luisa Brussino

Background: Chronic cough is characterized by sensory neuropathy. Vitamin B-12 (cobalamin) deficiency (Cbl-D) causes central and peripheral nervous system damage and has been implicated in sensory neuropathy and autonomic nervous system dysfunction.

Objectives: We evaluated whether Cbl-D has a role in chronic, unexplained cough.

Desing: Laryngeal threshold (histamine concentration that provokes a 25% decrease in the midinspiratory flow), bronchial threshold (histamine concentration that provokes a 20% decrease in the forced expiratory volume in 1 s), and cough threshold (histamine concentration that causes ≥5 coughs) in response to an inhaled histamine were assessed in 42 patients with chronic, unexplained cough [27 Cbl-D patients and 15 patients without Cbl-D (Cbl-N)] before and after intramuscular injections of cobalamin for 2 mo. Laryngeal, bronchial, and cough hyperresponsiveness was diagnosed when histamine concentration thresholds were ≤8 mg/mL. Seven Clb-D and 3 Cbl-N patients underwent an oropharyngeal biopsy before treatment.

Results: Cbl-D patients had a higher prevalence of laryngeal hyperresponsiveness than did Cbl-N patients (92.6% compared with 66.7%; P = 0.03), a thinner oropharyngeal epithelium [133.7 μm (95% CI: 95, 172 μm) compared with 230.8 μm (95% CI: 224, 237 μm); P = 0.002], a lower number of myelinated nerve fibers [2.25/mm2 (95% CI: 1.8, 2.7/mm2) compared with 3.44/mm2 (95% CI: 3, 3.8/mm2); P = 0.05], and a higher immunoreactive score for nerve growth factor (NGF) [6.7 (95% CI: 6, 7.3) compared with 2.8 (95% CI: 2.5, 3.1); P = 0.02]. After cobalamin supplementation, symptoms and laryngeal, bronchial, and cough thresholds were significantly improved in Cbl-D but not in Cbl-N patients.

Conclusions: This study suggests that Cbl-D may contribute to chronic cough by favoring sensory neuropathy as indicated by laryngeal hyperresponsiveness and increased NGF expression in pharyngeal biopsies of Cbl-D patients. Cbl-D should be considered among factors that sustain chronic cough, particularly when cough triggers cannot be identified.

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Permissive underfeeding and intensive insulin therapy in critically ill patients: a randomized controlled trial

Yaseen M Arabi, Hani M Tamim, Gousia S Dhar, Abdulaziz Al-Dawood, Muhammad Al-Sultan, Maram H Sakkijha, Salim H Kahoul, and Riette Brits

Background: Nutritional support has been recognized as an essential part of intensive care unit management. However, the appropriate caloric intake for critically ill patients remains ill defined.

Objectives: We examined the effect of permissive underfeeding compared with that of target feeding and of intensive insulin therapy (IIT) compared with that of conventional insulin therapy (CIT) on the outcomes of critically ill patients.

Desing: This study had a 2 × 2 factorial, randomized, controlled design. Eligible patients were randomly assigned to permissive underfeeding or target feeding groups (caloric goal: 60–70% compared with 90–100% of calculated requirement, respectively) with either IIT or CIT (target blood glucose: 4.4–6.1 compared with 10–11.1 mmol/L, respectively).

Results: Twenty-eight-day all-cause mortality was 18.3% in the permissive underfeeding group compared with 23.3% in the target feeding group (relative risk: 0.79; 95% CI: 0.48, 1.29; P = 0.34). Hospital mortality was lower in the permissive underfeeding group than in the target group (30.0% compared with 42.5%; relative risk: 0.71; 95% CI: 0.50, 0.99; P = 0.04). No significant differences in outcomes were observed between the IIT and CIT groups.

Conclusions: In critically ill patients, permissive underfeeding may be associated with lower mortality rates than target feeding. This trial was registered at controlled-trials.com as ISRCTN96294863.

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Maternal vitamin D status during pregnancy and body composition and cardiovascular risk markers in Indian children: the Mysore Parthenon Study

Ghattu V Krishnaveni, Sargoor R Veena, Nicola R Winder, Jacqueline C Hill, Kate Noonan, Barbara J Boucher, Samuel C Karat, and Caroline HD Fall

Background: Metabolic consequences of vitamin D deficiency have become a recent research focus. Maternal vitamin D status is thought to influence musculoskeletal health in children, but its relation with offspring metabolic risk is not known.

Objectives: We aimed to examine the association between maternal vitamin D status and anthropometric variables, body composition, and cardiovascular risk markers in Indian children.

Desing: Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured at 28–32 wk gestation in 568 women who delivered at Holdsworth Memorial Hospital, Mysore, India. Anthropometric variables, glucose and insulin concentrations, blood pressure, and fasting lipid concentrations were measured in the offspring at 5 and 9.5 y of age. Muscle-grip strength was measured by using a hand-held dynamometer at age 9.5 y. Arm-muscle area was calculated as a measure of muscle mass. Fasting insulin resistance was calculated by using the homeostasis model assessment equation.

Results: Sixty-seven percent of women had vitamin D deficiency [serum 25(OH)D concentration <50 nmol/L]. At ages 5 and 9.5 y, children born to vitamin D–deficient mothers had smaller arm-muscle area in comparison with children born to mothers without deficiency (P < 0.05). There was no difference in grip strength between offspring of women with and without vitamin D deficiency. At 9.5 y, children of vitamin D–deficient mothers had higher fasting insulin resistance than did children of nondeficient women (P = 0.04). There were no associations between maternal vitamin D status and other offspring risk factors at either age.

Conclusions: Intrauterine exposure to low 25(OH)D concentrations is associated with less muscle mass and higher insulin resistance in children.

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The role of reducing intakes of saturated fat in the prevention of cardiovascular disease: where does the evidence stand in 2010?

Arne Astrup, Jørn Dyerberg, Peter Elwood, Kjeld Hermansen, Frank B Hu, Marianne Uhre Jakobsen, Frans J Kok, Ronald M Krauss, Jean Michel Lecerf, Philippe LeGrand, Paul Nestel, Ulf Risérus, Tom Sanders, Andrew Sinclair, Steen Stender, Tine Tholstrup, and Walter C Willett

Current dietary recommendations advise reducing the intake of saturated fatty acids (SFAs) to reduce coronary heart disease (CHD) risk, but recent findings question the role of SFAs. This expert panel reviewed the evidence and reached the following conclusions: the evidence from epidemiologic, clinical, and mechanistic studies is consistent in finding that the risk of CHD is reduced when SFAs are replaced with polyunsaturated fatty acids (PUFAs). In populations who consume a Western diet, the replacement of 1% of energy from SFAs with PUFAs lowers LDL cholesterol and is likely to produce a reduction in CHD incidence of ≥2–3%. No clear benefit of substituting carbohydrates for SFAs has been shown, although there might be a benefit if the carbohydrate is unrefined and has a low glycemic index. Insufficient evidence exists to judge the effect on CHD risk of replacing SFAs with MUFAs. No clear association between SFA intake relative to refined carbohydrates and the risk of insulin resistance and diabetes has been shown. The effect of diet on a single biomarker is insufficient evidence to assess CHD risk. The combination of multiple biomarkers and the use of clinical endpoints could help substantiate the effects on CHD. Furthermore, the effect of particular foods on CHD cannot be predicted solely by their content of total SFAs because individual SFAs may have different cardiovascular effects and major SFA food sources contain other constituents that could influence CHD risk. Research is needed to clarify the role of SFAs compared with specific forms of carbohydrates in CHD risk and to compare specific foods with appropriate alternatives.

This is a free access article, distributed under terms (http://www.nutrition.org/publications/guidelines-and-policies/license/) which permit unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Baseline leptin and leptin reduction predict improvements in metabolic variables and long-term fat loss in obese children and adolescents: a prospective study of an inpatient weight-loss program

Stefanie B Murer, Bruno H Knöpfli, Isabelle Aeberli, Andreas Jung, Johannes Wildhaber, Joanne Wildhaber-Brooks, and Michael B Zimmermann

Background: It is unclear whether high plasma leptin in obese individuals represents leptin resistance or whether individuals with marked reductions in leptin concentrations in response to weight loss may be at greater risk of regaining weight. Moreover, whether changes in leptin predict metabolic improvements during weight loss is uncertain.

Objectives: The objective was to prospectively examine associations between plasma leptin, body fat, and weight and metabolic risk factors in obese children during weight loss.

Desing: In obese children and adolescents [n = 203; mean age: 14.1 y, >98th body mass index (BMI) percentile for age and sex] participating in a 2-mo inpatient weight-loss program, we measured changes in body composition (by dual-energy X-ray absorptiometry), plasma leptin, insulin, and lipids. After discharge, anthropometric measures and plasma leptin were remeasured at 6 (n = 139) and 12 (n = 100) mo.

Results: During the 2-mo program, mean (±SD) weight and fat loss were 13.9 ± 4.0 kg and 9.2 ± 2.5 kg, respectively; and mean plasma leptin decreased by 76%. Weight and fat loss were sustained, and no significant differences in BMI-SD score (SDS) or body composition were found between 12 and 2 mo. Baseline leptin was a negative predictor for percentage fat loss at 2, 6, and 12 mo (P < 0.05). The percentage change in leptin during the 2-mo intervention positively correlated with the relative change in fasting insulin, the relative change in LDL cholesterol at 2 mo, percentage fat loss, and change in BMI-SDS at 2 and 6 mo (P < 0.02).

Conclusions: Even in obese children with strongly elevated baseline leptin, large leptin reductions that predict short- and long-term loss of body fat and improvements in lipids and insulin sensitivity can be achieved. Thus, increased plasma leptin in obese children may not necessarily reflect leptin resistance; many children appear to remain leptin sensitive at this age.

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The association between breastfeeding and the cardiovascular system in early childhood

Annemieke MV Evelein, Caroline C Geerts, Frank LJ Visseren, Michiel L Bots, Cornelis K van der Ent, Diederick E Grobbee, and Cuno SPM Uiterwaal

Background: Breastfeeding is suggested to have beneficial effects on children's health and future health status. However, its cardiovascular effects in childhood and possibly later in life remain largely unclear.

Objective: The aim of the present study was to determine the cardiovascular effects of exclusive breastfeeding in early childhood.

Desing: We used the ongoing WHeezing Illnesses STudy LEidsche Rijn (WHISTLER) birth cohort to obtain data on infant feeding. In the first 306 children who were 5 y of age, ultrasonographic measurements of the carotid artery were performed to obtain carotid intima-media thickness (CIMT), distensibility, and elastic modulus.

Results: At 5 y of age, children who had been exclusively breastfed in infancy for 3 to 6 mo had a CIMT that was 21.1 μm greater than that of exclusively formula-fed children (95% CI: 5.0, 37.2 μm; P = 0.01, adjusted for confounders). CIMT was not significantly different between children exclusively breastfed for either <3 or >6 mo and formula-fed children. In addition, no significant differences in carotid stiffness were observed between groups.

Conclusions: The duration of exclusive breastfeeding in infancy is related to properties of the carotid arterial wall at the age of 5 y, as shown by the greater CIMT in children who were exclusively breastfed for 3 to 6 mo. This relation was independent of early growth in infancy and current cardiovascular disease risk factors. The choice of infant feeding appears to have an effect on the vascular system already in early childhood.

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A high-fat diet impairs cardiac high-energy phosphate metabolism and cognitive function in healthy human subjects

Cameron J Holloway, Lowri E Cochlin, Yaso Emmanuel,Andrew Murray, Ion Codreanu, Lindsay M Edwards, Cezary Szmigielski, Damian J Tyler, Nicholas S Knight, Brian K Saxby, Bridget Lambert, Campbell Thompson, Stefan Neubauer, and Kieran Clarke

Background: High-fat, low-carbohydrate diets are widely used for weight reduction, but they may also have detrimental effects via increased circulating free fatty acid concentrations.

Objective: We tested whether raising plasma free fatty acids by using a high-fat, low-carbohydrate diet results in alterations in heart and brain in healthy subjects.

Desing: Men (n = 16) aged 22 ± 1 y (mean ± SE) were randomly assigned to 5 d of a high-fat, low-carbohydrate diet containing 75 ± 1% of calorie intake through fat consumption or to an isocaloric standard diet providing 23 ± 1% of calorie intake as fat. In a crossover design, subjects undertook the alternate diet after a 2-wk washout period, with results compared after the diet periods. Cardiac 31P magnetic resonance (MR) spectroscopy and MR imaging, echocardiography, and computerized cognitive tests were used to assess cardiac phosphocreatine (PCr)/ATP, cardiac function, and cognitive function, respectively.

Results: Compared with the standard diet, subjects who consumed the high-fat, low-carbohydrate diet had 44% higher plasma free fatty acids (P < 0.05), 9% lower cardiac PCr/ATP (P < 0.01), and no change in cardiac function. Cognitive tests showed impaired attention (P < 0.01), speed (P < 0.001), and mood (P < 0.01) after the high-fat, low-carbohydrate diet.

Conclusions: Raising plasma free fatty acids decreased myocardial PCr/ATP and reduced cognition, which suggests that a high-fat diet is detrimental to heart and brain in healthy subjects.

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Physical activity and gain in abdominal adiposity and body weight: prospective cohort study in 288,498 men and women

Ulf Ekelund, Herve Besson, Jian'an Luan, Anne M May, Stephen J Sharp, Søren Brage, Noemie Travier, Antonio Agudo, Nadia Slimani, Sabina Rinaldi, Mazda Jenab, Teresa Norat, Traci Mouw, Sabine Rohrmann, Rudolf Kaaks, Manuela M Bergmann, Heiner Boeing, Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault, Kim Overvad, Marianne Uhre Jakobsen, Nina Føns Johnsen, Jytte Halkjaer, Carlos A Gonzalez, Laudina Rodriguez, Maria José Sanchez, Larraitz Arriola, Aurelio Barricarte, Carmen Navarro, Timothy J Key, Elisabeth A Spencer, Philippos Orfanos, Androniki Naska, Antonia Trichopoulou, Jonas Manjer, Eiliv Lund, Dominico Palli, Valeria Pala, Paolo Vineis, Amalia Mattiello, Rosario Tumino, H Bas Bueno-de-Mesquita, Saskia W van den Berg, Andreani D Odysseos, Elio Riboli, Nicolas J Wareham, and Petra H Peeters

Background: The protective effect of physical activity (PA) on abdominal adiposity is unclear.

Objective: We examined whether PA independently predicted gains in body weight and abdominal adiposity.

Desing: In a prospective cohort study [the EPIC (European Prospective Investigation into Cancer and Nutrition)], we followed 84,511 men and 203,987 women for 5.1 y. PA was assessed by a validated questionnaire, and individuals were categorized into 4 groups (inactive, moderately inactive, moderately active, and active). Body weight and waist circumference were measured at baseline and self-reported at follow-up. We used multilevel mixed-effects linear regression models and stratified our analyses by sex with adjustments for age, smoking status, alcohol consumption, educational level, total energy intake, duration of follow-up, baseline body weight, change in body weight, and waist circumference (when applicable).

Results: PA significantly predicted a lower waist circumference (in cm) in men (β = −0.045; 95% CI: −0.057, −0.034) and in women (β = −0.035; 95% CI: −0.056, −0.015) independent of baseline body weight, baseline waist circumference, and other confounding factors. The magnitude of associations was materially unchanged after adjustment for change in body weight. PA was not significantly associated with annual weight gain (in kg) in men (β = −0.008; 95% CI: −0.02, 0.003) and women (β = −0.01; 95% CI: −0.02, 0.0006). The odds of becoming obese were reduced by 7% (P < 0.001) and 10% (P < 0.001) for a one-category difference in baseline PA in men and women, respectively.

Conclusions: Our results suggest that a higher level of PA reduces abdominal adiposity independent of baseline and changes in body weight and is thus a useful strategy for preventing chronic diseases and premature deaths.

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Trends in carbohydrate, fat, and protein intakes and association with energy intake in normal-weight, overweight, and obese individuals: 1971–2006

Gregory L Austin, Lorraine G Ogden, and James O Hill

Background: The prevalence of obesity in the United States has increased dramatically.

Objective: The aim of this study was to determine trends in carbohydrate, fat, and protein intakes in adults and their association with energy intake by using data from the National Health and Nutrition Examination Survey (NHANES)—a representative sample of the US population.

Desing: Data on adults aged 20–74 y from the first NHANES (NHANES I, 1971–1975; n = 13,106) were compared with data from NHANES 2005–2006 (n = 4381). Normal weight was defined as a body mass index (BMI; in kg/m2) of 19 to <25, overweight as a BMI of 25 to <30, and obese as a BMI of ≥30. Carbohydrate, fat, and protein intakes were obtained by dietary recall. Regression analyses were adjusted for potential confounders.

Results: The prevalence of obesity increased from 11.9% to 33.4% in men and from 16.6% to 36.5% in women. The percentage of energy from carbohydrates increased from 44.0% to 48.7%, the percentage of energy from fat decreased from 36.6% to 33.7%, and the percentage of energy from protein decreased from 16.5% to 15.7%. Trends were identical across normal-weight, overweight, and obese groups. Energy intake increased substantially in all 3 BMI groups. In NHANES 2005–2006, a 1% increase in the percentage of energy from protein was associated with a decrease in energy intake of 32 kcal (substituted for carbohydrates) or 51 kcal (substituted for fat). Similar findings were seen across all BMI categories, in men and women, and in NHANES I.

Conclusions: Energy intake and the prevalence of obesity have increased dramatically. Dietary interventions should focus on decreasing energy intake and potentially by substituting protein for fat or carbohydrates.

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