The evolution of very-low-calorie diets: an update and meta-analysis

Objective: Very‐low‐calorie diets (VLCDs), providing <800 kcal/d, have been used since the 1970s to induce rapid weight loss. Previous reviews of the literature have disagreed concerning the relative efficacy of VLCDs vs. conventional low‐calorie diets (LCDs) for achieving long‐term weight loss. Research Methods and Procedures: We sought to update findings on the clinical use, safety, and efficacy of VLCDs and to perform a meta‐analysis of randomized trials that compared the long‐term efficacy of LCDs and VLCDs. Original research articles were retrieved by a Medline search and from prior reviews of VLCDs. Trials were included only if they were randomized comparisons of LCDs and VLCDs and included a follow‐up assessment at least 1 year after maximum weight loss. Data were abstracted by both authors regarding: duration of VLCD, total length of treatment, attrition, short‐ and long‐term weight loss, changes in weight‐related comorbidities, and adverse effects. Results: Six randomized trials were found that met inclusion criteria. VLCDs, compared with LCDs, induced significantly greater short‐term weight losses (16.1 ± 1.6% vs. 9.7 ± 2.4% of initial weight, respectively; p = 0.0001) but similar long‐term losses (6.3 ± 3.2% vs. 5.0 ± 4.0%, respectively; p > 0.2). Attrition was similar with VLCD and LCD regimens. Discussion: VLCDs did not produce greater long‐term weight losses than LCDs. In the United States, the use of liquid meal replacements as part of a 1000 to 1500 kcal/d diet may provide an effective and less expensive alternative to VLCDs. In Europe, VLCDs are used with less intensive medical supervision than in the United States, which reduces the cost of this approach.     

Pre-meal water consumption reduces meal energy intake in older but not younger subjects

Objective: To determine whether the consumption of water 30 minutes before an ad libitum meal reduces meal energy intake in young and older adults. Research Methods and Procedures: Healthy, non‐obese young (n = 29; age, 21 to 35 years) and older (n = 21; age, 60 to 80 years) individuals were provided with an ad libitum lunch meal on two occasions. Thirty minutes before the lunch meals, subjects were given either a water preload (WP: 375 mL, women; 500 mL, men) or no preload (NP). Energy intake at the two lunch meals was measured. Visual analog scales were used to assess changes in hunger, fullness, and thirst during the meal studies. Results: There was no significant difference in meal energy intake between conditions in the young subjects (892 + 51 vs. 913 ± 54 kcal for NP and WP, respectively; p = 0.65). However, meal energy intake after the WP was significantly reduced relative to the NP condition in the older subjects (682 + 53 vs. 624 ± 56 kcal for NP and WP, respectively; p = 0.02). This effect was caused primarily by the reduction in meal energy intake after water consumption in older men. Hunger ratings were lower and fullness ratings were higher in older compared with younger adults (p < 0.01). Fullness ratings were higher in the WP condition compared with the NP condition for all subjects (p = 0.01). No age differences in thirst were detected during the test meals. Discussion: Under acute test meal conditions, pre‐meal water consumption reduces meal energy intake in older but not younger adults. Because older adults are at increased risk for overweight and obesity, intervention studies are needed to determine whether pre‐meal water consumption is an effective long‐term weight management strategy for the aging population.     

Physical fitness in community‐dwelling older adults is linked to dietary intake,gut microbiota,and metabolomic signatures

When humans age, changes in body composition arise along with lifestyle‐associated disorders influencing fitness and physical decline. Here we provide a comprehensive view of dietary intake, physical activity, gut microbiota (GM), and host metabolome in relation to physical fitness of 207 community‐dwelling subjects aged +65 years. Stratification on anthropometric/body composition/physical performance measurements (ABPm) variables identified two phenotypes (high/low‐fitness) clearly linked to dietary intake, physical activity, GM, and host metabolome patterns. Strikingly, despite a higher energy intake high‐fitness subjects were characterized by leaner bodies and lower fasting proinsulin‐C‐peptide/blood glucose levels in a mechanism likely driven by higher dietary fiber intake, physical activity and increased abundance of Bifidobacteriales and Clostridiales species in GM and associated metabolites (i.e., enterolactone). These factors explained 50.1% of the individual variation in physical fitness. We propose that targeting dietary strategies for modulation of GM and host metabolome interactions may allow establishing therapeutic approaches to delay and possibly revert comorbidities of aging.     

Increase of neuronal histamine in obese rats is associated with decreases in body weight and plasma triglycerides

Objective: The purpose of the present study was to examine the metabolic effects of a specific histamine H₃ receptor antagonist, the cinnamic amide NNC 0038‐0000‐1202 (NNC 38‐1202). Research Methods and Procedures: Effects of NNC 38‐1202 on paraventricular levels of histamine and acute effects on food intake were followed in normal rats, whereas effects on body weight homeostasis and lipid metabolism were studied in a rat model of diet‐induced obesity (DIO). Results: NNC 38‐1202, administered as single oral doses of 15 and 30 mg/kg, significantly (p < 0.01) increased paraventricular histamine by 339 ± 54% and 403 ± 105%, respectively, compared with basal levels. The same doses produced significant (p < 0.01) reductions in food intake. In DIO rats receiving NNC 38‐1202 in a daily dose of 5 mg/kg for 22 days, a decrease in food intake was associated with a significant (p < 0.001) net loss of body weight (?11.0 ± 4.8 grams), compared with rats receiving vehicle, which gained 13.6 ± 3.0 grams. Also, NNC 38‐1202 significantly (p < 0.05) reduced plasma triglycerides by ～42%, in parallel with increases in plasma free fatty acids and β‐hydroxybutyrate levels. Despite reductions in food intake and body weight following administration of NNC 38‐1202, no sign of a decrease in energy expenditure was observed, and whole‐body lipid oxidation was significantly (p < 0.05) increased in the period after dosing. Discussion: The present study suggests that antagonistic targeting of the histamine H₃ receptor decreases food intake, body weight, and plasma TG levels and, thus, represents an interesting approach to treatment of obesity and associated hyperlipidemia.     

Eveningness is associated with skipping breakfast and poor nutritional intake in Brazilian undergraduate students

Some studies have proposed that self-reported eveningness, which reflects the preference of performing activities in the evening, may harm nutritional health and influence the eating behavior and nutritional status of individuals. However, the relationship between these variables (eveningness and nutritional status) and the consumption of breakfast, which is currently considered a marker of health, has been insufficiently explored by studies. The aim of this study was to investigate, in undergraduate students, the association between diurnal preference, being overweight, and food consumption (with special focus on breakfast). The study included 721 undergraduate students from a Brazilian public university. Dietary intake was assessed by 24-hour food recall, and the usual time for breakfast was identified. Body weight, height, and waist circumference were measured by trained researchers. Diurnal preference was determined by the Horne and Ostberg questionnaire validated for the Brazilian population, and the participants were classified into three categories: evening (coefficient: 16–41), intermediate type (coefficient: 42–58) or morning type (coefficient: 59–86). The prevalence of skipping breakfast was higher among the evening types (p = 0.02), when compared with morning and intermediate types. A negative association between the diurnal preference coefficient and total caloric (coefficient ?0.25, p = 0.007, r² adjusted = 0.12), carbohydrate (coefficient ?0.19, p = ?0.04, r² adjusted = 0.04) and lipid intake (coefficient ?0.18, p = 0.04, r² adjusted = 0.05) was also found in the breakfast skippers but not in breakfast eaters. In other words, breakfast skippers with diurnal preference values indicative of eveningness consumed more calories, carbohydrates and fats. Evening types presented significant odds of skipping breakfast (OR = 1.7, CI = 1.1–2.9, p = 0.02) when compared with morning and intermediate chronotypes. We conclude that eveningness is associated with skipping breakfast and a higher consumption of calories, carbohydrates and fats in breakfast skippers. These eating behaviors may predispose these individuals to being overweight.     

Analysis of feed intake and energy balance of high-yielding first lactating Holstein cows with fixed and random regression models

At the dairy research farm Karkendamm, the individual roughage intake was measured since 1 September 2005 using a computerised scale system to estimate daily energy balances as the difference between energy intake and calculated energy requirements for lactation and maintenance. Data of 289 heifers with observations between the 11th and 180th day of lactation over a period of 487 days were analysed. Average energy-corrected milk yield, feed intake, live weight and energy balance were 31.8kg, 20.6kg, 584 kg and 13.6 MJ NEL (net energy lactation), respectively, per day. Fixed and random regression models were used to estimate repeatabilities, correlations between cow effects and genetic parameters. The resulting genetic correlations in different lactation stages demonstrate that feed intake and energy balance at the beginning and the middle of lactation are genetically different traits. Heritability of feed intake is low with h2=0.06 during the first days after parturition and increases in the middle of lactation, whereas the energy balance shows the highest heritability with h2=0.34 in the first 30 days of lactation. Genetic correlations between energy balance and feed intake and milk yield, respectively, illustrate that energy balance depends more on feed intake than on milk yield. Genetic correlation between body condition score and energy balance decreases rapidly within the first 100 days of lactation. Hence, to avoid negative effects on health and reproduction as consequences of strong energy deficits at the beginning of lactation, the energy balance itself should be measured and used as a selection criterion in this lactation stage. Since the number of animals is rather small for a genetic analysis, the genetic parameters have to be evaluated on a more comprehensive dataset.     

Milk intake and carbon dioxide production of piglets determined with the doubly labelled water technique

The present study was undertaken to study different methodological aspects of quantifying CO2 production and milk intake of suckling piglets using the doubly labelled water (DLW) technique. In total, 37 piglets were enriched intraperitoneally with DLW to study equilibration time of 18O (n = 3), to validate the estimation of milk intake and CO2 production (n = 10) of piglets fed milk replacer and to quantify milk intake and CO2 production of piglets nursed ordinarily by sows (n = 24). Enrichment of 18O in expired air was analysed without any sample preparation, whereas enrichment of 18O in serum was analysed after a minimum step of sample preparation, which included pipetting of the sample, blowing gaseous CO2 into the vial for 3 s and equilibrating for 24 h. The 18O enrichment of CO2 in expired air was constant within 30-40 min of intraperitoneal injection, suggesting that DLW was equilibrated within the body water by that time. For piglets fed milk replacer, the estimation of the daily CO2 production by the DLW method (64.0 ± 2.7 l CO2/day) was in agreement with that obtained by respiration trials (64.7 ± 1.8 l CO2/day). Furthermore, the intake of milk replacer (891 ± 63 g/day) determined by deuterium oxide (D2O) dilution was similar in magnitude to that found by weighing the milk disappearance (910 ± 58 g/day). The milk intake of piglets fed milk replacer was comparable with that of sucking piglets, but sucking piglets had a remarkably higher CO2 production than artificially reared piglets, which likely was caused by a higher intake of milk solids and a higher activity level. For sucking piglets, the daily CO2 production increased curvilinearly with increasing live weight (LW) in kg: piglet CO2 production (l/day) = 25.75 × LW - 1.01 × LW2. In conclusion, 18O equilibrates fast within the body water pool when administered intraperitoneally, and the accuracy of assessing milk intake and rate of CO2 production using the DLW technique is promising. Assessment of excess enrichment of 18O in serum proved to be robust. Finally, the CO2 production of piglets fed milk replacer differs considerably from that of sucking piglets.     

Daily protein and energy intakes of infants fed a commercial infant formula with a reduced protein concentration of 2.2 g/100 kcal: an impact of feeding interval on energy intake

ABSTRACT

We evaluated the protein and energy intakes of infants fed commercial infant Formula A (protein, 2.2 g/100 kcal; energy, 68 kcal/100 mL) and examined whether changes in feeding intervals are involved in constant energy intake. Daily nutritional intake of 378 Formula A-fed infants was assessed using reference values and compared to that of infants fed Formulas B (protein: 2.3 g/100 kcal, energy: 68 kcal/100 mL) and C (protein: 2.4 g/100kcal, energy: 70 kcal/100 mL). From 15 to 149 days of age, the mean formula volume and protein intake were 758–887 mL/day and 11.4–13.3 g/day, respectively, higher than the protein intake of breast-fed infants. Daily energy intake (86–129 kcal/kg/day) was comparable to the estimated energy requirements. Feeding intervals were shorter in infants fed Formulas A and B than in those fed Formula C, whereas energy intake was similar. The protein intake of infants decreased as the protein concentration per energy in infant formula was reduced, and accordingly the protein intake of Formula A-fed infants was significantly lower than that of Formula C-fed infants. In conclusion, the new composition of Formula A is suitable in protein and energy intake of infants, and daily energy intake remains constant by shortening in feeding intervals when the energy concentration in infant formula is reduced.

Clinical Trial Registration: UMIN000023110     

Tissue fatty acid deposition is influenced by an interaction of dietary oil source and energy intake level in rats

To investigate the net tissue fatty acid deposition in response to graded levels of energy restriction and modification of diet fatty acid composition, rats were randomly assigned into four dietary groups and fed for 10 weeks diets containing 40% as energy of either fish, safflower, or olive oil, or beef tallow, consumed ad libitum or energy restricted to 85% or 68% of ad libitum intake by reducing diet carbohydrate content. An additional eight rats were killed before the diet regimen, to provide baseline data from which fatty acid deposition rates were calculated. Body weight, and heart, liver and fat mass gains were decreased with energy restriction (P<0.001). Olive oil feeding resulted in higher body weight gain (P < 0.03) than tallow feeding, whereas fish oil feeding was associated with highest (P < 0.007) liver weight and lowest (P < 0.03) fat mass gains. Energy deficit-related differences in the deposition of stearic, linoleic, arachidonic, and docosahexaenoic acids in heart and palmitic and docosahexaenoic acids in liver were dependent on the dietary oil consumed (P < 0.03). Similarly, interactive effects of restricted food intake and dietary oil type were found in the gain of palmitic, stearic, oleic, and linoleic acids in adipose tissue (P < 0.01) when expressed in relation to the amount of each fatty acid consumed. These data suggest that energy intake level can influence the deposition pattern, as well as oxidation rate, of tissue fatty acids as a function of tissue type, fatty acid structure, and dietary fatty acid composition.     

Long term ‘marine diet’ in Eskimos is not associated with altered urinary excretion of total tetranor prostaglandin metabolites

The total urinary excretion of tetranor prostaglandin metabolites, measured as tetranorprostanedioic acid (TPD), was quantified in traditionally living Greenland Eskimos (E) and compared with that in Caucasian Danes (D). TPD excretion (μg/24h) was not significantly different between both groups, neither for males (331 ± 62.4 (E) vs. 331 ± 25.7 (D), mean ± SEM, n = 9 and 10) nor for females (190 ± 31.7 (E) vs. 264 ± 27.4 (D), n = 11 and 10, P₂ > 0.05). Since urinary prostaglandin metabolites are thought to reflect the total prostaglandin turnover in vivo, these results suggest that a long-term intake of relatively large amounts of polyunsaturated fatty acids of the (n-3) family does not alter total prostaglandin turnover in vivo. This is in contrast to stimulated prostanoid formation in vitro, and thus suggests a different regulatory role of dietary and tissue fatty acids for ‘stimulated’ and ‘basal’ prostaglandin production.     

Pretreatment dietary intake is associated with tumor suppressor DNA methylation in head and neck squamous cell carcinomas

Diet is associated with cancer prognosis, including head and neck cancer (HNC), and has been hypothesized to influence epigenetic state by determining the availability of functional groups involved in the modification of DNA and histone proteins. The goal of this study was to describe the association between pretreatment diet and HNC tumor DNA methylation. Information on usual pretreatment food and nutrient intake was estimated via food frequency questionnaire (FFQ) on 49 HNC cases. Tumor DNA methylation patterns were assessed using the Illumina Goldengate Methylation Cancer Panel. First, a methylation score, the sum of individual hypermethylated tumor suppressor associated CpG sites, was calculated and associated with dietary intake of micronutrients involved in one-carbon metabolism and antioxidant activity, and food groups abundant in these nutrients. Second, gene specific analyses using linear modeling with empirical Bayesian variance estimation were conducted to identify if methylation at individual CpG sites was associated with diet. All models were controlled for age, sex, smoking, alcohol and HPV status. Individuals reporting in the highest quartile of folate, vitamin B12 and vitamin A intake, compared with those in the lowest quartile, showed significantly less tumor suppressor gene methylation, as did patients reporting the highest cruciferous vegetable intake. Gene specific analyses identified differential associations between DNA methylation and vitamin B12 and vitamin A intake when stratifying by HPV status. These preliminary results suggest that intake of folate, vitamin A and vitamin B12 may be associated with the tumor DNA methylation profile in HNC and enhance tumor suppression.     

Pretreatment dietary intake is associated with tumor suppressor DNA methylation in head and neck squamous cell carcinomas

Diet is associated with cancer prognosis, including head and neck cancer (HNC), and has been hypothesized to influence epigenetic state by determining the availability of functional groups involved in the modification of DNA and histone proteins. The goal of this study was to describe the association between pretreatment diet and HNC tumor DNA methylation. Information on usual pretreatment food and nutrient intake was estimated via food frequency questionnaire (FFQ) on 49 HNC cases. Tumor DNA methylation patterns were assessed using the Illumina Goldengate Methylation Cancer Panel. First, a methylation score, the sum of individual hypermethylated tumor suppressor associated CpG sites, was calculated and associated with dietary intake of micronutrients involved in one-carbon metabolism and antioxidant activity, and food groups abundant in these nutrients. Second, gene specific analyses using linear modeling with empirical Bayesian variance estimation were conducted to identify if methylation at individual CpG sites was associated with diet. All models were controlled for age, sex, smoking, alcohol and HPV status. Individuals reporting in the highest quartile of folate, vitamin B12 and vitamin A intake, compared with those in the lowest quartile, showed significantly less tumor suppressor gene methylation, as did patients reporting the highest cruciferous vegetable intake. Gene specific analyses identified differential associations between DNA methylation and vitamin B12 and vitamin A intake when stratifying by HPV status. These preliminary results suggest that intake of folate, vitamin A and vitamin B12 may be associated with the tumor DNA methylation profile in HNC and enhance tumor suppression.     

Percent ash‐free dry weight as a robust method to estimate energy density across taxa

Determining how energy flows through ecosystems reveals underlying ecological patterns that drive processes such as growth and food web dynamics. Models that assess the transfer of energy from producers to consumers require information on the energy content or energy density (ED) of prey species. ED is most accurately measured through bomb calorimetry, but this method suffers from limitations of cost, time, and sample requirements that often make it unrealistic for many studies. Percent dry weight (DW) is typically used as a proxy for ED, but this measure includes an indigestible portion (e.g., bones, shell, salt) that can vary widely among organisms. Further, several distinct models exist for various taxonomic groups, yet none can accurately estimate invertebrate, vertebrate and plant ED with a single equation. Here, we present a novel method to estimate the ED of organisms using percent ash‐free dry weight (AFDW). Using data obtained from 11 studies diverse in geographic, temporal and taxonomic scope, AFDW, DW as well as percent protein and percent lipid were compared as predictors of ED. Linear models were produced on a logarithmic scale, including dummy variables for broad taxonomic groups. AFDW was the superior predictor of ED compared to DW, percent protein content and percent lipid content. Model selection revealed that using correction factors (dummy variables) for aquatic animals (AA) and terrestrial invertebrates (TI) produced the best‐supported model—log₁₀(ED) = 1.07*log₁₀(AFDW) ? 0.80 (R² = 0.978, p < .00001)—with an intercept adjustment of 0.09 and 0.04 for AA and TI, respectively. All models including AFDW as a predictor had high predictive power (R² > 0.97), suggesting that AFDW can be used with high degrees of certainty to predict the ED of taxonomically diverse organisms. Our AFDW model will allow ED to be determined with minimal cost and time requirements and excludes ash‐weight from estimates of digestible mass. Its ease of use will allow for ED to be more readily and accurately determined for diverse taxa across different ecosystems.     

Timing of daily calorie loading affects appetite and hunger responses without changes in energy metabolism in healthy subjects with obesity

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Postnatal growth retardation is associated with intestinal mucosa mitochondrial dysfunction and aberrant energy status in piglets

Individuals with postnatal growth retardation (PGR) are prone to developing chronic disease. Abnormal development in small intestine is casually implicated in impaired growth performance. However, the exact mechanism is still unknown. In this present study, PGR piglets (aged 42 days) were employed as a good model to analyse changes in nutrient absorption and energy metabolism in the intestinal mucosa. The results showed lower serum concentrations of free amino acids, and lipid metabolites in PGR piglets, which were in accordance with the down‐regulated mRNA expressions involved in fatty acid and amino acid transporters in the jejunal and ileal mucosa. The decreased activities of digestive enzymes and the marked swelling in mitochondria were also observed in the PGR piglets. In addition, it was found that lower ATP production, higher AMP/ATP ratio, deteriorated mitochondrial complex III and ATP synthase, and decreased manganese superoxide dismutase activity in the intestinal mucosa of PGR piglets. Furthermore, altered gene expression involved in energy metabolism, accompanied by decreases in the protein abundance of SIRT1, PGC‐1α and PPARγ, as well as phosphorylations of AMPKα, mTOR, P70S6K and 4E‐BP1 were observed in intestinal mucosa of PGR piglets. In conclusion, decreased capability of nutrient absorption, mitochondrial dysfunction, and aberrant energy status in the jejunal and ileal mucosa may contribute to PGR piglets.     

Habitat fragmentation is associated with dietary shifts and microbiota variability in common vampire bats

Host ecological factors and external environmental factors are known to influence the structure of gut microbial communities, but few studies have examined the impacts of environmental changes on microbiotas in free‐ranging animals. Rapid land‐use change has the potential to shift gut microbial communities in wildlife through exposure to novel bacteria and/or by changing the availability or quality of local food resources. The consequences of such changes to host health and fitness remain unknown and may have important implications for pathogen spillover between humans and wildlife. To better understand the consequences of land‐use change on wildlife microbiotas, we analyzed long‐term dietary trends, gut microbiota composition, and innate immune function in common vampire bats (Desmodus rotundus) in two nearby sites in Belize that vary in landscape structure. We found that vampire bats living in a small forest fragment had more homogenous diets indicative of feeding on livestock and shifts in microbiota heterogeneity, but not overall composition, compared to those living in an intact forest reserve. We also found that irrespective of sampling site, vampire bats which consumed relatively more livestock showed shifts in some core bacteria compared with vampire bats which consumed relatively less livestock. The relative abundance of some core microbiota members was associated with innate immune function, suggesting that future research should consider the role of the host microbiota in immune defense and its relationship to zoonotic infection dynamics. We suggest that subsequent homogenization of diet and habitat loss through livestock rearing in the Neotropics may lead to disruption to the microbiota that could have downstream impacts on host immunity and cross‐species pathogen transmission.     

Genetic interaction is associated with lower metabolic connectivity and memory impairment in clinically mild Alzheimer's disease

Metabolic connectivity as showed by [18F] fluorodeoxyglucose (FDG) positron emission tomography (FDG‐PET) reflects neuronal connectivity. The aim of this study was to investigate the genetic impact on metabolic connectivity in default mode subnetworks and its clinical‐pathological relationships in patients with Alzheimer's disease (AD). We separately investigated the modulation of 2 default mode subnetworks, as identified with independent component analysis, by comparing APOE‐ε4 carriers to noncarriers with AD. We further analyzed the interaction effects of APOE (APOE‐ε4 carriers vs noncarriers) with PICALM (rs3851179‐GG vs rs3851179‐A‐allele carriers) on episodic memory (EM) deficits, reduction in cerebral metabolic rate for glucose (CMRgl) and decreased metabolic connectivity in default mode subnetworks. The metabolic connectivity in the ventral default mode network (vDMN) was positively correlated with EM scores (β =0.441, P < .001). The APOE‐ε4 carriers had significantly lower metabolic connectivity in the vDMN than the APOE‐ε4 carriers (t(96) = ?2.233, P = .028). There was an effect of the APOE‐PICALM (rs3851179) interactions on reduced CMRgl in regions of vDMN (P < .001), and on memory deficits (F_3,93 =5.568, P = .020). This study identified that PICALM may modulates memory deficits, reduced CMRgl and decreased metabolic connectivity in the vDMN in APOE‐ε4 carriers. [18F] FDG‐PET‐based metabolic connectivity may serve a useful tool to elucidate the neural networks underlying clinical‐pathological relationships in AD.