Human Milk Components and the Infant Gut Microbiome at 6 Months: Understanding the Interconnected Relationship.

BACKGROUND: Human milk oligosaccharides have been shown to relate to the infant gut microbiome. However, the impact of other human milk components on infant gut bacterial colonization remains unexplored. OBJECTIVES: Our cross-sectional analysis aimed to investigate associations between human milk components (energy, macronutrients, free amino acids, inflammatory markers, and hormones) and infant gut microbiome diversity and composition (phylum, family, and genus) at 6 mo of age. METHODS: Human milk and infant stool samples were collected at 6 mo postpartum. The infant gut microbiome was profiled using 16S rRNA sequencing. Linear regression models were performed to examine associations, adjusting for pregravid BMI (kg/m2), delivery mode, duration of human milk feeding, and infant sex, with q < 0.2 considered significant. RESULTS: This analysis included a total of 54 mothers (100% exclusively feeding human milk) and infants (n = 28 male; 51.9%). Total energy in human milk showed a negative association with α-diversity measures (Chao1 and Shannon). Interleukin (IL)-8 in human milk was positively associated with Chao1 and observed operational taxonomic units. At the family level, human milk glutamine and serine levels showed a negative association with the abundance of Veillonellaceae, whereas isoleucine showed a positive association with Bacteroidaceae. Human milk IL-8 and IL-6 concentrations were positively associated with Bacteroidaceae abundance. IL-8 also had a positive relationship with Bifidobacteriaceae, whereas it had a negative relationship with Streptococcacea and Clostridiaceae. Human milk IL-8 was positively associated with the phylum Bacteroidetes, and negatively associated with Proteobacteria. At the genus level, human milk IL-8 exhibited a positive relationship with Bacteroides, whereas human milk isoleucine had a negative relationship with Bacteroides and Ruminococcus. Pregravid BMI and sex effects were observed. CONCLUSIONS: IL-8 in human milk could potentially prepare the infant's immune system to respond effectively to various microorganisms, potentially promoting the growth of beneficial gut bacteria and protecting against pathogens.

Energetics of a World-Tour Female Road Cyclist During a Multistage Race (Tour de France Femmes).

Despite the increased popularity of female elite road cycling, research to inform the fueling requirements of these endurance athletes is lacking. In this case study, we report for the first time the energetics of a female world-tour cyclist competing in the 2023 Tour de France Femmes, an 8-day race of the Union Cycliste Internationale. The 29-year-old athlete presented with oligomenorrhea and low T3 before the race. Total daily energy expenditure assessed with the doubly labeled water technique was 7,572 kcal/day (∼4.3 physical activity levels), among the highest reported in the literature to date for a female. Crank-based mean maximal power was consistent with female world-tour cyclists (5 min, mean 342 W, 4.8 W/kg; 20 min 289 W, 4.1 W/kg). The average daily energy intake measured with the remote food photography method (Stage Days 1-7) was 5,246 kcal and carbohydrate intake was 13.7 g/kg (range 9.7-15.9 g/kg), and 84 g/hr during stages, and an average fat intake of 15% of daily energy intake. An estimated 2,326 kcal/day energy deficit was evidenced in a 2.2 kg decrease in body mass. Notwithstanding the high carbohydrate intake, the athlete was unable to match the energy requirements of the competition. Despite signs of energy deficiency preexisting (oligomenorrhea and low T3), and other further developing during the race (weight loss), performance was in line with that of other world-tour cyclists and a best personal performance was recorded for the last stage. This case study emphasizes the need for further research to inform energy requirements for female athletes' optimal performance and health.

New frontiers in the measurement of energy metabolism.

This perspective highlights three key areas of current and future energy metabolism research: intergenerational health, climate change, and interplanetary exploration. We describe the recent advances in determining estimated energy requirements for a large subset of the general population using the gold standard method for free-living total daily energy expenditure estimates, the doubly labeled water method. The global rise in overweight and obesity demands particular attention to energy requirements in pregnancy and early life, as accumulating evidence contributes to our understanding of intergenerational health transmission and the potential for epigenetic programming in utero. We also acknowledge some gaps in necessary guidelines and understandings of energy requirements for underrepresented populations (i.e., individuals from low and middle-income countries) or those who undergo major physiological changes in new environment (e.g., astronauts). The rising prevalence of excess weight gain, together with climate change, cumulate into a global syndemic exposing vulnerable populations to both malnutrition and the effects of unpredictable and severe weather events, emphasizing the need for varied energetic data accounting for rapid physiological and socioeconomic changes. Finally, we relate how specific estimated energy requirements are needed to account for the energetic challenges specific to extended space travel and ensure the success of interplanetary exploration.

Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome†.

STUDY QUESTION: What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? SUMMARY ANSWER: International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS. WHAT IS KNOWN ALREADY: The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist. STUDY DESIGN, SIZE, DURATION: The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations, with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and diversity and inclusion were considered throughout. PARTICIPANTS/MATERIALS, SETTING, METHODS: This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC). MAIN RESULTS AND THE ROLE OF CHANCE: The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management. LIMITATIONS, REASONS FOR CAUTION: Overall, recommendations are strengthened and evidence is improved, but remains generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided. WIDER IMPLICATIONS OF THE FINDINGS: The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the Guideline with an integrated evaluation program. STUDY FUNDING/COMPETING INTEREST(S): This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and European Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the partnering organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker's fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker's fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker's fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker's fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker's fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC.

Co-designing a community lifestyle intervention program to reduce postpartum weight retention.

BACKGROUND: Postpartum weight retention is a major contributor to obesity in later life resulting in long-term health consequences in women. Postpartum lifestyle interventions are known to be effective in reducing postpartum weight retention and improving the overall health and wellbeing of mothers but have poor reach and engagement. This study describes the engagement of mothers with young children in the development of a theory- and evidence-based intervention to reduce postpartum weight retention. METHODS: A participatory design methodology with input from a community mothers' group, literature reviews and an expert advisory group was applied. Mothers who were members of 'Mothers of Preschoolers' (MOPS) were invited to participate in a focus group discussion and two co-design workshop sessions. RESULTS: Thirteen women participated in a focus group discussion and 12 women in each co-design workshop. We found that mothers valued having social support from their peers, practical support such as meal delivery, and learning opportunities that focus on the mother's health and wellbeing. The advisory group suggested leveraging the unique skills and prior experiences of mothers within the group and developing a curriculum that mothers can be trained to deliver. CONCLUSION: A program that emphasizes the strengths and value of mothers can increase their self-worth and self-confidence resulting in intrinsic motivation to improve lifestyle behaviours. An intervention designed to be implemented by MOPS for its members and incorporated into their regular sessions has the potential for feasibility and acceptability among mothers with young children. PATIENT OR PUBLIC CONTRIBUTION: Mothers with young children were part of the program planners and were involved in the design and conduct of this study and in the interpretation of the findings. A member of a community mothers' group recruited other mothers with young children within the group to participate in a series of sessions to discuss their experiences of the postpartum period and preferences for a lifestyle program. The mothers identified the behavioural outcomes and program goals for a postpartum lifestyle program and then generated the program ideas based on these.

Lifestyle interventions in pregnancy targeting GDM prevention: looking ahead to precision medicine.

Gestational diabetes mellitus (GDM) is the most prevalent pregnancy-related endocrinopathy, affecting up to 25% of pregnancies worldwide. Pregnant individuals who develop GDM have an increased risk of complications during pregnancy and birth, as well as future development of type 2 diabetes mellitus and CVD. This increased risk is subsequently passed along to the offspring, perpetuating a cycle of metabolic dysfunction across generations. GDM prevention strategies have had mixed results for many years, but more recent systematic reviews and meta-analyses have suggested potential new avenues of prevention. The objective of this review is to summarise the literature examining the efficacy of lifestyle interventions for the prevention of GDM and to uncover if specific individual-level characteristics influence this outcome. Based on the present literature, we determined that future trials should be designed to understand if initiation of lifestyle intervention in the preconception period is more effective to reduce GDM. Furthermore, trials initiated during pregnancy should be developed through the lens of precision prevention. That is, trials should tailor intervention approaches based on individual-level risk defined by the presence of modifiable and non-modifiable risk factors. Finally, future interventions might also benefit from just-in-time adaptive intervention designs, which allow for interventions to be modified in real-time based on objective assessments of an individual's response.

Predicting energy intake in adults who are dieting and exercising.

BACKGROUND: When a lifestyle intervention combines caloric restriction and increased physical activity energy expenditure (PAEE), there are two components of energy balance, energy intake (EI) and physical activity energy expenditure (PAEE), that are routinely misreported and expensive to measure. Energy balance models have successfully predicted EI if PAEE is known. Estimating EI from an energy balance model when PAEE is not known remains an open question. OBJECTIVE: The objective was to evaluate the performance of an energy balance differential equation model to predict EI in an intervention that includes both calorie restriction and increases in PAEE. DESIGN: The Antonetti energy balance model that predicts body weight trajectories during weight loss was solved and inverted to estimate EI during weight loss. Using data from a calorie restriction study that included interventions with and without prescribed PAEE, we tested the validity of the Antonetti weight predictions against measured weight and the Antonetti EI model against measured EI using the intake-balance method at 168 days. We then evaluated the predicted EI from the model against measured EI in a study that prescribed both calorie restriction and increased PAEE. RESULTS: Compared with measured body weight at 168 days, the mean (±SD) model error was 1.30 ± 3.58 kg. Compared with measured EI at 168 days, the mean EI (±SD) model error in the intervention that prescribed calorie restriction and did not prescribe increased PAEE, was -84.9 ± 227.4 kcal/d. In the intervention that prescribed calorie restriction combined with increased PAEE, the mean (±SD) EI model error was -155.70 ± 205.70 kcal/d. CONCLUSION: The validity of the newly developed EI model was supported by experimental observations and can be used to determine EI during weight loss.

Assessment of Eating Behaviors and Perceptions of Time-Restricted Eating During Pregnancy.

BACKGROUND: The maternal metabolic milieu is challenged during pregnancy and may result in unwarranted metabolic complications. A time-restricted eating (TRE) pattern may optimize the metabolic response to pregnancy by improving glucose metabolism and reducing circulating glucose concentrations, as it does in nonpregnant individuals. OBJECTIVES: The objectives of this study were to 1) assess eating timing in pregnant women; 2) understand the perceptions of adopting a TRE pattern; 3) determine the barriers and support mechanisms for incorporating a TRE pattern; and 4) identify those most willing to adopt a TRE pattern during pregnancy. METHODS: This was a cross-sectional quantitative and quasi-qualitative online survey study for women who were pregnant at the time of study completion or had given birth in the prior 2 years. Group analyses were performed based off willingness to try a TRE pattern using chi-squared analyses, independent samples t-tests, or an analysis of variance. Three separate reviewers reviewed qualitative responses. RESULTS: A total of 431 women (BMI, 27.5 ± 0.3 kg/m2) completed the study. Of the participating women, 23.7% reported willingness to try a TRE pattern during pregnancy. Top barriers to adopting a TRE pattern during pregnancy were concerns for 1) safety; 2) nausea; and 3) hunger. The highest ranked support mechanisms were: 1) the ability to choose the eating window; 2) more frequent prenatal visits to ensure the health of the baby; and 3) receiving feedback from a dietician/nutritionist. Women who did not identify as White/Caucasian expressed a higher willingness to try a TRE pattern during pregnancy (P = 0.01). Women who were nulliparous expressed a higher willingness to try a TRE pattern (P = 0.05). DISCUSSION: TRE, an alternative dietary strategy shown to optimize metabolic control, may be effective to prevent and manage pregnancy-related metabolic impairments. To create an effective TRE intervention during pregnancy, the input of pregnant mothers is necessary to increase adherence and acceptability.

The moderating role of the built environment in prenatal lifestyle interventions.

This study examined whether the neighborhood built environment moderated gestational weight gain (GWG) in LIFE-Moms clinical trials. Participants were 790 pregnant women (13.9 weeks' gestation) with overweight or obesity randomized within four clinical centers to standard care or lifestyle intervention to reduce GWG. Geographic information system (GIS) was used to map the neighborhood built environment. The intervention relative to standard care significantly reduced GWG (coefficient = 0.05; p = 0.005) and this effect remained significant (p < 0.03) after adjusting for built environment variables. An interaction was observed for presence of fast food restaurants (coefficient = -0.007; p = 0.003). Post hoc tests based on a median split showed that the intervention relative to standard care reduced GWG in participants living in neighborhoods with lower fast food density 0.08 [95% CI, 0.03,0.12] kg/week (p = 0.001) but not in those living in areas with higher fast food density (0.02 [-0.04, 0.08] kg/week; p = 0.55). Interaction effects suggested less intervention efficacy among women living in neighborhoods with more grocery/convenience stores (coefficient = -0.005; p = 0.0001), more walkability (coefficient -0.012; p = 0.007) and less crime (coefficient = 0.001; p = 0.007), but post-hoc tests were not significant. No intervention x environment interaction effects were observed for total number of eating establishments or tree canopy. Lifestyle interventions during pregnancy were effective across diverse physical environments. Living in environments with easy access to fast food restaurants may limit efficacy of prenatal lifestyle interventions, but future research is needed to replicate these findings.

Calorie Restriction and Aging in Humans.

Calorie restriction (CR), the reduction of dietary intake below energy requirements while maintaining optimal nutrition, is the only known nutritional intervention with the potential to attenuate aging. Evidence from observational, preclinical, and clinical trials suggests the ability to increase life span by 1-5 years with an improvement in health span and quality of life. CR moderates intrinsic processes of aging through cellular and metabolic adaptations and reducing risk for the development of many cardiometabolic diseases. Yet, implementation of CR may require unique considerations for the elderly and other specific populations. The objectives of this review are to summarize the evidence for CR to modify primary and secondary aging; present caveats for implementation in special populations; describe newer, alternative approaches that have comparative effectiveness and fewer deleterious effects; and provide thoughts on the future of this important field of study.

A Role for Exercise to Counter Skeletal Muscle Clock Disruption.

Disruption of the skeletal muscle circadian clock leads to a preferential shift toward lipid oxidation while reducing carbohydrate oxidation. These effects are apparent at the whole-body level, including glucose intolerance, increased energy expenditure, and fasting hyperglycemia. We hypothesize that exercise counters these metabolic disturbances by modifying the skeletal muscle clock and reverting substrate metabolism back toward an optimal substrate balance.

Effect of 2 years of calorie restriction on liver biomarkers: results from the CALERIE phase 2 randomized controlled trial.

PURPOSE: Calorie restriction (CR) is an effective treatment for obesity-related liver and metabolic disease. However, CR studies in individuals without obesity are needed to see if CR could delay disease onset. Liver biomarkers indicate hepatic health and are linked to cardiometabolic disease. Our aim was to examine the effects of a 2-year CR intervention on liver biomarkers in healthy individuals without obesity. METHODS: The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study was a 2-year randomized controlled trial. Overall, 218 participants (body mass index: 25.1 ± 1.7 kg/m2) were enrolled into a control group (n = 75) that ate ad libitum (AL), or a CR group (n = 143) that aimed to decrease energy intake by 25%. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin were measured during the trial. RESULTS: At month 24, relative to the AL group, ALP (- 7 ± 1 IU/L; P < 0.01) and GGT (- 0.11 ± 0.04 log IU/L; P = 0.02) decreased and bilirubin increased (0.21 ± 0.06 log mg/dL; P < 0.01) in the CR group; no between-group differences in ALT (- 1 ± 1 IU/L; P > 0.99) or AST (2 ± 2 IU/L; P = 0.68) were revealed. However, sex-by-treatment-by-time interactions (P < 0.01) were observed, with CR (vs. control) inducing reduced ALT and GGT and increased AST in men only (P ≤ 0.02). CONCLUSIONS: In metabolically healthy individuals without obesity, 2 years of CR improves several liver biomarkers, with potentially greater improvements in men. These data suggest that sustained CR may improve long-term liver and metabolic disease risk in healthy adults. TRIAL REGISTRATION: Clinicaltrials.gov (NCT00427193). Registered January 2007.

One-year postpartum anthropometric outcomes in mothers and children in the LIFE-Moms lifestyle intervention clinical trials.

BACKGROUND/OBJECTIVES: Excess gestational weight gain (GWG) is a risk factor for maternal postpartum weight retention and excessive neonatal adiposity, especially in women with overweight or obesity. Whether lifestyle interventions to reduce excess GWG also reduce 12-month maternal postpartum weight retention and infant weight-for-length z score is unknown. Randomized controlled trials from the LIFE-Moms consortium investigated lifestyle interventions that began in pregnancy and tested whether there was benefit through 12 months on maternal postpartum weight retention (i.e., the difference in weight from early pregnancy to 12 months) and infant-weight-for-length z scores. SUBJECTS/METHODS: In LIFE-Moms, women (N = 1150; 14.1 weeks gestation at enrollment) with overweight or obesity were randomized within each of seven trials to lifestyle intervention or standard care. Individual participant data were combined and analyzed using generalized linear mixed models with trial entered as a random effect. The 12-month assessment was completed by 83% (959/1150) of women and 84% (961/1150) of infants. RESULTS: Compared with standard care, lifestyle intervention reduced postpartum weight retention (2.2 ± 7.0 vs. 0.7 ± 6.2 kg, respectively; difference of -1.6 kg (95% CI -2.5, -0.7; p = 0.0003); the intervention effect was mediated by reduction in excess GWG, which explained 22% of the effect on postpartum weight retention. Lifestyle intervention also significantly increased the odds (OR = 1.68 (95% CI, 1.26, 2.24)) and percentage of mothers (48.2% vs. 36.2%) at or below baseline weight at 12 months postpartum (yes/no) compared with standard care. There was no statistically significant treatment group effect on infant anthropometric outcomes at 12 months. CONCLUSIONS: Compared with standard care, lifestyle interventions initiated in pregnancy and focused on healthy eating, increased physical activity, and other behavioral strategies resulted in significantly less weight retention but similar infant anthropometric outcomes at 12 months postpartum in a large, diverse US population of women with overweight and obesity.

Racial differences in body composition and cardiometabolic risk during the menopause transition: a prospective, observational cohort study.

BACKGROUND: Obesity disproportionately affects more women than men. The loss of ovarian function during the menopause transition coincides with weight gain, increases in abdominal adiposity, and impaired metabolic health. Racial differences in obesity prevalence that results from the menopause transition are not well understood. OBJECTIVE: The purpose of the study was to assess longitudinal changes in body composition and cardiometabolic risk among black and white women during the menopausal transition. STUDY DESIGN: In a secondary analysis of a prospective, observational cohort study (the Healthy Transitions study), 161 women ≥43 years old with a body mass index of 20-40 kg/m2 and who had not yet transitioned through menopause were enrolled at Pennington Biomedical Research Center. Women were seen annually for body composition by dual-energy X-ray absorptiometry, for abdominal adipose tissue distribution by computed tomography, for sex steroid hormones, and for cardiometabolic risk factors that include fasting glucose, insulin, and lipids. Surrogate measures of insulin sensitivity were also calculated. RESULTS: Ninety-four women (25 black, 69 white) transitioned through menopause and were included within the analyses. At menopause onset, black women weighed more (77.8±3.0 vs 70.8±1.8 kg) and had a higher systolic (125±16 vs 118±14 mm Hg) and diastolic (80±8 vs 74±7 mm Hg) blood pressure compared with white women (all P≤.05). No other differences in body composition, sex steroid hormones, or cardiometabolic risk factors were observed at menopause onset. Before menopause, white women gained significant weight (3 kg), total body adiposity (6% percent body fat, 9% fat mass, 12% trunk fat mass) and abdominal adipose tissue (19% subcutaneous fat, 15% visceral fat, 19% total adipose tissue), which coincided with significant decreases in estradiol, sex hormone-binding globulin, and estrone sulfate and increases in follicle-stimulating hormone, total cholesterol, and low-density lipoprotein cholesterol. Conversely, black women had more abdominal adipose tissue before menopause, which was maintained across the menopause transition. Black women also had significant decreases in estrone sulfate and total testosterone and increases in follicle-stimulating hormone before menopause. In the postmenopausal years, abdominal subcutaneous adipose tissue, total adipose tissue, follicle-stimulating hormone, total cholesterol, and low-density and high-density lipoprotein cholesterol increased only in white women. CONCLUSION: White women gained more abdominal adiposity during the menopause transition compared with black women, which, in part, may be due to differences in the pattern of sex steroid hormone changes between women of different racial backgrounds. The gains in abdominal adiposity in white women were observed in tandem with increased cardiometabolic risk factors. Future studies should consider comprehensive lifestyle approaches to target these increased gains in abdominal adiposity (ie, nutrition and physical activity coaching), while taking into account the potential interactions of race, body adiposity, sex steroid hormones, and their influence on cardiometabolic risk.

Safety and pharmacokinetics of naringenin: A randomized, controlled, single-ascending-dose clinical trial.

AIMS: To evaluate the safety and pharmacokinetics of naringenin in healthy adults consuming whole-orange (Citrus sinensis) extract. METHODS AND METHODS: In a single-ascending-dose randomized crossover trial, 18 adults ingested doses of 150 mg (NAR150), 300 mg (NAR300), 600 mg (NAR600) and 900 mg (NAR900) naringenin or placebo. Each dose or placebo was followed by a wash-out period of at least 1 week. Blood safety markers were evaluated pre-dose and 24 hours post-dose. Adverse events (AEs) were recorded. Serum naringenin concentrations were measured before and over 24 hours following ingestion of placebo, NAR150 and NAR600. Four- and 24-hour serum measurements were obtained after placebo, NAR300 and NAR900 ingestion. Data were analysed using a mixed-effects linear model. RESULTS: There were no relevant AEs or changes in blood safety markers following ingestion of any of the naringenin doses. The pharmacokinetic variables were: maximal concentration: 15.76 ± 7.88 µM (NAR150) and 48.45 ± 7.88 µM (NAR600); time to peak: 3.17 ± 0.74 hours (NAR150) and 2.41 ± 0.74 hours (NAR600); area under the 24-hour concentration-time curve: 67.61 ± 24.36 µM × h (NAR150) and 199.05 ± 24.36 µM × h (NAR600); and apparent oral clearance: 10.21 ± 2.34 L/h (NAR150) and 13.70 ± 2.34 L/h (NAR600). Naringenin half-life was 3.0 hours (NAR150) and 2.65 hours (NAR600). After NAR300 ingestion, serum concentrations were 10.67 ± 5.74 µM (4 hours) and 0.35 ± 0.30 µM (24 hours). After NAR900 ingestion, serum concentrations were 43.11 ± 5.26 µM (4 hours) and 0.24 ± 0.30 µM (24 hours). CONCLUSIONS: Ingestion of 150 to 900 mg doses of naringenin is safe in healthy adults, and serum concentrations are proportional to the dose administered. Since naringenin (8 µM) is effective in primary human adipocytes, ingestion of 300 mg naringenin twice/d will likely elicit a physiological effect.

Obesity "complements" preeclampsia.

Preeclampsia (PE) is a devastating adverse outcome of pregnancy. Characterized by maternal hypertension, PE, when left untreated, can result in death of both mother and baby. The cause of PE remains unknown, and there is no way to predict which women will develop PE during pregnancy. The only known treatment is delivery of both the fetus and placenta; therefore, an abnormal placenta is thought to play a causal role. Women with obesity before pregnancy have an increased chance of developing PE. Increased adiposity results in a heightened state of systemic inflammation that can influence placental development. Adipose tissue is a rich source of proinflammatory cytokines and complement proteins, which have been implicated in the pathogenesis of PE by promoting the expression of antiangiogenic factors in the mother. Because an aggravated inflammatory response, angiogenic imbalance, and abnormal placentation are observed in PE, we hypothesize that maternal obesity and complement proteins derived from adipose tissue play an important role in the development of PE.

Dyslipidemia and the role of adipose tissue in early pregnancy in the BPH/5 mouse model for preeclampsia.

The hypertensive pregnancy disorder preeclampsia (PE) is a leading cause of fetal and maternal morbidity/mortality. Obesity increases the risk to develop PE, presumably via the release of inflammatory mediators from the adipose tissue, but the exact etiology remains largely unknown. Using obese PE-like blood pressure high subline 5 (BPH/5) and lean gestational age-matched C57Bl6 mice, we aimed to obtain insight into differential reproductive white adipose tissue (rWAT) gene expression, circulating lipids and inflammation at the maternal-fetal interface during early pregnancy. In addition, we investigated the effect of 7 days 25% calorie restriction (CR) in early pregnancy on gene expression in rWAT and implantation sites. Compared with C57Bl6, female BPH/5 are dyslipidemic before pregnancy and show an amplification of rWAT mass, circulating cholesterol, free fatty acids, and triacylglycerol levels throughout pregnancy. RNA sequencing showed that pregnant BPH/5 mice have elevated gene enrichment in pathways related to inflammation and cholesterol biosynthesis at embryonic day (e) 7.5. Expression of cholesterol-related HMGCS1, MVD, Cyp51a1, and DHCR was validated by quantitative reverse-transcription-polymerase chain reaction. CR during the first 7 days of pregnancy restored the relative mRNA expression of these genes to a level comparable to C57Bl6 pregnant females and reduced the expression of circulating leptin and proinflammatory prostaglandin synthase 2 in both rWAT and implantation sites in BPH/5 mice at e7.5. Our data suggest a possible role for rWAT in the dyslipidemic state and inflammatory uterine milieu that might underlie the pathogenesis of PE. Future studies should further address the physiological functioning of the adipose tissue in relation to PE-related pregnancy outcomes.

The Panacea of Human Aging: Calorie Restriction Versus Exercise.

Primary aging is the progressive decline in health and fitness and depends on metabolic rate and oxidative stress. Untoward changes in body composition and metabolic function characterize secondary aging. We hypothesize that both exercise and calorie restriction (CR) improve secondary aging, but only CR improves primary. However, CR followed with exercise is a superior strategy to maintain overall health and quality of life with age.

Mood and quality of life changes in pregnancy and postpartum and the effect of a behavioral intervention targeting excess gestational weight gain in women with overweight and obesity: a parallel-arm randomized controlled pilot trial.

BACKGROUND: Intensive lifestyle interventions in pregnancy have shown success in limiting gestational weight gain, but the effects on mood and quality of life in pregnancy and postpartum are less known. The purpose was to quantify changes in mental and physical quality of life and depressive symptoms across pregnancy and the postpartum period, to determine the association between gestational weight gain and change in mood and quality of life, and to assess the effect of a behavioral intervention targeting excess gestational weight gain on these outcomes. METHODS: A three group parallel-arm randomized controlled pilot trial of 54 pregnant women who were overweight or obese was conducted to test whether the SmartMoms® intervention decreased the proportion of women with excess gestational weight gain. Individuals randomized to Usual Care (n = 17) did not receive any weight management services from interventionists. Individuals randomized to the SmartMoms® intervention (n = 37) were provided with behavioral weight management counseling by interventionists either in clinic (In-Person, n = 18) or remotely through a smartphone application (Phone, n = 19). In a subset of 43 women, mood and mental and physical quality of life were assessed with the Beck Depression Inventory-II and the Rand 12-Item short form, respectively, in early pregnancy, late pregnancy, 1-2 months postpartum, and 12 months postpartum. RESULTS: The SmartMoms® intervention and Usual Care groups had higher depressive symptoms (p < 0.03 for SmartMoms® intervention, p < 0.01 for Usual Care) and decreased physical health (p < 0.01) from early to late pregnancy. Both groups returned to early pregnancy mood and physical quality of life postpartum. Mental health did not change from early to late pregnancy (p = 0.8), from early pregnancy to 1-2 months (p = 0.5), or from early pregnancy to 12 months postpartum (p = 0.9), respectively. There were no significant intervention effects. Higher gestational weight gain was associated with worsened mood and lower physical quality of life across pregnancy. CONCLUSION: High depressive symptoms and poor quality of life may be interrelated with the incidence of excess gestational weight gain. The behavioral gestational weight gain intervention did not significantly impact these outcomes, but mood and quality of life should be considered within future interventions and clinical practice to effectively limit excess gestational weight gain. TRIAL REGISTRATION: NCT01610752 , Expecting Success, Registered 31 May 2012.

Change in self-efficacy, eating behaviors and food cravings during two years of calorie restriction in humans without obesity.

Calorie restriction (CR) enhances longevity in humans who are normal weight, overweight and obese. While dietary regimens can change self-efficacy, eating behaviors, and food cravings in individuals with obesity, the responses of these measures to prolonged CR in individuals who are exclusively not obese is unknown. The aim of this analysis was to test the effects of a two-year CR intervention on self-efficacy and eating attitudes and behaviors in humans without obesity by analyzing data from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE 2) study. Participants (n = 218, BMI range = 21.3-29.0 kg/m2) were randomized to a 25% CR group or an ad libitum (AL) group. Eating attitudes and behaviors and self-efficacy were assessed using validated questionnaires at baseline, month 12, and month 24. Dietary restraint and self-efficacy increased in the CR compared to the AL group (ES ≥ 0.32). Increased self-efficacy was negatively related to weight change (ρ < -0.24). In the CR group, males showed a reduction in cravings for carbohydrates and fats at month 24, whereas females did not. The CR group showed elevations in state hunger, which were transient, and disinhibited eating (ES ≥ 0.37). In individuals without obesity, dietary restraint and self-efficacy could be important in promoting long-term CR for individuals looking to use CR as a tool to improve longevity.