Physiologic Adaptation to Macronutrient Change Distorts Findings from Short Dietary Trials: Reanalysis of a Metabolic Ward Study.

An influential 2-wk cross-over feeding trial without a washout period purported to show advantages of a low-fat diet (LFD) compared with a low-carbohydrate diet (LCD) for weight control. In contrast to several other macronutrient trials, the diet order effect was originally reported as not significant. In light of a new analysis by the original investigative group identifying an order effect, we aimed to examine, in a reanalysis of publicly available data (16 of 20 original participants; 7 female; mean BMI, 27.8 kg/m2), the validity of the original results and the claims that trial data oppose the carbohydrate-insulin model of obesity (CIM). We found that energy intake on the LCD was much lower when this diet was consumed first compared with second (a difference of -1164 kcal/d, P = 3.6 × 10-13); the opposite pattern was observed for the LFD (924 kcal/d, P = 2.0 × 10-16). This carry-over effect was significant (P interaction = 0.0004) whereas the net dietary effect was not (P = 0.4). Likewise, the between-arm difference (LCD - LFD) was -320 kcal/d in the first period and +1771 kcal/d in the second. Body fat decreased with consumption of the LCD first and increased with consumption of this diet second (-0.69 ± 0.33 compared with 0.57 ± 0.32 kg, P = 0.007). LCD-first participants had higher ß-hydroxybutyrate levels while consuming the LCD and lower respiratory quotients while consuming LFD when compared with LFD-first participants on their respective diets. Change in insulin secretion as assessed by C-peptide in the first diet period predicted higher energy intake and less fat loss in the second period. These findings, which tend to support rather than oppose the CIM, suggest that differential (unequal) carry-over effects and short duration, with no washout period, preclude causal inferences regarding chronic macronutrient effects from this trial.

A Mediterranean diet plan in lactating women with obesity reduces maternal energy intake and modulates human milk composition - a feasibility study.

Introduction: Maternal obesity is associated with increased concentrations of human milk (HM) obesogenic hormones, pro-inflammatory cytokines, and oligosaccharides (HMOs) that have been associated with infant growth and adiposity. The objective of this pilot study was to determine if adherence to a Mediterranean meal plan during lactation modulates macronutrients and bioactive molecules in human milk from mothers with obesity. Methods: Sixteen healthy, exclusively breastfeeding women with obesity (body mass index ≥30 kg/m2) enrolled between 4 and 5 months postpartum. The women followed a 4-week Mediterranean meal plan which was provided at no cost. Maternal and infant anthropometrics, HM composition, and infant intakes were measured at enrollment and at weeks 2 and 4 of the intervention. Thirteen mother-infant dyads completed the study. Additionally, participants from an adjacent, observational cohort who had obesity and who collected milk at 5 and 6 months postpartum were compared to this cohort. Results: Participants' healthy eating index scores improved (+27 units, p < 0.001), fat mass index decreased (-4.7%, p < 0.001), and daily energy and fat intake were lower (-423.5 kcal/day, p < 0.001 and-32.7 g/day, p < 0.001, respectively) following the intervention. While HM macronutrient concentrations did not change, HM leptin, total human milk oligosaccharides (HMOs), HMO-bound fucose, Lacto-N-fucopentaose (LNFP)-II, LNFP-III, and difucosyllacto-N-tetrose (DFLNT) concentrations were lower following the intervention. Infant intakes of leptin, tumor necrosis factor (TNF)-α, total HMOs, HMO-bound fucose, LNFP-III and DFLNT were lower following the intervention. Specific components of the maternal diet (protein and fat) and specific measures of maternal diet quality (protein, dairy, greens and beans, fruit and vegetables) were associated with infant intakes and growth. Discussion: Adherence to a Mediterranean meal plan increases dietary quality while reducing total fat and caloric intake. In effect, body composition in women with obesity improved, HM composition and infants' intakes were modulated. These findings provide, for the first time, evidence-based data that enhancing maternal dietary quality during lactation may promote both maternal and child health. Longer intervention studies examining the impact of maternal diet quality on HM composition, infant growth, and infant development are warranted.

Design and conduct of a randomized controlled feeding trial in a residential setting with mitigation for COVID-19.

BACKGROUND: Evaluating effects of different macronutrient diets in randomized trials requires well defined infrastructure and rigorous methods to ensure intervention fidelity and adherence. METHODS: This controlled feeding study comprised two phases. During a Run-in phase (14-15 weeks), study participants (18-50 years, BMI, ≥27 kg/m2) consumed a very-low-carbohydrate (VLC) diet, with home delivery of prepared meals, at an energy level to promote 15 ± 3% weight loss. During a Residential phase (13 weeks), participants resided at a conference center. They received a eucaloric VLC diet for three weeks and then were randomized to isocaloric test diets for 10 weeks: VLC (5% energy from carbohydrate, 77% from fat), high-carbohydrate (HC)-Starch (57%, 25%; including 20% energy from refined grains), or HC-Sugar (57%, 25%; including 20% sugar). Outcomes included measures of body composition and energy expenditure, chronic disease risk factors, and variables pertaining to physiological mechanisms. Six cores provided infrastructure for implementing standardized protocols: Recruitment, Diet and Meal Production, Participant Support, Assessments, Regulatory Affairs and Data Management, and Statistics. The first participants were enrolled in May 2018. Participants residing at the conference center at the start of the COVID-19 pandemic completed the study, with each core implementing mitigation plans. RESULTS: Before early shutdown, 77 participants were randomized, and 70 completed the trial (65% of planned completion). Process measures indicated integrity to protocols for weighing menu items, within narrow tolerance limits, and participant adherence, assessed by direct observation and continuous glucose monitoring. CONCLUSION: Available data will inform future research, albeit with less statistical power than originally planned.