Effects of total fat intake on body fatness in adults

Background: The ideal proportion of energy from fat in our food and its relation to body weight is not clear. In order to prevent overweight and obesity in the general population, we need to understand the relationship between the proportion of energy from fat and resulting weight and body fatness in the general population. Objectives: To assess the effects of proportion of energy intake from fat on measures of body fatness (including body weight, waist circumference, percentage body fat and body mass index) in people not aiming to lose weight, using all appropriate randomised controlled trials (RCTs) of at least six months duration. Search methods: We searched CENTRAL, MEDLINE, Embase, Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) to October 2019. We did not limit the search by language. Selection criteria: Trials fulfilled the following criteria: 1) randomised intervention trial, 2) included adults aged at least 18 years, 3) randomised to a lower fat versus higher fat diet, without the intention to reduce weight in any participants, 4) not multifactorial and 5) assessed a measure of weight or body fatness after at least six months. We duplicated inclusion decisions and resolved disagreement by discussion or referral to a third party. Data collection and analysis: We extracted data on the population, intervention, control and outcome measures in duplicate. We extracted measures of body fatness (body weight, BMI, percentage body fat and waist circumference) independently in duplicate at all available time points. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity, funnel plot analyses and GRADE assessment. Main results: We included 37 RCTs (57,079 participants). There is consistent high-quality evidence from RCTs that reducing total fat intake results in small reductions in body fatness; this was seen in almost all included studies and was highly resistant to sensitivity analyses (GRADE high-consistency evidence, not downgraded). The effect of eating less fat (compared with higher fat intake) is a mean body weight reduction of 1.4 kg (95% confidence interval (CI) -1.7 to -1.1 kg, in 53,875 participants from 26 RCTs, I2 = 75%). The heterogeneity was explained in subgrouping and meta-regression. These suggested that greater weight loss results from greater fat reductions in people with lower fat intake at baseline, and people with higher body mass index (BMI) at baseline. The size of the effect on weight does not alter over time and is mirrored by reductions in BMI (MD -0.5 kg/m2, 95% CI -0.6 to -0.3, 46,539 participants in 14 trials, I2 = 21%), waist circumference (MD -0.5 cm, 95% CI -0.7 to -0.2, 16,620 participants in 3 trials; I2 = 21%), and percentage body fat (MD -0.3% body fat, 95% CI -0.6 to 0.00, P = 0.05, in 2350 participants in 2 trials; I2 = 0%). There was no suggestion of harms associated with low fat diets that might mitigate any benefits on body fatness. The reduction in body weight was reflected in small reductions in LDL (-0.13 mmol/L, 95% CI -0.21 to -0.05), and total cholesterol (-0.23 mmol/L, 95% CI -0.32 to -0.14), with little or no effect on HDL cholesterol (-0.02 mmol/L, 95% CI -0.03 to 0.00), triglycerides (0.01 mmol/L, 95% CI -0.05 to 0.07), systolic (-0.75 mmHg, 95% CI -1.42 to -0.07) or diastolic blood pressure(-0.52 mmHg, 95% CI -0.95 to -0.09), all GRADE high-consistency evidence or quality of life (0.04, 95% CI 0.01 to 0.07, on a scale of 0 to 10, GRADE low-consistency evidence). Authors' conclusions: Trials where participants were randomised to a lower fat intake versus a higher fat intake, but with no intention to reduce weight, showed a consistent, stable but small effect of low fat intake on body fatness: slightly lower weight, BMI, waist circumference and percentage body fat compared with higher fat arms. Greater fat reduction, lower baseline fat intake and higher baseline BMI were all associated with greater reductions in weight. There was no evidence of harm to serum lipids, blood pressure or quality of life, but rather of small benefits or no effect

Cu(II)-Ion-Catalyzed Solvolysis of <i>N,N-</i>Bis(2-picolyl)ureas in Alcohol Solvents: Evidence for Cleavage Involving Nucleophilic Addition and Strong Assistance of Bis(2-picolyl)amine Leaving Group Departure

The kinetics and products for solvolysis of <i>N</i>-<i>p</i>-nitrophenyl-<i>N</i>′,<i>N</i>′-bis­(pyridin-2-ylmethyl) urea (<b>7a</b>), <i>N</i>-methyl-<i>N</i>-<i>p</i>-nitrophenyl-<i>N</i>′,<i>N</i>′-bis­(pyridin-2-yl methyl) urea (<b>7b</b>), and <i>N</i>-phenyl-<i>N</i>′,<i>N</i>′-bis­(pyridin-2-yl-methyl) urea (DPPU) (<b>7c</b>) promoted by Cu­(II) ion in methanol and ethanol were studied under _s^spH-controlled conditions at 25 °C. Methanolysis and ethanolysis of these substrates proceeds rapidly at a 1:1 ratio of substrate:metal ion, the half-times for decomposition of the Cu­(II):<b>7a</b> complexes being ∼150 min in methanol and 15 min in ethanol. In all cases, the reaction products are the Cu­(II) complex of bis­(2-picolyl)­amine and the <i>O</i>-methyl or <i>O</i>-ethyl carbamate of the parent aniline, signifying that the point of cleavage is the bis­(2-picolyl)NCO bond. Reactions of the Cu­(II):<b>7b</b> complexes in each solvent proceed about 3–5 times slower than their respective Cu­(II):<b>7a</b> complexes, excluding an elimination mechanism that proceeds through an isocyanate which subsequently adds alcohol to give the observed products. The reactions also proceed in other solvents, with the order of reactivity ethanol > methanol >1-propanol >2-propanol > acetonitrile (with 0.2% methanol) > water spanning a range of 150-fold. The mechanism of the reactions is discussed, and the reactivity and mode of cleavage are compared with that of the M­(II)-promoted ethanolytic cleavage of a mono-2-picolyl derivative, <i>N</i>-<i>p</i>-nitrophenyl-<i>N</i>′-(pyridin-2-yl-methyl) urea (<b>4a</b>), which had previously been shown to cleave at the aniline N–CO bond. The large estimated acceleration of the rate of attack of ethoxide on <b>7b</b> of at least 2 × 10¹⁶ provided by associating Cu­(II) with the departing group in this urea is discussed in terms of a trifunctional role for the metal ion involving Lewis acid activation of the substrate, intramolecular delivery of a Cu­(II)-coordinated ethoxide, and metal-ion-assisted leaving group departure