Dietary sulfur amino acid restriction in humans with overweight and obesity: Evidence of an altered plasma and urine sulfurome, and a novel metabolic signature that correlates with loss of fat mass and adipose tissue gene expression.

BACKGROUND: In animals, dietary sulfur amino acid restriction (SAAR) improves metabolic health, possibly mediated by altering sulfur amino acid metabolism and enhanced anti-obesogenic processes in adipose tissue. AIM: To assess the effects of SAAR over time on the plasma and urine SAA-related metabolites (sulfurome) in humans with overweight and obesity, and explore whether such changes were associated with body weight, body fat and adipose tissue gene expression. METHODS: Fifty-nine subjects were randomly allocated to SAAR (∼2 g SAA, n = 31) or a control diet (∼5.6 g SAA, n = 28) consisting of plant-based whole-foods and supplemented with capsules to titrate contents of SAA. Sulfurome metabolites in plasma and urine at baseline, 4 and 8 weeks were measured using HPLC and LC-MS/MS. mRNA-sequencing of subcutaneous white adipose tissue (scWAT) was performed to assess changes in gene expression. Data were analyzed with mixed model regression. Principal component analyses (PCA) were performed on the sulfurome data to identify potential signatures characterizing the response to SAAR. RESULTS: SAAR led to marked decrease of the main urinary excretion product sulfate (p < 0.001) and plasma and/or 24-h urine concentrations of cystathionine, sulfite, thiosulfate, H2S, hypotaurine and taurine. PCA revealed a distinct metabolic signature related to decreased transsulfuration and H2S catabolism that predicted greater weight loss and android fat mass loss in SAAR vs. controls (all pinteraction < 0.05). This signature correlated positively with scWAT expression of genes in the tricarboxylic acid cycle, electron transport and ß-oxidation (FDR = 0.02). CONCLUSION: SAAR leads to distinct alterations of the plasma and urine sulfurome in humans, and predicted increased loss of weight and android fat mass, and adipose tissue lipolytic gene expression in scWAT. Our data suggest that SAA are linked to obesogenic processes and that SAAR may be useful for obesity and related disorders. TRIAL IDENTIFIER: https://clinicaltrials.gov/study/NCT04701346.

Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial.

BACKGROUND: Dietary sulfur amino acid restriction (SAAR) improves metabolic health in animals. In this study, we investigated the effect of dietary SAAR on body weight, body composition, resting metabolic rate, gene expression profiles in white adipose tissue (WAT), and an extensive blood biomarker profile in humans with overweight or obesity. METHODS: N = 59 participants with overweight or obesity (73% women) were randomized stratified by sex to an 8-week plant-based dietary intervention low (~ 2 g/day, SAAR) or high (~ 5.6 g/day, control group) in sulfur amino acids. The diets were provided in full to the participants, and both investigators and participants were blinded to the intervention. Outcome analyses were performed using linear mixed model regression adjusted for baseline values of the outcome and sex. RESULTS: SAAR led to a ~ 20% greater weight loss compared to controls (ß 95% CI - 1.14 (- 2.04, - 0.25) kg, p = 0.013). Despite greater weight loss, resting metabolic rate remained similar between groups. Furthermore, SAAR decreased serum leptin, and increased ketone bodies compared to controls. In WAT, 20 genes were upregulated whereas 24 genes were downregulated (FDR < 5%) in the SAAR group compared to controls. Generally applicable gene set enrichment analyses revealed that processes associated with ribosomes were upregulated, whereas processes related to structural components were downregulated. CONCLUSION: Our study shows that SAAR leads to greater weight loss, decreased leptin and increased ketone bodies compared to controls. Further research on SAAR is needed to investigate the therapeutic potential for metabolic conditions in humans. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04701346, registered Jan 8th 2021, https://www. CLINICALTRIALS: gov/study/NCT04701346.

Front-of-Pack Nutrition Labels: Comparing the Nordic Keyhole and Nutri-Score in a Swedish Context.

The extent to which different front-of-pack nutrition labels (FOPNLs) agree or contradict each other has been insufficiently investigated. Considering the 2020 proposal from the European Commission to create a harmonized FOPNL, the aim of this study was to assess agreements and disagreements between two FOPNL schemes-the Keyhole and the Nutri-Score-in a Swedish context. The current Keyhole criteria and the updated Nutri-Score 2022 algorithm were applied to 984 food items and their nutrient compositions, obtained from the food database of the Swedish Food Agency. Agreements (Keyhole-eligible and Nutri-Score A or B; or not Keyhole-eligible and Nutri-Score C, D, or E) and disagreements (Keyhole-eligible and Nutri-Score C, D, or E, or not Keyhole-eligible and Nutri-Score A or B) were calculated as percentages for all items and by food group. An agreement was found for 81% of included items. The lowest level of agreement was found for the groups of flour, grains, and rice (62% agreement) and for plant-based meat and fish analogues (33% agreement). There is generally a good level of agreement between the Keyhole and the Nutri-Score for food items on the Swedish market. Large disagreements found for plant-based meat and fish analogues, and products based on cereals/grains, highlight important considerations for the development of a harmonized FOPNL within Europe.

Effect of aerobic exercise and low-carbohydrate high-fat diet on glucose tolerance and android/gynoid fat in overweight/obese women: A randomized controlled trial.

The study was designed to compare the effects of weight loss induced by a low-carbohydrate-high-fat diet or a normal diet, with and without exercise, on glucose tolerance measured as area under the curve (AUC), and android (A) and gynoid (G) fat distribution. The study was registered at clinicaltrials.gov; NCT04100356. In total, 57 women classified as overweight or obese (age 40 ± 3.5 years, body mass index 31.1 ± 2.6 kg/m2) were randomly assigned and completed a 10-week intervention using a low-carbohydrate high-fat diet or a normal diet, with or without aerobic interval exercise. An equal deficit of 700 kcal/day was prescribed, either restricting the diet only, or moderately restricting diet and including three 50-min high-intensity bicycle sessions per week. There were thus four groups: normal diet (NORM); low-carbohydrate-high-fat diet (LCHF); normal diet with exercise (NORM-EX); and low-carbohydrate-high-fat diet with exercise (LCHF-EX). Linear mixed models was used to assess differences between groups. With all groups pooled, the intervention resulted in a weight loss of 6.7 ± 2.5% (p < 0.001). The intervention did not result in differences between groups in AUC glucose, nor in fasting glucose or indicis for insulin resistance such as Homeostatic Model Assessment, Matsuda Insulin Sensitivity Index, insulinogenic index and disposition index. Post-intervention android fat was lower in LCHF than NORM (3,223 ± 727 vs. 2,533 ± 535 g, p = 0.041). LCHF reached a lower A/G ratio than NORM (0.94 ± 0.12 vs. 1.04 ± 0.09, p = 0.011) and LCHF-EX (0.94 ± 0.12 vs. 1.09 ± 0.09, p < 0.001) after the intervention. LCHF resulted in lower android fat mass compared to NORM and the lowest A/G ratio compared to the other matched groups, but with no accompanying improvement in AUC glucose. In conclusion, although all groups achieved improvements in glucose tolerance, no superior effect was observed with the LCHF diet, neither with nor without exercise.

The association of fasting plasma thiol fractions with body fat compartments, biomarker profile, and adipose tissue gene expression.

People with high plasma total cysteine (tCys) have higher fat mass and higher concentrations of the atherogenic apolipoprotein B (apoB). The disulfide form, cystine, enhanced human adipogenesis and correlated with total fat mass in a Middle-Eastern cohort. In 35 European adults with overweight (88.6% women) and with dual-X-ray absorptiometry measurements of regional fat, we investigated how cystine compared to other free disulfides in their association with total regional adiposity, plasma lipid and glucose biomarkers, and adipose tissue lipid enzyme mRNA (n = 19). Most total plasma homocysteine (tHcy) (78%) was protein-bound; 63% of total glutathione (tGSH) was reduced. tCys was 49% protein-bound, 30% mixed-disulfide, 15% cystine, and 6% reduced. Controlling for age and lean mass, cystine and total free cysteine were the fractions most strongly associated with android and total fat: 1% higher cystine predicted 1.97% higher android fat mass (95% CI 0.64, 3.31) and 1.25% (0.65, 2.98) higher total fat mass (both p = 0.005). A positive association between tCys and apoB (ß: 0.64%; 95% CI 0.17, 1.12%, p = 0.009) was apparently driven by free cysteine and cystine; cystine was also inversely associated with the HDL-associated apolipoprotein A1 (ß: -0.57%; 95% CI -0.96, -0.17%, p = 0.007). No independent positive associations with adiposity were noted for tGSH or tHcy fractions. Plasma cystine correlated with CPT1a mRNA (Spearman's r = 0.68, p = 0.001). In conclusion, plasma cystine-but not homocysteine or glutathione disulfides-is associated with android adiposity and an atherogenic plasma apolipoprotein profile. The role of cystine in human adiposity and cardiometabolic risk deserves investigation. ClinicalTrials.gov identifiers: NCT02647970 and NCT03629392.

Changes in dietary habits and BMI z-score after a 6-month non-randomized cluster-controlled trial among 6-12 years old overweight and obese Norwegian children.

Background: Effective prevention programs to address the high prevalence of childhood overweight and obesity and the concomitant health consequences have been warranted. Objective: To improve dietary habits and weight status among Norwegian children with overweight/obesity in the primary care setting. Design: A 6-month non-randomized cluster-controlled intervention among 137 children, aged 6-12 years, with overweight/obesity and their parents. Intervention and control groups were recruited by public health nurses and followed-up by 12 Healthy Life Centers across Norway. The intervention group received individual family counseling and participated in nutrition courses and physical activity groups. A frequency questionnaire assessing sociodemographic characteristics and dietary habits was completed by the parents. Trained public health nurses measured height and weight using standardized methods to calculate body mass index (BMI) and BMI z-scores. Results: The intervention resulted in an increased odds of consuming evening meals (OR: 3.42), a decreased availability of salty snacks (ß = -0.17), a decreased intake of salty snacks (-0.18), an increased consumption of water (ß = 0.20), and a decreased estimated total intake of energy (ß = -0.17), carbohydrates (ß = -0.17), mono- and disaccharides (ß = -0.21), sucrose (ß = -0.24), and saturated fatty acids (ß = -0.17). The intervention directly predicted lower BMI z-score (ß = -0.17), and post-treatment levels of energy (ß = -0.65), saturated fat (ß = 0.43), and total carbohydrates (ß = 0.41) were directly linked to BMI z-score after intervention. Age and sex were indirectly associated with BMI after intervention through energy and saturated fat intake. Conclusions: The intervention had a beneficial impact on nutrient intake and weight status among children with overweight/obesity. These findings provide support for implementing complex intervention programs tailored to local primary care settings. Trial registration: Clinicaltrials.gov, NCT02290171. Registered 13. November 2014, https://clinicaltrials.gov/ct2/show/NCT02290171.

Cysteine restriction-specific effects of sulfur amino acid restriction on lipid metabolism.

Decreasing the dietary intake of methionine exerts robust anti-adiposity effects in rodents but modest effects in humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing methionine and eliminating cysteine. Such diets exert both methionine restriction (MR) and cysteine restriction (CR), that is, sulfur amino acid restriction (SAAR). Contrarily, SAAR diets formulated for human consumption included cysteine, and thus might have exerted only MR. Epidemiological studies positively correlate body adiposity with plasma cysteine but not methionine, suggesting that CR, but not MR, is responsible for the anti-adiposity effects of SAAR. Whether this is true, and, if so, the underlying mechanisms are unknown. Using methionine- and cysteine-titrated diets, we demonstrate that the anti-adiposity effects of SAAR are due to CR. Data indicate that CR increases serinogenesis (serine biosynthesis from non-glucose substrates) by diverting substrates from glyceroneogenesis, which is essential for fatty acid reesterification and triglyceride synthesis. Molecular data suggest that CR depletes hepatic glutathione and induces Nrf2 and its downstream targets Phgdh (the serine biosynthetic enzyme) and Pepck-M. In mice, the magnitude of SAAR-induced changes in molecular markers depended on dietary fat concentration (60% fat >10% fat), sex (males > females), and age-at-onset (young > adult). Our findings are translationally relevant as we found negative and positive correlations of plasma serine and cysteine, respectively, with triglycerides and metabolic syndrome criteria in a cross-sectional epidemiological study. Controlled feeding of low-SAA, high-polyunsaturated fatty acid diets increased plasma serine in humans. Serinogenesis might be a target for treating hypertriglyceridemia.

A nationwide school fruit and vegetable policy and childhood and adolescent overweight: A quasi-natural experimental study.

BACKGROUND: School free fruit and vegetable (FFV) policies are used to promote healthy dietary habits and tackle obesity; however, our understanding of their effects on weight outcomes is limited. We assess the effect of a nationwide FFV policy on childhood and adolescent weight status and explore heterogeneity by sex and socioeconomic position. METHODS AND FINDINGS: This study used a quasi-natural experimental design. Between 2007 and 2014, Norwegian combined schools (grades 1-10, age 6 to 16 years) were obligated to provide FFVs while elementary schools (grades 1-7) were not. We used 4 nationwide studies (n = 11,215 children) from the Norwegian Growth Cohort with longitudinal or cross-sectional anthropometric data up to age 8.5 and 13 years to capture variation in FFV exposure. Outcomes were body mass index standard deviation score (BMISDS), overweight and obesity (OW/OB), waist circumference (WC), and weight to height ratio (WtHR) at age 8.5 years, and BMISDS and OW/OB at age 13 years. Analyses included longitudinal models of the pre- and post-exposure trajectories to estimate the policy effect. The participation rate in each cohort was >80%, and in most analyses <4% were excluded due to missing data. Estimates were adjusted for region, population density, and parental education. In pooled models additionally adjusted for pre-exposure BMISDS, there was little evidence of any benefit or unintended consequence from 1-2.5 years of exposure to the FFV policy on BMISDS, OW/OB, WC, or WtHR in either sex. For example, boys exposed to the FFV policy had a 0.05 higher BMISDS (95% CI: -0.04, 0.14), a 1.20-fold higher odds of OW/OB (95% CI: 0.86, 1.66) and a 0.3 cm bigger WC (95% CI: -0.3, 0.8); while exposed girls had a 0.04 higher BMISDS (95% CI: -0.04, 0.13), a 1.03 fold higher odds of OW/OB (95% CI: 0.75, 1.39), and a 0-cm difference in WC (95% CI: -0.6, 0.6). There was evidence of heterogeneity in the policy effect estimates at 8.5 years across cohorts and socioeconomic position; however, these results were inconsistent with other comparisons. Analysis at age 13 years, after 4 years of policy exposure, also showed little evidence of an effect on BMISDS or OW/OB. The main limitations of this study are the potential for residual confounding and exposure misclassification, despite efforts to minimize their impact on conclusions. CONCLUSIONS: In this study we observed little evidence that the Norwegian nationwide FFV policy had any notable beneficial effect or unintended consequence on weight status among Norwegian children and adolescents.

Overweight, obesity, and thinness among a nationally representative sample of Norwegian adolescents and changes from childhood: Associations with sex, region, and population density.

OBJECTIVE: To estimate the prevalence of overweight, obesity, and thinness among Norwegian 13-year-olds and the changes from childhood (age 8 years) to adolescence (age 13 years); and to explore associations with sex, region, and population density from childhood to adolescence. DESIGN: We used longitudinal, anthropometric data collected by school health nurses conducted in Norway. Weight status was classified according to the International Obesity Task Force cut-offs for overweight, obesity, and thinness, and according to mean body mass index (kg/m2). PARTICIPANTS: The Norwegian Youth Growth Study, consisting of a nationally representative sample of Norwegian 13-year-olds (n = 1852; 50.7% girls), which is a part of The Norwegian Growth Cohort. RESULTS: Among 13-year-old Norwegians, the prevalence of overweight (including obesity), obesity, and thinness was 15.8%, 2.5%, and 7.3%, respectively. There was little evidence that these had changed from 8 to 13 years. From 8 to 13 years, the odds of obesity was highest in the Northern region of Norway compared to the South-East (odds ratio (OR): 3.78 (95% confidence interval (CI): 1.13, 12.65; p = 0.036) and in rural areas (OR: 4.76 (95% CI: 1.52, 14.90; p = 0.027). Over the same age period, girls had a trend towards a higher odds of thinness compared to boys (OR: 1.65 (95% CI: 0.98, 2.78; p = 0.057). CONCLUSIONS: In Norway, the prevalence of overweight, obesity, and thinness among 13-year-olds seem to be established by age 8 years. The prevalence of obesity was higher in the North and in rural areas. The results indicate the continued need for early prevention and treatment, and targeted interventions to certain areas.

Sulfur amino acid restriction, energy metabolism and obesity: a study protocol of an 8-week randomized controlled dietary intervention with whole foods and amino acid supplements.

BACKGROUND: Dietary sulfur amino acid (SAA) restriction is an established animal model for increasing lifespan and improving metabolic health. Data from human studies are limited. In the study outlined in this protocol, we will evaluate if dietary SAA restriction can reduce body weight and improve resting energy expenditure (REE) and parameters related to metabolic health. METHOD/DESIGN: Men and women (calculated sample size = 60), aged 18-45 years, with body mass index of 27-35 kg/m2 will be included in a double-blind 8-week dietary intervention study. The participants will be randomized in a 1:1 manner to a diet with either low or high SAA. Both groups will receive an equal base diet consisting of low-SAA plant-based whole foods and an amino acid supplement free of SAA. Contrasting SAA contents will be achieved using capsules with or without methionine and cysteine (SAAhigh, total diet SAA ~ 50-60 mg/kg body weight/day; SAAlow, total diet SAA ~ 15-25 mg/kg body weight/day). The primary outcome is body weight change. Data and material collection will also include body composition (dual X-ray absorptiometry), resting energy expenditure (whole-room indirect calorimetry) and samples of blood, urine, feces and adipose tissue at baseline, at 4 weeks and at study completion. Measures will be taken to promote and monitor diet adherence. Data will be analyzed using linear mixed model regression to account for the repeated measures design and within-subject correlation. DISCUSSION: The strength of this study is the randomized double-blind design. A limitation is the restrictive nature of the diet which may lead to poor compliance. If this study reveals a beneficial effect of the SAAlow diet on body composition and metabolic health, it opens up for new strategies for prevention and treatment of overweight, obesity and its associated disorders. Trial registration ClinicalTrials.gov: NCT04701346, Registration date: January 8th, 2021.

Effects of short-term methionine and cysteine restriction and enrichment with polyunsaturated fatty acids on oral glucose tolerance, plasma amino acids, fatty acids, lactate and pyruvate: results from a pilot study.

OBJECTIVE: In this 7-day pilot study we randomized healthy, normal-weight men and women to either a dietary intervention with methionine and cysteine restriction enriched in PUFA (Met/Cyslow + PUFA, n = 7) or with high contents of methionine, cysteine and SFA (Met/Cyshigh + SFA, n = 7). The objective was to describe the short-term responses in oral glucose tolerance, amino acid profile, total fatty acid profile, pyruvate and lactate following a Met/Cyslow + PUFA diet vs. Met/Cyshigh + SFA. RESULTS: The diet groups consisted of five women and two men, aged 20-38 years. After the 7-d intervention median pre- and post-oral glucose tolerance test (OGTT) glucose concentrations were 5 mmol/L and 4 mmol/L respectively in the Met/Cyslow + PUFA group. In the Met/Cyshigh + SFA group, median pre- and post-OGTT glucose concentrations were 4.8 mmol/L and 4.65 mmol/L after the 7-d intervention. The responses in the amino acid profiles were similar in both groups during the intervention with the exception of serine. Fatty acids decreased from baseline to day 7 in both groups. Plasma lactate and pyruvate were similar for both groups with an increase to day 3 before approaching baseline values at day 7. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02647970, registration date: January 6th 2016.

The effects of an abrupt increase in taxes on candy and soda in Norway: an observational study of retail sales.

BACKGROUND: Fiscal policies are used to promote a healthier diet; however, there is still a call for real-world evaluations of taxes on unhealthy foods and beverages. We aimed to evaluate the effect of an abrupt increase, of respectively 80 and 40%, in the excising Norwegian taxes on candy and beverages on volume sales of candy and soda. We expected sales to fall. METHODS: We analyzed electronic point of sale data covering approximately 98% of volume sales of grocery stores in Norway. In two pre-registered models with weekly (log-)sales of taxed candy and soda from 3884 individual stores, we modeled the difference between the jump (discontinuity) in the trend around the time of the increase in taxes and the corresponding jump in the trend in a control season from the previous years (Model 1). In addition, we modeled the difference between the intervention and the control season in their changes in average sales (Model 2). RESULTS: Model 1 showed a 6.1% (one-sided 95% CI: not applicable (NA), 23.4, p-value = 0.26) increase and a - 3.9% (95% CI: NA, 4.9, p-value = 0.23) reduction in the differences in the jump in the trends, for candy and soda, respectively. The second model showed a relative decrease of - 4.9% (95% CI: NA, 1.0, p-value = 0.08) in the average sales of candy and an increase of 1.5% (95% CI: NA, 5.0, p-value = 0.24) in sales of soda. Supplementary analyses suggested that the results were sensitive to clustering on the time dimension. CONCLUSIONS: When using two different quasi-experimental designs to model changes in volume sales of taxed candy and soda, we were not able to detect reductions in sales that coincided with an increase in the taxes. Variation across time makes it difficult to detect potentially small changes in sales even when using an entire country's worth of sales data on the level of individual stores. We speculate that the tax increases were too modest to affect the prices to alter sales sufficiently.

Postprandial effects of a meal low in sulfur amino acids and high in polyunsaturated fatty acids compared to a meal high in sulfur amino acids and saturated fatty acids on stearoyl CoA-desaturase indices and plasma sulfur amino acids: a pilot study.

OBJECTIVE: The sulfur amino acid (SAA) cysteine is positively related, whereas polyunsaturated fatty acids (PUFAs) are inversely related to activity of the lipogenic enzyme stearoyl-CoA desaturase (SCD). High SCD activity promotes obesity in animals, and plasma activity indices positively associates with fat mass in humans. SCD may thus be a target for dietary intervention with SAA restriction and PUFA enrichment with unknown potential benefits for body composition. We randomized ten healthy individuals to a meal restricted in SAAs and enriched with PUFAs (Cys/Metlow + PUFA) (n = 5) or a meal enriched in SAA and saturated fatty acids (Cys/Methigh + SFA) (n = 5). We measured plasma SCD activity indices (SCD16 and SCD18) and SAAs response hourly from baseline and up to 4 h postprandial. RESULTS: SCD16 was unchanged whereas SCD18 tended to increase in the Cys/Metlow + PUFA compared to the Cys/Methigh + SFA group (ptime*group interaction = 0.08). Plasma concentrations of total cysteine fractions including free and reduced cysteine decreased in the Cys/Metlow + PUFA compared to the Cys/Methigh + SFA group (both ptime*group interaction < 0.001). In conclusion, a meal low in SAA but high in PUFAs reduced plasma cysteine fractions but not SCD activity indices. This pilot study can be useful for the design and diet composition of future dietary interventions that targets SCD and SAA. Trial registration ClinicalTrials.gov: NCT02647970, registration date: 6 January 2016.

Effects of dietary methionine and cysteine restriction on plasma biomarkers, serum fibroblast growth factor 21, and adipose tissue gene expression in women with overweight or obesity: a double-blind randomized controlled pilot study.

BACKGROUND: Dietary restriction of methionine and cysteine is a well-described model that improves metabolic health in rodents. To investigate the translational potential in humans, we evaluated the effects of dietary methionine and cysteine restriction on cardiometabolic risk factors, plasma and urinary amino acid profile, serum fibroblast growth factor 21 (FGF21), and subcutaneous adipose tissue gene expression in women with overweight and obesity in a double-blind randomized controlled pilot study. METHODS: Twenty women with overweight or obesity were allocated to a diet low (Met/Cys-low, n = 7), medium (Met/Cys-medium, n = 7) or high (Met/Cys-high, n = 6) in methionine and cysteine for 7 days. The diets differed only by methionine and cysteine content. Blood and urine were collected at day 0, 1, 3 and 7 and subcutaneous adipose tissue biopsies were taken at day 0 and 7. RESULTS: Plasma methionine and cystathionine and urinary total cysteine decreased, whereas FGF21 increased in the Met/Cys-low vs. Met/Cys-high group. The Met/Cys-low group had increased mRNA expression of lipogenic genes in adipose tissue including DGAT1. When we excluded one participant with high fasting insulin at baseline, the Met/Cys-low group showed increased expression of ACAC, DGAT1, and tendencies for increased expression of FASN and SCD1 compared to the Met/Cys-high group. The participants reported satisfactory compliance and that the diets were moderately easy to follow. CONCLUSIONS: Our data suggest that dietary methionine and cysteine restriction may have beneficial effects on circulating biomarkers, including FGF21, and influence subcutaneous adipose tissue gene expression. These results will aid in the design and implementation of future large-scale dietary interventions with methionine and cysteine restriction. Trial registration ClinicalTrials.gov Identifier: NCT03629392, registration date: 14/08/2018 https://clinicaltrials.gov/ct2/show/NCT03629392.

Low-Carbohydrate High-Fat Diet and Exercise: Effect of a 10-Week Intervention on Body Composition and CVD Risk Factors in Overweight and Obese Women-A Randomized Controlled Trial.

We assessed the effect of weight-loss induced with a low-carbohydrate-high-fat diet with and without exercise, on body-composition, cardiorespiratory fitness and cardiovascular risk factors. A total of 57 overweight and obese women (age 40 ± 3.5 years, body mass index 31.1 ± 2.6 kg∙m-2) completed a 10-week intervention using a low-carbohydrate-high-fat diet, with or without interval exercise. An equal deficit of 700 kcal∙day-1 was prescribed, restricting diet only, or moderately restricting diet and adding exercise, producing four groups; normal diet (NORM); low-carbohydrate-high-fat diet (LCHF); normal diet and exercise (NORM-EX); and low-carbohydrate-high-fat diet and exercise (LCHF-EX). Linear Mixed Models were used to assess between-group differences. The intervention resulted in an average 6.7 ± 2.5% weight-loss (p < 0.001). Post-intervention % fat was lower in NORM-EX than NORM (40.0 ± 4.2 vs. 43.5 ± 3.5%, p = 0.024). NORM-EX reached lower values in total cholesterol than NORM (3.9 ± 0.6 vs. 4.7 ± 0.7 mmol/L, p = 0.003), and LCHF-EX (3.9 ± 0.6 vs. 4.9 ± 1.1 mmol/L, p = 0.004). Post intervention triglycerides levels were lower in NORM-EX than NORM (0.87 ± 0.21 vs. 1.11 ± 0.34 mmol/L, p = 0.030). The low-carbohydrate-high-fat diet had no superior effect on body composition, V˙O2peak or cardiovascular risk factors compared to a normal diet, with or without exercise. In conclusion, the intervention decreased fat mass, but exercise improved body composition and caused the most favorable changes in total cholesterol and triglycerides in the NORM-EX. Exercise increased cardiorespiratory fitness, regardless of diet.

A comprehensive multicomponent school-based educational intervention did not affect fruit and vegetable intake at the 14-year follow-up.

The intake of fruit and vegetables is associated with beneficial health outcomes, and studies aimed at increasing fruit and vegetable intake lack long-term follow-up. The primary objective of this study was to evaluate the long-term (14-year) effects of a multicomponent school-based educational intervention targeted to increase fruit and vegetable intake in children. The secondary objective was to evaluate the potential synergistic effect between free school fruit and the educational program. A cluster randomized school-based intervention was initiated in 2001 in Norway, known as the Fruit and Vegetable Make the Marks study. In total, 38 schools were randomized; for the intervention (n = 18) and as control schools (n = 20). A subsample of the intervention schools (n = 9) were additionally given free school fruit, resulting in two intervention groups - one with and one without free fruit. Participants completed questionnaires in September 2001 (baseline, mean age 11.8), May 2002 (at the end of the intervention), May 2003, May 2005, September 2009 and throughout 2016 (mean age 26.5). Of 1950 participants, 982 (50.4%) completed the 14-year follow-up and were considered as the current study sample. Analysis yielded no 14-year effects of the educational program on fruit and vegetable intake. A synergistic effect between the educational program and free fruit was not observed either. Future studies might benefit from increased focus on more extensive parental involvement, increased home availability, and a longer intervention period. However, more long-term studies are needed to evaluate the effects of school-based interventions into adulthood. Trial registration number: Ethical approval and research clearance was obtained from The National Committees for Research Ethics in Norway (file number S-01076) and The Norwegian Centre for Research Data (file number 12395).

Combining Dietary Sulfur Amino Acid Restriction with Polyunsaturated Fatty Acid Intake in Humans: A Randomized Controlled Pilot Trial.

Dietary and plasma total cysteine (tCys) have been associated with adiposity, possibly through interaction with stearoyl⁻CoA desaturase (SCD), which is an enzyme that is involved in fatty acid and energy metabolism. We evaluated the effect of a dietary intervention with low cysteine and methionine and high polyunsaturated fatty acids (PUFAs) on plasma and urinary sulfur amino acids and SCD activity indices. Fourteen normal-weight healthy subjects were randomized to a seven-day diet low in cysteine and methionine and high in PUFAs (Cys/Metlow + PUFA), or high in saturated fatty acids (SFA), cysteine, and methionine (Cys/Methigh + SFA). Compared with the Cys/Methigh + SFA group, plasma methionine and cystathionine decreased (p-values < 0.05), whereas cystine tended to increase (p = 0.06) in the Cys/Metlow + PUFA group. Plasma total cysteine (tCys) was not significantly different between the groups. Urinary cysteine and taurine decreased in the Cys/Metlow + PUFA group compared with the Cys/Methigh + SFA group (p-values < 0.05). Plasma SCD-activity indices were not different between the groups, but the change in cystine correlated with the SCD-16 index in the Cys/Metlow + PUFA group. A diet low in methionine and cysteine decreased plasma methionine and urinary cysteine and taurine. Plasma tCys was unchanged, suggesting that compensatory mechanisms are activated during methionine and cysteine restriction to maintain plasma tCys.