A randomized controlled trial of a weight loss maintenance program in adults with obesity: the WLM3P study.

BACKGROUND/OBJECTIVES: The escalating obesity epidemic necessitates effective, sustainable weight loss (WL) and maintenance strategies. This study aimed to evaluate the effectiveness of the Weight Loss Maintenance 3 Phases Program (WLM3P) in achieving a clinically significant long-term weight loss (WL) (≥5% initial WL at 18 months) in adults with obesity compared to a standard low-carbohydrate diet (LCD). SUBJECTS/METHODS: In this two-phase trial, 112 participants targeting initial WL (0-6 months) and subsequent maintenance (7-18 months) were randomly assigned to either WLM3P or LCD groups. Outcomes assessed included change in body weight (kg, %), improvements in body composition, and metabolic profile. RESULTS: Of 112 randomized participants, 69% (n = 77) completed the study. At 18 months, WL in the WLM3P group (n = 40) was 15.5 ± 8.3% compared to 9.6 ± 8.5% in the LCD group (n = 37) (p < 0.001). The odds ratio of achieving WL ≥ 10% and ≥15% were significantly higher in the WLM3P group. Complete-case analysis revealed significantly greater improvements in BMI, body fat mass, visceral fat area, waist circumference, waist-to-hip ratio, HDL, and triglyceride/HDL ratio in WLM3P than in LCD. No serious adverse events were reported. CONCLUSION: Both programs effectively promoted clinically relevant WL and its maintenance. However, the WLM3P program was more successful in helping participants achieve greater WL targets of ≥10% and ≥15%, along with other clinical benefits, after an 18-month intervention. TRIAL REGISTRATION NUMBER: NCT04192357.

Body Composition Evaluation and Clinical Markers of Cardiometabolic Risk in Patients with Phenylketonuria.

Cardiovascular diseases are the main cause of mortality worldwide. Patients with phenylketonuria (PKU) may be at increased cardiovascular risk. This review provides an overview of clinical and metabolic cardiovascular risk factors, explores the connections between body composition (including fat mass and ectopic fat) and cardiovascular risk, and examines various methods for evaluating body composition. It particularly focuses on nutritional ultrasound, given its emerging availability and practical utility in clinical settings. Possible causes of increased cardiometabolic risk in PKU are also explored, including an increased intake of carbohydrates, chronic exposure to amino acids, and characteristics of microbiota. It is important to evaluate cardiovascular risk factors and body composition in patients with PKU. We suggest systematic monitoring of body composition to develop nutritional management and hydration strategies to optimize performance within the limits of nutritional therapy.

Empowerment-based nutrition interventions on blood pressure: a randomized comparative effectiveness trial.

Introduction: Empowerment lifestyle programs are needed to reduce the risk of hypertension. Our study compared the effectiveness of two empowerment-based approaches toward blood pressure (BP) reduction: salt reduction-specific program vs. healthy lifestyle general program. Methods: Three hundred and eleven adults (median age of 44 years, IQR 34-54 years) were randomly assigned to a salt reduction (n = 147) or a healthy lifestyle program (n = 164). The outcome measures were urinary sodium (Na+) and potassium (K+) excretion, systolic (SBP) and diastolic (DBP) blood pressure, weight, and waist circumference. Results: There were no significant differences in primary and secondary outcomes between the two program groups. When comparing each program to baseline, the program focused on salt reduction was effective in lowering BP following a 12-week intervention with a mean change of -2.5 mm Hg in SBP (95% CI, -4.1 to -0.8) and - 2.7 mm Hg in DBP (95% CI, -3.8 to -1.5) in the intention-to-treat (ITT) analysis. In the complete-case (CC) analysis, the mean change was -2.1 mm Hg in SBP (95% CI, -3.7 to -0.5) and - 2.3 mm Hg in DBP (95% CI, -3.4 to -1.1). This effect increases in subjects with high-normal BP or hypertension [SBP - 7.9 mm Hg (95% CI, -12.5 to -3.3); DBP - 7.3 mm Hg (95% CI, -10.2 to -4.4)]. The healthy lifestyle group also exhibited BP improvements after 12 weeks; however, the changes were less pronounced compared to the salt reduction group and were observed only for DBP [mean change of -1.5 mm Hg (95% CI, -2.6 to -0.4) in ITT analysis and - 1.4 mm Hg (95% CI, -2.4 to -0.3) in CC analysis, relative to baseline]. Overall, improvements in Na+/K+ ratio, weight, and Mediterranean diet adherence resulted in clinically significant SBP decreases. Importantly, BP reduction is attributed to improved dietary quality, rather than being solely linked to changes in the Na+/K+ ratio. Conclusion: Salt-focused programs are effective public health tools mainly in managing individuals at high risk of hypertension. Nevertheless, in general, empowerment-based approaches are important strategies for lowering BP, by promoting health literacy that culminates in adherence to the Mediterranean diet and weight reduction.

Essential Trace Elements Status in Portuguese Pregnant Women and Their Association with Maternal and Neonatal Outcomes: A Prospective Study from the IoMum Cohort.

Cobalt (Co), copper (Cu), manganese (Mn), molybdenum (Mo), and zinc (Zn) are essential trace elements (ETEs) and important cofactors for intermediary metabolism or redox balance. These ETEs are crucial during pregnancy, their role on specific pregnancy outcomes is largely unknown. This prospective study (#NCT04010708) aimed to assess urinary levels of these ETEs in pregnancy and to evaluate their association with pregnancy outcomes. First trimester pregnant women of Porto and Lisbon provided a random spot urine sample, and sociodemographic and lifestyle data. Clinical data were obtained from clinical records. Urinary ETEs were quantified by inductively coupled plasma mass spectrometry (ICP-MS). A total of 635 mother:child pairs were included. Having urinary Zn levels above the 50th percentile (P50) was an independent risk factor for pre-eclampsia (PE) (aOR [95% CI]: 5.350 [1.044-27.423], p = 0.044). Urinary Zn levels above the P50 decreased the risk of small for gestational age (SGA) birth head circumference (aOR [95% CI]: 0.315 [0.113-0.883], p = 0.028), but it increased the risk SGA length (aOR [95% CI]: 2.531 [1.057-6.062], p = 0.037). This study may provide valuable information for public health policies related to prenatal nutrition, while informing future efforts to de-fine urinary reference intervals for ETEs in pregnant women.

Impact on Diet Quality and Burden of Care in Sapropterin Dihydrochloride Use in Children with Phenylketonuria: A 6 Month Follow-Up Report.

INTRODUCTION: In phenylketonuria (PKU) changes in dietary patterns and behaviors in sapropterin-responsive populations have not been widely reported. We aimed to assess changes in food quality, mental health and burden of care in a paediatric PKU sapropterin-responsive cohort. METHODS: In an observational, longitudinal study, patient questionnaires on food frequency, neophobia, anxiety and depression, impact on family and burden of care were applied at baseline, 3 and 6-months post successful sapropterin-responsiveness testing (defined as a 30% reduction in blood phenylalanine levels). RESULTS: 17 children (10.8 ± 4.2 years) completed 6-months follow-up. Patients body mass index (BMI) z-scores remained unchanged after sapropterin initiation. Blood phenylalanine was stable. Natural protein increased (p < 0.001) and protein substitute intake decreased (p = 0.002). There were increases in regular cow's milk (p = 0.001), meat/fish, eggs (p = 0.005), bread (p = 0.01) and pasta (p = 0.011) intakes but special low-protein foods intake decreased. Anxiety (p = 0.016) and depression (p = 0.022) decreased in caregivers. The impact-on-family, familial-social impact (p = 0.002) and personal strain (p = 0.001) lessened. After sapropterin, caregivers spent less time on PKU tasks, the majority ate meals outside the home more regularly and fewer caregivers had to deny food choices to their children. CONCLUSION: There were significant positive changes in food patterns, behaviors and burden of care in children with PKU and their families after 6-months on sapropterin treatment.

Procedures in Fecal Microbiota Transplantation for Treating Irritable Bowel Syndrome: Systematic Review and Meta-Analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disease with no effective treatment. Altered microbiota composition seems implicated in disease etiology and therefore fecal microbial transplantation (FMT) has emerged as a possible treatment therapy. To clarify the clinical parameters impacting FMT efficacy, we conducted a systematic review with subgroup analysis. METHODS: A literature search was performed identifying randomized controlled trials (RCTs) comparing FMT with placebo in IBS adult patients (8-week follow-up) with a reported improvement in global IBS symptoms. RESULTS: Seven RCTs (489 participants) met the eligibility requirements. Although FMT seems not to be effective in global improvement of IBS symptoms, subgroup analysis shows that FMT through gastroscopy or nasojejunal tube are effective IBS treatments (RR 3.03; 95% CI 1.94-4.73; I2 = 10%, p < 0.00001). When considering non-oral ingestion routes, IBS patients with constipation symptoms are more likely to benefit from FMT administration (p = 0.003 for the difference between IBS subtypes regarding constipation). Fresh fecal transplant and bowel preparation seem also to have impact on FMT efficacy (p = 0.03 and p = 0.01, respectively). CONCLUSION: Our meta-analysis revealed a set of critical steps that could affect the efficacy of FMT as clinical procedure to treat IBS, nevertheless more RCTs are needed.

The Effect of Regular Consumption of Reformulated Breads on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Bread is a major source of grain-derived carbohydrates worldwide. High intakes of refined grains, low in dietary fiber and high in glycemic index, are linked with increased risk for type 2 diabetes mellitus (T2DM) and other chronic diseases. Hence, improvements in the composition of bread could influence population health. This systematic review evaluated the effect of regular consumption of reformulated breads on glycemic control among healthy adults, adults at cardiometabolic risk or with manifest T2DM. A literature search was performed using MEDLINE, Embase, Web of Science and the Cochrane Central Register of Controlled Trials. Eligible studies employed a bread intervention (≥2 wk) in adults (healthy, at cardiometabolic risk or manifest T2DM) and reported glycemic outcomes (fasting blood glucose, fasting insulin, HOMA-IR, HbA1c, and postprandial glucose responses). Data were pooled using generic inverse variance with random-effects model and presented as mean difference (MD) or standardized MD between treatments with 95% CIs. Twenty-two studies met the inclusion criteria (n = 1037 participants). Compared with "regular" or comparator bread, consumption of reformulated intervention breads yielded lower fasting blood glucose concentrations (MD: -0.21 mmol/L; 95% CI: -0.38, -0.03; I2 = 88%, moderate certainty of evidence), yet no differences in fasting insulin (MD: -1.59 pmol/L; 95% CI: -5.78, 2.59; I2 = 38%, moderate certainty of evidence), HOMA-IR (MD: -0.09; 95% CI: -0.35, 0.23; I2 = 60%, moderate certainty of evidence), HbA1c (MD: -0.14; 95% CI: -0.39, 0.10; I2 = 56%, very low certainty of evidence), or postprandial glucose response (SMD: -0.46; 95% CI: -1.28, 0.36; I2 = 74%, low certainty of evidence). Subgroup analyses revealed a beneficial effect for fasting blood glucose only among people with T2DM (low certainty of evidence). Our findings suggest a beneficial effect of reformulated breads high in dietary fiber, whole grains, and/or functional ingredients on fasting blood glucose concentrations in adults, primarily among those with T2DM. This trial was registered at PROSPERO as CRD42020205458.

Association between Elevated Iodine Intake and IQ among School Children in Portugal.

The goal of this work was to examine whether elevated iodine intake was associated with adverse effects on IQ among school-age children in Portugal. In a representative sample of children from the north of the country, IQ percentiles by age (assessed with Raven's Colored Progressive Matrices) were dichotomized to <50 ("below-average" IQs) and ≥50. Morning urine iodine concentrations, corrected for creatinine, were dichotomized to <250 µg/g and ≥250 µg/g, according to the European Commission/Scientific Committee on Food's tolerable upper level of daily iodine intake for young children. Data were examined with Chi-square tests, logistic regression, and GLM univariate analysis. The sample (N = 1965) was classified as generally iodine-adequate (median urinary iodine concentration = 129 µg/L; median iodine-to-creatinine ratio = 126 µg/g) according to the WHO's criteria. A greater proportion of children in the ≥250 µg/g group had below-average IQs, compared to children with less than 250 µg/g (p = 0.037), despite a sizable (though non-significant) proportion of children in the less-than-250 µg/g group also presenting below-average IQs, at the bottom of the iodine distribution (<50 µg/g). The proportion of below-average IQs increased with increasingly elevated iodine concentrations (p = 0.047). The association remained significant after the adjustment for confounders, with the elevated iodine group showing increased odds of having below-average IQs when compared with the non-elevated iodine group (OR 1.55; 95% CI 1.11−2.17; p = 0.011). Consistently, the former group presented a lower mean IQ than the latter (p = 0.006). High iodine intake was associated with lower IQs even in a population classified as iodine-adequate. These results bear on child cognition and on initiatives involving iodine supplementation.

Is the Phenylalanine-Restricted Diet a Risk Factor for Overweight or Obesity in Patients with Phenylketonuria (PKU)? A Systematic Review and Meta-Analysis.

Although there is a general assumption that a phenylalanine (Phe)-restricted diet promotes overweight in patients with phenylketonuria (PKU), it is unclear if this presumption is supported by scientific evidence. This systematic review aimed to determine if patients with PKU are at a higher risk of overweight compared to healthy individuals. A literature search was carried out on PubMed, Cochrane Library, and Embase databases. Risk of bias of individual studies was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, and the quality of the evidence for each outcome was assessed using the NutriGrade scoring system. From 829 articles identified, 15 were included in the systematic review and 12 in the meta-analysis. Body mass index (BMI) was similar between patients with PKU and healthy controls, providing no evidence to support the idea that a Phe-restricted diet is a risk factor for the development of overweight. However, a subgroup of patients with classical PKU had a significantly higher BMI than healthy controls. Given the increasing prevalence of overweight in the general population, patients with PKU require lifelong follow-up, receiving personalised nutritional counselling, with methodical nutritional status monitoring from a multidisciplinary team in inherited metabolic disorders.

Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity.

Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.Trial registration: NCT04370808.

Gut Microbiota Diversity and C-Reactive Protein Are Predictors of Disease Severity in COVID-19 Patients.

The risk factors for coronavirus disease 2019 (COVID-19) severity are still poorly understood. Considering the pivotal role of the gut microbiota on host immune and inflammatory functions, we investigated the association between changes in the gut microbiota composition and the clinical severity of COVID-19. We conducted a multicenter cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: (1) the WHO Clinical Progression Scale-mild, 19 (16.5%); moderate, 37 (32.2%); or severe, 59 (51.3%), and (2) the location of recovery from COVID-19-ambulatory, 14 (household isolation, 12.2%); hospitalized in ward, 40 (34.8%); or hospitalized in the intensive care unit, 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing, and the data obtained were further related to the clinical parameters of COVID-19 patients. The risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models. In comparison to mild COVID-19 patients, the gut microbiota of moderate and severe patients have: (a) lower Firmicutes/Bacteroidetes ratio; (b) higher abundance of Proteobacteria; and (c) lower abundance of beneficial butyrate-producing bacteria such as the genera Roseburia and Lachnospira. Multivariable regression analysis showed that the Shannon diversity index [odds ratio (OR) = 2.85, 95% CI = 1.09-7.41, p = 0.032) and C-reactive protein (OR = 3.45, 95% CI = 1.33-8.91, p = 0.011) are risk factors for severe COVID-19 (a score of 6 or higher in the WHO Clinical Progression Scale). In conclusion, our results demonstrated that hospitalized patients with moderate and severe COVID-19 have microbial signatures of gut dysbiosis; for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker of COVID-19 severity.

Iodine knowledge is associated with iodine status in Portuguese pregnant women: results from the IoMum cohort study.

Lack of knowledge about iodine has been suggested as a risk factor for iodine deficiency in pregnant women, but no studies have addressed this issue in Portugal. So, the aim of this study was to investigate iodine knowledge among Portuguese pregnant women and its association with iodine status. IoMum, a prospective observational study, included 485 pregnant women recruited at Centro Hospitalar e Universitário de S. João, Porto, between the 10th and 13th gestational weeks. Partial scores for knowledge on iodine importance, on iodine food sources or on iodised salt were obtained through the application of a structured questionnaire. Then, a total iodine knowledge score was calculated and grouped into low, medium and high knowledge categories. Urinary iodine concentration (UIC) was measured in spot urine samples by inductively coupled plasma MS. Of the pregnant women, 54 % correctly recognised iodine as important to neurocognitive development, 32 % were unable to identify any iodine-rich food and 71 % presented lack of knowledge regarding iodised salt. Of the women, 61 % had a medium total score of iodine knowledge. Knowledge on iodine importance during pregnancy was positively associated with iodine supplementation and also with UIC. Nevertheless, median UIC in women who correctly recognised the importance of iodine was below the cut-off for adequacy in pregnancy (150 µg/l). In conclusion, knowledge on iodine importance is positively associated with iodine status. Despite this, recognising iodine importance during pregnancy may not be sufficient to ensure iodine adequacy. Literacy-promoting actions are urgently needed to improve iodine status in pregnancy.

The association of milk and dairy consumption with iodine status in pregnant women in Oporto region.

The role of milk and dairy products in supplying iodine to pregnant women is unknown in Portugal. The aim of this study was to evaluate the association between milk and dairy product consumption and the iodine status of pregnant women in the IoMum cohort of the Oporto region. Pregnant women were recruited between 10 and 13 weeks of gestation, when they provided a spot urine sample and information on lifestyle and intake of iodine-rich foods. Urinary iodine concentration (UIC) was determined by inductively coupled plasma MS. A total of 468 pregnant women (269 iodine supplement users and 199 non-supplement users) were considered eligible for analysis. Milk (but not yogurt or cheese) intake was positively associated with UIC, in the whole population (P = 0·02) and in the non-supplement users (P = 0·002), but not in the supplement users (P = 0·29). In non-supplement users, adjusted multinomial logistic regression analysis showed that milk consumption <3 times/month was associated with a five times increased risk of having UIC < 50 µg/l when compared with milk consumption ≥2 times/d (OR 5·4; 95 % CI 1·55, 18·78; P = 0·008). The highest UIC was observed in supplement users who reported consuming milk once per d (160 µg/l). Milk, but not yogurt or cheese, was positively associated with iodine status of pregnant women. Despite the observed positive association, daily milk consumption may not be sufficient to ensure adequate iodine intake in this population.

Daily intake of wheat germ-enriched bread may promote a healthy gut bacterial microbiota: a randomised controlled trial.

PURPOSE: Wheat bran fibre has a beneficial effect on gastrointestinal function, but evidence for wheat germ is scarce. Accordingly, we evaluated the effects of daily intake of wheat germ on gastrointestinal discomfort and gut microbiota by adding wheat germ to refined (white) wheat bread, the most consumed bread type. We hypothesised that an improvement in the composition of refined bread could beneficially affect intestinal health without compromising consumers' acceptance. METHODS: Fifty-five healthy adults were recruited for a randomised, double-blind, crossover, controlled trial comprising two 4-week intervention periods separated by a 5-week washout stage. During the first 4-week period, one group consumed wheat bread enriched with 6 g of wheat germ and the control group consumed non-enriched wheat bread. RESULTS: Wheat germ-enriched bread was well-appreciated and the number of participants that demonstrated minimal gastrointestinal improvements after wheat-germ intake was higher than in the control arm. Importantly, intake of wheat germ-enriched bread decreased the perceived gastrointestinal discomfort-related quality of life (subscale worries and concerns) over refined white bread. The improvements in the gastrointestinal function were accompanied by favourable changes in gut microbiota, increasing the number of Bacteroides spp. and Bifidobacterium spp. CONCLUSIONS: Adding wheat germ to industrially made white bread without altering sensory properties may promote a healthy gut bacterial microbiota and the gastrointestinal health.

Does intake of bread supplemented with wheat germ have a preventive role on cardiovascular disease risk markers in healthy volunteers? A randomised, controlled, crossover trial.

OBJECTIVE: Intake of whole grains is associated with a reduced risk of cardiovascular disease (CVD). This evidence is also strong for bran alone, but findings about germ are conflicting. Our aim was to elucidate the role of germ in primary prevention of cardiovascular events, and therefore, a staple food was selected for 6 g of germ supplementation. This corresponds to sixfold increase in the global mean consumption of germ, while preserving the sensory proprieties of refined bread which is crucial for consumer's acceptance. DESIGN: Randomised, double-blinded, crossover, controlled clinical trial with 15-week follow-up comprising a 2-week run-in, two intervention periods of 4 weeks each and a 5-week washout period. SETTING: A single centre in the north of Portugal. PARTICIPANTS: 55 eligible healthy adults (mean age of 34 years and body mass index between 19 and 38 kg/m2) were randomly assigned. INTERVENTIONS: The study consisted of two intervention periods including daily intake of refined wheat bread enriched with 6 g of wheat germ and control (non-enriched bread). OUTCOMES: Changes in fasting cholesterol and triglycerides, fasting and postprandial glucose, insulin sensitivity and C reactive protein. RESULTS: We observed no significant effect of daily intake of wheat germ on cholesterol and triglycerides levels, on postprandial glucose response and on insulin sensitivity. Incremental area under curve glucose and homeostasis model assessment for insulin resistance did not change, suggesting that 6 g of wheat germ have no effect on glucose metabolism. No effect was also observed in the subgroup of participants who complied with the protocol (n=47). CONCLUSIONS: The absence of alterations on lipid and glucose profiles suggests that germ up to 6 g/day may have no preventive effect on CVD risk. However, it is important to investigate other food vehicles that can accommodate higher doses of wheat germ in future studies. TRIAL REGISTRATION NUMBER: NCT02405507.

Iodine Status and Iodised Salt Consumption in Portuguese School-Aged Children: The Iogeneration Study.

The World Health Organization promotes salt iodisation to control iodine deficiency. In Portugal, the use of iodised salt in school canteens has been mandatory since 2013. The present study aimed to evaluate iodine status in school-aged children (6-12 years) and to monitor the use of iodised salt in school canteens. A total of 2018 participants were randomly selected to participate in a cross-sectional survey in northern Portugal. Children's urine and salt samples from households and school canteens were collected. A lifestyle questionnaire was completed by parents to assess children's eating frequency of iodine food sources. Urinary iodine concentration (UIC) was measured by inductively coupled plasma-mass spectrometry. The median UIC was 129 µg/L which indicates the adequacy of iodine status and 32% of the children had UIC < 100 µg/L. No school canteen implemented the iodised salt policy and only 2% of the households were using iodised salt. Lower consumption of milk, but not fish, was associated with a higher risk of iodine deficiency. Estimation of sodium intake from spot urine samples could be an opportunity for adequate monitoring of population means. Implementation of iodine deficiency control policies should include a monitoring program aligned with the commitment of reducing the population salt intake.

Can wheat germ have a beneficial effect on human health? A study protocol for a randomised crossover controlled trial to evaluate its health effects.

INTRODUCTION: Cardiovascular diseases (CVD) are the leading cause of mortality worldwide and diet is an important contributor to CVD risk. Thus, several food derivatives are being investigated for their beneficial impact on reducing cardiometabolic risk factors, either in risk groups or in healthy population as a preventive measure. Wheat germ is a food by-product with high nutritional value, especially as a concentrated source of dietary fibre and essential fatty acids, but its incorporation into the diet has been rare up to now. Previous studies do not clarify the hypothesised potential causal relationship between the consumption of wheat germ and benefits for human health. METHODS AND ANALYSIS: We are conducting a randomised, double-blinded, crossover, placebo-controlled clinical trial designed to assess the physiological effects of daily consumption of wheat germ-enriched bread (containing 6 g of wheat germ) compared with non-enriched bread, over a 4-week period with a 15-week follow-up, in a healthy human population. A total of 55 participants (healthy volunteers, aged 18-60) have been recruited from the Porto metropolitan area in northern Portugal. Our aim is to evaluate the health effects of wheat germ on blood cholesterol and triglycerides, postprandial glycaemic response, gastrointestinal function and discomfort, and changes in intestinal microbiota and insulin resistance as secondary outcomes. The study follows the best practices for evaluating health claims in food according to the European Food Safety Authority (EFSA) scientific opinion, namely random allocation, double blinding, reporting methods to measure and maximise compliance, and validated outcomes with beneficial physiological effects as recommended by EFSA. ETHICS AND DISSEMINATION: The study has been approved by the Health Ethics Committee of São João Hospital Centre (156-15) and the Ethics Committee of Faculty of Medicine of the University of Porto (PCEDCSS-FMUP07/2015). Results will be disseminated through peer-reviewed publications and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NCT02405507; pre-results.