Development and validation of next generation sequencing based 35-gene hereditary cancer panel.

BACKGROUND: Understanding the genetic basis of cancer risk is a major international endeavor. The emergence of next-generation sequencing (NGS) in late 2000's has further accelerated the discovery of many cancer susceptibility genes. The use of targeted NGS-based multigene testing panels to provide comprehensive analysis of cancer susceptible genes has proven to be a viable option, with the accurate and robust detection of a wide range of clinically relevant variants in the targeted genes being crucial. METHODS: We have developed and validated a targeted NGS-based test for hereditary cancer risk assessment using Illumina's NGS platform by analyzing the protein-coding regions of 35 hereditary cancer genes with a bioinformatics pipeline that utilizes standard practices in the field. This 35-gene hereditary cancer panel is designed to identify germline cancer-causing mutations for 8 different cancers: breast, ovarian, prostate, uterine, colorectal, pancreatic, stomach cancers and melanoma. The panel was validated using well-characterized DNA specimens [NIGMS Human Genetic Cell Repository], where DNA had been extracted using blood of individuals whose genetic variants had been previously characterized by the 1000 Genome Project and the Coriell Catalog. RESULTS: The 35-gene hereditary cancer panel shows high sensitivity (99.9%) and specificity (100%) across 4820 variants including single nucleotide variants (SNVs) and small insertions and deletions (indel; up to 25 bp). The reproducibility and repeatability are 99.8 and 100%, respectively. CONCLUSIONS: The use of targeted NGS-based multigene testing panels to provide comprehensive analysis of cancer susceptible genes has been considered a viable option. In the present study, we developed and validated a 35-gene panel for testing 8 common cancers using next-generation sequencing (NGS). The performance of our hereditary cancer panel is assessed across a board range of variants in the 35 genes to support clinical use.

Associations of vitamin D status with dietary intakes and physical activity levels among adults from seven European countries: the Food4Me study.

PURPOSE: To report the vitamin D status in adults from seven European countries and to identify behavioural correlates. METHODS: In total, 1075 eligible adult men and women from Ireland, Netherlands, Spain, Greece, UK, Poland and Germany, were included in the study. RESULTS: Vitamin D deficiency and insufficiency, defined as 25-hydroxy vitamin D3 (25-OHD3) concentration of <30 and 30-49.9 nmol/L, respectively, were observed in 3.3 and 30.6% of the participants. The highest prevalence of vitamin D deficiency was found in the UK and the lowest in the Netherlands (8.2 vs. 1.1%, P < 0.05). In addition, the prevalence of vitamin D insufficiency was higher in females compared with males (36.6 vs. 22.6%, P < 0.001), in winter compared with summer months (39.3 vs. 25.0%, P < 0.05) and in younger compared with older participants (36.0 vs. 24.4%, P < 0.05). Positive dose-response associations were also observed between 25-OHD3 concentrations and dietary vitamin D intake from foods and supplements, as well as with physical activity (PA) levels. Vitamin D intakes of ≥5 µg/day from foods and ≥5 µg/day from supplements, as well as engagement in ≥30 min/day of moderate- and vigorous-intensity PA were associated with higher odds (P < 0.05) for maintaining sufficient (≥50 nmol/L) 25-OHD3 concentrations. CONCLUSIONS: The prevalence of vitamin D deficiency varied considerably among European adults. Dietary intakes of ≥10 µg/day of vitamin D from foods and/or supplements and at least 30 min/day of moderate- and vigorous-intensity PA were the minimum thresholds associated with vitamin D sufficiency.

The Ketogenic Diet and Sport: A Possible Marriage?

The ketogenic diet (KD) is used widely as a weight loss strategy and, more rarely, as therapy for some diseases. In many sports, weight control is often necessary (boxing, weightlifting, wrestling, etc.), but the KD usually is not considered. Our hypothesis is that KD might be used to achieve fat loss without affecting strength/power performance negatively.

Effects of Twenty Days of the Ketogenic Diet on Metabolic and Respiratory Parameters in Healthy Subjects.

PURPOSE: The effects of the ketogenic diet (KD) on weight loss, metabolic, and respiratory parameters were investigated in healthy subjects. METHODS: Thirty-two healthy subjects were randomized into two groups. The KD group followed a ketogenic diet for 20 days (KD t 0-t 20), then switched to a low-carbohydrate, no-ketogenic diet for 20 days (KD t 20-t 40), and finally was on a Mediterranean diet (MD) for 2 more months (KD t 40-t 2m). The MD group followed a MD for 20 days (MD t 0-t 20), then followed a MD of 1400 kcal over the next 20 days (MD t 20-t 40), and completed the study with the MD for 2 months (MD t 40-t 2m). Body weight, body fat, respiratory rate, and respiratory gas parameters (including respiratory exchange ratio (RER) and carbon dioxide end-tidal partial pressure (PETCO2), oxygen uptake (VO2), carbon dioxide production (VCO2), and resting energy expenditure (REE)) were measured at each point. RESULTS: A significant decrease (p < 0.05) in RER was observed after 20 and 40 days in the KD group, but not in the MD group. In the KD group, significant reductions were observed for both carbon dioxide output and PETCO2, however, there was no significant change in VO2, VCO2, and REE. While both diets significantly decreased body fat mass, the KD diet overall proved to have a higher percentage of fat loss versus the MD diet. CONCLUSION: The KD may significantly decrease carbon dioxide body stores, which may theoretically be beneficial for patients with increased carbon dioxide arterial partial pressure due to respiratory insufficiency or failure.

Effects of n-3 polyunsaturated fatty acids (ω-3) supplementation on some cardiovascular risk factors with a ketogenic Mediterranean diet.

BACKGROUND: the ketogenic diet (KD) has become a widely used nutritional approach for weight loss. Some of the KD's positive effects on metabolism and cardiovascular risk factors are similar to those seen after n-3 polyunsaturated fatty acids (ω-3) supplementation. We hypothesized that a ketogenic Mediterranean diet with phytoextracts combined with ω-3 supplementation may have increased positive effects on cardiovascular risk factors and inflammation. METHODS: We analyzed 34 male overweight subjects; aged between 25 and 65 years who were overall healthy apart from overweight. The subjects followed a ketogenic diet protocol for four weeks; with (KDO3) or without (KD) ω-3 supplementation. RESULTS: All subjects experienced a significant loss of body weight and body fat and there was no significant differences between treatment (body weight: KD-4.7 kg, KDO3-4.03 kg, body fat KD-5.41 kg, KDO3-5.86 kg). There were also significant decreases in total cholesterol, LDL-c, and glucose levels. Triglycerides and insulin levels decreased more in KDO3 vs. KD subjects, with a significant difference. All the investigated inflammatory cytokines (IL-1ß, IL-6, TNF-α) decreased significantly in KDO3 subjects whilst only TNF-α showed a significant decrease in KD subjects over the 12 month study period. No significant changes were observed in anti-inflammatory cytokines (IL-10 and IL-1Ra), creatinine, urea and uric acid. Adiponectin increased significantly only in the KDO3 group. CONCLUSIONS: ω-3 supplementation improved the positive effects of a ketogenic Mediterranean diet with phytoextracts on some cardiovascular/metabolic risk factors and inflammatory state.

High-Intensity Interval Resistance Training (HIRT) influences resting energy expenditure and respiratory ratio in non-dieting individuals.

BACKGROUND: The benefits of exercise are well established but one major barrier for many is time. It has been proposed that short period resistance training (RT) could play a role in weight control by increasing resting energy expenditure (REE) but the effects of different kinds of RT has not been widely reported. METHODS: We tested the acute effects of high-intensity interval resistance training (HIRT) vs. traditional resistance training (TT) on REE and respiratory ratio (RR) at 22 hours post-exercise. In two separate sessions, seventeen trained males carried out HIRT and TT protocols. The HIRT technique consists of: 6 repetitions, 20 seconds rest, 2/3 repetitions, 20 secs rest, 2/3 repetitions with 2'30″ rest between sets, three exercises for a total of 7 sets. TT consisted of eight exercises of 4 sets of 8-12 repetitions with one/two minutes rest with a total amount of 32 sets. We measured basal REE and RR (TT0 and HIRT0) and 22 hours after the training session (TT22 and HIRT22). RESULTS: HIRT showed a greater significant increase (p < 0.001) in REE at 22 hours compared to TT (HIRT22 2362 ± 118 Kcal/d vs TT22 1999 ± 88 Kcal/d). RR at HIRT22 was significantly lower (0.798 ± 0.010) compared to both HIRT0 (0.827 ± 0.006) and TT22 (0.822 ± 0.008). CONCLUSIONS: Our data suggest that shorter HIRT sessions may increase REE after exercise to a greater extent than TT and may reduce RR hence improving fat oxidation. The shorter exercise time commitment may help to reduce one major barrier to exercise.

Effect of ketogenic Mediterranean diet with phytoextracts and low carbohydrates/high-protein meals on weight, cardiovascular risk factors, body composition and diet compliance in Italian council employees.

BACKGROUND: There has been increased interest in recent years in very low carbohydrate ketogenic diets (VLCKD) that, even though they are much discussed and often opposed, have undoubtedly been shown to be effective, at least in the short to medium term, as a tool to tackle obesity, hyperlipidemia and some cardiovascular risk factors. For this reason the ketogenic diet represents an interesting option but unfortunately suffers from a low compliance. The aim of this pilot study is to ascertain the safety and effects of a modified ketogenic diet that utilizes ingredients which are low in carbohydrates but are formulated to simulate its aspect and taste and also contain phytoextracts to add beneficial effects of important vegetable components. METHODS: The study group consisted of 106 Rome council employees with a body mass index of ≥ 25, age between 18 and 65 years (19 male and 87 female; mean age 48.49 ± 10.3). We investigated the effects of a modified ketogenic diet based on green vegetables, olive oil, fish and meat plus dishes composed of high quality protein and virtually zero carbohydrate but which mimic their taste, with the addition of some herbal extracts (KEMEPHY ketogenic Mediterranean with phytoextracts). Calories in the diet were unlimited. Measurements were taken before and after 6 weeks of diet. RESULTS: There were no significant changes in BUN, ALT, AST, GGT and blood creatinine. We detected a significant (p < 0.0001) reduction in BMI (31.45 Kg/m2 to 29.01 Kg/m2), body weight (86.15 kg to 79.43 Kg), percentage of fat mass (41.24% to 34.99%), waist circumference (106.56 cm to 97.10 cm), total cholesterol (204 mg/dl to 181 mg/dl), LDLc (150 mg/dl to 136 mg/dl), triglycerides (119 mg/dl to 93 mg/dl) and blood glucose (96 mg/dl to 91 mg/dl). There was a significant (p < 0.0001) increase in HDLc (46 mg/dl to 52 mg/dl). CONCLUSIONS: The KEMEPHY diet lead to weight reduction, improvements in cardiovascular risk markers, reduction in waist circumference and showed good compliance.

A multifactorial analysis of obesity as CVD risk factor: use of neural network based methods in a nutrigenetics context.

BACKGROUND: Obesity is a multifactorial trait, which comprises an independent risk factor for cardiovascular disease (CVD). The aim of the current work is to study the complex etiology beneath obesity and identify genetic variations and/or factors related to nutrition that contribute to its variability. To this end, a set of more than 2300 white subjects who participated in a nutrigenetics study was used. For each subject a total of 63 factors describing genetic variants related to CVD (24 in total), gender, and nutrition (38 in total), e.g. average daily intake in calories and cholesterol, were measured. Each subject was categorized according to body mass index (BMI) as normal (BMI ≤ 25) or overweight (BMI > 25). Two artificial neural network (ANN) based methods were designed and used towards the analysis of the available data. These corresponded to i) a multi-layer feed-forward ANN combined with a parameter decreasing method (PDM-ANN), and ii) a multi-layer feed-forward ANN trained by a hybrid method (GA-ANN) which combines genetic algorithms and the popular back-propagation training algorithm. RESULTS: PDM-ANN and GA-ANN were comparatively assessed in terms of their ability to identify the most important factors among the initial 63 variables describing genetic variations, nutrition and gender, able to classify a subject into one of the BMI related classes: normal and overweight. The methods were designed and evaluated using appropriate training and testing sets provided by 3-fold Cross Validation (3-CV) resampling. Classification accuracy, sensitivity, specificity and area under receiver operating characteristics curve were utilized to evaluate the resulted predictive ANN models. The most parsimonious set of factors was obtained by the GA-ANN method and included gender, six genetic variations and 18 nutrition-related variables. The corresponding predictive model was characterized by a mean accuracy equal of 61.46% in the 3-CV testing sets. CONCLUSIONS: The ANN based methods revealed factors that interactively contribute to obesity trait and provided predictive models with a promising generalization ability. In general, results showed that ANNs and their hybrids can provide useful tools for the study of complex traits in the context of nutrigenetics.

A comparison of a ketogenic diet with a LowGI/nutrigenetic diet over 6 months for weight loss and 18-month follow-up.

BACKGROUND: Obesity and its related metabolic disturbances represent a huge health burden on society. Many different weight loss interventions have been trialled with mixed efficacy, as demonstrated by the large number of individuals who regain weight upon completion of such interventions. There is evidence that the provision of genetic information may enhance long-term weight loss, either by increasing dietary adherence or through underlying biological mechanisms. METHODS: The investigators followed 114 overweight and obese subjects from a weight loss clinic in a 2-stage process. 1) A 24-week dietary intervention. The subjects self-selected whether to follow a standardized ketogenic diet (n = 53), or a personalised low-glycemic index (GI) nutrigenetic diet utilising information from 28 single nucleotide polymorphisms (n = 61). 2) After the 24-week diet period, the subjects were monitored for an additional 18 months using standard guidelines for the Keto group vs standard guidelines modified by nutrigenetic advice for the low-Glycaemic Index nutrigenetic diet (lowGI/NG) group. RESULTS: After 24 weeks, the keto group lost more weight: - 26.2 ± 3.1 kg vs - 23.5 ± 6.4 kg (p = 0.0061). However, at 18-month follow up, the subjects in the low-GI nutrigenetic diet had lost significantly more weight (- 27.5 ± 8.9 kg) than those in the ketogenic diet who had regained some weight (- 19.4 ± 5.0 kg) (p < 0.0001). Additionally, after the 24-week diet and 18-month follow up the low-GI nutrigenetic diet group had significantly greater (p < 0.0001) improvements in total cholesterol (ketogenic - 35.4 ± 32.2 mg/dl; low-GI nutrigenetic - 52.5 ± 24.3 mg/dl), HDL cholesterol (ketogenic + 4.7 ± 4.5 mg/dl; low-GI nutrigenetic + 11.9 ± 4.1 mg/dl), and fasting glucose (ketogenic - 13.7 ± 8.4 mg/dl; low-GI nutrigenetic - 24.7 ± 7.4 mg/dl). CONCLUSIONS: These findings demonstrate that the ketogenic group experienced enhanced weight loss during the 24-week dietary intervention. However, at 18-month follow up, the personalised nutrition group (lowGI/NG) lost significantly more weight and experienced significantly greater improvements in measures of cholesterol and blood glucose. This suggests that personalising nutrition has the potential to enhance long-term weight loss and changes in cardiometabolic parameters. TRIAL REGISTRATION: NCT04330209, Registered 01/04/2020, retrospectively registered.

Precision Nutrition and the Microbiome Part II: Potential Opportunities and Pathways to Commercialisation.

Modulation of the human gut microbiota through probiotics, prebiotics and dietary fibre are recognised strategies to improve health and prevent disease. Yet we are only beginning to understand the impact of these interventions on the gut microbiota and the physiological consequences for the human host, thus forging the way towards evidence-based scientific validation. However, in many studies a percentage of participants can be defined as 'non-responders' and scientists are beginning to unravel what differentiates these from 'responders;' and it is now clear that an individual's baseline microbiota can influence an individual's response. Thus, microbiome composition can potentially serve as a biomarker to predict responsiveness to interventions, diets and dietary components enabling greater opportunities for its use towards disease prevention and health promotion. In Part I of this two-part review, we reviewed the current state of the science in terms of the gut microbiota and the role of diet and dietary components in shaping it and subsequent consequences for human health. In Part II, we examine the efficacy of gut-microbiota modulating therapies at different life stages and their potential to aid in the management of undernutrition and overnutrition. Given the significance of an individual's gut microbiota, we investigate the feasibility of microbiome testing and we discuss guidelines for evaluating the scientific validity of evidence for providing personalised microbiome-based dietary advice. Overall, this review highlights the potential value of the microbiome to prevent disease and maintain or promote health and in doing so, paves the pathway towards commercialisation.

Improved weight management using genetic information to personalize a calorie controlled diet.

BACKGROUND: Gene-environment studies demonstrate variability in nutrient requirements depending upon individual variations in genes affecting nutrient metabolism and transport. This study investigated whether the inclusion of genetic information to personalize a patient's diet (nutrigenetics) could improve long term weight management. METHODS: Patients with a history of failures at weight loss were offered a nutrigenetic test screening 24 variants in 19 genes involved in metabolism. 50 patients were in the nutrigenetic group and 43 patients attending the same clinic were selected for comparison using algorithms to match the characteristics: age, sex, frequency of clinical visits and BMI at initial clinic visit. The second group of 43 patients did not receive a nutrigenetic test. BMI reduction at 100 and > 300 days and blood fasting glucose were measured. RESULTS: After 300 days of follow-up individuals in the nutrigenetic group were more likely to have maintained some weight loss (73%) than those in the comparison group (32%), resulting in an age and gender adjusted OR of 5.74 (95% CI 1.74-22.52). Average BMI reduction in the nutrigenetic group was 1.93 kg/m2(5.6% loss) vs. an average BMI gain of 0.51 kg/m2(2.2% gain) (p < 0.023). Among patients with a starting blood fasting glucose of > 100 mg/dL, 57% (17/30) of the nutrigenetic group but only 25% (4/16) of the non-tested group had levels reduced to < 100 mg/dL after > 90 days of weight management therapy (OR for lowering glucose to < 100 mg/dL due to diet = 1.98 95%CI 1.01, 3.87, p < 0.046). CONCLUSION: Addition of nutrigenetically tailored diets resulted in better compliance, longer-term BMI reduction and improvements in blood glucose levels.

Mediterranean Diet Adherence and Genetic Background Roles within a Web-Based Nutritional Intervention: The Food4Me Study.

Mediterranean Diet (MedDiet) adherence has been proven to produce numerous health benefits. In addition, nutrigenetic studies have explained some individual variations in the response to specific dietary patterns. The present research aimed to explore associations and potential interactions between MedDiet adherence and genetic background throughout the Food4Me web-based nutritional intervention. Dietary, anthropometrical and biochemical data from volunteers of the Food4Me study were collected at baseline and after 6 months. Several genetic variants related to metabolic risk features were also analysed. A Genetic Risk Score (GRS) was derived from risk alleles and a Mediterranean Diet Score (MDS), based on validated food intake data, was estimated. At baseline, there were no interactions between GRS and MDS categories for metabolic traits. Linear mixed model repeated measures analyses showed a significantly greater decrease in total cholesterol in participants with a low GRS after a 6-month period, compared to those with a high GRS. Meanwhile, a high baseline MDS was associated with greater decreases in Body Mass Index (BMI), waist circumference and glucose. There also was a significant interaction between GRS and the MedDiet after the follow-up period. Among subjects with a high GRS, those with a high MDS evidenced a highly significant reduction in total carotenoids, while among those with a low GRS, there was no difference associated with MDS levels. These results suggest that a higher MedDiet adherence induces beneficial effects on metabolic outcomes, which can be affected by the genetic background in some specific markers.

Weekday sunlight exposure, but not vitamin D intake, influences the association between vitamin D receptor genotype and circulating concentration 25-hydroxyvitamin D in a pan-European population: the Food4Me study.

SCOPE: Little is known about diet- and environment-gene interactions on 25-hydroxyvitamin D (25(OH)D concentration. This cross-sectional study aimed to investigate (i) predictors of 25(OH)D concentration and relationships with vitamin D genotypes and (ii) whether dietary vitamin D intake and sunlight exposure modified these relationships. METHODS AND RESULTS: Participants from the Food4Me study (n = 1312; age 18-79) were genotyped for vitamin D receptor (VDR) and vitamin D binding protein at baseline and a genetic risk score was calculated. Dried blood spot samples were assayed for 25(OH)D concentration and dietary and lifestyle information collected. Circulating 25(OH)D concentration was lower with increasing genetic risk score, lower in females than males, higher in supplement users than non-users and higher in summer than winter. Carriage of the minor VDR allele was associated with lower 25(OH)D concentration in participants with the least sunlight exposure. Vitamin D genotype did not influence the relationship between vitamin D intake and 25(OH)D concentration. CONCLUSION: Age, sex, dietary vitamin D intake, country, sunlight exposure, season, and vitamin D genetic risk score were associated with circulating 25(OH)D concentration in a pan-European population. The relationship between VDR genotype and 25(OH)D concentration may be influenced by weekday sunlight exposure but not dietary vitamin D intake.

Can genetic-based advice help you lose weight? Findings from the Food4Me European randomized controlled trial.

Background: There has been limited evidence about whether genotype-tailored advice provides extra benefits in reducing obesity-related traits compared with the benefits of conventional one-size-fits-all advice.Objective: We determined whether the disclosure of information on fat-mass and obesity-associated (FTO) genotype risk had a greater effect on a reduction of obesity-related traits in risk carriers than in nonrisk carriers across different levels of personalized nutrition.Design: A total of 683 participants (women: 51%; age range: 18-73 y) from the Food4Me randomized controlled trial were included in this analysis. Participants were randomly assigned to 4 intervention arms as follows: level 0, control group; level 1, dietary group; level 2, phenotype group; and level 3, genetic group. FTO (single nucleotide polymorphism rs9939609) was genotyped at baseline in all participants, but only subjects who were randomly assigned to level 3 were informed about their genotypes. Level 3 participants were stratified into risk carriers (AA/AT) and nonrisk carriers (TT) of the FTO gene for analyses. Height, weight, and waist circumference (WC) were self-measured and reported at baseline and months 3 and 6.Results: Changes in adiposity markers were greater in participants who were informed that they carried the FTO risk allele (level 3 AT/AA carriers) than in the nonpersonalized group (level 0) but not in the other personalized groups (level 1 and 2). Mean reductions in weight and WC at month 6 were greater for FTO risk carriers than for noncarriers in the level 3 group [-2.28 kg (95% CI: -3.06, -1.48 kg) compared with -1.99 kg (-2.19, -0.19 kg), respectively (P = 0.037); and -4.34 cm (-5.63, -3.08 cm) compared with -1.99 cm (-4.04, -0.05 cm), respectively, (P = 0.048)].Conclusions: There are greater body weight and WC reductions in risk carriers than in nonrisk carriers of the FTO gene. This trial was registered at clinicaltrials.gov as NCT01530139.

Proposed guidelines to evaluate scientific validity and evidence for genotype-based dietary advice.

Nutrigenetic research examines the effects of inter-individual differences in genotype on responses to nutrients and other food components, in the context of health and of nutrient requirements. A practical application of nutrigenetics is the use of personal genetic information to guide recommendations for dietary choices that are more efficacious at the individual or genetic subgroup level relative to generic dietary advice. Nutrigenetics is unregulated, with no defined standards, beyond some commercially adopted codes of practice. Only a few official nutrition-related professional bodies have embraced the subject, and, consequently, there is a lack of educational resources or guidance for implementation of the outcomes of nutrigenetic research. To avoid misuse and to protect the public, personalised nutrigenetic advice and information should be based on clear evidence of validity grounded in a careful and defensible interpretation of outcomes from nutrigenetic research studies. Evidence requirements are clearly stated and assessed within the context of state-of-the-art 'evidence-based nutrition'. We have developed and present here a draft framework that can be used to assess the strength of the evidence for scientific validity of nutrigenetic knowledge and whether 'actionable'. In addition, we propose that this framework be used as the basis for developing transparent and scientifically sound advice to the public based on nutrigenetic tests. We feel that although this area is still in its infancy, minimal guidelines are required. Though these guidelines are based on semi-quantitative data, they should stimulate debate on their utility. This framework will be revised biennially, as knowledge on the subject increases.

Effect of personalized nutrition on health-related behaviour change: evidence from the Food4Me European randomized controlled trial.

Background: Optimal nutritional choices are linked with better health, but many current interventions to improve diet have limited effect. We tested the hypothesis that providing personalized nutrition (PN) advice based on information on individual diet and lifestyle, phenotype and/or genotype would promote larger, more appropriate, and sustained changes in dietary behaviour. Methods: : Adults from seven European countries were recruited to an internet-delivered intervention (Food4Me) and randomized to: (i) conventional dietary advice (control) or to PN advice based on: (ii) individual baseline diet; (iii) individual baseline diet plus phenotype (anthropometry and blood biomarkers); or (iv) individual baseline diet plus phenotype plus genotype (five diet-responsive genetic variants). Outcomes were dietary intake, anthropometry and blood biomarkers measured at baseline and after 3 and 6 months' intervention. Results: At baseline, mean age of participants was 39.8 years (range 18-79), 59% of participants were female and mean body mass index (BMI) was 25.5 kg/m 2 . From the enrolled participants, 1269 completed the study. Following a 6-month intervention, participants randomized to PN consumed less red meat [-5.48 g, (95% confidence interval:-10.8,-0.09), P = 0.046], salt [-0.65 g, (-1.1,-0.25), P = 0.002] and saturated fat [-1.14 % of energy, (-1.6,-0.67), P < 0.0001], increased folate [29.6 µg, (0.21,59.0), P = 0.048] intake and had higher Healthy Eating Index scores [1.27, (0.30, 2.25), P = 0.010) than those randomized to the control arm. There was no evidence that including phenotypic and phenotypic plus genotypic information enhanced the effectiveness of the PN advice. Conclusions: Among European adults, PN advice via internet-delivered intervention produced larger and more appropriate changes in dietary behaviour than a conventional approach.

Physical activity attenuates the effect of the FTO genotype on obesity traits in European adults: The Food4Me study.

OBJECTIVE: To examine whether the effect of FTO loci on obesity-related traits could be modified by physical activity (PA) levels in European adults. METHODS: Of 1,607 Food4Me participants randomized, 1,280 were genotyped for FTO (rs9939609) and had available PA data. PA was measured objectively using accelerometers (TracmorD, Philips), whereas anthropometric measures [BMI and waist circumference (WC)] were self-reported via the Internet. RESULTS: FTO genotype was associated with a higher body weight [ß: 1.09 kg per risk allele, (95% CI: 0.14-2.04), P = 0.024], BMI [ß: 0.54 kg m(-2) , (0.23-0.83), P < 0.0001], and WC [ß: 1.07 cm, (0.24-1.90), P = 0.011]. Moderate-equivalent PA attenuated the effect of FTO on BMI (P[interaction] = 0.020). Among inactive individuals, FTO increased BMI by 1.06 kg m(-2) per allele (P = 0.024), whereas the increase in BMI was substantially attenuated among active individuals (0.16 kg m(-2) , P = 0.388). We observed similar effects for WC (P[interaction] = 0.005): the FTO risk allele increased WC by 2.72 cm per allele among inactive individuals but by only 0.49 cm in active individuals. CONCLUSIONS: PA attenuates the effect of FTO genotype on BMI and WC. This may have important public health implications because genetic susceptibility to obesity in the presence of FTO variants may be reduced by adopting a physically active lifestyle.

The impact of MTHFR 677C → T risk knowledge on changes in folate intake: findings from the Food4Me study.

BACKGROUND: It is hypothesised that individuals with knowledge of their genetic risk are more likely to make health-promoting dietary and lifestyle changes. The present study aims to test this hypothesis using data from the Food4Me study. This was a 6-month Internet-based randomised controlled trial conducted across seven centres in Europe where individuals received either general healthy eating advice or varying levels of personalised nutrition advice. Participants who received genotype-based personalised advice were informed whether they had the risk (CT/TT) (n = 178) or non-risk (CC) (n = 141) alleles of the methylenetetrahydrofolate reductase (MTHFR) gene in relation to cardiovascular health and the importance of a sufficient intake of folate. General linear model analysis was used to assess changes in folate intake between the MTHFR risk, MTHFR non-risk and control groups from baseline to month 6 of the intervention. RESULTS: There were no differences between the groups for age, gender or BMI. However, there was a significant difference in country distribution between the groups (p = 0.010). Baseline folate intakes were 412 ± 172, 391 ± 190 and 410 ± 186 µg per 10 MJ for the risk, non-risk and control groups, respectively. There were no significant differences between the three groups in terms of changes in folate intakes from baseline to month 6. Similarly, there were no changes in reported intake of food groups high in folate. CONCLUSIONS: These results suggest that knowledge of MTHFR 677C → T genotype did not improve folate intake in participants with the risk variant compared with those with the non-risk variant. TRIAL REGISTRATION: ClinicalTrials.gov NCT01530139.