Review and gap analysis: molecular pathways leading to fetal alcohol spectrum disorders.

Alcohol exposure during pregnancy affects the development of the fetus in various ways and may lead to Fetal Alcohol Spectrum Disorders (FASD). FASD is one of the leading preventable forms of neurodevelopmental disorders. In the light of prevention and early intervention, knowledge on how ethanol exposure induces fetal damage is urgently needed. Besides direct ethanol and acetaldehyde toxicity, alcohol increases oxidative stress, and subsequent general effects (e.g., epigenetic imprinting, gene expression, and metabolite levels). The current review provides an overview of the existing knowledge about specific downstream pathways for FASD that affects e.g., the SHH pathway, cholesterol homeostasis, neurotransmitter signaling, and effects on the cytoskeleton. Available human data vary greatly, while animal studies with controlled ethanol exposition are only to a certain limit transferable to humans. The main deficits in knowledge about FASD are the lack of pathophysiological understanding and dose-response relationships, together with the lack of reliable biomarkers for either FASD detection or estimation of susceptibility. In addition to single outcome experiments, omics data should be generated to overcome this problem. Therefore, for future studies we recommend holistic data driven analysis, which allows integrative analyses over multiple levels of genetic variation, transcriptomics and metabolomics data to investigate the whole image of FASD development and to provide insight in potential drug targets for intervention.

Optimising SME Potential in Modern Healthcare Systems: Challenges, Opportunities and Policy Recommendations.

The expansion of European small and medium-sized enterprises (SMEs) into the healthcare innovation arena suggests that this should be an important EU policy priority that can significantly benefit the economy, society and citizens, including patients. Deepening and widening of Europe's SMEs' growth and activities is part of the EU objectives as set out by the European Commission in its Communications "Small Business Act" for Europe [1] and "Small Business, Big World" [2]. However, innovative healthcare SMEs have struggled to get traction despite the sector being worth more than EUR 250 billion. The 1991 Maastricht Treaty gave the Union new competences in public health and more scope for cross-border cooperation in this area [3]. Nevertheless, health initiatives here have tripped over each other, due to the fact that the delivery of healthcare is a national competence [4]. As such, EU healthcare-driven policy has never truly found its footing as a singular policy area despite the fact that a tenth of the EU's GDP is spent on healthcare and more than 17 million people are employed in Europe in this sector [5]. Taking into account the necessity of bringing innovation into healthcare, and the willingness of SMEs to undertake the risk to be at the forefront of it, there is a need for a renewed effort to support SMEs so as to provide solutions for citizens and patients throughout the bloc in different healthcare settings [6]. This policy paper brings together two separate strands of analysis: firstly, a policy review of the main challenges and opportunities; secondly, a proposal for policy recommendations.

MECP2 variation in Rett syndrome-An overview of current coverage of genetic and phenotype data within existing databases.

Rett syndrome (RTT) is a monogenic rare disorder that causes severe neurological problems. In most cases, it results from a loss-of-function mutation in the gene encoding methyl-CPG-binding protein 2 (MECP2). Currently, about 900 unique MECP2 variations (benign and pathogenic) have been identified and it is suspected that the different mutations contribute to different levels of disease severity. For researchers and clinicians, it is important that genotype-phenotype information is available to identify disease-causing mutations for diagnosis, to aid in clinical management of the disorder, and to provide counseling for parents. In this study, 13 genotype-phenotype databases were surveyed for their general functionality and availability of RTT-specific MECP2 variation data. For each database, we investigated findability and interoperability alongside practical user functionality, and type and amount of genetic and phenotype data. The main conclusions are that, as well as being challenging to find these databases and specific MECP2 variants held within, interoperability is as yet poorly developed and requires effort to search across databases. Nevertheless, we found several thousand online database entries for MECP2 variations and their associated phenotypes, diagnosis, or predicted variant effects, which is a good starting point for researchers and clinicians who want to provide, annotate, and use the data.

Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations.

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow-up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.

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.

Combining traditional dietary assessment methods with novel metabolomics techniques: present efforts by the Food Biomarker Alliance.

FFQ, food diaries and 24 h recall methods represent the most commonly used dietary assessment tools in human studies on nutrition and health, but food intake biomarkers are assumed to provide a more objective reflection of intake. Unfortunately, very few of these biomarkers are sufficiently validated. This review provides an overview of food intake biomarker research and highlights present research efforts of the Joint Programming Initiative 'A Healthy Diet for a Healthy Life' (JPI-HDHL) Food Biomarkers Alliance (FoodBAll). In order to identify novel food intake biomarkers, the focus is on new food metabolomics techniques that allow the quantification of up to thousands of metabolites simultaneously, which may be applied in intervention and observational studies. As biomarkers are often influenced by various other factors than the food under investigation, FoodBAll developed a food intake biomarker quality and validity score aiming to assist the systematic evaluation of novel biomarkers. Moreover, to evaluate the applicability of nutritional biomarkers, studies are presently also focusing on associations between food intake biomarkers and diet-related disease risk. In order to be successful in these metabolomics studies, knowledge about available electronic metabolomics resources is necessary and further developments of these resources are essential. Ultimately, present efforts in this research area aim to advance quality control of traditional dietary assessment methods, advance compliance evaluation in nutritional intervention studies, and increase the significance of observational studies by investigating associations between nutrition and health.

Policy Making in Newborn Screening Needs a Structured and Transparent Approach.

PURPOSE: Newborn bloodspot screening (NBS) programs have expanded significantly in the past years and are expected to expand further with the emergence of genetic technologies. Historically, NBS expansion has often occurred following ad hoc consideration of conditions, instead of a structured and transparent approach. In this review, we explore issues pertinent to NBS policy making, through the lens of the policy cycle: (a) agenda setting, (b) policy advice, (c) policy decision, (d) implementation, and (e) evaluation. METHODS: A literature search was conducted to gather information on the elements specific to NBS and its policy making process. RESULTS: The review highlighted two approaches to nominate a condition: a structured approach through horizon scanning; and an ad hoc process. For assessment of a condition, there was unanimous support for a robust process based on criteria. While the need to assess harms and benefits was a repeated theme in the articles, there is no agreed-upon threshold for benefit in decision-making. Furthermore, the literature was consistent in its recommendation for an overarching, independent, multidisciplinary group providing recommendations to government. An implementation plan focusing on the different levels on which NBS operates and the information needed on each level is essential for successful implementation. Continuously monitoring, and improving a program is vital, particularly following the implementation of screening for a new condition. An advisory committee could advise on implementation, development, review, modification, and cessation of (parts of) NBS. CONCLUSION: The results highlight that there are a wave of issues facing NBS programs that policy makers must take into account when developing policy processes. What conditions to screen, and the technologies used in NBS, are both up for debate.

The action spectrum for vitamin D3: initial skin reaction and prolonged exposure.

Vitamin D3 photosynthesis in the skin is formulated as a set of reaction equations, including side-reactions to lumisterol, tachysterol and toxisterols, and the accompanying reverse reactions, isomerisation of previtamin D3 to vitamin D3 and photodegradation of vitamin D3. The solution of this set is given for the stationary irradiance spectrum. The effective action spectrum for the instantaneous vitamin D3 production changes shape as a function of exposure, and therefore, no single action spectrum can be used. We assessed the action spectrum for unexposed skin and for skin that has been exposed to 7.5 Standard Erythemal Doses (SED). We constructed two new estimates: (1) the RIVM action spectrum, based on absorption spectra, quantum yields and skin transmission spectra, and (2) the modified QUT action spectrum, which is adjusted for self-absorption and skin transmission. For previously unexposed skin, the modified QUT action spectrum gives a qualitatively similar, but larger estimate than the RIVM action spectrum. We have not been able to solve the lack of quantitative agreement between the vitamin D production estimates from the three action spectrum estimates (RIVM, modified QUT and CIE). All new action spectra have stronger emphasis on the short wavelengths than the CIE action spectrum. We showed that, for wavelengths larger than 300 nm, the bandwidth that was used in the experiment that formed the basis of the CIE action spectrum, gives a red-shift of about 1 nm. Generally, with the formation of previtamin D3, the return reaction to provitamin D3 limits the production of vitamin D3. After some exposure, the new action spectrum has negative values for the longer wavelengths in the UVB. For the RIVM action spectrum, this happens after 7.5 SED, for the modified QUT action spectrum already after 1.25 SED, and after 7.5 SED the net production rate is largely cancelled. Thus prolonged exposure of previously unexposed skin saturates vitamin D3 formation. For maximum vitamin D production after 1.25 SED, sunscreens should block wavelengths larger than 310 nm. Sunscreens that block only UVB could result in reduction in vitamin D production after prolonged exposure, or even a destruction of vitamin D that has just been formed.

Specific polymorphisms in the vitamin D metabolism pathway are not associated with susceptibility to Chlamydia trachomatis infection in humans.

Chlamydia trachomatis is the most common sexually transmitted bacterium worldwide. Its often asymptomatic course of infection increases chances of transmission, and increases risk of late complications. Genetic variations in the host immune system are known to impact the course of infections. Recent studies have shown a positive impact of vitamin D on the regulation of the immune system. This study assesses the impact of eight polymorphisms in five genes [VDR (rs1544410 G > A, rs2228570 C > T), CYP27B1 (rs10877012 G > T), DHCR7 (rs7944926 G > A, rs3829251 G > A), GC (rs3755967) and CYP2R1 (rs10741657 G > A, rs2060793 G > A)] on susceptibility to Chlamydia infections in humans. These polymorphisms could influence protein expression or function, and thus influence the immune system. Samples of women visiting the STD outpatient clinic in South Limburg were genotyped using the Roche Lightcycler 480. In this study, we did not observe statistically significant differences between the genotype distributions of these polymorphisms in women with or without a Chlamydia infection. This suggests that VDR, CYP27B1, DHCR7, GC and CYP2R1 do not affect the susceptibility to Chlamydia infections. However, due to its pleiotropic nature in the immune system a role for the vitamin D pathway may not be excluded from the whole clinical course of Chlamydia infections (e.g. late complications), and further research is required.

The impact of personalized medicine of Type 2 diabetes mellitus in the global health context.

Advances in the fields of genomic sciences have given rise to personalized medicine. This new paradigm draws upon a patient's genetic and metabolic makeup in order to tailor diagnostics and treatment. Personalized medicine holds remarkable promises to improve prevention and management of chronic diseases of global relevance, such as Type 2 diabetes mellitus (T2DM). This review article aims at summarizing the evidence from genome-based sciences on T2DM risk and management in different populations and in the Global Health context. Opinions from leading experts in the field were also included. Based on these findings, strengths and weaknesses of personalized approach to T2DM in a global context are delineated. Implications for future research and implementation on that subject are discussed.

Preferences for genetic testing for colorectal cancer within a population-based screening program: a discrete choice experiment.

This study explored individuals' preferences for genetic testing for colorectal cancer (CRC) in a screening situation and their willingness to participate in genetic testing for Lynch syndrome, familial adenomatous polyposis (FAP), and familial colorectal cancer (FCC). For that purpose, 532 respondents aged 55-65 years completed a Discrete Choice Experiment. Using panel latent class models, the preferences for two screening situation characteristics (the probability of being genetically predisposed and the probability of developing CRC) and screening test characteristics (the frequency of preventive colonoscopies and CRC survival) were estimated. Based on these preferences, respondents' willingness to participate in the three screening initiatives was estimated. Lower-educated respondents and respondents who express serious anxiety and worries found colonoscopy frequency and the probability of developing CRC relatively more important and survival relatively less important compared with higher-educated respondents and respondents who express no anxiety and worries. These differences in preferences resulted in opposite preferences for participation in FCC and FAP screening. In conclusion, the general population is willing to participate in genetic screening for CRC. If individuals are suspected of genetic or familial CRC, they should at least be informed about their increased risk of being genetically predisposed and about the importance of participating in all preventive follow-up colonoscopies in order to maximize survival.

Dietary fat intake and development of specific breast cancer subtypes.

We prospectively evaluated fat intake as predictor of developing breast cancer (BC) subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2), in a large (n = 337327) heterogeneous cohort of women, with 10062 BC case patients after 11.5 years, estimating BC hazard ratios (HRs) by Cox proportional hazard modeling. High total and saturated fat were associated with greater risk of ER(+)PR(+) disease (HR = 1.20, 95% confidence interval [CI] = 1.00 to 1.45; HR = 1.28, 95% CI = 1.09 to 1.52; highest vs lowest quintiles) but not ER(-)PR(-) disease. High saturated fat was statistically significantly associated with greater risk of HER2(-) disease. High saturated fat intake particularly increases risk of receptor-positive disease, suggesting saturated fat involvement in the etiology of this BC subtype.

Fatty acid patterns and risk of prostate cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Fatty acids in blood may be related to the risk of prostate cancer, but epidemiologic evidence is inconsistent. Blood fatty acids are correlated through shared food sources and common endogenous desaturation and elongation pathways. Studies of individual fatty acids cannot take this into account, but pattern analysis can. Treelet transform (TT) is a novel method that uses data correlation structures to derive sparse factors that explain variation. OBJECTIVE: The objective was to gain further insight in the association between plasma fatty acids and risk of prostate cancer by applying TT to take data correlations into account. DESIGN: We reanalyzed previously published data from a case-control study of prostate cancer nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. TT was used to derive factors explaining the variation in 26 plasma phospholipid fatty acids of 962 incident prostate cancer cases matched to 1061 controls. Multiple imputation was used to deal with missing data in covariates. ORs of prostate cancer according to factor scores were determined by using multivariable conditional logistic regression. RESULTS: Four simple factors explained 38% of the variation in plasma fatty acids. A high score on a factor reflecting a long-chain n-3 PUFA pattern was associated with greater risk of prostate cancer (OR for highest compared with lowest quintile: 1.36; 95% CI: 0.99, 1.86; P-trend = 0.041). CONCLUSION: Pattern analyses using TT groupings of correlated fatty acids indicate that intake or metabolism of long-chain n-3 PUFAs may be relevant to prostate cancer etiology.

Application of the BRAFO tiered approach for benefit-risk assessment to case studies on dietary interventions.

The respective examples, described in this paper, illustrate how the BRAFO-tiered approach, on benefit-risk assessment, can be tested on a wide range of case studies. Various results were provided, ranging from a quick stop as the result of non-genuine benefit-risk questions to continuation through the tiers into deterministic/probabilistic calculations. The paper illustrates the assessment of benefits and risks associated with dietary interventions. The BRAFO tiered approach is tested with five case studies. In each instance, the benefit-risk approach is tested on the basis of existing evaluations for the individual effects done by others; no new risk or benefit evaluations were made. The following case studies were thoroughly analysed: an example of food fortification, folic acid fortification of flour, macronutrient replacement/food substitution; the isocaloric replacement of saturated fatty acids with carbohydrates; the replacement of saturated fatty acids with monounsaturated fatty acids; the replacement of sugar-sweetened beverages containing mono- and disaccharides with low calorie sweeteners and an example of addition of specific ingredients to food: chlorination of drinking water.

Endogenous sex steroids and risk of cervical carcinoma: results from the EPIC study.

BACKGROUND: Epidemiologic data and animal models suggest that, despite the predominant role of human papillomavirus infection, sex steroid hormones are also involved in the etiology of invasive cervical carcinoma (ICC). METHODS: Ninety-nine ICC cases, 121 cervical intraepithelial neoplasia grade 3 (CIN3) cases and 2 control women matched with each case for center, age, menopausal status and blood collection-related variables, were identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Circulating levels of testosterone (T) and estradiol (E(2)); dehydroepiandrosterone sulfate (DHEAS); progesterone (premenopausal women); and sex hormone-binding globulin (SHBG) were measured using immunoassays. Levels of free (f) T and E(2) were calculated from absolute concentrations of T, E(2), and SHBG. Odds ratios (ORs) and 95% confidence intervals (CI) were computed using regularized conditional logistic regression. RESULTS: Among premenopausal women, associations with ICC were observed for fT (OR for highest vs. lowest tertile = 5.16, 95% CI, 1.50-20.1). SHBG level was associated with a significant downward trend in ICC risk. T, E(2), fE(2), and DHEAS showed nonsignificant positive association with ICC. Progesterone was uninfluential. Among postmenopausal women, associations with ICC were found for T (OR = 3.14; 95% CI, 1.21-9.37), whereas E(2) and fT showed nonsignificant positive association. SHBG level was unrelated to ICC risk in postmenopausal women. No associations between any hormone and CIN3 were detected in either pre- or postmenopausal women. CONCLUSIONS: Our findings suggest for the first time that T and possibly E(2) may be involved in the etiology of ICC. IMPACT: The responsiveness of cervical tumors to hormone modulators is worth exploring.

Hepatocellular carcinoma risk factors and disease burden in a European cohort: a nested case-control study.

BACKGROUND: To date, no attempt has been made to systematically determine the apportionment of the hepatocellular carcinoma burden in Europe or North America among established risk factors. METHODS: Using data collected from 1992 to 2006, which included 4,409,809 person-years in the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 125 case patients with hepatocellular carcinoma, of whom 115 were matched to 229 control subjects. We calculated odds ratios (ORs) for the association of documented risk factors for hepatocellular carcinoma with incidence of this disease and estimated their importance in this European cohort. RESULTS: Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (OR = 9.10, 95% confidence interval [CI] = 2.10 to 39.50 and OR = 13.36, 95% CI = 4.11 to 43.45, respectively), obesity (OR = 2.13, 95% CI = 1.06 to 4.29), former or current smoking (OR = 1.98, 95% CI = 0.90 to 4.39 and OR = 4.55, 95% CI = 1.90 to 10.91, respectively), and heavy alcohol intake (OR = 1.77, 95% CI = 0.73 to 4.27) were associated with hepatocellular carcinoma. Smoking contributed to almost half of all hepatocellular carcinomas (47.6%), whereas 13.2% and 20.9% were attributable to chronic HBV and HCV infection, respectively. Obesity and heavy alcohol intake contributed 16.1% and 10.2%, respectively. Almost two-thirds (65.7%, 95% CI = 50.6% to 79.3%) of hepatocellular carcinomas can be accounted for by exposure to at least one of these documented risk factors. CONCLUSIONS: Smoking contributed to more hepatocellular carcinomas in this Europe-wide cohort than chronic HBV and HCV infections. Heavy alcohol consumption and obesity also contributed to sizeable fractions of this disease burden. These contributions may be underestimates because EPIC volunteers are likely to be more health conscious than the general population.

Functional foods and dietary supplements: products at the interface between pharma and nutrition.

It is increasingly recognized that most chronic diseases of concern today are multifactorial in origin. To combat such diseases and adverse health conditions, a treatment approach where medicines and nutrition complement each other may prove to be the most successful. Within nutrition, apart from (disease-related) dietetic regimes, an increasing number of functional foods and dietary supplements, each with their own health claim, are marketed. These food items are considered to be positioned between traditional foods and medicines at the so-called 'Pharma-Nutrition Interface'. This paper encompasses aspects related to the regulatory framework and health claims of functional foods and dietary supplements. The use of functional foods or dietary supplements may offer opportunities to reduce health risk factors and risk of diseases, both as monotherapy and in combination with prescription drugs. Nevertheless, the potential caveats of these products should not be overlooked. These caveats include the increased risk for food-drug interactions due to the elevated amounts of specific functional ingredients in the diet, and the stimulation of self-medication potentially resulting in lower adherence to drug therapy. Health technology assessments should be used more to compare the cost-effectiveness and benefit-risk ratios of drugs, functional foods and dietary supplements, and to evaluate the added value of functional foods or dietary supplements to drug therapy.

Costs and health effects of adding functional foods containing phytosterols/-stanols to statin therapy in the prevention of cardiovascular disease.

The present modelling study aimed to evaluate if and by how much functional foods containing phytosterols/-stanols add to the benefits of statins in the prevention of cardiovascular disease in terms of cost-effectiveness. Long-term health effects, measured as quality-adjusted life-years gained, and costs for scenarios with additional phytosterol/-stanol use were compared to scenarios without extra use. Phytosterols/-stanols were given only to persons who were eligible for use according to their 10-year absolute risk of fatal cardiovascular disease (SCORE-risk). Intake levels and discontinuation rates as observed in daily practice were included in the model. Two situations were compared: 1) A real-life situation in which persons at high SCORE-risk were identified through clinical case-finding and, 2) A theoretical maximum situation where universal screening was implemented resulting in known SCORE-risks for the whole Dutch population aged 35-75 years (8.4 million people). Sensitivity analyses were performed for variations in the cholesterol-lowering effect and intake level of phytosterols/-stanols, indirect health care costs, time horizon and discount rates. At the model's start year, a total of 1.0 (real-life situation) to 3.3 (maximum situation) million persons qualified for phytosterol/-stanol use based on their SCORE-risk (both statin users and statin non-users). Over the model's time horizon, this resulted in a gain of 2700 to 16,300 quality-adjusted life-years, and yielded cost-effectiveness ratios that ranged between €92,000 and €203,000 per quality-adjusted life-year. This simulation study showed that the cost-effectiveness of phytosterols/-stanols as monotherapy and as add-on to statins is above thresholds for cost-effectiveness, generally ranging between €20,000 and €50,000, and is thus a non-cost-effective strategy to reduce cardiovascular disease.

Influence of the use of functional foods enriched with phytosterols/-stanols on adherence to statin therapy.

PURPOSE: Subjects using functional foods with approved health claims may be more likely to be non-adherent with prescribed drug therapy. This study aimed to assess the influence of the use of phytosterol/-stanol-enriched functional foods on adherence to statin therapy among patients initiating treatment. METHODS: We used data from the statin intervention research project, a randomized controlled trial aimed at improving adherence to statins. In the trial, new statin users were randomized to receive either usual care or extensive pharmaceutical care consisting of five individual counseling sessions. Customary use of phytosterol/-stanol-enriched products was identified by questionnaires filled out by all participants. Automated pharmacy-dispensing records were used to assess adherence in terms of discontinuation of therapy and the medication possession ratio. Analyses were performed for the overall population, as well as stratified for receiving pharmaceutical or usual care. RESULTS: The use of functional foods enriched with phytosterols/-stanols was not related to discontinuation of statin therapy, neither in the overall population (overall population adjusted hazard rate ratio (HR(adj)): 0.80 [95%CI: 0.59-1.08]), nor when stratified by randomization arm (pharmaceutical care HR(adj): 0.77 [95%CI: 0.49-1.23]); usual care HR(adj): 0.81 [95%CI: 0.54-1.21]). The median medication possession ratio was significantly lower in users of phytosterols/-stanols in the usual care group, but the difference was not clinically relevant. CONCLUSIONS: Customary use of phytosterol/-stanol-enriched functional foods did not affect adherence to statins in new users that are well informed on the beneficial effects of statin therapy. In daily medical practice, general practitioners and pharmacists should urge subjects not to take phytosterol/-stanol-enriched functional foods as replacement for their prescribed medication.