Coffee consumption is inversely associated with cognitive decline in elderly European men: the FINE Study.

OBJECTIVE: To investigate whether coffee consumption is associated with 10-year cognitive decline in elderly men, as results of previous studies obtained hitherto have been controversial and prospective information on this association has been lacking. DESIGN, SUBJECTS AND SETTING: Six hundred and seventy six healthy men born between 1900 and 1920 from Finland, Italy and the Netherlands participated in a 10-year prospective cohort study. Cognitive functioning was assessed using the Mini-Mental State Examination (0-30 points, with a higher score indicating better cognitive performance). Coffee consumption was estimated in cups per day. A mixed longitudinal model was used to investigate the association between baseline coffee consumption and 10-year cognitive decline. Multiple adjustments were made. RESULTS: Men who consumed coffee had a 10-year cognitive decline of 1.2 points (4%). Non-consumers had an additional decline of 1.4 points (P<0.001). An inverse and J-shaped association was observed between the number of cups of coffee consumed and cognitive decline, with the least cognitive decline for three cups of coffee per day (0.6 points). This decline was 4.3 times smaller than the decline of non-consumers (P<0.001). CONCLUSIONS: Findings suggest that consuming coffee reduces cognitive decline in elderly men. An inverse and J-shaped association may exist between the number of cups of coffee consumed and cognitive decline, with the least cognitive decline for men consuming three cups of coffee per day.

The impact of migraine on quality of life in the general population: the GEM study.

OBJECTIVE: To assess health-related quality of life (HRQOL) in migraineurs in the general population. DESIGN: Cross-sectional study within the context of a population-based study monitoring health characteristics of the Dutch adult population in two municipalities representative of the general population in the Netherlands. Migraine was assessed in a multistaged procedure that included a semistructured clinical interview by telephone. Final diagnosis met 1988 International Headache Society criteria. HRQOL was measured with the self-administered RAND 36-item Health Survey (RAND-36), including physical functioning, social functioning, role limitations, and physical perception. HRQOL of migraineurs was compared with that of nonmigraineurs. To compare and study the effect of comorbidity, the authors also identified subjects with asthma or chronic musculoskeletal pain. There were 5998 people with complete data, 620 of whom had migraine in the last year. RESULTS: Compared with nonmigraineurs, significantly more migraineurs had asthma (OR = 1.6; 95% CI 1.1, 2.4) or chronic musculoskeletal pain (OR = 1.7; 95% CI 1.5, 2.1). Migraineurs reported diminished functioning and well-being on all eight domains as compared with nonmigraineurs. HRQOL was inversely related to attack frequency (p < 0.0002). Migraineurs had a poorer HRQOL than did those reporting asthma, except for dimensions concerning physical functioning and general health perception, but they had a better HRQOL than did subjects with chronic musculoskeletal pain. Comorbidity of asthma or chronic musculoskeletal pain in migraine further reduced HRQOL. CONCLUSIONS: Migraineurs report more asthma and chronic musculoskeletal pain. Compared with nonmigraineurs and to others with chronic conditions, migraineurs report compromised physical, mental, and social functioning, particularly those with a high frequency of attack.

Gliotoxin analogues as inhibitors of reverse transcriptase. 1. Effect of lipophilicity.

The reaction scheme, developed for the synthesis of the gliotoxin analogue 2, was found to be of general applicability for analogues with varying substituents at N(1) and C(2). Analogues 11b-g prepared by this method are inhibitors of reverse transcriptase (RNA-directed DNA polymerase). Their inhibitory activity seems to be related to the lipophilicity of the effector molecules: the most lipophilic compound is the most active inhibitor. The techniques of reversed-phase thin-layer chromatography with silylated, precoated plates as well as reversed-phase high-performance liquid chromatography were used to measure the relative lipophilicities; both techniques gave analogous results.

Gliotoxin analogues as inhibitors of reverse transcriptase. 2. Resolution and X-ray crystal structure determination.

A novel, simple, and efficient method for the chemical resolution of epidithiodioxopiperazines is reported, which is based upon covalent formation of diastereomers. This method might be a general one for the resolution of chiral cyclic disulfides. Dithiol 5, prepared from 2 by reduction with NaBH4, was allowed to react with the disulfenyl chloride 8 to yield 9 and 10, which were separated by short-column chromatography on silica gel. From these, the optically pure enantiomers 11 and 12, respectively, were obtained by reduction with NaBH4, followed by reoxidation with I2-pyridine. In this way the precursor 7 of the resolving agent could also be recovered. The absolute configurations of 11 and 12 were derived from CD spectra. Kinetic asymmetric transformation of the gliotoxin analogue 2 with the diphosphine 6 gave a 19% enrichment in one enantiomer of the starting material. Surprisingly, both enantiomers were found to inhibit reverse transcriptase, the RNA-dependent DNA polymerase, to the same degree, indicating that there is no relation between this property of epidithiodioxopiperazines and their bridgehead configurations. From the X-ray crystal structure determination it can be seen that there is a considerable torsional and conformational strain in compound 2, which might enhance the ease of cleavage of the S-S bond. A possible relationship between this property and the biological activity of 2 is discussed.

Which chronic conditions are associated with better or poorer quality of life?

The objective of the present study is to compare the QL of a wide range of chronic disease patients. Secondary analysis of eight existing data sets, including over 15,000 patients, was performed. The studies were conducted between 1993 and 1996 and included population-based samples, referred samples, consecutive samples, and/or consecutive samples. The SF-36 or SF-24 were employed as generic QL instruments. Patients who were older, female, had a low level of education, were not living with a partner, and had at least one comorbid condition, in general, reported the poorest level of QL. On the basis of rank ordering across the QL dimensions, three broad categories could be distinguished. Urogenital conditions, hearing impairments, psychiatric disorders, and dermatologic conditions were found to result in relatively favorable functioning. A group of disease clusters assuming an intermediate position encompassed cardiovascular conditions, cancer, endocrinologic conditions, visual impairments, and chronic respiratory diseases. Gastrointestinal conditions, cerebrovascular/neurologic conditions, renal diseases, and musculoskeletal conditions led to the most adverse sequelae. This categorization reflects the combined result of the diseases and comorbid conditions. If these results are replicated and validated in future studies, they can be considered in addition to information on the prevalence of the diseases, potential benefits of care, and current disease-specific expenditures. This combined information will help to better plan and allocate resources for research, training, and health care.

Lifestyle risk factors for cancer: the relationship with psychosocial work environment.

BACKGROUND: Psychosocial work characteristics (job demands, control, support, job strain and iso-strain [high job strain combined with social isolation at work]) may be linked to cancer risk, by affecting cancer-related lifestyles like smoking, high alcohol consumption, low intake of fruits and vegetables and lack of physical activity. METHODS: Cross-sectional data obtained from 3309 respondents participating in an ongoing prospective cohort study in the Netherlands on psychosocial factors and cancer risk were used to study the association between psychosocial job characteristics and lifestyle. Information on job characteristics and risk factor prevalence was collected from 20-65-year-old men and women, through self-administered questionnaires. Multiple logistic and linear regression analyses were undertaken by gender, with adjustment for age and education. RESULTS: No differences in the prevalence of lifestyle risk factors for cancer were found amongst the psychosocial work characteristics studied. Moreover, little evidence was found for a relation between job (or iso-) strain and cancer-related lifestyles in multivariate analyses. CONCLUSIONS: The present study found no support for the hypothesis that job strain or iso-strain are associated with a cancer-related lifestyle. Further research on the role of other psychosocial factors-like personality or social support outside work-in mediating associations between job characteristics and lifestyle, is warranted.

A measurement of social support in epidemiological research: the social experiences checklist tested in a general population in The Netherlands.

STUDY OBJECTIVE: This study aimed to examine in a general population the psychometric qualities of an instrument designed to measure positive and negative social experiences that had been developed in a clinical setting. DESIGN: The Netherlands monitoring project on cardiovascular disease risk factors, a large scale population based study (comprising 36,588 men and women aged 20 to 59 years) carried out in three Dutch towns (Amsterdam, Doetinchem, and Maastricht) offered the possibility of testing the strength of this instrument cross sectionally. MEASUREMENTS AND MAIN RESULTS: The social experiences checklist (SEC) which resulted from a research project on the quality of life of cancer patients was used. The independence of positive and negative experiences was confirmed. The reliability of both the positive and negative experiences dimension was good (Cronbach's alpha = 0.82 and 0.72 respectively). In accordance with the results of a study on cancer patients, the theoretically derived four dimensions in the experience of social support did not seem to be independent. The validity of the SEC was confirmed by Pearson correlations with neuroticism and coping styles. Neuroticism seemed to be negatively correlated with positive social experiences and was positively correlated with negative social experiences. The coping style of seeking information and direct action was positively correlated with positive social experiences. Coping by withdrawal was negatively correlated with negative social experiences. Women and highly educated people seemed to have more positive and fewer negative social experiences than men and people with less education. Younger people had more positive social experiences than older people. The oldest group in the study, those aged 50 to 59, reported fewer negative social experiences than any other age group. CONCLUSIONS: Similar results were found in a study of cancer patients. This underlines the usefulness of the instrument not only for cancer patients but also in survey research in a general population.

Psychosocial problems in primary care: some results from the Dutch National Study of Morbidity and Interventions in General Practice.

According to standardized screening instruments, mental distress is a common phenomenon among many patients who visit their general practitioner. However, a number of patients who seem to be in need of mental help do not put forward such a demand for help, whereas other patients who express psychosocial problems to their GP are not considered to be in need, according to a standardized measure. In this paper, a distinction has been made between the objectified needs of the patient as expressed by a standardized assessment, and the demands of the patient, expressed by the Reason for Encounter, stated during their visit at the GP. Results of a follow-up study of two cohorts of patients have been presented: one cohort presented during a 3 month period at least one articulated demand for psychosocial help, a second cohort presented at least one somatic complaint, considered by the GP as being psychological by character, without presenting any psychosocial complaint in that period. Objective needs for mental help of patients in both cohorts were assessed by means of the General Health Questionnaire. During one year all consultations of these two cohorts were registered. The following questions have been put forward: what demands for help have been put forward by the patients, what treatment have these patients got, and what has been the course of the problems during one year of patients with different needs and demands. From the results the following conclusions may be drawn: many patients with a probable mental illness (according to their objective need) present only physical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

An orientation toward help-seeking for emotional problems.

In recent years, many researchers tried to explain the social selection in use of mental health care services. A modest role is attributed to the orientation toward help-seeking. This article studies this orientation. Our research-population consisted of 10,171 Dutch persons, aged 18 and older. Analysis showed that most people are prone to seek help for one or more emotional problems. People who are more prone to seek help are younger, have had more education and have a higher family income. They have more often acquaintances working in mental health care. People who are more prone to seek help do not see chance as the locus of control of health. These people are less dependent on their GP for common disorders and are more open about mental health matters. The results of discriminant analysis are not satisfactory, but when we try to distinguish the groups of people who are and who are not willing to seek help, we see that the best discriminating factor is their help-seeking attitude for common disorders. People who have high expectations from the GP for common disorders, clearly do have a preference to seek help for the emotional problems. The groups of people who are more willing to seek help from the GP compared to mental health professionals cannot be distinguished by these expectations. Here the level of education discriminates fairly well: people who are more prone to seek help from a GP have a lower educational level. Future research should be focussed on the testing of a theoretical model that explains the orientation toward help-seeking for emotional problems and selection in help-seeking with longitudinal data.

Social support and stressful events in two dimensions: life events and illness as an event.

Previous research on the buffering effects of social support focused mainly on life events as stressors, and mental illness as outcome. Furthermore, the question as to why support influences illness has not been subjected to theoretical or empirical study much. In this article we develop a hypothesis on the basis of the theory of social capital. We hypothesize that specific types of social resources are more relevant to the consequences of some events than of others. We test this hypothesis in two ways: (1) by taking life events as stressor and occurrence of illness as outcome, and, which is somewhat unusual, (2) by taking illness as stressor and duration and disabilities of illness as the outcome. Analyses of a representative sample of the Dutch population (N = 10,110) reveal that receiving specific types of support does not lead to better health or less illness in cases of stress. On the contrary, people who are under stress and receive more support, also appear to report more illness, more disabilities and a longer duration. We suggest that in an open sample like ours, the disease level measured is not severe enough to assess buffer effects of social support.

The acetylation-deacetylation equilibrium of sulfadimidine in ruminant calves.

Plasma disappearance curves of sulfadimidine (SDM) in calves show at high doses a pattern resembling that of capacity-limited elimination. The half-life of the first part of the elimination phase of SDM when administered at high doses ranged between 6.4 and 11.5 h, while that of the terminal end of the plasma concentration-time curves was similar to that obtained at a low level application, ranging between 2.5 and 6.0 h. The percentage of N4-acetylsulfadimidine (N4-SDM) in plasma was low, viz. 2.2 to 5.8% of the total sulfadimidine concentration measured. The acetylation-deacetylation equilibrium was established within 3 h p.i. The N4-SDM plasma concentration-time curves were parallel to those of SDM beyond 3 h p.i. At high doses (66-235 mg/kg) the percentage of N4-SDM was slightly higher than that found at the low dose level. A small proportion of N4-acetylsulfadimidine, injected as the parent compound, was deacetylated to SDM. The intrinsic elimination half-life of N4-SDM was 0.9 h. It may be concluded that ultra-trace concentrations of N4-SDM, left in edible tissues of ruminants at slaughter, have in case of negative sulfonamide-sensitive bioassays no significance for the public health.

State of the art in benefit-risk analysis: medicines.

Benefit-risk assessment in medicine has been a valuable tool in the regulation of medicines since the 1960s. Benefit-risk assessment takes place in multiple stages during a medicine's life-cycle and can be conducted in a variety of ways, using methods ranging from qualitative to quantitative. Each benefit-risk assessment method is subject to its own specific strengths and limitations. Despite its widespread and long-time use, benefit-risk assessment in medicine is subject to debate and suffers from a number of limitations and is currently still under development. This state of the art review paper will discuss the various aspects and approaches to benefit-risk assessment in medicine in a chronological pathway. The review will discuss all types of benefit-risk assessment a medicinal product will undergo during its lifecycle, from Phase I clinical trials to post-marketing surveillance and health technology assessment for inclusion in public formularies. The benefit-risk profile of a drug is dynamic and differs for different indications and patient groups. In the end of this review we conclude benefit-risk analysis in medicine is a developed practice that is subject to continuous improvement and modernisation. Improvement not only in methodology, but also in cooperation between organizations can improve benefit-risk assessment.

State of the art in benefit-risk analysis: consumer perception.

Benefit and risk perception with respect to food consumption, have been a part of human daily life from beginning of time. In today's society the food chain is long with many different types of actors and low degree of transparency. Making informed food choices where knowledge of benefits and risks is part of the decision making process are therefore complicated for consumers. Thus, to understand how consumers perceive benefits and risks of foods, their importance in relation to quality evaluations are aspects that need to be addressed. The objective of this paper is to discuss state of the art in understanding consumer perceptions of benefits and risks of foods in order to improve understanding of consumer behaviour in the food domain. Risks may be associated with both acute and long term consequences, some of which may have serious effects. Perceived risks are connected to morbidity and mortality along two dimensions relating to unknown risk, and to which extent the risk is dreaded by the consumer. Unfamiliar, uncertain, unknown, uncontrollable, and severe consequences are some factors associated with risk perception. Novel food processing techniques, for instance, score high on several of these parameters and are consequently regarded with suspicion and perceived as risky by consumers. On a daily basis, benefits of foods and food consumption are more important in most consumers' minds than risks. Benefits are often associated with food's ability to assuage hunger, and to provide pleasure through eating and socialising. In addition, two main categories of benefits that are important for acceptance of product innovations are health and environmental benefits. Benefit and risk perception of foods seem to be inversely correlated, so when something is perceived as being highly beneficial, it is correspondingly perceived as having low risk. However, slightly different paths are used in the formation of these perceptions; benefit perception is based on heuristics and experience, while risk perception is to a larger extent the result of cognitive information processing. Consumers are particularly conservative when it comes to perception and acceptance of foods compared to other products. Benefit-risk evaluations tend to be skewed towards acceptance of all that is traditional and well-known (benefits), and rejection or suspicion towards anything that is novel or highly processed (risks) regardless of actual risk. Knowledge of how consumers perceive benefits and risks of foods, may contribute to understanding benefit-risk perception in other areas related to personal, societal or environmental perspectives.

State of the art in benefit-risk analysis: economics and marketing-finance.

All market participants (e.g., investors, producers, consumers) accept a certain level of risk as necessary to achieve certain benefits. There are many types of risk including price, production, financial, institutional, and individual human risks. All these risks should be effectively managed in order to derive the utmost of benefits and avoid disruption and/or catastrophic economic consequences for the food industry. The identification, analysis, determination, and understanding of the benefit-risk trade-offs of market participants in the food markets may help policy makers, financial analysts and marketers to make well-informed and effective corporate investment strategies in order to deal with highly uncertain and risky situations. In this paper, we discuss the role that benefits and risks play in the formation of the decision-making process of market-participants, who are engaged in the upstream and downstream stages of the food supply chain. In addition, we review the most common approaches (expected utility model and psychometrics) for measuring benefit-risk trade-offs in the economics and marketing-finance literature, and different factors that may affect the economic behaviour in the light of benefit-risk analyses. Building on the findings of our review, we introduce a conceptual framework to study the benefit-risk behaviour of market participants. Specifically, we suggest the decoupling of benefits and risks into the separate components of utilitarian benefits, hedonic benefits, and risk attitude and risk perception, respectively. Predicting and explaining how market participants in the food industry form their overall attitude in light of benefit-risk trade-offs may be critical for policy-makers and managers who need to understand the drivers of the economic behaviour of market participants with respect to production, marketing and consumption of food products.

State of the art in benefit-risk analysis: introduction.

Risk-taking is normal in everyday life if there are associated (perceived) benefits. Benefit-Risk Analysis (BRA) compares the risk of a situation to its related benefits and addresses the acceptability of the risk. Over the past years BRA in relation to food and food ingredients has gained attention. Food, and even the same food ingredient, may confer both beneficial and adverse effects. Measures directed at food safety may lead to suboptimal or insufficient levels of ingredients from a benefit perspective. In BRA, benefits and risks of food (ingredients) are assessed in one go and may conditionally be expressed into one currency. This allows the comparison of adverse and beneficial effects to be qualitative and quantitative. A BRA should help policy-makers to make more informed and balanced benefit-risk management decisions. Not allowing food benefits to occur in order to guarantee food safety is a risk management decision much the same as accepting some risk in order to achieve more benefits. BRA in food and nutrition is making progress, but difficulties remain. The field may benefit from looking across its borders to learn from other research areas. The BEPRARIBEAN project (Best Practices for Risk-Benefit Analysis: experience from out of food into food; http://en.opasnet.org/w/Bepraribean) aims to do so, by working together with Medicines, Food Microbiology, Environmental Health, Economics & Marketing-Finance and Consumer Perception. All perspectives are reviewed and subsequently integrated to identify opportunities for further development of BRA for food and food ingredients. Interesting issues that emerge are the varying degrees of risk that are deemed acceptable within the areas and the trend towards more open and participatory BRA processes. A set of 6 'state of the art' papers covering the above areas and a paper integrating the separate (re)views are published in this volume.

State of the art in benefit-risk analysis: food microbiology.

Over the past years benefit-risk analysis (BRA) in relation to foods and food ingredients has gained much attention; in Europe and worldwide. BRA relating to food microbiology is however a relatively new field of research. Microbiological risk assessment is well defined but assessment of microbial benefits and the weighing of benefits and risk has not been systematically addressed. In this paper the state of the art in benefit-risk analysis in food microbiology is presented, with a brief overview of microbiological food safety practices. The quality and safety of foods is commonly best preserved by delaying the growth of spoilage bacteria and contamination by bacterial pathogens. However, microorganisms in food can be both harmful and beneficial. Many microorganisms are integral to various food production processes e.g. the production of beer, wine and various dairy products. Moreover, the use of some microorganisms in the production of fermented foods are often claimed to have beneficial effects on food nutrition and consumer health. Furthermore, food safety interventions leading to reduced public exposure to foodborne pathogens can be regarded as benefits. The BRA approach integrates an independent assessment of both risks and benefits and weighs the two using a common currency. Recently, a number of initiatives have been launched in the field of food and nutrition to address the formulation of the benefit-risk assessment approach. BRA has recently been advocated by EFSA for the public health management of food and food ingredients; as beneficial and adverse chemicals can often be found within the same foods and even the same ingredients. These recent developments in the scoping of BRA could be very relevant for food microbiological issues. BRA could become a valuable methodology to support evaluations and decision making regarding microbiological food safety and public health, supplementing other presently available policy making and administrative tools for microbiological food safety management.

State of the art in benefit-risk analysis: environmental health.

Environmental health assessment covers a broad area: virtually all systematic analysis to support decision making on issues relevant to environment and health. Consequently, various different approaches have been developed and applied for different needs within the broad field. In this paper we explore the plurality of approaches and attempt to reveal the state-of-the-art in environmental health assessment by characterizing and explicating the similarities and differences between them. A diverse, yet concise, set of approaches to environmental health assessment is analyzed in terms of nine attributes: purpose, problem owner, question, answer, process, use, interaction, performance and establishment. The conclusions of the analysis underline the multitude and complexity of issues in environmental health assessment as well as the variety of perspectives taken to address them. In response to the challenges, a tendency towards developing and applying more inclusive, pragmatic and integrative approaches can be identified. The most interesting aspects of environmental health assessment are found among these emerging approaches: (a) increasing engagement between assessment and management as well as stakeholders, (b) strive for framing assessments according to specific practical policy needs, (c) integration of multiple benefits and risks, as well as (d) explicit incorporation of both scientific facts and value statements in assessment. However, such approaches are yet to become established, and many contemporary mainstream environmental health assessment practices can still be characterized as relatively traditional risk assessment.

Looking beyond borders: integrating best practices in benefit-risk analysis into the field of food and nutrition.

An integrated benefit-risk analysis aims to give guidance in decision situations where benefits do not clearly prevail over risks, and explicit weighing of benefits and risks is thus indicated. The BEPRARIBEAN project aims to advance benefit-risk analysis in the area of food and nutrition by learning from other fields. This paper constitutes the final stage of the project, in which commonalities and differences in benefit-risk analysis are identified between the Food and Nutrition field and other fields, namely Medicines, Food Microbiology, Environmental Health, Economics and Marketing-Finance, and Consumer Perception. From this, ways forward are characterized for benefit-risk analysis in Food and Nutrition. Integrated benefit-risk analysis in Food and Nutrition may advance in the following ways: Increased engagement and communication between assessors, managers, and stakeholders; more pragmatic problem-oriented framing of assessment; accepting some risk; pre- and post-market analysis; explicit communication of the assessment purpose, input and output; more human (dose-response) data and more efficient use of human data; segmenting populations based on physiology; explicit consideration of value judgments in assessment; integration of multiple benefits and risks from multiple domains; explicit recognition of the impact of consumer beliefs, opinions, views, perceptions, and attitudes on behaviour; and segmenting populations based on behaviour; the opportunities proposed here do not provide ultimate solutions; rather, they define a collection of issues to be taken account of in developing methods, tools, practices and policies, as well as refining the regulatory context, for benefit-risk analysis in Food and Nutrition and other fields. Thus, these opportunities will now need to be explored further and incorporated into benefit-risk practice and policy. If accepted, incorporation of these opportunities will also involve a paradigm shift in Food and Nutrition benefit-risk analysis towards conceiving the analysis as a process of creating shared knowledge among all stakeholders.

State of the art in benefit-risk analysis: food and nutrition.

Benefit-risk assessment in food and nutrition is relatively new. It weighs the beneficial and adverse effects that a food (component) may have, in order to facilitate more informed management decisions regarding public health issues. It is rooted in the recognition that good food and nutrition can improve health and that some risk may be acceptable if benefit is expected to outweigh it. This paper presents an overview of current concepts and practices in benefit-risk analysis for food and nutrition. It aims to facilitate scientists and policy makers in performing, interpreting and evaluating benefit-risk assessments. Historically, the assessments of risks and benefits have been separate processes. Risk assessment is mainly addressed by toxicology, as demanded by regulation. It traditionally assumes that a maximum safe dose can be determined from experimental studies (usually in animals) and that applying appropriate uncertainty factors then defines the 'safe' intake for human populations. There is a minor role for other research traditions in risk assessment, such as epidemiology, which quantifies associations between determinants and health effects in humans. These effects can be both adverse and beneficial. Benefit assessment is newly developing in regulatory terms, but has been the subject of research for a long time within nutrition and epidemiology. The exact scope is yet to be defined. Reductions in risk can be termed benefits, but also states rising above 'the average health' are explored as benefits. In nutrition, current interest is in 'optimal' intake; from a population perspective, but also from a more individualised perspective. In current approaches to combine benefit and risk assessment, benefit assessment mirrors the traditional risk assessment paradigm of hazard identification, hazard characterization, exposure assessment and risk characterization. Benefit-risk comparison can be qualitative and quantitative. In a quantitative comparison, benefits and risks are expressed in a common currency, for which the input may be deterministic or (increasingly more) probabilistic. A tiered approach is advocated, as this allows for transparency, an early stop in the analysis and interim interaction with the decision-maker. A general problem in the disciplines underlying benefit-risk assessment is that good dose-response data, i.e. at relevant intake levels and suitable for the target population, are scarce. It is concluded that, provided it is clearly explained, benefit-risk assessment is a valuable approach to systematically show current knowledge and its gaps and to transparently provide the best possible science-based answer to complicated questions with a large potential impact on public health.