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Benefit-risk assessment of plant sterols in margarine: A QALIBRA case study
... As examples, while the first RBA studies focused on one single food (e.g. fish) (e.g Hoekstra, Fransen, et al., 2013;Skåre et al., 2015) or one single food component (e.g. folic acid (Hoekstra et al., 2008)) and investigated risks and benefits in the population as a whole, recent work has taken into account the health effects of substitution of foods in overall dietary patterns, or variation in the population in terms of susceptibility or dietary preferences (see Sections 3.2 and 3.3). ...
... The majority of published RBA in the area of food safety and nutrition focused on single foods (Berjia et al., 2014;Eneroth et al., 2017;Hoekstra, Fransen, et al., 2013;, with fish being most frequently evaluated (Boué, Guillou, Antignac, Bizec, & Membré, 2015). These RBA studies aimed to assess the overall impact of a food consumed while considering different levels of exposure and different factors affecting human health related to the fields of nutrition and/or microbiology and/or toxicology. ...
... It is the metric of choice for the Global Burden of Disease studies (Anonymous, 2017b), and has been shown to be a valuable instrument for risk ranking of foodborne hazards (Havelaar et al., 2012(Havelaar et al., , 2015. It has also been applied in RBA studies to summarize the overall health impacts of foods (Berjia et al., 2014;Eneroth et al., 2017;Hoekstra, Fransen, et al., 2013;. While a single DALY estimate is usually the final estimate in burden of disease studies, the difference in DALYs between a reference and an alternative scenario (ΔDALY) has been used as the final estimate of RBA studies (Eneroth et al., 2017;Firew Berjia et al., 2012). ...
Whilst risk management measures, including food policy, are developed for the protection of public health and the environment, they may also lead to a reduction in health benefits. Policy decisions require then consideration of these necessary trade-offs, which leads to an increasing need to apply formal risk-benefit assessment (RBA) of foods. In this context, the European Food Safety Authority sponsored a Risk-Benefit Assessment Workshop on “past, current and future developments within the risk-benefit assessment of foods (RBA)” held in May 2017. The overall aims of the RBA Workshop were to discuss existing methods, challenges and needs within RBA, and to draft a roadmap for future development of RBA. The specific objectives were to i) identify RBA activities in Europe and globally; ii) discuss how to further develop and optimize RBA methodology; iii) identify challenges and opportunities within RBA; and iv) increase collaboration internationally. The two-day workshop gathered 28 participants from 16 institutions in 11 countries. It included technical presentations of RBA methods and case studies, and two break-out sessions for group discussions. All participants agreed that RBA has substantial potential to inform risk-management decisions in the areas of food safety, nutrition and public health. Several activities to optimize further developments within RBA were suggested. This paper provides a summary of workshop presentations, a discussion of challenges that limit progress in this area, and suggestions of next steps for this promising approach supporting a science-based decision process in the area of risk-benefit management of foods.
... It has been reported that margarine supplemented with plant sterol could save eight healthy years per 1000 people (Hoekstra et al., 2013a). ...
... The term "benefit" is unanimously used to mirror the risk but we found different terms used to mirror the term "hazard": "positive effect" (Boobis et al., 2013;Hoekstra et al., 2012;Schutte et al., 2012;Verhagen et al., 2012a;Watzl et al., 2012), "benefit" (EFSA, 2006;Hoekstra et al., 2013a;Hoekstra et al., 2008),"positive health effect" (EFSA, 2010; Hellberg et al., 2012), "beneficial effect" , etc. Nevertheless, in the field of nutrition, the same agent could be a source of risk and benefit depending on the consumer exposure (Renwick et al., 2004). In this context, we propose to use a more general term to encompass the term hazard and its counterpart on the benefit side. ...
... RBA must also consider both uncertainty and variability. More and more in RBA studies, stochastic approaches have been used to consider quantitatively the variability of inputs by integrating for instance variables profiles of nutrients and chemicals in food (Afonso et al., 2016;Afonso et al., 2015;Becker et al., 2007;Cardoso et al., 2015;Cardoso et al., 2013;Dewailly et al., 2008;FDA, 2009;GAO et al., 2015;Glynn et al., 2013;Groth, 2017;Hendriksen et al., 2011;Hoekstra et al., 2013a;Hoekstra et al., 2013b;Husoy et al., 2008;Laird et al., 2013;Matos et al., 2015;Maulvault et al., 2013;Reyes, 2016;SACN/COT, 2004;Schutte et al., 2012;Seal et al., 2008;. It is also recommended to include "an appropriate" expression of uncertainty in the BRAFO tiered approach with at least a qualitative assessment of all different sources which can be easily communicated through a table listing sources of uncertainty with potential magnitude and direction of influence, as done in (Hoekstra et al., 2013b). ...
The objective of the present PhD project was to develop a conceptual and methodological framework to assess quantitatively the overall impact of food on human health, including microbiological, chemical and nutritional dimensions.
This methodology was developed using a case study on infant milk-based diet (breast milk and infant formulas) taking into account the following selected factors: Cronobacter sakazakii, Cryptosporidium, arsenic, dioxin like polychlorinated biphenyls and docosahexaenoic acid. Five probabilistic mathematical models were developed to quantify risks / benefits associated with these factors. When possible, they were harmonised using a common public health indicator, the DALY. Results were obtained by second-order Monte Carlo simulation in order to quantify separately the uncertainty and the variability.
Probabilistic techniques enabled to take into account on the one hand the biology related to variability (heterogeneity between individuals of the same population) and on the other hand the uncertainty linked to the lack of knowledge and data. In addition, separation of variability and uncertainty strengthened the evaluation by enabling a more accurate interpretation of results and by providing more comprehensive information for policy makers.
The method used in this PhD thesis can be considered as a robust basis for other case studies and can be used to continue methodological development in risk-benefit assessment. This approach is also part of a broader area: the multi-criteria decision analysis of agronomic and food systems.
... The study estimated 19 [95% CI = 8-33] DALY per 100,000 people per year for CRC and 21 [95% CI = 12-32] DALY per 100,000 people per year for CVD, associated with the consumption of red meat. As done previously (Cardoso et al., 2018;Hoekstra et al., 2013aHoekstra et al., , 2013bThomsen et al., 2018Thomsen et al., , 2019Verhagen et al., 2012;Wikoff et al., 2018), the present work will be included in a more comprehensive risk and benefit assessment. ...
The consumption of red meat has been associated with colorectal cancer (CRC) and cardiovascular disease (CVD) worldwide. The objective of this study was to assess quantitatively the burden of disease of CRC and CVD due to the consumption of red meat in France. A probabilistic risk assessment model quantifying the risk, deaths and disability adjusted life years (DALY) of both outcomes was built. In the model, uncertainty and variability were propagated separately. The model used data on current CRC and CVD incidence and red meat consumption in France, as well as dose-response from epidemiological studies. Results were given by age class and gender. A total of 19 [95% CI = 8–33] DALY per 100,000 people per year for CRC associated with red meat consumption was estimated. For CVD, 21 [95% CI = 12–32] DALY per 100,000 people per year was estimated. The uncertainty was mainly due to the dose-response, as revealed by a sensitivity analysis. A scenario analysis, performed on red meat intake, highlighted that consumption of less than 65 g per day could limit the risk of CRC and CVD in the most affected sub-populations.
... As part of the BRAFO project, a number of relevant riskbenefit studies that illustrate the usefulness of a tiered approach for RBAs have been performed (Hoekstra et al., 2008;Schütte et al., 2012;Verhagen et al., 2012b;Watzl et al., 2012). A specific software tool, QALIBRA, has been developed to facilitate the performance of quantitative assessments in the final tier Hoekstra, Fransen et al., 2013). ...
Background
Risk-benefit assessment (RBA) of foods aims to assess the combined negative and positive health effects associated with food intake. RBAs integrate chemical and microbiological risk assessment with risk and benefit assessment in nutrition.
Scope and Approach
Based on the past experiences and the methodological differences between the underlying research disciplines, this paper aims to describe the recent progress in RBAs, identifying the key challenges that need to be addressed for further development, and making suggestions for meeting these challenges.
Key Findings and Conclusions
Ten specific challenges are identified and discussed. They include the variety of different definitions and terminologies used in the underlying research disciplines, the differences between the “bottom-up” and the “top-down” approaches and the need for clear risk-benefit questions. The frequent lack of data and knowledge with their consequential uncertainties is considered, as well as the imbalance in the level of scientific evidence associated with health risks and benefits. The challenges that are consequential to the need of considering substitution issues are discussed, as are those related to the inclusion of microbiological hazards. Further challenges include the choice of the integrative health metrics and the potential scope of RBAs, which may go beyond the health effect. Finally, the need for more practical applications of RBA is stressed. Suggestions for meeting the identified challenges include an increased interdisciplinary consensus, reconsideration of methodological approaches and health metrics based on a categorisation of risk-benefit questions, and the performance of case studies to experience the feasibility of the proposed approaches.
... This is because complete avoidance of food risks is not possible, and because food has cultural, symbolic, familial, and religious connotations which must be taken into account when developing risk messages ( Frewer et al. 2015). In addition, food may simultaneously be associated with risks, such as inclusion of contaminants, and benefits, such as nutritional advantages (Cohen et al. 2005;Hoekstra et al. 2013aHoekstra et al. , 2013bvan der Voet, de Mul, and van Klaveren 2007) suggesting that both risk and benefit perceptions associated with foods need to be considered when developing risk communication strategies (van Dijk, Fischer, and Frewer 2011;Hooper 2006;Saba and Messina 2003). ...
Considerable research effort is invested in the development of evidence to help policy makers and industry deal with the challenges associated with existing and emerging food safety threats. This research aimed to elicit expert views regarding the relationship between the drivers of existing and emerging food safety risks, in order to facilitate their control and mitigation, and to provide the basis for further international policy integration. A Delphi approach involving repeated polling of n = 106 global food safety experts was adopted. The primary drivers of existing and emerging food safety risks were identified to be demographic change, economic driving forces, resource shortages, environmental driving forces, increased complexity of the food supply chain, water security and malevolent activities. The identification of socio-economic and biophysical drivers emphasises the need for a transdisciplinary and systems approach to food safety management and mitigation. The mitigation of hazards on a case-by-case basis is unlikely to have a major impact on food safety hazards but may have unintended effects (where positive or negative) across a broad spectrum of food safety issues. Rather a holistic or systems approach is required which can address both the intended and unintended effects of different drivers and their interactions.
... This is because complete avoidance of food risks is not possible, and because food has cultural, symbolic, familial, and religious connotations which must be taken into account when developing risk messages . In addition, food may simultaneously be associated with risks, such as inclusion of contaminants, and benefits, such as nutritional advantages (Cohen et al. 2005;Hoekstra et al. 2013aHoekstra et al. , 2013bvan der Voet, de Mul, and van Klaveren 2007) suggesting that both risk and benefit perceptions associated with foods need to be considered when developing risk communication strategies (van Dijk, Fischer, and Frewer 2011;Hooper 2006;Saba and Messina 2003). ...
Important determinants of risk perceptions associated with foods are the extent to which the potential hazards are perceived to have technological or naturally occurring origins, together with the acute vs. chronic dimension in which the potential hazard is presented (acute or chronic). This study presents a case study analysis based on an extensive literature review examining how these hazard characteristics affect people’s risk and benefit perceptions, and associated attitudes and behaviors. The cases include E. coli incidences (outbreaks linked to fresh spinach and fenugreek sprouts), contamination of fish by environmental pollutants, (organochlorine contaminants in farmed salmon), radioactive contamination of food following a nuclear accident (the Fukushima accident in Japan), and GM salmon destined for the human food chain. The analysis of the cases over the acute vs. chronic dimension suggests that longitudinal quantification of the relationship between risk perceptions and impacts is important for both acute and chronic food safety, but this has infrequently been applied to chronic hazards. Technologies applied to food production tend to potentially be associated with higher levels of risk perception, linked to perceptions that the risk is unnatural. However, for some risks (e.g. those involving biological irreversibility), moral or ethical concerns may be more important determinants of consumer responses than risk or benefit perceptions. (Lack of) trust has been highlighted in all of the cases suggesting transparent and honest risk–benefit communications following the occurrence of a food safety incident. Implications for optimizing associated risk communication strategies, additional research linking risk perception, and other quantitative measures, including comparisons in time and space, are suggested.
... This is because complete avoidance of food risks is not possible, and because food has cultural, symbolic, familial, and religious connotations which must be taken into account when developing risk messages . In addition, food may simultaneously be associated with risks, such as inclusion of contaminants, and benefits, such as nutritional advantages (Cohen et al. 2005;Hoekstra et al. 2013aHoekstra et al. , 2013bvan der Voet, de Mul, and van Klaveren 2007) suggesting that both risk and benefit perceptions associated with foods need to be considered when developing risk communication strategies (van Dijk, Fischer, and Frewer 2011;Hooper 2006;Saba and Messina 2003). ...
Important determinants of risk perceptions associated with foods are the extent to which the potential hazards are perceived to have technological or naturally occurring origins, together with the acute versus chronic dimension in which the potential hazard is presented (acute or chronic). This study presents a case study analysis to examine how these hazard characteristics affect people’s risk and benefit perceptions, and associated attitudes and behaviors. The cases include E.coli incidences (outbreaks linked to fresh spinach and fenugreek sprouts), contamination of fish by environmental pollutants, (organochlorine contaminants in farmed salmon), radioactive contamination of food following a nuclear accident (the Fukushima accident in Japan), and GM salmon destined for the human food chain. The analysis of the cases over the acute versus chronic dimension suggests that longitudinal quantification of the relationship between risk perceptions and impacts is important for both acute and chronic food safety, but this has infrequently been applied to chronic hazards. Technologies applied to food production tend to potentially be associated with higher levels of risk perception, linked to perceptions that the risk is unnatural. However, for some risks (for example those involving biological irreversibility) moral or ethical concerns may be more important determinants of consumer responses than risk or benefit perceptions. (Lack of) trust has been highlighted in all of the cases suggesting transparent and honest risk-benefit communications following the occurrence of a food safety incident. Implications for optimizing associated risk communication strategies, additional research linking risk perception and other quantitative measures, including comparisons in time and space, are suggested.
... This is because complete avoidance of food risks is not possible, and because food has cultural, symbolic, familial, and religious connotations which must be taken into account when developing risk messages . In addition, food may simultaneously be associated with risks, such as inclusion of contaminants, and benefits, such as nutritional advantages (Cohen et al. 2005;Hoekstra et al. 2013aHoekstra et al. , 2013bvan der Voet, de Mul, and van Klaveren 2007) suggesting that both risk and benefit perceptions associated with foods need to be considered when developing risk communication strategies (van Dijk, Fischer, and Frewer 2011;Hooper 2006;Saba and Messina 2003). ...
Important determinants of risk perceptions associated with foods are the extent to which the potential hazards are perceived to have technological or naturally occurring origins, together with the temporal dimension in which the potential hazard is presented (acute or chronic). This study presents a case study analysis to examine how these hazard characteristics affect people’s risk and benefit perceptions, and associated attitudes and behaviours. The cases include E.coli incidences (outbreaks linked to fresh spinach and fenugreek sprouts), contamination of fish by environmental pollutants, (organochlorine contaminants in farmed salmon), radioactive contamination of food following a nuclear accident (the Fukushima accident in Japan), and GM salmon destined for the human food chain. The analysis of the cases over the temporal dimension suggests that longitudinal quantification of the relationship between risk perceptions and impacts is important for both acute and chronic food safety, but this has infrequently been applied to chronic hazards. Technologies applied to food production tend to potentially be associated with higher levels of risk perception, linked to perceptions that the risk is unnatural. However, for some risks (for example those involving biological irreversibility) moral or ethical concerns may be more important determinants of consumer responses than risk or benefit perceptions. (Lack of) trust has been highlighted in all of the cases suggesting transparent and honest risk-benefit communications following the occurrence of a food safety incident. Implications for optimising associated risk communication strategies, additional research linking risk perception and other quantitative measures, including comparisons in time and space, are suggested.
The framework of risk analysis has become the principal procedure for dealing with food safety issues. Risk analysis consists of three components: risk management, risk assessment, and risk communication, while risk assessment is defined as the scientific evaluation of possibility and consequences of adverse health outcomes resulting from food-borne hazards exposure in the case of food safety issues. Risk assessment is a scientifically based process consisting of the following steps: hazard identification, hazard characterization, exposure assessment, and risk characterization. The procedures of risk assessment of chemical hazards and microbiological hazards are a little bit different. This chapter would focus on the chemical hazards. On the other hand, positive and adverse effects may be induced concurrently by a single food item, e.g., fish, whole grain products, or even a single food component, e.g., folic acid, phytosterols, in which scenarios the risk-benefit assessment should be adopted. The principles and main steps of risk-benefit assessment are the same with risk assessment. Risk-benefit assessment comprises three parts, i.e., risk assessment, benefit assessment, and risk-benefit comparison, among which risk-benefit comparison is the trickiest one, usually a common metric of the health outcome is needed. Risk-benefit assessment is a valuable approach to systematically integrating the current evidence to provide the best science-based answers to address complicated questions in the areas of food and nutrition, especially in evaluating nutrient fortification policy, developing a tolerable upper intake of nutrient, and recommending a particular dietary pattern.KeywordsRisk assessmentRisk-benefit assessmentRisk analysisFood safety
As reported by the European Centre for Disease Prevention and Control and the European Food Safety Authority, red meat is a major food source that is responsible for foodborne illnesses due to microbiological hazards. The first objective of this study was to aggregate the available data in the literature in order to identify and characterise the main microbiological hazards associated with red meat consumption in France. Next, the associated numbers of foodborne illnesses, deaths and the subsequent burden of diseases, expressed in Disability Adjusted Life Years (DALY), were estimated. Using the eight foodborne pathogens kept in the assessment, a probabilistic risk model was built and uncertainty from the data was considered. Campylobacter spp. was ranked as the worst pathogen in terms of the number of human cases associated with red meat consumption, with 210 [95% confidence interval (CI) = 500–520] cases per 100,000 population. The pathogen that induced the highest mortality was non-typhoidal S. enterica, with 0.04 [95% CI = 0.01–0.10] deaths per 100,000 population. These cases were mostly related to pork consumption. However, the major contributor to the number of years in good health lost from red meat consumption in France was hepatitis E, with 33 [95% CI = 1-64] DALY per 100,000 population; this effect was mainly due to pork liver consumption. In terms of foodborne bacteria, for beef and pork meat, Campylobacter spp., non-typhoidal S. enterica, C. perfringens and STEC represented a mean of 2.2 [95% CI = 1.0–4.0] DALY per 100,000 individuals per year. The estimations provided in this study might help authorities to focus on these hazards and ultimately reduce their impact on the health of the French population.
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.
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.
There is evidence that consumption of fish, especially oily fish, has substantial beneficial effects on health. In particular an inverse relationship of oily fish intake to coronary heart disease incidence has been established. These beneficial effects are ascribed to fish oil components including long chain ω-3 polyunsaturated fatty acids. On the other hand it should be noted that oily fish also contains hazardous substances such as dioxins, PCBs and methylmercury. Soy consumption has been associated with potential beneficial and adverse effects. The claimed benefits include reduced risk of cardiovascular disease; osteoporosis, breast and prostate cancer whereas potential adverse effects include impaired thyroid function, disruption of sex hormone levels, changes in reproductive function and increased breast cancer risk The two cases of natural foods highlight the need to consider both risks and benefits in order to establish the net health impact associated to the consumption of specific food products. Within the Sixth Framework programme of the European Commission, the BRAFO project was funded to develop a framework that allows for the quantitative comparison of human health risks and benefits in relation to foods and food compounds. This paper describes the application of the developed framework to two natural foods, farmed salmon and soy protein. We conclude that the BRAFO methodology is highly applicable to natural foods. It will help the benefit-risk managers in selecting the appropriate dietary recommendations for the population.
Despite the well-known beneficial effects of statins, many patients do not adhere to chronic medication regimens.
To implement and assess the effectiveness of a community pharmacy-based pharmaceutical care program developed to improve patients' adherence to statin therapy.
An open-label, prospective, randomized controlled trial was conducted at 26 community pharmacies in the Netherlands. New users of statins who were aged 18 years or older were randomly assigned to receive either usual care or a pharmacist intervention. The intervention consisted of 5 individual counseling sessions by a pharmacist during a 1-year period. During these sessions, patients received structured education about the importance of medication adherence, lipid levels were measured, and the association between adherence and lipid levels was discussed. Adherence to statin therapy was assessed as discontinuation rates 6 and 12 months after statin initiation, and as the medication possession ratio (MPR), and compared between the pharmaceutical care and usual care groups.
A total of 899 subjects (439 in the pharmaceutical care group and 460 in the usual care group) were evaluable for effectiveness analysis. The pharmaceutical care program resulted in a significantly lower rate of discontinuation within 6 months after initiating therapy versus usual care (HR 0.66, 95% CI 0.46 to 0.96). No significant difference between groups was found in discontinuation at 12 months (HR 0.84, 95% CI 0.65 to 1.10). Median MPR was very high (>99%) in both groups and did not differ between groups.
These results demonstrate the feasibility and effectiveness of a community pharmacy-based pharmaceutical care program to improve medication adherence in new users of statins. Frequent counseling sessions (every 3 months) are necessary to maintain the positive effects on discontinuation. Although improvements are modest, the program can be applied easily to a larger population and have a large impact, as the interventions are relatively inexpensive and easy to implement in clinical practice.
Background:
The potential impact fraction is a measure of effect that calculates the proportional change in disease risk after a change in the exposure of a related risk factor. Potential impact fractions are increasingly used to calculate attributable fractions when the lowest exposure is non-zero.
Methods:
Risk-factor exposure can be expressed as a categorical or a continuous variable. For a categorical risk factor, a change in risk-factor exposure can be expressed as a change in the proportion of the population in each category ('proportions shift'). For a continuous risk factor, the change is expressed as a change in its parameters ('distribution shift'). A third method ('RR shift') takes elements of both the categorical and the continuous approach. We compare the three calculation methods using hypothetical data on BMI and an intervention that affects the obese category.
Results:
The 'proportion shift' calculation produces non-linear artefacts and is best avoided. The 'RR shift' and 'distribution shift' calculation require the estimation of an RR function to describe excess risk, but perform much better.
Conclusion:
The 'proportion shift' calculation is best avoided. The 'RR shift' and 'distribution shift' calculation produce virtually the same results. For evaluating high-risk strategies, the 'RR shift' calculation is the simplest and therefore preferred. The 'distribution shift' is best suited for evaluating population strategies.
It is unclear whether plant stanols lower serum LDL-cholesterol concentrations and cholesterol-standardized fat-soluble antioxidant concentrations dose-dependently when consumption exceeds the recommended daily intakes of 2.0-3.0 g.
The objective was to study the relation between plant stanols provided as plant stanol esters on changes in serum concentrations of LDL cholesterol and fat-soluble antioxidants.
Healthy subjects (n = 93) with slightly elevated serum total cholesterol concentrations (5.0-8.0 mmol/L) received, after a 3-wk run-in period, control products (n = 22) or products (margarine and soy-based yogurt) providing 3 g (n = 24), 6 g (n = 22), or 9 g (n = 25) plant stanols provided as fatty acid esters for 4 wk.
Serum LDL cholesterol decreased dose-dependently. Compared with control, decreases in the 3-g group were 0.32 mmol/L (7.4%; P = 0.005 after adjustment for multiple comparisons). An intake of 6 g plant stanols caused an additional decrease of 0.18 mmol/L (4.5%; P = 0.100 compared with the 3-g group). In the 9-g group, a further decrease of 0.22 mmol/L (5.4%) was observed (P = 0.048 compared with the 6-g group). Serum LDL-cholesterol concentrations were lowered by 17.4% in the 9-g group compared with the control group. No effects on cholesterol-standardized beta-carotene concentrations were observed. Even the change of -0.01 mumol/mmol cholesterol (or -9.2%; P = 0.341) in the 3-g group compared with the control group was not statistically significant because of the large variation in response. Serum HDL-cholesterol and triacylglycerol concentrations, cholesterol-standardized alpha-tocopherol and lutein concentrations, and plasma markers reflecting liver and renal function were not affected.
Daily consumption of plant stanols up to 9 g reduces serum LDL-cholesterol concentrations linearly up to 17.4%. For cholesterol-standardized fat-soluble antioxidant concentrations, such a relation could not be ascertained.
Consumption of plant sterols has been reported to reduce low density lipoprotein (LDL) cholesterol concentrations by 5-15%. Factors that affect plant sterol efficacy are still to be determined.
To more precisely quantify the effect of plant sterol enriched products on LDL cholesterol concentrations than what is reported previously, and to identify and quantify the effects of subjects' characteristics, food carrier, frequency and time of intake on efficacy of plant sterols as cholesterol lowering agents.
Fifty-nine eligible randomized clinical trials published from 1992 to 2006 were identified from five databases. Weighted mean effect sizes were calculated for net differences in LDL levels using a random effect model.
Plant sterol containing products decreased LDL levels by 0.31 mmol/L (95% CI, -0.35 to -0.27, P= < 0.0001) compared with placebo. Between trial heterogeneity was evident (Chi-square test, P = <0.0001) indicating that the observed differences between trial results were unlikely to have been caused by chance. Reductions in LDL levels were greater in individuals with high baseline LDL levels compared with those with normal to borderline baseline LDL levels. Reductions in LDL were greater when plant sterols were incorporated into fat spreads, mayonnaise and salad dressing, milk and yoghurt comparing with other food products such as croissants and muffins, orange juice, non-fat beverages, cereal bars, and chocolate. Plant sterols consumed as a single morning dose did not have a significant effect on LDL cholesterol levels.
Plant sterol containing products reduced LDL concentrations but the reduction was related to individuals' baseline LDL levels, food carrier, and frequency and time of intake.
Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)-lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a continuous dose-response relationship that would allow predicting the LDL-C-lowering efficacy of different phytosterol doses. Eighty-four trials including 141 trial arms were included. A nonlinear equation comprising 2 parameters (the maximal LDL-C lowering and an incremental dose step) was used to describe the dose-response curve. The overall pooled absolute (mmol/L) and relative (%) LDL-C-lowering effects of phytosterols were also assessed with a random effects model. The pooled LDL-C reduction was 0.34 mmol/L (95% CI: -0.36, -0.31) or 8.8% (95% CI: -9.4, -8.3) for a mean daily dose of 2.15 g phytosterols. The impacts of subject baseline characteristics, food formats, type of phytosterols, and study quality on the continuous dose-response curve were determined by regression or subgroup analyses. Higher baseline LDL-C concentrations resulted in greater absolute LDL-C reductions. No significant differences were found between dose-response curves established for plant sterols vs. stanols, fat-based vs. non fat-based food formats and dairy vs. nondairy foods. A larger effect was observed with solid foods than with liquid foods only at high phytosterol doses (>2 g/d). There was a strong tendency (P = 0.054) towards a slightly lower efficacy of single vs. multiple daily intakes of phytosterols. In conclusion, the dose-dependent LDL-C-lowering efficacy of phytosterols incorporated in various food formats was confirmed and equations of the continuous relationship were established to predict the effect of a given phytosterol dose. Further investigations are warranted to investigate the impact of solid vs. liquid food formats and frequency of intake on phytosterol efficacy.
Previous studies have shown that canola oil (CA), compared with soybean oil (SO), shortens the life span of stroke-prone spontaneously hypertensive (SHRSP) rats, a widely used model for hemorrhagic stroke. SHRSP rats are highly sensitive to dietary cholesterol manipulations because a deficiency of membrane cholesterol makes their cell membranes weak and fragile. Phytosterols, abundant in CA but not in SO, can inhibit the absorption of cholesterol and also replace a part of cholesterol in cell membranes. This study was performed to determine whether the high concentration of phytosterols in CA might account for its life-shortening effect on SHRSP rats. Male, 35-d-old SHRSP rats (n = 28/group) were fed semipurified diets containing CA, SO, CA fortified with phytosterols (canola oil + phytosterols, CA + P), SO fortified with phytosterols (soybean oil + phytosterols, SO + P), corn oil (CO), olive oil (OO) or a fat blend that mimicked the fat composition of a representative Canadian diet (Canadian fat mimic, CFM; 10 g/100 g diet). These fats provided 97, 36, 207, 201, 114, 27 and 27 mg phytosterols/100 g diet, respectively. Ten rats from each group were killed after 30-32 d for blood and tissue analyses. The remaining rats (18/group) were used for determination of life span. The life span of SHRSP rats fed the high phytosterol oils (CA, CA + P, SO + P and CO) was significantly (P<0.05) shorter than that of CFM- and SO-fed rats. At 30-32 d, the groups fed the high phytosterol oils had greater levels of phytosterols and significantly (P<0.05) higher ratios of phytosterols/cholesterol in plasma, RBC, liver and kidney, and a significantly (P<0.05) lower RBC membrane deformabilty index than the groups fed oils low in phytosterols (SO, OO and CFM). The mean survival times were correlated with RBC deformability index (r(2) = 0.91, P = 0.0033) and cholesterol concentration (r(2) = 0.94, P = 0.0016), and inversely correlated with RBC phytosterol concentration (r(2) = 0.58, P = 0.0798) and phytosterols/cholesterol (r(2) = 0.65, P = 0.0579), except in the OO group. This study suggests that the high concentration of phytosterols in CA and the addition of phytosterols to other fats make the cell membrane more rigid, which might be a factor contributing to the shortened life span of SHRSP rats.
Plant-sterol-enriched spreads lower LDL cholesterol but may also lower lipid-standardized carotenoids.
Our objective was to assess whether advice to consume specific daily amounts of foods high in carotenoids prevents a reduction in plasma carotenoid concentrations in subjects who consume plant sterol or stanol esters.
Forty-six hypercholesterolemic free-living subjects completed a 3-way, double-blind, randomized crossover comparison. Subjects consumed each of the following 3 spreads (25 g/d) for 3 wk: control-1 (sterol-free), sterol ester-1 (2.3 g plant sterol esters), and stanol ester-1 (2.5 g plant stanol esters). During the 3-wk interventions, subjects were advised to eat > or =5 servings of vegetables and fruit/d, of which > or =1 serving was to be carrots, sweet potatoes, pumpkins, tomatoes, apricots, spinach, or broccoli.
The dietary advice resulted in a 13% increase in plasma beta-carotene in subjects who consumed control-1 (P = 0.04). The plasma beta-carotene concentrations of subjects who consumed control-1 did not differ significantly from those of subjects who consumed stanol ester-1 or sterol ester-1. This result was achieved by an increase of one daily serving of high-carotenoid vegetables or fruit. LDL cholesterol decreased 7.7% and 9.5% after consumption of sterol ester-1 and stanol ester-1, respectively (P < 0.001 for both), and differences between the LDL-cholesterol values obtained were not significant.
Dietary advice to consume an additional daily serving of a high-carotenoid vegetable or fruit when consuming spreads containing sterol or stanol esters maintains plasma carotenoid concentrations while lowering LDL-cholesterol concentrations significantly.
Reliable and comparable analysis of risks to health is key for preventing disease and injury. Causal attribution of morbidity and mortality to risk factors has traditionally been conducted in the context of methodological traditions of individual risk factors, often in a limited number of settings, restricting comparability.
In this paper, we discuss the conceptual and methodological issues for quantifying the population health effects of individual or groups of risk factors in various levels of causality using knowledge from different scientific disciplines. The issues include: comparing the burden of disease due to the observed exposure distribution in a population with the burden from a hypothetical distribution or series of distributions, rather than a single reference level such as non-exposed; considering the multiple stages in the causal network of interactions among risk factor(s) and disease outcome to allow making inferences about some combinations of risk factors for which epidemiological studies have not been conducted, including the joint effects of multiple risk factors; calculating the health loss due to risk factor(s) as a time-indexed "stream" of disease burden due to a time-indexed "stream" of exposure, including consideration of discounting; and the sources of uncertainty.
Foods with plant stanol or sterol esters lower serum cholesterol levels. We summarize the deliberations of 32 experts on the efficacy and safety of sterols and stanols. A meta-analysis of 41 trials showed that intake of 2 g/d of stanols or sterols reduced low-density lipoprotein (LDL) by 10%; higher intakes added little. Efficacy is similar for sterols and stanols, but the food form may substantially affect LDL reduction. Effects are additive with diet or drug interventions: eating foods low in saturated fat and cholesterol and high in stanols or sterols can reduce LDL by 20%; adding sterols or stanols to statin medication is more effective than doubling the statin dose. A meta-analysis of 10 to 15 trials per vitamin showed that plasma levels of vitamins A and D are not affected by stanols or sterols. Alpha carotene, lycopene, and vitamin E levels remained stable relative to their carrier molecule, LDL. Beta carotene levels declined, but adverse health outcomes were not expected. Sterol-enriched foods increased plasma sterol levels, and workshop participants discussed whether this would increase risk, in view of the marked increase of atherosclerosis in patients with homozygous phytosterolemia. This risk is believed to be largely hypothetical, and any increase due to the small increase in plasma plant sterols may be more than offset by the decrease in plasma LDL. There are insufficient data to suggest that plant stanols or sterols either prevent or promote colon carcinogenesis. Safety of sterols and stanols is being monitored by follow-up of samples from the general population; however, the power of such studies to pick up infrequent increases in common diseases, if any exist, is limited. A trial with clinical outcomes probably would not answer remaining questions about infrequent adverse effects. Trials with surrogate end points such as intima-media thickness might corroborate the expected efficacy in reducing atherosclerosis. However, present evidence is sufficient to promote use of sterols and stanols for lowering LDL cholesterol levels in persons at increased risk for coronary heart disease.
Plant sterols are naturally occurring molecules that humanity has evolved with. Herein, we have critically evaluated recent literature pertaining to the myriad of factors affecting efficacy and safety of plant sterols in free and esterified forms. We conclude that properly solubilized 4-desmetyl plant sterols, in ester or free form, in reasonable doses (0.8-1.0 g of equivalents per day) and in various vehicles including natural sources, and as part of a healthy diet and lifestyle, are important dietary components for lowering low density lipoprotein (LDL) cholesterol and maintaining good heart health. In addition to their cholesterol lowering properties, plant sterols possess anti-cancer, anti-inflammatory, anti-atherogenicity, and anti-oxidation activities, and should thus be of clinical importance, even for those individuals without elevated LDL cholesterol. The carotenoid lowering effect of plant sterols should be corrected by increasing intake of food that is rich in carotenoids. In pregnant and lactating women and children, further study is needed to verify the dose required to decrease blood cholesterol without affecting fat-soluble vitamins and carotenoid status.
Detailed assumptions used in constructing a new indicator of the burden of disease, the disability-adjusted life year (DALY), are presented. Four key social choices in any indicator of the burden of disease are carefully reviewed. First, the advantages and disadvantages of various methods of calculating the duration of life lost due to a death at each age are discussed. DALYs use a standard expected-life lost based on model life-table West Level 26. Second, the value of time lived at different ages is captured in DALYs using an exponential function which reflects the dependence of the young and the elderly on adults. Third, the time lived with a disability is made comparable with the time lost due to premature mortality by defining six classes of disability severity. Assigned to each class is a severity weight between 0 and 1. Finally, a three percent discount rate is used in the calculation of DALYs. The formula for calculating DALYs based on these assumptions is provided.
We investigated the feasibility of increasing ursodeoxycholic acid (UDCA) in the enterohepatic circulation of pigs by administering living bacteria capable of epimerising endogenous amidated chenodeoxycholic acid (CDCA) to UDCA. We first demonstrated that combining Bifidobacterium animalis DN-173 010, as a bile salt-hydrolysing bacterium, and Clostridium absonum ATCC 27555, as a CDCA to UDCA epimerising bacterium, led to the efficient epimerisation of glyco- and tauro-CDCA in vitro, with respective UDCA yields of 55.8 (SE 2.8) and 36.6 (SE 1.5)%. This strain combination was then administered to hypercholesterolaemic pigs over a 3-week period, as two daily preprandial doses of either viable (six experimental pigs) or heat-inactivated bacteria (six controls). The main effects of treatment were on unconjugated bile acids (P=0.035) and UDCA (P<0.0001) absorbed into the portal vein, which increased 1.6-1.7- and 3.5-7.5-fold, respectively, under administration of living compared with inactivated bacteria. In bile, UDCA did not increase significantly, but the increase in biliary lithocholic acid with time in the controls was not observed in the experimental pigs (P=0.007), and the same trend was observed in faeces. All other variables (biliary lipid equilibrium, plasma lipid levels and partition of cholesterol between the different lipoprotein classes) remained unaffected by treatment throughout the duration of the experiment. In conclusion, it is feasible to increase the bioavailability of UDCA to the intestine and the liver by administering active bacteria. This may represent an interesting new probiotic activity, provided that in future it could be expressed by a safe food micro-organism.
Detailed assumptions used in constructing a new indicator of the burden of disease, the disability-adjusted life year (DALY), are presented. Four key social choices in any indicator of the burden of disease are carefully reviewed. First, the advantages and disadvantages of various methods of calculating the duration of life lost due to a death at each age are discussed. DALYs use a standard expected-life lost based on model life-table West Level 26. Second, the value of time lived at different ages is captured in DALYs using an exponential function which reflects the dependence of the young and the elderly on adults. Third, the time lived with a disability is made comparable with the time lost due to premature mortality by defining six classes of disability severity. Assigned to each class is a severity weight between 0 and 1. Finally, a three percent discount rate is used in the calculation of DALYs. The formula for calculating DALYs based on these assumptions is provided.
The wood-derived compound, β-sitosterol (purity >90%), was shown to be estrogenic in fish. It induced the expression of the vitellogenin gene in the liver of juvenile and methyltestosterone-treated rainbow trout. Structural similarities to β-sitosterol notwithstanding, cholesterol, citrostadienol, β-sitostanol, and 5-androstene-3β,17β-diol, an estrogenic member of the androstenic steroid group, were inactive. An abietic acid mixture (37% abietic acid, 6% dehydroabietic acid, and a remainder of unknown compounds) showed slight hormonal activity in feed, but it was completely inactive when given intraperitoneally in implants. The estrogenic component of the abietic acid preparation was not identified. In addition to β-sitosterol and abietic acid, several other wood-derived compounds including betulin, isorhapontigenin, isorhapontin, and pinosylvin were estrogenic in breast cancer cells (MCF-7 or T-47D). However, betulin and pinosylvin, available in sufficient amounts forin vivotesting, did not induce the expression of the vitellogenin gene. Differences in the primary sequences of human and fish estrogen receptors (hormone as well as DNA-binding regions) or uptake and metabolism of the compounds may explain the discrepancy between the two estrogen bioassays. Wood-derived compounds such as β-sitosterol, present in pulp and paper mill effluents, may account for the weak estrogenicity of debarking effluent seen at the vitellogenin expression bioassay.
The regulations and/or directives in force for functional foods primarily focus on the warrant of safety before the particular foods reach the consumer. Aspects that come into the picture after marketing are not structurally and/or regulatory dealt with at this moment. This absence of clear guidelines about responsibility, timing and contents of a postlaunch monitoring (PLM) system hamper the establishment of an internationally standardized and stakeholder-adopted framework. The current paper describes a proposal for PLM and is illustrated with a case study on phytosterols/-stanols.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
To determine if plant stanols and plant sterols differ with respect to their low-density lipoprotein cholesterol (LDL-CH) lowering efficacies across a continuous dose range.
Dose-response relationships were evaluated separately for plant stanols and plant sterols and reductions in LDL-CH, using a first-order elimination function.
Altogether, 113 publications and 1 unpublished study report (representing 182 strata) complied with the pre-defined inclusion and exclusion criteria and were included in the assessment. The maximal LDL-CH reductions for plant stanols (16.4%) and plant stanol ester (17.1%) were significantly greater than the maximal LDL-CH reductions for plant sterols (8.3%) and plant sterol ester (8.4%). These findings persisted in several additional analyses.
Intakes of plant stanols in excess of the recommended 2g/day dose are associated with additional and dose-dependent reductions in LDL-CH, possibly resulting in further reductions in the risk of coronary heart disease (CHD).
The use of margarines enriched with phytosterols or phytostanols is recommended as an appropriate adjunctive therapy for patients with certain lipid profiles, but may result in a behavioral modification leading to a change in person's adherence to lipid-lowering drug treatment. This study aimed to examine the influence of the use of margarines enriched with phytosterols/-stanols on adherence to statin therapy.
Retrospective data from food frequency questionnaires were used to assess phytosterol/-stanol-enriched margarine intake from a population based, longitudinal cohort between 1998 and 2007. Intake data were linked to pharmacy-dispensing records. Multivariate Cox proportional-hazards models were used to calculate hazard ratios for discontinuation of statin therapy. Drug-taking compliance was compared between users and non-users of enriched margarine using the Mann-Whitney U-test. Pre-defined subgroup analyses were performed to evaluate differences in adherence between prevalent statin users and starters of statins.
Among 4848 subjects, 522 used statins only and 60 combined these drugs with phytosterol/-stanol-enriched margarine. Overall statin discontinuation rates were not significantly different between the users and non-users of enriched margarine, but more combination users discontinued statin therapy within 12 months in the subgroup of starters (HR(adj) : 2.52 [95%CI: 1.06-6.00]). Drug-taking compliance was high in both users and non-users of enriched margarine and was slightly lower in combination users (P<0.10).
These results imply that persons who combine enriched margarines with statins may neglect taking their drug according to the prescription. Further investigations in larger populations are important, especially among patients susceptible to a low adherence to drug therapy.
BRAFO stands for Benefit–Risk Analysis for Foods. This European Commission funded project aims at developing a framework that allows quantitative comparison of human health risks and benefits of foods and food compounds based on a common scale of measurement.
A methodology group brought together methodologies from several disciplines relevant to the evaluation of risks and benefits in food. This group reviewed and assembled the methodologies available. They produced this guidance document that describes a tiered (‘stepwise’) approach for performing a risk and benefit assessment of foods. This process starts with pre-assessment and problem formulation to set the scope of the assessment. This includes defining two scenarios, the reference and an alternative that are compared in the assessment. The approach consists of four tiers. In many cases, a lower tier assessment in which risks and benefits are qualitatively evaluated may be sufficient to show a clear difference between the health impacts of the two scenarios. In other cases, increasingly sophisticated methods to integrate risks and benefits quantitatively are used at higher tiers to assess the net health impact.
Plant sterols and stanols are plant steroids with a similar chemical structure and cellular function to human cholesterol, and are recommended as dietary modifiers of serum lipids. Plant sterols have a higher degree of absorption than plant stanols, suggesting differential efficacy between the two.
A meta-analysis of randomized controlled trials was performed to summarize direct comparisons between the effect of plant sterols vs plant stanols on serum lipid levels in healthy patients and patients with hypercholesterolemia.
A systematic literature search of MEDLINE, EMBASE, Cochrane CENTRAL, and the Natural Medicines Comprehensive Database was conducted from January 1950 through January 2009. Trials were included in the analysis if they were randomized controlled trials evaluating the effect of plant sterols vs plant stanols in healthy patients or patients with hypercholesterolemia who reported efficacy data on total, low-density lipoprotein, and high-density lipoprotein cholesterols or triglycerides. The weighted mean difference (WMD) of the change from baseline (in mg/dL) with 95% confidence interval was calculated as the difference between the means in the plant sterol and plant stanol groups using a random-effects model.
Fourteen studies (n=531 patients) met the inclusion criteria. Upon meta-analysis, the results showed that there is no statistically or clinically significant difference between plant sterols and plant stanols in their abilities to modify total cholesterol (WMD -1.11 mg/dL [-0.0286 mmol/L], 95% confidence interval [CI] -4.12 to 1.90, P=0.47), low-density lipoprotein cholesterol (WMD -0.35 mg/dL [-0.0091 mmol/L], 95% CI -2.98 to 2.28, P=0.79), high-density lipoprotein cholesterol (WMD -0.28 mg/dL [-0.00073 mmol/L], 95% CI -1.18 to 0.62, P=0.54), or triglycerides (WMD -1.80 mg/dL [-0.0203 mmol/L], 95% CI -6.80 to 3.21, P=0.48).
Plant sterols and plant stanols do not have statistically or clinically relevant differing effects on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride levels. The selection of plant sterols vs plant stanols should then be based on potential differences in safety parameters and further study is required to elucidate such differences.
Functional foods are closely associated with claims on foods. There are two categories of claims on foods: nutrition claims and health claims. Health claims on (functional) foods must be scientifically substantiated. In December 2006, the European Union published its Regulation 1924/2006 on nutrition and health claims made on foods. As concerns scientific evaluation, the EU-project PASSCLAIM resulted in a set of criteria for the scientific substantiation of health claims on foods. The European Food Safety Authority provides the scientific advise to the European Commission for health claims submitted under Regulation 1924/2006 and has hitherto published several hundreds of opinions on health claims, part of which are positive, part which are negative and a few with insufficient evidence. Antioxidant claims have been approved for the general function of vitamins but not for direct health effects in humans. Another issue with claims is consumer understanding. Consumers can hardly distinguish between graded levels of evidence, and they do make only little or no distinction between nutrition and health claims. Consumers understand nutrition and health claims different from scientists and regulators. Therefore, innovation in industry can readily proceed via approved nutrition claims and approved health claims. The market and the shelves in the stores will not be empty; rather they will look different in the years to come.
Risk-benefit analyses are introduced as a new paradigm for old problems. However, in many cases it is not always necessary to perform a full comprehensive and expensive quantitative risk-benefit assessment to solve the problem, nor is it always possible, given the lack of required date. The choice to continue from a more qualitative to a full quantitative risk-benefit assessment can be made using a tiered approach. In this article, this tiered approach for risk-benefit assessment will be addressed using a decision tree. The tiered approach described uses the same four steps as the risk assessment paradigm: hazard and benefit identification, hazard and benefit characterization, exposure assessment, and risk-benefit characterization, albeit in a different order. For the purpose of this approach, the exposure assessment has been moved upward and the dose-response modeling (part of hazard and benefit characterization) is moved to a later stage. The decision tree includes several stop moments, depending on the situation where the gathered information is sufficient to answer the initial risk-benefit question. The approach has been tested for two food ingredients. The decision tree presented in this article is useful to assist on a case-by-case basis a risk-benefit assessor and policymaker in making informed choices when to stop or continue with a risk-benefit assessment.
In this report vitamin A intake is assessed. From these analyses, 17 to 30 per cent of the adults in our study were found to have an inadequate vitamin A intake to maintain sufficient vitamin A stores. A substantial proportion of these individuals had a level of intake greatly less than required. Our data were taken from the third Dutch National Food Consumption Survey (1997/98) and we applied a method proposed in a previous study (Waijers et al., 2004), taking into account within- and between-individual variation in intakes and requirements. The term vitamin A refers to retinoids and provitamin A carotenoids, with vitamin A intake expressed in retinol equivalents. Because retinol equivalent ratios used in the Netherlands are dated, we estimated retinol (activity) equivalents for all products in the Dutch food composition table from 2001. Next, we estimated the usual vitamin A intake from the observed intakes. We also estimated average vitamin A requirements, adapting a formula from the American Institute of Medicine, using characteristics of the Dutch population. The probability approach was then applied to estimate the proportion of individuals with an intake under their requirement, combining the usual intake and the requirement distribution. Considering the inadequate vitamin A supply to a considerable proportion of the Dutch population we recommend sound monitoring of developments in the vitamin A intake and investigation of the health consequence of the current low vitamin A supply. In dit rapport is de vitamine A inneming getoetst aan de behoefte. Voor 17 tot 30 procent van de volwassenen bleek de inneming inadequaat. Voor een aanzienlijk aantal daarvan was de vitamine A inneming meer dan 20 procent lager dan het niveau nodig om een adequate levervoorraad te kunnen handhaven. De gebruikte voedselconsumptiegegevens zijn afkomstig uit VCP-3 (1997/1998). De toegepaste methode is beschreven in een voorgaand rapport: 'Methode voor schatting van de prevalentie van inadequate innemingen van micronutrienten' (Waijers et al., 2004). De inneming van en behoefte aan vitamine A, een verzamelnaam voor retinol en provitamine A carotenooden, wordt uitgedrukt in retinolequivalenten. Omdat in Nederland nog verouderde equivalenties gebruikt worden, is voor dit rapport het aantal retinolequivalenten voor alle producten in het NEVO-bestand 2001 geschat uitgaande van de hogere omrekeningsfactoren. Vervolgens is uit de waargenomen inneming de gebruikelijke vitamine A inneming geschat. De Nederlandse voedingsnorm voor vitamine A dateert uit 1989. Voor de meeste leeftijdscategorieen zijn geen gegevens beschikbaar betreffende de gemiddelde behoefte. Daarom zijn deze geschat met behulp van een formule overgenomen van het Amerikaanse Institute of Medicine en karakteristieken van de Nederlandse bevolking. Aan de hand van de gebruikelijke innemingverdeling en de vitamine A behoefte is met behulp van de waarschijnlijkheidsbenadering het percentage individuen geschat waarvoor de inneming lager was dan de behoefte. De betekenis voor de gezondheid van de marginale vitamine A voorziening voor een aanzienlijk deel van de Nederlandse bevolking dient nader te worden onderzocht. Daarnaast moeten ontwikkelingen in de vitamine A voorziening nauwlettend worden gevolgd.
Intake of 2-3 g/d of plant stanols as esters lowers LDL cholesterol level, but there is no information about the efficacy and safety of a respective very high daily intake. We studied the effects of 8.8 g/d of plant stanols as esters on serum lipids and safety variables in subjects with mild to moderate hypercholesterolemia.
In a randomized, double-blind, placebo-controlled study the intervention (n=25) and control (n=24) groups consumed spread and drink enriched or not with plant stanol esters for 10 weeks.
Plant stanols reduced serum total and LDL cholesterol concentrations by 12.8 and 17.3% from baseline and by 12.0 and 17.1% from controls (P<0.01 for all). Liver enzymes, markers of hemolysis, and blood cells were unchanged. Serum vitamins A, D, and gamma-tocopherol concentrations, and the ratios of alpha-tocopherol to cholesterol were unchanged. Serum beta-carotene concentrations decreased significantly from baseline and were different from controls even when adjusted for cholesterol. Serum alpha-carotene concentration and alpha-carotene/cholesterol ratio were not different from controls.
High intake of plant stanols reduced LDL cholesterol values without any other side effects than reduction of serum beta-carotene concentration. However, the end product, serum vitamin A levels, were unchanged. The results suggest that plant stanol ester intake can be increased to induce a greater cholesterol lowering effect.
For many years the American Heart Association (AHA) has advocated modification of risk factors as a safe and effective means of reducing coronary heart disease (CHD). The major risk factors are elevated plasma lipids (especially cholesterol), hypertension, smoking, diabetes mellitus, and obesity. Since Americans in general have relatively high cholesterol levels that appear to enhance risk for CHD, the AHA has recommended a dietary plan designed to reduce the plasma cholesterol to a safer level for the general public. The essential feature of this plan is curtailed intakes of total fat, saturated fatty acids, and cholesterol. Adoption of the AHA recommendation for the general public, however, may not be sufficient for patients with definite hyperlipidemia. This document has been prepared to guide the physician in treatment of patients with proven hyperlipidemia. Particular attention has been directed to dietary therapy as the initial mode of treatment. This therapy consists of a progressive reduction in total fat, saturated fatty acids, and cholesterol. The first step in the plan corresponds to AHA dietary recommendation for the general public. If the response to this first step is inadequate, further dietary restrictions are advocated. An attempt has been made to develop a unified approach to dietary therapy of hyperlipidemia. Nonetheless, causes of hyperlipidemia are multiple and patients differ from one another; individualization of therapy may be required in some cases.
Administration of estradiol/progesterone to ovariectomized animals significantly increased the uterine weight, RNA, DNA and protein concentrations. Similarly, administration of beta-sitosterol alone or in combination with estradiol caused a marked increase in the above parameters and the maximum influence was evident only after median and high dose treatments. However, administration of median/high dose of beta-sitosterol along with progesterone accentuated only the RNA and protein concentrations but exerted an inhibitory effect on sitosterol-induced increment in uterine weight and DNA concentrations.
To estimate by how much and how quickly a given reduction in serum cholesterol concentration will reduce the risk of ischaemic heart disease.
Data on the incidence of ischaemic heart disease and serum cholesterol concentration were analysed from 10 prospective (cohort) studies, three international studies in different communities, and 28 randomised controlled trials (with mortality data analysed according to allocated treatment to ensure the avoidance of bias).
Decrease in incidence of ischaemic heart disease or mortality for a 0.6 mmol/l (about 10%) decrease in serum cholesterol concentration.
For men results from the cohort studies showed that a decrease of serum cholesterol concentration of 0.6 mmol/l (about 10%) was associated with a decrease in incidence of ischaemic heart disease of 54% at age 40 years, 39% at age 50, 27% at 60, 20% at 70, and 19% at 80. The combined estimate from the three international studies (for ages 55-64 years) was 38% (95% confidence interval 33% to 42%), somewhat greater than the cohort study estimate of 27%. The reductions in incidence of ischaemic heart disease in the randomised trials (for ages 55-64 years) were 7% (0 to 14%) in the first two years, 22% (15% to 28%) from 2.1-5 years, and 25% (15% to 35%) after five years, the last estimate being close to the estimate of 27% for the long term reduction from the cohort studies. The data for women are limited but indicate a similar effect.
The results from the cohort studies, international comparisons, and clinical trials are remarkably consistent. The cohort studies, based on half a million men and 18,000 ischaemic heart disease events, estimate that a long term reduction in serum cholesterol concentration of 0.6 mmol/l (10%), which can be achieved by moderate dietary change, lowers the risk of ischaemic heart disease by 50% at age 40, falling to 20% at age 70. The randomised trials, based on 45,000 men and 4000 ischaemic heart disease events show that the full effect of the reduction in risk is achieved by five years.
The wood-derived compound, beta-sitosterol (purity > 90%), was shown to be estrogenic in fish. It induced the expression of the vitellogenin gene in the liver of juvenile and methyltestosterone-treated rainbow trout. Structural similarities to beta-sitosterol notwithstanding, cholesterol, citrostadienol, beta-sitostanol, and 5-androstene-3 beta,17 beta-diol, an estrogenic member of the androstenic steroid group, were inactive. An abietic acid mixture (37% abietic acid, 6% dehydroabietic acid, and a remainder of unknown compounds) showed slight hormonal activity in feed, but it was completely inactive when given intraperitoneally in implants. The estrogenic component of the abietic acid preparation was not identified. In addition, to beta-sitosterol and abietic acid, several other wood-derived compounds including betulin, isorhapontigenin, isorhapontin, and pinosylvin were estrogenic in breast cancer cells (MCF-7 or T-47D). However, betulin and pinosylvin, available in sufficient amounts for in vivo testing, did not induce the expression of the vitellogenin gene. Differences in the primary sequences of human and fish estrogen receptors (hormone as well as DNA-binding regions) or uptake and metabolism of the compounds may explain the discrepancy between the two estrogen bioassays. Wood-derived compounds such as beta-sitosterol, present in pulp and paper mill effluents, may account for the weak estrogenicity of debarking effluent seen at the vitellogenin expression bioassay.
Coronary patients with low baseline ratios of serum cholestanol and plant sterols to cholesterol (indicating low cholesterol absorption) but not those with high ratios (high absorption) experienced reduced recurrences of coronary events during simvastatin treatment in the Scandinavian Simvastatin Survival Study. Thus, in the present study, serum cholesterol, its precursor sterols (reflecting cholesterol synthesis), plant sterols (campesterol and sitosterol), and cholestanol were measured before and during a 5-year period of placebo treatment (n=433) and simvastatin treatment (n=434) in patients from a subgroup of the Scandinavian Simvastatin Survival Study to determine whether changes in cholesterol synthesis and serum levels were related to cholesterol absorption. Serum cholesterol level was unchanged, the ratios of cholesterol precursor sterols to cholesterol were decreased, and the ratios of plant sterols to cholesterol were increased in relation to increasing baseline ratios of cholestanol quartiles. The latter predicted 5-year ratios and simvastatin-induced reductions of the precursor sterols, with the lowering of the ratios (cholesterol synthesis reduction) being almost twice higher in the lowest versus the highest quartile. The ratios of plant sterols, especially campesterol, to cholesterol were markedly increased during simvastatin treatment, mostly in subjects with the highest baseline cholestanol quartiles. Simvastatin reduced serum cholesterol more (P=0.003) in the lowest versus the highest cholestanol quartile during the 5-year treatment period. The results show for the first time that baseline cholesterol metabolism, measured by serum noncholesterol sterols, predicts the effectiveness of simvastatin in reducing cholesterol synthesis and serum levels of cholesterol. The drug suppresses the synthesis of cholesterol markedly more effectively in subjects with high than with low baseline synthesis but reduces respective serum cholesterol levels less markedly than synthesis. Subjects with high cholesterol absorption and low synthesis may need a combination therapy to lower more effectively their serum cholesterol levels and prevent an increase in the levels of plant sterols.
Blood cholesterol levels are affected by diet and in particular by the type and amount of fat intake. In recent years, vegetable oil spreads containing plant sterols/stanols (as their fatty acid esters) have been developed. Numerous clinical trials on spreads with added plant sterols/stanols have shown that they have much greater cholesterol-lowering properties than conventional vegetable oil spreads. Plant sterols decrease both dietary and biliary cholesterol absorption in the small intestine, with a consequential increase in excretion of cholesterol. It is also recognized that plant sterol/stanol-enriched, cholesterol-lowering spreads, if consumed regularly, may induce a 10-20% decrease in plasma carotenoids, adjusted for changes in plasma lipids. A 10-20% decrease in plasma carotenoids falls well within the seasonal variation observed in individuals. Our current understanding of the physiological functions of carotenoids does not indicate any health risk associated with the slight decrease in their blood levels due to the intake of plant sterol/stanol. The questions that have been raised, though, are how plant sterols/stanols affect plasma carotenoid levels, and in addition, what quantity of fruits and vegetables (the richest dietary sources of carotenoids) would have to be consumed to improve plasma carotenoid levels? The current mini-review covers the cholesterol-lowering effect of plant sterols, their mechanisms of action and effect on blood carotenoids, and concludes with the potential heath benefits of daily intake of plant sterol-enriched spreads.
In patients with the inherited disease of phytosterolemia, elevated concentrations of plant sterols (eg, campesterol and sitosterol) have been implicated as a risk factor for premature atherosclerosis. Whether plasma concentrations of campesterol and sitosterol are risk factors for coronary heart disease (CHD) in nonphytosterolemia subjects has not been established. Therefore, the present study examined the role of plant sterols in patients admitted for elective artery coronary bypass graft (ACBG). Serum concentrations of campesterol and sitosterol, as well as lathosterol, desmosterol, cholestanol, and lipoproteins were analyzed in 42 men and 11 women without lipid-lowering treatment during the past. Twenty-six patients reported a positive family history in their first-degree relatives for CHD. Lipid profile and other risk factors were comparable in both groups. Patients with a positive family history for CHD had significant higher plasma levels of campesterol (.50 +/-.17 v.38 +/-.16 mg/dL; P =.011), sitosterol (.40 +/-.11 v.31 +/-.11 mg/dL; P =.004) and their ratios to cholesterol. Lathosterol, desmosterol, cholestanol, and their ratios to cholesterol were not significantly different. Analysis of covariance (ANCOVA) analysis showed no influence of sex, age, triglycerides, total-, low-density lipoprotein (LDL)-, and high-density lipoprotein (HDL)-cholesterol on the results, but confirmed a strong influence of plant sterols. These findings support the hypothesis that plant sterols might be an additional risk factor for CHD.
To study differences in dietary intake between adults with different socioeconomic status (SES) and trends over time.
Cross-sectional study based on data of three Dutch National Food Consumption Surveys (DNFCS-1 1987/88; DNFCS-2 1992; DNFCS-3 1997/98), obtained from a panel by a stratified probability sample of the non-institutionalized Dutch population.
A total of 6008 men and 6957 women aged 19 y and over.
Dietary intake was assessed with a 2 day dietary record. Background information was obtained by structured questionnaire. Sociodemographic variables were available from panel information. SES, based on educational level, occupation and occupational position was categorized into (very) low, middle and high. Analysis of variance with age as covariable was used to explore the effects of SES on dietary intake and anthropometry. Statistical tests for trend were carried out with models in which week-weekend-day effects and an interaction term of time with SES were also included.
The prevalence of obesity and skipping of breakfast was higher among people with a low SES. In all three surveys, subjects in the (very) low SES group reported having a higher consumption of potatoes, meat and meat products, visible fats, coffee and soft drinks (men only). Subjects with a high SES reported consuming more vegetables, cheese and alcohol. As regards nutrients, in all surveys a higher SES was associated with higher intake of vegetable protein, dietary fibre and most micronutrients. A higher SES was also associated with a lower fat intake but the differences between social classes were rather small and not consistent when the contribution of alcohol to energy intake was taken into account.
In general, dietary intake among subjects in higher SES groups tended to be closer to the recommendations of the Netherlands Food and Nutrition Council and this phenomenon was quite stable over a period of 10 y.
Two groups of 20 stroke prone spontaneously hypertensive rats (SHRSP) at 5 weeks old were fed a diet containing 10 w/w% rapeseed (canola) oil or soybean oil as the only dietary fat, and given drinking water containing 1% NaCl. Life span of the canola oil group (62+/-2 days) was shorter than that of the soybean oil group (68+/-3 days). Stroke-related symptoms were observed in every animal, but the onset of those in the canola oil group, at 47+/-1 days after starting the administration was earlier than that in the soybean oil group, 52+/-2 days. Incidence of cerebral hemorrhage was similar in these groups, and no differences were found between lesions of organs in the groups. In another experiment, two groups of ten SHRSP at 5 weeks of age were fed the defatted diet and given canola oil or soybean oil by gavage at 10 w/w% of consumed food for 4 weeks without NaCl loading. After the 4-week administration, mean systolic blood pressure in the canola oil group and the soybean oil group were 233+/-2 and 223+/-0.3 mmHg, respectively. Phytosterol levels in both plasma and erythrocyte membranes reflected those contained in the oils ingested. Na(+), K(+)-ATPase activities in the brain, heart and kidney were enhanced in the canola oil group. These results indicate that promotion of hypertension-related deterioration in organs is likely to have relevance to the short life span in the canola oil group. Enhanced Na(+), K(+)-ATPase activity by phytosterols in the oil ingested may play a role in these changes.
To determine by how much statins reduce serum concentrations of low density lipoprotein (LDL) cholesterol and incidence of ischaemic heart disease (IHD) events and stroke, according to drug, dose, and duration of treatment.
Three meta-analyses: 164 short term randomised placebo controlled trials of six statins and LDL cholesterol reduction; 58 randomised trials of cholesterol lowering by any means and IHD events; and nine cohort studies and the same 58 trials on stoke.
Reductions in LDL cholesterol according to statin and dose; reduction in IHD events and stroke for a specified reduction in LDL cholesterol.
Reductions in LDL cholesterol (in the 164 trials) were 2.8 mmol/l (60%) with rosuvastatin 80 mg/day, 2.6 mmol/l (55%) with atorvastatin 80 mg/day, 1.8 mmol/l (40%) with atorvastatin 10 mg/day, lovastatin 40 mg/day, simvastatin 40 mg/day, or rosuvastatin 5 mg/day, all from pretreatment concentrations of 4.8 mmol/l. Pravastatin and fluvastatin achieved smaller reductions. In the 58 trials, for an LDL cholesterol reduction of 1.0 mmol/l the risk of IHD events was reduced by 11% in the first year of treatment, 24% in the second year, 33% in years three to five, and by 36% thereafter (P < 0.001 for trend). IHD events were reduced by 20%, 31%, and 51% in trials grouped by LDL cholesterol reduction (means 0.5 mmol/l, 1.0 mmol/l, and 1.6 mmol/l) after results from first two years of treatment were excluded (P < 0.001 for trend). After several years a reduction of 1.8 mmol/l would reduce IHD events by an estimated 61%. Results from the same 58 trials, corroborated by results from the nine cohort studies, show that lowering LDL cholesterol decreases all stroke by 10% for a 1 mmol/l reduction and 17% for a 1.8 mmol/l reduction. Estimates allow for the fact that trials tended to recruit people with vascular disease, among whom the effect of LDL cholesterol reduction on stroke is greater because of their higher risk of thromboembolic stroke (rather than haemorrhagic stroke) compared with people in the general population.
Statins can lower LDL cholesterol concentration by an average of 1.8 mmol/l which reduces the risk of IHD events by about 60% and stroke by 17%.