Open Access Grey Literature

Risk-benefit Assessment of Foods in Sweden -Developing a Working Procedure

H. Eneroth, L. Abramsson Zetterberg, C. Andersson, W. Becker, P. O. Darnerud, A. Glynn, R. Lindqvist, S. Sand, N. G. Ilbäck

European Journal of Nutrition & Food Safety, Page 75-78
DOI: 10.9734/EJNFS/2016/24207

Background: Assessments of food-related health risks and benefits performed by national or international experts are still to a large extent separate processes. Diets, foods, and even single food ingredients, may potentially be associated with both beneficial and adverse health effects. Therefore in some cases it is important to consider both health risks and benefits, by assessing the balance between potential risks and benefits, ideally by expressing risk and benefit on the same scale.


In Sweden risk-benefit assessments in the food sector are the responsibility of the Risk and Benefit Assessment Department at the National Food Agency (NFA), which brings together the scientific disciplines toxicology, nutrition and microbiology and related fields. In 2012 a project was initiated to develop a general procedure for risk-benefit assessments at the NFA. The results of this project, and an in-house working procedure, have been published in a governmental report [1] and presented at the Scientific conference “Shaping the Future of Food Safety Together” hosted by the European Food Safety Authority (EFSA) in Milan, Italy, in October 2015 (


The objectives of the project were to:


• Summarize previous national and international experiences in the field of risk-benefit assessment
• Develop a working procedure for practical use at the NFA
• Test the procedure in a case study


Principles of Risk-benefit Assessment


From the overview and evaluation of the risk and benefit assessment literature it was concluded that no international consensus on the general principles or approaches for conducting risk-benefit assessment of foods and food components has so far been reached. The workflow suggested by EFSA [2] was used as a starting point for the development of the proposed NFA procedure for risk-benefit assessment.


Tiered, stepwise approaches have been the preferred procedure in the majority of published risk-benefit assessments. In such an approach the nature of the question and the availability and type of data on for example food composition, exposure and health consequences determine at what tier the assessment can be stopped. The advantage of a stepwise methodology is that it is conceptually easy to use by the assessors and promotes transparency of the process.


The NFA Procedure for Risk-benefit Assessment


The developed risk-benefit assessment procedure contains three steps, from a qualitative assessment of risks and benefits separately to a quantitative assessment expressing risks and benefits on the same scale:


1) Initial assessment of risks and benefits separately
2) Enhanced assessment where different metrics for risks and benefits are weighted
3) Expressing risks and benefits on the same scale, for example mortality or DALYs (Disability Adjusted Life Years).




Fig. 1. The relation between the three different steps in the NFA working procedure (1). Dialogue between the risk-benefit assessor and the risk-benefit manager is crucial after each step


Case Study of the Risk-benefit Assessment Procedure


The procedure was applied in a case study to assess the risk and benefits with a decreased content of nitrite and salt in processed meat, when done in combination with a decreased maximum storage temperature [3]. The potential health benefits for the general population, in terms of lower risk of exceeding ADI and lower risk of high blood pressure of decreased nitrite and salt intake was weighed against an increased risk of Clostridium botulinum and Listeria monocytogenes infections.


The two first steps of the procedure could be applied, and it was concluded that the reduction of salt and nitrite levels would only have marginal effects on public health. Moreover, this reduction would not result in increased growth of microorganisms. The reduction of storage temperature from 8°C to 5°C would however result in a positive effect due to a reduction of growth of L. monocytogenes, but no effect on growth of C. botulinum.


Future Activities at NFA


Considering the complexity and the continuous development of the risk-benefit assessment area there is a need for national and international collaboration. At NFA we have initiated collaborative work with the Karolinska Institutet in Stockholm in order to increase the awareness of risk-benefit assessment in the academic environment, as well as to acquire valuable input from other experts. To promote cooperation on this subject in a Nordic setting we aim to host a workshop on risk-benefit assessment methods for Nordic countries during 2016. We are also open for collaboration in the risk-benefit assessment area within the EU.




The described working procedure is based on current best practices on how to perform risk-benefit assessments. The NFA working procedure share many features with for example the BEPRARIBEAN [4], BRAFO [5] and EFSA procedures [2]. Thus, our intention has been to incorporate experience and knowledge from previously published assessments and suggested procedures into a suitable in-house method. Our risk-benefit procedure is applied to relevant risk assessment questions at NFA. The case study regarding reduction of salt and nitrite content of processed meat helped us to identify critical points in the working procedure since it covered various aspects in microbiology, nutrition and toxicology.


In our work and report we have identified several challenges associated with risk-benefit assessments. This emphasizes the need to develop a commonly accepted and feasible working procedure within the EU.


The complete report can be downloaded free from:

Open Access Grey Literature

Risk Assessment of Beta-carotene in Food Supplements

Helle Margrete Meltzer, Kristin Holvik, Kirsten B. Holven, Martinus Løvik

European Journal of Nutrition & Food Safety, Page 79-82
DOI: 10.9734/EJNFS/2016/23739

Beta-carotene is a provitamin, i.e. a precursor of vitamin A (retinol), which is classified as an essential nutrient for humans. Beta-carotene is one of many carotenoids found in plants, fungi and bacteria. Carotenoids are therefore predominantly obtained through foods of plant origin or food supplements. Carrots contribute approximately half of the total beta-carotene intake in the Norwegian diet, followed by mixed frozen vegetables, tomatoes, fruits and berries. VKM emphasises that this opinion on upper level (UL) for beta-carotene addresses beta-carotene in food supplements only. Beta-carotene from regular foods such as vegetables and fruits is not considered to be a health concern.


In 2002, the Scientific Committee on Food (SCF) established a tolerable upper intake level (UL) for vitamin A (SCF, 2002). However, the SCF opinion covers only retinol compounds (various forms of vitamin A). The bioconversion of carotenoids to vitamin A in the body is well regulated and therefore only intake of vitamin A has been considered relevant for vitamin A toxicity (Blomhoff et al., 2003; EFSA, 2008). The Norwegian Food Safety Authority is considering whether beta-carotene should be regulated separately from retinol compounds.


Beta-carotene seems to have a carcinogenic effect in smokers. A number of studies have been published where possible mechanisms of this negative health effect are discussed. The suggested mechanisms are either related to effects on cytochrome P450-related activities, altered retinoid signalling or to a pro-oxidant activity of beta-carotene.


No UL has been established for beta-carotene. Several risk-assessment bodies have, however, previously attempted to establish safe levels or temporary guidelines, summarised in the following table:




Seven randomised controlled trials (RCTs) have been included in this VKM opinion, conducted either in Europe or the USA, with almost 47 100 participants in the beta-carotene groups. In six of these RCTs there were no observed increased risk of cancer, but the large Finnish ATBC study found an increased risk of lung cancer in the beta-carotene group.


Two prospective studies were included, one Danish and one from the USA, with 125 000 participants all together. The Danish study found that risk of lung cancer increased in smokers with increasing doses of beta-carotene supplements.


In addition, eleven meta-analyses were included; one with age-related macular degeneration as endpoint, one with a mixture of cardiovascular disease (CVD) and cancer as endpoints, four on cancer as only endpoint, one on a mixture of CVD and all-cause mortality as endpoints and four on all-cause mortality alone. One of the meta-analyses on all-cause mortality was later excluded.


There were no significant findings in the meta-analysis on macula degeneration. One of the two meta-analyses on CVD found a small increased risk in the beta-carotene arm (Vivekananthan et al., 2003). The combined CVD and cancer meta-analysis did not have sufficient statistical power to get significant results, but found a probable increase in lung cancer incidence in high-risk subgroups (smokers and asbestos workers (Fortmann et al., 2013).


In the five meta-analyses studying cancer, there were no effect on other cancer forms than lung cancer.


The four meta-analyses on all-cause mortality used information from the same RCTs as included in this VKM-opinion. They extracted information on numbers of death in each study and used these numbers to analyse risk of death in the beta-carotene versus placebo groups. Alarmingly, they all found an increased risk of all-cause mortality. These meta-analyses have been discussed thoroughly.


To complete the risk characterisation of beta-carotene, VKM has followed the steps 1 – 4 as suggested by SCF in their Guidelines for the development of tolerable upper intake levels for vitamins and minerals (SCF, 2000a).


Step 1 and 2. Hazard identification and characterisation


Up until two decades ago, beta-carotene was thought to be harmless even in large doses. In the wake of the Finnish ATBC study which found an increased risk of lung cancer and death in male smokers, animal studies have indicated three possible mechanisms for such a detrimental effect. Although conclusive mechanistic explanations for the negative effects have not yet been agreed upon, there is a scientific rationale for the argument that population groups with vulnerable lungs may also have increased risk from beta-carotene supplements.


The dose used in the Finnish ATBC study was 20 mg beta-carotene/day. The effect was only observed during the intervention period; in follow-up studies conducted after the active period was finished, the risk declined and was no longer significant. 20 mg beta-carotene may thus be considered as a LOAEL.


The Danish prospective study found a dose-dependent increase in lung cancer risk with increased intake of supplemental beta-carotene. Unfortunately, the paper does not allow for setting a NOAEL or LOAEL based on the published data.


In the four meta-analyses on all-cause mortality, all found a 6-7% increased risk of death. One of the meta-analyses also found an increased risk of CVD in smokers. However, all results were driven, statistically, by the ATBC study. Studies with a more mixed population (both men and women) and with a more typical prevalence of smokers (10–20%), found no such increased risk.


Step 2, continued: Derive at a UL, taking into account the scientific uncertainties in the data. ULs may be derived for various life-stage groups within the population


VKM found it extraordinary challenging to decide which uncertainty factor to use for beta-carotene. The present SCF guidelines for establishment of tolerable upper intake levels do not give clear guidance/advice in deciding the numeric level of the uncertainty factor. This seems to leave the decision to scientific judgement.


If the NOAEL is based on human data, an uncertainty factor of 10 is recommended as a starting point to encompass inter-individual variation and sensitivity. The SCF guidelines state that a small uncertainty factor is to be used if the judgement is that little population variability is expected for the adverse effects, and a larger uncertainty factor (close to 10) may be used if variability is expected to be large.


For beta-carotene, a NOAEL is not available, and an uncertainty factor may be applied to account for the uncertainty in deriving a UL from the LOAEL. The size of the uncertainty factor involves a judgement based on the severity and incidence of the observed effect at the LOAEL and the steepness (slope) of the dose response, if this is possible to estimate. For beta-carotene, we have not found the data necessary to make a dose-response curve.


In addition, the following considerations were discussed before deciding on an uncertainty factor:


•The study which found a negative effect of beta-carotene supplementation (the Finnish ATBC study) was very large (n=29 133) which indicates that it encompasses inter-individual variation and sensitivity. Additionally, the most vulnerable groups, in this case smokers, was an inclusion criteria. Both these factors indicate that the uncertainty factor can be in the lower end.
•The meta-analyses for the endpoint “increased risk of all-cause mortality” found an increased risk of death in the beta-carotene groups. This is severe, and indicates that a maximum uncertainty factor should be applied. However, as all results in the all-cause mortality meta-analyses were driven statistically, by the ATBC study on smokers, we choose to use a lower factor.


Based on the above considerations, VKM has chosen to use 5 as an uncertainty factor for beta-carotene.

An UL for beta-carotene cannot be derived, but a tentative upper level (TUL) is set at 4 mg/day, based on a LOAEL of 20 mg and the uncertainty factor of 5.


Smokers and anyone else in the population with vulnerable lungs (e.g. asthmatics, COPD patients) should be discouraged from taking beta-carotene containing supplements all together.


Step 3. Exposure assessment – evaluates the distribution of usual total daily nutrient intakes among members of the general population


In the food survey Småbarnskost 2007, the mean intake of beta-carotene in 2-year-olds was 1.5 mg/day. In Norkost 3, the estimated mean intake in adults was 2.4 mg/day and 6.9 mg/day in the 95th percentile. About 3% of the adults reported use of beta-carotene supplements. The use of tanning pills containing beta-carotene may have been underreported.


Beta-carotene from regular foods such as vegetables and fruits is, however, not considered to be of any health concern. Negative health effects from beta-carotene in natural foods have never been reported. On the contrary, the consumption of vegetables and fruits should be increased, and the recommendation of “5 a day” should be achieved in all age groups of the population.


Step 4. Risk characterisation – analyses of the conclusions from steps 1 through 3 and characterises the risk. The risk will depend on the fraction of the population exceeding the UL and the magnitude and duration of excessive intake


As beta-carotene from food, irrespective of amount, is considered innocuous, it is only intake of beta-carotene from supplements that is considered as relevant.


VKM concludes that with a LOAL of 20 mg beta-carotene/day and a safety factor of 5, 4 mg beta-carotene/day is an appropriate tentative upper level for supplemental beta-carotene.

Open Access Original Research Article

Food Allergy Knowledge, Attitudes and Practices: A Pilot Study of the General Public and Food Handlers

K. Lessa, M. Lozano, M. J. Esteve, A. Frigola

European Journal of Nutrition & Food Safety, Page 58-64
DOI: 10.9734/EJNFS/2016/20696

Objective: We have assessed the factors that might improve the free food allergen at the restaurants. In addition, we have compared food handlers knowledge with the general public knowledge about food allergens.

Design:  Cross-sectional, via questionnaires.

Participants: A total of 182 participants (80 food handlers and 102 of general public).

Main Outcome Measures: Dependent variables: Food allergy knowledge, attitudes and practices.

Analysis: The analysis of variance (ANOVA) and independent t-test. Questionnaires were hand coded and data was analyzed using Statistical Package for Social Sciences (SPSS) version 19.0.

Results: The survey showed that food handlers and general public had some knowledge on the issue, a major proportion of both group do not believe the meals produced in restaurants are safe in terms of food allergies.

Conclusions and Implications: Allergic people must stay on the alert, questioning the place where they are going to have their meals in terms of the ingredients used, verifying whether the food is really free of allergens. This study can be used by restaurants to develop food allergy policies.

Open Access Original Research Article

Maillard Reaction Products in Powder Based Food for Infants and Toddlers

Merichel Plaza, Elin Östman, Eden Tareke

European Journal of Nutrition & Food Safety, Page 65-74
DOI: 10.9734/EJNFS/2016/19150

Aim: To investigate the formation of Maillard reaction products (MRPs) during 28 days storage of the two most consumed brands (B1, B2) of gruel products on the Swedish market.

Methodology: The MRPs; furfural, 5-hydroxymethyl furfural (HMF), N-(1-Carboxyethyl)-L-Lysine (CEL), N-(1-Carboxymethyl)-L-Lysine (CML), fluorescent advanced glycation end products (AGEs) and melanoidins (brown colour) were selected for analysis. High performance liquid chromatography coupled to UV spectrophotometry, fluorescence spectrophotometry or tandem mass spectrometry was used for analysis.

Results: In general, MRPs were higher in B2 than in B1 at the time of opening the package. The initial content of MRPs in B1 and B2 respectively was as follows: 4.39 and 13.74 µg/g of furfural; 1.11 and 1.47 µg/g of HMF; 73.64 and 134.3 µg/g of total CML; 19.79 and 30.42 µg/g of total CEL; 51.11 and 73.01 AU/g of fluorescent AGEs; 0.52 and 1.45 AU/g of MRPs that absorb light at 420 nm and 1.40 and 3.22 AU/g of MRPs that absorb light at 360 nm. During storage for 28 days, furfural, HMF, MRPs that absorb light at 360 nm and at 420 nm as well as fluorescent MRPs increased significantly by respectively 7, 30, 60, 83 and 21% in B2. In B1, only the fluorescent MRPs (21%) increased during storage.

Conclusion: A higher initial content and more pronounced increase of MRPs during 28 days storage time was observed in B2. Consequently, children consuming gruel from B2 are exposed to 1.3-3.1 times more MRPs compared to B1. Considering that a child often sticks to one gruel brand throughout the first years of life and that some MRPs are inflammatory drivers, more studies are required to understand the role of food-process induced chemicals at an early age for future health of the children.

Open Access Review Article

The Functional Nutrients of Flaxseed and Their Effect on Human Health: A Review

Abebe Ayelign, Taddese Alemu

European Journal of Nutrition & Food Safety, Page 83-92
DOI: 10.9734/EJNFS/2016/16318

Introduction: Humans have consumed flaxseed (Linum usitatissimum) since the earliest times. It has been used as ready-to-eat breakfast cereals, breakfast drinks, salad dressings, porridge, and as beverages. To date, flaxseed is recognized as a functional food in the world’s food market because of its health benefits besides the basic nutrition.

Objectives: To review the functional nutrients of flaxseed with their respective health benefits. 

Methods: Electronic search of Pub Med, Health Inter Network Access to Research Initiative (HINARI), and Google Scholar databases was conducted. Outcomes of interest were the functional nutrients of flaxseed and potential health benefits mainly; antioxidant, free radical scavenging, anti-carcinogenic, and anti-hypercolesterolemic. 

Findings: Majority of the articles reviewed showed that flaxseed contains essential nutrients and non-nutrients such as alpha linolenic acid (ALA), lignans known as secoisolariciresinol diglucoside (SDG), and crude fiber that have important health benefits to humans.

Conclusions: Eating flaxseed meal in different forms may have beneficial effect in preventing or reducing various forms of cancer, cardiovascular disease, hypertension, diabetes, constipation, diverticular disease and others. Further studies about the Recommended Daily Intake (RDI) and more in vivo studies to ascertain the health benefits of flaxseed nutrients are recommended.