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Very low calorie diets (VLCD products) are formulated products with 450 – 800 kcal per day intended to replace the whole diet. Regulation of VLCD is not harmonised in the EU, and there is no specific national Norwegian legislation for these products. The Norwegian Food Safety Authority has requested VKM to propose minimum and maximum limits for the content of fat/ fatty acids, protein, carbohydrates, vitamins and minerals in VLCD products based on acknowledged scientific documentation. VKM is also asked to evaluate if VLCD products are suitable in the treatment of obese subjects with type 2 diabetes, and possible contraindications for use of VLCD. This assessment is based upon the SCOOP-report “Collection of data on products intended for use in very-low-calorie-diets” (SCOOP, 2002) and new literature mainly after 2002. Based on the available scientific literature, the VKM Panel on nutrition, dietetic products novel food and allergy has concluded that, on a daily basis, VLCD products should provide minimum 55 g carbohydrates, 10 g fibres, 50 g high quality protein and 7 g fat, including 3 g from linoleic acid and 0.5 g from α-linolenic acid. The amino acid scoring pattern should be in accordance with the protein-digestibility-corrected amino acid score. VLCD products should provide minimum 10 µg vitamin D per day, and the minimum recommended daily intake for the other vitamins and minerals. No maximum limits are suggested for carbohydrates, protein or fat, as the energy will be the limiting factor. The fibre content should not exceed 30 g per day, and the VKM Panel recommends that the maximum limits for vitamins, minerals and trace elements should equal two times the recommended daily intake. VLCD will give short-term weight loss and improvement in blood pressure, serum lipids and glycemia in obese subjects with type 2 diabetes, and no serious adverse effects have been reported. VLCD may impede the educational process needed in the treatment of diabetes, and should therefore only be used as part of an educational program in obese subjects with type 2 diabetes, and only under medical supervision. VLCD is contraindicated in children, adolescents, pregnant and lactating women, elderly (above 65 years old) and in subjects with heart failure, cerebrovascular disease, gallstone disease, kidney- and liver diseases, psychiatric disorders, and in subjects with BMI ≤ 30 kg/m2. In addition one should be aware of the reducing effect of VLCD on blood pressure and the effect on hyperglycaemia which may cause problems if pharmacological therapies for these conditions are given. Medical supervision is recommended if VLCD treatment exceeds 3 weeks. To prepare this report, VKM established an ad hoc group (members listed above). The VKM Panel on Nutrition, Dietetic Products, Novel Food and Allergy has discussed and adopted this opinion.

On 10. March 2006 , The Norwegian Food Safety Authority (Mattilsynet) decided that, on the basis of VKM’s previous risk assessment (2005), Nutramigen 1 with Lactobacillus rhamnosus GG (LGG) could not be marketed in Norway as medical foods for infants (0-4 months). In addition, The Norwegian Food Safety Authority (Mattilsynet) decided (08. November 2006) to withdraw permission for marketing of Nutramigen 2 with LGG, which is a milk supplement for infants aged between 4 and 6 months, with cow’s milk and soy protein allergy. On 13. December 2006, Mead Johnson Nutritionals appealed against this decision from The Norwegian Food Safety Authority (Mattilsynet). The Norwegian Food Safety Authority forwarded the appeal from the companies, asked the VKM Panel on biological hazards and the VKM Panel on nutrition, dietetic products, novel food and allergy, for a new risk assessment including the new data provided in the appeal. LGG is one of the most studied probiotic strains. Lactic acid produced by LGG in the human gut results in a decrease in faecal pH, which in turn inhibits colonisation by potentially pathogenic bacteria. Short-term beneficial effects from administration of LGG to infants and young children with infectious diarrhoea have been reported in a number of studies, but a prophylactic effect on diarrhoea has not been documented. Furthermore, whilst some studies have reported a prophylactic, or even a curative, effect of LGG on atopic eczema in young children, more recent studies do not report such effects. Some even suggest an increased incidence of allergic sensitization in children receiving LGG supplemented formula at an early age. There are no published data that demonstrate long-term clinical benefits of infant formula supplemented with LGG for children between 4 months and 3 years, although no immediate deleterious effects of LGG have been found. Possible long-term effects of LGG on intestinal colonisation, and its effects on long-term gastrointestinal and immune functions, are not known. LGG, as an ingredient in infant formula and baby foods, is intended for daily use in the target group, and not for short-term, specific treatment. Furthermore, the targeted consumer group includes children below the age of twelve months. These two aspects demand particular consideration with regard to the unknown effects of long-term treatment with large doses of live bacteria on the ecology of the microbiota of the gastrointestinal tract and on the immune system. Neither of these systems is fully matured in infants and small children, and therefore may be particularly susceptible. There is no documented prophylactic effect of LGG on any disease in children. The effect of treatment with LGG-supplemented formula in small children is questionable, except for a documented short-term effect on infectious diarrhoea. Panel on Biological Hazards and Panel on nutrition, dietetic products, novel food and allergy at the Norwegian Scientific Committee for Food Safety find that the data available are not sufficient to support the suggested beneficial effects, or the safety, of LGG in infant formula and baby foods for children aged between 4 months and 3 years, when the products are intended for daily use.

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has at the request of the Norwegian Food Safety Authority (Mattilsynet) conducted an assessment of creatine in sports products (e.g. supplements). The evaluation has been performed by an ad hoc group, and assessed by the VKM Panel on nutrition, dietetic products, novel food and allergy. The evaluation of safety and possible risks of creatine supplementation in this opinion is based on previous reports, 23 original papers and 14 reviews from literature searches. Marketing and sales of sport products are increasing in the Nordic countries, with creatine supplements being one of four most common categories. In addition to be used by athletes, the use of creatine supplements seems to increase among general exercisers and young people. Creatine supplements are mainly used for their supposed effects on muscles mass and high intensity and short duration sport performances. Supplementation has been shown to result in higher concentration of creatine phosphate in the muscles, which is the limited substrate. For athletes, it is recommended a loading dose of 10-20 g/day for 4-7 days and a maintenance dose of 2-5 g/day for weeks or months. Some athletes continue the maintenance dose for several years. It is well documented that creatine supplementation has positive effects on muscle mass combined with strength training and performance during maximal exercise. There are however large individual variation in the response, and there are responders and non-responders. The new scientific literature, including long term studies, is in line with the EFSA (European Food Safety Authority) opinion from 2004. VKM Panel on nutrition, dietetic products, novel food and allergy supports the EFSA conclusion that supplementation of creatine in doses below 3 g/day is unlikely to pose any risks if the purity of the creatine compound is adequate. Scientific long-term studies with doses up to 5-10 g/day in adult athletes have shown no harmful effects, but there are no dose-response studies indicating a safe upper limit for creatine. The potential negative effects (impaired kidney function, weight gain and gastrointestinal disturbances) which have been published in non scientific journals and anecdotal reports have not found support in controlled systematic studies on healthy subjects. It has been indicated that individuals with impaired kidney functions should refrain from creatine supplements. Creatine-monohydrate is the most studied form of creatine supplements, and only creatine monohydrate has been included in the scientific investigations on adverse effects.

The Norwegian Scientific Committee for Food Safety (VKM) has appointed an ad hoc-group of experts to answer a request from the Norwegian Food Safety Authority regarding benefit and risk assessment of Lactobacillus paracasei ssp. paracasei F19 (F19) in processed cerealbased baby foods intended for small children 1-3 years. This assessment is based on the literature provided by the notifier as well as that found by a MEDLINE search. A notification regarding two products of processed cereal-based baby foods (hereafter called cereals), intended for small children and supplemented with the bacterium F19 initiated this work. A daily supply of a monoculture of a particular bacterial strain in large quantities to an age group without a fully established intestinal flora, may have unknown adverse effects. There are however, to our knowledge, no studies investigating possible short or long term adverse health effects of F19 in processed cereal-based baby food given to children 13 months onwards. The documentation and information provided by the notifier regarding the genetic stability of F19 in the two products during processing and storage, is considered insufficient and does not allow any conclusions to be drawn. Moreover, the documentation obtained is not conclusive regarding the antibiotic resistance pattern of the bacterial strain used in the products in question, as the information on different antibiotics is partly inconsistent. The information about specific localization (chromosomal, plasmid) of the resistance genes is not sufficient. Studies demonstrate that F19, as well as other bacterial strains considered probiotic, is able to “crosstalk” with enterocytes in mice and that the result of the “crosstalk” depends upon the microbiota present. Whether F19 has a similar “crosstalk-profile” in humans is unknown. However, as the strain is originally of human origin, it seems reasonable to assume that such “crosstalk” may occur. Thus, before giving F19 daily for months and years, it seems reasonable to ask for additional molecular and physiological studies to unravel the functional impact of possible changes in genetic expression in children. Lactobacillus infections do occasionally occur, mainly as bacteremia, endocarditis and localized infections (e.g. abscesses, peritonitis, and meningitis) in patients with severe underlying diseases. Most of them are elderly, but children are not excluded. The species most often isolated are L. casei and L. rhamnosus, followed by L. paracasei. The increasing use of immunosuppressive therapy and broad spectrum antibiotics which are ineffective against Lactobacillus, might increase the importance of these bacteria as possible pathogens. In order to be able to draw any conclusions regarding beneficial effects of F19, there is a need for randomized placebo-controlled studies in larger populations and in the relevant age group. According to EFSA, Lactobacillus paracasei ssp. paracasei F19 is sufficiently characterized. The documentation provided is, however, not sufficient to claim positive health effects and thus F19 is not proven to be probiotic. There are no published dose-response studies of F19 in children, neither regarding survival of F19 in the gastrointestinal tract, nor possible negative health effects. Thus the potential for negative health effects as e.g. spreading of antimicrobial resistance or unfavourable impact on the genetic expression in children related to the frequency and/or dose of a monoculture of F19 cannot be assessed.

The Norwegian Scientific Committee for Food Safety (VKM) has appointed an ad hoc-group of experts to answer a request from the Norwegian Food Safety Authority regarding benefit and risk assessment of B. lactis Bb12 in baby foods focusing on the age groups 4-6 months, 612 months and 1-3 years. This assessment is based on the literature provided by the notifier as well as that found by a MEDLINE search. An notification for use of processed cereal-based baby foods (from now on called cereals) intended for infants and small children supplemented with the microorganism Bifidobacterium lactis (B. lactis) Bb12 in Norway initiated this work. Studies of potential hazards and positive health effects from cereals containing B. lactis Bb12 intended for infants and young children have not been reported in the available literature. However, reports on safety of and positive health effects from infant and follow on formula supplemented with B. lactis Bb12 are available and have been assessed by VKM. In most of these clinical studies B. lactis Bb12 was administered in combination with other probiotic strains. Clinical studies report no serious adverse events of infant formula supplemented with B. lactis Bb12. The effect of long term daily consumption of such supplemented formula by the actual age groups is not known. A few studies have demonstrated some effect of supplementing baby food with probiotics, including B. lactis Bb12, on diarrhoea and atopic eczema while other studies do not show such effects. Thus, the scientific evidence for a favourable effect of supplementing formula or solid food with B. lactis Bb12, is weak and in some cases lacking. There are no studies demonstrating a positive effect of cereals supplemented with B. lactis Bb12 intended for infants and small children. Several health claims related to probiotics have been assessed by EFSA, including claims on reduction of gastro-intestinal discomfort, normal functioning of the alimentary tract, building of the natural intestinal barrier, improvement of the general immunity, mental and cognitive developments of children and immune system of children during growth. In the opinions so far, EFSA has concluded that a cause and effect relationship has not been established between the consumption of the probiotic containing products and the claimed effect. None of the products assessed so far contained B. lactis Bb12 (1 November 2009). Commercially produced cereals are frequent given to infants and small children in Norway from an early age and this is particularly important for the establishment of the intestinal bacterial flora and the development of the intestinal mucosal immune system. According to the notifier, one portion (25gram) of the cereal powder contains 1 x 109 B. lactis Bb12 in monoculture. Taking into consideration that the daily intake is often greater than one portion of cereals, even in infants below 6 months of age, this would represent a daily intake of 1-2 x 109 cfu B. lactis Bb12 for an infant 4-6 months and even more in infants above 6 months. If a considerable amount of the B. lactis Bb12 survives the transport to the small intestine, it would represent a dominating and monocultural supply, often several times a day, to the small intestine. The immaturity and vulnerability of the intestinal microbiota and the immune system makes the two lowest age groups, 4 – 6 and 6 – 12 months, at the highest risk of unwanted health effects due to the daily intake of probiotics.

In 2006 the, the Panel on Nutrition, Dietetic Products, Novel Food and Allergy in the Norwegian Scientific Committee for Food Safety (VKM) adapted a Danish model for assessing applications concerning food fortification into Norwegian conditions. The fortification model is presently used by the Norwegian Food Safety Authorities as a tool in the management of applications on food fortification. The model from 2006 was based on intake calculations from dietary surveys from 1997-2000. Since then, new national dietary surveys have been published. These are the comprehensive nationwide Norwegian dietary surveys among adults (Norkost 3, 2010-2011), among young children (Småbarnskost, 2007) and infants (Spedkost, 2006-2007). The Norwegian Food Safety Authority has requested VKM to implement the new data into the fortification model from 2006. In the model from 2006 it is assumed that 25% of the energy in the diet can be derived from fortified foods and drinks. Information from the Norwegian Food Safety Authority, including about a pilot study for Norkost 3 suggested that the overall intake of fortified foods and drinks was marginal. From management of applications for fortified foods, the Norwegian Food Safety Authority also experienced that there are few fortified foods on the market in Norway. The Norwegian Food Safety Authority has therefore requested VKM to evaluate whether the assumption that 25 energy percent (E%) deriving from fortified foods can be reduced to 15 E%, and if such a reduction will have health implications. In addition, the Norwegian Food Safety Authority has asked VKM to perform an evaluation of the safety factors in the model. VKM argues that the model for fortification should be based on the dietary intake of vitamins and minerals at the 95th percentile level in various age groups. This is in accordance with risk assessments performed in European Food Safety Authority (EFSA), and will assure that the dietary intake in a majority of the population will be covered, still within a reasonable secure use of dietary exposure calculations. Mean intake of vitamins and minerals from food supplements (among users only) was chosen, in an attempt to reduce the impact of those with a high intake of supplements. The intake at 95th percentile from the diet plus the mean nutrient intake from supplements is deducted from the tolerable upper intake level (UL) for each nutrient in each age group, giving the maximum amount of nutrients that can be “allocated” for food fortification. The maximum amount of a nutrient that can be “allocated” is then distributed over the energy intake at the 95th percentile level. In this manner an estimate is made showing which age group is most likely to have an excessive intake of a certain nutrient. VKM does not have access to any other information about available fortified foods on the Norwegian market than the information given by the Norwegian Food Safety Authority. However, based on this information, VKM considers that it seems reasonable that the energy intake from fortified foods is reduced to 15 E%. In this revised fortification model the assumption from 2006 that 25 E% of the total energy intake will be derived from fortified foods, have therefore been reduced to 15 E%. This adjustment implies that the addition of e.g. vitamin D, vitamin E, thiamine, riboflavin, niacin, folic acid, vitamin B12, vitamin C and calcium per 100 kcal can be increased without risk of exceeding UL. No changes are made for e.g. vitamin A, beta-carotene, magnesium, iron, zinc or copper. A more summary is presented in Table 1 and Appendix 1. The Panel on nutrition, dietetic products, novel food and allergy considers that this model for management of fortification will reduce health risk that could be caused by unauthorised food fortification.

The changes in the feed of farmed Atlantic salmon (Salmo salar) towards a more plant-based diet affect the nutritional value of the fillets. By compiling the contents of a range of nutrients in 1108 samples of Norwegian farmed Atlantic salmon collected between 2005 and 2020, we found that the median contents of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) have decreased by > 60%. However, farmed Atlantic salmon remains a considerable source of EPA and DHA, with one and two portions being sufficient to meet the weekly adequate intake of EPA and DHA for adults (175 g) and two-year-olds (80 g), respectively. Farmed Atlantic salmon also remains a considerable source of protein, selenium, vitamin B12, and vitamin D3. Together, we demonstrate that farmed Atlantic salmon can contribute substantially to the nutrient intake of the consumers. These data are important for the Norwegian food composition table and future risk–benefit assessments on fatty fish consumption. publishedVersion

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of "other substances" in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis while regulating "other substances" in food supplements. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional and/ or physiological e ffect. It is added mainly to food supplements, but also to energy drinks and other foods. In this series of risk assessments of "other substances" the VKM has not evaluated any claimed beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of specified doses of L-threonine in food supplements, and it is based on previous risk assessments and articles retrieved from literature searches. According to information from NFSA, L-threonine is an ingredient in food supplements sold in Norway. NSFA has requested a risk assessment of 1000, 1200, 1500, 2000 and 2400 mg/day of L-threonine from food supplements. L-threonine is an essential amino acid not known to cause any adverse health effects. Previous reports do not indicate a tolerable upper intake level, apart from an approval of a dose of 1150 mg/day by the Scientific Committee of the Spanish Agency for Food Safety and Nutrition (AESAN). Long-term studies in humans were not found. The only available human studies were: a small uncontrolled one-year pilot study with doses ranging from 0.5 to 2.5 g/day, one eight-week randomised controlled trial (RCT) using a dose of 7.5 g/day, and two 2-week RCTs using doses of 6 and 4.5 g/day. No adverse effects (diary method of registration of adverse effects) were reported in the eight-week clinical trial, and the only adverse effects observed in the two-week trials were one case of indigestion and one case of diarrhoea. A four-week rodent toxicity study indicated a no observed adverse effect level (NOAEL) of 854.3 mg/kg bw per day (only dose tested, no adverse effects observed). The value used for comparison with the estimated exposure in the risk characterisation is the NOAEL defined in an 8-week randomised placebo controlled study in humans, 7500 mg/day. For a 70-kg individual, this corresponds to 107 mg/kg bw per day. Two human two-week studies and a small one-year pilot study support the notion that this dose will be well tolerated. The overall mean threonine intake according to NHANES III (3 g/day) is slightly larger than the doses requested for evaluation in the present risk assessment. No studies in children (10 to

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of "other substances" in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis for regulating "other substances" in food supplements. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional and / or physiological effect. It is added mainly to food supplements, but also to energy drinks and other foods. In this series of risk assessments of "other substances" VKM has not evaluated any claimed beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of specified doses of L-histidine in food supplements, and it is based on previous risk assessments and articles retrieved from a literature search.Histidine; food supplement According to information from NFSA, L-histidine is an ingredient in food supplements and energy drinks sold in Norway. NSFA has requested a risk assessment of 550 and 600 mg/day of L-histidine from food supplements. The recommended dietary allowance (RDA) for adults of L-histidine is 14 mg/kg body weight/day (IOM, 2005), which corresponds to 980 mg/day for a 70 kg person. Oral doses has a bioavailiability of 80% or higher. Foods rich in histidine are generally protein rich foods such as meat, dairy products, legumes, fish, nuts, seeds, eggs and whole grains. Based on NHANES III (1988-1994), the overall mean intake of Lhistidine from food and food supplements in the United States was 2.2 g/day. L-histidine is a conditionally essential amino acid which is a normal constituent of most body proteins. L-histidine is also a part of many plasma proteins. It has anti-oxidant and antiinflammatory properties. Moreover, L-histidine is also a precursor of histamine and is necessary for the regulation and metabolism of trace elements such as metal ions. The human body has a large pool of L-histidine in plasma proteins, but also as carnosine in skeletal muscles and in haemoglobin. Due to the lack of adequate scientific information, a no observed adverse effect level (NOAEL) or lowest observed adverse effect level (LOAEL) have not been identified, and a tolerable upper intake level for histidine has not been established. Effects of histidin supplementation have been studied in trials with duration of up to 3-4 months. Previous risk assessments concluded that supplementation with 4.0 to 4.5 g/day of L-histidine above the dietary content does not have adverse effects in human beings, and new data retrieved in the present literature search were in accordance with these conclusions. No particular population groups have been identified as particularly susceptible to adverse effects of consuming histidine supplements. We have not identified any studies in children or adolescents. VKM concludes that: In adults (≥18 years), the specified doses 550 and 600 mg/day L-histidine in food supplements are unlikely to cause adverse health effects. In adolescents (14 to

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of "other substances" in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis while regulating "other substances" in food supplements. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional and / or physiological effect. It is added mainly to food supplements, but also to energy drinks and other foods. In this series of risk assessments of "other substances" the VKM has not evaluated any claimed beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of specified doses of L-serine in food supplements, and it is based on previously published risk assessments and scientific papers retrieved from a comprehensive literature search. L-serine is a non-essential amino acid which is produced endogenously and is supplied from the diet. In addition to its role in protein synthesis, L-serine has an important role as a major contributor to the one-carbon pool and is involved in the metabolism of several key compounds, including glycine, cysteine, taurine, and phospholipids and of D-serine. According to information from NFSA, L-serine is an ingredient in food supplements sold in Norway. NSFA has requested a risk assessment of 50, 500, 1000, 1250, 1500 and 1750 mg/day of L-serine from food supplements. Most dietary proteins contain about 4-5% L-serine. Rich sources of proteins are meat, dairy products, legumes, fish, nuts, seeds, eggs and whole grains. Dietary intake of L-serine in Norway is not known, but results show an overall mean intake of L-serine from food and food supplements of 3.5 g/day in the United States (NHANES III, USA). In the first phase of the present evaluation of "other substances", previous reports that have assessed the safety of L-serine supplementation in humans were identified. In the second phase, a systematic literature search was performed to retrieve scientific papers published before 11 May 2016 (human studies literature search) and before 28 July 2016 (animal studies literature search). Based on this search, we did not identify any long-term studies in healthy individuals that could be used for safety evaluations. On the other hand, three relevant animal studies were included in this report. The animal studies revealed no adverse health effects as a result of the tested doses of Lserine (840-3000 mg/kg bw per day). For the risk characterisation of L-serine, in the absence of long-term studies in healthy individuals, VKM based the value of comparison on the no observed adverse effect level (NOAEL), 3000 mg/kg bw per day which was the highest dose tested in a 90-days toxicological study in rats. This value was used to calculate the Margin of Exposure (MOE) values for daily intake of 50, 500, 1000, 1250, 1500 and 1750 mg L-serine in children (10 to

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of "other substances" in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis for regulating the addition of "other substances" to food supplements. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional or physiological effect. "Other substances" are added mainly to food supplements, but also to energy drinks and other foods. VKM has not in this series of risk assessments of "other substances" evaluated any claimed beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of L-tryptophan and is based on previous risk assessments of L-tryptophan and scientific papers retrieved from systematic literature searches. L-tryptophan is an indispensable amino acid in humans, which in addition to its role in protein synthesis, also participates in complex metabolic pathways where it acts as a precursor to the potent neurotransmitter serotonin, the hormone melatonin, and the vitamin niacin (vitamin B3). L-tryptophan is available from a wide variety of protein-rich foods in the normal diet, including meat, fish, milk and dairy products, egg, beans, lentils and also bread and grains, pasta, rice, fruit and vegetables. According to information from NFSA, L-tryptophan is an ingredient in food supplements sold in Norway. NFSA has requested a risk assessment of the following doses of L-tryptophan in food supplements: 250 mg/day, 300 mg/day, and 450 mg/day for adults, adolescents and children 10 years and above. Usual dietary intake of L-tryptophan in Norway is not known, but data from the USA and the UK suggest an average dietary intake of about 900 mg/day of which the main part is bound in food protein. In phase 1 we have identified seven previous reports that have aimed to assess the safety of L-tryptophan supplementation in humans; the most recent was published by VKM in 2013. To complement the existing reports, a literature search was performed in MEDLINE and EMBASE to retrieve studies published in the period 2012-2015. This search retrieved two recent randomised trials with L-tryptophan. In addition, we performed a literature search concerning safety of L-tryptophan in children and adolescents with no time restriction. This search retrieved no relevant results that met the inclusion criteria. Four aspects related to safety of L-tryptophan were identified in previous reports: 1) adverse effects reported at high doses, including appetite suppression, nausea and vomiting, faintness, dizziness, drowsiness, tremor, fatigue, and headache; 2) a suggested, but not established, increased risk of cataract; 3) the eosinophilia-myalgia syndrome (EMS), which is thought to be caused by contaminants produced in the manufacturing of L-tryptophan supplements, however this is still unresolved; 4) the risk of adverse drug reactions caused by excessive serotonergic action by concomitant use of antidepressants, including monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants and other drugs, known as the serotonin syndrome. According to previous reports, doses of 3 to 6 g/day of L-tryptophan have been associated with adverse effects. Using an uncertainty factor of 10, conclusions in previous reports have suggested a maximum level of 220 mg/day for adults. An upper tolerable intake level (UL) of 220 mg/day was first proposed in a report by the UK Committee on the Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) in 2004, and was derived from the average dose of L-tryptophan consumed as a prescription drug against depression in the UK at the time (2228 mg/day). This level has been maintained in later reports by other committees, most recently VKM in 2013 as a tentative guidance level. Additional information from the publications retrieved in the literature search did not provide evidence of sufficient weight to change the previous conclusions concerning UL. There is a lack of well-designed supplementation studies with L-tryptophan in humans designed to address adverse effects and dose-response relationship as primary outcome. There is also a lack of data about potential adverse health effects of L-tryptophan supplementation in children and adolescents. Patients using antidepressant drugs constitute a specific vulnerable subgroup of the population with regard to possible adverse effects of L-tryptophan supplements, due to the potentially life-threatening drug interaction effects that occur from excessive serotonergic action. The Norwegian Scientific Committee for Food Safety (VKM) concludes that: In adults (≥18 years), the specified doses 250, 300, and 450 mg/day L-tryptophan in food supplements may represent a risk of adverse health effects. In adolescents (14 to

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of "other substances" in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis while regulating the addition of "other substances" to food supplements. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional and/or physiological effect. It is added mainly to food supplements, but also to energy drinks and other foods. VKM has not in this series of risk assessments of "other substances" evaluated any claimed beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of L-phenylalanine and DL-phenylalanine and is based on previous risk assessments. According to information from the Norwegian Food Safety Authority, L- and DL-phenylalanine are ingredients in food supplements sold in Norway. NFSA has requested a risk assessment of the following doses of L-phenylalanine and DL-phenylalanine in food supplements: L-phenylalanine 100, 250, 500, 750 and 1000 mg/day and DL-phenylalanine 50 and 75 mg/day. L-phenylalanine is an essential amino acid which means it has to be obtained from the diet. Amino acids are building blocks for proteins and present in protein rich food such as milk, meat, fish, eggs and cheese. No data on adverse health effects after chronic ingestion of supplemental phenylalanine in apparently healthy subjects are available, thus no tolerable upper intake level (UL) can be established. Patients with phenylketonuria (PKU), a genetic disorder that impairs phenylalanine hydroxylase (PAH), an enzyme involved in the metabolism of phenylalanine, must keep plasma levels of phenylalanine low in order to maintain normal growth and brain development. In Norway, all newborns are routinely screened for PKU three days after birth. The mean dietary intake of phenylalanine in the EU population range from 0.4-4.1 g/day corresponding to 79.0 mg/kg bw per day for adolescents (10-17 years) and 58.7 mg/kg bw per day for adults, respectively (EFSA, 2013). The sweetener aspartame contains phenylalanine. Taking the molecular weight of phenylalanine into account, the proportion of to phenylalanine exposure from aspartame is 56%. The ADI of 40 mg aspartame/day/kg bw (providing 22.4 mg phenylalanine/day/kg bw) JECFA (1981) was re-evaluated and maintained in 2013, based on the notion that elevated plasma levels of phenylalanine in pregnant women leads to developmental toxicity in their children (EFSA, 2013). The literature search did not provide novel information on adverse health effects related to intake of L-phenylalanine and no information related to DL-phenylalanine. VKM concludes that: In adults (≥ 18 years), the specified doses 100, 250, 500, 750 and 1000 mg/day L-phenylalanine in food supplements are considered unlikely to cause adverse health effects. In adolescents (14 to < 18 years), the specified doses 100, 250, 500, 750 and 1000 mg/day L-phenylalanine in food supplements are considered unlikely to cause adverse health effects. In children (10 to < 14 years), the specified doses 100, 250, 500, 750 and 1000 mg/day L-phenylalanine in food supplements are considered unlikely to cause adverse health effects. Although the highest dose provides 23 mg/kg bw per day which slightly exceeds 22.4 mg/kg bw per day, it is considered unlikely to cause adverse health effects in healthy children 10 to < 14 years. None of the above conclusions are applicable for patients with phenylketonuria (PKU). No conclusion can be made regarding DL-phenylalanine. Children below 10 years were not included in the terms of reference.

The regulation of infant formulas is under revision, including the national restriction on sales of infant formulas with partially hydrolysed proteins to pharmacies only. In December 2007 the Norwegian Food Safety Authority requested an opinion from the Norwegian Scientific Committee for Food Safety on infant formulas with partially hydrolysed protein. The opinion should cover an evaluation of risks associated with the replacement of conventional infant formulae (based on intact protein) by infant formula based on partially hydrolysed protein, including a specification of the risks associated with the consumption of infant formula based on partially hydrolysed proteins among infants with cow’s milk allergy. Furthermore, the opinion should include an evaluation of the preventive effect from formula with partially hydrolysed proteins on development of cow’s milk allergy. To complete this task, VKM has established an ad hoc group that has prepared this report. The Panel on Nutrition, Dietetic Products, Novel Food and Allergy has discussed and adopted this opinion. The main conclusions are that although no studies show that partially hydrolysed formulas have negative effect on growth, measures should be taken in order to avoid that partially hydrolysed formulas replace regular infant formulas in the general population. Hydrolysed proteins have a high absorption rate, and ingestion of hydrolysed proteins have been shown to increase gastric emptying and plasma glucose-dependent insulinotropic polypeptide relative to the intact protein forms. Feeding partially hydrolysed formulas to infants with cow’s milk allergy constitutes a risk of eliciting an allergic reaction which in worst case may be fatal. The risk that an infant with cow’s milk allergy will receive partially hydrolysed formula may increase if the products are sold with claims such as reduced risk towards cow’s milk allergy and reduced risk of developing cow’s milk allergy together with ordinary infant formula outsides pharmacies. The risk of developing cow’s milk allergy is not shown to be reduced by introducing partially hydrolysed formula instead of regular formula during the first 4-6 months. There has not been demonstrated any preventive effect from hydrolysed formulas after the age of 6 months on the development of allergic disease.

Background: The toxic effects of prenatal methylmercury (MeHg) include neurological abnormalities and developmental delay of which infants and children are particular susceptible. Studies on the effects of low and moderate exposure show conflicting results. Seafood is the main dietary source of MeHg, but also contributes with nutrients regarded as beneficial for development. Objectives: To measure the change in total hair mercury concentration (THHg) after an intervention of lunch meals with fatty fish or meat in Norwegian preschool children, and to examine the associations between THHg and cognitive function. Methods: Children (n = 232) 4–6 years old were randomized to lunch meals with fatty fish (n = 114) or meat (n = 118) three times a week for 16 weeks. THHg was determined using a Direct Mercury Analyzer, and cognitive function was assessed by the Wechsler Preschool and Primary Intelligence Scale-III (WPPSI-III) pre- and post-intervention. Linear mixed effect models were used to analyze changes in THHg and WPPSI-III scores. Results: The mean (SD) THHg pre-intervention was 0.373 (0.204) mg kg−1. Children in the fish group had an increase in THHg (change 0.162, 95% CI 0.111, 0.213 mg kg−1), whereas children in the meat group had decreased THHg (−0.053, 95% CI −0.103, −0.002 mg kg−1). There were no notable associations between THHg and the WPPSI-III raw scores at baseline or after 16 weeks of the fish/meat intervention. Conclusions: Lunch meals including fatty fish led to a significant increase in THHg, but the values remain below the point of departures used for risk assessment by the EFSA, WHO and US-EPA. We observed no associations between THHg and cognitive function. Keywords: Hair mercury, Methylmercury, Fish consumption, Cognitive development, Preschool children

Marine fish from the North East Atlantic Ocean (NEAO) are nutrient rich and considered a valuable economic resource. However, marine fish are also a major dietary source of several contaminants, including persistent organic pollutants (POPs) and heavy metals. Using one of the world’s largest seafood datasets (n > 25,000 individuals), comprising 12 commercially important fish species collected during 2006–2019 in the NEAO, we assessed the co-occurrence of elements and POPs, and evaluated potential risks to human consumers. Several positive correlations between concentrations of mercury (Hg), dioxins, polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) were observed. Concentrations of Hg, dioxins, PCBs and PBDEs increased from North to South and associations between marine sediment contamination, sea temperature, and fish Hg and POPs concentrations were identified using multi-linear regression (MLR) models. In general, Hg concentrations in fillet and liver of fish were positively associated with increases in both sediment contamination and sea temperature. POPs concentrations in both fillet and liver were positively associated with increases in sediment contamination, and only POPs concentrations in the liver of benthopelagic and demersal species were found to be positively correlated with sea temperature. Using a probabilistic approach to estimate human contaminant exposure from seafood, we showed that intake of pelagic species posed the highest risk of dioxins and dioxin-like PCBs (DL-PCBs) exposure, while intake of benthopelagic and demersal species posed the highest risk of Hg exposure. This study can serve as a model to further understand the distribution, co-occurrence, and trends of contaminants in seafood harvested from the NEAO and their potential risks to human consumers. publishedVersion

Oily seafood is an important food source which contains several key nutrients beneficial for human health. On the other hand, oily seafood also contains persistent organic pollutants (POPs), including the dioxin-like compounds (DLCs) polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/Fs) and dioxin-like-polychlorinated biphenyls (dl-PCBs), potentially detrimental to human health. For a comprehensive comparison of the beneficial and potentially adverse health effects of seafood consumption, risk–benefit analyses are necessary. Risk-benefit analyses require reliable quantitative data and sound knowledge of uncertainties and potential biases. Our dataset comprised more than 4000 analyses of DLCs and more than 1000 analyses each of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and vitamin D in the three most important Norwegian commercial oily seafood species: Atlantic herring (Clupea harengus), Atlantic mackerel (Scomber scombrus) and farmed Atlantic salmon (Salmo salar). The levels of several DLC congeners were below the limit of quantification (LOQ), making estimation of true levels challenging. We demonstrate that the use of upper bound substitution of censored data will overestimate, while lower bound substitution will underestimate the actual levels of DLCs. Therefore, we implement an alternative robust statistical method by combining Maximum Likelihood Estimation, Regression on Order Statistics and Kaplan-Meier analyses, which is better suited for providing estimations of levels of these contaminants in seafood. Moreover, we illustrate the impact of the toxic equivalency factor (TEF) system on estimation of the sums of DLCs by comparing the TEF system to an alternative system of relative effect potency (REP) factors (Consensus Toxicity Factors). The levels of nutrients and contaminants were related to adequate intake (AI) and tolerable weekly intake (TWI), respectively. We used AI and the TWI values established by the European Food Safety Authority (EFSA). The benefit and the risk were further viewed in the context of the Norwegian average intake of oily fish, and the Norwegian governmental official dietary recommendations of oily fish. Our results showed that both benefit and risk are met at the levels found of nutrients and DLCs in oily seafood. The comprehensive quantitative data presented here will be a key for future risk–benefit assessment of oily fish consumption. Together, our results underline that a refined formalized integrative risk–benefit assessment of oily fish in the diet is warranted, and that the data and methodology presented in this study are highly relevant for future integrated and multidisciplinary assessment of both risks and benefits of seafood consumption for human health.

Fillets from marine fish species contain n-3 polyunsaturated fatty acids (PUFAs) in the form of phospholipids (PLs). To investigate the importance of PL-bound n-3 PUFAs in mediating the anti-obesogenic effect of lean seafood, we compared the anti-obesogenic properties of fillets from cod with fillets from pangasius, a fresh water fish with a very low content of PL-bound n-3 PUFAs. We prepared high-fat/high-protein diets using chicken, cod and pangasius as the protein sources, and fed male C57BL/6J mice these diets for 12 weeks. Mice fed the diet containing cod gained less adipose tissue mass and had smaller white adipocytes than mice fed the chicken-containing diet, whereas mice fed the pangasius-containing diet were in between mice fed the chicken-containing diet and mice fed the cod-containing diet. Of note, mice fed the pangasius-containing diet exhibited reduced glucose tolerance compared to mice fed the cod-containing diet. Although the sum of marine n-3 PUFAs comprised less than 2% of the total fatty acids in the cod-containing diet, this was sufficient to significantly increase the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA) in mouse tissues and enhance production of n-3 PUFA-derived lipid mediators as compared with mice fed pangasius or chicken.

Purpose. Iodine is an essential trace element necessary for thyroid hormone synthesis. Iodine deficiency is a continuing public health problem despite international efforts to eliminate it. Studies on iodine status in preschoolers are scarce. Thus, the aims of the current study were to determine the iodine status and to investigate possible associations between urinary iodine concentration (UIC) and estimated 24 h iodine extraction (UIE) and iodine-rich foods. Methods. Data are cross-sectional baseline data, obtained from the two-armed randomized controlled dietary trial “Fish Intervention Studies-KIDS” (FINS-KIDS) conducted in Bergen, Norway. UIC was determined by inductively coupled plasma-mass spectrometry in spot urine samples. Inadequate UIC was defined as median

Background It studies on the factors that affect the stability of fatty acid profiles from human blood specimens are generally performed by evaluating the effect of a single factor on an individual fatty acid and excluding a considerable amount of data from the total fatty acid profiles. Methods The stability of fatty acids from plasma, serum and red blood cells (RBC) was evaluated in terms of time, temperature, antioxidant and thawing. The fatty acids were methylated and analyzed by gas chromatography. The large volume of data is evaluated simultaneously and automatically by observing an Excel-based colour scale that indicates whether the fatty acid profiles have changed significantly as a result of the storage time (0–52 weeks), temperature (− 20 °C/− 80 °C), butylated hydroxytoluene (BHT) antioxidant (presence/absence) or thawing (single/multiple). Results Fatty acids from plasma were stable at both temperatures (− 20 °C/− 80 °C) regardless of BHT. Fatty acids from serum without BHT degrades faster at − 80 °C than − 20 °C and fatty acids from RBC without BHT degrades faster at − 20 °C than − 80 °C. Addition of BHT inhibits this effect in serum and RBC. Multiple thawing of RBC without BHT demonstrated that polyunsaturated fatty acids were generally more susceptible for changes at − 80 °C than at − 20 °C while BHT prevents partially this effect. Conclusions This study draws attention to the importance of pre-analytical considerations when storing blood samples in biobanks and the need of careful judgments when analyzing fatty acids profiles.

The Norwegian Scientific Committee for Food and Environment (Vitenskapskomiteen for mat og miljø, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), evaluated the intake of manganese from the diet and 1, 5 or 10 mg manganese per day in food supplements. The former maximum limit for manganese in food supplements was 5 mg per daily dose. Manganese (Mn) is an essential dietary mineral for mammals, and is a component of metalloenzymes such as superoxide dismutase, arginase and pyruvate carboxylase. Manganese is involved in amino acid-, lipid- and carbohydrate metabolism and in proteoglycan synthesis in bone formation. In 2013, the European Food Safety Authority (EFSA) suggested 3 mg/day to represent an adequate intake (AI) of manganese because data was considered insufficient to set an average requirement (AR). Reports of adverse effects resulting from manganese exposure in humans are associated primarily with inhalation in occupational settings. Excess oral exposure to manganese, especially from contaminated water sources, has been shown to cause permanent neurological disorder known as “manganism” which can be irreversible. The amount of manganese absorbed is inversely related to the concentration of manganese in the diet. This regulation seems to be part of the adaptive changes to the amount of dietary manganese intake, which allow the maintenance of manganese homeostasis over a wide range of intakes. Manganese is mainly absorbed as Mn(II), and absorption is reported to be below 10% of ingested manganese. The main route of elimination of manganese from the body is via bile to the small intestine, while very little is excreted in the urine. Half-life for manganese can vary from 13 to 37 days, with a longer half-life in women than in men, but large inter-individual variation exists. In Norway, manganese content in drinking water is low, and does not contribute to any magnitude of manganese intake. Daily dietary intake of manganese in Norway is not known, but it is proposed that manganese intake is adequate in the Scandinavian countries (NNR Project Group, 2012). Results from the Swedish Market Basket study, 2015, indicate an average daily manganese intake of 4.2 mg per person and day. Calculations based on data from Denmark, 2013 and 2015, evaluate mean dietary intake of manganese to 3.9 mg/day for adults and up to 6.9 mg/day in the higher intake groups. EFSA report on an observed mean intake in EU around 3 mg/day for adults. Main contributor to dietary manganese intake is cereals (57%) followed by fruit, vegetables, nuts and coffee/tea. Irreversible neurotoxic adverse effects from intakes of manganese close to adequate intakes have been reported in humans (SCF, 2000). The Scientific Committee on Food (SCF) could not set a no observed adverse effect level (NOAEL), because no relevant dose-response animal studies were found. Consequently SCF did not set a tolerable upper intake level (UL) for manganese. VKM considers that any dose of manganese as an ingredient in food supplements may be associated with increased risk of negative health effects. VKM emphasises that the current assessment of maximum limits for manganese in food supplements is merely based on published reports concerning upper levels from the IOM (2001, USA), SCF (2003, EU), EVM (2003, UK) and NNR (2012, Nordic countries). VKM has not conducted any systematic review of the literature for the current opinion, as this was outside the scope of the terms of reference from NFSA.

The Norwegian Scientific Committee for Food and Environment (Vitenskapskomiteen for mat og miljø, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), evaluated the intake of vitamin K in the diet. VKM has also assessed the consequences of establishing maximum limits for vitamin K in food supplements at 100, 200, 300, 600 or 800 µg/day. The former maximum limit for vitamin K of 200 µg/day in food supplements was repealed 30 May 2017. Vitamin K is a fat-soluble vitamin required for the carboxylation of glutamic acid residues in proteins that regulate blood coagulation and bone metabolism. The naturally occurring forms of vitamin K present in food and supplements are phylloquinone (vitamin K1) mainly produced by plants, and a range of menaquinones (vitamin K2) mainly produced by bacteria. The chemical structure of vitamin K is characterised by a methylated naphtoquinone ring structure assumed to be responsible for its function, in addition to a side chain which differs in length and degree of saturation. Due to the varying side chains, the different forms of vitamin K are thought to behave differently with regard to absorption, metabolism, bioavailability and thereby also toxic potential. Dark green leafy vegetables are rich sources of phylloquinone. Meat and liver products provide menaquinone-4, the most common menaquinone in Western diets, while other menaquinones are found in fermented foods and cheese. An Adequate Intake (AI) of phylloquinone of 1 µg/kg body weight per day was set by the Scientific Committee on Food (SCF) in 1993 and maintained by the European Food Safety Authority (EFSA) in 2017. No dietary reference values (DRVs) have been established for menaquinones due to insufficient evidence. Furthermore, no tolerable upper intake levels (ULs) have been established for any form of vitamin K due to insufficient evidence, but previous reports stated that no adverse effects associated with vitamin K consumption from food or supplements had been reported in humans or animals. In 2003, the UK Expert Group on Vitamins and Minerals (EVM) proposed a guidance level (GL) for safe upper intake of supplemental phylloquinone of 1 mg/day in adults. The GL was set by applying an uncertainty factor of 10 for inter-individual variation to the supplemental dose of 10 mg/day that had been consumed by eight female athletes (age 20-44) for 30 days with no reported adverse effects. The UK expert group emphasised that GLs had been derived from limited data and were less secure than safe upper levels. This GL was supported by a double-blind randomised study cited in the Nordic Nutrition Recommendations (2012), in which 440 postmenopausal women with osteopenia received a daily supplement of 5 mg phylloquinone or placebo for up to four years with no difference in adverse events between the randomised groups. Corresponding GLs for children and adolescents have been derived by adjusting for reference body weights0.75 by Rasmussen et al. (2006). The distribution of intakes of vitamin K across age groups in Norway is not known, since food composition data is not available. However, habitual intakes in a representative sample of middle-aged and older adults in Western Norway were assessed in the population-based Hordaland Health Study 1997-2000, and revealed higher intakes than those estimated from dietary surveys in the other Nordic countries. Due to lack of representative estimates of vitamin K intakes in the Norwegian population, information on vitamin K intakes from other Nordic countries is included in the current opinion. This includes the distribution of vitamin K intakes in Sweden and Finland reported by EFSA, and the distribution of vitamin K intakes in Denmark, assessed by the Technical University of Denmark (DTU). In middle-aged and older Western Norwegians participating in the Hordaland Health Study 1997-2000, estimated mean intakes of total vitamin K (denoting the sum of K1+K2) ranged from 109 to 148 µg/day in four groups based on age and gender, while the 95-percentiles ranged from 261 to 329 µg/day. Average intakes of total vitamin K in the other Nordic countries are in the magnitude of 100 µg/day in adults, while 95-percentiles in adults are in the magnitude of 200 µg/day. To illustrate the consequences of establishing maximum limits for vitamin K at 100, 200, 300, 600 or 800 µg/day in food supplements, VKM has compared these levels to the age-specific GLs for supplemental phylloquinone proposed by EVM (2003). The GLs are: 1000 µg/day for adults, 870 µg/day at age 15-17 years, 670 µg/day at age 11-14 years, 500 µg/day at age 710 years, 370 µg/day at age 4-6 years and 270 µg/day at age 1-3 years. VKM concludes that: In adults and adolescents 15-17 years old, maximum limits of 100, 200, 300, 600 and 800 µg/day are below GL. In adolescents 11-14 years old, maximum limits of 100, 200, 300 and 600 µg/day are below GL while the maximum limit of 800 µg exceeds GL. In children 4-10 years old, maximum limits of 100, 200 and 300 µg/day are below GL while maximum limits of 600 µg/day and 800 µg/day exceeds GL. In children 1-3 years old, maximum limits of 100 µg/day and 200 µg/day are below GL while maximum limits of 300, 600 and 800 µg/day exceeds GL. VKM notes that the current conclusions apply to phylloquinone (vitamin K1) only, while there is insufficient evidence to appraise potential health consequences of maximum limits of menaquinones (vitamin K2). VKM emphasises that the current assessment of maximum limits for vitamin K in food supplements is merely based on published reports concerning upper levels from the IOM (2001, USA), SCF (2003, EU), EVM (2003, UK) and NNR (2012, Nordic countries). VKM has not conducted any systematic review of the literature for the current opinion, as this was outside the scope of the terms of reference from NFSA.

Aims: To describe the rationale, study design, population and dietary compliance in a randomized controlled trial (RCT) investigating the effect of fatty fish on cognitive performance and mental health in adolescents. Method: In the Fish Intervention Studies-TEENS (FINS-TEENS) study we individually randomized 478 adolescents (14–15-year-olds) from eight secondary schools in Norway to receive school meal lunches with fatty fish or meat or n-3 supplements three times a week for 12 weeks. Demographic factors, psychological tests and biological measures were collected pre-and post-intervention. Duplicate portions of lunch meals were collected and individual intake recorded throughout the study. Results: In total, 481 out of 785 adolescents (61%) agreed to participate and 34 (7%) dropped out. Breakfast consumption was the only group difference in background characteristics. Analyses of selected nutrients in the lunch meals showed higher levels of n-3 fatty acids, vitamin D and n-6 fatty acids in the fish compared to the meat meals. Dietary compliance (score 0–144) revealed that the intake in the Fish group (mean = 59, standard deviation (SD) = 35) were lower than in the Meat group (mean = 83, SD = 31, p < 0.01) and Supplement group (mean = 105, SD = 25, p < 0.01). Conclusions: The results show that it is possible to conduct a RCT with fatty fish in a school-based setting. The results also emphasize the importance of collecting detailed records of dietary compliance, as this information is important when interpreting and analysing the outcome of dietary interventions.