Search

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 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 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 the addition of "other substances" to food supplements and other foods. "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. 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 limited to the use of L-tyrosine in food supplements. Risks related to tyrosine added to food and drinks, protein hydrolysates or high dietary protein intake are outside the scope of the opinion. The report is based on previous risk assessments of tyrosine and scientific papers retrieved from a comprehensive literature search. L-tyrosine, an aromatic amino acid, is considered a conditionally indispensable amino acid because it can be synthesised from L-phenylalanine in the liver. The magnitude of endogenous synthesis of L-tyrosine is not known, but is related to the intake of phenylalanine. L-tyrosine is a precursor of several biologically active substances, including catecholamine neurotransmitters, thyroid hormones and melanin skin pigments. L-tyrosine is available from all protein-containing foods such as meat, eggs, fish, dairy products, grains and pulses. According to information from the NFSA, L-tyrosine is an ingredient in food supplements sold in Norway. The NFSA has requested a risk assessment of the following doses of L-tyrosine food supplements: 1250 mg/day, 1500 mg/day, 1750 mg/day, and 2000 mg/day. Dietary intake of tyrosine in Norway is not known, but data from NHANES III (USA) suggest a mean dietary intake of about 2.8 g per day. In phase 1 seven previous reports that assessed the safety of L-tyrosine supplementation in humans were identified. For the present report, a literature search was performed to retrieve relevant human or animal studies on the safety of L-tyrosine. One relevant animal study assessing the toxicity of tyrosine by feeding rats different doses of tyrosine daily by oral gavage for 13 weeks was identified. No human studies have been identified. No major specific issues related to adverse effects from L-tyrosine used as food supplements were identified in previous reports. However, a lack of studies in healthy adult individuals as well as in children was pointed out, and in particular the absence of long-term studies in healthy individuals. A lowest observed adverse effect level (LOAEL) and a no observed adverse effect level (NOAEL) of 2000 and 600 mg/kg bw per day, respectively, for tyrosine have been identified in a 90-day toxicological study in rats. At 2000 mg/kg bw per day, significant increases, were found in weights of livers and kidneys in addition to increased plasma lipids and hypertrophy of centrilobular hepatocytes in both sexes. The NOAEL at 600 mg/kg per day was used to calculate the margin of exposure (MOE), the ratio of the NOAEL to the specified doses of 1250, 1500, 1750 and 2000 mg/day of Ltyrosine in food supplements. The MOE-values range from 13 for the highest supplement dose in children to 34 for the lowest supplement dose in adults. Given the low MOE-values (range 13-34), and the severity of the adverse effects at the LOAEL (3.3 times the NOAEL), VKM concludes that all the specified doses may represent a risk of adverse effects. No evidence was found to assume specific tolerance levels for L-tyrosine for children or adolescents. Therefore, a similar tolerance as for adults relative to body weight was assumed for these age groups. Based on these data, the Norwegian Scientific Committee for Food Safety (VKM) concludes that: In adults (≥18 years), the specified doses of 1250, 1500, 1750, and 2000 mg/day Ltyrosine 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 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.

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

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.

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

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.

"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, and may be added to food supplements or e.g. energy drinks. In the series of risk assessments of "other substances" the VKM has not evaluated any claimed beneficial effects from these substances, but merely possible adverse effects at specified doses used in Norway. This statement regards the substance L-methionine per se, and no specific products. According to information from the Norwegian Food Safety Authority (NFSA), L-methionine is an ingredient in food supplements sold in Norway. NFSA has requested a risk assessment of the intake of 200, 300, 500, 600 and 700 mg L-methionine per day from food supplements. The total L-methionine exposure from other sources than food supplements is not included in the risk assessment. This statement is based on a previous risk assessment from VKM of L-methionine, as well as scientific papers retrieved from a systematic search in literature published from 2012 up till 19 February 2016. The literature search aimed at retrieving human studies on adverse effects caused by L-methionine. VKM concludes that: VKM maintains the guidance level from 2013 at 210 mg methione per day.

Objectives The aims of this study were to determine vitamin D status (serum 25-hydroxyvitamin D3 [s-25(OH)D3]) and examine possible associations between vitamin D status and vitamin D–rich dietary sources, sun exposure, and body mass index in preschool children ages 4 to 6 y. Methods This is a cross-sectional study based on baseline data (collected in January-February 2015) from the two-armed randomized controlled trial Fish Intervention Studies-KIDS (FINS-KIDS) conducted in Bergen, Norway. S-25(OH)D3 concentration was determined by liquid chromatography–tandem mass spectrometry. Information regarding habitual dietary intake, recent sun vacations, and body mass index were assessed with questionnaires answered by the children's caregivers. Results The children (n = 212) had a mean (standard deviation) s-25(OH)D3 of 60.7 (13.8) nmol/L; 18.9% had s-25(OH)D3 ≤50 nmol/L. In logistic regression models, non-overweight versus overweight status was inversely associated with s-25(OH)D3 ≤50 nmol/L (odds ratio: 0.41; 95% confidence interval, 0.18–0.95; P = 0.037). Non-sun versus sun vacations were associated with s-25(OH)D3 ≤75 nmol/L (odds ratio: 5.33; 95% confidence interval, 1.93–14.77; P = 0.001). Conclusions The majority of the preschool children (81%) had s-25(OH)D3 >50 nmol/L. Children with overweight status had an increased risk of s-25(OH)D3 ≤50 nmol/L, and children who had not been on sun vacations were at a greater risk of s-25(OH)D3 ≤75 nmol/L.

// Ingvild Eide Graff 1 , Jannike Oyen 1 , Marian Kjellevold 1 , Livar Froyland 1 , Clara Gram Gjesdal 2,3 , Bjorg Almas 4 , Grethe Rosenlund 5 and Oyvind Lie 1 1 National Institute of Nutrition and Seafood Research (NIFES), Bergen, Norway 2 Department of Rheumatology, Haukeland University Hospital, Bergen, Norway 3 Department of Clinical Science, University of Bergen, Bergen, Norway 4 Hormone Laboratory, Haukeland University Hospital, Bergen, Norway 5 Skretting Aquaculture Research Centre, Stavanger, Norway Correspondence to: Jannike Oyen, email: // Keywords : Atlantic salmon, bone health, vitamin D, vitamin K, bone biomarkers, Gerotarget Received : March 09, 2016 Accepted : June 09, 2016 Published : August 14, 2016 Abstract Suboptimal vitamin D status is common among humans, and might increase bone resorption with subsequent negative effects on bone health. Fatty fish, including Atlantic salmon, is an important dietary vitamin D source. However, due to a considerable change in fish feed composition, the contribution of vitamin D from salmon fillet has been reduced. The main objective was to investigate if intake of vitamin D 3 enriched salmon or vitamin D 3 tablets decreased bone biomarkers (urinary N-telopeptides, deoxypyridinoline, serum bone-specific alkaline phosphatase, and osteocalcin) compared to a low vitamin D 3 intake. The 122 healthy postmenopausal women included in this 12 weeks intervention trial were randomized into four groups: three salmon groups (150 grams/two times/week) and one tablet group (800 IU vitamin D and 1000 mg calcium/day). The salmon groups also received calcium supplements. The salmon had three different vitamin D 3 /vitamin K 1 combinations: high D 3 +high K 1 , low D 3 +high K 1 , or high D 3 +low K 1 . Increased intake of salmon containing high levels of vitamin D 3 (0.35-0.38 mg/kg/fillet) and supplements with the same weekly contribution had a positive influence on bone health as measured by bone biomarkers in postmenopausal women. Consequently, an increased level of vitamin D 3 at least to original level in feed for salmonids will contribute to an improved vitamin D 3 status and may improve human bone health.

The European Food Safety Authority (EFSA) published a risk assessment of erucic acid (22:1n-9) in 2016, establishing a Tolerable Daily Intake (TDI) for humans of 7 mg kg&minus, 1 body weight per day. This report largely excluded the contribution of erucic acid from fish and seafood, due to this fatty acid often not being reported separately in seafood. The Institute of Marine Research (IMR) in Norway analyzes erucic acid and has accumulated extensive data from analyses of fish feeds, farmed and wild fish, and seafood products. Our data show that rapeseed oil (low erucic acid varieties) and fish oil are the main sources of erucic acid in feed for farmed fish. Erucic acid content increases with total fat content, both in farmed and wild fish, and it is particularly high in fish liver, fish oil, and oily fish, such as mackerel. We show that the current TDI could be exceeded with a 200 g meal of mackerel, as at the maximum concentration analyzed, such a meal would contribute 143% to the TDI of a 60 kg person. These data cover a current knowledge gap in the scientific literature regarding the content of erucic acid in fish and seafood.

Background: Adolescence involves changes in dietary habits that may induce imbalances in the intake of different nutrients. Fish is an important dietary source of omega-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFAs), vitamin D, several minerals and high-quality protein. By using secondary outcomes and exploratory analyses, the aims of this paper were to evaluate if nutritional biomarkers (red blood cell fatty acids, serum (s)-25(OH)D, s-ferritin and urinary iodine concentration (UIC)) were altered during a dietary intervention, and if they mediated previously reported changes in attention performance. In addition, to examine the status of the biomarkers and explore associations between dietary pattern, biomarkers and attention performance cross-sectionally at baseline. Methods: The Fish Intervention Studies-TEENS (FINS-TEENS) was a three-armed intervention trial, including adolescents from eight secondary schools (n = 415; age: 14–15y) in Bergen, Norway. Participants were individually randomized to receive either fish meals, meat meals or n-3 LCPUFA supplements, three times a week for a total of 12 weeks. Blood and urine samples were collected pre and post intervention and attention performance was assessed with the d2 test of attention. Analyses of covariance (ANCOVA) assessed differences between groups in changes of biomarkers and linear mixed models were applied in analyses of attention performance and biomarkers. The trial is registered in ClinicalTrials.gov (NCT02350322). Results: At baseline, the mean omega-3 index was 5.8 ± 1.3% and deficient status were identified for s-25(OH)D (54%), s-ferritin (10%) and UIC (40%). The intervention resulted in an increase in DHA and the omega-3 index which was larger in the supplement group compared to the fish and meat group (P < 0.01), and in the fish group compared to the meat group (P < 0.01). No differences between the groups were observed for changes in 25(OH)D, s-ferritin or UIC. None of the biomarkers mediated performance in the d2 test. The intake of fatty fish and a healthy dietary pattern was associated with scores in processing speed at baseline. Conclusions: These results show that Norwegian adolescents have insufficient status of important nutrients, which may be improved with fatty fish consumption or n-3 LCPUFA supplements. However, nutritional status was not associated with scores in the d2 test of attention. publishedVersion

Background Marine resources including fatty fish are important sources of n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFAs), which are important for brain development. To our knowledge, this is the first randomized controlled trial (RCT) investigating the impact of fatty fish on cognition in preschool children. The purpose of the trial was to investigate whether an increased intake of fatty fish compared to meat improves cognitive function in children 4–6 years old. Methods The children (n = 232) in this two-armed RCT, Fish Intervention Studies-KIDS (FINS-KIDS) were recruited from 13 kindergartens in Bergen, Norway. They were randomly assigned to lunch meals with fatty fish (herring/mackerel) or meat (chicken/lamb/beef) three times a week for 16 weeks. The fish and meat were weighed before and after the meals to record the exact consumption (dietary compliance). The primary outcome was cognitive function measured by the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition (WPPSI-III) and fine-motor coordination measured by the 9-Hole Peg Test (9-HPT) at pre- and post-intervention. Biological samples (blood, urine, hair), and questionnaires to the caregivers were included at both time points. Linear mixed effect models with a random intercept for kindergarten were used to analyze changes from pre- to post-intervention in the primary outcome variables. Results There were 218 children included in the trial (105 in the fish, and 113 in the meat group). The children consumed a mean (standard deviation) of 2070 (978) g fish or 2675 (850) g meat from the study meals (p < 0.0001). The fish group had a significant increase of red blood cell n-3 LC-PUFAs. The intervention had no effect on the WPPSI-III scores (mean change total raw score; fish group 17.7, 95% confidence interval (CI) 14.8–20.7 vs meat group 17.8, 95% CI 15.0–20.6, p = 0.97) in the main analyses. In the sub-analyses, adjusting for dietary compliance, the fish group showed a higher improvement on total raw score (20.4, 95% CI 17.5–23.3) compared to the meat group (15.2, 95% CI 12.4–18.0, p = 0.0060); docosahexaenoic acid mediated this effect. Conclusions There was no beneficial effect of fatty fish compared to meat on cognitive functioning in the preschool children. When considering dietary compliance, we found a beneficial effect of fatty fish on cognitive scores. Trial registration ClinicalTrials.gov, NCT02331667 December 17, 2014. Electronic supplementary material The online version of this article (10.1186/s12916-018-1020-z) contains supplementary material, which is available to authorized users.

Request from the Norwegian Food Safety Authority (NFSA) In September 2013, the Norwegian Food Safety Authority requested VKM to update relevant parts of the benefit-risk assessment of fish in the Norwegian diet published by VKM in 2006. The background for the request was new knowledge and data on the content of some nutrients and contaminants both for wild and farmed fish since 2006. The proportion of vegetable ingredients used in farmed fish feed has in recent years increased, and new national dietary surveys for adults and children have been conducted. The Norwegian Food Safety Authority referred to VKM’s report from 2006, which pointed out that the positive impact of fish consumption on public health was especially due to the content of polyunsaturated fatty acids and vitamin D in fish. Further, VKM concluded that the contaminants that could pose a potential risk to public health through fish consumption mainly were methylmercury, dioxins and dioxin-like PCBs (dl-PCBs). Grey Literature Skare et al.; EJNFS, 5(4): 260-266, 2015; Article no.EJNFS.2015.023 261 The request included a reassessment of fish consumption in Norway with focus on specific nutrients; n-3 fatty acids (eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), vitamin D, and the minerals iodine and selenium, and on specific contaminants; mercury, dioxins and dl-PCBs. VKM was asked to address the main changes in the use of raw materials in farmed fish feed and how these affect the levels of nutrients, mercury, dioxins and dl-PCBs and in fish feed. Further, VKM was asked to address to what extent levels of nutrients and contaminants in fish have changed since 2006, to describe these changes and estimate the human intake of the substances in question on the basis of recent dietary data. VKM was also requested to consider the benefits of eating fish with regard to the intake of nutrients and the risks associated with the intake of mercury, dioxins and dl-PCBs and comment on whether this change the conclusions from the report in 2006. Additionally, on the basis of updated knowledge, VKM was asked to comment whether other substances, like pesticide and residues of veterinary medicinal products, could affect the conclusions with regard to the impact on public health. The Norwegian Food Safety Authority and the Directorate of Health will use the updated assessment as a basis for public recommendations concerning the consumption of fish and fish products. How VKM has Addressed the Request The VKM appointed a working group consisting of VKM members and external experts to answer the request. Several of the scientific panels of VKM reviewed the report during its preparation. The Scientific Steering Committee of VKM has given their final assessment and approval of the current report. In the current report, VKM has mainly used data from national surveillance and monitoring programs for nutrient and contaminant concentrations in fish feed, farmed fish and wild caught fish, but occurrence data have also been derived from peer reviewed articles. VKM has estimated fish consumption in three population groups (2-year-olds, adults and pregnant women). The estimated fish consumption was compared to national dietary guidelines. To assess health effects of fish consumption, the current estimated fish intakes were also compared with assessments done by recognised international bodies and results from epidemiological studies addressing possible associations between fish consumption and specific health outcomes. Literature searches were done to identify relevant epidemiological studies. VKM has not systematically assessed reviews or meta-analyses nor individual studies for weight of evidence, but merely summarised the studies retrieved from the literature search. It was considered being beyond the scope of this assessment to review individual studies included in reviews or meta-analyses. Furthermore, based on current fish consumption in the various population groups, intake of nutrients and exposure to contaminants from fish were estimated. For benefit characterisation of the specific nutrients the estimated nutrient intake was compared with national recommendations of nutrients intake and for EPA and DHA a comparison was also done with European recommendations. For risk characterization of contaminant exposure from fish, VKM used health based guidance values set by international risk assessment bodies (WHO, EFSA). VKM noted that the request from NFSA was restricted to fish, whereas the VKM report in 2006 included both fish and other seafood. VKM focused on specific nutrients and contaminants as requested by the NFSA. In addition, VKM also commented on other substances that could affect the risk assessment, such as residues of veterinary medicinal products including residues of antibiotics, new contaminants from fish feed like the pesticide endosulfan, polycyclic aromatic hydrocarbons (PAHs), mycotoxins, the synthetic antioxidants ethoxyquin, butylhydroxyanisole (BHA) and butylhydroxytoluene (BHT), as well as environmental contaminants like brominated flame retardants and perfluorated organic compounds. Skare et al.; EJNFS, 5(4): 260-266, 2015; Article no.EJNFS.2015.023

This study investigated the effects of fatty fish on sleep, daily functioning and biomarkers such as heart rate variability (HRV), vitamin D status (serum 25-hydroxyvitamin D (25OHD), and eicosapentaenoic acid (EPA, 20:5n-3) + docosahexaenoic acid (DHA, 22:6n-3) in red blood cells. Moreover the relationship among sleep, daily functioning, HRV, vitamin D status, and levels of EPA+DHA was investigated.Ninety-five male forensic patients from a secure forensic inpatient facility in the USA were randomly assigned into a Fish or a Control group. The Fish group received Atlantic salmon three times per week from September to February, and the Control group was provided an alternative meal (e.g., chicken, pork, beef), but with the same nutritional value as their habitual diet, three times per week during the same period. Sleep (sleep latency, sleep efficiency, actual sleep time, and actual wake time), self-perceived sleep quality and daily functioning, as well as vitamin D status, EPA+DHA, and HRV, were assessed pre- and post-intervention period.There was a significant increase in sleep latency from pre- to post-test in the Control group. The Fish group reported better daily functioning than the Control group during post-test. Fish consumption throughout the wintertime had also an effect on resting HRV and EPA+DHA, but not on vitamin D status. However, at post-test, the vitamin D status in the Fish group was still closer to the level regarded as optimal compared to the Control group. Vitamin D status correlated negatively with actual wake time and positively with sleep efficiency during pre-test, as well as positively with daily functioning and sleep quality during post-test. Finally, HRV correlated negatively with sleep latency and positively with daily functioning.Fish consumption seemed to have a positive impact on sleep in general and also on daily functioning, which may be related to vitamin D status and HRV.

Assessment of adolescents’ dietary habits is challenging. Reliable instruments to monitor dietary trends are required to promote healthier behaviours in this group. The purpose of this cross-sectional study was to assess adolescents’ adherence to Norwegian dietary recommendations with a diet score and to report results from, and test-retest reliability of, the score. The diet score involved seven food groups and one physical activity indicator, and was applied to answers from a semi-quantitative food frequency questionnaire (FFQ) administered twice. Reproducibility of the score was assessed with Cohen’s Kappa (κ statistics) at an interval of three months. The setting was eight lower-secondary schools in Hordaland County, Norway, and subjects were adolescents (n = 472) aged 14–15 years and their caregivers. Results showed that the proportion of adolescents consistently classified by the diet score was 87.6% (κ = 0.465). For food groups, proportions ranged from 74.0% to 91.6% (κ = 0.249 to κ = 0.573). Less than 40% of the participants were found to adhere to recommendations for frequencies of eating fruits, vegetables, added sugar, and fish. Highest compliance to recommendations was seen for choosing water as beverage and limit the intake of red meat. The score was associated with parental socioeconomic status. The diet score was found to be reproducible at an acceptable level. Health promoting work targeting adolescents should emphasize to increase the intake of recommended foods to approach nutritional guidelines.

Adequate iodine concentration in breastmilk (BMIC) is essential for optimal neonatal thyroid hormone synthesis and neurological development in breastfed infants. For many decades, iodine deficiency has been a public health problem in Nepal. However, recently, excessive iodine intakes among Nepali infants have been reported. This study aimed to measure BMIC and urinary iodine concentration (UIC) among lactating women in a peri-urban area of Nepal. Iodine concentration was measured in spot urine (n = 485) and breastmilk samples (n = 291) of 500 randomly selected lactating women. The median (p25, p75) BMIC and median UIC were 250 (130, 370) µg/L and 230 (135–377) µg/L, respectively. Around 82% had BMIC > 100 µg/L, 61% had BMIC > 200 µg/L and 81% had UIC > 100 µg/L, 37% had >300 µg/L and 20% had >500 µg/L. In multiple linear regression models, time since birth (β 3.0, 95% CI (0.2, 5.0)) and UIC (β 1.0, 95% CI (0.1, 2.0)) were associated with BMIC, explaining 26% of the variance. A large proportion of the women had adequate BMIC and UIC; however, a subset had high iodine concentrations. These findings emphasize the importance of carefully monitoring iodine intake to minimize the risk of iodine excess and subsequently preventing transient iodine-induced hypothyroidism in breastfed infants. publishedVersion

STUDY DESIGN: A randomized controlled trial. OBJECTIVE: The aim of this study was to evaluate whether a tailored and manualized cognitive behavior therapy (CBT) or nutritional supplements of seal oil and soy oil had any additional benefits over a brief cognitive intervention (BI) on return to work (RTW). SUMMARY OF BACKGROUND DATA: Brief intervention programs are clinically beneficial and cost-effective for patients with low back pain (LBP). CBT is recommended for LBP, but evidence on RTW is lacking. Seal oil has previously been shown to have a possible effect on muscle pain, but no randomized controlled trials have so far been carried out in LBP patients. METHODS: Four hundred thirteen adults aged 18 to 60 years were included. Participants were sick-listed 2 to 10 months due to LBP. Main outcome was objectively ascertained work participation at 12-month follow-up. Participants were randomly assigned to BI (n = 100), BI and CBT (n = 103), BI and seal oil (n = 105), or BI and soy oil (n = 105). BI is a two-session cognitive, clinical examination program followed by two booster sessions, while the CBT program is a tailored, individual, seven-session manual-based treatment. RESULTS: At 12-month follow-up, 60% of the participants in the BI group, 50% in the BI and CBT group, 51% in the BI and seal oil group, and 53% in the BI and soy oil group showed reduced sick leave from baseline, and had either partly or fully RTW. The differences between the groups were not statistically significant (χ = 2.54, P = 0.47). There were no significant differences between the treatment groups at any of the other follow-up assessments either, except for a significantly lower sick leave rate in the BI group than the other groups during the first 3 months of follow-up (χ = 9.50, P = 0.02). CONCLUSION: CBT and seal oil had no additional benefits over a brief cognitive intervention on sick leave. The brief cognitive intervention alone was superior in facilitating a fast RTW. Cognitive Interventions and Nutritional Supplements (The CINS Trial): A Randomized Controlled, Multicenter Trial Comparing a Brief Intervention with Additional Cognitive Behavioral Therapy, Seal Oil, and Soy Oil for Sick-Listed Low Back Pain Patients The Research Council of Norway, the GC Rieber Funds and Mills DA funds were received in support of this work.

Dietary intervention studies to assess the cardioprotective effects of oily fish are scarce in China. The present study aimed to examine the effects of the oily fish, Norwegian salmon, herring and local farmed pompano (Trachinotus ovatus) on CVD risk markers when included in the Chinese diet. In this 8-week, parallel-arm, randomised intervention study, 126 Chinese women with hypertriacylglycerolaemia, aged 35–70 years, were assigned to four groups to consume an experimental lunch containing 80 g fillets of either one of three oily fish or a mix of commonly eaten meats (pork/chicken/beef/lean fish) for 5 d/week. The results showed that inclusion of the three oily fish significantly increased the intake ofn-3 long-chain PUFA (LC-PUFA) while decreasing the dietaryn-6:n-3 PUFA ratio. Compared to the control group, significant increases of DHA, EPA+DHA and totaln-3 PUFA in plasma choline phosphoglyceride were observed in the three oily fish groups. Plasma TAG levels were significantly reduced only in the salmon and herring groups. When compared to the baseline level, the three oily fish diets significantly decreased serum concentrations of TAG, apoB, apoCII and apoCIII, but only the salmon and herring diets significantly lowered TNF-α and raised adiponectin levels in serum. The salmon diet additionally decreased the serum concentration of IL-6. To conclude, dietary inclusion of salmon, herring and pompano as oily fish can effectively increase serumn-3 LC-PUFA content and are associated with favourable biochemical changes in dyslipidaemic middle-aged and elderly Chinese women, and these beneficial effects are mainly associated withn-3 LC-PUFA contents.

Docosahexaenoic acid (DHA, 22:6, n-3) is a long-chain polyunsaturated fatty acid necessary for normal brain growth and cognitive development. Seafood and dietary supplements are the primary dietary sources of DHA. This study addresses the associations between DHA status in pregnant women and healthy, term-born infant problem-solving skills assessed using the Ages and Stages Questionnaire. The fatty acid status of maternal red blood cells (RBCs) was assessed in the 28th week of gestation and at three months postpartum. The infants’ fatty acid status (RBC) was assessed at three, six, and twelve months, and problem-solving skills were assessed at six and twelve months. Maternal DHA status in pregnancy was found to be positively associated with infants’ problem-solving skills at 12 months. This association remained significant even after controlling for the level of maternal education, a surrogate for socio-economic status. The infants’ DHA status at three months was associated with the infants’ problem solving at 12 months. The results accentuate the importance for pregnant and lactating women to have a satisfactory DHA status from dietary intake of seafood or other sources rich in DHA.

The present study investigates the impact of seafood intake on biological markers in blood such as the marine very long-chain polyunsaturated omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), 25-hydroxyvitamin D (25(OH)D), in addition to heart rate variability (HRV), which is an important biological marker of good health, both physical and mental. A total of 53 male inmates from a Norwegian prison were randomly assigned to intervention and control groups, although attrition reduced some comparisons at the end of the study to 13 (intervention group (n = 6) and control group (n = 7). The intervention group received seafood (mainly fatty fish, > 8% fat) for dinner three times per week for a period of 6 months. Both groups were requested to eat their usual diet provided by the prison. Blood samples were collected and HRV (high frequency (HF) and low frequency (LF) power) was measured before and after the study period. Overall, the intervention group showed significant increase in levels of 25(OH)D and HF-power, and a significant reduction in the sympathovagal balance (LF/HF). The present findings may have important implications with regard to health improvement.

An approach to the estimation of possible different sources of variation found in proficiency testing experiments is described. Four errors namely, technique, analyst, laboratory and geographical location are considered and calculated by using a rational experimental design based on hierarchical classification. The treatment of the confidence of the design over different experimental arrangements is explored and visualised by calculating a function that depends only on the design and not on the experimental response. An illustrative example based on simulated data is used to show how the theory could be applied in practice.

Whilst human and animal experimentation receives much attention every year by the general media, the public and the scientific community, little has been done on how to reduce the number of living subjects to be submitted to experimental research. Researchers who design human and animal experiments are conscious that trials on such subjects present a problem, which is not only scientific, but also ethical. The national research and ethics committees regulate the selection and number of patients or mammals to be treated and make the justification of the number of living subjects an aspect of paramount importance in different scientific disciplines. However, a rational methodology to estimate a sensible number that is in accordance with the parameters of the Association of Research Ethics Committees has not been well explored. In this article, a simple statistical approach for the study of the confidence in a model is proposed. The approach can pave the way to a potentially useful method to estimate a sensible number of subjects which is in accordance with the general principles of ethical bodies from all over the world.

Atlantic salmon were sampled in June, September and February of the consecutive year and were stored on ice for up to 14 days in order to test the effect of harvest time and subsequent ice storage on meat quality. Texture and gaping frequency were analysed and were related to colour, protein degradation, collagen solubility, collagen types and final pH as well as lipid oxidation in the fillets to test possible interactions between harvest time and quality degradation during storage. In February, the connective tissue contained more soluble collagen and less insoluble collagen, as well as more of both types I and V collagen, than in the samples collected in June. During ice storage, fish became softer with a concomitant increase in the number of fish displaying very high gaping. pH increased during ice storage and fillet colour became lighter and redder, while yellowness changed in the fattier fillets upon ice storage. Ice storage resulted in changes in pepsin-soluble collagen (PSC) depending on harvest time as did both types I and V collagen. The softer the fish, the higher the gaping score and the more insoluble collagen, the less gaping occurred.