ABSTRACT
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 The former maximum limit for vitamin K of 200 µg/day in food supplements was repealed 30 May 2017.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.
ABSTRACT
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 molybdenum. VKM has also conducted scenario calculations to illustrate the consequences of amending maximum limits for molybdenum to 100, 250, 500 or 1000 µg/day in food supplements. The previous maximum limit was 250 µg/day. Molybdenum is as a cofactor for some important enzymes in humans. These enzymes are involved in the catabolism of sulfur amino acids and heterocyclic compounds, including purines and pyridines. A distinct molybdenum deficiency has not been described in animals when subjected to molybdenum restriction, despite considerable reduction in the activity of molybdoenzymes. Molybdenum deficiency is not observed in healthy humans. The estimated Adequate Intake (AI) proposed by the European Food Safety Authority (EFSA) is 65 µg per day for men and women. Legumes, grains, and nuts are major contributors of molybdenum in the diet. Molybdenum is a potential antagonist to copper absorption, but symptoms of copper deficiencies due to excess molybdenum intake have only been observed in ruminants. Based on the effect on reproduction and growth in animals, tolerable upper intake levels (ULs) have been estimated to be 2 mg/day by the U.S. Institute of Medicine (IOM) in 2001 and 0.6 mg/day by the Scientific Committee on Food (SCF) in 2000. These ULs were based on the same scientific evidence, but IOM used an uncertainty factor (UF) of 30 and SCF used a UF of 100 because the evidence base was considered to be weak. Because of the limited safety data on molybdenum, VKM support the use of the default uncertainty factors at 100 for extrapolation of data from animal studies to humans. Additionally, molybdenum deficiency is very rare and no studies have indicated a nutritional need for additional molybdenum from dietary supplements. The ULs for children were derived by adjusting the adult UL according to default body weights. According to the scenario estimations, only the highest suggested maximum limit of 1000 µg molybdenum from food supplements will lead to exceedance of the UL for adults. For 1-3 year old children, all the suggested maximum limits for molybdenum will lead to exceedance of the UL. In children 4-10 years, supplements with 250, 500 or 1000 µg molybdenum will lead to exceedance of the ULs, whereas for adolescents 11-17 years, the UL will be exceeded with supplemental doses at 500 or 1000 µg per day. VKM emphasises that the current assessment of maximum limits for molybdenum in food supplements is merely based on published reports concerning upper levels from the SCF (2000, EU), IOM (2001, USA), 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.
ABSTRACT
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.
ABSTRACT
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 associated with magnesium in food supplements. VKM is requested to evaluate upper tolerable intake levels for magnesium and high and low intakes in the Norwegian population. Pending establishment of common maximum limits in the EU, the NFSA is evaluating the national maximum limits for vitamins and minerals in food supplements. This risk assessment is the scientific basis for NFSA's evaluation of national limits for magnesium. Directive 2002/46/EC on food supplements was implemented in Norwegian law in 2004 in Regulation 20 May 2004 No. 755 on food supplements. Common maximum and minimum levels of vitamins and minerals in food supplements shall be set in the EU. Until common limits are established in the EU, the national limits apply. The present report is a risk assessment of magnesium in food supplements. It is based on published articles retrieved from literature searches and previous risk assessments of magnesium. Magnesium is an essential alkaline mineral and occurs as free cation Mg2+ in aqueous solution, or as the mineral part of a large variety of compounds such as chlorides, carbonates and hydroxides. Dietary sources of magnesium include green leafy vegetables, legumes, whole grain cereals, dark chocolate, nuts, fish and seafood, banana and coffee. NFSA has especially requested VKM to consider water as a source of magnesium. A few waterworks reported magnesium concentrations at 10 mg/L. Consumption of water from these waterworks may contribute up to 10% of recommended magnesium intake. However, most waterworks reported negligible magnesium concentrations. Magnesium has multiple functions in the body; it is a required cofactor for more than 300 enzyme systems in the body; for energy-dependent membrane transport, for gene regulation, and for sustained electrical potential in excitable cells. Magnesium also plays a major role in bone and mineral homeostasis. No tolerable upper intake level (UL) has been established for magnesium intake from food sources for the reason that no adverse effects have been recognised in healthy populations. Magnesium salts in food supplements may cause osmotic diarrhoea which is the most frequently reported adverse effect. However, these effects are considered relatively mild. Previous reports have arrived on UL or guidance levels (GLs) for supplemental magnesium ranging from 250 mg/day in the EU (Scientific Committee for Food (SCF, 2001)) through 350 mg/day in the USA (Institute of Medicine (IOM, 1997)) and up to 400 mg per day in the UK (Expert group on Vitamins and Minerals (EVM, 2003)). The UL from SCF (2001) is below the recommended daily dietary intakes for adults. Since the critical endpoint (gastrointestinal symptoms) is mild, rapidly reversible and no NOAEL could be identified, VKM finds it appropriate to base the UL for magnesium salts in food supplements on the LOAEL from IOM (1997). For the same reason, an uncertainty factor of 1 may be applicable for establishing a UL for magnesium salts in food supplements. VKM therefore proposes an amendment of the ULs suggested by SCF (2001) for magnesium in supplements. The IOM (1997) suggestion of a UL at 350 mg supplementary magnesium per day for adults was based on a LOAEL for mild diarrhea. VKM found no results to support an alteration of this UL. VKM therefore suggests a UL of 350 mg magnesium in food supplements per day in adults which is in accordance with the UL suggested by (IOM, 1997). This UL will also cover the recommended intakes for the adult population. VKM suggests that the ULs for children equal the recommended intakes for each age group: Age group ULs (mg/day) Children 1-3 years 85 Children 3-10 years 120-200 Children (10-<14 years) 280 Adolescents (14-<18 years) 280 Adults (≥18 years) 350 According to the habitual dietary intakes of magnesium estimated from nationwide dietary surveys in Norway, about 25% of adults have intakes of magnesium below the recommendations from food and supplements. Almost the same percentage was below the recommended intakes among 9-year-old children, while approximately 70% of 13-year-olds had an intake of magnesium below the recommendations. It should be noted that the intakes have been estimated with use of different dietary survey methods for the different age categories and a comparison of estimates across age groups can be misleading and has a high degree of uncertainty. Concentration of magnesium in water is low and about 60% of the waterworks reporting to the Norwegian Waterworks Registry had a magnesium concentration below 2 mg/L, indicating water as a negligible source of magnesium for the majority of the population.
ABSTRACT
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 intake of iron in the Norwegian population in relation to tolerable upper intake levels (ULs). The existing maximum limit for iron in food supplements is 27 mg/day. VKM has also conducted scenario calculations to illustrate the consequences of amending the maximum limit to 5, 10, 20, 30, 40 or 50 mg/day. Iron deficiency is one of the most common nutritional disorders in the world. Individuals with increased iron demand such as growing children and pregnant women, those who experience blood loss such as menstruating women are particularly at risk for the consequences or iron deficiency. Iron deficiency can lead to fatigue and anaemia. The most common adverse effects of iron supplementation are reversible gastrointestinal symptoms. Chronic iron excess can lead to iron overload which is associated with several irreversible severe health outcomes such as cancers and cardiovascular diseases. Up to 1% of the population have a genetic trait that leads to accumulation of iron and renders them more vulnerable to iron excess. An adult needs approximately 10 mg iron per day to overcome daily loss. The tolerable upper intake level (UL) for iron in adults range from 45 to 60 mg/day. However, all previous reports acknowledge the challenges in defining upper levels. The Expert Group on Vitamins and minerals (EVM), UK report provided a guidance level (GL) of 17 instead of a UL and the Nordic Nutrition Recommendations (NNR) (2012) suggested an UL of 60 mg/day, but did not suggest any clear upper levels for children. Institute of Medicine (IOM), US (2001) gives the most substantiated tolerable upper intake levels based on gastrointestinal effects, which is 40 mg/day for infants and children, regardless of age, and 45 mg/day for adolescents and adults. The Joint FAO/WHO Expert Committee on Food Additives 2003 (JECFA) also took the potential serious effects of iron overload into account and suggested a GL of 50 mg/day in adults or 0.8 mg/kg per day in children and adolescents. Because the risks and consequences from overload are significant and potentially serious, VKM suggests that the GL from JECFA (2003) is used. Using the GL from JECFA (2003), none of the suggested doses can be given to 2 or 4-yearold children, 9 year olds can add 5 mg iron from supplements, 13 year olds 20, and adults 30 mg without exceeding the guidance levels.
ABSTRACT
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 intake of vitamin B6 (pyridoxine) in the Norwegian population in relation to tolerable upper intake levels (ULs). The existing maximum limit for vitamin B6 in food supplements is 4.2 mg/day. VKM has also conducted scenario calculations to illustrate the consequences of amending the maximum limitto 2, 6, 8, 10, 20 or 25 mg/day. Vitamin B6 is water soluble and comprises six compounds with vitamin B6 activity; pyridoxine (PN, an alcohol), pyridoxal (PL, an aldehyde) and pyridoxamine (PM, the amine) and their corresponding phosphates; pyridoxine 5’-phosphate (PNP), pyridoxal 5’ -phosphate (PLP) and pyridoaxamin 5’ –phosphate (PMP). These six forms of vitamin B6 are all present in food in addition to the glycosylated form, pyridoxine-5’-β-δ-glucoside (PNG), in some plants. In food supplements the most common vitamin B6 form is pyridoxine hydrochloride. Eighty to ninety percent of vitamin B6 in the body is found in muscles and estimated body stores in adults amount to about 170 mg with a half-life of 25-33 days. Vitamin B6 deficiency is mostly seen in combination with deficiency of other B vitamins. Symptoms of vitamin B6 deficiency are anaemia and neurological abnormalities (EFSA, 2016). Intakes of vitamin B6 from the diet alone have not been reported to cause adverse effects. Sensory neuropathy has been reported to be the most sensitive adverse health effect of vitamin B6 supplementation. VKM proposes to adopt the tolerable upper intake level (UL) set by the Scientific Committee for Food (SCF) in 2000 at 25 mg/day for vitamin B6, which was based on a lowest observed adverse effect level (LOAEL) of 100 mg/day found in one randomised controlled trial. VKM recognises that there are no well-designed dose-response studies of long-term use available. However, for adults, no adverse effects have been reported at doses with vitamin B6 up to 25 mg/day. Dietary calculations have been performed for mean intakes and in various percentiles (P5, P25, P50, P75 and P95) in children (2-, 4- and 9-year-olds), adolescents (13-year-olds) and in adults. To illustrate the consequences of amending the maximum limit for vitamin B6 in food supplements to 2, 6, 8, 10, 20 or 25 mg/day in the different age groups, VKM has used the scenarios with P95 from food and added the alternative amounts of supplements. VKM has compared these scenarios with the tolerable upper intake levels set by the Scientific Committee for Food in 2000 for adults, adolescents and children. In these scenarios, the 2- and 4-year-old children will exceed the tolerable upper intake level with use of 6 mg/day or higher vitamin B6 in supplements. The 9-year-old children will exceed the tolerable upper intake level with supplemental use of 10 mg/day. The 13-year-old adolescents will exceed the tolerable upper intake level with 20 mg/day of vitamin B6 in supplements. Adults will exceed the tolerable upper intake level with use of 25 mg/day of vitamin B6/pyridoxine in supplements.
ABSTRACT
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 intake of vitamin E (alpha-tocopherol) in the Norwegian population in relation to tolerable upper intake levels (ULs). The existing maximum limit for vitamin E in food supplements is 30 mg/day. VKM was also requested to conduct scenario calculations to illustrate the consequences of amending the maximum limit for alpha-tocopherol to 15, 50, 100, 150, 200 and 300 mg/day. Naturally vitamin E is a fat soluble compound synthesised by plants and consists of eight different tocopherols (α-, β-, γ- and δ- tocopherols and α-, β-, γ- and δ- tocotrienols) with varying vitamin E antioxidant activity. α-Tocopherol is recognised to meet human vitamin E requirements and accounts for 90% of the activity in human tissue. Vitamin E activity in food is expressed as α-tocopherol equivalents (α-TE) and 1 α-TE is defined as 1 mg d-αtocopherol. The physiological role of vitamin E is to react with free radicals in cell membranes and other lipid milieu, thereby preventing polyunsaturated fatty acids (PUFA) from being damaged by lipid peroxidation. This antioxidant activity is important to maintain membrane integrity and takes place in all cells in the body. Vitamin E deficiency symptoms include peripheral neuropathy, ataxia, myopathy and retinopathy. Vitamin E is dependent on lipid and lipoprotein metabolism and it takes decades for body depletion. The Norwegian recommended intakes for vitamin E for adults are 10 αTE/day for men and 8 α-TE/day for women. There is no evidence of adverse effects from the consumption of vitamin E naturally occurring in foods. Animal studies have shown that α-tocopherol is not mutagenic, carcinogenic or teratogenic. However, high doses of α-tocopherol supplements can cause haemorrhage and interrupt blood coagulation. VKM propose to adopt the tolerable upper intake level set by the Scientific Committee for Food Safety (SCF) which is based on one human dose-response study. Hence, the upper level for supplemental vitamin E is suggested to 300 mg/day for adults. The upper level for children and adolescents is derived from scaling the adult upper level based on body surface area (body weight 0.75). The tolerable upper intake levels set for vitamin E concern only intake from supplements, since intake of vitamin E from the diet is considered safe. VKM has therefore not conducted or evaluated scenarios with intake from both diet and supplements. Dietary calculations have, however, been performed for intake in various percentiles (P) P5, P25, mean, P50, P75 and P95 in children (2- 4- and 9-year-olds), adolescents (13-year-olds) and in adult men and women as background information. Mean and median intakes of vitamin E are above the recommended intakes for all age groups. No age group reaches the recommended intake at P5, and 9- and 13-year-old boys and 9-year-old girls do not reach the recommended intake at P25 from diet alone. Because the tolerable upper intake level for supplemental vitamin E for adults is 300 mg/day, none of the suggested amendments of the maximum limit in food supplements (to 15, 50, 100, 150, 200 and 300 mg/day) will lead to exceedance of this upper level in adults. In 13year-olds supplements with 300 mg/day vitamin E will lead to exceedance of the upper level. In 9-year-olds supplements with 200 mg/day vitamin E will lead to exceedance of the upper level. In 4- and 2-year-olds supplements with 150 mg/day vitamin E will lead to exceedance of the upper level. Vitamin E intake from fortified products is not included in the calculations, but are however, evaluated to be very low.
ABSTRACT
The Norwegian Food Safety Authority (NFSA, Mattilsynet) has requested the Norwegian Scientific Committee for Food Safety (VKM) to assess the intake of iron zinc in the Norwegian population in relation to tolerable upper intake levels (ULs). The existing maximum limit for zinc in food supplements is 25 mg/day. VKM has also conducted scenario calculations to illustrate the consequences of amending the maximum limit to 1, 2, 5, 10, 15 or 20 mg/day. Zinc is an essential trace element required for RNA, DNA and protein synthesis, cellular division, differentiation and growth (Mac Donald, 2000). Zinc is required for catalytic function in several enzymes and participates in all major biochemical pathways in the body. The function of the immune system depends on the ability of its cells to proliferate and differentiate, which is impaired in individuals with suboptimal zinc status (Barton et al. 2000). Due to its role in cell division and differentiation, adequate zinc nutrition is particularly important in children, and the requirements per kg body weight are highest in early life. The endogenous intestinal losses can vary from 7 mmol/day (0.5 mg/day) to more than 45 mmol/day (3 mg/day), depending on zinc intake (King and Turnlund, 1989). The requirements for zinc vary according to age and bioavailability. Several bioactive compounds in food such as tannins and phytic acids interact with zinc absorption and increase zinc requirements. The requirements vary twenty-fold according to life stage and diet. Zinc supplements, even at or slightly above the recommended intakes, can cause nausea and vomiting. The main concern with chronic zinc excess is, however, copper deficiency which is associated with several chronical illnesses. However, copper deficiency is uncommon due to the ubiquitous presence of copper in the diet. VKM proposes to use the ULs set by IOM (2001) as they provide values also for children and adolescents. The tolerable upper intake level set for adults is 40 mg zinc per day from food (and water) and supplements. Based on the scenario estimations, a dietary zinc intake at the 95th percentile and additionally 20 mg zinc from food supplements will lead to an intake close to the tolerable upper intake level established by IOM for adults. For adolescents and child populations the maximum amounts are 15 and 5 mg for 13- and 9-year-olds, respectively. For 2 and 4-yearolds, P95 from intake of zinc from food alone exceeds the UL.
ABSTRACT
The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), evaluated the intake of vitamin C and calcium in the Norwegian population. VKM has also conducted scenario estimations to illustrate the consequences of amending maximum limits for vitamin C (to 100, 300, 500, 600, 800 or 1000 mg/day) and calcium (to 800, 1200 or 2000 mg/day) in food supplements. Vitamin C: Vitamin C refers to both ascorbic acid and dehydroascorbic acid. Scurvy is the manifestation of vitamin C deficiency which is preventable by a daily intake of 5-10 mg/day. Fruits, berries and vegetables are important food sources of vitamin C and especially citrus fruit are important contributors. The Norwegian recommendation for dietary intake of vitamin C is 75 mg/day for adults (Helsedirektoratet, 2014). Vitamin C is absorbed from the intestine by an active process that is dose dependent. The bioavailability is at least 80% for doses up to 100 mg, 70% for doses of 200-500 mg and less than 50% for doses exceeding 1000 mg. Intestinal discomfort and diarrhea have been reported by persons using large doses (>1000 mg/day) of vitamin C supplementation. In 2000 the Institute of Medicine (IOM) in the USA proposed a tolerable upper intake level (UL) for vitamin C intake from food and supplements of 2000 mg/day for adults. ULs for children and adolescents were extrapolated based on body weight; 400 mg for children 1-3 years, 650 mg/day for children 4-8 years, 1200 mg/day for 9-13 years old adolescents, 1800 mg/day for 14-18 years old (IOM, 2000). In the assessment of vitamin C, VKM uses the Norwegian recommendations for intakes (Helsedirektoratet, 2014), and the acceptable dose for supplemental vitamin C from EFSA (2004) for adults and the tolerable upper intake levels established by the IOM (2000) for children and adolescents. Daily intakes of vitamin C from diet and supplements are estimated from nationwide dietary surveys performed in selected age groups: Adults 18-70 years, adolescents aged 13 years, and children aged 2, 4, and 9 years. Not all age-groups in the Norwegian population reach the recommended intake of vitamin C. At the 5th percentile, only 13-year-olds have an intake of vitamin C from food alone above the recommendations. At the 25th percentile, all age groups except adults have a vitamin C intake from food alone at or above the recommendations. At the 40th percentile, adults reach the recommended intake of vitamin C. The whole population would reach the recommended dietary intake with supplementation of 100 mg vitamin C per day. All the alternative maximum limits for vitamin C in food supplements listed in the terms of reference from NFSA (100, 300, 500, 600, 800 or 1000 mg/day) will be within the acceptable dose for supplemental vitamin C suggested by EFSA (2004) for adults. None of the alternative maximum limits for vitamin C in food supplements listed in the terms of reference (100, 300, 500, 600, 800 or 1000 mg/day) leads to exceedance of the tolerable upper intake levels established by IOM in adults, 13- year-olds or 9-year-olds, even with intakes from food at the 95th percentile. However, the tolerable upper intake level proposed by the IOM will be exceeded for 4-year-old children at supplemental doses above 500 mg vitamin C per day, and for 2-year-old children at doses higher than 100 mg/day. Calcium: Calcium is the most abundant mineral in the body and constitutes approximately 1200 g and 1400 g in adult women and men, respectively. More than 99% of the calcium in the body is bound to hydroxyapatite in bone and tooth enamel. Calcium is crucial for many bodily functions such as cell signalling, coagulation, muscular contraction, and neural transmission as well as skeletal integrity. Milk and dairy products are the main dietary sources of calcium, but foods such as fish, pulses, nuts, seeds (especially millet) and green vegetables may contribute to the total intake. The Norwegian recommendation for dietary intake of calcium is 800 mg/day for adults. The bioavailability of calcium is dependent on the amount of calcium ingested as well as the individual’s vitamin D status and physiological needs, like e.g. growth and pregnancy. Adverse effects of excessive calcium intake include symptoms of hypercalcaemia such as e.g. anorexia, weight loss, polyuria, heart arrhythmias, fatigue and soft tissue calcification (Jones, 2008 in IOM, 2011), deterioration of kidney function, kidney stone formation, the milk-alkali syndrome and vascular calcification. In 2012 the European Food Safety Authority (EFSA) established a tolerable upper intake level (UL) for calcium at 2500 mg/day from food and supplements for adults. No UL was set for children and adolescents. In 2011, IOM established a UL for 1-8 years old children to 2500 mg/day and 3000 mg/day for 9-18 years old children and adolescents (IOM, 2011). VKM however suggests that the UL established for adults by EFSA (2012) is used for the purpose of this VKM opinion also for children and adolescents, as the ULs from IOM for children and adolescents are considered to be high. In the assessment of calcium, VKM uses the Norwegian recommendations for intakes (Helsedirektoratet, 2014) and the tolerable upper intake levels established by the European Food Safety Authority for adults (includes both foods and supplements) (EFSA, 2012). Daily intakes of calcium from diet and supplements are estimated from nationwide dietary surveys performed in selected age groups: Adults 18-70 years, adolescents aged 13 years, and children aged 2, 4, and 9 years. Not all age groups in the Norwegian population reach the recommended intake of calcium. At the 5th percentile, no age groups fulfil the recommended daily intakes of calcium from food alone, and in the 50th percentile the 13-year-olds did not reach the recommended intake for calcium from food alone. At approximately the 65th percentile, the 13-year-olds reach the recommended intake for calcium. The whole population would reach the recommended dietary intake with supplementation of 800 mg calcium per day. For calcium, three alternative maximum limits were listed in the terms of reference (800, 1200 and 2000 mg/day). In the scenarios for high intakes of calcium, a dietary calcium intake at the 95th percentile and additionally 800 mg calcium from food supplements, will lead to an intake close to the tolerable upper intake level established by EFSA for the adult population, and supplements with 1200 or 2000 mg calcium per day will lead to exceedance of the tolerable upper intake level in adults. Children and adolescents with a dietary intake at the 95th percentile and additionally 2000 mg calcium from food supplements, will all exceed the UL suggested for adults by EFSA in 2012. All age groups except 4-year-olds will also exceed the UL with 1200 mg supplemental calcium. With 800 mg supplemental calcium 13-year-old adolescents, 9-year-old, 4 year-old and 2-year-old children will not exceed the suggested UL.
ABSTRACT
The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), evaluated the intake of potassium in the Norwegian population. VKM has also evaluated the consequences of amending the existing maximum limit for potassium at 1000 mg/day to 300, 2000 or 3000 mg/day in food supplements. Potassium is an essential mineral to humans and is important as the osmotically active element inside the cells, whereas sodium and chloride are the main elements outside the cells. The enzyme Na+/K+ -ATPase pumps potassium ions into the cells and sodium ions out of the cells and helps keep the intracellular potassium concentration about 30 times higher than that of plasma and interstitial fluids. The plasma potassium concentration is maintained within narrow limits (3.5 to 5.0 mmol/L) by multiple mechanisms making up the potassium homeostasis. The strict regulation is essential for a broad array of important physiological processes, like the resting cellular membrane potential and the transmission action in neuronal, muscular and cardiac tissue. Potassium is also important for hormone secretion, vascular tone, systemic blood pressure control, gastrointestinal motility, acid-base balance, glucose and insulin metabolism, mineralocorticoid action, renal concentration ability and fluid and electrolyte balance. Both hypo- and hyperkalaemia result in increased mortality. The EFSA recommendations (2016) for adequate intake (AI) of potassium is 3500 mg/day for adults, both sexes, whereas the recommended intake (RI) in the Nordic Nutrition recommendations (2012) is 3500 mg/day for men and 3100 mg/day for women. Tolerable upper intake levels have not been established for potassium from food, because intake from food has not caused adverse health effects in the healthy population. In children the renal function rapidly reaches the normal adult level in early childhood and no concern about high intake of potassium from food has been put forward. Potassium chloride supplement has, however, resulted in hyperkalaemia and case reports have described heart failure and cardiac arrest at plasma concentrations above 5.5 mmol/L and doses over 6.5 - 6.8 g supplementary potassium per day. VKM proposes to use 3000 mg/day of potassium as an upper guidance level for daily dose of supplemental potassium in adults since this dose has not been shown to cause hyperkalaemia or heart failure, and has not resulted in gastrointestinal lesions. The proposed upper guidance level for adults extrapolated for body weights corresponds to 2630 mg/day for adolescents 14 to <18 years, 1860 mg/day for children 10 to < 14 years and 990 mg/day for children 3 to 10 years. For vulnerable groups all doses of potassium supplementation could lead to hyperkalaemia. Vulnerable groups such as persons with impaired kidney function and elderly have been estimated to comprise 15-20% of the population of Norway. However, most of the vulnerable individuals will be aware of the condition and be under medical supervision. Accordingly, all the evaluated doses from NFSA (300, 1000, 2000 and 3000 mg/day of potassium in food supplements are at or below the suggested upper guidance level for supplemental potassium for adults (>18 years). In adolescents 14 to <18 years, the supplemental doses of 300, 1000 and 2000 mg/day are below the suggested upper guidance level. For the younger age groups, only 300 mg/day is below the suggested upper guidance level for supplemental potassium.
ABSTRACT
The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), evaluated the intake of phosphorus in the Norwegian population. VKM has also conducted scenario calculations to illustrate the consequences of amending maximum limits for phosphorus (to 1000, 2000 or 2500 mg/day) in food supplements. Phosphorus is an essential nutrient and is involved in many physiological processes, such as in the cell’s energy cycle, in regulation of the body’s acid-base balance, as a component of the cell structure, in cell regulation and signalling, and in the mineralisation of bones and teeth. In the human body, phosphorus is present in different forms. Serum contains mainly inorganic phosphates (Pi) (dihydrogen and monohydrogen phosphate), bone contains phosphorus largely in the form of hydroxyapatite, whereas the soft tissues and extracellular fluids contain organic phosphates in complex with carbohydrates, lipids and proteins. Phosphorus is the main mineral constituent of bones. About 85% of the body’s phosphorus is in bones and teeth, and together with calcium account for around 80-90% of bone composition. The remaining 15% of the body’s phosphorus is essential in functions ranging from the transfer of genetic information to energy utilisation. Phosphorus is a structural component of the nucleic acids DNA and RNA and thus involved in the storage and transmission of genetic material. It is an essential component of phospholipids (e.g. phosphatidylcholine) that form all membrane bilayers throughout the body. Phosphorus is also an essential component of adenosine triphosphate (ATP), the body’s key energy source. Currently there is no reliable biomarker of phosphorus status, and serum phosphorus increases for a short period after ingestion of a meal and then decreases and remains within a relatively narrow range as a result of homeostatic mechanisms. The EFSA recommendations (2015) for adequate intake (AI) of phosphorus is 550 mg/day for adults, both sexes, whereas the recommended intake (RI) in the Nordic Nutrition Recommendations (2012) is 600 mg/day. Adolescents have a higher requirement of phosphorous because of bone accretion (640 mg/day EFSA and 700 mg/day NNR). EFSA (2005) concluded that the available data were not sufficient to establish a tolerable upper level for phosphorus, however, data indicate that normal healthy individuals can tolerate phosphorus intakes up to 3000 mg/day. EFSA advised supplemental intake not to exceed 750 mg/day, because mild gastrointestinal symptoms have been reported when this dose was increased. EFSA gave no UL suggestions for children, lactating or pregnant women, while Institute of Medicine set a UL for total intake of phosphorous for children at 3000 mg/day and 4000 mg/day for adolescents and adults and 3500 mg/day for lactating women. In accordance with EFSA (2005), VKM suggests to use 3000 mg/day as a provisional UL for total intake of phosphorous for adults, and suggests 750 mg/day as an upper level for supplements. Because of lack of data no provisional ULs are set for adolescents or children. Accordingly, all the suggested doses from NFSA (1000, 2000 and 2500 mg/day) in supplements exceed 750 mg/day, the suggested UL for supplemental phosphorus for adults.
ABSTRACT
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 chromium. VKM has also conducted scenario calculations to illustrate the consequences of establishing maximum limit for chromium at 50, 125, 200 or 300 μg/day in food supplements. The former maximum limit for chromium of 125 μg/day in food supplements was revoked 30 May 2017. Chromium is present in food and supplements mainly as trivalent chromium, Cr(III), whereas in drinking water, chromium is present mainly as Cr(VI). Trivalent chromium has been reported to be an essential trace element in that it has been postulated to be necessary for the efficacy of insulin in regulation of the metabolism of carbohydrates, lipids and proteins. However, no mechanisms for these roles have been identified. Absorption of Cr(III) from food has been estimated to range from 0.4 to 2.5%, depending among other factors on the chemical properties of the ingested source and the presence of other dietary components. Absorption efficiency of supplemental Cr(III) has been reported to be between 0.1 and 5.2%, and to vary between the chromium complex ingested. In general, Cr(III) has very low toxicity by the oral route (ATSDR, 2012), and there are hardly any well-documented observations of toxicity after peroral intake in humans. In a series of animal repeat dose toxicity studies, the no observed adverse effect level (NOAEL) for general toxicity was consistently the highest dose tested (EFSA, 2014b). Chromium is ubiquitous in foods, and rich sources include meat and meat products, oils and fats, breads and cereals, fish, pulses and spices. There are no Norwegian recommendations for intake of chromium. The Nordic Nutrition Recommendations and the European Food Safety Authority (EFSA) concluded that no recommendations could be given for chromium due to lack of sufficient evidence (EFSA, 2014a; NNR Project Group, 2012). Furthermore, no tolerable upper intake levels (UL) have been established for chromium. However, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) suggested a tolerable daily intake (TDI) at 300 μg trivalent chromium per kg bodyweight per day based on a NOAEL in a rat study and an uncertainty factor at 1000. Due to uncertainty in the available data on developmental and reproduction toxicity, the EFSA Panel applied an uncertainty factor of 10 in addition to the default uncertainty factor of 100 for the extrapolations from rodents to humans and for human variability. The chromium intake in Norway is not known, since Norwegian food composition data are not available. VKM has therefore based this evaluation upon intake data from EFSA. Values from EFSA are likely to be valid also for Norway. Median dietary chromium intakes were 28.6 -44.0 μg/day (medians of lower and upper bound) in the category toddlers (1 to < 3 years), 55.4-76.2 μg/day in other children (3 to < 10 years), 52.1-69.4 μg/day in adolescents (≥10 to <14 years), 73.6-98.1 in adolescents (≥14 to <18 years) and 63.0-84.0 μg/day in adults (18-65 years) (EFSA, 2014b). These values are 80-300 times lower than the suggested tolerable daily intake (TDI). To illustrate the consequences of amending maximum limits for chromium to 50, 125, 200 or 300 μg per daily dose in food supplements, VKM has compared these levels and various intakes from food to the TDI at 300 μg/kg bw per day. Even with the highest level of supplemental intake and additional median levels as well as the 95 percentile intakes from food, the estimated exposure will be 16-48 times lower than the TDI of 300 μg/kg bw per day in all age groups except for the 95 th percentile intake in toddlers, where it will be about nine times lower. VKM emphasises that the current assessment of maximum limits for Cr(III) in food supplements is merely based on published reports concerning upper levels from the WHO (1996), IOM (2001, USA), SCF (2003, EU), EVM (2003, UK) , NNR (2012, Nordic countries), and EFSA (2014b). 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.
ABSTRACT
The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), evaluated the intake of copper in the Norwegian population in relation to tolerable upper intake levels (ULs). VKM has also conducted scenario calculations to illustrate the consequences of amending maximum limits for copper to 1, 2, or 3, mg/day in food supplements. The existing maximum limit is 4 mg/day. Copper is a micronutrient essential for energy utilisation, brain function (neurotransmitter regulation), soft tissue and bone (collagen synthesis), nutrient metabolism (especially iron) and antioxidant defence against free radicals. Foods account for 90% or more of copper intake in adults when the copper content in drinking water is low (< 0.1 mg/L). If the copper content is higher (> 1-2 mg/L), water may account for up to 50% of total intake (EFSA, 2015). We reviewed four risk assessments undertaken by the Institute of Medicine (IOM), Scientific Committee on Food (SCF), Expert Committee on Vitamins and Minerals (EVM), and the Nordic Nutrition Recommendations (NNR). Liver damage was selected as a critical endpoint from which to derive a UL because it was judged to be the most reliable marker and consequence of a long-term chronic high copper intake. However, copper-related liver damage is observed almost exclusively in patients with genetic predispositions of copper accumulation. VKM suggest to use the UL at 5 mg/day (NNR Project Group, 2012; SCF, 2003). This UL was derived from human studies.In the light of the evidence, SCF decided that an uncertainty factor (UF) of 2 was adequate to allow for potential variability within the normal population, whereas the Institute of Medicine (IOM) applied a UF of 1. VKM find the higher UF suitable because human data is limited, the uncertainty of the copper content of drinking water and the potential severe and irreversible adverse effects. According to the scenario calculations, adults and 13-year-olds with high copper intakes from regular foods (95 th percentile) will exceed the ULs with supplemental copper at doses of 3 mg/day or higher. 9-year-old children will exceed the UL with use of 2 mg supplemental copper per day. For younger children the ULs will be exceeded in more than 5% without adding supplemental copper. In our calculations, copper from drinking water is not included. Copper concentrations in annual samples from waterworks are in general below 0.1 mg/L (Nordheim et al., 2016).
ABSTRACT
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 intake of niacin in the Norwegian population. NFSA has also requested that VKM conduct scenario calculations to illustrate the consequences of establishing separate maximum limits for nicotinic acid (1, 4, 8 or 10 mg/day) and nicotinamide (100, 500, 700 or 900 mg/day) in food supplements, by assessing these scenarios against existing tolerable upper intake levels (ULs). The current maximum limit for niacin added to food supplements is 32 mg/day, including nicotinic acid, nicotinamide and inositol hexanicotinate. The term niacin (vitamin B3) comprises the two main water-soluble forms nicotinic acid and nicotinamide (niacinamide). The human body can get niacin from the diet or synthesise it from the essential amino acid tryptophan. Dietary intakes are expressed as milligram niacin equivalents (NEs), which correspond to 1 mg of pure niacin or 60 mg of tryptophan. In the body, niacin primarily functions as a component of the coenzymes NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate) which are present in all cells. These coenzymes play essential roles for the functioning of a wide range of enzymes involved in the metabolism of carbohydrates, amino acids and fat. In addition to its function in coenzymes, niacin is involved in DNA repair and gene stability. Niacin has a half-life of 20-40 minutes in the human body. Late symptoms of severe niacin deficiency (pellagra) include fatigue, headache, apathy, depression, memory loss, dementia, pigmented skin rash after sun exposure, bright red tongue, vomiting, diarrhoea, and constipation. Flushing (burning and itching of the face, arms and chest) and stomach irritation are the main side effects of moderately high supplemental intake of nicotinic acid (>35 mg/day). Long-term use of high doses (≥3000 mg/day) of nicotinic acid as a cholesterol-lowering drug can also be toxic to the liver. Nicotinamide, however, does not have these effects. In general, the risk of nicotinamide toxicity appears to be quite low. VKM proposes to adopt the ULs of nicotinic acid and nicotinamide set by the Scientific Committee for Food Safety (SCF) in 2002, which are based on one human dose-response study (nicotinic acid) and several human dose-response studies (nicotinamide), respectively. Hence, the UL for supplemental nicotinic acid is suggested to 10 mg/day for adults and the UL for supplemental nicotinamide to 900 mg/day for adults. The ULs for children and adolescents have been derived on the basis of their body weights. The ULs set for nicotinic acid and nicotinamide concern only intake from supplements since intake of nicotinic acid and nicotinamide from regular foods is considered to be without risk of negative health effects. Therefore, VKM has not conducted or evaluated scenarios with intake from both diet and the separated new maximum limits for nicotinic acid and nicotinamide in food supplements suggested by NFSA. Dietary calculations, however, have been performed for niacin intakes (includes both nicotinic acid and nicotinamide) in various percentiles (P5, P25, mean, P50, P75 and P95) in children (2-, 4- and 9-year-olds), adolescents (13-year-olds) and adults as background information. Mean and median intakes of niacin from the diet alone are above or at the recommended intakes for all age groups. Because UL for supplemental nicotinic acid is 10 mg/day for adults, none of the suggested maximum limits in food supplements (1, 4, 8, or 10 mg/day) will lead to exceedance of this UL in adults. In 13-year-olds and 9-year-olds, supplements with 8 mg nicotinic acid per day will lead to exceedance of UL, and in 4-year-olds and 2-year-olds supplementation of 4 mg nicotinic acid per day will lead to exceedance of the UL for nicotinic acid. Because UL for supplemental nicotinamide is 900 mg/day for adults, none of the suggested maximum limits in food supplements (100, 500, 700 or 900 mg/day) will lead to exceedance of UL in adults. In 13-year-olds, supplements with 700 mg nicotinamide per day will lead to exceedance of UL. In 9-year-olds, 4-year-olds and 2-year-olds, supplementation of 500 mg nicotinamide per day will lead to exceedance of the UL for nicotinic acid.
ABSTRACT
The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), evaluated the intake of selenium in the Norwegian population. VKM has also conducted scenario calculations to illustrate the consequences of amending maximum limits for selenium to 50, 150 or 200 μg/day in food supplements. The existing maximum limit is 100 μg/day. Selenium is a cofactor for enzymes and proteins with vital importance in antioxidant defence, thyroid hormone and insulin function and regulation of cell growth. We reviewed four risk assessments undertaken by the Institute of Medicine (IOM), Scientific Committee on Food (SCF), Expert Committee on Vitamins and Minerals (EVM), and the Nordic Nutrition Recommendations (NNR). Because of limited evidence from human studies and due to the selection of a high uncertainty factor (UF), we decided to use the tolerable upper intake levels (ULs) set by the SCF (2000) and later adopted by NNR (2012). Early signs of selenium toxicity are a garlic breath and a metallic taste. Severe selenosis results in fast hair loss and brittle nails, as well as other gastrointestinal symptoms such as nausea, vomiting, diarrhea, fatigue, irritability, and rash. Acute selenium intoxication and chronical overexposure may affect the nervous system and result in nerve damage. The SCF established a UL for selenium at 300 μg/day for adults, including pregnant and lactating women. This UL was based on a no observed adverse effect level (NOAEL) of 850 μg/day for clinical selenosis applying a UF of 3, and was supported by three studies reporting no adverse effects for selenium intake between about 200 and 500 μg/day. As there were no data to derive specific ULs for children, the SCF (2000) extrapolated the UL from adults to children based on reference body weights. The proposed UL values for children and adolescents ranged from 60 μg/day (1–3 years) to 250 μg selenium/day (15–17 years). According to the scenario estimations in adults, the dietary selenium intake at the 95th percentile and additionally 150 μg selenium from food supplements will be below the UL while 200 μg selenium from food supplements will lead to exceedance of the UL for adults. For 13- and 9-year-olds, supplemental doses of 100 and 50 μg selenium per day, respectively, do not lead to exceedance of the ULs in these age groups. For 2- and 4-year-olds, all the suggested doses in food supplements will lead to exceedance of the ULs.
ABSTRACT
Beta-carotene is a provitamin, i.e. a precursor of vitamin A (retinol), which is classified as an essential nutrient for humans. Beta-carotene is one of many carotenoids found in plants, fungi and bacteria. Carotenoids are therefore predominantly obtained through foods of plant origin or food supplements. Carrots contribute approximately half of the total beta-carotene intake in the Norwegian diet, followed by mixed frozen vegetables, tomatoes, fruits and berries. VKM emphasises that this opinion on upper level (UL) for beta-carotene addresses beta-carotene in food supplements only. Beta-carotene from regular foods such as vegetables and fruits is not considered to be a health concern. In 2002, the Scientific Committee on Food (SCF) established a tolerable upper intake level (UL) for vitamin A (SCF, 2002). However, the SCF opinion covers only retinol compounds (various forms of vitamin A). The bioconversion of carotenoids to vitamin A in the body is well regulated and therefore only intake of vitamin A has been considered relevant for vitamin A toxicity (Blomhoff et al., 2003; EFSA, 2008). The Norwegian Food Safety Authority is considering whether betacarotene should be regulated separately from retinol compounds. Beta-carotene seems to have a carcinogenic effect in smokers. A number of studies have been published where possible mechanisms of this negative health effect are discussed. The suggested mechanisms are either related to effects on cytochrome P450-related activities, altered retinoid signalling or to a pro-oxidant activity of beta-carotene. No UL has been established for beta-carotene. Several risk-assessment bodies have, however, previously attempted to establish safe levels or temporary guidelines, summarised in the following table: Previous reports Conclusion SCF, 2000, EU No dose-response relationship could be derived. Supplementation of 20 mg beta-carotene per day or more is contraindicated for use in current heavy smokers. There is insufficient evidence to set an UL for beta-carotene. IOM, 2000, USA No UL was established for beta-carotene or carotenoids. Beta-carotene supplementation is not recommended in the general population. EVM, 2003, UK The LOAEL was set to 20 mg/day. An uncertainty factor of 3 was applied to extrapolate from LOAEL to a NOAEL. A Safe Upper Level for beta-carotene supplements was set at 7 mg/day (equivalent to 0.11 mg/kg body weight/day for a 60 kg adult). NNR, 2012, Nordic countries No specific beta-carotene recommendation or UL. Rasmussen, 2006, Denmark A Temporary Guidance Level for beta-carotene equal to the average dietary level of 5 mg/day for all age groups was suggested. Seven randomised controlled trials (RCTs) have been included in this VKM opinion, conducted either in Europe or the USA, with almost 47 100 participants in the beta-carotene groups. In six of these RCTs there were no observed increased risk of cancer, but the large Finnish ATBC study found an increased risk of lung cancer in the beta-carotene group. Two prospective studies were included, one Danish and one from the USA, with 125 000 participants all together. The Danish study found that risk of lung cancer increased in smokers with increasing doses of beta-carotene supplements. In addition, eleven meta-analyses were included; one with age-related macular degeneration as endpoint, one with a mixture of cardiovascular disease (CVD) and cancer as endpoints, four on cancer as only endpoint, one on a mixture of CVD and all-cause mortality as endpoints and four on all-cause mortality alone. One of the meta-analyses on all-cause mortality was later excluded. There were no significant findings in the meta-analysis on macula degeneration. One of the two meta-analyses on CVD found a small increased risk in the beta-carotene arm (Vivekananthan et al., 2003). The combined CVD and cancer meta-analysis did not have sufficient statistical power to get significant results, but found a probable increase in lung cancer incidence in high-risk subgroups (smokers and asbestos workers (Fortmann et al., 2013). In the five meta-analyses studying cancer, there were no effect on other cancer forms than lung cancer. The four meta-analyses on all-cause mortality used information from the same RCTs as included in this VKM-opinion. They extracted information on numbers of death in each study and used these numbers to analyse risk of death in the beta-carotene versus placebo groups. Alarmingly, they all found an increased risk of all-cause mortality. These meta-analyses have been discussed thoroughly. To complete the risk characterisation of beta-carotene, VKM has followed the steps 1 – 4 as suggested by SCF in their Guidelines for the development of tolerable upper intake levels for vitamins and minerals (SCF, 2000a). Step 1 and 2. Hazard identification and characterisation Up until two decades ago, beta-carotene was thought to be harmless even in large doses. In the wake of the Finnish ATBC study which found an increased risk of lung cancer and death in male smokers, animal studies have indicated three possible mechanisms for such a detrimental effect. Although conclusive mechanistic explanations for the negative effects have not yet been agreed upon, there is a scientific rationale for the argument that population groups with vulnerable lungs may also have increased risk from beta-carotene supplements. The dose used in the Finnish ATBC study was 20 mg beta-carotene/day. The effect was only observed during the intervention period; in follow-up studies conducted after the active period was finished, the risk declined and was no longer significant. 20 mg beta-carotene may thus be considered as a LOAEL. The Danish prospective study found a dose-dependent increase in lung cancer risk with increased intake of supplemental beta-carotene. Unfortunately, the paper does not allow for setting a NOAEL or LOAEL based on the published data. In the four meta-analyses on all-cause mortality, all found a 6-7% increased risk of death. One of the meta-analyses also found an increased risk of CVD in smokers. However, all results were driven, statistically, by the ATBC study. Studies with a more mixed population (both men and women) and with a more typical prevalence of smokers (10–20%), found no such increased risk. Step 2, continued: Derive at a UL, taking into account the scientific uncertainties in the data. ULs may be derived for various life-stage groups within the population VKM found it extraordinary challenging to decide which uncertainty factor to use for beta-carotene. The present SCF guidelines for establishment of tolerable upper intake levels do not give clear guidance/advice in deciding the numeric level of the uncertainty factor. This seems to leave the decision to scientific judgement. If the NOAEL is based on human data, an uncertainty factor of 10 is recommended as a starting point to encompass inter-individual variation and sensitivity. The SCF guidelines state that a small uncertainty factor is to be used if the judgement is that little population variability is expected for the adverse effects, and a larger uncertainty factor (close to 10) may be used if variability is expected to be large. For beta-carotene, a NOAEL is not available, and an uncertainty factor may be applied to account for the uncertainty in deriving a UL from the LOAEL. The size of the uncertainty factor involves a judgement based on the severity and incidence of the observed effect at the LOAEL and the steepness (slope) of the dose response, if this is possible to estimate. For beta-carotene, we have not found the data necessary to make a dose-response curve. In addition, the following considerations were discussed before deciding on an uncertainty factor: · The study which found a negative effect of beta-carotene supplementation (the Finnish ATBC study) was very large (n=29 133) which indicates that it encompasses inter-individual variation and sensitivity. Additionally, the most vulnerable groups, in this case smokers, was an inclusion criteria. Both these factors indicate that the uncertainty factor can be in the lower end. · The meta-analyses for the endpoint “increased risk of all-cause mortality” found an increased risk of death in the beta-carotene groups. This is severe, and indicates that a maximum uncertainty factor should be applied. However, as all results in the all-cause mortality metaanalyses were driven statistically, by the ATBC study on smokers, we choose to use a lower factor. Based on the above considerations, VKM has chosen to use 5 as an uncertainty factor for betacarotene. An UL for beta-carotene cannot be derived, but a tentative upper level (TUL) is set at 4 mg/day, based on a LOAEL of 20 mg and the uncertainty factor of 5. Smokers and anyone else in the population with vulnerable lungs (e.g. asthmatics, COPD patients) should be discouraged from taking beta-carotene containing supplements all together. Step 3. Exposure assessment – evaluates the distribution of usual total daily nutrient intakes among members of the general population In the food survey Småbarnskost 2007, the mean intake of beta-carotene in 2-year-olds was 1.5 mg/day. In Norkost 3, the estimated mean intake in adults was 2.4 mg/day and 6.9 mg/day in the 95th percentile. About 3% of the adults reported use of beta-carotene supplements. The use of tanning pills containing beta-carotene may have been underreported. Beta-carotene from regular foods such as vegetables and fruits is, however, not considered to be of any health concern. Negative health effects from beta-carotene in natural foods have never been reported. On the contrary, the consumption of vegetables and fruits should be increased, and the recommendation of “5 a day” should be achieved in all age groups of the population. Step 4. Risk characterisation – analyses of the conclusions from steps 1 through 3 and characterises the risk. The risk will depend on the fraction of the population
ABSTRACT
Se describe el diseño, construcción y validación de un instrumento para evaluar las competencias docentes de los profesores de pregrado de la Universidad Católica de Colombia. El instrumento evalúa siete competencias básicas para el ejercicio de la función docente: planificación curricular, utilización adecuada de diseño metodológico y organización de actividades de enseñanza, competencia científica tecnológica, interacción adecuada con estudiantes, competencia para evaluar, competencia para realizar tutorías, autorreflexión sobre la práctica docente. Se construyeron así los indicadores de competencias del docente de la Universidad Católica de Colombia, prueba que fue validada por medio del juicio de 60 expertos. Con los resultados se diseñó el instrumento de evaluación de las competencias, que una vez ajustado fue aplicado a 20 docentes de la Facultad de Psicología de la Universidad Católica de Colombia.
We describe the design, construction and validation processes of a instrumentaimed to the evaluation of teaching skills of the Catholic University of Colombias undergraduate level teachers. The instrument evaluatesseven skills that are basic to the exercise of teaching: curriculum planning, appropriate usage of methodological designs and organization of teaching activities, scientific technological competence, appropriate interaction with students, evaluative competence, tutorial skills, and self-reflection on teaching practices. The indicators of teachers competence were thus constructed, and the test was validated by the opinion of 60 expert judges. The results of this process were used to design the final instrument, which once adjusted, was applied to 20 teachers of the Catholic University of Colombia.