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 The former maximum limit for vitamin K of 200 µg/day in food supplements was repealed 30 May 2017.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 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.