Risk Assessment of "Other Substances" – L-Histidine

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 <14 years) and adolescents (14 to <18 years) were identified. Based on the included literature there was no evidence indicating that age affects the tolerance for relevant doses of threonine. Therefore, in this risk characterisation a tolerance as for adults, based on body weight, was assumed for these age groups. VKM concludes that: In adults (≥18 years), the specified doses 1000, 1200, 1500, 2000 and 2400 mg/day L-threonine in food supplements are unlikely to cause adverse health effects. In adolescents (14 to <18 years), the specified doses 1000, 1200, 1500, 2000 and 2400 mg/day L-threonine in food supplements are unlikely to cause adverse health effects. In children (10 to <14 years), the specified doses 1000, 1200, 1500, 2000 and 2400 mg/day L-threonine in food supplements are unlikely to cause adverse health effects. Children younger than 10 years were not within the scope of the present risk assessment.

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Risk Assessment of "Other Substances" – L-phenylalanine and DL-phenylalanine

European Journal of Nutrition & Food Safety ◽

10.9734/ejnfs/2020/v12i330205 ◽

2020 ◽

pp. 32-34

Author(s):

Livar Frøyland ◽

Margaretha Haugen ◽

Kristin Holvik ◽

Martinus Løvik ◽

Tor A. Strand ◽

...

Keyword(s):

Risk Assessment ◽

Food Safety ◽

Health Effects ◽

Plasma Levels ◽

Energy Drinks ◽

Food Supplements ◽

Risk Assessments ◽

Adverse Health Effects ◽

Adverse Health ◽

Other Substances

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.

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Risk Assessment of "Other Substances" – L-lysine

European Journal of Nutrition & Food Safety ◽

10.9734/ejnfs/2020/v12i830262 ◽

2020 ◽

pp. 58-60

Author(s):

Sigrun Henjum ◽

Livar Frøyland ◽

Margaretha Haugen ◽

Kristin Holvik ◽

Martinus Løvik ◽

...

Keyword(s):

Risk Assessment ◽

Adverse Effects ◽

Health Effects ◽

Literature Search ◽

Present Report ◽

Food Supplements ◽

Risk Assessments ◽

Adverse Health Effects ◽

Adverse Health ◽

Other Substances

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 limited to the use of L-lysine in food supplements. Risks related to lysine 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 lysine and scientific papers retrieved from a comprehensive literature search. According to information from the NFSA, L-lysine is an ingredient in food supplements sold in Norway. NSFA has requested a risk assessment of 1000, 2000, 2500, 2750 and 3000 mg/day of L-lysine from food supplements. Foods rich in L-lysine are generally protein rich foods such as meat, dairy products, eggs, legumes, and some fish. Based on NHANES III (19881994), the overall mean intake of L-lysine from food and food supplements in the United States was 5.3 g/day (IOM, 2005). L-Lysine, an indispensable amino acid, is present in all proteins in the human body. Its catabolisation takes place mainly in the liver. The two nitrogen groups are transferred to alpha-ketoglutarate to form glutamate. The remaining carbon skeleton is broken down to acetoacetyl-CoA. Lysine is exclusively ketogenic i.e. does not enter gluconeogenesis for the production of glucose. In the first phase of the present evaluation of L-lysine, previous reports evaluating the safety of L-lysine supplementation in humans were identified. In the second phase, two systematic literature searches have been performed to retrieve scientific papers published before 11 May 2016 (human studies literature search) and before 28 September 2016 (animal studies literature search). Based on these searches, we identified two human studies and one study in rats that could be used for risk assessment of L-lysine in food supplement. According to a report from the Institute of Medicine in the USA (IOM, 2005), several clinical trials of lysine with intakes ranging from 0.6 to 3.0 g/day for 3 to 6 months have not reported any adverse effects. The same was the case for the two human randomised controlled trials (RCTs) included in this report providing 6 g/day L-lysine orally for 8 weeks to schizophrenic patients. One 90-days subchronic toxicity study with rats was identified, showing a no observed adverse effect level (NOAEL) of 3357 mg/kg bw per day (the highest dose tested), with no functional, biochemical or histological changes in renal function. In the present report, the value of comparison is set to 86 mg/kg bw per day, corresponding to 6000 mg per day in a 70 kg adult; the daily dose provided in the two human RCTs. The calculated margins of exposures (MOE-values) range from 1.2 to 6.0 for the specified supplement doses with 1000-3000 mg/day of L-lysine. MOE-values below 10 (for interindividual differences in humans) is regarded as acceptable since L-lysine is a nutrient that does not cause any known adverse effects. In addition, the overall mean lysine intake according to NHANES III (5.3 g/day) is close to the the doses considered in the present risk assessment. The requirement for lysine, 30 mg/kg bw per day, corresponding to 2.1 g/day in a 70 kg adult, is close to the doses considered in the present risk assessment. The NOAEL suggested in the 90 days subchronic rat study supports the suggestion that these doses are well tolerated in humans even with somewhat low MOE-values. VKM concludes that: In adults (≥18 years), the specified doses 1000, 2000, 2500, 2750 and 3000 mg/day L-lysine in food supplements are unlikely to cause adverse health effects. In adolescents (14 to <18 years), the specified doses 1000, 2000, 2500, 2750 and 3000 mg/day L-lysine in food supplements are unlikely to cause adverse health effects. In children (10 to <14 years), the specified doses 1000, 2000, 2500, 2750 and 3000 mg/day L-lysine in food supplements are unlikely to cause adverse health effects. Children younger than 10 years were not within the scope of the present risk assessment.

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Risk Assessment of "Other Substances" – L- tryptophan

European Journal of Nutrition & Food Safety ◽

10.9734/ejnfs/2020/v12i830268 ◽

2020 ◽

pp. 75-77

Author(s):

Kristin Holvik ◽

Livar Frøyland ◽

Margaretha Haugen ◽

Martinus Løvik ◽

Tor A. Strand ◽

...

Keyword(s):

Risk Assessment ◽

Adverse Effects ◽

Health Effects ◽

Literature Search ◽

Food Supplements ◽

Risk Assessments ◽

Adverse Health Effects ◽

Adverse Health ◽

Other Substances ◽

The Uk

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 <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 children (10 to <14 years), the specified doses 250, 300, and 450 mg/day L-tryptophan in food supplements may represent a risk of adverse health effects. Children below 10 years were not included in this assessment.

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Risk Assessment of "Other Substances" – L-serine

European Journal of Nutrition & Food Safety ◽

10.9734/ejnfs/2020/v12i830267 ◽

2020 ◽

pp. 72-74

Author(s):

Tonje Holte Stea ◽

Livar Frøyland ◽

Margaretha Haugen ◽

Sigrun Henjum ◽

Kristin Holvik ◽

...

Keyword(s):

Risk Assessment ◽

Health Effects ◽

Animal Studies ◽

Literature Search ◽

Food Supplements ◽

Risk Assessments ◽

Adverse Health Effects ◽

Adverse Health ◽

Scientific Papers ◽

Other Substances

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 <14 years), adolescents (14 to <18 years) and adults (≥18 years). The MOE-values ranged from 74 to 4200, which were considered acceptable since L-serine is a nutrient that does not cause any well documented adverse effects and because studies indicate a high endogenous production (Snell, 1986) and a high dietary intake of L-serine (NHANES III, USA) compared to the doses considered in the present risk assessment. Thus, VKM concludes that: In adults (≥18 years), the specified doses 50, 500, 1000, 1250, 1500 and 1750 mg/day L-serine in food supplements are unlikely to cause adverse health effects. In adolescents (14 to <18 years), the specified doses 50, 500, 1000, 1250, 1500 and 1750 mg/day L-serine in food supplements are unlikely to cause adverse health effects. In children (10 to <14 years), the specified doses 50, 500, 1000, 1500 and 1800 mg/day L-serine in food supplements are unlikely to cause adverse health effects. Children younger than 10 years were not within the scope of the present risk assessment.

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Risk Assessment of "Other Substances" – L-Tyrosine

European Journal of Nutrition & Food Safety ◽

10.9734/ejnfs/2020/v12i830269 ◽

2020 ◽

pp. 78-80

Author(s):

Livar Frøyland ◽

Margaretha Haugen ◽

Sigrun Henjum ◽

Kristin Holvik ◽

Martinus Løvik ◽

...

Keyword(s):

Food Safety ◽

Adverse Effects ◽

Health Effects ◽

Present Report ◽

Food Supplements ◽

Risk Assessments ◽

Adverse Health Effects ◽

Adverse Health ◽

Adverse Effect Level ◽

Other Substances

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 <18 years), the specified doses of 1250, 1500, 1750, and 2000 mg/day L-tyrosine in food supplements may represent a risk of adverse health effects. In children (10 to <14 years), the specified doses of 1250, 1500, 1750, and 2000 mg/day L-tyrosine in food supplements may represent a risk of adverse health effects. Children below 10 years were not included in the terms of reference.

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Risk Assessment of Other Substances in Food Supplements - L-methionine

European Journal of Nutrition & Food Safety ◽

10.9734/ejnfs/2020/v12i830263 ◽

2020 ◽

pp. 61-62

Author(s):

Tor A. Strand ◽

Livar Frøyland ◽

Margaretha Haugen ◽

Sigrun Henjum ◽

Kristin Holvik ◽

...

Keyword(s):

Risk Assessment ◽

Adverse Effects ◽

Food Supplement ◽

Physiological Effect ◽

Food Supplements ◽

Risk Assessments ◽

Beneficial Effects ◽

Scientific Papers ◽

Other Substances ◽

Per Se

"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.

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Risk Assessment of Specific Strains of Lactobacillus rhamnosus Used as "Other Substances"

European Journal of Nutrition & Food Safety ◽

10.9734/ejnfs/2019/v9i430076 ◽

2019 ◽

pp. 315-316

Author(s):

Siamak Yazdankhah ◽

Danica Grahek-Ogden ◽

Karl Eckner ◽

Georg Kapperud ◽

Jørgen Lassen ◽

...

Keyword(s):

Risk Assessment ◽

Adverse Effects ◽

Intestinal Tract ◽

Lactobacillus Rhamnosus ◽

Food Supplements ◽

Risk Assessments ◽

Age Group ◽

Other Substances ◽

Gastro Intestinal Tract

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 sold in Norway. These risk assessments will provide NFSA with the scientific basis for regulation of 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 and/or physiological effect. It is added mainly to food supplements, but also to 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 Lactobacillus rhamnosus Rosell-11 ND, Lactobacillus rhamnosus W71, Lactobacillus rhamnosus GG and Lactobacillus rhamnosus Lr-329 based on previous risk assessments and also publications retrieved from literature search. The risk of the Lactobacillus strains listed above was assessed for the general population. However, in previous assessments of probiotics published by VKM, concerns have been identified for specific groups. Therefore, the risk was assessed for the age group with immature gastro-intestinal microbiota (age group 0-36 months), population with mature gastro-intestinal microbiota (>3 years) and vulnerable groups with mature gastro-intestinal tract. VKM has also assessed the risk of L. rhamnosus Rosell-11 ND, L. rhamnosus W71, L. rhamnosus GG and L. rhamnosus Lr-329 in food supplements and other foods independent of the dose and have assessed exposure in general terms. VKM concludes that it is unlikely that L. rhamnosus Rosell-11 ND, L. rhamnosus W71, L. rhamnosus GG and L. rhamnosus Lr-329 would cause adverse health effects in the general healthy population with mature gastro-intestinal tract. However, no data on long-term adverse effects on infants and young children were identified. As evidence is accruing that the early microbial composition of the neonatal gut is important for the development of the gut microbiota and the immune system of the growing child, it is not possible to exclude that a daily supply of a single particular bacterial strain over a prolonged period of time to an immature gastro-intestinal tract may have long-term, although still unknown, adverse effects on that development.

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Risk Assessment of Specific Strains of Lactobacillus acidophilus Used as "Other Substances"

European Journal of Nutrition & Food Safety ◽

10.9734/ejnfs/2019/v9i230049 ◽

2019 ◽

pp. 110-111

Author(s):

Siamak Yazdankhah ◽

Danica Grahek-Ogden ◽

Karl Eckner ◽

Georg Kapperud ◽

Jørgen Lassen ◽

...

Keyword(s):

Risk Assessment ◽

Adverse Effects ◽

Lactobacillus Acidophilus ◽

Intestinal Tract ◽

Food Supplements ◽

Risk Assessments ◽

Age Group ◽

Other Substances ◽

Gastro Intestinal Tract

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 sold in Norway. These risk assessments will provide NFSA with the scientific basis for regulation of 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 and/or physiological effect. It is added mainly to food supplements, but also to 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 Lactobacillus acidophilus W37, Lactobacillus acidophilus DDS-1, Lactobacillus acidophilus La-5 and Lactobacillus acidophilus La-14 based on previous risk assessments and also publications retrieved from literature search. The risk of the Lactobacillus strains listed above was assessed for the general population. However, in previous assessments of probiotics published by VKM, concerns have been identified for specific groups. Therefore, the risk was assessed for the age group with immature gastro-intestinal microbiota (age group 0-36 months), population with mature gastro-intestinal microbiota (>3 years) and vulnerable groups with mature gastro-intestinal tract. VKM has also assessed the risk of L. acidophilus W37, L. acidophilus DDS-1, L. acidophilus La-5 and L. acidophilus La-14 in food supplements and other foods independent of the dose and have assessed exposure in general terms. VKM concludes that it is unlikely that L. acidophilus W37, L. acidophilus DDS-1, L. acidophilus La-5 and L. acidophilus La-14 would cause adverse health effects in the general healthy population with mature gastro-intestinal tract. However, no data on long-term adverse effects on infants and young children were identified. As evidence is accruing that the early microbial composition of the neonatal gut is important for the development of the gut microbiota and the immune system of the growing child, it is not possible to exclude that a daily supply of a single particular bacterial strain over a prolonged period of time to an immature gastro-intestinal tract may have long-term, although still unknown, adverse effects on that development.

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Risk Assessment of Specific Strains of Bifidobacterium spp. Used as "Other Substances"

European Journal of Nutrition & Food Safety ◽

10.9734/ejnfs/2019/v9i230048 ◽

2019 ◽

pp. 108-109

Author(s):

Siamak Yazdankhah ◽

Danica Grahek-Ogden ◽

Karl Eckner ◽

Georg Kapperud ◽

Jørgen Lassen ◽

...

Keyword(s):

Risk Assessment ◽

Food Safety ◽

Adverse Effects ◽

Intestinal Tract ◽

Food Supplements ◽

Risk Assessments ◽

Age Group ◽

Other Substances ◽

Gastro Intestinal Tract

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 sold in Norway. These risk assessments will provide NFSA with the scientific basis for regulation of 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 and/or physiological effect. It is added mainly to food supplements, but also to 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 Bifidobacterium lactis Bi-07, Bifidobacterium bifidum W23, Bifidobacterium longum Rosell-175, Bifidobacterium breve Rosell-70, and Bifidobacterium animalis sub. lactis Bb12 based on previous risk assessments and also publications retrieved from literature search. The risk of the Bifidobacterium strains listed above was assessed for the general population. However, in previous assessments of probiotics published by VKM, concerns have been identified for specific groups. Therefore, the risk was assessed for the age group with immature gastro-intestinal microbiota (age group 0-36 months), population with mature gastro-intestinal microbiota (>3 years) and vulnerable groups with mature gastro-intestinal tract. VKM has also assessed the risk of Bifidobacterium spp. in food supplements and other foods independent of the dose and have assessed exposure in general terms. VKM concludes that it is unlikely that B. lactis Bi-07, B. bifidum W23, B. longum Rosell-175, B. breve Rosell-70, and B. animalis sub. lactis Bb12 would cause adverse health effects in the general healthy population with mature gastro-intestinal tract. However, no data on long-term adverse effects on infants and young children were identified. As evidence is accruing that the early microbial composition of the neonatal gut is important for the development of the gut microbiota and the immune system of the growing child, it is not possible to exclude that a daily supply of a single particular bacterial strain over a prolonged period of time to an immature gastro-intestinal tract may have long-term, although still unknown, adverse effects on that development.

Download Full-text