1.             In 2022, the Department for Environment, Food and Rural Affairs (Defra) held a consultation on the Bread and Flour Regulations (BFR) 1998  to increase the fortification level of non-wholemeal wheat flour with calcium as calcium carbonate, iron and niacin to allow harmonisation with EU retained Regulation (EU) No 1169/2011. Defra asked whether the consultees agreed with the proposal to raise the minimum levels of these nutrients, added to 15% of their respective nutrient reference values (NRV). The current minimum amounts of calcium, iron and niacin required to be present in non-wholemeal wheat flour are 11.75%, 12% and 10% of their NRVs, respectively. The minimum amount of thiamin required to be present in non-wholemeal wheat flour would remain unchanged, at 19% of its NRV. NRVs are established guidelines for recommended daily nutrient consumption.

2.             Further to Defra’s proposal, the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) have been asked by the Department of Health and Social Care (DHSC) to provide a risk assessment of dietary exposure to calcium, iron, niacin (vitamin B3) and thiamin (vitamin B1), based on current and proposed fortification levels. The risk assessment provides a comparison of estimated dietary exposure to the UK Expert Group on Vitamins and Minerals (EVM) guidance levels for the four nutrients, and allows for a conclusion on whether there is a potential risk to human health from the proposed increased fortification in non-wholemeal wheat flour.

3.    The BFR 1998 stipulates the levels of calcium as calcium carbonate, iron, thiamin (vitamin B1) and niacin that are required to be present in all wheat flour other than wholemeal (i.e., non-wholemeal wheat flour). Calcium is added in the form of calcium carbonate. Natural calcium found in food would not be present in the form of calcium carbonate. Therefore, exposure to calcium from fortified food can be distinguished from natural or supplementary sources when analysed. Niacin is added to flour in the form of either nicotinic acid or nicotinamide.

4.    The existing BFR (1998) set a minimum fortification level for thiamin (vitamin B1) of 0.24 mg thiamin hydrochloride, which is equivalent to 0.21 mg of thiamin (supplied by 100 g of non-wholemeal wheat flour) or 19% of the NRV. The proposed minimum fortification levels of calcium, iron and niacin have been set at 15% of their respective NRVs, as stated in Annex XIII of regulation EC No. 1169/2011 (in point 1 of Part A). In practice, foods are not currently fortified at these respective levels, but industry are looking to increase fortification to the set minimum levels. The daily NRVs for calcium, iron, niacin and thiamin (vitamin B1) are 800 (or 2,000 as calcium carbonate), 14, 16 and 1.1 mg, respectively.  

Calcium

5.    High intakes of calcium carbonate of around 4,000 mg/day (equivalent to 1,600 mg calcium) can result in a condition called milk-alkali syndrome in people with underlying medical conditions such as peptic ulcers (EFSA, 2006). This condition is characterised by hypercalcaemia, alkalosis and renal impairment, which is associated with hypertension, neurological problems, abdominal pain and tissue calcification (EVM, 2003).

6.    Calcium supplements have been administered to people with colonic polyps or people who are at risk of colonic polyps. Gastrointestinal (GI) effects were reported in a small number of patients receiving 1,600 or 2,000 mg/day of calcium (EVM, 2003).  

7.    High calcium diets can affect the bioavailability of other minerals such as iron, zinc, magnesium and phosphorous by inhibiting the absorption of iron salts, haem-iron and zinc, reducing magnesium absorption and excretion, and the binding of calcium acetate and calcium carbonate to phosphate in the intestinal lumen (EFSA, 2006).

Iron

8.    Iron toxicity is particularly hazardous in children and most poisoning cases are reported in children consuming iron supplements intended for adults. Symptoms in infants include GI irritation at acute doses of around 20 mg/kg bw and systemic effects which occur at doses >60 mg/kg bw. The lethal dose in children is between 200-300 mg/kg bw (EVM, 2003).

9.    In adults, GI effects such as constipation, nausea, vomiting and diarrhoea have been reported at therapeutic doses of 50-220 mg/person/day (EFSA, 2006). Iron toxicity can lead to inflammation and perforation of the GI tract and iron disrupts cellular metabolism in the central nervous system, liver and heart. Free iron in the serum enters and concentrates in the mitochondria where it forms free radicals, which can impair energy metabolism and can eventually lead to cell death (Baranwal and Singhi, 2003; Yuen and Becker, 2022). However, iron poisoning (where iron is in its free form) in adults is rare, Individual case reports suggest a lethal dose of 1,400 mg/kg bw (EVM, 2003).

Niacin (vitamin B3)

10.    Symptoms of acute toxicity from niacin include flushing, itchy skin, nausea, vomiting and GI issues (such as diarrhoea and constipation). Long term intakes of 3,000 mg/day of niacin have been reported to cause jaundice, hyperglycaemia and abdominal pain. In addition to elevated serum bilirubin, increased alkaline phosphatase and aminotransferase levels, indicative of effects on the liver, have been reported in a small number of cases. Anorexia, ophthalmological effects, skin hyperpigmentation and precipitation of incipient psychosis have also been reported as side effects of niacin therapy (EVM, 2003).

11.    Patients with hypercholesterolaemia that have been treated with niacin at 3-9 g/day over a period of months to years showed symptoms of severe liver dysfunction, which has the potential to be life threatening and may require liver transplantation (EFSA, 2006).

Thiamin (Vitamin B1)

12.    Thiamin is considered to be of very low toxicity, with symptoms such as headache, nausea, irritability, insomnia, rapid pulse and weakness being seen at high oral doses of ≥7,000 mg thiamin hydrochloride (EVM, 2003).

13.    However, a small number of case reports have shown association with adverse effects such as muscle tremors, rapid pulse and nerve hyperirritability at daily doses as low as 17 mg/day of thiamin hydrochloride. In one case, a patient consuming thiamin at 100 mg/day for a period of 15 days, 2 months prior to consumption of a single oral dose of thiamin of 100 mg, experienced an anaphylactic reaction followed by death. In another case, a patient experienced exacerbated eczema after receiving an oral dose of 200 mg of thiamin in an experimental provocation (EVM, 2003). In a 2018 report, a few patients with Parkinson’s disease treated with 2-3 intramuscular doses of 100 mg of thiamin/week experienced adverse effects of discomfort, unrest and an overall worsening of symptoms of Parkinson’s disease, and a medium intensity migraine (Costantini and Fancellu, 2018).  

14.    The COT noted that alcohol consumption may be a confounding factor in some of the case reports. Most cases of thiamin deficiency were associated with chronic alcoholism, where absorption and utilisation of thiamin are impaired (EVM, 2003).                                                        

15.    No tolerable upper levels (TUL) or safe upper levels (UL) have been established for calcium, iron, niacin and thiamin by the EVM due to the lack of sufficient animal and human data (EVM, 2003).

16.    However, the EVM stated that “1,500 mg/day of supplemental calcium would not be expected to result in any adverse effect, but that higher doses could result in adverse GI symptoms in a few people” (EVM, 2003). The Scientific Committee on Food (SCF) established a TUL of 2,500 mg/day for calcium in 2003 (SCF, 2003). This TUL was based on long duration intervention studies of different time periods in which total daily calcium intakes of 2,500 mg from both diet and supplements were tolerated without adverse effects and was endorsed by EFSA in 2012 (EFSA, 2012).

17.    The EVM proposed that a supplemental intake of 17 mg/person/day (0.22 mg/kg bw per day for a 78.6 kg adult) (based on the average body weight in the UK National Diet and Nutrition Survey (NDNS) data) (Bates et al., 2014, 2016, 2020; Roberts et al., 2018) for iron would not be expected to produce adverse effects in the majority of individuals. However, this guidance value does not apply to individuals who have an increased susceptibility to iron overload, a condition which is associated with a homozygous haemochromatosis genotype (with an estimated prevalence of up to 0.4% in the Caucasian population). An UL for iron has not been established by EFSA. The National Institutes of Health Office of Dietary Supplements in the United States have advised ULs of 40 mg/day/person for individuals aged 0 months to 13 years and 45 mg/day for individuals aged 14 years and over (Institute of Medicine, 2001). However, it has been reported that ingestion <20 mg/kg of elemental iron is non-toxic and moderate symptoms of iron toxicity can occur between 20 to 60 mg/kg (Yuen and Becker, 2022).

18.    The EVM proposed that a guidance level of 17 mg/day for niacin would not be expected to result in any adverse effects. However, it was noted by the EVM that this guidance level is for supplementation only, as adverse effects from niacin seem to be related to acute, bolus intakes. Adverse effects from long term exposure of niacin in food would be less likely as free niacin levels in food are low. Additionally, the EVM noted that the guidance level is based on intakes of conventional formulations of niacin. This would not be applicable to sustained release preparations but niacin contained in dietary supplements is not in the sustained release form (EVM, 2003). In 2002, the SCF set an UL of 10 mg/day for niacin based on flushing of skin (EFSA, 2014).

19.    The EVM proposed a guidance level for supplemental thiamin of 100 mg/day, which would not be expected to result in adverse effects. The EVM noted however that this guidance level was applicable only to the water-soluble forms of thiamin. Furthermore, the study by Gokhale et al. (1999), used to derive the guidance level, was conducted in young women (EVM, 2003) who may not be representative of the population in general. An UL for thiamin was not established by the SCF as there were only limited data on adverse effects in humans and lack of dose-response studies (EFSA, 2016). Whilst there is a lack of evidence of toxicity from a high intake of thiamin from food or supplements (Martel et al., 2021), symptoms such as headache, nausea, irritability, insomnia, rapid pulse and weakness have been observed at high oral doses of ≥7,000 mg/day thiamin hydrochloride (EVM, 2003).

20.    Exposures to calcium, iron, niacin and thiamin were estimated using consumption data from the Diet and Nutrition Survey of Infants and Young Children (DNSIYC) and the NDNS. Levels of these nutrients in the entire diet were obtained from the nutrient databank (Bates et al., 2014, 2016, 2020; Roberts et al., 2018). Levels of nutrients in non-wholemeal wheat flour used in the exposure assessment were those currently in use by industry. Exposure to the nutrients based on the proposed increases were also determined, except for thiamin, where no increases have been proposed. Table 2 provides information about current and proposed fortification levels for each nutrient where applicable. Exposures to these nutrients were calculated in Crème Global, the software used by the FSA to interrogate dietary data and calculate exposure. Exposure estimates were derived by multiplying food consumption amounts by the levels of the nutrients in the foods. Chronic exposures or intakes of these nutrients are presented. Chronic intake is estimated from the average amount of flour consumed per day over the survey days multiplied by the levels of nutrients. Chronic exposure or intake is calculated for each consumer. The mean and 97.5^th percentile are then calculated.

Table 1. Concentration data used to estimate exposure to calcium, iron, niacin and thiamin.

Methodology for estimating actual and proposed exposures from non-wholemeal wheat flour

21.    Exposures based on actual and proposed levels of fortification were calculated from foods containing non-wholemeal wheat flour. This, by definition, is wheat flour without whole grain wheat. The recipe database associated with the NDNS food groupings identified foods containing non-wholemeal wheat flour (n = 1835). A selection of food groups (foods with non-wholemeal wheat flour), each containing more than 20 foods, is shown in Table A1 in Annex A.

22.    The fortification level for thiamin remains unchanged, therefore exposures at the proposed fortification levels were calculated only for calcium, iron, and niacin.

23.    Exposures to these nutrients from supplements were also considered. Data for supplements were obtained from market sources (e.g., websites of major retailers). Doses of calcium supplements ranged from 200 - 1200 mg/day for adults and 80 - 450 mg/day for children. Whereas doses of iron supplements ranged from 14 - 28 mg/day in adults and 2.8 - 7.5 mg/day in children. Doses of niacin supplements ranged from 50 – 1,000 mg/day in adults and 4.8 - 20 mg/day in children. Doses of thiamin supplements ranged from 100 - 500 mg/day for adults and 0.5 – 5.0 mg/day for children.    

Exposures from the entire diet and from flour at the actual and proposed fortification levels

24.    Exposures to the nutrients from the entire diet (including food groups containing non-wholemeal wheat flour at the actual and proposed levels of fortification) was estimated using all food groups from NDNS years 1 - 11, and are presented in Table A2 of Annex A. All food groups, including the foods containing non-wholemeal wheat flour. are detailed in Table A1 of Annex A. The levels of the nutrients for each of the foods included were derived from the nutrient databank from the NDNS.

25.    It should be noted that the nutrient data from NDNS used in the assessment of the entire diet accounts for industry use of overage (the industry practice of increasing the level of fortificants added to food in order to account for degradation during manufacture and storage) only in foods such as flour but not in other foods such as breakfast cereals and is therefore a potential source of uncertainty. Estimates for flour at the actual and proposed fortification levels, also do not account for overage as they are based on nutrient levels that are stipulated by legislation, not the nutrient databank, and is also a source of uncertainty.   

26.    Estimated exposure to calcium, iron, niacin and thiamin from the entire diet and from non-wholemeal wheat flour fortification at actual and proposed levels are shown in Tables 2-5.

27.    For calcium, across all age groups (4 months to 65+ years), the maximum mean and maximum 97.5^th percentile exposures at the current actual level of fortification were 68 and 140 mg/person/day, respectively. The maximum mean and 97.5^th percentile exposures at the proposed level of fortification are 87 and 180 mg/person/day, respectively. The maximum exposures to calcium from the entire diet are 820 and 1,600 mg/person/day at mean and 97.5^th percentile levels, respectively (Table 3).

28.    For iron, across all age groups (4 months to 65+ years), the maximum mean and maximum 97.5^th percentile exposures at the current actual level of fortification are 1.2 and 2.5 mg/person/day respectively. The maximum mean and 97.5^th percentile exposures at the proposed level of fortification are 1.5 and 3.2 mg/person/day respectively. The maximum exposures to iron from the entire diet are 10 and 19 mg/person/day at mean and 97.5^th percentile levels, respectively (Table 4).

29.    For niacin, across all age groups (4 months to 65+ years), the maximum mean and maximum 97.5^th percentile exposures at the current actual level of fortification are 1.2 and 2.4 mg/person/day, respectively. The maximum mean and 97.5^th percentile exposures at the proposed level of fortification are 1.7 and 3.6 mg/person/day, respectively. The maximum exposure to niacin from the entire diet are 36 and 68 at the mean and 97.5^th percentile, respectively (Table 5).

30. For thiamin, across all age groups (4 months to 65+ years), the maximum mean and maximum 97.5^th percentile exposures at the current actual level of fortification are 0.17 and 0.36 mg/person/day, respectively. No increase in the fortification level of thiamin is proposed. The maximum exposures to thiamin from the entire diet are 1.5 and 2.8 mg/person/day at the mean and 97.5^th percentile, respectively (Table 6).

Table 2. Estimated chronic exposures to calcium from the diet and from non-wholemeal wheat flour fortification at actual and proposed levels (15% of the nutrient reference value supplied by 100 g flour) levels.

Table 3. Estimated chronic exposures to iron from the diet and non-wholemeal wheat from flour fortification at actual and proposed (15% of the nutrient reference value supplied by 100 g flour) levels.

Table 4. Estimated chronic exposures to niacin equivalents from the diet and from non-wholemeal wheat flour fortification at current and proposed (15% of the nutrient reference value supplied by 100 g flour) levels.

Table 5. Estimated chronic exposures to thiamin in the diet and from non-wholemeal wheat flour fortification at actual (19% of the nutrient reference value supplied by 100g flour; there is no proposed increase to thiamin) levels.

* Rounded to 2 significant figures.

Exposure from supplements

31.    It should be noted that supplements data were derived from various online sources and are shown in Tables A7 – A10 in Annex A. The highest doses of calcium, iron, niacin and thiamin in supplements were used as the values for the upper exposures from supplements. The exact consumption by the population was unknown therefore exposures were calculated based on recommended dose sizes. The exposure data for supplements do not take into account industry use of overage in this assessment and is therefore a potential source of uncertainty.

32.    Across all age groups (4 months to 65+ years) the upper exposures to supplemental calcium were up to 1,200 mg/day. In adults aged over 18 years, this exposure is equivalent to 1.48- and 0.75-fold the mean (2,000 mg/day) and 97.5^th percentile (2,800 mg/day) calcium exposures from the entire diet (which includes all food groups including non-wholemeal wheat flour), respectively.   

33.    Across all age groups (4 months to 65+ years) the upper exposures to supplemental iron were up to 28 mg/day. In adults aged over 18 years, this exposure is equivalent to 3- and 1.6-fold the mean (38 mg/day) and 97.5^th percentile (47 mg/day) iron exposures from the entire diet, respectively.

34.    Across all age groups (4 months to 65+ years) the upper exposures to supplemental niacin were up to 1,000 mg/day. In adults aged over 18 years this exposure is equivalent of up to 32- and 19-fold of the mean (1000 mg/day) and 97.5^th (1000 mg/day) percentile niacin exposures from the entire diet, respectively.

35.    Across all age groups (4 months to 65+ years) the upper exposures to supplemental thiamin were up to 500 mg/day. In adults aged over 18 years, this exposure is equivalent to 330- and 185-fold the mean (500 mg/day) and 97.5^th percentile (500 mg/day) thiamin exposures from the entire diet.

Exposures from food

36.    Chronic exposure to calcium from non-wholemeal wheat flour at the current actual and proposed fortification levels (Table 2) did not exceed the guidance level of 1,500 mg/person/day (EVM, 2003) or 2,500 mg/day (EFSA, 2012), in any age group. Exposure from the entire diet was up to 1,600 mg/person day, which, although marginally exceeding the EVM guidance level, is below the SCF TUL of 2,500 mg/day.

37.    Chronic exposures to iron from non-wholemeal wheat flour at the current actual and proposed fortification levels (Table 3) did not exceed the guidance levels of 17 mg/day (EVM, 2003) in any age group. Exposures from the entire diet were up to 19 mg/person/day, which would result in marginal exceedance of the EVM guidance level. However, it is important to note that the guidance level is based on supplemental intake and not dietary intake. The level did not exceed that reported to cause moderate symptoms of iron toxicity, i.e. 20 mg/kg bw per day (1572 mg per person/day for a 78.6 kg adult) (Madiwale and Liebelt, 2006). Hence, it is not anticipated that there would be a risk to health from exposure to iron in the entire diet in most of the population. However, the EVM guidance value does not apply to individuals who have an increased susceptibility to iron overload, a condition which is associated with a homozygous haemochromatosis genotype. Such individuals would normally be under medical supervision to ensure their exposure to iron was appropriate.

38.    Chronic exposures to niacin equivalents from non-wholemeal wheat flour (Table 4) at the current actual and proposed fortification levels did not exceed the guidance level for niacin of 17 mg/day (EVM, 2003) in any age group. Exposures to niacin from the entire diet were up to 68 mg/person/day, which exceed the EVM guidance level up to 4-fold. However, the EVM guidance level is for supplementation only, as adverse effects from niacin seem to be related to acute, bolus intakes. It is unlikely that there would be a risk of adverse health effects at these exposures from the diet, although there is some uncertainty.

39.    Chronic exposures to thiamin at the actual fortification level (Table 5) did not exceed the current guidance level of 100 mg/day (EVM, 2003) in any age group. Exposures to thiamin from the entire diet were up to 2.8 mg/person/day which were also well below the EVM guidance level, and it is unlikely that there would be any adverse health effects from thiamin in the diet.

Exposure from supplements

40.    Daily exposure to calcium supplements did not exceed the EVM guidance level of 1,500 mg/day (EVM, 2003) or the SCF guidance level of 2,500 mg/day in adults and children (SCF, 2003). Exposure to higher dosage iron supplements (i.e., 28 mg/day) can result in exceedance of the guidance level of 17 mg/day (EVM, 2003) by up to 1.6-fold in adults. Daily exposure to niacin supplements could result in exceedances of the guidance level of 17 mg/day (EVM, 2003), by between 3- and 60-fold. For thiamin supplements, daily exposure could lead to up to a 5-fold exceedance of the guidance level of 100 mg/day (EVM, 2003).

Combined exposure from supplements and food

41.    Mean calcium exposures from food (the entire diet and flour at the current and proposed fortification levels) and supplements (Table A3, Annex A) were up to 2,000 mg/person/day, respectively and below either the EVM guidance level and/or the SCF TUL, with the exception of 65+ years, in whom there was a 30% exceedance of the guidance level. Exposures associated with 97.5^th percentile consumption were between 1,700 and 2,800 mg/person/day. For population groups below 19 years of age, the exposures are below the SCF TUL and it is unlikely that there would be a risk of adverse health effects. Population groups of 18 years and over marginally exceeded the SCF TUL but it is unlikely that there would be a risk of adverse health effects at these exposures, given the assumptions made in this assessment.  

42.    Mean and 97.5^th percentile iron exposures from food and supplements were up to 25 mg/person/day (Table A4, Annex A) and included values which were either below or slightly exceeded the guidance level of 17 mg/day (EVM, 2003) in those aged up to 18 years. There is unlikely to be a risk of adverse health effects in these populations due to exposures from iron, given the assumptions made in this assessment. In the 19-64 and 65+ years age groups, mean and 97.5^th percentile iron exposures were up to 38 and 47 mg/person/day, which exceeded the guidance level by up to 2.2-fold and 2.8-fold, respectively.  It is unlikely that there is a risk of adverse health effects in the majority of the population, as it was assumed that all individuals use supplements, at the maximum reported iron levels. It should be noted that the EVM guidance value does not apply to individuals who have an increased susceptibility to iron overload, a condition which is associated with a homozygous haemochromatosis genotype, and who should be advised appropriately by a medical practitioner.

43.    Mean and 97.5^th percentile niacin exposure from food (entire diet) and supplements (Table A5, Annex A) exceeded the guidance level of 17 mg/day (EVM, 2003) in all age groups. In those aged up to 18 years, exceedances were up to 3- and 4.4-fold for mean and 97.5^th percentile consumption, respectively. In individuals aged up to 3 years the exceedances were approximately half of these (up to 2.2- and 1.06-fold) for mean and 97.5^th percentile consumers, respectively). In those aged over 18 years the exceedances were up to 59- and 65-fold for mean and 97.5^th percentile consumers, respectively. Much of this exceedance comes from the consumption of supplements containing niacin at 1,000 mg. It is important to note that the guidance level of 17 mg/day is based on supplemental intake.

44.    As noted previously, the EVM guidance level is for supplementation only, as adverse effects from niacin seem to be related to acute, bolus intakes. Hence, adverse effects from long term exposure to niacin in food would be less likely. Exposures from consumption of supplements containing high levels of niacin e.g., 1,000 mg could result in increased risk of adverse health effects, especially when consumed consistently at these high levels over a prolonged period of time.

45. Exposures to thiamin from food and supplements (Table A6, Annex A) for all age groups below 18 years of age are below the guidance level of 100 mg/day (EVM, 2003). Mean and 97.5^th percentile intakes from food and supplements exceeded the guidance level for thiamin only in the 19-64 years and 65+ years age groups. These age groups both exceeded the guidance level by 5-fold. This was predominantly from consumption of supplements, which may contain up to 500 mg.  It is unlikely that dietary exposures would cause adverse health effects, as the EVM guidance level is based on supplemental intake.

46.    Chronic exposures to calcium (as calcium carbonate), iron and niacin from non-wholemeal wheat flour at the current actual and proposed fortification levels, and to thiamin (for which no change was proposed) at the current actual fortification level did not exceed their respective guidance levels. For each of the nutrients, the difference in exposure between current and proposed levels of fortification is at most 4%, when compared to exposures form the entire diet and even less when compared with combined exposure from the diet and supplements. Therefore, the change to the proposed levels of fortification would not result in any material increase in the risk of adverse health effects, particularly when considering the entire diet and consumption of supplements.

47.    Independent of the proposed increase in the level of fortification, calcium exposure from food and supplements exceeded the EFSA TUL of 2,500 mg/day, however the exceedance was marginal and only in high (97.5^th percentile) consumers in those aged over 18 years. The TUL used in the risk characterisation for calcium is based on supplemental intake, making the assessment conservative for exposures from an increase in calcium in non-wholemeal wheat flour and the entire diet. There is unlikely to be a risk of adverse health effects.

48.    Iron exposures from food and supplements exceeded the guidance levels of 17 mg/day in some age groups, up to a maximum of 2.8-fold, independent of the proposed increase in the level of fortification. It is unlikely that there is a risk of adverse health effects in the majority of the population, as not all individuals use supplements, and those that do, do not all use those with the maximum reported iron levels. However, the NHS advises that you should be able to get all the iron you need from your daily diet (NHS, 2020). For individuals not consuming iron supplements in addition to their daily diet, there is unlikely to be any risk of adverse health effects. However, the EVM guidance value does not apply to individuals who have an increased susceptibility to iron overload, a condition which is associated with a homozygous haemochromatosis genotype. For these individuals, medical advice would be necessary on the appropriate level of iron intake.

49.    In those aged less than18 years, niacin exposure from food and supplements exceeded the guidance level of 17 mg/day (EVM, 2003), up to 3- and 4.4-fold for mean and 97.5^th percentile consumption, respectively. In those aged over 18 years the exceedances of the 17 mg/day guidance level were up to 59- and 65-fold for mean and 97.5^th percentile consumers, respectively. These exceedances were independent of the proposed increase in the level of fortification of non-wholemeal wheat flour. Most of the exceedances are due to consumption of supplements containing niacin at 1,000 mg. Adverse effects from long term exposure to niacin in food would be less likely. However, there is some uncertainty because of the data used to establish the EVM guidance level. It is intended for supplements and is more relevant for a bolus intake. Exposures from consumption of supplements containing high levels of niacin e.g., 1,000 mg could lead to increased risk of adverse health effects, especially when consumed consistently over a prolonged period of time.

50.    No change in the fortification level of thiamin was proposed. Actual exposures to thiamin from food and supplements for all age groups below 18 years of age are below the guidance level of 100 mg/day (EVM, 2003). Mean and 97.5^th percentile intakes from food and supplements exceeded the guidance level for thiamin only in consumers aged over 18, by a maximum of up to 5-fold. This was predominantly from consumption of supplements which may contain up to 500 mg. It is unlikely that these exposures would cause adverse health effects for the reasons explained above.

51.    Although not materially impacted by the level of fortification of non-wholemeal wheat flour (actual current or proposed), it was noted that intakes of calcium from supplements alone did not exceed the guidance level for this mineral whereas consumption of higher dosage iron, niacin and thiamin supplements may result in exceedances of the respective guidance levels.

52.    As discussed in paragraph 23 it should be noted that the estimates for non-wholemeal wheat flour at the actual and proposed fortification levels do not account for overage as they are based on nutrient levels stipulated by legislation and not nutrient levels in the databank, creating a source of uncertainty in this review.

53.    Overall, the COT concluded that an increase in the minimum fortification level of calcium (as calcium carbonate), iron and niacin to 15% of the NRV would not result in any material increase in risk when compared to actual current fortification levels.

COT

May 2023

Statement 03/23

Bates B, Lennox A, Prentice A, Bates C, Page P, Nicholson S, Swan G (2014). National Diet and Nutrition Survey Results from Years 1, 2, 3 and 4 (combined) of the Rolling Programme (2008/2009 – 2011/2012): Main heading (publishing.service.gov.uk)

Bates, B.; Cox, L.; Nicholson, S.; Page, P.; Prentice, A.; Steer, T.; Swan, G. (2016) National Diet and Nutrition Survey Results from Years 5 and 6 (combined) of the Rolling Programme (2012/2013 – 2013/2014): Main heading (publishing.service.gov.uk)

Bates, B.; Collins, D.; Jones, K.; Page, P.; Roberts, C.; Steer, T.; Swan, G.(2020) National Diet and Nutrition Survey Results from years 9, 10 and 11 (combined) of the Rolling Programme (2016/2017 to 2018/2019): National Diet and Nutrition Survey (publishing.service.gov.uk)

Baranwal, A.K. and Singhi, S.C. (2003) ‘Acute iron poisoning: management guidelines’, Indian Pediatrics, 40(6), pp. 534–540.

Costantini and Fancellu (2018). Effects of overdose of high-dose thiamine treatment. Gerontology & Geriatrics Studies, 4(1): Effects of Overdose of High-Dose Thiamine Treatment (crimsonpublishers.com)

DH (2013). Diet and Nutrition Survey of Infants and Young Children (DNSIYC), 2011: Diet and nutrition survey of infants and young children, 2011 - GOV.UK (www.gov.uk)

EFSA (2006). Tolerable Upper Intake Levels for Vitamins and Minerals. Scientific Committee on Food: complet_chapitres.indd (europa.eu)

EFSA (2012). Scientific opinion on the tolerable upper intake level of calcium. EFSA Journal, 10(7), p.2814: Scientific Opinion on the Tolerable Upper Intake Level of calcium (wiley.com)

EFSA (2014). Scientific opinion on dietary reference values for niacin. EFSA Journal 2014;12(7):3759: Scientific Opinion on Dietary Reference Values for niacin (wiley.com)

EFSA (2016). Dietary reference values for thiamin. EFSA Journal, 14(12), p.e04653: Dietary reference values for thiamin (wiley.com)

Expert Group on Vitamins and Minerals (2003). Safe Upper Levels for Vitamins and Minerals: vitmin2003.pdf (food.gov.uk)

Gokhale, LB (1996). Curative treatment of primary (spasmodic) dysmenorrhea. Indian Journal of Medical Research 103, 227-231.

Institute of Medicine: Food and Nutrition Board. (2001) Dietary Reference intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc: a Report of the Panel on Micronutrients.

Madiwale, T. and Liebelt, E. (2006). Iron: not a benign therapeutic drug. Current opinion in pediatrics, 18(2), pp.174-179.

Martel, J.L., Kerndt, C.C., Doshi, H. and Franklin, D.S. (2021). Vitamin B1 (thiamine). In StatPearls [Internet]. StatPearls Publishing.

Roberts, C.; Steer, T.; Maplethorpe, N.; Cox, L.; Meadows, S.; Page, P.; Nicholson, S.; Swan, G. (2018) National Diet and Nutrition Survey Results from Years 7 and 8 (combined) of the Rolling Programme (2014/2015 – 2015/2016).

Scientific Committee on Food (2003). SCF (Scientific Committee on Food), 2003. Opinion on the Tolerable Upper Intake Level of Calcium. CF/CS/NUT/UPPLEV/64 Final, 39 pp.

Yuen, H.-W. and Becker, W. (2022) ‘Iron Toxicity’, in StatPearls. Treasure Island (FL): StatPearls Publishing: Iron Toxicity - StatPearls - NCBI Bookshelf (nih.gov) (Accessed: 30 August 2022).

Secretariat

March 2023

Table A7. Online sources for calcium supplement data.

Table A8. Online sources for iron supplement data.

Table A9. Online sources for Niacin supplement data.

Table A10. Online sources for thiamin supplement data.

Table A1: A selection of food groups containing foods with non-wholemeal wheat flour.

Table A2: All food groups from the NDNS used to estimate the intake of nutrients from the entire diet.

Table A3: Calcium exposure from foods and supplements.

Table A4: Iron exposure from food and supplements.

Table A5: Exposure to niacin from food and supplements.

Table A6: Exposure to thiamin from food and supplements.