Vitamin D and Health

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would not have a lower tolerance for vitamin D than adults. A UL of 100 μg/d (4000 IU/d) was therefore set for children aged 10-17 y. A UL of 50 μg/d (2000 IU/d) was set for children aged 1-10y to take account of their smaller body size. 7.40 COT agreed that the ULs for vitamin D set by EFSA, of 50 and 100 μg/d (2000 and 4000 IU/d) for children aged 1-10y and 11-17y respectively, were appropriate. Groups in which the ULs may not be protective 7.41 The ULs for vitamin D intake proposed for children and adults in the general UK population might not be protective for individuals with medical disorders that pre-dispose to hypercalcaemia. These include: normocalcaemic hyperparathyroidism; granulomatous diseases such as sarcoidosis and tuberculosis; and genetic pre-disposition such as occurs in IIH. Single and/or occasional doses of vitamin D 7.42 Results from most controlled studies in which occasional high doses of vitamin D have been administered suggest that serum 25(OH)D concentrations would not reach levels associated with toxicity. One study of infants (aged 1-20m), however, reported that vitamin D 2 doses of 15,000 µg (600,000 IU) every 3 months increased serum 25(OH)D concentration by up to 1000 nmol/L and hypercalcaemia occurred in 34% of participants. 7.43 The COT concluded that vitamin D doses of 7500 µg (300,000 IU) at intervals of 3 months or longer would not be expected to cause adverse effects in adults. There is greater uncertainty about the effects of larger doses, which might cause hypercalcaemia in some individuals, even if given infrequently. The data were insufficient to specify a safe upper limit for single doses in children but the limited available information suggests that toxicity could occur in infants at doses ≥ 15,000 µg (600,000 IU). Summary & conclusions 7.44 Acute and chronic exposure to excess vitamin D intake can result in hypercalcaemia, demineralisation of bone, soft tissue calcification and renal damage. Hypercalcaemia is the most appropriate endpoint on which to base ULs for vitamin D since adverse effects that might occur at lower doses, through other mechanisms, have not been reliably established. 7.45 ULs for vitamin D recommended by EFSA, of 100 µg/d (4000 IU/d) for adults and children aged 11- 17 y, 50 µg/d (2000 IU/d) for children aged 1-10 y, and 25 µg/d (1000 IU) for infants, are considered appropriate. The ULs do not distinguish between total and supplementary vitamin D intake since dietary intakes of vitamin D make only a small contribution to total exposures at the ULs. 7.46 The ULs proposed may not provide adequate protection for individuals with medical disorders that pre-dispose to hypercalcaemia. These include normocalcaemic hyperparathyroidism, granulomatous diseases (e.g., sarcoidosis and tuberculosis) and genetic predisposition (e.g., IIH). 7.47 Doses of 7500 µg (300,000 IU) at intervals of 3 months or longer would not be expected to cause adverse effects in adults but there is greater uncertainty about the effects of larger doses, which might cause hypercalcaemia in some individuals. There are insufficient data to specify a safe upper limit for single doses in children but the limited information that is available indicates toxicity could occur in infants at doses ≥ 15,000 µg (600,000 IU). 107
8. Dietary vitamin D intakes and serum/plasma 25(OH)D concentrations in the UK 8.1 Nationally representative data on vitamin D intakes and serum/plasma 25(OH)D concentrations of the general population in the UK were drawn from the National Diet and Nutrition Survey (NDNS) rolling programme (RP), a continuous survey of diet and nutrition in adults and children aged 18m upwards. The results presented here are based on a UK representative sample of 3,450 adults aged 19y and above and 3,378 children aged 1½-18y collected over years 1-4 combined (2008/09 to 2011/12) (Bates et al., 2014). Data on institutionalised adults (1994/5) were obtained from the NDNS of people aged 65y and above (Finch et al., 1998). Representative data collected from boosted samples for Scotland (n=867 adults & 828 children), Wales (n=461 adults & 391 children) and Northern Ireland (n=470 adults & 512 children) were obtained from the NDNS RP Scotland (2008/09-2011/12) 82 , the NDNS RP Wales (2009/10-2012/13) 83 and the NDNS RP Northern Ireland (2008/09-2011/12) 84 reports respectively. 8.2 Data on low income populations in the UK (aged 2y and above) from 2003-2005 were obtained from the Low Income Diet and Nutrition Survey (LIDNS) (Nelson et al., 2007a; Nelson et al., 2007b). 8.3 Data on infants and young children (aged 4-18m) were obtained from the 2011 UK Diet and Nutrition Survey of Infants and Young Children (DNSIYC) (Lennox et al., 2013). 8.4 Additional data were obtained from the Health Survey for England (HSE) 2005 85 and 2010 86 and the Scottish Health Survey (SHS) (FSA Scotland 87 , 2013). 8.5 Nationally representative data are not available for pregnant or breastfeeding women. Data presented for pregnant women were obtained from UK based cohort studies. Assessment of vitamin D intakes 8.6 In the NDNS rolling programme, diet was assessed by a food diary of all foods and drinks consumed over 4 consecutive days. Since dietary surveys are reliant on self-reported measures of intake, misreporting of food consumption (generally under-reporting) is known to be a problem in all dietary surveys, including the NDNS. This is an important consideration in the interpretation of the findings. 8.7 In the NDNS, reported total energy intake in children and adults (4-65+ y) was on average 12-34% lower than reported total energy intake measured by the doubly labelled water (DLW 88 ) technique. The discrepancy is probably due to a combination of under-reporting of actual consumption and changing the diet during the recording period. It is not possible to extrapolate these estimates of under-reporting of energy intake to individual foods or nutrients nor to correct or adjust intake estimates to take account of under-reporting. 82 NDNS RP: results from Years 1- 4 (combined) for Scotland (2008/09-2011/12) http://www.food.gov.uk/sites/default/files/ndns-scotland-fullreport.pdf 83 NDNS RP: results from Years 2-5 (combined) for Wales (2009/10-2012/13) http://gov.wales/statistics-and-research/national-diet-nutrition-surveyrolling-programme/?lang=en 84 NDNS RP: results from Years 1- 4 (combined) for Northern Ireland (2008/09-2011/12) http://www.food.gov.uk/sites/default/files/ndns-ni-fullreport.pdf 85 National Centre for Social Research, University College London. Department of Epidemiology and Public Health. (2011). Health Survey for England, 2005. [data collection]. 3rd Edition. UK Data Service. SN: 5675, http://dx.doi.org/10.5255/UKDA-SN-5675-1. 86 NatCen Social Research, Royal Free and University College Medical School. Department of Epidemiology and Public Health. (2015).Health Survey for England, 2010. [data collection]. 3rd Edition. UK Data Service. SN: 6986, http://dx.doi.org/10.5255/UKDA-SN-6986-3. 87 Food Standards Agency. 88 The DLW technique is included as an objective biomarker to validate energy intakes estimated from reported food consumption. 108
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Vitamin D and Health i 2016
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Contents Preface ..................
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Preface The Scientific Advisory Com
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Adviser (Ultraviolet radiation expo
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Ms Gemma Paramor Lay representative
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Metabolism S.5 Vitamin D is convert
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Two studies reported an increase in
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Recommendations S.35 Serum 25(OH)D
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1.8 The terms of reference were: to
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1.18 In assessing the evidence on v
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there is not absolute correspondenc
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Metabolism Absorption of dietary vi
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UVB ▼ SKIN: ▼ Previtamin D 3
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2.49 A number of studies have repor
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using a bolus dose (I 2 =77%) compa
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2.75 Another RCT 21 (Cashman et al.
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3. Photobiology of vitamin D Ultrav
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Erythema and skin cancer 3.10 Two m
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CIE spectrum for photoconversion of
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Effect of skin pigmentation on skin
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increase in mean serum 25(OH)D conc
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4. Measuring vitamin D exposure (fr
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the authors cautioned care in the i
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24,25(OH) 2 D 3 which can contribut
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5. Relationship between vitamin D e
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latitudes > 49.5 o N or S (which we
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increase 25(OH)D concentrations > 5
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22.5 nmol/L (IQR, 16.8-34.3) in sum
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6.7 Although serum 25(OH)D concentr
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calcium intake, although this is mo
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Evidence considered (Tables 1-5, An
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6.43 Preece et al. (1975) measured
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irths (December-February) in the vi
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large loss to follow-up 45 and, sin
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6.81 A pilot RCT in India (Khadilka
Page 71 and 72: Evidence considered (Tables 16-18,
Page 73 and 74: Intervention studies 6.107 A 3-year
Page 75 and 76: Compared with men in the top quarti
Page 77 and 78: chair-rising test. Mean baseline se
Page 79 and 80: heterogeneity among trials for dose
Page 81 and 82: the 600 µg (24,000 IU) vitamin D 3
Page 83 and 84: Bone health indices beyond rickets
Page 85 and 86: Intervention studies 6.177 An RCT i
Page 87 and 88: maternal serum 25(OH)D concentratio
Page 89 and 90: Cancers 6.201 Ecological studies ha
Page 91 and 92: (Gallicchio et al., 2010; Mondul et
Page 93 and 94: 6.226 A systematic review and meta-
Page 95 and 96: Summary - CVD and hypertension 6.23
Page 97 and 98: 6.251 VDRs are expressed in cells o
Page 99 and 100: 10 nmol/L increase in cord blood 25
Page 101 and 102: Evidence considered since IOM repor
Page 103 and 104: difference was not significant (RR=
Page 105 and 106: 6.304 Out of 7 RCTs published subse
Page 107 and 108: (300 µg/12,000 IU per capsule) for
Page 109 and 110: serum 25(OH)D concentration in neon
Page 111 and 112: linked specific VDR gene polymorphi
Page 113 and 114: factors that affect cancer risk. Ob
Page 115 and 116: As a result, cut-offs for deficienc
Page 117 and 118: 7.8 The IOM noted the paucity of lo
Page 119 and 120: years) compared to the placebo grou
Page 121: children (n=179) received weekly do
Page 125 and 126: Food FISH TABLE 1- Vitamin D conten
Page 127 and 128: Serum/plasma 25(OH)D concentrations
Page 129 and 130: Serum/plasma 25(OH)D concentration
Page 131 and 132: 9. Review of DRVs for vitamin D Bri
Page 133 and 134: musculoskeletal health at serum 25(
Page 135 and 136: Modelling the summer sunshine expos
Page 137 and 138: 9.30 Two possible approaches were c
Page 139 and 140: FIGURE 8: Relation between serum 25
Page 141 and 142: UK general population aged under 11
Page 143 and 144: Summary & conclusions 9.59 The RNI
Page 145 and 146: 10. Overall summary and conclusions
Page 147 and 148: tight homeostatic control. As a mar
Page 149 and 150: 10.30 Evidence from RCTs suggest th
Page 151 and 152: Serum/plasma 25(OH)D concentration
Page 153 and 154: 10.53 An RNI of 10 µg/d (400 IU/d)
Page 155 and 156: 11. Recommendations 11.1 Serum 25(O
Page 157 and 158: References Abnet CC, Chen Y, Chow W
Page 159 and 160: Beadle PC, Burton JL & Leach JF (19
Page 161 and 162: Brooke OG, Brown IR, Bone CD, Carte
Page 163 and 164: Clarke B (2008) Normal bone anatomy
Page 165 and 166: Diffey BL (2010) Modelling the seas
Page 167 and 168: Ganji V, Milone C, Cody MM, McCarty
Page 169 and 170: Heaney RP, Armas LA, Shary JR, Bell
Page 171 and 172: Javaid MK, Crozier SR, Harvey NC, G
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Lappe J, Cullen D, Haynatzki G, Rec
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Mantell DJ, Owens PE, Bundred NJ, M
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Murad MH, Elamin KB, Abu Elnour NO,
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Pirotta S, Kidgell DJ & Daly RM (20
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one mass, and renal function in the
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Sperati F, Vici P, Maugeri-Sacca M,
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Vervel C, Zeghoud F, Boutignon H, T
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Weisse K, Winkler S, Hirche F, Herb
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Annexes ANNEX (1) SACN working proc
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ANNEX (2) Studies considered in rel
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Cardiovascular disease Table 40 Tab
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Study/year/country Population Ricke
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Table 2: Observational studies on r
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Table 3: Before and after studies o
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Table 4: Case control studies on ri
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Table 5: Intervention studies on ri
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Table 7: Case reports of osteomalac
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Table 9: Cohort studies on associat
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Children and adolescents Table 11:
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Table 13: Intervention studies on e
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Table 16: RCTs on effects of vitami
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Table 22: Meta-analyses of trials o
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Table 24: Prospective studies on as
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Table 25: Meta-analyses of RCTs on
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Table 27: Prospective studies on as
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Table 28: Meta-analyses of RCTs on
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Study Methods Results Author conclu
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NON-MUSCULOSKELETAL HEALTH OUTCOMES
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Table 32: Intervention studies on e
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Table 36: Observational studies on
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Table 38: Meta analyses of RCTs and
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Table 39: Prospective studies on 25
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Study/Country Population Mean follo
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Cardiovascular disease Table 40: Me
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Hypertension Table 42: Meta-analyse
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All-cause mortality Table 44: Syste
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Immune modulation Table 46: Systema
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Table 48: Intervention studies on v
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Reference/Country Population Follow
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Infectious disease Table 50: Meta-a
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Table 51: RCTs on vitamin D supplem
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Table 52: Observational studies on
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Neuropsychological functioning Tabl
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Abbreviations used in studies 25(OH
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Table 1: Percentage contribution of
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Table 2 (continued) Food group a Me
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Table 3 (continued) Food group Age
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Table 4 (continued) Food group a Ag
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Table 5 (continued) Food group a Na
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Table 6: Percentage contribution of
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Table 7: Average daily intake of vi
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Table 9: Average daily intake of Vi
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Table 11: Average daily intake of v
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Table 15: Average daily intake of V
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Serum/plasma 25(OH)D concentrations
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Table 20: UK - Adults and children
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Table 22: Northern Ireland - adults
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Table 24: England - adults 65 years
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Table 26: UK - by month blood sampl
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Table 29: English regions by season
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Table 33: England - by ethnicity, a
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Table 36: Scotland - by Body Mass I
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Calcitonin A peptide hormone, produ
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Osteoclast Osteocyte Osteoid Osteom
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