Vitamin D and Health

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Published July 2016 ©Crown copyright 2016 This report is available online at: https://www.gov.uk/government/groups/scientific-advisory-committee-on-nutrition ii
Contents Preface ............................................................................................................................................. v Membership of Scientific Advisory Committee on Nutrition: Working Group on Vitamin D ........... vi Membership of Scientific Advisory Committee on Nutrition ......................................................... viii Summary .......................................................................................................................................... x 1. Introduction ............................................................................................................................ 1 2. Biology and metabolism .......................................................................................................... 5 3. Photobiology of vitamin D .................................................................................................... 18 4. Measuring vitamin D exposure (from diet and skin synthesis) ............................................... 28 5. Relationship between vitamin D exposure (from diet & skin synthesis) and serum 25(OH)D concentration ........................................................................................................................ 34 6. Vitamin D and health outcomes ............................................................................................ 41 Musculoskeletal health outcomes ......................................................................................... 42 Rickets.......................................................................................................................... 45 Osteomalacia ............................................................................................................... 47 Other musculoskeletal health outcomes (beyond rickets and osteomalacia) by life stage ............................................................................................................................ 48 Conclusions - vitamin D and musculoskeletal outcomes .............................................. 67 Non-musculoskeletal health outcomes ................................................................................. 69 Pregnancy and lactation: non-skeletal outcomes in mother and baby ......................... 69 Cancers ........................................................................................................................ 74 Cardiovascular disease & hypertension ........................................................................ 76 All-cause mortality ....................................................................................................... 80 Immune modulation ..................................................................................................... 81 Infectious diseases ....................................................................................................... 86 Neuropsychological functioning (cognitive function, depression, dementia, autism, schizophrenia) .............................................................................................................. 91 Oral health ................................................................................................................... 94 Age-related macular degeneration .............................................................................. 96 Conclusions – non-musculoskeletal health outcomes .................................................. 97 Selection of health outcomes to inform the setting of DRVs for vitamin D ........................... 98 7. Potential adverse effects of high vitamin D intakes/serum 25(OH)D concentration ............ 101 8. Dietary vitamin D intakes and serum/plasma 25(OH)D concentrations in the UK ............... 108 9. Review of DRVs for vitamin D .............................................................................................. 116 10. Overall summary and conclusions ....................................................................................... 130 iii
Page 1: Vitamin D and Health i 2016
Page 5 and 6: Preface The Scientific Advisory Com
Page 7 and 8: Adviser (Ultraviolet radiation expo
Page 9 and 10: Ms Gemma Paramor Lay representative
Page 11 and 12: Metabolism S.5 Vitamin D is convert
Page 13 and 14: Two studies reported an increase in
Page 15 and 16: Recommendations S.35 Serum 25(OH)D
Page 17 and 18: 1.8 The terms of reference were: to
Page 19 and 20: 1.18 In assessing the evidence on v
Page 21 and 22: there is not absolute correspondenc
Page 23 and 24: Metabolism Absorption of dietary vi
Page 25 and 26: UVB ▼ SKIN: ▼ Previtamin D 3
Page 27 and 28: 2.49 A number of studies have repor
Page 29 and 30: using a bolus dose (I 2 =77%) compa
Page 31 and 32: 2.75 Another RCT 21 (Cashman et al.
Page 33 and 34: 3. Photobiology of vitamin D Ultrav
Page 35 and 36: Erythema and skin cancer 3.10 Two m
Page 37 and 38: CIE spectrum for photoconversion of
Page 39 and 40: Effect of skin pigmentation on skin
Page 41 and 42: increase in mean serum 25(OH)D conc
Page 43 and 44: 4. Measuring vitamin D exposure (fr
Page 45 and 46: the authors cautioned care in the i
Page 47 and 48: 24,25(OH) 2 D 3 which can contribut
Page 49 and 50: 5. Relationship between vitamin D e
Page 51 and 52: latitudes > 49.5 o N or S (which we
Page 53 and 54:
increase 25(OH)D concentrations > 5
Page 55 and 56:
22.5 nmol/L (IQR, 16.8-34.3) in sum
Page 57 and 58:
6.7 Although serum 25(OH)D concentr
Page 59 and 60:
calcium intake, although this is mo
Page 61 and 62:
Evidence considered (Tables 1-5, An
Page 63 and 64:
6.43 Preece et al. (1975) measured
Page 65 and 66:
irths (December-February) in the vi
Page 67 and 68:
large loss to follow-up 45 and, sin
Page 69 and 70:
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 and 122:
children (n=179) received weekly do
Page 123 and 124:
8. Dietary vitamin D intakes and se
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
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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
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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
Page 173 and 174:
Lappe J, Cullen D, Haynatzki G, Rec
Page 175 and 176:
Mantell DJ, Owens PE, Bundred NJ, M
Page 177 and 178:
Murad MH, Elamin KB, Abu Elnour NO,
Page 179 and 180:
Pirotta S, Kidgell DJ & Daly RM (20
Page 181 and 182:
one mass, and renal function in the
Page 183 and 184:
Sperati F, Vici P, Maugeri-Sacca M,
Page 185 and 186:
Vervel C, Zeghoud F, Boutignon H, T
Page 187 and 188:
Weisse K, Winkler S, Hirche F, Herb
Page 189 and 190:
Annexes ANNEX (1) SACN working proc
Page 191 and 192:
ANNEX (2) Studies considered in rel
Page 193 and 194:
Cardiovascular disease Table 40 Tab
Page 195 and 196:
Study/year/country Population Ricke
Page 197 and 198:
Table 2: Observational studies on r
Page 199 and 200:
Table 3: Before and after studies o
Page 201 and 202:
Table 4: Case control studies on ri
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Table 5: Intervention studies on ri
Page 205 and 206:
Table 7: Case reports of osteomalac
Page 207 and 208:
Table 9: Cohort studies on associat
Page 209 and 210:
Children and adolescents Table 11:
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Table 13: Intervention studies on e
Page 213 and 214:
Table 16: RCTs on effects of vitami
Page 215 and 216:
Table 22: Meta-analyses of trials o
Page 217 and 218:
Table 24: Prospective studies on as
Page 219 and 220:
Table 25: Meta-analyses of RCTs on
Page 221 and 222:
Table 27: Prospective studies on as
Page 223 and 224:
Table 28: Meta-analyses of RCTs on
Page 225 and 226:
Study Methods Results Author conclu
Page 227 and 228:
NON-MUSCULOSKELETAL HEALTH OUTCOMES
Page 229 and 230:
Table 32: Intervention studies on e
Page 231 and 232:
Table 36: Observational studies on
Page 233 and 234:
Table 38: Meta analyses of RCTs and
Page 235 and 236:
Table 39: Prospective studies on 25
Page 237 and 238:
Study/Country Population Mean follo
Page 239 and 240:
Cardiovascular disease Table 40: Me
Page 241 and 242:
Hypertension Table 42: Meta-analyse
Page 243 and 244:
All-cause mortality Table 44: Syste
Page 245 and 246:
Immune modulation Table 46: Systema
Page 247 and 248:
Table 48: Intervention studies on v
Page 249 and 250:
Reference/Country Population Follow
Page 251 and 252:
Infectious disease Table 50: Meta-a
Page 253 and 254:
Table 51: RCTs on vitamin D supplem
Page 255 and 256:
Table 52: Observational studies on
Page 257 and 258:
Neuropsychological functioning Tabl
Page 259 and 260:
Abbreviations used in studies 25(OH
Page 261 and 262:
Table 1: Percentage contribution of
Page 263 and 264:
Table 2 (continued) Food group a Me
Page 265 and 266:
Table 3 (continued) Food group Age
Page 267 and 268:
Table 4 (continued) Food group a Ag
Page 269 and 270:
Table 5 (continued) Food group a Na
Page 271 and 272:
Table 6: Percentage contribution of
Page 273 and 274:
Table 7: Average daily intake of vi
Page 275 and 276:
Table 9: Average daily intake of Vi
Page 277 and 278:
Table 11: Average daily intake of v
Page 279 and 280:
Page 281 and 282:
Table 15: Average daily intake of V
Page 283 and 284:
Page 285 and 286:
Serum/plasma 25(OH)D concentrations
Page 287 and 288:
Table 20: UK - Adults and children
Page 289 and 290:
Table 22: Northern Ireland - adults
Page 291 and 292:
Table 24: England - adults 65 years
Page 293 and 294:
Table 26: UK - by month blood sampl
Page 295 and 296:
Table 29: English regions by season
Page 297 and 298:
Table 33: England - by ethnicity, a
Page 299 and 300:
Table 36: Scotland - by Body Mass I
Page 301 and 302:
Calcitonin A peptide hormone, produ
Page 303 and 304:
Osteoclast Osteocyte Osteoid Osteom
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