The case for expanding vitamin D fortification in the UK

Adrian Martineau

Potential Conflicts & Disclaimer• I have published research demonstrating health

benefits of vitamin D supplementation• I sat on the NICE Public Health Advisory Committee

on increasing vitamin D supplement use among at-risk groups

• The views expressed in this presentation are my own, and not necessarily those of NICE or of any funder who has supported my research

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

• The practice of deliberately increasing the content of vitamin D in a food in order to provide a public health benefit with minimal risk to health

Vitamin D fortification

Vitamin D fortification

Voluntary Mandatory

Bioaddition

Vitamin D fortificationChemical addition

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

• Reference Nutrient Intake (age ≥4 years)• The amount of vitamin D that is required to

ensure that 97.5% of the population are not deficient: 400 IU/day

• Safe Intake (age <4 years)• The amount judged to be enough for almost

everyone, but below a level that could have undesirable effects: 340-400 IU/day (age<1year), 400 IU/day (1-3 years)

Recommended intakes

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

Vitamin D deficiency

7-dehydrocholesterol Vitamin D

25(OH)D

25(OH)D

1,25(OH)2D 1,25(OH)2D

25(OH)D

1,25(OH)2D 1,25(OH)2D

25(OH)D: how much is enough?

25(OH)D: how much is enough?

Enough for what?

25-30 nmol/L

50 nmol/LMalabanan, Lancet 1998

75 nmol/LPriemel et al, JBMR 2010

Luxwolda et al, Brit J Nut 2012

115 nmol/L

25 nmol/L

Roth et al, in press, ANYAS 2018

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

Prevalence of vitamin D deficiency by age, UK

Age Prevalence5m-3y 2-8%4-10y 12-16%11-18y 20-24%19-64y 22-24%≥65y 17-24%

SACN, 2016

05

1015202530354045

9 EU

Denm

ark

Norw

ayGr

eece

Gree

ceIre

land

Germ

any

UK UKGe

rman

yNo

rway

Neth

erla

nds

Neth

erla

nds

Icela

ndFi

nlan

dIre

land

Finl

and

Norw

ayDe

nmar

kCa

nada USA

% Below 30 nmol/L

Prevalence of vitamin D deficiency by country

Cashman et al, 2016

Hyppönen & Power, Am J Clin Nut 2007

Prevalence of vitamin D deficiency by season and geography, UK

Group PrevalenceAsian / British Asian women, Surrey1 75-79%Pregnant women, London2 29%Sheltered accommodation, London3 25%

Prevalence of vitamin D deficiency in at-risk groups, UK

1. Darling et al, Ost Int 20132. SACN, 20163. Jolliffe et al, J Ster Biochem Mol Biol 2016

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

• Retrospective review, South East England: 2000-2006• Sixteen infants (6 South Asian, 10 Black African or Afro-

Caribbean ethnicity) with dilated cardiomyopathy attributed to vitamin D deficiency were identified

• Age 3 weeks-8 months; all breast-fed. • Six suffered cardiac arrest. Three died. Two referred for

cardiac transplantation.Maiya et al, Heart 2007

Hospitalisation for rickets, 1963-2011

Goldacre et al, Lancet 2014

• Ninety-one confirmed/probable cases of hypocalcaemicseizure due to vitamin D deficiency in children aged 0–15 years, Sep 2011 – Sep 2013, UK & Ireland

Basatemur & Sutcliffe, JCEM 2015

SAMPLE TITLE

Nutritional Rickets Presenting to Secondary Care in Children: a UK Surveillance Study

British Paediatric Surveillance UnitDr Priscilla Julies, Royal Free Hospital, London; Professor Mitch Blair, Imperial College, London; Karina Pall, Marina Leoni and Dr Richard Lynn, BPSU, London; Dr Alastair Calder, Great Ormond Street Hospital, London; Prof Zulf Mughal, Manchester University Hospital, Manchester; Dr Nicholas Shaw, Birmingham Children’s Hospital; Dr Helen McDevitt; Dr Ciara McDonnell

SAMPLE TITLE

MethodsBPSU online reporting methodologyStudy period: March 2015 – March 2017Case Definition:

Clinical rickets with any of the following:• Leg deformity(bowing or knock knees)/Swollen wrists or knees or ribs (Rachitic

Rosary) AND 250H vitamin D <25nmol/L with one or more abnormalities of serum calcium, alkaline phosphatase, phosphate, parathyroid hormone,

OR

Radiological rickets with:• Widening, cupping, splaying of metaphysis (of any long bone) AND 25OHVitamin D

<25nmol/L

SAMPLE TITLE

Results

• 130 cases of clinical / radiological rickets• 2 deaths due to dilated cardiomyopathy

• 26% had pathological increase in osteoid (OV/BV>2%)

• No participants with 25(OH)D >75 nmol/L had increased osteoid

Priemel et al, JBMR 2010

Acute Respiratory Infection

• Meta-analysis of individual participant data from 10,933 participants in 25 trials

• Vitamin D supplementation protected against acute respiratory infections overall (aOR 0.88, 95% CI 0.81 to 0.96; P=0.003)

• Protection was stronger in deficient participants (aOR 0.58, 95% CI 0.40 to 0.82; P=0.002)

Martineau et al, BMJ 2017

Asthma Exacerbation

• Meta-analysis of individual participant data from 955 participants in 7 trials

• Vitamin D supplementation protected against asthma exacerbation overall (aIRR 0.72, 95% CI 0.55- 0.95, P=0.02)

• Trend towards stronger protection in deficient participants (aIRR 0.33, 95% CI 0.12-0.92, P=0.03)

Jolliffe et al, Lancet Respir Med 2017

COPD Exacerbation

• Meta-analysis of individual participant data from 469 participants in 3 trials

• No protective effect against COPD exacerbation overall (aIRR 0.94, 95% CI 0.78-1.13, P=0.52)

• Protective effect seen in deficient participants only (aIRR 0.55, 95% CI 0.36-0.84, P=0.006)

Jolliffe et al, submitted

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

UV dose effective for vitamin D synthesis by month, UK

O’Neill et al, J Ster Biochem Mol Biol 2016

15.5%<25 nmol/L

3.2%<25 nmol/L

Hyppönen & Power, Am J Clin Nut 2007

25(OH)D by month, UK 45-year-olds

Action spectra for skin erythema vs. cutaneous vitamin D synthesis

SACN 2016

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

Male FemaleChildren 80 IU 76 IUAdolescents 96 IU 76 IUAdults 124 IU 104 IUOlder adults 156 IU 116 IU

Dietary vitamin D intake, UK

Whiting & Calvo, Vitamin D (4th Ed), in press 2018

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

Supplement uptake• Healthy start: uptake of 3-10% where means-tested1

• Uptake boosted to 17% where free of charge2

• Over-the-counter use:• In Ireland, 16% of adults in Ireland take a vitamin D

supplement3

• In UK, 24% of adults aged 19-64 and 40% of adults aged ≥65 years take a dietary supplement4

1. SACN, 20162. Moy et al, Arch Dis Childhood 20123. Black et al, J Nutr 20154. NDNS 2016

Vitamin D supplement use, Canadian women

Greene-Finestone et al, Appl Physiol Nutr Metab 2013

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

Fortification: safety

Group Upper LimitInfants 1000 IU/dayChildren aged 1-10y 2000 IU/day

Children aged 11-17y 4000 IU/day

Adults 4000 IU/day

Fortification: safety

Food Country Vitamin D per serving

Cow’s milk, 1 cup (250 ml)

Canada, USA, Finland

100 IU

Bread (100 g) Jordan, USA 58-90 IUBreakfast cereal (0.75 cup)

USA, Canada 40-100 IU

Cheese slice (16g) USA 60 IU

Blank et al, Am J Public Health 1995

• Inadvertent over-fortification of milk by one dairy, USA 1985-1991

• 35 definite cases of hypervitaminosis D; average 25(OH)D level 560 nmol/L

• 7 developed renal impairment• 2 deaths:

• 1 dysrhythmia attributed to hypercalcaemia• 1 ‘opportunistic infection secondary to the use of

immunosuppressants for hypercalcemia’

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

Effectiveness of vitamin D fortification

Black et al, J Nutr 2012

Black et al, J Nutr 2012

Effectiveness of vitamin D fortification

United Kingdom

No mandatory fortification

Canada

Mandatory Fortification

Male Female Male FemaleChildren 80 IU 76 IU 248 IUAdolescents 96 IU 76 IU 292 IU 216 IUAdults 124 IU 104 IU 232 IU 204 IUOlder adults 156 IU 116 IU 268 IU 244 IU

% below 30 nmol/LTotal Population

24 % 7.4 %

Dietary vitamin D intake:UK vs. Canada

• Vitamin D deficiency is common in the UK• It has a major adverse impact on public health• Recommended intakes of vitamin D are not

being met by cutaneous synthesis, dietary intake or supplement use

• Expanding vitamin D fortification in the UK is likely to be safe, effective and cost-effective

The case for expanding vitamin D fortification in the UK

Costs of implementing mandatory vitamin D fortification:• Cholecalciferol,

marketing and education, food control and monitoring

Savings due to improved population vitamin D status:• ↓ rickets / osteomalacia• ↓ acute respiratory

infections, asthma and COPD exacerbations

Cost-effectiveness

*

*11 euro cents per person per year for 800 IU/day: Sandmannet al, Public Health Nutrition 2015

Where next?

• Formal health economic evaluation of differentmodels: expanded voluntary vs mandatory

• Further work to identify suitable vehicle foods• Qualitative work to evaluate attitudes

Conclusion

• The current policy of recommending use of vitamin D supplements to meet the RNI for vitamin D is not working at a population level

• Expanding fortification of foods with vitamin D represents an alternative strategy that is worthy of serious consideration.