Clarifying which food formats and vitamin D forms are most effective for delivering vitamin D for immunity

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1 Clarifying which food formats and vitamin D forms are most effective for delivering vitamin D for immunity Dr Simon Penson Head of Cereals and Ingredients Processing Campden BRI simon.penson@campdenbri.co.uk

2 Content Overview of roles of vitamin D in health and immunity Current status of vitamin D nutrition The vitamin D 2 -D 3 project Future prospects Acknowledgements

3 Vitamin D - Introduction Vitamin D is a pro-hormone Only nutrient where main source is not one of diet but UVB exposure UVB exposure must be at nm In the UK, we only make vitamin D from sunlight between April to September Exists in two forms: D 2 (vegetable-based sources) and D 3 (animal-based sources) Natural form in humans is D 3 ; dietary supplements tend to use D 2

4 Metabolism of Vitamin D3

5 Role of vitamin D in calcium metabolism is well documented Slide courtesy of Prof K Cashman

6 Increasing evidence showing role for vitamin D in regulating immunity

7 Significant seasonal vitamin D deficiency and insufficiency in the UK population Hypponen and Powers AJCN 2007; 85:

8 Recent study showed considerable vitamin D insufficiency in Caucasian women in late autumn and winter; Asian women extremely deficient throughout the year 2 5 (O H )D n m o l/l P r e C a u c a s ia n P o s t C a u c a s ia n 6 0 P o s t A s ia n 5 0 P re A s ia n 4 0 m e a n + /-S E M M i x e d b e t w e e n - w it h i n 1 0 s u b je c ts A N O V A : s e a s o n x g r o u p 0 p < S u m m e r A u tu m n W in te r S p rin g Lanham-New et al, Proceedings of the Nutrition Society (2008), 67 (OCE8), E320

9 UK guidance on daily intake is out of line with many other countries Age group DRI NEW (Institute of Medicine, 2010) RNI (Department of Health, 1991) 0-6 months 15 μg (600 IU) 8.5 μg (340 IU) 7 mo - 3 y 15 μg (600 IU) 7 μg (280 IU) 4-50 years 15 μg (600 IU) 0 μg years 15 μg (600 IU) 0 μg years 20 μg (800 IU) 10 μg (400 IU) 71 + years 25 μg (800 IU) 10 μg (400 IU)

10 Key questions arise before routine dietary supplementation can be recommended Which form is most effective at raising serum 25(OH)D? Does the food matrix affect bioavailability? Do different ethnic groups show any difference in their response to dietary supplementation?

11 Ergocalciferol (Vitamin D 2 ) vs. cholecalciferol (Vitamin D 3 ) food fortification: comparative efficiency in raising 25OHD status in Caucasian/Asian women and mechanisms of action The D 2 -D 3 Study L Tripkovic, L Wilson, K Hart, CP Smith, G Bucca, G Chope, S Penson, E Hypponen, J Berry, S Lanham-New

12 The D 2 -D 3 Study will provide vital knowledge to guide key stakeholders The D2 D3 Study will provide: The Food Industry: with information on the comparative effectiveness of the two different forms of vitamin D as food fortificants in raising 25(OH)D levels in UK populations with known insufficiency (Caucasian) and deficiency (Asian) The Scientific Community: with detailed data on the mechanisms of action of any such differences in vitamin D 2 vs. vitamin D 3 in Caucasian and South Asians The General Population: with examples of how to improve vitamin D intakes through food fortification, particularly Asian groups who are so prone to vitamin D deficiency

13 Vitamin D2 vs. Vitamin D3 American Journal of Clinical Nutrition (2012) Vol. 95, pg Associated editorial: pg Impact Factor: 6.7 Osteoporosis Review (2013) Vol. 21 No.2, pg Circ. 35,000 healthcare professionals Nutrition Bulletin (2013) Vol. 38, pg Circ. 27,000

14 The D2-D3 Study objectives Compare the efficiency of 15µg/d [600IU/d] of vitamin D 2 (ergocalciferol) vs. vitamin D 3 (cholecalciferol) fortification of food products in raising 25OHD levels in South Asian/Caucasian women Determine which vehicle for fortification (i.e. a SOLID vs. FLUID food) with vitamin D 2 vs. vitamin D 3 is more effective in raising 25OHD levels, independent of ethnicity Investigate if 15µg/d is effective in raising wintertime 25OHD levels above the 25OHD thresholds of 25nmol/l and 50nmol/l respectively and if there are differences in vitamin D 2 vs. vitamin D 3 fortification Investigate the mechanisms (genetic/enzymatic) for the differences observed in (i), (ii) & (iii).

15 Randomisation of participants Study design Screening Informed consent Medical history & Screening bloods Check inclusion/exclusion criteria Randomisation Caucasian n=265, S.Asian n=90 Screening failures Group A BISCUIT: 600IU/15µg Ergocalciferol (Vitamin D 2 ) JUICE: Placebo Caucasian n=53, S.Asian n=18 Group B JUICE: 600IU/15µg Ergocalciferol (Vitamin D 2 ) BISCUIT: Placebo Caucasian n=53, S.Asian n=18 Group C BISCUIT: 600IU/15µg Cholecalciferol (Vitamin D 3 ) JUICE: Placebo Caucasian n=53, S.Asian n=18 Group D JUICE: 600IU/15µg Cholecalciferol (Vitamin D 3 ) BISCUIT: Placebo Caucasian n=53, S.Asian n=18 Group E JUICE & BISCUIT: Placebo Caucasian n=53, S.Asian n=18

16 Randomisation of participants Screening Informed consent Medical history & Screening bloods Check inclusion/exclusion criteria Randomisation Caucasian n=245, S.Asian n=90 Screening failures Group A BISCUIT: 600IU/15µg Ergocalciferol (Vitamin D 2 ) JUICE: Placebo Caucasian n=47, S.Asian n=17 Group B JUICE: 600IU/15µg Ergocalciferol (Vitamin D 2 ) BISCUIT: Placebo Caucasian n=49, S.Asian n=18 Group C BISCUIT: 600IU/15µg Cholecalciferol (Vitamin D 3 ) JUICE: Placebo Caucasian n=51, S.Asian n=19 Group D JUICE: 600IU/15µg Cholecalciferol (Vitamin D 3 ) BISCUIT: Placebo Caucasian n=49, S.Asian n=19 Group E JUICE & BISCUIT: Placebo Caucasian n=49, S.Asian n=17

17 Study Design Cohort 1 ran November 2011 to April 2012; Cohort 2 ran November 2012 to April 2013 Week 0 Week 6 Week 12 Informed Consent Height & weight Waist circumference Blood pressure Fasted blood sample pqct scan of radius Food diary Dosimeter Assigned intervention products Adverse event & compliance interview Weight Waist circumference Blood pressure Fasted blood sample Continue with intervention products Adverse event & compliance interview Weight Waist circumference Blood pressure Fasted blood sample Food diary Dosimeter

18 Intervention Products

19 Continuing work and potential next steps Full analysis of the 25(OH)D status of study cohort Genetic and biochemical analysis to quantify the impact of ethnicity responses to vitamin D 2 and D 3 If observed, establish a mechanism any divergence of efficacy between vitamin D 2 and D 3 in raising serum 25(OH)D levels Establish optimum dosing levels in a wide range of products

20 The D 2 -D 3 Study G Bucca K Hart CP Smith L Tripkovic L Wilson S Lanham-New G Chope S Penson E Hypponen J Berry

21 Campden BRI The partner of choice for the development and application of technical knowledge and commercially relevant solutions for the food and drink supply chain no no. 1207

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