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National Diet and Nutrition Survey

What is ‘vitamin’ D and what does it do?

But…Vitamin D receptors are expressed on most cells and it appears to have effects on cell proliferation and differentiation, immune system function, cardiovascular tissue, CNS etc.

What are the results of low levels?

Design Number of participants ComparatorOdds/hazard ratio or relative risk§ (95% CI)

All cause mortalityAutier and Gandini, 200710

Meta-analysis of 18 vitamin D

supplementation studies

57 311 Supplemented v unsupplemented

RR 0.93 (0.87 to 0.99)

Ginde et al, 200912 Prospective observational study in individuals >65 years*

3265 Serum 25-OHD concentration >100 nmol/l v <25 nmol/l

HR 0.55 (0.34 to 0.88)

Dobnig et al, 200813 Prospective cohort study with coronary angiography†

3258 Median serum 25-OHD concentration 70 nmol/l

v 19 nmol/l‡

HR 0.48 (0.37 to 0.630

Cardiovascular mortalityGinde et al, 200912 Prospective

observational study in individuals >65 years*

3265 Serum 25-OHD concentration >100 nmol/l v <25 nmol/l

HR 0.42 (0.21 to 0.85)

Dobnig et al, 200813 Prospective cohort study with coronary angiography†

3258 Median serum 25-OHD concentration 70 nmol/l

v 19 nmol/l‡

HR 0.45 (0.32 to 0.64)

DiabetesType 1 Zipitis and Akobeng, 200818

Meta-analysis of four case-control studies of

vitamin D supplementation

6455 Supplemented v unsupplemented

OR 0.71 (0.60 to 0.84)

Type 2 Pittas et al, 200714 Meta-analysis of four

observational studies6784 (non-black) Serum 25-OHD

concentration 63-95 nmol/l v 25-58 nmol/l

OR 0.36 (0.16 to 0.80)

CancerColorectal  Yin et al, 200915 Meta-analysis of six

case-control studies3556 Per 50 nmol/l increase in

serum 25-OHD concentration

OR 0.57 (0.43 to 0.76)

Breast Chen et al, 200916 Meta-analysis of seven

observational studies11 330 Highest quartile serum

25-OHD concentration v lowest quartile

OR 0.55 (0.38 to 0.80)

Multiple sclerosisMunger et al, 200617 Nested case-control

study444 Per 50 nmol/l increase in

serum 25-OHD concentration

OR 0.59 (0.36 to 0.97)

Diagnosis and management of vitamin D deficiencySimon Pearce, Tim CheethamBMJ 2010; 340(11 January 2010)

Evidence of benefit?

• Cochrane April 2014 – Hip fractures in older adults• Mean/median age 80yrs+• 53 trials, 91,791 participants• Vitamin D AND Calcium supplements• Results– Community residents. Risk from 8 to 7/1000/yr– Institution residents. Risk from 54 to 45/1000/yr

Cochrane: Vitamin D and mortalityJan 2014

• 56 randomised trials with 95,286 participants• Mean 4.4 years of supplementation• Most trials included women over 70years• VitaminD3 only reduced all cause mortality• 11.4% to 11.0% RR 0.94 (0.91-0.98) P0.002• 150 treated for 5yrs to save one life• 1000 treated for 5-7yrs to save 4 cancer deaths• May decrease mortality in elderly people living

independently• but…substantial dropout of participants…risk of type 1

error…more RCTs needed.

Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses ofobservational studies and randomised trials BMJ April 2014

Scientific Advisory Committee on Nutrition

• Draft Vitamin D and Health Report 2015– <25ng/ml Vitamin D is probably associated with

poor musculoskeletal health– 10mcg/day is probably good for us and safe

• Limited data on health outcomes for treatment– Even for rickets and osteomalacia

However…

• Case control study within the WHI study• Higher VitD levels (>30ng/mL) assoc. with…– Lower fracture risk in white women (OR.82)– Higher fracture risk in • Black women (OR 1.45)• Asian women (OR 2.78)

• “the optimal level of VitD for skeletal health may differ in white and black women”

Serum 25-hydroxyvitamin D and clinical fracture risk in a multiethnic cohort of women: the Women's Health Initiative (WHI). J Bone Mine Res Oct 2011

“The diversity of opinions onthis topic has created lively discussions

because the conclusionbased on randomized controlled trials (RCTs)

differsfrom the conclusions based on the large body

of observational studies.”

Optimal Vitamin D Status: A Critical Analysis on the Basis of Evidence-Based Medicine.

J Clin Endocrinl Metab Aug 2013

• 20-30mins sunlight at midday on face and arms 2-3times per week sufficient for fair skin (2000IU VitD per session) April-Sept

• 2-10 fold increase in exposure needed if pigmented skin.

• Eat oily fish• Probably…

What should we do?

• NICE say: Offer supplementation to ‘at-risk’ groups – All pregnant and breastfeeding women (10mcg=400IU D3)– Infants and children under 5 years (5drops healthy start drops= 7.5mcg D3)– People over 65– People who have low or no exposure to the sun. – People who have darker skin.

• Only test in symptomatic patients (and those at high risk according to NICE)

• Treat Vitamin D deficiency (<25nmol/L or <30nmol/L according to NOS)– Adults 300,000IU over 6-10weeks– Children 3000IU per day for 3months

• Offer 800IU with calcium to the elderly to reduce risk of fracture (over 80s in institutions?)

• Await Further research eg VITAL (2017) and VIDA (2016/17)

https://www.surveymonkey.com/r/CT6TF2Z

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