Vit D

Question 1

Sources

Answer 1

Oily fish, including trout, salmon, mackerel, herring, anchovies, pilchards, fresh tuna.
Amount will depend on preparation.
E.g. smoked herring (4ug/100g) vs. raw herring (40ug/100g).
Cod liver oil and other fish oils
Egg yolk
0.5ug per yolk
Mushrooms
Small quantities
Supplemented breakfast cereals
Typically between 2ug and 8ug per 100g
Margarine and infant formula
Statutory supplementation in the UK

Question 2

Dietary contribution to Status is much smaller

Answer 2

Cutaneous synthesis during winter occurs to only a minimal level (extremely limited vitamin D synthesis between October-March in UK).

Therefore during winter, along with stores in fat, dietary sources become more important.

However, dietary sources are limited and intake is relatively low.

Question 3

Vitamin D physiology

Answer 3

Diet -> Cholecalciferol

25-hydroxylase
-> 25(OH)D

1-α-hydroxylase
-> 24-hydroxylase

1, 25(OH)2D
24,25(OH)2D

Nuclear actions and non-genomic actions

-> Calcium Homeostasis:
Increase intestinal absorption
-> Cell Proliferation & Differentiation

Secretion of Insulin, Parathyroid and Thyroid Hormones

Modulation of Immune System Response

Question 4

How do we assess vitamin D status?

Answer 4

Total 25(OH)D metabolite
Reflects both subcutaneous synthesis and dietary intake
Half-life long enough to provide a circulating store to measure

Question 5

Difficult to apply a universally “normal” level for all sub-groups of the population:

Answer 5

Disease states
Age differences
BMI
Ethnic differences - Black vs. white
Optimum status may be different depending on the disease you are trying to prevent.

Question 6

What is vitamin D deficiency?

Answer 6

The most commonly used measurement of vitamin D status is total 25-hydroxyvitamin D (25(OH)D):

25(OH)D <30nmol/l indicates deficiency
25(OH)D <50nmol/l indicates insufficiency
25(OH)D >50nmol/l is sufficient

Question 7

Population sub-groups at risk of vitamin D deficiency and risk factors for deficiency

Answer 7

Infants
High use of sunscreen
Obesity
Disease state
Liver disease
Kidney disease
Malabsorption syndrome
Darker skin colour

Decreased exposure to sun due to traditional dress

Failure to go outdoors
Low activity levels
institutionalised

High latitudes

Younger adults (particularly 19-24 years)

Elderly (particularly institutionalised & 85+)

Question 8

Prevalence of vitamin D deficiency in the UK?

Answer 8

35% of 65+ are below the 25(OH)D threshold

Question 9

Older age and 25(OH)D deficiency

Answer 9

It is generally accepted that older people are at high risk of vitamin D deficiency.

However, when we look at the prevalence of vitamin D deficiency in those aged 65+ it is actually the oldest old (85+) or those institutionalised that are at highest risk.

Question 10

Mechanisms for deficiency in older age?

Answer 10

less sun

less consumption of vit d

less 25(OH)D

Question 11

What are the consequences of vitamin D deficiency/insufficiency?

Answer 11

In the elderly – muscle weakness, increased risk of falls, lower bone mineral density and increased risk of fracture.
Osteoporosis and osteomalacia.

Children – Rickets.

All age groups: Associations with many other disease states (remember mostly just observational links with limited causal effect evidence to date): Asthma, COPD, depression, many types of cancer, diabetes, infection, CVD, MS….and many more…

Question 12

Mechanisms of vitamin Ddeficiency/insufficiency in younger age groups?

Answer 12

We found that the lower vitamin D levels in younger healthy adults compared to levels in healthy older adults (n=106) was not because of:
less sunshine exposure in healthy young adults.
Lower amount of the proteins that carry vitamin D in the blood in healthy young adults.

We did find that likely contributors to the lower levels of vitamin D in younger healthy adults are:
less dietary intake of vitamin D than in healthy older people.
faster metabolism of vitamin D in the body than in healthy older people.

Question 13

Evidence to indicate that serum 25(OH)D is inversely associated with obesity

Answer 13

Higher BMI, lower serum 25(OH)D

Question 14

Vitamin D levels in Obesity in Sheffield

Answer 14

Obese people have lower vitamin D levels than leaner people.
We wanted to know what the cause of low vitamin D in obesity was and whether low vitamin D in obesity actually matters.
We also wanted to find out how vitamin D levels are affected by age in Sheffield.

Question 15

Mechanisms of low 25(OH)D in Obesity?

Answer 15

We found that low vitamin D in obesity was not because of:
less dietary intake of vitamin D than in leaner people
less sunshine exposure than in leaner people
faster metabolism of vitamin D in the body
Lower amount of the proteins that carry vitamin D in the blood.

We did find that low vitamin D levels in obese people is likely to be due to a greater volume of distribution. This means that the vitamin D in obese people is distributed into a larger volume of fat, muscle and other tissue than in leaner counterparts, leading to lower levels in the blood.

Question 16

Consequences of low vitamin D in obesity?

Answer 16

We also found that low blood levels of vitamin D in obese people is not associated with higher bone turnover, lower bone density or poorer physical function. We did not find any evidence that low vitamin D affects bone health in obesity.

There are no apparent adverse consequences of low vitamin D for bone health in obesity. Low blood levels of vitamin D in obesity may not indicate vitamin D deficiency due to availability of vitamin D from fat stores and so bodyweight needs to be considered when interpreting vitamin D levels in the blood.

Question 17

Supplementation in people living with obesity – Do they need more?

Answer 17

25(OH)D deficiency more severe in individuals with higher BMI
Lower levels of 25(OH) in obesity

Increase in 25(OH)D levels after vitamin D loading is greater in normal weight women than in overweight or obese

After peaking 25(OH)D levels drop more slowly in obese and overweight vs. normal weight

The lower peak 25(OH)D but longer persistence (slowerdecline) of 25(OH)D could also be due to the larger bodyof volume and a slower release into circulation of vitaminD stored in the adipose tissue
supports the volumetric dilution model

Suggests that fat mass seems to have an important role inthe distribution of 25(OH)D within the body

Question 18

SACN (Scientific Advisory Committee for Nutrition)

Answer 18

Advises the government on all aspects of nutrition
The evidence on Vitamin D and health was last considered by SACN in 2007 (Update on Vitamin D, Position Statement)
Since then, further evidence has become available:
October 2010
SACN - agreed to review the DRVs for Vitamin D intake
July 2017
New vitamin D and health report published with new recommendations

Question 19

Current Vitamin D Recommendations

Answer 19

An RNI for vitamin D, of 10 μg/d (400 IU/d), is recommended for the UK population aged 4y and above.

This is the average amount needed by 97.5% of the population to maintain a serum 25(OH)D concentration ≥ 25 nmol/L when UVB sunshine exposure is minimal

Question 20

What management strategies are being employed to address vitamin D deficiency in the UK?

Answer 20

Revision of DRVs: SACN Vitamin D and Health Report (2017) recently released in July 2017.

ADVICE ON SUNEXPOSURE

Question 21

What management strategies are being employed to address vitamin D deficiency in the UK?

Answer 21

extend range of food fortified with vit d
GP are much more aware of vit d
Blood tests looked at
Greater public awareness

Question 22

Vitamin D and falls prevention

Answer 22

Impaired lower extremity function is a risk factor for falls, hip fractures, frailty and loss of autonomy

Vitamin D supplementation has been proposed as a possible preventative strategy to delay functional decline through a direct effect on muscle strength

Definitive data is lacking on the effectiveness of vitamin D supplementation and the dose requirements related to improving lower extremity function

Some RCT’s have shown that older age groups at risk of deficiency demonstrate a benefit from vitamin D supplementation on lower extremity function

A 2011 Meta-analysis of 17 RCTs indicates a benefit of vitamin D on lower extremity strength primarily in those with vitamin D deficiency (Stockton et al., 2011)

Meta-analyses of RCTs among those 65 years and over and at risk of vitamin D deficiency consistently show a benefit of vitamin D supplementation in the prevention of falls and hip fractures

Question 23

Vitamin D & Falls – are there potential adverse effects of high doses?

Answer 23

Those reaching the highest quartile of 25(OH)D level at 12-months had the most falls vs. those reaching the lowest quartile of 25(OH)D (P = 0.01)

Monthly high doses or single bolus doses of vitamin D may have a potentiallydeleterious effect on falls​
Too much of a good thing may not be a good thing!
may be a threshold effect?

Physiology behind possible detrimental effect of high monthly bolus dose of vitamin D on muscle function and falls is unclear and needs further investigation

Question 24

Why might high dose vitamin D cause falls in older people?

Answer 24

Hypothesis: The VDBP is saturated with such a high dose leading to a disproportionate rise in free 25(OH)D and other vitamin D metabolites, leading to hypercalcaemia

Huge dose can saturate the vit d binding area
Too much free vit d = unwanted effects, calcimia

Question 25

What literature is published to link vitamin D with communicable disease?
(Martineau et al, 2016)

Answer 25

Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001).

Question 26

What literature is published to link vitamin D with COVID-19?

Answer 26

Data from observational studies suggest that low levels of 25-hydroxyvitamin D (25(OH)D) may be a risk factor for severe covid-19. However, this association could be due to reverse causality or confounding.

Question 27

What might some of the limitations be with this literature?

Answer 27

Cannot establish causality!

Vitamin D is an acute phase reactant

Many retrospective

Potential confounders =
physical activity and BMI

Question 28

To investigate the effect of a single high dose of vitamin D3 on hospital length of stay in patients with COVID-19.

Critical Considerations: Limitations

Answer 28

No power calculation

Heterogeneity of sample

Low percentage of patients with 25(OH)D deficiency

Mean onset of symptoms to administration

25(OH)D not gold standard measurement – LC-MS/MS is gold standard

Question 29

Summary

Answer 29

Quality of observational studies to date is very poor and decisions on advocating large dose supplementation should NOT be based on these studies

It is wrong to advocate vitamin D supplementation to prevent COVID-19 based on findings from observational study outcomes on hospitalised patients.

We have only limited clinical trial data (three reviewed today) – show no effect on covid outcomes.

We await results from ongoing clinical trials – these may show different findings.

Sensible to advocate 10ug (400IU) per day (as per SCAN guidelines!), particularly if not getting unprotected sunlight exposure – this is enough to maintain vitamin D levels in the UK and is in line with expert advice…