Vitamin D: The good, bad and the ugly

Vitamin D: The good, bad and the ugly
Karthik Balachandran
Sri Ramachandra Institute of Higher Education and Research
April 6,2019

Riddle
What is made with the help of sun and is associated with
everything under the sun?
Karthik Vitamin D :Good,Bad & the Ugly April 6,2019 2 / 64

Vitamin:
/ˈvɪtəmɪn,ˈvΛɪtəmɪn/
A vitamin is an organic molecule (or related set of
molecules) that is an essential micronutrient that an
organism needs in small quantities for the proper
functioning of its metabolism*
Wikipedia

Vitamin D or Hormone D?
Vitamin Hormone

Physiology

Basic physiology

Non calcemic actions1
1
Michael F Holick (2007). “Vitamin D deficiency”. In: New England Journal of
Medicine 357.3, pp. 266–281.

The lay of the land

Bigger role for vitamin D?
Non traditional associations
• Cardiovascular disease
• Adiposity
• Glucose metabolism
• Mood disorders
• Immunology - URTI , Asthma exacerbationsa
• Muscular function
• Tuberculosis
• Colorectal adenomas /malignancies
a
Philippe Autier, Patrick Mullie, et al. (2017). “Effect of vitamin D
supplementation on non-skeletal disorders: A systematic review of meta-analyses
and randomised trials”. In: The Lancet Diabetes & Endocrinology 5.12,
pp. 986–1004.

So why the buzz?
• Correlation is not causation
• Discrepancy between observational and interventional studies
• Vitamin D may be a marker of ill health, not a cause2
2
Philippe Autier, Mathieu Boniol, et al. (2014). “Vitamin D status and ill health: A
systematic review”. In: The Lancet Diabetes & Endocrinology 2.1, pp. 76–89.

Do we really have a pandemic?

Screening

Screening - Endocrine society ∩ IOM
Who should be screened?
• Rickets
• Osteomalacia
• Osteoporosis
• Malabsorption syndromes
• Hyperparathyroidism
• CKD , CLD
• Granuloma forming disorders
• Some lymphomas
Adapted from Endocrine Society Guidelines

What test to use?
• Serum 25(OH)D
• Fasting not required
• ELISA commonly used , but LC MS-MS is the most accurate
• No commercially available VDBP test in India

Diagnosis

What is normal?
“ The Institute of Medicine makes recommendations for
19 nutrients..For virtually all of them, there are sev-
eral unresolved questions..the most important of which,
is What is normal?
Robert Heany
”

Relationship between D and PTH
Sai et al : J Clin Endocrinol Metab 96: E436 –E446, 2011

Vitamin D testing - some problems
• Abuse
✓ Testing is costlier than treating
✓ “Perceived” high therapeutic index
✓ “Associations” with a wide variety of diseases

Vitamin D testing - some problems
• Abuse
✓ Testing is costlier than treating
✓ “Perceived” high therapeutic index
✓ “Associations” with a wide variety of diseases
• Assays
✓ Metabolites
✓ Binding proteins
✓ Racial differences

Vitamin D testing over the years
Zhao S et al London J Prim Care 2015;7(2):15–22

Quiz
The tallest mountain in the world is?
1 Mt Everest
2 Mauna Kea
3 Chimborazo

Quiz
The tallest mountain in the world is?
1 Mt Everest
2 Mauna Kea
3 Chimborazo
4 All of the above

Why does it matter?
• VDSP recommends a 10% coefficient variability (C.V.) for clinical
laboratories
• For example, a 25(OH)D laboratory result of 30 ng/mL meeting the
10% C.V. VDSP recommendation means that the “true” value is
between 24 and 36 ng/m

Hormone Testing -What can you do?
• Ask if your lab tests are stardardized (Vitamin D, Testosterone,
E2)
• Keep up with developments in hormone testing
• Educate colleagues on the need for standardization and rational
use of tests
Some Thoughts

Prevention

Vitamin D requirement across age groups
Prevention(IU/day) Upper Limit(IU/day) Treatment(IU/day)
Premature Neonates 400 1000 1000
Term neonates 400 1000 2000
1-9 years 600 3000 3000
9-18 years 600 4000 3000-6000

Vitamin D requirement across age groups
Prevention(IU/day) Upper Limit(IU/day) Treatment(IU/day)
Premature Neonates 400 1000 1000
Term neonates 400 1000 2000
1-9 years 600 3000 3000
9-18 years 600 4000 3000-6000
Infants - 400 IU/day
Others - 600 IU/day
Prevention

Fortification
• Vitamin D fortified milk and calcium fortified laddoos tried in India3
• No significant adverse events
• Costly as a public health measure, succesful in a few western countries
eg.Finland
3
Srinivasa Pm and Harinarayan Cv (2015). “Vitamin D deficiency in India: Fortify or
let the sun shine in?” In: JCSR 4.3, pp. 220–226.

How much Calcium to take?
• UK BioBank - > 4L patients no
↑ in CV mortality
• Up to 2500 mg/day (NOF and
American society of preventive
cardiology)
• Estimate total intake - diet +
supplement

Treatment

Preparations
• D3 > D2 in efficacy
• D2 (Ergocalciferol) not available in India
• Calcium carbonate -40% calcium. cheap & preferred with food
• Calcium citrate - alternative in achlorhydria

Regimens
• 60000 IU of cholecalciferol per week x 8 weeks
• Maintenance dose of 1000-2000 IU per day

Regimens
• 60000 IU of cholecalciferol per week x 8 weeks
• Maintenance dose of 1000-2000 IU per day
Do NOT use Calcitriol for Vitamin D supplementation - risk of toxicity
Caution

Who are at risk?
Which of the following group of patients are deemed high risk and require
high doses?
1 Dark skinned individuals
2 Obese
3 Pregnancy and lactation
4 Older adults with non traumatic fracture
Rosen et al J Clin Endocrinol Metab 97: 1146–1152, 2012

Who are at risk?
Which of the following group of patients are deemed high risk and require
high doses?
1 Dark skinned individuals
2 Obese
3 Pregnancy and lactation
4 Older adults with non traumatic fracture
5 None of the above
Rosen et al J Clin Endocrinol Metab 97: 1146–1152, 2012

IOM vs Endocrine Society
• 25(OH)D > 30 ng/ml is provides extra health benefits compared
to 20 ng/ml
• < 20 ng/ml is deficiency in ALL people
• The identified high risk groups
IOM disagrees ...

Amount of vitamin D in preparations4

Amount of vitamin D in preparations4
4
Khadgawat R, Ramot R, Chacko K M, Marwaha R K. Disparity in cholecalciferol
content of commercial preparations available in India. Indian J Endocr Metab
2013;17:1100-3

FAQs

Question 1
“ How much sun expsosure should I have and when?
”

How much sun exposure should I have?
• 1/2 hour skin exposure
whole body /week for
children
• 2 hour per week for adults* a
• Timing - 11 AM to 2 PM b
• No single amount of
sunlight exposure is
optimal for all
a
De Groot 7th Edn
b
CV Harinarayan et al

How much sun exposure do we need5
?
Important variables
• Fitzpatrick skin type
• Clothing
• Latitude
• Season
• Pollution
• Time spent outdoors
• Physical activity
• BMI
• Sex
• Polymorphisms in vitamin D binding protein
5
Elio Kechichian and Khaled Ezzedine (2017). “Vitamin D and the Skin: An Update
for Dermatologists”. In: American journal of clinical dermatology.

Question 2
“ India is so hot with lot of sunlight exposure. How can we
possibly have Vitamin D deﬁciency?
”

Why is it common in India?
Vitamin D deficiency in India
Diet high in phytates
Low calcium intake
Darker pigmentation
Sociocultural practices
Environmental pollution
Absence of fortification
Genetic factors

Question 3
“ I am a lactose intolerant vegan. I heard commercial vitamin D is
non-veg.
What can I do?
”

Protip
DBT Grant on Vitamin D for vegan sources

Question 4
“ I like milk. Are some types of milk better than others?
Should I take as much milk as Dhoni?
”

Milk and Vitamin D
Appl Physiol Nutr Metab. 2016 May;41(5):516-521

Milk and Vitamin D
Packet Color Milk type % Fat
Magenta Double Toned Milk 1.5 %
Blue Toned Milk 3 %
Green Standardized Milk 4.5 %
Orange Full Cream Milk 6 %

Milk and Vitamin D
Packet Color Milk type % Fat
Magenta Double Toned Milk 1.5 %
Blue Toned Milk 3 %
Green Standardized Milk 4.5 %
Orange Full Cream Milk 6 %
How much?
Two 8 ounce servings per day [2 cups]

Question 5
“ I can’t take high fat milk, I am already obese. Why
can’t we get fortiﬁed milk?
Better still why can’t we add vitamin D to municipal
water?
”

Water soluble vitamin D
• Micellized vitamins (A and D) have both been shown to have better
bioavailablity6
• Theoretically water miscible vitamin D is possible, although the cost
will be prohibitive - ANYAY?
6
Raman K Marwaha et al. (2016). “Efficacy of micellized vs. fat-soluble vitamin D3
supplementation in healthy school children from northern India”. In: Journal of Pediatric
Endocrinology and Metabolism 29.12, pp. 1373–1377.

Question 6
“ You only talk about calcium.What about other trace el-
ements?
My friend is taking magnesium supplements
”

Should we supplement trace elements?
Magnesium No
Fluoride No
Strontium No
Boron No
Hurley et al Use of Vitamins and Minerals in Skeletal Health:AACE position statement

Question 7
“ Could taking Vitamin K , C or E improve vitamin D
deﬁciency? My neighbour has Kai Kal Kudaichal syn-
drome and vitamin D didn’t beneﬁt her?
”

Other Vitamins
Vitamin K Cofactor of γ carboxylase & causes γ carboxylation of
osteocalcin.
No hard evidence to support supplementation
Vitamin E Conflicting results. α tocopherol may even be harmful in
excess
Vitamin C No signficant benefit.

Question 8
“ I saw some ﬁxed dose combinations of cardiac and di-
abetic drugs with Vitamin D. Is that like killing two
birds with one stone?
”

Vitamin D FDCs
• FDC (fixed drug combinations) may improve compliance, but the
cost again is high
• Simple tip ⇒ Do the math !
• By the way, it’s not killing two birds with one stone - since the only
one making a ’killing’ is the company

Question 9
“ I am fat. Do I need more vitamin D than thin people?
”

Obesity and vitamin D
• Obesity is associated with low vitamin D
• Controversy regarding dosing 7
• IOM - no need to give more than usual dose
• Endocrine society - yeh dil maange more
• No easy answer : use discretion
7
Encourage patient to lose weight !

Question 10
“ I have been treated for Vitamin D deﬁciency. Should I
test again to see if it has improved?
”

Follow up
• Surprisingly little guidance from Endocrine society and IOM
• Australasian endocrine society - repeat at 3 months
• If assay issues are there, they are likey to persist
• Use discretion

Q & A
Question Answer
Is there a pandemic of D-ficiency? No

Q & A
Question Answer
Does obesity cause low D levels? Yes

Q & A
Question Answer
Does low fat milk lead to D-ficiency? Probably

Q & A
Question Answer
Should I prescribe D stack? No

Q & A
Question Answer
Are there vegan sources of D? Yes

Q & A
Question Answer
Can I get ‘too much’ vitamin D? Yes

Q & A
Question Answer
Can I get ‘too much’ vitamin D? Yes
Should I do repeat testing? Yes±No

Conclusions
Take home messages
• There is no vitamin D pandemic
• No advantage of having Vitamin D > 20 ng/ml
• Testing - Standardization matters
• Prevention - 600 IU/day enough, don’t forget
calcium,sunlight,fortified foods and maintain healthy weight
• Treatment - oral > injectable Quality matters
• Follow up - retesting after 3 months*

“ Three* roads diverged in a wood, and I—
I took the one less traveled by,
And that has made all the difference
Robert Frost*
”

Vitamin D: The good, bad and the ugly

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Vitamin D: The good, bad and the ugly

Similar to Vitamin D: The good, bad and the ugly (20)

More from Dr Karthik Balachandran

More from Dr Karthik Balachandran (19)

Recently uploaded

Recently uploaded (20)

Vitamin D: The good, bad and the ugly