importance of vit.D

1. Vitamin D

5. TM
Vitamin D Metabolism

6. Endocrine, paracrine and intracrine functions of
Vitamin D

8. Vitamin D from sunlight exposure
• Vitamin D is manufactured in your skin
following direct exposure to sun.
• Amount varies with time of day, season,
latitude and skin pigmentation.
• 10–15 minutes exposure of hands, arms
and face 2–3 times/week may be
sufficient (depending on skin sensitivity).
• Clothing, sunscreen, window glass and
pollution reduce amount produced.
Source: National Osteoporosis Foundation Web site; retrieved July 2005 at http://www.nof.org

9. Toxic >150 nmol/L
(60 mcg/L)
Check calcium Stop treatment
(enough to suppress PTH)

10. Definition of vitamin D deficiency & sufficiency based on serum 25(OH)D
concentrations
Vitamin D Deficiency & Insufficiency
Davies JH & Shaw NJ. Arch Dis Child. 2010 Jul 23. [Epub ahead of print]

15. System and Tissue Distribution of Nuclear
Vitamin D Receptors (VDR)
System Tissue
Immune Thymus, bone marrow, macrophages, B cells, T cells
Gastrointestinal Esophagus, stomach, small intestine, colon, rectum
Cardiovascular Endothelial cells, smooth muscle cells, myocytes
Respiratory Lung alveolar cells
Hepatic Liver parenchyma cells
Renal Proximal and distal tubules, collecting duct
Endocrine Parathyroid, thyroid, pancreatic beta cells
Exocrine Parotid gland, sebaceous gland
CNS Brain neurons, astrocytes, microglia
Epidermis/appendage Skin, breast, hair follicles
Musculoskeletal Osteoblasts, osteocytes, chondrocytes, striated muscle
Connective Tissue Fibroblasts, stroma
Reproductive Testis, ovary, placenta, uterus, endometrium, yolk sac

16. Vitamin D Deficiency
Rickets, Osteomalacia
Influenza, Tuberculosis
MS, RA, SLE, Type I diabetes
Hypertension, CAD, PVD, CHF
Syndrome X, Type 2 Diabetes
Chronic Fatigue, SAD,
Depression
Cataracts, Infertility
Osteoporosis
Cancer

17. Holick BMJ June 2008;336:1318-1319
Possible Consequences of Vitamin D Deficiency

18. 18
What May Vitamin D Improve?
-Improved bone health
-Increased absorption of calcium
-Reduced risk of falls and bone fractures
-Reduced coronary artery disease
-Improved muscular function
-Lowering of high blood pressure
-Improved blood sugar tolerance
-Improved nerve function
-Improved kidney function
-Reduced risk of 17 cancers
-Reduced influenza, cold infections, tuberculosis
-Reduced risk of some types of dementia

19. Vitamin D & Innate Immunity
Adequate serum 25(OH)D
Innate immunity
 Toll like receptors recognise
pathogens

  expression of VDR & CYP27B1
enzyme
25(OH)D  1,25(OH)2D
 1,25(HO)2D leads to production of
antimicrobial proteins (AMPs)
 AMPs (e.g. Cathelcidin) important
role in
defence against bacterial & viral
infections

20. Role of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al, Diabetes, Obesity and Metabolism, 2008

21. 21
Inverse Relationship between Vitamin D and
Morning Blood Glucose Levels in 1,614 Men and
Women
5.9
6.0
6.1
6.2
6.3
6.4
6.5
6.6
6.7
6.8
6.9
0 20 40 60 80 100 120
Median 25OHD (nmol/L)
MedianGlucose(mmol/L)
Lu ZX et al, unpublished data

22. 22
1
2
1
2
1,25(OH)2 vitamin D sites of action
Calcium sites of action
Harrison’s On-line
Effects of Vitamin D and Calcium on Insulin Sensitivity

23. 23
Effects of Vitamin D and Calcium on Insulin
Sensitivity
Entire Group
(n=80)
Vitamin D3 2000 IU/d +
Calcium Carbonate 1200
mg/d
(n=40)
Placebo
(n=40)
Randomisation* 8 weeks
* Randomisation in block and Stratification according to sex, age (< or >50 yo)
and BMI (< or >30 kg/m2)
† If 25OHD < 75 nmol/L
Extra vitamin D3
2000 IU/d†
or placebo
Extra placebo

24. Schematic representation of the multitude of other potential physiologic
action of vitamin D for cardiovascular health, cancer prevention, regulation
of immune function and decreased risk of autoimmune diseases
Holick, Am J Clin Nutr, 2004

25. 25
Vitamin D Anti-microbial Activity
Endogenous Anti-microbial Peptides
MACROPHAGE
N
Cathelicidin
Gene
Activation
25(OH)D
1,25-(OH)2D
1-hydroxylase
Microbes
+

26. 26
Infectious Diseases - Colds

27. 27
Infectious Diseases - Epidemic Influenza
• Influenza outbreaks were inversely correlated
with solar UVB
• Epidemic influenza is seasonal in part due to
seasonal variations of solar UVB and vitamin D
Hope-Simpson RE. J Hyg (Lond). 1981; 8:35-47
Cannell JJ, et al. Epidemiol Infect. 2006; 134:1129-40

28. 28
Relationship of 25(OH)D and Activation
of Latent Tuberculosis (n=155)
• Serum 25(OH)D lower in those with no TB (55 nmol/L),
latent TB (37 nmol/L) & TB/pastTB (16 nmol/L) p<0.01
Any vs. no TB Infection
TB/past TB vs. latent TB Infection
Gibney K et al, Clin Inf Disease 2008

29. Tuberculosis Treated with Sunshine

30. 30
Vitamin D and Cancer
● Inverse correlation between incidence, mortality and or
survival rates for many cancers including breast,
colorectal, ovarian, and prostate cancers.
● Emerging evidence that more than 17 cancers are likely
to be vitamin D sensitive.
● 1000 IU/day could reduce cancers 7% for men, 9% for
women in US.
● 25(OH)D level of 52 ng/ml reduced breast cancer by
50%
● 60-80 ng/ml may be optimal for most individuals
● 25(OH)D level increase from 29 to 39 reduced cancer
risk by 60% after 4 years.

31. 31
Vitamin D and Cancer
Apperly first demonstrated an association between
latitude and cancer mortality in 1941
Cancers associated with low vitamin D include:
•Breast and Ovarian Cancer
•Prostate Cancer
•Digestive system cancer, including Colon Cancer

32. 32
Vitamin D and Calcium Supplementation
Reduces Cancer Risk
• A 4-yr prospective, placebo-controlled study of
1100 IU vitamin D3 and/or 1400 mg calcium and
cancer risk in 1179 post-menopausal women
• Serum 25(OH)D rose from 71.8 to 96.0 nmol/L
• The all-cancer incidence for women over the age
of 55 years at time of enrollment was reduced by
60% (p=0.01)
Lappe JM et al. Am J Clin Nutr 2007 85: 1586-91

33. 33
Vitamin D Deficiency is Associated with Increased
Risk of Breast Cancer Recurrence and Death
• 512 women (mean age 50 yrs) with early stage breast cancer
• After 11 yrs, 85% of women with sufficient levels survived
compared with 74% of deficient women
• After 10 yrs, women with deficient levels were 94% more likely to
have distant metastases
Goodwin P et al. ASCO (abstract) 2008

34. Northern vs. Southern U.S.
1 – 2 extra
skin cancer
deaths
(per
100,000)
30 – 40 extra
deaths for
other major
cancers (per
100,000)

35. June, 2007 American Journal of Clinical
Nutrition
 Women who regularly took vitamin D3 and
calcium had a 60% reduction in all-cancer
incidence compared with a group taking placebo
and a 77% reduction when the analysis was
confined to cancers diagnosed after the first 12
months.

36. 36
Vitamin D and Mortality Rates
• The risk of dying from any cause in subjects who
participated in randomized trials of vitamin D
supplementation
• 18 independent randomized, controlled trials,
including 57,311 participants
• 4777 deaths from any cause occurred
• Mean daily vitamin D dose was 528 IU, 5.7 year
average follow-up
• The relative risk for mortality from any cause was 0.93
(95% CI, 0.87-0.99)
Autier P, Gandini S Arch Intern Med 2007 167(16):1730-7

37. 37
Cardiovascular Disease
• A graded increase in cardiovascular risk across
categories of serum 25(OH)D, with hazard ratios of 1.53
for levels 25 to 38 nmol/L and 1.8 for levels < 25 nmol/L
• Highest risk was in those with hypertension and vitamin
D deficiency
Wang TJ et al, Circulation 2008;117: 503-11

38. 38
Vitamin D and the Heart
Low levels of vitamin D associated with increased risk
of cardiovascular disease and mortality.
One study: Low vitamin D risk increase of
Coronary Artery Disease - 45%
Stroke - 78%
Heart attack - 50%
Death – 77-100%
25-57% USA adults
may be deficient

39. 39
Vitamin D and Obesity
• Obese subjects vs. normal weight controls have
– Lower serum 25OHD levels
– Higher PTH and inconsistent results for 1,25(OH)2 vitamin D
• Two possible explanations
– Less sunlight exposure
– Decreased bioavailability of vitamin D due to sequestration in adipose tissue
Liel et al, Calcif Tissue Int, 1988
Wortsman et al, Am J Clin Nutr, 2000

40. 40
Vitamin D and MS
Multiple Sclerosis: Vitamin D levels of 40 ng/ml
or higher may confer some protection against
MS.
Patients receiving Magnesium, Calcium and
5000 IU vitamin D significantly reduced MS
exacerbations (14 vs 32).

41. 41
Vitamin D and Dementia
● Vitamin D may be primarily associated with cognitive
domains other than memory , such as executive cognitive
functions, depression, bipolar disorders, and
schizophrenia.
● Low 25(OH)D may be a risk factor for cognitive
impairment (41-60%).
● Receptors for Vitamin D are present in brain cells.
Increased Vitamin D may improve cognitive function in
patients with Alzheimer's

42. 42
Vitamin D and Falls
Low vitamin D may result in more falls and
fractures since muscles contain vitamin D
receptors.
Vitamin D activation increases protein
synthesis in muscles.
13 studies using 800-1000 IU consistently
demonstrated beneficial effects on muscle
strength and balance with aged 60 or older.

43. 43
Vitamin D and the Lungs
Asthma: Early studies indicate may reduce severe
exacerbations, exercise induced bronchoconstriction
Lower respiratory tract infections are more frequent in
those with low 25(OH)D levels.
2000 IU Vitamin D abolished the seasonality of influenza
and dramatically reduced the self-reported incidence.
Vitamin D reduces inflammation and viral pathogens.

44. 44
Vitamin D and the Lungs
One Vitamin D Influenza study showed:
334 children 6-15 years
50% -1200 D3 4 months vs placebo
Flu: 10.8% (with D) vs 18.6%
Asthma children – 93% reduced attacks
Low vitamin D adults: double risk of viral infections

45. Vitamin D Assessment
 Lab assays are available to measure both 25(OH)D and
1,25-D.
 25(OH)D closely reflects total amount of vit D produced
in the skin and from diet
 D2 and D3: have similar biological activity
 Both D2 and D3 should be measured
 DO NOT USE - 1,25-D. This can often be normal with vit
D deficiency

46. Who is at greatest risk?
 Low dietary intake: BF infants, children who do not drink
fortified milk
 Malabsorption syndrome
 Severe liver disease
 Kidney disease
 Drugs
 Higher latitudes
 People who spend little
time outside
 Older adults
 Decreased
sun exposure due to
cultural reasons
 Races with
high skin melanin levels

47. 47
Malabsorption Drug Interactions
and Storage
Patients who may require more vitamin D
intake include those with:
● Intestinal fat-malabsorption syndromes
● Anticonvulsive medications
● Glucocorticoids and related medications
● Less ability to absorb sunlight (elderly)
● Excess fat (vitamin D stored in fat is not
available)

48. 48
Vitamin D Sources
The Sunshine Vitamin
Fortified foods:
Typically supply 150 IU per day, but highly
variable (100 - 400 IU per day).
Supplements:
-Over-the-counter usually vitamin D3
-Prescription versions are usually vitamin D2
(synthetic).
-Vitamin D3 is more than three times
powerful than D2.

49. 49
How Much Vitamin D
is Needed?
Estimated body requirements per day are 3000-5000
IU.
Obese and elderly may need the higher levels.
10,000 IU per day may be the new recommended upper
limit.(10)
The only way to know how much is needed is to test
25(OH)D.
Everyone should be tested!
Goal: 25(OH)D between 60-80 ng/ml after a consistent
intake level over 2 months.
100 IU of vitamin D raises 25(OH)D about 1 ng/ml.

50. Vitamin D Supplementation
Deficiency (<25 nmol/l or 10 mcg/l)
 Oral Therapy
– 1st line agent:
Fultium-D3 ® (Cholecalciferol) 800 iu capsules x4/d
(licensed product) - 3200 iu daily for 8-12 weeks.
– 2nd line:
Dekristol® (Cholecalciferol) capsules 20,000 units
(unlicensed import). Prescribe 1 capsule (20,000 units) once
per week for 8-12 weeks.
Where oral therapy not appropriate
Ergocalciferol 300,000 (or 600,000) iu single dose by
intramuscular injection. The injection is gelatin free and may
be preferred for some populations.

51. Vitamin D Supplementation
Insufficiency (25-50 nmol/l or 10-20 mcg/l) or for
long-term maintenance following rx of deficiency
 1st line therapy
– Fultium-D3® 800iu capsules x2/d (licensed) - 1600iu per
day (a dose between 1000 – 2000 units daily is
appropriate).
 2nd line:
– Prescribe Dekristol® capsules 20 000 units [unlicensed
import]. Prescribe 1 capsule (20,000 units) once per
fortnight.
 Alternatively where oral therapy not appropriate
– Ergocalciferol 300,000 international units single dose by
intramuscular injection once or twice a YEAR.

52. Alfacalcidol/Calcitriol
 Alfacalcidol (1 alpha- vitamin D) and Calcitriol
have no routine place in the management of
primary vitamin D deficiency
 Reserved for use in renal disease, liver disease
and hypoparathyroidism.

53. 53
Who is at risk to overdose on
Vitamin D?
Anyone who takes Vitamin D supplements CAN take too much
Vitamin D. But the majority of documented overdose on vitamin D
are from:
• Children whose parents accidentally give them massive doses of
vitamin D
• Elderly people who incorrectly take massive vitamin D dosages
• Adults who take more than 10,000 IU's per day for long periods of
time.
• 'Industrial Accidents' where massive quantities of vitamin D are
put into fortified foods in error
These categories comprise nearly all people who have had an
overdose on Vitamin D.

54. FAQ

55. Yes , any increase in BMD
results in fructure reduction
Decrease BMD despite
adequate R/ , pt. should be
reevaluated for compliance or
a 2ry cause of loss

56. No definite time limit to bisphosphonate use for osteoporosis.
Maintenance or increase in BMD with use of Alendronate for up to 10 years,
Risedronate for at least 5 years.
Normalization of BMD on therapy reasonable to cosider stopping the agent.

57.  No , only some pt. with osteopenia need to be treated for example :
 h/o a law trauma fracture .
 Pts. deserve to be treated.
 Pts. At high risk of fracture due to , prior fracture ,T-score ≤ 1.8, poor
mobility or poor overall health status

58.  It shouldn’t be used for more than 2 years , stop it and switch pt. to
a bisphosphonate .

59. 15 minutes between 10:00 am and 2:00
pm should provide adequate sunlight.

60.  No , it needs massive doses of vit. D given chronically to induce
toxicity (> 10,000 IU/day)
 Don’t be afraid and give appropriate supplementation (some pt. on
anticonvulsant therapy may need 4000 IU/day to achieve adequate
vit. D level )

61.  Fracture at time of menopause is less than
at old age .
 The incidence of spine and hip fractures
begins to increase starting at the age of 60
or 65.
 Women with several lifestyle risk factors
(e.g. on steroid therapy or breast CA on R/) ,
should be screened earlier than age 65 to
identify who would benefit from
pharmacological R/.
 Counsel all women on life style strategies
(calcium,vit. D ,exercise, and nonsmoking.

62. Summary
You are never too old or too young
to improve your bone health
• Adults
– At least 30 minutes of moderate physical activity a day
– Strength and balance training
– Protect from falls
– Eye exam to check for visual impairments
– Bone density test with a fracture after age 50, and for everyone with risk factors
– Bone density test for all women over age 65
– Extra calcium and vitamin D over age 50
– Medication, if indicated, to prevent
bone loss or build new bone

63. • Children & Teens
– Teens are at greater risk for poor bone health because of rapidly growing bones
and poor diet
– At least one hour of physical activity a day
– Increase calcium during teens
• Babies
– Bone health begins before birth
Summary
You are never too old or too young
to improve your bone health

64. “Men grow old, pearls
grow yellow, there is
no cure for it “
Chinese proverb