1. The document discusses vitamin D functions, deficiency, testing, and treatment recommendations. It provides guidelines on screening for deficiency, preferred tests, dosing for deficiency treatment in different populations, and use of vitamin D supplements for non-skeletal benefits like immunity and cancer reduction. 2. Treatment of vitamin D deficiency requires supplementation, not just dietary changes, with recommendations to use cholecalciferol over ergocalciferol. Dosing depends on factors like age and compliance monitoring is advised. 3. Beyond bone health, evidence is mixed on other benefits of vitamin D supplementation though fall prevention is recommended. Judicious evaluation of other causes is advised when vitamin D replacement does not resolve symptoms.

1. Vitamin D
Ahmed Yehia Ismaeel, MD
Internal medicine,
Clinical immunology (Rheumatology &
Allergy)

3. What are vitamin D functions?
Vitamin D receptor distribution in human organs and tissues.

6. A lot of
questions
A lot of debate

8. What is the commonest presentation
of vitamin D deficiency?
Largely asymptomatic and
physical examination is
typically unremarkable
unless severe enough.
Subclinical vitamin D deficiency

9. Many with
subclinical
vitamin D
deficiency
relative
hypocalcemia
high serum
PTH levels
Osteoporosis
increased risk
of fractures &
falls in older
adults.

10. Please, DR.,
would you measure my
vitamin D
for reassurance?
????
????
So,….

11. • Neither the Endocrine Society, the
Mayo Clinic, the U.S. Preventive
Services Task Force, nor the American
Association of Clinical
Endocrinologists recommends
universal screening for vitamin D
deficiency among the general
population or asymptomatic
individuals.

12. He was on vitamin D
Osteomalacia

13. Would you
test for
vitamin D?

14. • Neither the Endocrine Society, the Mayo
Clinic, the U.S. Preventive Services Task
Force, nor the American Association of
Clinical Endocrinologists recommends
universal screening for vitamin D deficiency
among the general population or
asymptomatic individuals. However, they
do recommend screening in individuals
with risk factors for vitamin D deficiency.

15. Individuals
at risk for
deficiency
• Rickets
• Osteomalacia
• Osteoporosis
• Chronic kidney disease
• Hepatic failure
• Malabsorption
syndromes
• Cystic fibrosis
• Inflammatory bowel
disease
• Bariatric surgery
• Radiation enteritis
• Hyperparathyroidism
• Some lymphomas
• Medications
• Antiepileptic drugs (AEDs)
• Glucocorticoids >Cholestyramine
• AIDS medications
• Antifungals, e.g. ketoconazole
• Pregnant & lactating women
• Elderly with history of falls
• Elderly with history of
nontraumatic fractures
• Obese children and adults
(BMI 30 kg/m2)
• Granuloma-forming disorders
• Sarcoidosis
• Tuberculosis
• Histoplasmosis
• Coccidiomycosis
• Berylliosis

16. Causes of vitamin D deficiency or resistance
• Deficient intake or absorption
• Dietary
• Malabsorption
• Gastric bypass (bariatric surgery, gastrectomy)
• Small bowel disease
• Pancreatic insufficiency
• Decreased skin synthesis
• Inadequate sunlight exposure
• Full sunscreen use
• Darkly pigmented skin

17. Causes of vitamin D deficiency or resistance
• Defective 25-hydroxylation
• Cirrhosis
• Increased catabolism of vitamin D to inactive metabolites
• Anticonvulsants
• Loss of vitamin D binding protein
• Nephrotic syndrome
• Defective 1-alpha 25-hydroxylation
• Hypoparathyroidism
• Renal failure
• 1-alpha hydroxylase deficiency (vitamin D-dependent rickets, type 1)
• Defective target organ response to calcitriol
• Hereditary vitamin D-resistant rickets (vitamin D-dependent rickets, type 2)

19. • 1.1 We recommend screening for vitamin D deficiency in
individuals at risk for deficiency. We do not recommend
population screening for vitamin D deficiency in
individuals who are not at risk (1|QQQQ).

20. Back to presentation
• Generalized
bone pain
• muscle
weakness
• waddling gait
• pseudofractures

21. Please, DR.,
I have diffuse aches.
????
????

22. Vitamin
D
After full assessment
Is there further
assessment?

23. Case: How
would you test
for vitamin D?
S. vitamin D
S. 25 OH vitamin D
S. 1, 25 (OH) vitamin D

24. • 1.2 We recommend using the serum circulating 25-hydroxyvitamin D [25(OH)D]
level, measured by a reliable assay, to evaluate vitamin D status in patients who are at
risk for vitamin D deficiency. We recommend against using the serum 1,25-
dihydroxyvitamin D [1,25(OH)2 D] assay for this purpose & are in favor of using it
only in monitoring certain conditions, such as acquired and inherited disorders of
vitamin D and phosphate metabolism (1|QQQQ).

25. • There is, of course, a
seasonal variation in
serum 25(OH)D
concentrations with the
highest levels at the end
of summer and the
lowest levels at the end of
winter, but the tracking of
serum 25(OH)D
concentrations over time
reveals that a single
measurement of serum
25(OH)D at a given time
point provides an
estimate of future
25(OH)D levels (even if
years apart) which is
similar to the tracking of
blood pressure or blood
lipids.

26. Please, DR.,
My vitamin D level is 9
ng/dl. Is it OK?
??????????
??????????
??????????

27. Debate

28. Definitions
Vitamin D
adequacy—25(OH)D
levels 30 to 50 ng/mL
Vitamin D insufficiency—
25(OH)D levels 21 to 29
ng/mL
Vitamin D deficiency—25(OH)D levels
≤20 ng/mL
Vitamin D severe deficiency—25(OH)D levels ≤12
ng/mL

29. Please, DR.,
My vitamin D level is 9
ng/dl. Is it OK?
Your vit. D
is severely
deficient.

30. Please, DR.,
would you prescribe
dietary vitamin D
only?
??????????
??????????
?????????

31. •There is broad consensus that increased
intake of dietary vitamin D is not enough to
correct deficiency.
•Vitamin D supplementation is required.

32. Which vitamin D
to prescribe?

33. What are
types of
vitamin D?

34. What are types of vitamin D
available pharmaceutically?

35. What are types of vitamin D
to be used in practice?
3.1 We suggest
using either vitamin
D2 or vitamin D3
for the treatment
and prevention of
vitamin D
deficiency
(2|QQQQ).

36. • Cholecalciferol is not
regulated by the FDA
but is slightly more
efficient and predictable
than ergocalciferol at
raising 25(OH)D levels,
so its use is typically
favored when available.

37. •There has been debate regarding which
form of vitamin D should be used for
supplementation.
•We suggest supplementation with
cholecalciferol rather than
ergocalciferol when available.

38. • In a meta-analysis of 7 randomized trials
evaluating serum25(OH)D levels after
supplementation with cholecalciferol
versus ergocalciferol, cholecalciferol
increased serum 25(OH)D more
efficiently than ergocalciferol (mean
differencein serum 25[OH]D 6 ng/mL
[15.23 nmol/L]).
•The trials in the meta-analysis used
varying doses and treatment time
periods, resulting in significant
heterogeneity among studies.

39. Vitamin D3 (cholecalciferol) is available in 400, 800,
1000, 2000, 5000, 10,000, & 50,000unit capsules.
It is available in some countries as an intramuscular
injection, which can be extremely painful.
Vitamin D2 (ergocalciferol) is available for oral use in
400 and 50,000 unit capsules or in aliquid form (8000
unit/mL [200 mcg/mL]).
A previously available intramuscular preparation is now
difficult to obtain in USA.

40. How often do you
prefer?????
•Daily
•Weekly
•Monthly
•Yearly

41. •Large, intermittent (eg, monthly, yearly)
doses of vitamin D3 increase serum
25(OH)D levels.
•But we do not use them in patients with
normal absorptive capacity.
•In one trial, a large, annual oral dose of
500,000 IU vitamin D3 increased falls &
fractures in older adults.
•Monthly dosing with 60,000 IU & 100,000
IU increased risk of falling in older adults
& nursing home residents, respectively.

42. For how long
would you
treat?
Do you need
monitoring?

43. Assess patient risk
If high-risk
measure serum 25(OH)D
supplement with the amount estimated to be
needed to reach the target 25 (30) (OH)D level
remeasure 3: 4 months later to
verify that they achieved target.

44. Please, DR.,
My vitamin D level is still
11 ng/dl and I have
severe aches.
Your vit. D
is severely
deficient.

45. What is the problem? ???????

46. Surely, sir.
Are you
compliant with
the drugs?

47. Anti-tissue
transglutaminase

48. Please, DR.,
My vitamin D level is still
32 ng/dl and I have
severe aches.
??????????
??????????
??????????

49. T2T

50. No, if reaching the target,
start “maintenance dose”.
Is the target
the end?

51. Dose?
• 3.2 For infants and toddlers aged 0–1
yr who are vitamin D deficient, we
suggest treatment with 2000 IU/d of
vitamin D2 or D3, or with 50,000 IU of
vitamin D2 or D3 once weekly for 6 wk
to achieve a blood level of 25(OH)D
above 30 ng/ml, followed by
maintenance therapy of 400-1000
IU/d (2|QQQQ).

52. Dose?
• 3.3 For children aged 1–18 yr who are
vitamin D deficient, we suggest
treatment with 2000 IU/d of vitamin
D2 or vitamin D3 for at least 6 wk or
with 50,000 IU of vitamin D2 once a
week for at least 6 wk to achieve a
blood level of 25(OH)D above 30
ng/ml, followed by maintenance
therapy of 600-1000 IU/d (2|QQQQ).

53. Dose?
• 3.4 We suggest that all adults who are
vitamin D deficient be treated with
50,000 IU of vitamin D2 or vitamin D3
once a week for 8 wk or its equivalent
of 6000 IU of vitamin D2 or vitamin D3
daily to achieve a blood level of
25(OH)D above 30 ng/ml, followed by
maintenance therapy of 1500–2000
IU/d (2|QQQQ).

54. Dose?
• 3.5 In obese patients, patients with
malabsorption syndromes & patients on
drugs affecting vitamin D metabolism,
we suggest a higher dose (2 to 3 times
higher; at least 6000–10,000 IU/d) of
vitamin D to treat vitamin D deficiency
to maintain a 25(OH)D level above 30
ng/ml, followed by maintenance
therapy of 3000 –6000 IU/d (2|QQQQ).

55. Please, DR.,
would you prescribe
vitamin D
for my son’s immunity?
????
????

56. Please, DR.,
would you prescribe
vitamin D
for immunity?
????
????

57. • Beyond musculoskeletal effects, several studies investigated the
potential extra-skeletal actions of vitamin D. Cell culture and
animal studies as well as observational data support the hypothesis
that vitamin D is critical for a variety of common diseases including
for example, cardiovascular, autoimmune, and neurological
diseases, infections, pregnancy complications and cancer. By
contrast, RCTs have largely shown no effect of vitamin D
supplementation on nonskeletal health outcomes. Nevertheless,
some meta-analyses of RCTs documented beneficial vitamin D
effects on certain health outcomes such as respiratory tract
infections, asthma exacerbations, some pregnancy outcomes and
mortality. These data should, however, be interpreted with caution
due to some limitations such as heterogeneity, different sources of
potential bias, data quality of original trials and partially small
effect sizes.

58. • The association between
vitamin D status and cancer,
with several observational
studies showing an inverse
association between serum
25(OH)D concentrations and
cancer incidence as well as
mortality. Meta-analyses of
RCTs largely report a
moderate, yet significant
reduction in cancer mortality
by vitamin D
supplementation.

59. 4.0 Non-calcemic
benefits of vitamin D
• 4.1 We recommend prescribing
vitamin D supplementation for
fall prevention. We do not
recommend prescribing vitamin D
supplementation beyond
recommended daily needs for the
purpose of preventing
cardiovascular disease or death
or improving quality of life
(2|QQQQ).

60. Can we predict s.
25 OH vitamin D
response to
treatment?
• Regarding the precise vitamin
D intake serum 25(OH) D
dose–response curve, there
are slightly inconsistent results
in the literature (88, 91). As a
frequently quoted rough
summary, it can be estimated
that per intake of about 2.5 μg
(100 IU) of vitamin D per day,
the serum 25(OH)D
concentrations may increase
by about 2.5–5 nmol/L but
with quite significant
variability of such estimates in
the literature

61. Fashions
Uric acid
Vitamin D

63. Case
• A 55 years old female with history
of fatigue & 1 year of bony pains
presents to you with vitamin D
level 12 ng/ml. Would you give her
vitamin D?
• After vitamin D replacement, she
still complains. Would you request
further investigations?
• TSH>100.

64. Key message
• Vitamin D deficiency is so
prevalent, so it may be
accidentally found in many
patients. So, you should
judiciously assess for other causes
of the complaint.

65. Case: Could it be anything
other than vitamin D?

67. •Many patients, especially older adults,
take vitamin and mineral supplements
that contain vitamin D. The patient may
not be aware that these supplements
contain vitamin D. It is important to
inquire about additional dietary
supplements that patients may be taking
before prescribing extra vitamin D.
Caution