Vitamin D Deficiency is linked to bone disorders. However, there is insufficient data for establishing guidelines for "adequate levels". Its been close to a century since it was first discovered. But how much do we actually know about it?

1. Deepkamal Kaur,
MD
Nephrology
Fel low
Universi ty of
Iowa Hospi tals
and Cl inics
NEPHROLOGY
GRAND ROUNDS
HYPOVITAMINOSIS D –
HOW MUCH DO WE
KNOW?

2. HISTORY
 “ T h e E ng l is h Di s e a se”
 Sir Edward Mel lanby - 1919
 McCol lum – 1922
 Huldshinsky, Chick et al , Hess
& Unger, Steenbock, Hess & Weinstock
(Rickets and UV l ight)
 Vitamin D2- 1932
 7-dehydrocholesterol – 1935
 Vitamin D3 – 1937
 Pre-vitamin D3 – 1977, Hol ick MF et al
 Esvelt et al – Production under skin - 1978
Elmer V. McCollum

3. Holick MF, NEJM - 2007

4. Holick MF, NEJM - 2007

5. VITAMIN D DEFICIENCY – WHAT WE
KNOW?
Vitamin D2: Manufactured through the ultraviolet irradiation of
ergosterol from yeast. Prescription med.
Vitamin D3: Ultraviolet irradiation of 7-dehydrocholesterol from
lanol in.

6. VITAMIN D DEFICIENCY- GENERAL
POPULATION
“ 2 5 -hydroxyvitamin D levels and the risk of mor tal ity in the
g e ne ral p o p u l atio n” – Melamed M. et al , Archives of Internal
Medicine – Aug- 2008.
Cross-sectional multivariate analyses on 13 331 nationally
representative adults 20 years or older from the Third National
Health and Nutrition Examination Survey (NHANES I I I ) l inked
mor tal ity fi les. Vitamin D levels were col lected from 1988
through 1994.
Conclusion: The lowest quar ti le of 25(OH)D level (<17.8 ng/mL)
is independently associated with al l -cause mor tal ity in the
general population.

7. VITAMIN D DEFICIENCY- GENERAL
POPULATION
“ V i t amin D deficiency and risk of cardiovascular d i s e ase. ” Wa ng
et al , Circulation, jan-2008.
1739 Framingham Of fspring Study par ticipants (mean age 59
years; 55% women; al l white) without prior cardiovascular
disease.
Conclusion- Vitamin D deficiency is associated with incident
cardiovascular disease.

8. VITAMIN D DEFICIENCY – CKD AND/
ESRD POPULATION
“ V i t amin D deficiency is associated with cardiovascular disease,
the most common cause of mor tal ity in hemodialysis p a t i ent s . ”
Mai lliez S et al ; Kidney International, 2007.
“Act ivated injectable vitamin D and hemodialysis survival: a
historical cohor t s t u d y ” ; Teng M, Wolf M, Ofsthun MN, et al . ; J
Am Soc Nephrol 2005;16:1115–25.
“Lee GH, Benner D, Regidor DL, Kalantar-Zadeh K. Impact of
kidney bone disease and its management on survival of patients
on dialysis J Ren Nutr 2 0 07 ”

9. VITAMIN D DEFICIENCY –CKD STAGE 3-4
In patients with CKD Stages 3 and 4, therapy with an active oral
vitamin D sterol (calcitriol, alfacalcidol, or doxercalciferol) is
indicated when serum levels of 25(OH) -vitamin D are >30
ng/mL, and plasma levels of intact PTH are above the target
range for the CKD stage. - KDOQI

10. VITAMIN D DEFICIENCY –CKD STAGE 5
OR ESRD
Patients treated with hemodialysis or peritoneal dialysis with
serum levels of intact PTH levels >300 pg/mL (33.0 pmol/L)
should receive an active vitamin D sterol (such as calcitriol,
alfacalcidol, paricalcitol, or doxercalciferol) to reduce the
serum levels of PTH to a target range of 150 to 300 pg/mL
(16.5 to 33.0 pmol/L). - KDOQI

11. VITAMIN D DEFICIENCY – WHAT WE
KNOW?
Recommended Intakes – How were they determined?
“An assumption in developing the DRIs for calcium is that they
are predicated on intakes that meet requirements for vitamin D;
simi larly, DRIs for vitamin D rest on the assumption of intakes
that meet requirements for calcium. ” IOM – 2010
“ T h e cut -point levels of serum 25OHD intended to specify
deficiency for the purposes of interpreting laboratory analyses
and for use in cl inical practice are not specifically within the
charge to this committee. However, the committee noted with
some concern that serum 25OHD cut -points defined as
indicative of deficiency for vitamin D have not undergone a
systematic, evidence-based development process. ”

12. VITAMIN D DEFICIENCY – WHAT WE
KNOW?
-According to cer tain "reference ranges", about a bi l l ion people
worldwide have vitamin D deficiency. Prescrire Int. 2013
Oct;22(142):245-8.
US Institute of Medicine(IOM): Values <20 ng/ml – Deficiency
-Vitamin D Insuf ficiency: 21-29 ng/ml
-Vitamin D Deficiency: less than 20 ng/ml
*Hol ick MF et al , Evaluat ion, Treatment , and Prevent ion of Vi tamin D
Def iciency: an Endocr ine Society Cl inical Pract ice Guidel ine; Februar y 14,
2011 – JCEM (Journal of Cl inical Endocr inology & Metabol ism)

13. VITAMIN D DEFICIENCY - MEASUREMENTS
Electrochemiluminescence – Standard of testing.
Measures 25-OH Vitamin D; both D2 and D3.

14. VITAMIN D DEFICIENCY - MEASUREMENTS
Vitamin D-Binding Protein Modifies the Vitamin D-Bone Mineral
Density Relationship. JOURNAL OF BONE AND MINERAL RESEARCH, Powe et al ,
2011. - 49 heal thy young adul ts enrol led in the Metabol ic Abnormal i ties
in Col lege-Aged Students (MACS) study.

15. VITAMIN D DEFICIENCY – AFRICAN
AMERICAN POPULATION
“Low levels of total 25-hydroxyvitamin D are common among
black Americans. Vitamin D–binding protein has not been
considered in the assessment of vitamin D deficiency. ” Powe et
al , NEJM, Nov, 2013.

16. Levels of Total 25-Hydroxyvitamin D and Vitamin D–Binding Protein in Community-Dwelling
White and Black Study Participants.
Powe CE et al. N Engl J Med 2013;369:1991-2000.

17. Powe CE et al. N Engl J Med 2013;369:1991-2000.

18. Confl icting evidence. Uncer tain given lack of suf ficient data. But
cer tainly no randomized control led trials to prove common
recommendations.
Low total 25-hydroxyvi tamin D levels do not uni formly indicate
vi tamin D deficiency – Uncer tain.
No strong evidence to suggest signi ficant harm wi th i ts use!
Calcium, Phosphorus, PTH should also be taken into consideration
and not vi tamin D-25-OH levels alone.
Usefulness for cancer prevention!
More data needed!
CONCLUSION

19. THANK YOU!