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Vitamin d deficiency – myths & facts
1. Vitamin D Deficiency – Myths &
Facts
Vinod Naneria
Choithram Hospital & Research Centre
Indore, India
2. The truth is
• We are scared.
• We are scared of “ N” number of diseases
associated with Vitamin D & Calcium.
• Almost all reports from all corners of India
shows a deficiency state up to 80 -90%
• CH&RC statistics shows 76% deficiency and
18% insufficiency out of 400 cases in affluent
class.
5. There is a cause of Fear!
• VDR is present in the nucleus of many tissues.
• In epidermal keratinocytes, activated T cells of
the immune system, antigen-presenting cells,
macrophages and monocytes, and cytotoxic T
cells.
• Calcitriol regulates several hundred genes
throughout the body or as much as 5 percent of
the human genome.
• The 1α-hydroxylase (CYP27B1) gene has been
reported to be expressed in many extra-renal
tissues.
How it works – not known
6. The cause of Fear – Extra Renal
• Extra-renal 1a-hydroxylation sites that can act as
intracrine systems primarily involved in regulation of
cell or tissue growth: skin, gastrointestinal tract, or
glandular tissue, such as prostate and breast.
• Extra-renal CYP27B1 may be up-regulated during
inflammation, or down-regulated in cancerous tissue
proliferation.
• Extra-renal production of calcitriol is found in certain
pathological diseases, including granulomatous
conditions such as sarcoidosis, lymphoma, and
tuberculosis, which can be associated with
hypercalcemia.
7. Fear psychosis?
Risk Factors Diseases Clinical expressions
• ↑ Cholesterol → Coronary→ Myocardial infarct.
• ↑ B.P.→ Hypertension → Stroke.
• ↑ Uric acid → Gout → Arthritis.
• ↓ Vit D → ↓ General health → ↑ All cause mortality.
• ↓ Vit D → ↑ Osteoporosis → Fragility Fracture.
8. Hype about hip fractures?
Published in The New York Times, May 10, 2010,
Company With Osteoporosis Treatment Wins the
‘Super Bowl’ By LORA KOLODNY
Biologics MD team competing at Global Moot Corp.
Courtesy of McCombs School of Business, Texas Venture Labs
9. Mozart's Death Was Written in the Key of (Vitamin) D
Jennifer Welsh, LiveScience Staff Writer Date: 06 July 2011 Time: 01:35 PM ET
If Wolfgang Amadeus Mozart
had spent a few minutes
basking in the sun, it might have
forestalled his untimely
death, researchers are saying.
In many places during the
winters, UVB levels in sunlight
are too low to make the vitamin
in our skin. Where Mozart
lived, in Vienna, these low levels
of UVB rays would have easily
caused vitamin D
deficiencies, two researchers
write in a letter in the June issue
of the journal Medical Problems
of Performing Artists.
10. Mislabeling as “Vitamin”
• Contrary to common belief, vitamin d is not
actually a vitamin at all. "Vitamins" by
definition, are nutrients that cannot be produced
by the body, but are necessary for the proper
functioning of the body's tissues and organs.
• Vitamin d is produced by our bodies (when our
skin is exposed to ultraviolet rays from the sun)
technically, it can not be considered a vitamin.
• It is a Steroid.
H1N1 – Influenza virus – Swine flue
11. • A lot of money can be made from
healthy people who believe they are sick.
• A lot of money can be made by
telling healthy people that they are sick.
• The social construction of illness is being
replaced by the corporate construction of
disease.
Ray Moynihan, journalist, Iona Heath, general
practitioner, David Henry, professor of clinical pharmacology.
BMJ 2002;324:886-891
12. Change a number, create a patient
The number of people with at least one of four
major medical conditions has increased
dramatically in the past decade because of
changes in the definitions of disease. "The new
definitions ultimately label 75 percent of the
adult U.S. population as diseased," according
to calculations by two Dartmouth Medical
School researchers.
Suddenly sick: A special report by Susan Kelleher and Duff Wilson · June 26 - June 30,
2005
http://seattletimes.nwsource.com/news/health/suddenlysick/sickdefinitions26.html
13. The Number Game
Diagnosis Old Definition New definition People People % increase Year
under under
Old New
Diabetes Fasting Sugar Fasting 11.7 M 1.7 M 14% 1997
> 140mg/dl > 126mg/dl
Hypertension BP > 160/100 BP> 140/90 38.7 M 13.5 M 35% 1997
Cholesterol > 250mg/dl > 200mg/dl 49.5 M 42.6 M 86% 1998
Obesity BMI> 27kg/m² BMI> 25kg/m² 70.6 M 30.5 M 43% 1998
(BMI)
Pre Nil 120/80 to Nil 45 M - 2003
hypertension 139/89
Source: “Changing Disease Definitions: Implications for Disease Prevalence,”
Dr.Lisa Schwartz and Steven Woloshin, Effective Clinical Practice, March/April 1999.
14. Indian Scene
Authors No. Of Patients Deficiency Insufficiency Year / Journal
Arya V et al. 78.3 Osteoporosis
Int. 2004 Jan
Marwaha R.K. 1346 1228 (91.2%) 92 (6.8%). J Assoc
et al Physicians
India. 2011
Vupputuri MR 105 94.3% Am J Clin Nutr.
el al 2006 Jun;83
Harinarayan CV. 164 52% 30% Osteoporosis
Harinarayan CV Int. 2005 Apr
et al Rural M/F 44%, /70%, 39.5%, /29%, Am J Clin Nutr.
Urban M/F 62%, / 75%, 26% / 19%, 2007 Apr;85
Shivane VK et 1137 100% Postgrad Med
al J. 2011
Aug;87(1030
15. Indian scene
• A high prevalence of clinical and biochemical
hypovitaminosis D exists in apparently healthy
schoolchildren in northern India.
Am J Clin Nutr. 2005 Aug;82(2):477-82. Marwaha R et el
• We observed a high prevalence of physiologically
significant hypovitaminosis D among pregnant
women and their newborns.
Am J Clin Nutr. 2005 May;81(5):1060-4. High prevalence of vitamin D deficiency
among pregnant women and their newborns in northern India.
Sachan A et al.
16. Why South Asian are deficient?
Dr. Nikhil Tandon – AIIMS ND
• vitamin D deficiency epidemic across South Asia,
including India and Pakistan. He also offered insight
into some of the possible reasons:
"A lack of exposure to sunshine, genetic traits and
dietary habits, skin pigmentation and traditional
clothing, as well as air pollution and limited outdoor
activity in urban populations.“
• High Oxalates & Phytates in the food make
unabsorbable calcium salts in the intestine.
second annual 1st Asia-Pacific Osteoporosis Meeting in Singapore
17. Millions Of U.S. Children Low In
Vitamin D
• The researchers found that 7.6 million children
across the U.S., were vitamin D deficient, while
another 50.8 million, were vitamin D insufficient.
• Low vitamin D levels were especially common in
children who were older, female, African-
American, Mexican-American, obese, drank milk
less than once a week, or spent more than four
hours a day watching TV, playing videogames, or
using computers.
19. Vitamin D - One outfit for All
• Anti aging,
• Anti cancer,
• Anti diabetes,
• Anti infective,
• Anti depressant,
• Anti hypertensive,
• Cardiac protective
20. National Osteoporosis Foundation Vitamin D
Recommendations
• Deficiency is when 25-hydroxyvitamin D blood
level of below 10 ng/ml (25nmol)
• Insufficiency is defined as a 25-hydroxyvitamin
D blood level between 10 ng/ml - 30 ng/ml
• Sufficiency is defined as a 25-hydroxyvitamin D
blood level of 30ng/ml or higher
Multiply ng/ml by 2.5 to get nmol/litre
21. Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health* [1]
nmol/L** ng/mL* Health status
<30 < 25 <12 Associated with vitamin D
deficiency, leading to rickets in
infants and children and
osteomalacia in adults
30–50 25- 75 12–20 Generally considered
inadequate for bone and
overall health in healthy
individuals
≥50 75 - 250 ≥20 Generally considered
adequate for bone and overall
health in healthy individuals
>125 >250 >50 Emerging evidence links
potential adverse effects to
such high levels, particularly
>150 nmol/L (>60 ng/mL)
* Serum concentrations of 25(OH)D are reported in both nanomoles per liter (nmol/L)
and nanograms per milliliter (ng/mL). ** 1 nmol/L = 0.4 ng/mL
22. Why 30ng/ml optimal
Relationship between serum PTH and 25(OH)D
levels demonstrate a plateau in suppression of
PTH when the 25(OH)D level reaches
approximately 30 ng/mL.
This is the rationale for selecting 30 ng/mL as the
cut-off value.
Vitamin D level < 10 ng/ml will lead to rickets &
osteomalasia. This is another cut-off point.
Anything below is severe deficiency.
25. Recommended Dietary Allowances (RDAs) for Vitamin D [1]
Age Male Female Pregnancy Lactation
400 IU 400 IU
0–12 months* (10 mcg) (10 mcg)
600 IU 600 IU
1–13 years (15 mcg) (15 mcg)
600 IU 600 IU 600 IU 600 IU
14–18 years (15 mcg) (15 mcg) (15 mcg) (15 mcg)
600 IU 600 IU 600 IU 600 IU
19–50 years (15 mcg) (15 mcg) (15 mcg) (15 mcg)
600 IU 600 IU
51–70 years (15 mcg) (15 mcg)
800 IU 800 IU
>70 years (20 mcg) (20 mcg)
* Adequate Intake (AI)
27. Summary IOM 2010
• Outcomes related to cancer, cardiovascular
disease, hypertension, diabetes, metabolic
syndrome, falls, physical performance,
immune functioning, autoimmune disorders,
infections, neuropsychological functioning,
and preeclampsia could not be linked reliably
with calcium or vitamin D intake and were
often conflicting.
Exception: measures related to bone health.
28. Summary IOM 2010
• Although data related to cancer risk and vitamin
D are potentially of interest, a relationship
between cancer incidence and vitamin D (or
calcium) nutriture is not adequately and causally
demonstrated at present;
• indeed, for some cancers, there appears to be an
increase in incidence associated with higher
serum 25-hydroxyvitamin D (25OHD)
concentrations or higher vitamin D intake.
29. The U turn
• A U-shaped response curve describes the
relationship between serum 25(OH)D and various
disease risks.
• Finnish study, the risk of prostate cancer increases
below 40 nmol/L and above 60 nmol/L .
• In women from the United States, Finland and China,
mortality for 7 types of cancer (endometrial,
esophageal, gastric, kidney, non-Hodgkin's
lymphoma, pancreatic, ovarian) increases below 45
nmol/L and above 124 nmol/L.
30. The U turn
• Another transnational study reported that the risk of
pancreatic cancer is higher above 100 nmol/L.
• The Framingham Heart Study concluded that
cardiovascular disease risk increases below 50 nmol/L
and above 62.5 nmol/L,
• The NHANES III found higher all-cause mortality above
122.5 nmol/L.
• Perhaps most worrisome, animal and human studies
have indicated a U-shaped response curve for lifespan,
with premature ageing associated with both too little
and too much vitamin D.
32. Factors affecting – Vitamin D synthesis
• Latitude No effect
• Skin color No effect
• Dietary habit + ve effect
• Age + ve effect
• Life style + ve effect
• Lab errors! No standardization.
33. The Latitude The UVB exposure around the glob
White – developed countries
By: Tavera-Mendoza
34. The Latitude
• Surprisingly, geographic latitude does not
consistently predict average serum 25(OH)D
levels in a population.
• Ample opportunities exist to form vitamin D
(store it in the liver and fat) from exposure to
sunlight during the spring, summer, and fall
months even in the far north latitudes.
• Long lengthy days,
• Thin, low level, less cloudy atmosphere: > UV
penetration.
35. Sun Exposure
Ultraviolet (UV) B radiation with a wavelength of
290–320 nanometers penetrates uncovered skin
and converts cutaneous 7-dehydrocholesterol to
previtamin D3, which in turn becomes vitamin D3.
Season, time of day, length of day, cloud cover,
smog, skin melanin content, and sunscreen are
among the factors that affect UV radiation
exposure and vitamin D synthesis.
36. Sun Exposure
• Approximately 5–30 minutes of sun exposure
between 10 AM and 3 PM at least twice a
week to the face, arms, legs, or back without
sunscreen lead to sufficient vitamin D
synthesis.
• Minimal Erythrismal Dose.
• White skin synthesis more vit D than
Black/Brown during short time exposure.
37. SkinType General Pigment Sunburn
I Light Pale white or freckled Always
II Fair White Usually
III Medium White to Light Brown Sometimes
IV Olive Moderate Brown Rarely
V Brown Dark Brown Very Rarely
VI Black Very Dark Brown to Never
Black
38. Skin Colour Adaptation
Sub-Saharan African, Indian, Southern European, and Northern European
1,25, (HO)2 vitamin D3 level kept at a constant level regardless of skin colour
39. Sun exposure
• Prolonged exposure of the skin to sunlight
does not produce toxic amounts of vitamin D3
because of photoconversion of previtamin D3
and vitamin D3 to inactive metabolites.
• In addition, sunlight-induces production of
melanin, which reduces production of vitamin
D3 in the skin.
40. People with dark skin
Greater amounts of the pigment melanin in
the epidermal layer result in darker skin and
reduce the skin's ability to produce vitamin D
from sunlight.
It is not clear that lower levels of 25(OH)D for
persons with dark skin have significant health
consequences.
Skin color & Melanin synthesis is protective adaptation.
It can not itself be a cause of deficiency for normal habitat.
41. Dark Skin
• Among young, tanned Hawaiians with 22.4 hours per
week of unprotected sun exposure, 51% were found
to have serum 25(OH)D below 75 nmol/L (30ng/ml).
• A study from south India found levels below 50
nmol/L in 44% of the men and in 70% of the women.
The subjects were "agricultural workers starting their
day at 8am and working outdoors until 5pm with
their face, chest, back, legs, arms, and forearms
exposed to sunlight“ .
42. Extreme Examples
• Eskimo – extreme North – high latitude.
• African(sub Saharan) – at Equater plane - dark skin.
44. VDD in Eskimo
• Vit. D deficiency is common among northern
Native peoples.
• Higher latitudes that prevent vitamin D synthesis
most of the year.
• Darker skin that blocks solar UVB.
• Wear thick cloths.
• Fewer dietary sources of vitamin D.
• Vitamin D levels are clearly lower, it is less clear
that these lower levels indicate a deficiency.
45. VDD in Eskimo - compensation
• There is in fact evidence that the Eskimos have
compensated for decreased production of
vitamin D through increased conversion to its
most active form and through receptors that
bind more effectively.
• The Eskimos have normal serum calcium
despite low serum 25(OH)D and a calcium-
deficient diet.
– Vitamin D deficiency among northern Native Peoples: a real or
apparent problem? (Int J Circumpolar Health 2011; 70(x):xxx-xxx
Peter Frost
46. Adaptations to low vitamin D
• This may be why nearly half of African Americans
are classified as vitamin D deficient and yet few
show signs of calcium deficiency.
• In fact, this population has less osteoporosis,
fewer fractures and a higher bone mineral
density than do Euro-Americans.
• The same apparent contradiction emerges from
a survey of East African immigrant children in
Australia.
• None had rickets despite very low serum
25(OH)D, with 87% of them having less than 50
nmol/L and 44% having less than 25 nmol/L
47. Adaptations: cont….
• Darker-skinned humans seem to cope with low levels of
vitamin D by using this vitamin more efficiently or by
increasing calcium and phosphorus absorption via
other means. Thus, a single UVB exposure produces
less vitamin D3 in black subjects than in whites.
• The difference narrows, however, after liver
hydroxylation to 25(OH)D, and
• disappears after kidney hydroxylation to 1,25(OH)2D.
The most active form of vitamin D is thereby kept at a
constant level regardless of skin colour.
48. Adaptations: cont….
• To summarise, there are many possible
reasons why some human populations
have managed to survive and even
thrive despite apparently deficient
levels of vitamin D.
49. This vitamin may be less necessary!
– because stores of calcium and phosphorus are
used more efficiently,
– because these elements are absorbed from the
gut via alternate metabolic pathways,
– because vitamin D is transported more efficiently
through the bloodstream and into target tissues,
– because the vitamin D receptor binds more
strongly to this molecule, or
– because 25(OH)D is converted to 1,25(OH)2D at a
higher rate.
50. Example of Physiological adaptations
• During pregnancy:
– Increase calcium absorption from early days.
– Hypercalciurea,
– Real risk of Renal stone, if supplemented,
– Calcium transportation occurs in 3rd trimester.
– Total 1,25,(HO)2 D3 doubles up.
– DBP increases in plasma.
– No change in BMD
51. Example of Physiological adaptations
During lactation: Total calcium in the milk comes
from mother’s skeleton.
Mother’s BMD goes down – but recovers fully after
cessation of lactation later on.
Mother is ready for next pregnancy.
An adolescent (pregnancy + lactation) mother have
better BMD than a nulliparous woman.
52. Physiological adaptations
• People living in Northern Europe have better
vitamin D level than their counter part living in
southern Europe (Who are more close to
equatorial plane).
• The response to sun exposure is very quick in
white population than in black as an
adaptation.
53. Example of Physiological adaptations
• African Americans living in deferent
geographical location are Vitamin D deficient.
• They have High BMD
• They are resistant to Osteoporosis and
Fragility fractures.
55. African Sub- Saharan
• Increased pigmentation reducing vitamin D
production in the skin.
• Mean 25(OH)D levels are lower.
• Blacks have higher PTH levels and a high prevalence
of secondary hyperparathyroidism.
• Higher average levels of 1,25(OH)2D and lower
urinary calcium excretion but not higher
biochemical indices of bone turnover.
• The fracture risk is lower and BMD is high.
56. African Sub- Saharan
• Biochemical indices of bone formation osteocalcin
levels are lower.
• The black skeleton is resistant to the bone-resorbing
effects of PTH, whereas renal sensitivity to PTH is
maintained or perhaps even enhanced.
• Vitamin D supplementation studies in black women
have shown inconsistent benefits to BMD.
• Skeletal and renal adaptations to vitamin D deficiency
in blacks might be so effective that vitamin D
supplementation might not confer any further benefit
to the black skeleton.
57. What is the truth?
Where Do we stand?
• We are deficient as per IOM recommendation.
• These recommendations are for USA &
Canada as their main source of Vit D is diet.
• They are not applicable to us.
• We don’t need high calcium & Vitamin D.
• The association of D3+Calcium with other
diseases are still under observational stage.
• We have less incidence of Osteoporosis.
We have better adaptability to so called low levels of D
58. Recommendations
• Our diagnosis of deficiency state should be
clinical.
• H/o cramps, Proximal muscle myopathy +
Deep bone tenderness.
• If possible Lab assistance, serum calcium,
alkaline phosphatase, serum phosphate,
urinary excretion of calcium & phosphates,
25(HO)D3, & PTH.
• Taking > Vit D + Calcium may be toxic.
59. Goswami R et al, AIIMS – New Delhi
• 28 Indians with low serum 25(OH)D (mean
13.5 nmol/l) on screening during January-
March 2005. Serum parathyroid hormone
(PTH) level was supranormal in 30 % of them.
• Oral supplementation with 60,000 IU
cholecalciferol per week + 1g elemental Ca
daily for 8 weeks.
60. Goswami R et al, AIIMS – New Delhi
• At 8 weeks the mean 25(OH)D levels increased
to 82.4 nmol/l and serum PTH normalized in
all. Twenty-two of the twenty-three subjects
had 25(OH)D levels >49.9 nmol/l.
• At 1 year, the mean 25(OH)D level drop to
24.7 nmol/l & all subjects were 25(OH)D
deficient. Five subjects with supranormal iPTH
at baseline showed recurrence of biochemical
hyperparathyroidism.
Supplementations have temporary effect
61. Goswami R et al, AIIMS – New Delhi
• After initial supplementation Vit. D level return to
baseline with in one year.
• For sustained improvement in 25(OH)D levels
supplementation has to be ongoing after the initial
cholecalciferol loading.
Pattern of 25-hydroxy vitamin D response at
short (2 month) and long (1 year) interval after
8 weeks of oral supplementation with
cholecalciferol in Asian Indians with chronic
hypovitaminosis D.
Br J Nutr. 2008 Sep;100(3):526-9. Epub 2008 Feb 6.
Do we need extra calcium/ vitamin D?
62. Recommendations:
NICE,NOGG,CKS, NHS
• Due to a lack of supporting evidence, vitamin
D supplementation for active people younger
than 65 years of age is not recommend.
• People older than 65 years of age and those at
risk of vitamin D deficiency should aim for a
daily vitamin D intake of 10 - 20 micrograms
(400 -800 units).
63. Recommendations:
NICE,NOGG,CKS, NHS
• Evidence suggests that vitamin D alone is not
effective in reducing fractures in older people
(when compared with placebo),
• It can reduce the risk of falls in people 60 years of
age and older living in institutionalized care or in
the community.
• For elderly people who are housebound or living
in a nursing home, a higher dose of 20
micrograms (800 units), along with a daily dose of
1.0 g to 1.2 g calcium, is recommended to reduce
the risk of fractures.
64. Suggestions
• Supplementation of Vitamin D & Calcium
should be considered on clinical suspicion.
• Aches & pain, cramps, night restless legs,
frequent muscle pulls, knee pain.
• Clinically deep bone tenderness – shin tender.
• Proximal muscle weakness.
• Low serum calcium + high Alk PO4, low Vit. D,
high PTH + Urinary excretion of Ca + P.
65. Bottom line:-
• We must treat all deficiency status.
• Requirement of regular supplementation in
apparently healthy individuals with Calcium
and or Vitamin D at present does not appears
logical for Indians.
66. DISCLAIMER
• Information contained and transmitted by this presentation is
based on review of literature from internet and form Institute
of Medicine summary on DRI for Vitamin D & Calcium.
• It is intended for use only by the students of orthopaedic
surgery.
• Many Gif/Jpeg files are taken from Internet/Textbooks.
• Views and opinion expressed in this presentation are personal.
• For any confusion please contact the sole author for
clarification.
• Every body is allowed to copy or download and use the
material best suited to him.
• There is No financial involvement in preparation of this PPT.
• For any correction or suggestion please contact
naneria@yahoo.com
Editor's Notes
Michal L. Melamed, Juhi Kumar, Paul Muntner, Frederick J. Kaskel, and Susan M. Hailpern. Prevalence and Associations of 25-Hydroxyvitamin D Deficiency in Children and Adolescents in the United States: Results from NHANES 2001-2004. Pediatrics, August 3, 2009
1. J Bone Miner Res. 2007 Dec;22 Suppl 2:V34-8. Vitamin D economy in blacks. Cosman F, Nieves J, Dempster D, Lindsay R. Regional Bone Center and Clinical Research Centers, Helen Hayes Hospital, WestHaverstraw, New York, USA.