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Vitamin D
Curr Opin Endocrinol Diabetes Obes. 2008;15:489–494.
What is Vitamin D?
Fat-soluble vitamin and serves as a hormone in the body.1
The only vitamin human body makes itself.Vitamin D is naturally present in few selective foods, such as oily fish & in very low amount in cow's milk.
Types of Vitamin D
Vitamin D3 (Cholecalciferol)Produced in skin with direct sunlightPreferred form of supplementation
Vitamin D2 (Ergocalciferol)Found in plantsMade by UVB radiation of ergosterol
Vitamin D Metabolism
(Animals, Supplements)(Plants)
(Calcitriol: Active form of Vit D)
J Am Coll Cardiol. 2008;52:1949–1956.Osteoporos Int. 2010 Jul;21(7):1151-4.
Vitamin D Status
Vitamin D insufficiency, 25(OH)D levels <30ng/ml is prevalent, worldwide, especially in Middle East and South Asia.2
Vitamin D Deficiency is Common Even in Sunny India
More than 80 % of adult Indians not getting Enough Vitamin D
INDIA
Latitude of 22 ° 00' N
Longitude of 77 ° 00‘ W
1. Am J Clin Nutr. 2000;72: 472-75 2. Data on file
25(OH) D status of Normal Indians
All Indians suffer from Vitamin D Deficiency
SoldiersDepigmented subjects
Physicians & NursesPregnant women
Newborns Sales Team
Office staffDoctors
0
5
10
15
20
25
30
Vita
min
D L
evel
s (ng
/ml)
Signs and symptoms of Vitamin D deficiency
Musculoskeletal disorders
– Low back pain, joint pain
Fatigue and Muscular Weakness
• Increased susceptibility to infections
It thus adversely effects Quality of Life
ImmediateQuality of Life
FutureQuality of Life
Vitamin D Deficiency Affects Quality of Life
-Muscle pain and weakness
- Osteomalacia (Adults)
- Rickets (Children)
- Osteoporosis & Fractures
Other Chronic Disorders
– Diabetes
– Recurrent infections
– Hypertension
– Heart Disease
Reasonable Daily Allowance (IU/Day) Reasonable Allowance (IU/month)
0-6 months 400-1000 12000-30000
6-12 months 400-1000 12000-30000
Children (1-18 Yr) 1000-2000 30,000-60,0000
Adults (19-50 Yr) 1500-2000 45,000-60,000
Elderly (51-70 Yr) 1500-2000 45,000-60,000
Elderly (> 71 Yr) 1500-2000 45,000-60,000
Pregnancy 1500-2000 45,000-60,000
Lactation 1500-2000 45,000-60,000
Recommended Vitamin D Intake by Endo. Society Guidelines, 2011
Vitamin D by Michael H. Holick, II Ed. 2010.
MCQs
Q. 1 What is Vitamin D?
(a) Fat Soluble vitamin (b) Hormone necessary for the body(c) Water Soluble vitamin(d) Both (a) & (b)
MCQs
Q. 2 Conversion of Vitamin D3 to 25(OH) vitamin D3 takes place in the
(a) Liver(b) Heart(c) Kidney(d) All of the above
MCQs
Q. 3 The active form of Vitamin D is
(a) Cholecalciferol(b) 25(OH) vitamin D3(c) Ergocalciferol(d) Calcitriol
MCQs
Q. 4 What is the optimum level of Vitamin D in the body?
(a) 10 ng/ml(b) 20 ng/ml(c) > 30 ng/ml(d) None of the above
MCQs
Q. 5 What is vitamin D Deficiency
(a) High level of Vitamin D in the Body(b) Low level of Vitamin D in the Body(c) Optimum level of Vitamin D in the Body(d) None of the above
MCQs
Q. 6 How many Indians have Vitamin D Deficiency?
(a) 20%(b) 30%(c)50%(d) More than 80%
Major action of Vitamin D on Various Organs
Organ Actions
Bone
Promotes osteoblastic activity (improves bone mineralization)Regulates osteoclastic activity. (reduces bone resorption)
Parathyroid glands Inhibits parathyroid hormone secretion (Improves bone mineralization)
Kidneys Enhances Ca reabsorption
Intestine Enhances Ca and phosphate transport (absorption)
Muscles Strengthens muscles (Increases De Novo Protein Synthesis)Boosts immunity Decreases risk of recurrent infections.
Immune system
Osteoblast & Osteoclast
Osteoblasts• Cells responsible for
synthesis & mineralization of bone. Form bones
Osteoclasts• Cells responsible for
dissolution of bone. Cause bone resorption.
Vitamin D deficiency Syndrome
Osteomalacia
Muscle Weakness
Hypertension
Chronic pain & fatigue
Musculoskeletal disorders
Osteomalacia Osteoporosis
Physiology Abnormal bone building Degeneration of built bone
Occurrence Adults Elderly
Symptoms Muscle WeaknessBone Weakness & Pain
Frequent fracturesLoss on height (due to compression of spine
Complications Bone softeningBone bending Results in bone fragility & fractures
Prognosis Can be prevented by Ca & Vitamin D supplements Cannot be prevented. Can only be treated
Outcome Osteoporosis Fractures
Osteomalacia Vs. Osteoporosis
Osteomalacia • Softening of bones due to insufficient vitamin D, or problems
with metabolism of this vitamin.
• Osteomalacia in children is known as Rickets
• Signs & Symptoms– Bone Weakness– Bone Pain– Muscle Weakness
Rickets
Prevalence of Vitamin D Induced Osteomalcia & Rickets in India
• Osteomalacia & Rickets are the most common disorders due to Vitamin D Deficiency in India
• Osteomalacia present in 35.3% adults with Vitamin D deficiency1
• Rickets present in 30.3 % Indian infants with 25(OH)D <10ng/ml.2
1. Indian J Med Res. 2008;127:219-228. 2. Indian J Med Res. 2011;133:267-273
Osteoporosis• Weakening of Bones• In osteoporosis, bones become weak, fragile and brittle due to
loss of minerals like calcium • They get fractured more easily than normal bone.• 1 out of 8 males & 1 out of 3 females in India suffer from
Osteoporosis
OsteoporosisNormal BoneOsteoporosis Society of India New Delhi
OsteoporosisOsteomalacia
93 % of all patients With Musculoskeletal
Disorders, suffering from persistence pain,
were Vit D deficient
Low back pain83% patients < 22.5ng/ml
Osteoarthritis knee48% patients < 30 ng/ml
Spondolysis
Joint Pain94% patients with vit D <15 ng/ml
Muscle Weakness94% patients with Vit D < 15ng/ml
Vitamin D deficiency also affects Musculoskeletal health…
Over 90% of Fractures occur after fall and fall rate increases due to poor muscle strength and function.1
Adequate dose of Vitamin D found to be useful in reduction of persistent non specific pain & Fractures
Ca & Vitamin D Deficiency Causes Fractures
Osteoporosis
Increases risk & Rate of Fall
Increases risk of FractureMuscle Weakness
Osteomalacia
Medicographia. 2010;32(4):384-390
Vitamin D Status and Hip Fracture
Stroke 2001;32:1673-7
Vitamin D Deficiency : Summary
↓ Calcium in the serum
↑ PTH
Osteoblastic activityOsteoclastic activity
↑ calcium efflux from bone
OSTEOPOROSIS
Vitamin D deficiency
↑ Risk of Fracture
Muscle weakness
↑ Risk of falls
Osteomalacia
Vitamin D supplementation in vitamin D deficient Indians
↑ Calcium in the serum
↓ PTH
Osteoblastic activityOsteoclastic activity
↓ calcium efflux from bone
OSTEOPOROSIS
↑ Vitamin D
↓ Risk of Fracture
Muscle Strengthens
↓ Risk of falls
Osteomalacia
MCQs
Q. 1Vitamin D has the following actions on the body
(a) Increases bone mineralization(b) Inhibits PTH secretion(c) Increase calcium absorption from intestine(d) All of the above
MCQs
Q. 2 What are Osteoblasts?
(a) Cells which help bone formation(b) Cells which help bone resorption(c)Both (a) &(b)(d) None of the above
MCQs
Q. 3 Vitamin D Deficiency is associated with
(a) Osteomalacia(b) Musculoskeletal Disorders(c) Osteoporosis & Fractures(d) All of the above
MCQs
Q. 4 What is Osteomalacia?
(a) Softening of bones due to Vitamin D Deficiency
(b) Breaking of bones(c) Indigestion(d) None of the above
MCQs
Q. 5 Rickets occur commonly in
(a) Pregnant Women(b) Children (c) Adults (d) All of the above
MCQs
Q. 6 What is Osteoporosis?
(a) Disease caused due to iron deficiency(b) Disease caused by bacterial infection(c) Disease in which bones become fragile
resulting in fractures(d) None of the above
MCQs Q. 7 Choose the correct statement
(a) Vitamin D Deficiency also affects Musculoskeletal health
(b) Ca & Vitamin D Deficiency can cause fractures
(c) Vitamin D supplements can cause fractures
(d) Both (a) & (b)
How Much Vitamin D Supplement?
100 I.U./day of Vitamin D(3) increases circulating 25(OH)D by 1 ng/ml when taken for 2 months
If the typical serum 25 (OH)D level in Indians is 10 ng/ml…
And if the target serum 25 (OH)D level is 30 ng/ml…
Patients would require about 2000 IU/Day or 60000 IU per month
50-60% fractures can be reduced at ~30 ng/ml serum Vitamin D.1
1. Alt Med Rev. 2008;13(1):21-33
Dosage Regimen
Vitamin D deficient ( < 10 ng /ml) population:• Prevention of Osteoporosis:
• 60,000 IU (1gm Sachet /Month)
In Osteomalacia, treatment of osteoporosis– 60,000 IU (1 gm sachet )/week* 8 weeks– Followed by 60,000 IU (1 gm Sachet ) /month
Safety of Vitamin D intake
The safe upper limit for vitamin D intake for the general adult population was set at 2,000 IU per day in 1997
Recent evidence indicates that higher intakes are safe and that some elderly patients will need at least this amount to maintain optimal Vitamin D levels.
No toxicity reported with :Intake of 10000 IU/Day for 5 months
Indications & Dosage (Orthopedics)
• Osteomalacia • Muscloskeletal disorders• Osteoporosis • Fracture
Dosage:1 sachet/week for 8-12 weeks, followed by 1 sachet every month
Vitamin D status has been shown to be an independent predictor of functional recovery after hip fracture
Vitamin D accelerates initial fracture callus mineralization
Vitamin D stimulates transformation of fracture site stem cells to bone building osteoblast
Vitamin D Supplementation Helps Fracture Healing
Brown S; Better Bones.
Fall prevention with supplemental and active forms ofvitamin D: a meta-analysis of randomised controlled trials
Supplemental vitamin D in a dose of 700- 1000 IU a day reduced the risk of falling among older individuals by 19%
BMJ 2009;339:b3692
Vitamin D: Clinical Fracture Risk• N=2686: Men and women 65-85• Mean age: 74.7• Placebo or vitamin D 100,000 IU PO every 4 months• Fractures: Hip, wrist, spine and forearm• Treatment interval: 5 years
Trivedi D, et al. BMJ. 2003;326:469-474
Vitamin D supplementation Reduces Risk of Falls
• N =122• Ages: 63–99• Randomized, double-blind,controlled trial• 12-week duration
Bischoff HA, et al. J Bone Miner Res. 2003;18:343–351
Ca 1200 mg/dCa 1200 mg/d
+Vitamin D 800IU/d
Indication & Dosage (Pediatric)
• Rickets
Dosage:1 sachet/week for 8-12 weeks, followed by 1 sachet every month
Indications & Dosage (CP/GP)
• Low back pain• Joint pain• Osteomalacia• Perimenopausal osteoporosis
Dosage:1 sachet/week for 8-12 weeks, followed by 1 sachet every month
Indications & Dosage (Gynec)
• Low back pain• Joint pain• Osteomalacia• Perimenopausal osteoporosis
Dosage:1 sachet/week for 8-12 weeks, followed by 1 sachet every month
Most currently available supplements contain Calcium (500 mg)+ Vitamin D (500-800IU)
But in Indians .......High prevalence of Vitamin Deficiency (25 (OH)D ~10 ng/ml)
What about currently available Vitamin D ?Do they provide adequate Vitamin D ?
To achieve Sufficiency (target 25 (OH)D level = 30 ng/ml)…
Patients would require 2000 IU/Day (60,000 IU/month)
Existing products would increase vitamin D by only 5-8 ng/ml
Toxicity symptoms of Vitamin D
Vitamin D at very high doses (> 40,000 IU/day) may cause
• Pain due to kidney stone (Hypercalcemia)• Dehydration• Increased thirst• Vomiting • Constipation
Vitamin D by Michael H. Holick, II Ed. 2010.
0
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76.2
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20
40
60
80
100
Vitamin D 400IU/day
Vitamin D 600,000IU Injectable
Vitamin D 60,000IU once in a w eek
% P
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Des
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Vit D
Le
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Oral Vitamin D 60,000 IU ensures adequate rise in plasma vitamin D levels.Higher absorption of Vitamin D in plasma with oral supplement as compared to injectable Vitamin D1
Safety data: Oil-based IM injection, hence painful. Chances of hypercalcemia & hypercalciuria with injectable Vit D. 2
No reported adverse reactions with oral Vitamin D at the given dose.
Vitamin D Supplement: Oral Vs Injection
1. Endocrine Abstracts. 2011;26:P540 2. Med J Aus. 2005;183(1):10-12
Summary • High prevalence of vitamin D deficiency in India is a major
contributor to • Muscle weakness, musculoskeletal disorders • Recurrent infections • Osteomalacia• Osteoporosis • Rickets
• Vitamin D deficiency early in life predisposes to not only bone related disorders but also other chronic disorders
• Vitamin D supplementation with 60000 IU/month increases levels 25(OH)D by 20 ng/ml.
• Dose upto 10000 IU/day is safe to be used.
MCQs Q.6 What are the advantages of Vitamin D
oral supplement Vs. injection?(a) Higher absorption of Vitamin D with oral
supplement(b) Better safety profile with oral supplement(c) Both (a) & (b)(d) None of the above
Questions ?
• Lack of RBC Production
• Formation of immature RBCs
• Formation of more numbers of inactive RBCs
It thus leads to Iron Deficiency Anemia (IDA).
Vitamin D Deficiency Causes.....
Ann Hematol. 2010;89:447-452
Vitamin D Deficiency
Reduced uptake of iron in RBC
RBCs Malformation(Inactive & Immature RBCs)
Iron Deficiency Anemia
Vitamin D Malabsorption
1. Am J Clin Nutr. 1992;56(3):533-6 2. Plos One2010;5(1):e8770
Reduced absorption of fats in intestine
No wonder,
Iron deficiency is also epidemic in Indians
Leading to Twin Epidemic (Vit D & IDA)
- Affects Quality Of Life
TWIN EPIDEMIC AFFECTS Quality Of Life
ImmediateAnemia
Low back pain
Joint pain
General weakness
Fatigue
FutureOsteoporosis
Diabetes
CV diseases
All Indians with anemia require Vitamin D added to iron
To Tackle the Twin Epidemic
MCQs
Q.1 Vitamin D Deficiency can cause
(a) Reduced RBC production
(b) Formation of Inactive and Immature RBCs
(c) Both (a) & (b)
(d) None of the above
MCQs
Q.2 Iron Deficiency Anemia can lead to
(a) Reduced absorption of fats from intestine
(b) Reduced absorption of glucose from intestine
(c) Increased absorption of fats from intestine
(d) None of the above
MCQs Q. 3 Vitamin D deficiency can cause IDA.
IDA in turn lead to Vitamin D Deficiency.
(a) Only 1st statement is true
(b) Only 2nd statement is true
(c) None of the statements are true
(d) Both statements are true
MCQs
Q. 4 What is the Twin Epidemic?
(a) Vitamin B + Iron Deficiency
(b) Vitamin D + Iron Deficiency
(c) Vitamin C + Iron Deficiency
(d) Calcium + Iron Deficiency
MCQs
Q. 5 Twin Epidemic can cause
(a) Joint pain and weakness
(b) Fatigue
(c) Osteoporosis
(d) All of the above
MCQs
Q. 5 Twin Epidemic can be tackled by
(a) Vitamin D supplements alone(b) Vitamin D + iron supplements(c)Vitamin C supplements(d) None of the above
WHAT about twin epidemic in pregnancy & lactation ?
•84% of Indian Pregnant Women suffer from Iron Deficiency Anemia (IDA)1.
≈84% Indian women have 25(OH)D values < 22.5 ng/L.2
Infants are also deficient of vit D
Parameter Mothers3 Infants 3
Vitamin D Deficiency (< 15 ng/ml) 81.1% 66.7%
Vitmin D insufficiency (15-20 ng/ml 11.6% 19.8%
Severe Vitamin D Deficiency (<5 ng/ml) 23.2% 27.1%
1. Indian J Med Res. 2006;124:173-184 2. Am J Clin Nutr. 2005;81:1060-10643. Indian J Med Res. 2011;133:267-273.
Pregnant women with low serum 25(OH)D levels had 46% higher risk of developing anemia.1
> 50% infants with Iron Deficiency Anemia had low 25(OH)D levels.2
Twin Epidemic in Pregnant & Lactating Women
The Twin Epidemic in Pregnant & Lactating Women also affects their infants.
1. Plos One2010;5(1):e8770 2. Am J Clin Nutr. 1992;56:533-536
Twin Epidemic (Vit D & IDA) in Indian Women
- Affects present generations- Exhibits far reaching Impact on the future Generations
Impact of Twin Epidemic (Vit D & Iron Deficiency)
on the health of Pregnant women
Gestational Diabetes Pre-term birthPresence of diabetes during More than 2 fold increase in pregnancy risk of preterm birth
Preeclampsia Maternal MortalityDevelopment of hypertension in Pregancy (PIH) along with excretion Anemia (Even in Lactating of protein in urine (proteinuria). Mothers)
Prevalence of Osteomalacia Results in low back pain during pregnancy and post delivery
1. Am J Obstet Gynecol 2010;202:429.e1-9.
Impact of Twin Epidemic (Vit D & Iron Deficiency) in infants
- Congenital rickets- Low birth weight- Poor postnatal growth- Neonatal Hypocalcemia- Compromised Immunity : recurrent infections- Perinatal Mortality- Impaired brain development
Vit D & Iron Deficient Mother Vit D & Iron Deficient Child
Chronic complications in the Future
• Higher risk of fractures
• Osteoporosis
• Diabetes
Impact of Twin Epidemic in Future
To Combat the Twin Epidemic
Need of the Hour
To provide Iron and Vitamin D to all Pregnant & Lactating women
This twin epidemic (Vit.D & Iron Deficiency) affects
Mother…Child…and Future Generations….
How Much Vitamin D in Pregnancy & Lactation ?
1000 IU/day is necessary to achieve 25(OH)D levels more than 20 ng/ml in pregnant women.1, 2
Safety upper limit in Pregnancy & Lactation: 10,000 IU/day3
1. Indian J Med Res. 2011;133:250-252 2. Clinical protocols & guidelines, 20093. Vitamin D by Michael H. Holick, II Ed. 2010.
Adequate Vit D supplementation in Pregnant Women Helps to Reduce Risk of
Preeclampsia
No supplements > 800 IU/day0.00%
1.00%
2.00%
3.00%
4.00%
5.00%
6.00%
7.00%
% P
reec
lam
psia
Epidemiology. 2009;20(5):720-726
27% reduction in risk of preeclampsia compared with no supplements.
Adequate Vit D supplementation in Lactating Mothers improves status in infants
25(OH)D levels (ng/ml) in infants
J Am Coll Nutr. 2008;27(6):690-701
Iron Supplementation for Anemia Ideal dosage – 100mg/day (Prophylactic dose for IDA) in
pregnant & lactating women1
Iron Supplements are present as different salts:
– Ferrous ascorbate– Ferrous gluconate
– Ferrous fumarate
– Ferrous succinate
Most commonly used Iron Salt – Ferrous Ascorbate1. Govt. of India Guidelines for Pregnancy Care, 2005
Ferrous Ascorbate
Elemental Iron Salt of Ascorbic acid
• Fulfills Iron requirement of the body
• Vitamin C • Anti oxidant
• Enhances absorption of elemental iron from intestine
What is Ferrous Ascorbate ?
• Ascorbic acid enhances absorption of iron.1
• Forms soluble complex with iron in GI Tract. Hence, no
action of food inhibitors as the complex does not dissociate.1
• Maximum bioavailability (40%) unlike other iron salts.2
• In-built vitamin C (Antioxidant)
– Maintains iron in highly soluble ferrous form.1
– Prevents formation of free radicals. Less chances of side effects.3
1. J Nutr.2003;133:2978S-2984. 2. Eur J.Clin Nutr.2004;58:555-5583. Biochem J. 2006;399:513-524
Why Ferrous Ascorbate ?
• 100mg elemental Iron in Ferrous ascorbate ensures highest Hb rise (2.5-3.0%gm within 30 days)
• Clinical Data recommendations: 1000 IU/day Vitamin D is necessary to achieve 25(OH)D levels more than 20 ng/ml in pregnant women.1, 2
Vitamin D + Iron Supplement Twin Benefit in Pregnancy & Lactation
1. Indian J Med Res. 2011;133:250-252 2. Clinical protocols & guidelines, 2009
• 100 mg elemental iron provides synergistic effect with 1000 iu of vitamin D.
Role of Folic Acid & Vitamin B12 in Pregnancy & Lactation
1. Neural Tube Defects: Most common birth defects resulting in mental retardation & mortality in children. Occurs due to abnormal development of CNS in fetus.
2. Intrauterine Growth Retardation (IUGR): Poor growth of a baby while in the mother's womb during pregnancy.
3. Anemia
Dimorphic & protein deficiency: Deficiency of iron, folic acid and/or Vit B12
Macrocytic: Due to deficiency of folic acid and/or Vit B124. Gestational Diabetes
5. Preeclampsia
Folic Acid and Vitamin B12 Deficiency: Complications
How Much Folate & Vitamin B12 required in Pregnacy & Lactation ?
• RDA for folic acid supplements in Pregnancy is 400-800 mcg/day.1
• 500 mcg/day (prophylactic dose for Anemia) in pregnant women.2
• 1 mg/day folic acid for 3 months (treatment for Anemia) in pregnant women.2
RDA for Vitamin B12 supplements in Pregnancy is 2.6 mcg/day & Lactation is 2.8 mcg/day. 3
1. CDC recommendation2. Govt. of India Guidelines for Pregnancy Care, 20053. WHO recommendation
MCQs
Q. 1 Twin Epidemic in Pregnant Women can cause
(a) Gestational Diabetes
(b) Preeclampsia
(c) Pre-term birth
(d) All of the above
MCQs
Q. 2 What is Gestational Diabetes?
(a) Diabetes in Children
(b) Diabetes in Men
(c) Diabetes in Pregnant Women
(d) Diabetes in Elderly patients
MCQs
Q. 3 What is Preeclampsia?
(a) Development of Hypertension in Pregnancy
(b) Diabetes in Pregnancy
(c) Anemia in Pregnancy
(d) None of the above
MCQsQ. 4 Twin epidemic in infants causes
(a) Low birth Weight
(b) Congenital rickets
(c)Recurrent infections
(d) All of the above
MCQs Q. 5 Ideal dose of iron in Pregnancy &
Lactation is
(a) 50 mg
(b) 100 mg
(c) 500 mg
(d) 1000 mg
MCQs Q. 6 The iron salt with maximum
bioavailability is
(a) Ferrous sulphate
(b) Ferrous gluconate
(c) Ferrous ascorbate
(d) Ferrous fumarate
MCQs Q. 7 What are the advantages of Ferrous
Ascorbate?
(a) Ascorbate enhances the absorption of iron from GI tract
(b) It ensures highest hemoglobin rise
(c) It has least chances of side effects as compared to other salts
(d) All of the above
MCQs
Q. 8 How much Folic Acid is present in MASHYNE Tablets
(a) 0.5 mg
(b) 1 mg
(c) 2 mg
(d) 5 mg