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Vitamin D

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.

Curr Opin Endocrinol Diabetes Obes. 2008;15:489494.

Types of Vitamin D
Vitamin D3 (Cholecalciferol) Produced in skin with direct sunlight Preferred form of supplementation Vitamin D2 (Ergocalciferol) Found in plants Made by UVB radiation of ergosterol

Vitamin D Metabolism

(Animals, Supplements) (Plants)

(Calcitriol: Active form of Vit D)

Vitamin D Status

Vitamin D insufficiency, 25(OH)D levels <30ng/ml is prevalent, worldwide, especially in Middle East and South Asia.2

J Am Coll Cardiol. 2008;52:19491956. Osteoporos Int. 2010 Jul;21(7):1151-4.

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

25(OH) D status of Normal Indians


30 25 20 15

Vitamin D Levels (ng/ml)

10
5 0 Depigmented subjects Pregnant women Sales Team Soldiers Physicians & Nurses Newborns Office staff Doctors

All Indians suffer from Vitamin D Deficiency


1. Am J Clin Nutr. 2000;72: 472-75 2. Data on file

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

Vitamin D Deficiency Affects Quality of Life


Immediate Quality of Life Future Quality of Life

-Muscle pain and weakness


- Osteomalacia (Adults)

- Osteoporosis & Fractures


Other Chronic Disorders

Diabetes - Rickets (Children)


Recurrent infections Hypertension Heart Disease

Recommended Vitamin D Intake by Endo. Society Guidelines, 2011


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

Vitamin D by Michael H. Holick, II Ed. 2010.

MCQs
Q. 1 What is Vitamin D? (a) (b) (c) (d) Fat Soluble vitamin Hormone necessary for the body Water Soluble vitamin Both (a) & (b)

MCQs
Q. 2 Conversion of Vitamin D3 to 25(OH) vitamin D3 takes place in the (a) (b) (c) (d) Liver Heart Kidney All of the above

MCQs
Q. 3 The active form of Vitamin D is (a) (b) (c) (d) Cholecalciferol 25(OH) vitamin D3 Ergocalciferol Calcitriol

MCQs
Q. 4 What is the optimum level of Vitamin D in the body? (a) (b) (c) (d) 10 ng/ml 20 ng/ml > 30 ng/ml None of the above

MCQs
Q. 5 What is vitamin D Deficiency (a) (b) (c) (d) High level of Vitamin D in the Body Low level of Vitamin D in the Body Optimum level of Vitamin D in the Body 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
Bone

Actions
Promotes osteoblastic activity (improves bone mineralization) Regulates osteoclastic activity. (reduces bone resorption) Inhibits parathyroid hormone secretion (Improves bone mineralization) Enhances Ca reabsorption Enhances Ca and phosphate transport (absorption) Strengthens muscles (Increases De Novo Protein Synthesis) Boosts immunity Decreases risk of recurrent infections.

Parathyroid glands Kidneys Intestine Muscles 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


Chronic pain & fatigue

Muscle Weakness

Musculoskeletal disorders

Osteomalacia

Hypertension

Osteomalacia Vs. Osteoporosis


Osteomalacia Physiology Abnormal bone building Osteoporosis Degeneration of built bone

Occurrence

Adults

Elderly

Symptoms

Muscle Weakness Bone Weakness & Pain

Frequent fractures Loss on height (due to compression of spine

Complications

Bone softening Bone 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
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

Osteomalacia

Osteoporosis
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

Normal Bone
Osteoporosis Society of India New Delhi

Osteoporosis

Vitamin D deficiency also affects Musculoskeletal health

Muscle Weakness 94% patients with Vit D < 15ng/ml

Joint Pain 94% patients with vit D <15 ng/ml

93 % of all patients With Musculoskeletal Disorders, suffering from persistence pain, were Vit D deficient

Low back pain 83% patients < 22.5ng/ml Osteoarthritis knee 48% patients < 30 ng/ml

Spondolysis

Ca & Vitamin D Deficiency Causes Fractures

Osteomalacia

Osteoporosis

Muscle Weakness

Increases risk & Rate of Fall

Increases risk of Fracture

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
Medicographia. 2010;32(4):384-390

Vitamin D Status and Hip Fracture

Stroke 2001;32:1673-7

Vitamin D Deficiency : Summary


Vitamin D deficiency Muscle weakness Osteomalacia Calcium in the serum

PTH Risk of falls

Osteoblastic activity Osteoclastic activity calcium efflux from bone Risk of Fracture

OSTEOPOROSIS

Vitamin D supplementation in vitamin D deficient Indians


Vitamin D Muscle Strengthens Calcium in the serum

Osteomalacia

PTH
Risk of falls

Osteoblastic activity Osteoclastic activity calcium efflux from bone Risk of Fracture

OSTEOPOROSIS

MCQs
Q. 1Vitamin D has the following actions on the body (a) (b) (c) (d) Increases bone mineralization Inhibits PTH secretion Increase calcium absorption from intestine 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) (b) (c) (d) Osteomalacia Musculoskeletal Disorders Osteoporosis & Fractures 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) (b) (c) (d) Pregnant Women Children Adults 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 Supplementation Helps Fracture Healing


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

Brown S; Better Bones.

Fall prevention with supplemental and active forms of vitamin 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: 6399 Randomized, double-blind, controlled trial 12-week duration

Ca 1200 mg/d

Ca 1200 mg/d + Vitamin D 800IU/d

Bischoff HA, et al. J Bone Miner Res. 2003;18:343351

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

What about currently available Vitamin D ? Do they provide adequate Vitamin D ?


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) 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 58 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.

Vitamin D Supplement: Oral Vs Injection


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.
% Patient Achieved Desired Vit D Levels

100 80 60 40 20 0
Vitamin D 400 IU/day Vitamin D 600,000 Vitamin D 60,000 IU Injectable IU once in a w eek

76.2 57.1

1. Endocrine Abstracts. 2011;26:P540

2. Med J Aus. 2005;183(1):10-12

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.

Summary

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 ?

Vitamin D Deficiency Causes.....

Lack of RBC Production Formation of immature RBCs Formation of more numbers of inactive RBCs

It thus leads to Iron Deficiency Anemia (IDA).

Ann Hematol. 2010;89:447-452

Vitamin D Deficiency

Reduced uptake of iron in RBC

RBCs Malformation
(Inactive & Immature RBCs)

Iron Deficiency Anemia Reduced absorption of fats in intestine Vitamin D Malabsorption


1. Am J Clin Nutr. 1992;56(3):533-6 2. Plos One2010;5(1):e8770

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


Immediate
Anemia

Future
Osteoporosis

Low back pain


Joint pain General weakness

Diabetes
CV diseases

Fatigue

To Tackle the Twin Epidemic All Indians with anemia require Vitamin D added to iron

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 1 statement is true
st

(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
Parameter Mothers3 Infants 3

Vitamin D Deficiency (< 15 ng/ml)

81.1%

66.7%

Infants are also deficient of vit D


1. Indian J Med Res. 2006;124:173-184 Vitmin J insufficiency (15-20 ng/ml 3. Indian D Med Res. 2011;133:267-273. 2. Am J Clin Nutr. 2005;81:1060-1064
11.6% 19.8%

Twin Epidemic in Pregnant & Lactating Women


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

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
Presence of diabetes during pregnancy

Pre-term birth
More than 2 fold increase in risk of preterm birth

Preeclampsia
Development of hypertension in Pregancy (PIH) along with excretion of protein in urine (proteinuria).

Maternal Mortality
Anemia (Even in Lactating 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

Impact of Twin Epidemic in Future

Vit D & Iron Deficient Mother

Vit D & Iron Deficient Child

Chronic complications in the Future


Higher risk of fractures Osteoporosis Diabetes

This twin epidemic (Vit.D & Iron Deficiency) affects MotherChildand Future Generations.

To Combat the Twin Epidemic

Need of the Hour


To provide Iron and Vitamin D to all Pregnant & Lactating women

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 3. Vitamin D by Michael H. Holick, II Ed. 2010.

2. Clinical protocols & guidelines, 2009

Adequate Vit D supplementation in Pregnant Women Helps to Reduce Risk of Preeclampsia

27% reduction in risk of preeclampsia compared with no supplements.

Epidemiology. 2009;20(5):720-726

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 Ascorbate


1. Govt. of India Guidelines for Pregnancy Care, 2005

What is Ferrous Ascorbate ?


Ferrous Ascorbate

Elemental Iron
Fulfills Iron requirement of the body

Salt of Ascorbic acid


Vitamin C Anti oxidant Enhances absorption of elemental iron from intestine

Why 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 100mg elemental Iron in Ferrous ascorbate ensures highest Hb rise (2.5-3.0%gm within 30 days)
1. J Nutr.2003;133:2978S-2984. 3. Biochem J. 2006;399:513-524 2. Eur J.Clin Nutr.2004;58:555-558

Vitamin D + Iron Supplement Twin Benefit in Pregnancy & Lactation


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

100 mg elemental iron provides synergistic effect with 1000 iu of vitamin D.

1. Indian J Med Res. 2011;133:250-252

2. Clinical protocols & guidelines, 2009

Role of Folic Acid & Vitamin B12 in Pregnancy & Lactation

Folic Acid and Vitamin B12 Deficiency: Complications


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 B12 4. Gestational Diabetes 5. Preeclampsia

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 recommendation 2. Govt. of India Guidelines for Pregnancy Care, 2005 3. 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

MCQs
Q. 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

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

MCQs

(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