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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

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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


Indications & Dosage (CP/GP)

• Low back pain• Joint pain• Osteomalacia• Perimenopausal osteoporosis


Indications & Dosage (Gynec)

• Low back pain• Joint pain• Osteomalacia• Perimenopausal osteoporosis


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.

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Vitamin D 60,000IU once in a w eek

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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


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%

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7.00%

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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


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


MCQsQ. 4 Twin epidemic in infants causes

(a) Low birth Weight

(b) Congenital rickets

(c)Recurrent infections


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


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

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