Role of Calcium Supplementation and

Vitamin D3 in Pregnancy

Dr Sujoy DasguptaMBBS (Gold Medalist, Hons) MS (Obst & Gynae- Gold Medalist)

DNB, FIAOG

Consultant: RSV Hospital, KolkataIris Hospital, KolkataBehala Balananda Brahmachary Hospital, Kolkata

Secretary, Website and Bulletin Committee: Bengal Obstetric and Gynaecological Society (BOGS)- 2017-18Managing Committee Member: BOGS- 2017-18

15 Publications: National and International Journals

Best Obligate Parasite

Calcium demand for the baby

• A growing fetus needs 30 gram of calcium in total(80% in 3rd trimester)

• A suckling neonate requires even more calcium

• If not met→ draws maternal calcium→ makes maternal bone and teeth vulnerable

Calcium demand for the woman

• Each day 200-300 mg of Ca is transferred through the placenta or breast milk

• Increased demand for maternal altered physiology

Mother will try to compensate for this by

• Increasing intestinal absorption

• Decreasing renal excretion

• Increasing bone turnover

Recommended daily Allowance

Non pregnant 800 mg/d

Recommended daily Allowance

Non pregnant 800 mg/d

Pregnant 1100 mg/d

Recommended daily Allowance

Non pregnant 800 mg/d

Pregnant 1100 mg/d

Lactation 1300 mg/d

Indian women

• Decreased body store

• Poor dietary intake

• Vitamin D deficient

WHO. Guideline: Calcium supplementation in pregnant women. Geneva, 2013.

Calcium Physiology

How calcium is absorbed from intestine to enter blood ?

IntestineCalcium ( Ca2+ )

+ Vit D3

Vit D3

Vit D3 acts as mineral transporter (carrier ) and helps calcium ions to pass trough intestinal mucosa and reach in blood

Blood

+ Vit D3

Intestinal Moucosal cells

Vit D3

Vit D3

Ca2+

Ca2+

How calcium enters the bone?

Osteocalcin

Ca2+

Ca2+

Ca2+

Ca2+

Ca2+

OsteoblastBlood

Calcium gets coavalently bound to osteocalcin (protein) and gets transferred to osteoblast cells

Vat D3 is required by osteoblast to produce osteocalcin

How calcium is deposited on bone?

Ca2+

Ca2+

Ca2+

Osteoblast

Ca

PO4

Bone

CaPO4

Within osteoblast cells, calcium and phosphate unite. The calcium phosphate thus formed is deposited on bone

matrix. This completes deposition of calcium in bone

PO4

PO4PO4

18

Conventional Ca Supplements : Absorption

Calcium Carbonate

Ca citrate maleate

Ionized calcium Ca+2

CaCO3

HClHCl

Dissociate in stomach into calcium ions

19

• Magma formation- less calcium absorption

• Interferes with absorption of Fe, Mg, vitamins

• GI intolerance• Needs Vitamin D3 for

absorption

Ca+2

Combines with-

Fe, Mg, VitaminsCa

Fe

Conventional Calcium Supplements : Limitations

Mineral transporters (Carrier-mediated transport)

• Calcium chelates with transporter• Orotic acid, Aspartic acid

• The chelate does not break in the acidic medium of stomach and this prevents magma formation in the intestine.

• Thus chelated calcium reaches intestine through which it is absorbed as such

• Further in the blood, calcium chelate travels intact and is delivered to the target site.

Aspartate Orotate

Calcium Absorption : 85%

Calcium Absorption : 95%

Difference between Mineral transporters

Calcium Orotate dissociates inside osteoblast

Calcium aspartate dissociates in the cell membrane of osteoblast

In osteoporosis and calcium deficiency conditions, defective transport through cell membrane is reported.

Ensures calcium delivery to the target site.

Offers highest calcium absorption

www. Firstclassarticles.net Agressologie 1970; 11(6):495-502

Offers highest elemental calcium absorption

www. Firstclassarticles.net Agressologie 1970; 11(6):495-502

Calcium orotate

• Absorption is independent of gastric HCl

• Very high absorption rate

• Absorption does not need vitamin D

• No loss of calcium- better GI tolerance

• Can be concomitantly administered with iron, vitamins etc.

Vitamin D

• Not required for calcium orotate absorption

• Vitamin D is essential in pregnancy

Vitamin Hormone

UV radiation

Vitamin Hormone

7-dehydro-cholesterol in skin Cholecalciferol (Vitamin D3)

UV radiation

Vitamin Hormone

7-dehydro-cholesterol in skin Cholecalciferol (Vitamin D3)

UV radiation

Vitamin Hormone

25-OH-Cholecalfiferol/ Calcidiol/ 25-OH-D3

Liver

7-dehydro-cholesterol in skin Cholecalciferol (Vitamin D3)

UV radiation

Vitamin Hormone

25-OH-Cholecalfiferol/ Calcidiol/ 25-OH-D3

1,25-OH-Cholecalfiferol/ Calcitriol/ DHCC/ 1,25-(OH)2-D3

Liver

Kidney

Causes of vitamin D3 deficiency

• Limited sun exposure (Modernization that has increased hours spent indoor)

• Culture and clothing style

• Increased pollution that hampers ultraviolet rays, hence synthesis of vitamin D3

34

Incidence of Vitamin D deficiency in pregnant women - India

• Study done by AIIMS

Urvashi Mehlawat, et al., IPP, Vol 2 (2), 328-335, 2014 329

Incidence of vitamin D deficiency in pregnant mothers ranging from 67% to 96%

Recommendation of Vit. D3

1,000 IU/day of vitamin D3 is safe in pregnancy

Obstet Gynecol 2011 Jul;118(1):197-8

RCOG Recommendations

All women 400 IU/d

Women at risk (obese, skin pigmentation, decreased sunlight exposure)

1000 IU/d

High risk of preeclampsia 800 IU/d

Safety of Vitamin D in pregnancy

• Hungry Bone syndrome, hypercalcaemia

• Supraventricular aortic stenosis

• Sarcoidosis

• Absolutely safe, up to 4000 IU/dHollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D

supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res 2011;26:2341–57.

Composition:

Each tablet contains

Calcium Orotate...............740 mg

(Elemental calcium 20.6% i.e. 152.44 mg/tab)

Vitamin D3 ......................1000 IU

Presenting

Cdense

• Pregnancy & lactation• Low back pain

Dosage : 1 tablet once daily after lunch

Indications

Calcium Orotate vs OthersAmount of elemental calcium absorbed is HIGHEST

with calcium orotate Weight of

Tablet%

elemental calcium

Amount of elemental calcium (mg) in each

tablet

% of calcium

absorbed

Amt of calcium (mg)

absorbed from each tab

CaCO3

(1250mg)40 500 8 40

Ca citrate maleate

(1250mg)

20 250 40 100

Ca aspartate (560 mg)

12.5 70 85 59.5

Ca orotate (cdense)

(740 mg)

20.6 152.44 95 145

www.vitaminexpress.com/encyclopedia.php , http://www.ghchealth.com/forum/viewtopic

• Rangaraj P, Dhembare P. Obstetrics & Gynecology Today vol. XIV (10) 10 Dec. 2009

• Open label, balanced, randomised, three treatment, crossover study

Post dose comparison for serum calcium levelsPost dose comparison for serum calcium levels

Percent change in serum calcium levels

1

6

19

0

5

10

15

20

Placebo Caco3 Cdense

pe

rce

nt

(%)

Significant rise in serum calcium compared to calcium carbonate

+ Vit. D3

Postdose comparison for serum iPTH Postdose comparison for serum iPTH levelslevels

Significant decrease in circulating iPTH

93

-2

-41

-19

-71-80

-70

-60

-50

-40

-30

-20

-10

0

10

20

Placebo Caco3 Cdense

0.5 hrs

4.5 hrs

Algal source calcium

Coral calcium Calcium orotate

Source Made by heating Oyster (a type of animal) shell mixing with heated seaweed (Algae)

Not preferred by Vegetarians

Marine Animal (coral reef) also called coral calcium.

Not preferred by Vegetarians

Concern of contamination with lead and mercury

Synthetic Made by a chemical reaction of Calcium hydroxide or calcium chloride with orotic acid

Type of calcium

Calcium Hydroxide, calcium oxide and calcium carbonate

Elemental Calcium present is 150 mg

Calcium carbonate

Elemental Calcium present is 225 mg

Calcium orotate

Elemental Calcium present is 152.44 mg

% Calcium absorbed

No data available 8% = 18mg 95% =145mg

Co-administration

Calcium Orotate

Highest 95% absorption, bioavailability much higher than calcium carbonate + vitamin D3, proven in Indian subjects

Calcium absorption

Tolerability

Calcium Absorption

Co-administration

Tolerability

Calcium Orotate

No chance of Magma formation

So can be safely co-administered

with iron, magnesium, vitamin

supplements

Thank Yo u