GIVOCAL

General description
HO
O O
OH 2+
P O
2+
P O Ca HO Ca
HO O O O O

-isomer -isomer

Calcium content :19.04%

Ca/P
ratio: 1.3
Phosphorus content :14.8%

Solubility :20 g/l in water(at 15C)

Organoleptic: Tasteless and odorless

Particle size :95 % < 100 m

Aspect :White crystalline powder

2
General description
Glycerophosphate anion is a vector
for calcium
Physiochemica Organoleptic
l
GLYCEROPHOSPHATE

Organoleptic

Main organ tissues Cell

membranes

Phospholipid
3
s
Absorption of Calcium
salts
Calcium is better absorbed in ionised form

Calcium is absorbed in the small intestine

Calcium absorption is regulated by 4 physico-

chemical parameters

Ca salt solubility into stomach acid

compartment

Ca precipitation in the small intestine after

neutralisation by pancreatic secretion

Ca complexation with anions (phytates,

oxalates) in the small intestine

Digestive use coefficient : 50 25 %

4
Solubility of Calcium
salts
Comparative studes at different pH
3 mg/ml Ca + 2,35 mg/ml phosphate anios for salts
without P
pH adjusted with HCl or NaOH from 2 to 9

Stomach pH
Calcium lactate 2 4

Dicalcium phosphate 2 3

Calcium gluconate 2 5

Calcium glycerophosphate 2 9

Small intestine pH
5
Neutralisation of
acidity by Calcium
salts
A comparative study with an equivalent of 200
mg of calcium element

Calcium source mg ml HCl 0,05N

Calcium carbonate 500 200
Tricalcium phosphate 515 131
Calcium lactate 123 136
8
Calcium 105 96
glycerophosphate 0

Calcium glycerophosphate has the smallest

buffer power that means it is best solubilised
in stomach
6
In vivo
comportement of
Calcium salts
Calcium carbonate
CaCO3 is soluble at acid pH but it rapidly
neutralises gastric acidity

CaCO3 develops a neutral area in the stomach

where it becomes insoluble
CaCO3 is usually used as an antiacid compound

When CaCO3 arrives in the small intestine it is

neutralised

Tricalcium phosphate (Ca3(PO4)2)

Ca3(PO4)2 is soluble in pH < 4 but it has a high
buffer power

When pancreatic secretions enter in contact,

Ca3(PO4)2 precipitates
7
An excess of phosphates induces extrabone
Solubility/Absorpti
on of Calcium
salts Ca
Calcium source conten Solubility Absorption
t
Calcium carbonate 40,04% Insoluble 80%
become
insoluble
Tricalcium 38,76% Insoluble Not bad
phosphate
Calcium lactate 18,37% Soluble at Good
acid pH
Calcium 19,04% Soluble at all Good
glycerophosphate pH
Calcium carbonate has an alkaline effect and
modifies the electrolyte equilibrium. It also
might induce flatulencies, constipations,
nausea.
Tricalcium phosphate modifies the electrolyte
equilibrium 8
Calcium lactate & glycerophosphate are non
Phosphorus content
of Calcium salts

The biological ratio between Ca & has to

be 1 to 1,5

Calcium glycerophosphate: Ca/P = 1,3

Calcium carbonate: no P / Risk

hypophosophatenia

Tricalcium phosphate: Ca/P = 1,3

9
Glycerophosphate metabolism
Glycerophosphate is an intermediate of the cellular
metabolism

Potentiality to become integrated into well-known

mechanisms
Has an esssential place into the biosynthesis of
triglycerides and phospholipids
CH OH 2
L-glycerol-3-phosphate
OH C H
CH2 O P

2 R CO ~ S.CoA (R1 and R2)

2 CoA SH

CH2O CO R1
R2 CO O C H L--phosphatidate

CH2 O P
Pi

CH2O CO R1
L-1,2-diglyceride
R2 CO O C H
CH2OH

R3 CO ~ S.CoA

CoA SH

CH2O CO R1
R2 CO O C H Triglyceride 10
CH2 O CO R3
Glycerophosphate metabolism
L-glycerol-3-phosphate is the main acceptor of
actylated group which are characteristics of
lipidic structures. Triglycerides
Lecithines Cephalines

L-1,2-diglyceride

L--glycerophosphatidic acid

CDP-diacyl-glycerol

Inositides Phosphatidyl-
glycerol

Phosphatidyl-serine
Cardiolipids

It is then important for the lipids storage in the

adipous tissue, for blood lipoortein structure
11
(triglycerides and phospholipids) or biological
Glycerophosphate metabolism
Glycerophosphate acts very directly into the
general ways of glycolic metabolic regulation and
cell energy

Mitochondria
12
Glycerophosphate is able to become integrated
On the nervous system
Subjects: in vitro study protocol using rat
nerve cells
Design:
Survival of neurons
Differentiation of neurons cocultured with
astrocytes

Defined medium + 2 mM
GIVOCAL

Normal defined medium

13
On the nervous system
Results:
Calcium glycerophosphate enhances neuron
survival in tissue culture

Calcium glycerophosphate has more activity in

promoting the survival & differenciation of
neurons

Astrocytes cocultured with calcium

glycerophosphate were more shaped and thus
formed a greater number of interneuronal
connections

Calcium glycerophosphate stimulates the

energetic way (degradation of glucose to
14
pyruvate through its transofrmation into
Absorption of calcium
on bone tissue
Subjects: mice
Design:
Comparative absorption of diferent calcium salts
Diet supplemented with 0,5% calcium
Measurements of the femur resistance to fracture
Duration: 6 weeks

Results: calcium glycerophosphate leads to a better

fixation of calcium by the femoral bone in comparison
to other commonly employed calcim15salts and
Gastrointestinal
experiments
TNO dynamic models are unique tools to study
stability, release, dissolution, absorption &
bioconversion of nutrients, chemicals,
bioactive pharmaceutical compounds in
gastrointestinal tract

Subjects: TIM -1 (dynamic gastrointestinal

model) Simulation of gastrointestinal
conditions

Design: to determine the digestibility of

calcium glycerophosphate & calcium carbonate
durign passage through the stomach and small
intestine

Simulation dynamic conditions in gastric small

TNOtract
intestinal dynamic model of the stomach
and small& intestin
Body temperature (TIM-1)
pH curves
Concentration of electrolytes
16
Activity of enzymes in the stomach & small
 Gastrointestinal conditions

Experiments
performed under the
average physiological
conditions of the
gastrointestinal tract
as described for
young adults

Digested and
dissolved low
molecular compounds
are dialysed
continuously from the
17
jejunum and ileum
 Protocols of
experiments
2 experiments were down with the same
content of calcium
First with calcium glycerophosphate
Second with calcium carbonate

Sample preparations:
Solutions at a high calcium content are miwed
with artificial saliva
Total introduction in the gastric compartment:
300 g with 7,6g calcium
First experiment= 40 g calcium glycerophosphate
Second experiment = 19 g calcium carbonate

Duration:
During 3 hours 80% of the gastric contents is
gradually delivered in the small intestine
After 5 hours 80 % of the small intestin contents
18
are gradulally delivered into the large intestine
 Protocols of
experiments
Collection of gastric content
1 & 3 hours aliquots: G1 and G3

Every 1-2 hours dialysing & absorbed liquids of

jejunum & ileun compartments are changed and
total volumes are measured
Dialysing & absorbed liquids in jejunum: J

Dialysing & absorbed liquids in ileum: I

The liquid collected at the end of the model

correspond to the liquid which goes to the colon: C

Results analysis:
For calcium glycerophosphate: C RMN &
calcium ionic chromatography

For calcium carbonate : calcium 19

ionic
Calcium glycerophosphate:
C NMR analysis
Calcium glycerophosphate content in each
V x1 G1 x1
G3 x10

J x25 I x300
C x60

V control: 40 g
G1 first hour gastric sample: 38 g
G3 third hour gastric sample: 1 g 17,4 g calcium
glycerophosphate absorbed
J jejunum dialysis sample: 16 g 20
 Ionic chromatography
analysis of calcium
Calcium content of each compartment (with
calcium glycerophosphate)

V: 3,4% 7,6 g 100%

G1: 3% 6,3 g 83%
G3: 0,25% 0,053 g
J: 0,14% 3,2 g 42%

Calcium absorbed
I: 0,04% 0,97 g 13%
C: 0,1% 0,3 g 4%

Among 7,6 g of calcium initial intake, approximatively

4,17 g reach the small intestine and are absorbed. This
quantity roughly correspond to 5 times the calcium RDI

50 % of ingested calcium
21
Conclusions on Calcium
glycerophosphate

Calcium glycerophosphate resists to in

vitro gastric passage after 3h at pH 1,5

After gastric passage a part of calcium

glycerophosphate passes through
intestine mucous membranes during
300 minutes

As previously supposed
glycerophosphate anion seems to have
an important role in the absorption of
calcium
Glycerophosphate is absorbed without
degradations 22
Glycerophosphate is absorbed in the same
 Results with calcium
carbonate
During the mixing with artificial saliva
Formation of gas (probably CO2)
Increase of pH: 8,5-9,5 instead of 4

Increase of pH in the gastric compartment

23
 Results with calcium
carbonate
Calcium content of each compartment (with calcium
carbonate)

Non working
V: important sediments 0,01% 0,03g
results
G1: important sediments 0,1% 0,323g
G3: limpid solution 1,1% 0,981
0,204 g
g ->
2,7% calcium
J: absorbed
limpid solution 0,02% 0,677g ->
8,9%
I: limpid solution 0,01% 0,304 g ->
4%
C: slight sediment 0,02% 0,102 g Non
working result

Among 7,6 g of calcium initial intake, appreciatively 12,9 %

reach the small intestine and are absorbed.

As previously supposed calcium carbonate

24 is precipitated
Glycerophosphate/Carbo
nate comparison
With the same content of calcium, glycerophophate
permits a better aborption
7 times more in the jejunum
4 times more in the ileum

Nervertheless calcium carbonate permits (in the

experiments) to provide the calcium RDI (800-1000
mg)

2 hypothesis in the case of a normal oral intake

Absorbed % stay constant
Intake of 800 mg calcium through 4,2 g of calcium
glycerophosphate = (50%) 400 mg calcium absorbed
Intake of 800 mg calcium through 2 g of calcium carbonate=
(12,9 %) 103 mg calcium absorbed

Absorbed quantities stay constant (limite

absorption level)
Intake of 1000 mg calcium through 5,2 g calcium
25
glycerophosphate = ( 4170 mg) 1000 mg calcium absorbed