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Unlocking muscle growth

potential with phytase

Dr. Patrick Guggenbuhl, Senior Scientist

Jean-Paul Ruckebusch, Global Category Manager Enzymes

Exogenous phytases have been used Figure 1: Formation of myo-inositol in the small intestine
commercially since the early 1990s as a successful after quick degradation of IP6 to lower IP esters in the upper
digestive tract
tool for reducing the environmental impact of
industrial livestock production and improving
RONOZYME® HiPhos has the
poultry and swine profitability. These cost-saving capacity to degrade phytate
and sustainability benefits derive from the (IP6) down to IP1.
ability of phytase to liberate phosphorus from Under gastric circumstances
phytate. The breakdown of this poorly digestible the main conversion will be
from IP6 to IP4 and IP3.
compound improves animals’ phytate-phosphorus
retention and reduces the need to use inorganic IP6
+ H2O - Pi

phosphorus sources in the diet. IP5

The hydrolysis of phytate also delivers several additional

physiological benefits that extend beyond phosphorus
+ H2O RONOZYME®
alone. These include the retention of amino acids, trace - Pi Inositol HiPhos
minerals, calcium and energy, which has led to feed phytase
‘super-dosing’. The resulting performance improvements IP4
reported, particularly with DSM’s RONOZYME® HiPhos, are Endogenous
IP1
over and above what would be expected based on additional Phosphatases
+ H2O
phosphorus release and the reduction of anti-nutritive effects. - Pi
However, the exact cause of these enhanced benefits was not IP3
+ H2O IP2
until recently fully understood. - Pi

New research conducted by DSM has revealed important new + H2O - Pi

insights into the ‘extra-phosphoric’ (EPE) effects of phytase,

particularly on the role of myo-inositol. Endogenous phosphatases are present in the Duodenum and
Jejunum of most animals. These phosphatases partly convert

The role of myo-inositol

the lower IP esters (IP3,2,1) to a free myo-inositol ring.
IP3, IP2, IP1 and myo-inositol can all be absorbed in the
small intestine, increasing blood plasma levels. Part of the
Myo-inositol is a cyclical sugar alcohol that forms the core
conversion to myo-inositol continues post absorption as
of the phytate molecule. Phytase together with endogenous
phosphatases are also present in the blood stream and liver.
phosphatases can liberate phosphate groups from phytate to
increase the levels of circulating plasma myo-inositol (Figure 1).
Myo-inositol is known to have the property to increase insulin
sensitivity which can help in the distribution of blood glucose
to the different organs and in particular to skeletal muscles,
which will influence protein accretion and by that have a growth
promoting effect. Laboratory results suggest that baseline
plasma myo-inositol concentrations in broilers are around 30
mg/l and in pigs around 5-10 mg/l. The addition of a suitable
phytase can increase these levels with beneficial effects.
‘Extra-Phosphoric Effects’
(EPE) in pigs
A number of trials have also been carried out in pigs to
demonstrate the performance response to increasing doses of
RONOZYME® HiPhos when matrix values are applied. It is clear
that a high dose of RONOZYME® HiPhos can improve pig and
piglet performance over and above that of the positive control

Benefits to broilers
diet, beyond feed cost savings.
By increasing the phytate degradation efficiency, RONOZYME®
Although glucose metabolism is different in poultry and pigs, HiPhos has been shown to increase levels of myo-inositol
both have shown improved performance in response to oral in pigs and poultry. A study compared the EPE performance
doses of myo-inositol. Trials have shown that higher doses of improvements with myo-inositol levels in piglets. A PC diet
phytase improve weight gain and feed conversion ratio, as well was compared with a matrix control diet (MC) and the MC diet
as calcium, phosphorus and sodium retention. containing either a 1000 or 2000 FYT dose of RONOZYME®
HiPhos. The energy, Ca & P levels in the MC were adjusted
In a recent study, broiler chicks were fed either a diet
according to the respective matrix values for RONOZYME® HiPhos
containing insufficient (NC) or sufficient (PC) levels of available
at 1000 FYT dose. The piglets fed the MC1000 and MC2000 diets
phosphorus and calcium. RONOZYME® HiPhos was then
showed improvements in daily weight gain (DWG) and FCR above
added at 1000, 2000 and 3000 FYT/kg to both diets. The
that of the PC (Figure 2). A clear response to the addition of
supplementary phytase improved body weight gain and FCR
RONOZYME® HiPhos was also seen in the level of plasma
effects of the NC diet and of the PC diet and plasma myo-
myo-inositol and this followed the performance response.
inositol levels were also measured and remained elevated after
three to four weeks. Myo-inositol concentration increased in
both cases mirroring the effects on performance and by that
strengthening its role.

Figure 2: Higher doses of RONOZYME® HiPhos increased the DWG and FCR of piglets

450 1.70
400 1.65
1.605 1.661 1.467
350 1.499 1.60
300
1.55
250
1.50
200
1.45
150
1.40
100
50 1.35
313 280 317 350
0 1.30
PC MC MC + RONOZYME® MC + RONOZYME®
HiPhos 1000 U/kg HiPhos 2000 U/kg
Daily weight gain (day 0-28)

DWG (g) FCR

Latest findings
Phytase has been demonstrated to improve growth performance, meat breast weight, amino acid digestibility and plasma
myo-inositol concentration in broilers. New research recently presented by DSM demonstrates the potential interactions
between phytase supplementation, growth performance and host gene expression to identify potential associated biomarkers.
The addition of RONOZYME® HiPhos at 1000 FYT/kg to the negative control (NC) restored the body weight gain at the level
of the positive control (PC) in parallel with an increase of the plasma myo-inositol concentration driven by muscle growth as
illustrated by the positive effect on the breast muscle (filet) weight increase.
The most impacted pathways via myo-inositol stimulation in animals fed RONOZYME® HiPhos are those controlling the
formation of muscle tissue via the calcium/calmodulin-dependent kinase and IGF pathways (Figure 3).
Figure 3: Gene expression in skeletal muscle cells

IGF-1
myo-inositol myo-inositol effects on Insulin sensitivity IGF binding protein
(IGFBP) IGF-1 receptor

Phosphoinositide-kinases
α Polypeptide (PIK3CA) Phosphoinositide-3-kinase
myo-INO regulatory subunit 1
Phospholipase C bêta (PLCB)
(PIK3R1)
PIP2
PIP2 PIP3
IP3 Calmodulin (CALM1)
Calcium

3-phosphoinositide
dependent protein kinase-1
Protein phosphatase 3 (PPP3CB)
IP3 receptor (PDPK1)
Calcineurin A
Pkb/Akt
pathway
K(lysine)
acetyltransferase 2B Ribosomal protein S6
(KAT2B) kinase b-1 (RPS6KB1)
Myogenic
regulatory factor
Myocyte enhancer
(MYOD)
factor 2 (MEF2)

Protein synthesis

Skeletal muscle Skeletal muscle

hypertrophy differentiation

Myo-inositol can be related to both metabolic pathways affected in broilers’ muscle due firstly its involvement in the intra-cellular
enzyme activity and secondly as an insulin sensitivity enhancer. In spite of differences in the gastro-intestinal tract physiology
and metabolism between weaned piglets and broilers, phytase supplementation had similarly increased plasma myo-inositol in
both species which may influence muscle development and partly explain the better growth.
The results highlighted the importance of IP3 and myo-inositol (end products of phytic acid degradation by phytase) for
improving muscle growth through the specific biomarkers potentially related to phytase supplementation that have been
identified in the muscle.
Research will now focus on confirming these results in other species besides better understanding other mechanisms involved
in the extra phosphoric effects (EPE) resulting from high doses of microbial phytase.