| |

Received: 27 March 2018    Revised: 11 July 2018    Accepted: 22 August 2018

DOI: 10.1111/jpn.12990

REVIEW ARTICLE

Osmoregulatory function of betaine in alleviating heat stress in

poultry

Adi Ratriyanto1  | Rainer Mosenthin2

1
Department of Animal Science, Faculty
of Agriculture, Sebelas Maret University, Abstract
Surakarta, Indonesia This review focuses on the osmoregulatory function of betaine and its effect in terms
2
Institute of Animal Science, University of
of alleviating heat stress in poultry. Poultry appear to be particularly sensitive to
Hohenheim, Stuttgart, Germany
temperature‐associated environmental challenges, especially heat stress. High ambi‐
Correspondence
ent temperatures are deleterious to productive performance in poultry, including
Adi Ratriyanto, Department of Animal
Science, Faculty of Agriculture, Sebelas broilers, laying hens, quails and turkeys, resulting in considerable economic losses.
Maret University, Surakarta, Indonesia.
Heat stress impairs overall poultry production by decreasing feed intake and nega‐
Email: [email protected]
tively affecting intestinal development, leading to reduced nutrient digestibility.
Apart from inducing a high mortality rate, heat stress is known to depress growth
rate and reduce meat yield in broilers. In layers, lower feed intake impairs ovarian
function, leading to decreased feed efficiency, egg production and egg quality. In ad‐
dition, reduced immune functions, such as thyroid activity and antibody production,
are evident in poultry exposed to heat stress. Heat stress increases the production of
oxidants, causing oxidative stress and lipid peroxidation of cell membranes. Poultry
respond physiologically and behaviourally when encountering the negative effects of
heat stress, attempting to return the body to homeostasis. This requires energy at
the expense of weight gain or egg production. Due to its zwitterionic structure, be‐
taine has osmoprotective properties that aid in protecting intestinal cell proteins and
enzymes from environmental stress, including high ambient temperature, thereby
counteracting performance losses. Betaine also exerts an osmoregulatory role in
cells, regulating water balance, and this results in more stable tissue metabolism.
Inclusion of betaine in the diet may be beneficial for alleviating physical reactions to
heat stress, as indicated by increases in nutrient digestibility. In broilers, betaine sup‐
plementation increases weight gain and breast muscle yield, while improving feed
conversion. In layers, betaine supplementation improves egg production, egg quality
traits and immune indices. In conclusion, due to its osmoregulatory functions, be‐
taine plays an important role in alleviating heat stress in poultry.

KEYWORDS
broiler, compatible osmolyte, digestibility, layer, performance, physiology

1 | I NTRO D U C TI O N Heat stress negatively affects chickens’ feed intake, growth and lay‐
ing performance, reproductive performance and physiological traits
A hot environment is an important stressor for chickens, and such (Attia, Abdallah, Briekaa, El‐Hamid, & Abou‐Shehema, 2011; Chand,
conditions have become a major challenge in poultry production. Muhammad, Khan, Alhidary, & Rehman, 2016; Khan, Naz, & Dharma,

1634  |  wileyonlinelibrary.com/journal/jpn

© 2018 Blackwell Verlag GmbH J Anim Physiol Anim Nutr. 2018;102:1634–1650.
RATRIYANTO and MOSENTHIN |
      1635

2014). Heat stress occurs due to a negative balance between the the chickens’ physiology, immune response, nutrient digestibility
heat energy supplied from the environment to the birds and that and performance (Attia et al., 2016; Park & Kim, 2017; Sakomura
released by the birds (Attia et al., 2011). The factors influencing et al., 2013). The present paper aimed to review the osmoregula‐
heat stress include the temperature, duration of exposure, diurnal tory functions of betaine and its effect on nutrient digestibility and
temperature variation, relative humidity, poultry genotype and age performance traits in poultry under exposure to heat stress. Further
(Attia, Hassan, & Qota, 2009). attention will be paid to the potential effects of betaine with respect
Two major categories of heat stress can be distinguished, namely to poultry’s physiology and immune responses.
acute heat stress and chronic heat stress. Acute heat stress refers
to a short and rapid rise in ambient temperature, while chronic heat
stress refers to a high ambient temperature over a long period (days 2 | B E TA I N E A S A CO M PATI B LE
to weeks), permitting acclimation to the environment (Akbarian et OS M O LY TE
al., 2016). The optimum temperature for performance of poultry is
likely to be 18–22ºC (Khan et al., 2014, 2012 ). Betaine has received considerable attention as a compatible os‐
Modern poultry production is highly intensive including large molyte, and it is recognized to be the most effective osmopro‐
stocks with high stocking density and fast‐growing birds, resulting in tectant among other organic osmolytes, such as proline, glycine,
increased temperatures in chicken houses (Yalçin, Özkan, Türkmut, glutamine, sarcosine and taurine (Petronini, de Angelis, Borghetti,
& Siegel, 2001). Progress in the genetic selection of meat‐type birds Borghetti, & Wheelert, 1992; Yancey, 2001). Osmolytes are espe‐
has resulted in rapid growth with a high metabolic rate, which is cially important in situations of cellular dehydration, as these com‐
accompanied by a higher heat production (Tallentire, Leinonen, & pounds help in minimizing water loss against the prevailing osmotic
Kyriazakis, 2016). Since the birds maintain their body temperature gradient (Klasing, Adler, Remus, & Calvert, 2002). Compatible os‐
within a narrow range, increasing the ambient temperature leads to molytes, such as betaine, regulate water balance, exerting a stabi‐
a decline in the ability to dissipate heat (Yahav, 2009). Furthermore, lizing influence on tissue metabolism (Lipiński, Szramko, Jeroch, &
there are nutritional strategies available that can be applied to im‐ Matusevičius, 2012).
prove birds’ tolerance to heat stress such as dietary reduction in Betaine is absorbed from the duodenal enterocytes into circula‐
protein or energy (Laudadio et al., 2012; Ratriyanto, Indreswari, tion, and there is a positive correlation between the dietary betaine
Nuhriawangsa, & Arifin, 2017) and the introduction of dietary sup‐ intake and plasma betaine concentration (Awwad, Kirsch, Geisel, &
plements (Chand et al., 2016; Khan et al., 2011). Obeid, 2014; Patel & Mehta, 2015). It is carried to the liver and kid‐
Betaine, also referred to as trimethyl glycine and glycine beta‐ neys to be catabolized by a series of enzyme‐catalysed reactions,
ine, is a naturally occurring compound that has been found in micro‐ predominantly in the mitochondria, and participates in the methi‐
organisms, marine invertebrates, animals and plants such as sugar onine cycle (Patel & Mehta, 2015). The non‐catabolized betaine acts
beet, wheat and lucerne meal (Chendrimada, Neto, Pesti, Davis, & as an osmolyte and confers protection to the cells against environ‐
Bakalli, 2002; Craig, 2004; Hassan, Attia, & El‐Ganzory, 2005; Kidd, mental stresses, such as osmotic variation, adverse temperatures
Ferket, & Garlich, 1997). Sugar beet contains exceptionally high lev‐ and dehydration. It aids in water retention by regulating the surface
els of betaine, which accumulate in condensed molasses soluble, tension of water and thus maintains cellular volume (Patel & Mehta,
a by‐product of sugar beet processing (Eklund, Bauer, Wamatu, & 2015). Betaine performs osmoregulatory functions, for example, the
Mosenthin, 2005). Furthermore, betaine is available as a feed addi‐ hydration and transport of molecules across the intestine (Kettunen,
tive in a purified form, and it is most commonly added to animal diets Peuranen, & Tiihonen, 2001), sustenance of haemoglobin solvation
in the form of anhydrous betaine, betaine monohydrate or betaine (Hundahl, Fago, Malte, & Weber, 2003) and protection of renal cells
hydrochloride (Eklund et al., 2005; Ratriyanto, Mosenthin, Bauer, & from high concentrations of electrolytes (Horio et al., 2001). The
Eklund, 2009). In addition to exogenous sources in the diet, beta‐ concentration of betaine in the liver and kidneys and its availabil‐
ine can be synthesized endogenously from its metabolic precursor, ity as an osmoprotectant are controlled by the regulation of betaine
namely choline (Craig, 2004). homocysteine methyl transferase (Pajares & Pérez‐Sala, 2006). The
Chemically, betaine is a neutral methyl derivative of amino acid accumulation of betaine in vertebrates is stimulated by external hy‐
glycine with a positively charged trimethylammonium group and a perosmolarity in renal cells and macrophages (Nakanishi, Turner, &
negatively charged carboxyl group, a specific type of zwitterion that Burg, 1990; Park & Kim, 2017).
performs osmoregulation and methylation (Attia, Hassan, Shehatta, During heat stress, the body cells of poultry are subjected to
& Abd El‐Hady, 2005; Craig, 2004). Basically, betaine exerts two im‐ osmotic stress, since a high ambient temperature may cause water
portant metabolic properties, as it acts as methyl group donor and imbalances and osmotic changes in the cells via dehydration.
as compatible osmolyte, which aids in maintaining cellular osmolarity Betaine may help in maintaining the cell integrity and hydration
(Ratriyanto et al., 2009). Thus, the use of betaine may improve poul‐ under heat stress due to its osmoregulatory (Kidd et al., 1997) and
try tolerance to heat stress (Attia et al., 2011). anti‐stress functions (Saunderson & Mackinlay, 1990). Intracellular
Studies on the effects of betaine in poultry kept under high betaine has been shown to preserve the osmotic equilibrium and
environmental temperature revealed variable results concerning protect macromolecules against denaturation, allowing the cell to
 |
1636       RATRIYANTO and MOSENTHIN

maintain its metabolic activities (Tucker & Remus, 2001). In exert‐ inorganic ions and preventing enzymes and cell membranes from
ing osmoprotective effects, betaine must be accumulated in the being inactivated by inorganic ions (Klasing et al., 2002; Petronini
cells exposed to osmotic and ionic stress, thereby replacing the et al., 1992).

TA B L E 1   Effects of betaine on performance traits in meat‐type poultry reared under heat stress

Temperature (ºC) and

Poultry/breed Betaine level (%) Humidity (%) Betaine effects References

Cobb × Cobb, male 5–10 T 36 for 4 hr daily ↓ Water intake 1.5%–8.8% Zulkifli et al. (2004)
broiler chickens (day 36 to 41) No effects on performance
Broiler chickens 0.10 T 34.6 ↑ Feed intake 6.0% and weight gain 5.0% Farooqi et al. (2005)
Ross, male and female 0.10–0.20 T 25 (T 35 for 10 hr ↑ Weight gain 1.1%–3.1% Enting Eissen Los
broiler chickens daily) Mozos Álamo and
Ayala (2007)
Ross 308, male broiler 0.10–0.20 T 28.1–33.1 ↓ Weight gain 5.8%–7.0% and tibial width Konca et al. (2008)
chickens RH 37.0–50.3 4.1%–8.7%
El‐Salam, unsexed slow 0.05–0.10 T 28; RH 55 ↑ Weight gain 5.5%–10.4% and feed intake Attia et al. (2009)
growth chickens (T 38; RH 49 for 4 hr 2.9%–6.0%
in 3 successive days ↓ Feed conversion 2.4%–4.6%
per week)
Cobb 400, male broiler 0.08 T 25–33 ↑ Weight gain 2.9% and feed efficiency Rao et al. (2011)
chickens 14.5%
Cobb, broiler chickens 0.05–0.10 (drinking T 20; RH 80–100 ↑ Weight gain 32–36 day 2.8%–6.9% Sayed and Downing
water) (T 32 for 9 hr daily) No effects on intestinal morphology (2011)
Hubbard, unsexed 0.12 T 38–40 ↑ Weight gain 19.1% Khattak et al.
broiler chickens RH 40–93 ↓ Feed intake 9.8% and feed conversion (2012)
24.2%
Nicholas 300, turkey 0.10–0.15 T 27–38 ↑ Feed intake 0.8%–5.2% and body weight Al‐Shukri et al.
RH 55–60 3.1%–3.8% (2012)
↓ Feed conversion 5.7%–9.9%
Ross 308, male broiler 0.12 T 28 (T 35 for 6–8 hr ↑ Weight gain 6.4%–8.8% Amerah et al. (2013)
chickens daily)
Cobb, male broiler 0.05–0.10 T 25–31 ↑ Feed intake 3.0%–3.6% Sakomura et al.
chickens No effects on intestinal morphology (2013)
Lohmann, unsexed 0.07–0.14 T 25.7–32.9 No effects on performance traits Ratriyanto et al.
broiler chickens (2014a)
Lohmann, unsexed 0.07–0.14 T 25.7–32.9 ↑ Jejunum length 6.7%, ileum length 6.1%, Ratriyanto et al.
broiler chickens and total small intestine length 6.1% (2014b)
↓ Crypt: villi ratio 19.3%
Cobb × Hubbard, 0.05–0.10 T 28–36 ↑ Feed efficiency 8.1%–9.7% Kpodo (2015)
unsexed broiler
chickens
Inhas, unsexed broiler 0.10–0.20 T 26; RH 66.2 ↑ Weight gain 10.8%–15.4% Nofal et al. (2015)
chickens (T 39.5–41 for 5 hr ↓ Feed conversion 9.1%–11.8%
daily in 5 days)
Cobb 400, broiler 0.13–0.20 T 28–35 ↑ Feed intake 2.1%–2.4% and weight gain Singh et al. (2015)
chickens 2.4%–3.3%
Ross, male broiler 0.10 T 33.0 ↑ Feed intake 3.0% and weight gain 15.0% Akhavan‐Salamat
chickens ↓ Feed conversion 10.4% and Ghasemi
(2016)
Ducks 0.07–0.13 T 22–26; RH 50 ↑ Feed intake 6.8%–7.3% and body weight Park and Kim (2017)
T 33–43; RH 70 for 21.8%–23.3%
5 hr daily (day ↓ Feed conversion 12.1%–12.6%
22–42)
Broiler chickens 0.10–0.20 T 25.4–35.8 ↑ Feed intake 2.80%–8.75%, weight gain Chand et al. (2017)
RH 52–87 3.53%–12.58%
↓ Feed conversion 0.71%–3.43%

Note. T: temperature; RH: relative humidity; ↑: increase (p < 0.05); ↓: decrease (p < 0.05).

RATRIYANTO and MOSENTHIN |
      1637

The accumulation of osmolytes, such as betaine, in cells de‐ digestion, absorption and nutrient utilization in broiler chick‐
creases the cell osmotic potential, and thus, it maintains the water ens (Mahmoudnia & Madani, 2012). According to Clow, Treberg,
absorption and cell turgor pressure, which may contribute to sus‐ Brosnan, and Brosnan (2008), dietary betaine enhances the be‐
taining physiological processes. As an osmolyte, betaine increases taine concentration in the intestinal epithelium. It is involved in
the cytoplasmic volume and free water content of the cells at high the osmoregulation of the duodenal epithelium of broiler chickens
osmolarity, thereby permitting cell proliferation under stress condi‐ and affects the movement of water across the small intestinal ep‐
tions (Csonka, 1989). In addition, betaine stabilizes the protein and ithelium in vitro (Kettunen, Peuranen, et al., 2001). Furthermore,
cell components against the denaturing effects of high ionic strength betaine is a chemical chaperone that helps to stabilize proteins in
(Kempf & Bremer, 1998). their natural conformation; thus, it may be beneficial for the sur‐
Betaine may stimulate the protection of the intestinal ep‐ vival of intestinal microorganisms under stress conditions (Eklund
ithelium against osmotic disturbances, thereby improving et al., 2005).

TA B L E 2   Effects of betaine on carcass traits in meat‐type poultry reared under heat stress

Temperature (ºC) and

Poultry/breed Betaine level (%) Humidity (%) Betaine effects References

Cobb×Cobb, male broiler 5–10 T 36 for 4 hr daily (day No effects on abdominal fat Zulkifli et al. (2004)
chickens 36–41)
Ross, male and female broiler 0.10–0.20 T 25 (T 35 for 10 hr daily) ↑ Breast yield (male) 4.4%–4.9% Enting et al. (2007)
chickens
Ross 308, male broiler 0.10–0.20 T 28.1–33.1 No effects on carcass traits Konca et al. (2008)
chickens RH 37.0–50.3
El‐Salam, unsexed slow growth 0.05–0.10 T 28; RH 55 ↓ Meat dry matter 5.0%–6.2% Attia et al. (2009)
chickens (T 38; RH 49 for 4 hr in 3 ↑ Dressing percentage 0.3%–4.1%,
successive days per week) liver weight 7.6%–11.9% and
giblet weight 4.5%–6.3%
↑ Meat water holding capacity
2.0%–5.9%
Cobb 400, male broiler 0.08 T 25–33 ↑ Breast weight 5.9% Rao et al. (2011)
chickens
Nicholas 300, turkey 0.10–0.15 T 27–38 ↑ Breast muscle ratio 9.3%–12.7% Al‐Shukri et al.
RH 55–60 and breast yield 19.1%–29.3% (2012)
↓ Abdominal fat 12.5%–14.6%
Ross 308, male broiler 0.12 T 28 (and 35 for 6–8 hr ↑ Breast meat yield 6.0%–8.2% Amerah et al.
chickens daily) and carcass weight 2.2%–2.3% (2013)
↓ Abdominal fat 23.0%–27.5%
Cobb, male broiler chickens 0.05–0.10 T 25–31 No effects on carcass traits Sakomura et al.
(2013)
Ross, male and female broiler 0.025–0.08 T 24–39 ↑ Drumstick weight 2.6%–13.3% Al‐Hassani et al.
chickens (drinking water) RH 39–73 (2014)
Lohmann, unsexed broiler 0.06–0.12 T 25.7–32.9 ↑ Carcass yield 4.6% and breast Ratriyanto et al.
chickens yield 6.9% (2014a)
↓ Abdominal fat 16.5%
Cobb ×Hubbard, unsexed 0.05–0.10 T 28–36 No effects on carcass traits Kpodo (2015)
broiler chickens
Inhas, unsexed broiler 0.10–0.20 T 26; RH 66.2 (T 39.5–41 ↑ Carcass weight 22.6%–34.8%, Nofal et al. (2015)
chickens for 5 hr in 5 days) dressing percentage 14.0%–17.4%,
thigh percentage 16.0%–29.9%,
breast percentage 19.5%–31.7%,
and giblet percentage
11.7%–11.9%
Cobb 400, broiler chickens 0.13–0.20 T 28–35 ↑ Carcass yield 0.8%–2.9% Singh et al. (2015)
Broiler chickens 0.10–0.20 T 25.4–35.8 ↑ Dressing percentage Chand et al. (2017)
RH 52–87 1.76%–5.66%
No effects on abdominal fat pad

Note. T: temperature; RH: relative humidity; ↑: increase (p < 0.05); ↓: decrease (p < 0.05).

 |
1638       RATRIYANTO and MOSENTHIN

3 |  TH E E FFEC T O F B E TA I N E O N TH E The involvement of betaine in the lipid and protein metabolism is
PE R FO R M A N C E O F M E AT‐T Y PE P O U LTRY related to its methyl group donor properties (Attia et al., 2005; Eklund
et al., 2005; Hassan et al., 2005). Due to the enhancement in carcass
The detrimental effects of high environmental temperature on poultry lean and reduction in carcass fat content, betaine is often referred to as
production have been well documented (Chand et al., 2017; Farooqi et a “carcass modifier.” The mode of action of betaine as a carcass modi‐
al., 2005; Khan et al., 2012). Dietary supplementation of betaine rang‐ fier has been described previously (Eklund et al., 2005; Metzler‐Zebeli,
ing from 0.05% to 0.20% under high ambient temperature affects the Eklund, & Mosenthin, 2009; Ratriyanto et al., 2009), and it appears
performance and carcass characteristics of broiler chickens, turkeys to be related to an augmentation in the availability of methionine and
and meat‐type ducks, although the effects are variable (e.g., Al‐Shukri, cysteine for protein deposition, thereby contributing to a leaner car‐
Kaab, & Abdulwahab, 2012; Amerah, Gimenez‐Rico, & Ravindran, cass (Eklund et al., 2005). The improvement in the utilization of amino
2013; Park & Kim, 2017; Singh, Ghosh, Creswell, & Haldar, 2015). acids for protein synthesis would leave fewer amino acids for deamina‐
Effects of betaine supplementation on performance in meat‐type tion and, eventually, for the synthesis of adipose tissue (Wallis, 1999).
birds kept under high ambient temperature are presented in Table 1. Betaine can reduce the protein turnover rate, resulting in higher N re‐
Following betaine supplementation, several studies on meat‐type tention; this, in turn, has a positive effect on carcass leanness (Eklund
poultry have shown an enhancement in feed intake up to 9.8% (e.g., Al‐ et al., 2005). Furthermore, the effects of betaine on body fat may also
Shukri et al., 2012; Khattak et al., 2012). Moreover, body weight gain be related to its lipotropic activity. Betaine donates methyl groups to
increased by up to 23.3% (e.g., Nofal, Galal, Mousa, Yassein, & Bealsh, the synthesis of lecithin, which facilitates the transport of fat through‐
2015; Park & Kim, 2017), and feed conversion improved by up to 24.2% out the body (Saunderson & Mackinlay, 1990). Betaine also increases
due to betaine supplementation (e.g., Chand et al., 2017; Singh et al., the availability of choline for the synthesis of very‐low‐density lipo‐
2015). Khattak et al. (2012) observed that dietary supplementation of protein, which prevents fat deposition in the liver and increases the
0.12% betaine decreased feed intake in broiler chickens kept under fat removal from the liver (Hassan et al., 2005; Yao & Vance, 1989).
temperatures of up to 40°C, but the feed efficiency was enhanced, Moreover, betaine is associated with an improvement in the synthesis
resulting in higher body weight. Any improvement in the performance of methylated substances, such as carnitine and creatine, in the liver
of poultry raised under a hot environment indicates that betaine may and muscles (Zhan, Li, Xu, & Zhao, 2006). Carnitine transports the
assist poultry in alleviating heat stress (Ratriyanto et al., 2009). long‐chain fatty acids through the internal membrane of mitochon‐
Kpodo (2015) found higher levels of betaine in intestinal, liver dria, where fatty acid oxidation takes place (Wang, Xu, & Feng, 2004).
and plasma contents of broilers due to supplementation of 0.05%– In addition, betaine improves the antioxidant defences and decreases
0.10% betaine. In contrast, Konca, Kirkpinar, Mert, and Yaylak lipid peroxidation, resulting in the improved quality of broiler meat
(2008) reported that additional 0.10%–0.20% betaine in broiler (Alirezaei, Gheisari, Ranjbar, & Hajibemani, 2012).
diets had no beneficial effects under summer heat conditions. They
observed a decrease in weight gain in broiler chickens due to beta‐
ine supplementation, although the feed intake and feed conversion 4 | TH E E FFEC T S O F B E TA I N E O N TH E
were not affected. In their experiment (Konca et al., 2008), the diets PE R FO R M A N C E O F L AY E R S A N D B R E E D E R S
contained adequate levels of methionine and choline, and betaine
was supplemented at up to 0.20%, which was higher than the level in The effects of betaine on laying performance under high ambient
most other experiments. Betaine is an N‐containing substance that temperature are presented in Table 3. Dietary supplementation of
requires energy to be excreted (Eklund et al., 2005). Consequently, 0.05%–0.20% betaine under high ambient temperature increases
excessive betaine in the diet may cause energy loss and reduce its feed intake in breeders, laying hens, quails and ducks by up to 14.1%,
efficacy, as reflected in the lower weight gain in as observed by which is associated with an increase in egg production up to 23.6%
Konca et al. (2008). (e.g., Awad, Ibrahim, Fahim, & Beshara, 2014; Haryadi, Ratriyanto,
Different studies have shown considerable changes in the car‐ Indreswari, & Nuhriawangsa, 2015). Moreover, egg weight and egg
cass composition of poultry due to dietary betaine supplementa‐ mass have been improved by up to 17.5% (e.g., Attia et al., 2011;
tion under a high ambient temperature (Table 2), by increasing the Ratriyanto, Indreswari, & Nuhriawangsa, 2017), while feed conver‐
carcass weight, breast yield and breast–muscle ratio, in association sion improves by up to 12.6% (e.g., Attia et al., 2016; Ratriyanto,
with a reduction in abdominal fat deposition (e.g., Al‐Hassani, Al‐ Indreswari, Nuhriawangsa, & Haryanti, 2015).
Rubaye, Zangana, & Hanash, 2014; Amerah et al., 2013; Ratriyanto, The improvement in laying performance can be attributed to aug‐
Indreswari, & Sunarto, 2014a). Observation on broiler chickens mented oestrogen and progesterone levels in the blood (Attia et al.,
revealed that dietary 0.06%–0.20% betaine increases the carcass 2016). These hormones are involved in the regulation of the ovula‐
weight up to 34.8% and breast yield up to 31.7% (Nofal et al., 2015; tion rate and oviduct development (Etches, 1996). Attia et al. (2016)
Ratriyanto et al., 2014a). Moreover, supplementation of 0.12% beta‐ observed an increase in ovary and oviduct weight, as well as oviduct
ine reduced abdominal fat weight of up to 27.5% (Nofal et al, 2015), length, associated with an increase in large follicle weight due to sup‐
associated with a reduction in blood cholesterol and low‐density li‐ plementation of 0.10% betaine in laying hens, which is in favour of
poprotein levels (Ratriyanto et al., 2014a). higher egg production capacity. Moreover, Ratriyanto et al. (2015)
RATRIYANTO and MOSENTHIN |
      1639

TA B L E 3   Effects of betaine in layers and breeders reared under heat stress

Temperature (ºC) and

Strain/species Betaine level (%) Humidity (%) Betaine effects References

Laying hens 0.05–0.20 Heat stress ↓ Feed conversion 5.1%–10.5% Ryu, Cho, Shin, and
↑ Eggshell breaking strength 12.3%–16.7% Ryu (2002)
↑ Liver betaine 11.5%–74.6%
↓ Ileal digesta osmolality (numerical data not
available)
↑ Yolk colour score 3.5%–8.7%
Mandarah, breeder 0.10 T 22–24 ↑ Feed intake 5.0%, egg production 11.8%, egg Attia et al. (2011)
T 38, for 4 hr daily weight 5.7% and egg mass 17.5%
↑ Egg‐specific gravity 1.4%, shell percentage
6.7% and shell thickness 8.3%, albumen dry
matter 14.8% and yolk dry matter 10.1% and
Haugh unit 7.3%
↑ Fertility 20.3%
↓ Feed conversion 11.1%, albumen weight 2.6%
Matrouh, male and 0.10 T 23.6–34.7 Female: Ezzat et al. (2011)
female laying RH 31.8–80.7 ↑ Egg production 7.8% and egg mass 8.2%, shell
chickens thickness 5.6%, Haugh unit 2.1% and shell
percentage 3.7%
↓ Feed conversion 7.9%
Male:
↑ Sperm motility 6.7%
↓ Dead spermatozoa 21.0%
Label, laying hens 0.07–0.15 T 26 ↑ Egg production 16.3%–19.7% Gudev et al. (2011)
Domyati, male and 0.05–0.15 T 35.2–38.2 during Female: Awad et al. (2014)
female ducks midday ↑ Feed intake 3.3%–14.1%, egg production
RH 70–85 1.6%–14.0% and egg mass 3.0%–9.9%
↑ Hatchability 6.3%–31.9%
↓ Embryonic mortality 9.3%–47.6%
Male:
↑ Live sperms 1.5%–3.7%, seminal plasma
high‐density lipoprotein 18.2%–38.1%
↓ Abnormal sperms 7.5%–46.0%, seminal plasma
low‐density lipoprotein 4.1%–24.7%, triglycer‐
ide 7.3%–26.5% and total cholesterol
5.0%–27.1%
Laying quails 0.06–0.12 T 25.4–33.0 ↑ Feed intake 6.8%–12.4%, egg production Haryadi et al. (2015)
RH 55–75 23.5%–23.6% and protein efficiency ratio
15.8%–18.4%
↓ Feed conversion 9.8%–11.4%
Laying quails 0.12 T 25.4–33.0 ↑ Feed intake 7.1%, egg production 14.5%, egg Ratriyanto et al.
RH 55–75 weight 3.8%, yolk weight 17.1% and protein (2015)
efficiency ratio 10.7%
↓ Feed conversion 10.3%
↓ Yolk index 5.7%
Mandarah, laying hens 0.10 T 22–24, RH 45–55 ↑ Feed intake 4.7%, egg production 8.3% and Attia et al. (2016)
T 38, RH 55–65 for egg mass 11.0%
4 hr in three ↓ Feed conversion 7.0%
successive days a ↑ Liver weight 8.6%, ovary weight 10.4%, large
week follicle weight 35.0%, and oviduct weight 30.4%
and oviduct length 14.2%
Laying quails 0.06–0.12 T 25.4–33.0 ↑ Feed intake 4.3%–6.7%, egg production Ratriyanto,
RH 55–75 10.8%–15.2% and egg weight 4.2%–6.5% Indreswari, and
↓ Feed conversion 9.5%–12.6% Nuhriawangsa
↑ Protein efficiency ratio 10.8%–14.7% and (2017)
energy efficiency ratio 10.9%–14.9%
↑ Yolk weight 8.4%–12.0%, albumen weight
6.7%–8.0% and shell weight 4.6%

Note. T: temperature; RH: relative humidity; ↑: increase (p < 0.05); ↓:decrease (p < 0.05).

 |
1640       RATRIYANTO and MOSENTHIN

and Ratriyanto, Indreswari, and Nuhriawangsa (2017) reported an luminal content of the intestine is hyperosmotic in relation to blood
increase in protein and/or energy efficiency ratio in quails, indicating plasma (Eklund et al., 2005). Moreover, the process of nutrient di‐
improvement in the protein and energy utilization for egg production. gestion and absorption requires osmolytic protection mechanisms,
Accordingly, an improvement in egg quality was observed fol‐ since intestinal cells mediate the exchange of water, small solutes
lowing betaine supplementation under high ambient temperature. like ions, nutrients and macromolecules between the plasma and in‐
Inclusion of 0.10% betaine in the diet for breeding and laying hens testinal fluid (Eklund et al., 2005; Ratriyanto et al., 2009). Osmotic
improved egg‐specific gravity, shell weight and thickness, pointing protection maintains the water balance and intestinal cell volume,
towards an improvement in mineral availability and utilization (Attia thereby facilitating the secretion of digestive enzymes (Eklund
et al., 2011; Ezzat, Shoeib, Mousa, Bealish, & Ibrahiem, 2011). In sup‐ et al., 2005). Betaine is an important compatible osmolyte for the
port of these findings, dietary 0.06%–0.21% betaine increased crude control of the osmotic pressure inside the intestinal epithelial cells
ash digestibility, indicating a better mineral utilization, as observed by and supports intestinal microbes in encountering osmotic variation
Ratriyanto, Indreswari, Dewanti, and Sofyan (2012) and Ratriyanto, along the digestive tract (Eklund et al., 2005; Ratriyanto et al., 2009).
Indreswari, and Nuhriawangsa (2017). Furthermore, supplementa‐ For instance, betaine stabilizes the mucosal structure of chickens
tion of 0.10% betaine has been shown to improve the albumen and by decreasing the crypt: villus ratio (Kettunen, Tiihonen, Peuranen,
yolk weight and Haugh unit in chickens (Attia et al., 2011; Ezzat et Saarinen, & Remus, 2001; Ratriyanto, Indreswari, & Sunarto, 2014b).
al., 2011). According to Ratriyanto, Indreswari, and Nuhriawangsa Furthermore, Ratriyanto et al. (2014b) observed that supplementa‐
(2017), supplementation of 0.06%–0.12% betaine enhanced the egg tion of 0.7%–0.14% betaine increased the jejunum, ileum and total
weight in quails, in association with an improvement in the yolk and small intestine length of broiler chickens kept under high ambient
albumen weight in birds kept under natural tropical conditions, which temperature in the tropics. It is well known that the process of nutri‐
can be attributed to the involvement of betaine in protein and energy ent digestion and absorption depends on an intact gut epithelium;
metabolism (Ratriyanto et al., 2009), resulting in improved synthesis thus, betaine may positively affect nutrient digestibility (Ratriyanto
of the egg yolk and albumen precursor. Other observation revealed et al., 2009).
that addition of 0.14% betaine increased fat deposition in the yolk The effect of betaine on nutrient digestibility in poultry kept
(Ratriyanto, Indreswari, Dewanti, & Wahyuningsih, 2018). It appears under high ambient temperature is presented in Table 4. Following
that better egg quality is associated with changes in the blood profile, dietary betaine supplementation ranging between 0.05% and 0.21%
as indicated by an increase in lipase activity, high‐density lipoprotein to poultry kept under high environmental temperature conditions,
(Awad et al., 2014), total protein and globulin (Ezzat et al., 2011) as several studies have revealed improvements in the digestibility of
well as a decline in low‐density lipoprotein, triglycerides and total dry matter or organic matter in broilers (Ratriyanto et al., 2014a,
cholesterol (Awad et al., 2014; Ezzat et al., 2011). 2014b), laying quails (Ratriyanto et al., 2012; Ratriyanto, Indreswari,
Betaine supplementation has also shown beneficial reproduction & Nuhriawangsa, 2017) and laying ducks (Awad et al., 2014) up to
effects in poultry under high ambient temperatures. For example, 11.5%. These improvements correspond to higher digestibility of
Attia et al. (2011) reported that supplementation of 0.10% betaine other nutrients. For instance, supplementation of 0.05%–0.15% be‐
increased fertility in chickens, associated with the enhancement of taine enhanced crude protein digestibility by up to 11.4% in broilers
semen quality, as indicated by an increase in the viability and motil‐ (Ratriyanto et al., 2014a), laying hens (Ezzat et al., 2011) and laying
ity of spermatozoa, as well as a decrease in abnormal spermatozoa ducks (Awad et al., 2014) kept under high ambient temperature or
(Awad et al., 2014; Ezzat et al., 2011). There was also an improvement challenged with heat stress. The higher digestibility of crude protein
in the hatchability (Awad et al., 2014) and weight of 1‐day‐old chicks in poultry following betaine supplementation may result from the
due to betaine supplementation (Attia et al., 2011). The improve‐ osmotic support of intestinal cells (Eklund et al., 2005; Ratriyanto
ment in hatchability traits can be attributed to an indirect role of et al., 2009).
betaine through increasing growth hormone secretion and decreas‐ Supplementation of 0.05%–0.15% betaine increases crude fibre
ing insulin‐like growth factor binding protein‐1 (IGFBP‐1) secretion digestibility in broiler chickens, laying ducks and laying quails by up
by decreasing catabolic functions, which is reflected in the improve‐ to 49.4% (Awad et al., 2014; Ratriyanto et al., 2014a; Ratriyanto,
ment in chicks’ embryo growth and their immunity under heat stress Indreswari, & Nuhriawangsa, 2017). Since poultry intestines lack
(Jones & Clemmons, 1995). In addition, betaine may increase the cy‐ fibre‐degrading enzymes, improvements in crude fibre digestibility
toplasmic volume and free water content in the cells during osmotic point towards enhanced microbial fermentation of dietary fibre, as
disturbance and thus permit cell proliferation (Csonka, 1989). suggested by Ratriyanto et al. (2014a), Ratriyanto et al. (2009). In
support of these findings, betaine increased the number of Gram‐
positive bacteria, such as Enterococcus, in the crop of broiler chickens
5 |  TH E E FFEC T S O F B E TA I N E O N (Kettunen et al., 1999). Furthermore, a higher microbial fermenta‐
N U TR I E NT D I G E S TI B I LIT Y tion activity due to supplementation of 0.07%–0.13% betaine cor‐
responds to a higher incidence of microbial fermentation products
It is generally accepted that intestinal cells and intestinal microbes such as short‐chain fatty acids in ileal and caecal contents of broiler
encounter osmotic changes along the digestive tract, since the chickens and meat ducks (Kettunen et al., 1999; Park & Kim, 2017).
RATRIYANTO and MOSENTHIN |
      1641

TA B L E 4   Effects of betaine on nutrient digestibility in poultry reared under heat stress

Temperature (ºC) and Humidity

Strain/species Betaine level (%) (%) Betaine effects References

El‐Salam, unsexed slow 0.05–0.10 T 28; RH 55 ↑ Crude protein 1.7%–3.0% Attia et al. (2009)
growth chickens (T 38; RH 49 for 4 hr in 3
successive days per week)
Laying hens 0.10 T 23.6–34.7 ↑ Crude protein 1.0% and ether Ezzat et al. (2011)
RH 31.8–80.7 extract 1.5%
Laying quails 0.07–0.21 T 24.9–34.9 ↑ Dry matter 1.4%–3.8%, ether Ratriyanto et al.
RH 55–75 extract 2.4%–9.4% and crude (2012)
ash 14.4%–20.5%
Laying ducks 0.05–0.15 T 35.2–38.2 during midday ↑ Crude protein 0.3%–4.3%, Awad et al. (2014)
RH 70–85 crude fibre 5.3%–49.4%,
nitrogen‐free extract 2.4%–
3.5%, and crude ash 4.7%–14.1%
Broiler chickens 0.07–0.14 T 25.7–32.9 ↑ Dry matter 3.6%, crude protein Ratriyanto et al.
3.1%, and crude fibre 10.6% (2014a)
Broiler chickens 0.07–0.14 T 25.7–32.9 ↑ Organic matter 11.5% Ratriyanto et al.
(2014b)
Laying hens 0.10 T 22–24, RH 45–55 ↑ Crude protein 3.3% Attia et al. (2016)
T 38, RH 55–65 for 4 hr in three
successive days a week
Laying quails 0.06–0.12 T 25.4–33.0 ↑ Dry matter 5.6%–8.5%, crude Ratriyanto,
RH 55–75 protein 4.3%–11.4%, crude fibre Indreswari, and
14.9%–21.6%, and crude ash Nuhriawangsa
11.1%–25.6% (2017)

Note. T: temperature; RH: relative humidity; ↑: increase (p < 0.05); ↓: decrease (p < 0.05).

Eklund et al. (2005) suggested that intestinal cells and intestinal is associated with an increase in bile acids secretion. Furthermore,
microbes require compatible osmolytes, since they are exposed to improvement in ether extract digestibility has been associated
different osmotic gradients in the digestive tract. Hence, supple‐ with supplemental glycine in the diet (Han & Thacker, 2011).
mentation with betaine may improve microbial fermentation of fibre Betaine improves the availability of glycine (Eklund et al., 2005),
due to its osmoprotective properties. which conjugates with bile acids synthesized in the liver to form
The enhancement in fibre digestibility due to supplementation of bile salts (Powell, Bidner, & Southern, 2009). In addition, higher
0.05%–0.15% betaine corresponds to higher crude ash digestibility levels of short‐chain fatty acids along the intestinal tract may im‐
up to 25.6% in laying quails (Ratriyanto, Indreswari, & Nuhriawangsa, prove the absorption capacity of the intestinal epithelium, leading
2017) and laying ducks (Awad et al., 2014). According to Wenk, to an improved digestive capacity (Butzner et al., 1994). It has to
Kölliker, and Messikommer (1993), the fibre fraction holds nutri‐ be considered, however, that microbial activity is associated with
ents that may be released during fibre degradation. Furthermore, deconjugation of bile acids, which are required for lipid digestion,
short‐chain fatty acids generated from microbial fibre fermentation thereby exerting detrimental effects on ether extract digestibility
promote nutrient absorption, leading to an improvement in mineral (Jönsson, Midtvedt, Norman, & Midtvedt, 1995). This observation
absorption (Butzner, Meddings, & Dalal, 1994) and reduction in the is in line with the results of different studies, where no effect of
endogenous secretion of minerals (Krishnan, Ramakrishna, & Binder, betaine on ether extract digestibility was observed (e.g., Attia et al.,
1999). The improvement in mineral absorption, as indicated by the 2016; Ratriyanto et al., 2014a).
enhanced crude ash digestibility, is supported by previous findings,
in which betaine lowered the osmolality of the digesta in broiler
chickens (Hamidi, Jahanian, & Pourreza, 2010; Klasing et al., 2002) 6 | TH E E FFEC T S O F B E TA I N E O N
and laying hens (Ryu, Park, Shin, Na, & Ryu, 2003). PH YS I O LO G Y A N D I M M U N E R E S P O N S E S
Reports on the effect of betaine supplementation on ether
extract digestibility have shown variable results. In laying hens The effects of betaine on the behaviour, physiology and immune
and laying quails, supplementation of 0.10%–0.21% betaine im‐ response of poultry kept under high ambient temperature are pre‐
proved ether extract digestibility by up to 9.4% (Ezzat et al., 2011; sented in Table 5. High environmental temperature causing heat
Ratriyanto et al., 2012). Rørvik, Steien, Saltkjelsvik, and Thomassen stress in poultry leads to stressful behavioural responses, such as
(2000) suggest that the improvement in ether extract digestibility panting, an elevated respiratory rate and, consequently, dehydration
 |
1642       RATRIYANTO and MOSENTHIN

TA B L E 5   Effects of betaine on behaviour, physiology and immune responses in poultry reared under heat stress

Temperature (ºC) and

Strain/species Betaine level (%) Humidity (%) Betaine effects References

Cobb×Cobb, male 5–10 T 36 for 4 hr daily (day ↓ Rectal temperature 1.0%–1.9% Zulkifli et al. (2004)
broiler chickens 36–41) No effects on Newcastle disease antibody titre
Broiler chickens 0.10 T 34.6 ↑ Newcastle disease antibody titre 1.2%–8.6% Farooqi et al.
(2005)
Male broiler 0.1–0.2 T 28.1–33.1 ↓ Serum alanine aminotransferase 35.6%–42.3% Konca et al. (2008)
chickens RH 37.0–50.3
El‐Salam, unsexed 0.05–0.10 T 28; RH 55 (T 38; RH ↓ Rectal temperature 1.9%–3.0%, respiration rate Attia et al. (2009)
slow growth 49 for 4 hr in 3 10.7%–18.4%
chickens successive days per ↑ Packed cell volume 3.8%–9.4%, haemoglobin 34.9%,
week) plasma glucose 2.0%–4.0%, serum total protein
4.0%–7.0% and serum calcium 1.2%–2.6%
↓ Blood pH 0.6%–0.9%
↓ Plasma triglyceride 2.1%–5.5%
↑ Immune response to SRBC 7.1%–39.4%
Breeder 0.10 T 22–24 ↑ Erythrocyte 44.9%, lymphocyte 11.4%, phagocytic Attia et al. (2011)
T 38, for 4 hr daily activity 19.8% and phagocytic index 46.0%
↓ Eosinophil 27.4%, heterophil/lymphocyte ratio
10.1% and blood pH 2.8%
Laying hens 0.10 T 23.6–34.7 No effects on blood profile and antibody titre against Ezzat et al. (2011)
RH 31.8–80.7 SRBC
↑ Serum total protein 17.8% and globulin 24.5%
↓ Serum glucose 9.8%, high‐density lipoprotein
14.5%, cholesterol 5.5% and triglyceride 10.1%
Laying hens 0.07–0.15 T 26 ↑ Lymphocyte (numerical data not available) Gudev et al. (2011)
↓ Heterophil, haematocrit, erythrocyte and corticos‐
terone (numerical data not available)
Cobb 400, male 0.08 T 25–33 ↓ Liver weight 6.7% Rao et al. (2011)
broiler chickens ↑ Serum total protein 8.9% and globulin 13.2%
↓ Serum cholesterol 6.3%
No effects on Newcastle disease antibody titre
Broiler chickens 0.05–0.10 T 20; RH 80–100 (T No effects on electrolyte retention and blood profile Sayed and Downing
(drinking water) 32 for 9 hr daily) (2011)
Unsexed broiler 0.12 T 38–40 ↓ Mortality rate 93.3% Khattak et al.
chickens RH 40–93 ↓ Serum Na 25.0% and K 13.3% (2012)
↓ Leucocyte counts 53.1%
Laying ducks 0.05–0.15 T 35.2–38.2 during ↑ Erythrocyte 17.4%–37.8% Awad et al. (2014)
midday ↓ Heterophils 18.8%–33.7%, heterophil/lymphocyte
RH 70–85 ratio 25.5%–43.1%
↑ Serum high‐density lipoprotein 36.3%–43.1%
↓ Serum low‐density lipoprotein 17.8%–34.0% and
total cholesterol 30.2%–43.8%
Lohmann, unsexed 0.06–0.12 T 25.7–32.9 ↓ Blood cholesterol 12.7% and low‐density lipopro‐ Ratriyanto et al.
broiler chickens tein 19.9% (2014a)
Unsexed broiler 0.05–0.10 T 28–36 ↑ Intestinal betaine 8.6%–44.5%, liver betaine Kpodo (2015)
chickens 60.8%–162.8% and plasma betaine 67.9%–121.3%
↓ Glycerophosphocholine plasma 38.0%–57.6%
No effects on lymphoid organ weights and corticos‐
terone levels

(Continues)
RATRIYANTO and MOSENTHIN |
      1643

TA B L E 5   (Continued)

Temperature (ºC) and

Strain/species Betaine level (%) Humidity (%) Betaine effects References

Unsexed broiler 0.10–0.20 T 26; RH 66.2 (T ↓ Mortality rate 42.8%–42.9% Nofal et al. (2015)
chickens 39.5–41 for 5 hr in ↓ Rectal temperature 2.5%–3.3%, respiration rate
5 days) 20.4%–26.0%, blood pH 1.7%–2.6%
↑ Serum triiodothyronine 48.0%–69.1%
↓ Heterophil 34.1%, heterophil: lymphocyte ratio
40.8%
↑ Lymphocyte 11.36%
Broiler chickens 0.13–0.20 T 28–35 ↓ Rectal temperature and respiration rate (numerical Singh et al. (2015)
data not available)
↑ Serum CO2 25.2%–50.2%, thyrotropic stimulating
hormone 126.6%–174.6%, triiodothyronine
26.9%–43.4%, corticosterone 30.4%–30.6%
↓ Serum triglyceride 4.2%–31.6%
Ross, male broiler 0.10 T 33.0 No effects on serum antibody Akhavan‐Salamat
chickens No effects on leucocyte profile and Ghasemi
↓ Mortality rate 41.6% (2016)
↑ Serum glutathione peroxidase 15.9%
and superoxide dismutase 15.1%
Unsexed broiler 0.04–0.055 T 24.5–38.5 ↓ Body temperature 0.9%–1.6% Al‐Hassani and
chickens (drinking water) Al‐Shukri (2016)
Laying hens 0.10 T 22–24; RH 45–55 ↑ Survival rate 1.5% Attia et al. (2016)
T 38, RH 55–65 for ↑ Blood triiodothyronine 28.6% and thyroxine 28.8%
4 hr in 3 successive ↑ Thyroid gland weight 22.8% and spleen weight
days a week 15.9%
↑ Blood glucose 5.8%, oestrogen 16.5% and
progesterone 48.0%
Ross broilers 0.05 (drinking T 28.3–35.7 ↓ Tonic immobility 23.7% Egbuniwe et al.
water) RH 69–93 ↑ Glutathione peroxidase 10.6% (2016)
Meat ducks 0.07–0.13 T 22–26; RH 50 ↑ Red blood cell counts 12.2%–13.5%, haematocrit Park and Kim
T 33–43; RH 70 for 34.9%–35.8%, haemoglobin 24.6%–25.2%, corpuscu‐ (2017)
5 hr daily (day 22–42) lar volume 21.9%–25.5%, corpuscular haemoglobin
concentration 14.4%–15.8%, red cell distribution
width 27.4%–30.1%, platelet count 26.3%–30.2%,
platelet volume 27.5%–31.2%
↓ Blood pH 6.9%–7.5%
↑ Na+ 14.8%–18.0%, K+ 20.0%–23.5%,
Cl− 14.1%–17.6%
↑ Blood partial pressure of oxygen 30.2%–37.7% and
carbon dioxide 47.4%–50.2%, hydrogen carbonate
concentration 37.3%–42.7% and carbon dioxide
concentration 39.4%–45.5%
↑ Caecum acetic acid 90.1%–101.1%, propionic acid
50.1%–56.6% and total short‐chain fatty acids
43.6%–49.6%
↓ Caecum butyric acid 33.2%–38.1% and valeric acid
42.8%–55.1%
Broiler chickens 0.10–0.20 T 25.4–35.8 ↑ Lymphocyte 16.60%–22.59% Chand et al. (2017)
RH 52–87 ↑ Heterophil/lymphocyte ratio 4.89%–20.15%
↑ ND antibody titre 65.52%–103.48%

Note. T: temperature; RH: relative humidity; ↑: increase (p < 0.05); ↓: decrease (p < 0.05); SRBC: sheep red blood cells.

(Ayo, Egbuniwe, Kawu, & Sinkalu, 2014). It has been shown that hens studies revealed that dietary betaine supplementation ranged be‐
reared under heat stress and fed a diet without betaine supplemen‐ tween 0.10% and 0.20% alleviated heat stress, as indicated by a de‐
tation have lower survival rates, and postmortem investigations cline in the mortality rate (Akhavan‐Salamat & Ghasemi, 2016; Attia
showed that hens exhibited signs of heat stress, such as emphysema et al., 2016; Nofal et al., 2015), which associated with the role of be‐
and lung, liver and ovary haemorrhage (Attia et al., 2016). Several taine in stabilizing the physiological status and increasing immunity
 |
1644       RATRIYANTO and MOSENTHIN

indices under high environmental temperatures (Khattak et al., (2012) reported that supplementation of 0.12% betaine decreased
2012; Singh et al., 2015). serum Na and K ions in broilers exposed to heat stress, which could
Betaine addition ranging from 0.04% to 0.20% has been shown be due to the fact that K ions shift between muscle and extracellular
to decrease the rectal temperature and respiration rates in broilers, fluid during heat stress to maintain the cellular atmospheric pres‐
indicating a sequestering effect of betaine on the metabolic rates sure (Keskin & Durgun, 1997). Alternatively, it is suggested that K
of thermally stressed birds (Al‐Hassani & Al‐Shukri, 2016; Nofal et excretion from the kidney or uptake by the erythrocytes and skin is
al., 2015; Singh et al., 2015). Betaine plays an important role in alle‐ increased (Smith & Teeter, 1987).
viating the body temperature of heat‐stressed chickens through its Respiratory alkalosis is characterized by the excessive removal
osmotic functions, by decreasing dehydration and increasing fluid of CO2 through the panting process (Borges et al., 2004; Keskin
retention in the body (Zulkifli, Mysahra, & Jin, 2004). Increasing & Durgun, 1997). The CO2 in blood is a source of H2CO3, which is
water retention during heat stress improves the thermal dissipation required as a carbonate ion source for eggshell formation (Etches,
capacity via the peripheral blood and evaporation, assisting the birds 1996). Serum CO2 is a measure of birds’ metabolic activities, and its
to control their body temperature (Dai, Bessei, & Nasir, 2009). higher concentration in the blood suggests greater metabolic activ‐
Rapid shallow breathing caused by heat stress induces respi‐ ity (Singh et al., 2015). Furthermore, body temperature has shown
ratory alkalosis, as indicated by the increasing loss of electrolytes a negative correlation with blood CO2 levels (Pech‐Waffenschmidt,
in urine, resulting in elevated blood pH (Borges, Fischer da Silva, Bogin, Avidar, & Horst, 1995). It appears that betaine decreases the
Majorka, Hooge, & Cummings, 2004; Khattak et al., 2012). It is gen‐ respiration rate, which is correlated with a higher serum CO2 level
erally accepted that blood pH should be close to the physiological (Singh et al., 2015). Park and Kim (2017) suggested that betaine sup‐
limits of 7.35–7.45 for the maintenance of protein structure and plementation relieves heat stress by maintaining constant blood gas
function, which is an essential condition for the normal progression concentrations, as indicated by an enhancement in the concentra‐
of metabolic events (Khattak et al., 2012). Normally, the blood pH is tions of oxygen, hydrogen carbonate and carbon dioxide in the blood
controlled by the lungs and kidneys, and this control involves various of meat ducks exposed to heat stress.
buffer systems that prevent rapid changes in pH. Furthermore, the High environmental temperature has shown to enhance oxi‐
disturbances in birds’ acid–base balance due to heat stress causes dative stress (Rehman, Chand, & Khan, 2017). Poultry subjected
disruptions in the blood flow patterns, body water distribution, and to heat stress exhibits reduced welfare and intensified fear re‐
mineral and ionic balance (Ahmad et al., 2009; Ahmad, Sarwar, Nisa, sponses, as evidenced by the increased duration of tonic immobility
Haq, & Hasan, 2005). The rise in body temperature during heat (Egbuniwe, Ayo, Kawu, & Mohammed, 2016). Tonic immobility has
stress decreases the Na+ level in the blood and increases the loss been proposed as index of fearfulness, and its duration indicates the
of K+ in urine, while the decrease in the Cl– level may be due to the level of stress in birds (Ghareeb, Awad, Sid‐Ahmed, & Böhm, 2014).
–
elevation of Cl required in body fluids to compensate for the acidic Administration of 0.05% betaine to drinking water decreased the
reaction and stabilize the blood pH (Borges et al., 2004). Dietary be‐ tonic immobility in broiler chickens, which indicates that betaine de‐
taine supplementation has been shown to decrease the blood pH creased the fear response; this suggests that betaine may further
and increase Na+, K+ and Cl– levels in broiler chickens, laying hens potentiate the reduction of the adverse effects of heat stress on
and meat ducks exposed to heat stress (Attia et al., 2009; Nofal et al., the fear centre (amygdala) of the avian brain (Egbuniwe et al., 2016).
2015; Park & Kim, 2017). These findings suggest that betaine can al‐ The positive effects of betaine supplementation on alleviating the
leviate heat stress by maintaining constant blood electrolyte levels, fear response in heat‐stressed broiler may be associated with its
thereby stabilizing the osmotic pressure (Nofal et al., 2015; Park & ability to improve the birds’ antioxidant defences against heat stress
Kim, 2017). A stable osmotic pressure is important, since imbalances (Akhavan‐Salamat & Ghasemi, 2016; Egbuniwe et al., 2016), as beta‐
in blood electrolytes can decrease poultry’s feed intake and produc‐ ine has been demonstrated to improve the activity of the superoxide
tivity (Borges et al., 2004). dismutase (SOD) and glutathione peroxide (GPx) enzymes in heat‐
Supplementation with 0.05%–0.10% betaine in drinking water stressed broilers (Akhavan‐Salamat & Ghasemi, 2016; Alirezaei et al.,
increases betaine concentration in the intestinal tissues, leading to 2012; Egbuniwe et al., 2016). Betaine also improves the availabil‐
an enhanced cellular capability to maintain intracellular water and ity of glycine and cysteine (Eklund et al., 2005), which are used for
cope with osmotic stress, without the need to increase the cellular synthesis of glutathione by the sequential addition of cysteine and
water uptake (Sayed & Downing, 2011). For instance, betaine has glycine to glutamate (Forman, Zhang, & Rinna, 2009). Glutathione
been reported to inhibit the activity of Ca and Na/K ion pumps by is largely known to protect cells from oxidative damage (Forman et
73% and 64% respectively (Moeckel, Shadman, Fogel, & Sadrzadeh, al., 2009). It is well known that betaine enhances protein synthesis
2002). Thus, it can be assumed that the accumulation of betaine in (Apicella et al., 2013). Protein is used for several physiological activi‐
the intestinal tissues may control water movement by decreasing ties, including the synthesis and potentiation of the activities of anti‐
the activity of water pumps. According to Remus (2001), in the ab‐ oxidant enzymes, such as SOD and GPx (Egbuniwe et al., 2016). The
sence of osmolytes, such as betaine, approximately 30%–60% of the antioxidant activity of betaine may also be due to its ability to block
energy used in intestinal organs is related to the Na and K pump, the induction of mitochondrial lipid peroxidation (Ganesan, Rajesh,
which maintains the water balance in cells. In contrast, Khattak et al. Anandan, & Dhandapani, 2007).
RATRIYANTO and MOSENTHIN |
      1645

Betaine exerts its antioxidant effect by modulating heat‐shock supplementation of 0.10% betaine improves the immunity of birds
proteins (HSPs; Dangi et al., 2016). During thermal stress, cells during heat stress, as indicated by the improvement in serum anti‐
normally respond by synthesizing HSPs, which restore the func‐ body levels against Newcastle disease virus (Farooqi et al., 2005).
tionality of denatured proteins by refolding and preventing them This finding is in support of Alahgholi, Tabeidian, Toghyani, and
from aggregating (Metzler‐Zebeli et al., 2009), and they repair pro‐ Fosoul (2014), who observed that dietary 0.15% betaine supple‐
teins that have been damaged by reactive oxygen species (Cronje, mentation increased the bursa of fabricius weight and humoral im‐
2007). A study with broiler chickens revealed that exposure to mune response against a respiratory virus inactivated vaccine. The
heat stress increased the HSP‐70 density (Zulkifli, Al‐Aqil, Omar, improvement in immune response may have been due to sparing the
Sazili, & Rajion, 2009). The HSPs protect the intestinal mucosa effect of methionine with betaine (Attia et al., 2005), since the re‐
from damage due to heat stress by improving the SOD and GPx ac‐ duction in the concentration of dietary methionine affects immunity
tivities and inhibiting lipid peroxidation (Gu, Hao, & Wang, 2012). in chickens (Rao, Raju, Panda, Saharia, & Sunder, 2011).
Furthermore, betaine showed a dwindling effect on the expres‐ Heat stress impairs performance by elevating circulatory corti‐
sion of HSPs, suggesting another possible role of betaine in heat costeroids and decreasing thyroid activity, especially in adult birds,
stress alleviation (Dangi et al., 2016). Oliva, Bardag‐Gorce, Tillman, because the ability to dissipate heat decreases with age (Rosa et
and French (2011) also observed that betaine prevents the upreg‐ al., 2007). A high level of corticosteroids in the blood is one of the
ulation of HSP‐70 in vitro. Thus, the supplementation of betaine indicators of stress in poultry (Zulkifli et al., 2009). This hormone
enhanced the antioxidant defence in chickens and consequently may cause cell‐mediated and humoral immunity failure, as changes
improved their health and welfare. Moreover, if betaine is available in the concentration of this hormone affect the lymphoid tissue
for the cells before the prevalence of heat stress, it accumulates (Julian, 2000). A high ambient temperature stimulates the hypotha‐
in the cells and prevents the gene expression of HSP‐70, due to its lamic–pituitary–adrenal axis, leading to an increase in the secretion
own stabilizing effect on proteins (Sheikh‐Hamad, García‐Pérez, of corticosterone to assist birds in increasing their metabolism,
+
Ferraris, Peters, & Burg, 1994). Since the Na transporter for beta‐ which ensures the maintenance of homeostasis and recovery from
ine uptake is stimulated by extracellular hyperosmolarity, but not stress (Reddy, 2000). Reddy (2000) reported that corticosterone
by heat itself, betaine should be available to the cells before the stored in the adrenal cortex is released into the blood circulation
exposure to heat stress (Sheikh‐Hamad et al., 1994). Accordingly, when the body temperature increases due to exposure to a high
Metzler‐Zebeli et al. (2009) recommended administration of beta‐ ambient temperature. Moreover, Sahin, Ozbey, Onderci, Cikim, and
ine before and during the heat stress to efficiently prevent heat Aysondu (2002) reported that heat stress elevates plasma corti‐
stress in poultry. costerone concentration in quails parallel to the increases in serum
Heat stress depresses birds’ humoral immunity and causes a glucose, uric acid and triglyceride concentration due to a greater
reduction in antibody synthesis (Rehman et al., 2017; Zulkifli et al., catabolic effect of adrenocorticotropic hormone. In laying hens
2004). This reduction has been ascribed to heat stress increasing reared under moderately high environmental temperature (circa
the inflammatory cytokines, which stimulate the hypothalamic pro‐ 27°C), supplementation of 0.07%–0.15% betaine reduced plasma
duction of corticotrophin‐releasing factor, and depressing T‐helper corticosterone (Gudev et al., 2011), which may be due to the posi‐
cytokines, which are important for antibody production (Mashaly et tive effect of betaine on nitric oxide production; this, in turn, may
al., 2004). Exposure to heat stress decreased the numbers of mono‐ inhibit the biosynthesis of glucocorticoid (Monau, Vargas, Lubo
cytes and lymphocytes (cell‐mediated immunity) but increased the Zhang, Myers, & Ducsay, 2010; Singh et al., 2015). In addition, nitric
number of heterophils and heterophil/lymphocyte ratio (Zulkifli et oxide is a potent vasodilator which attenuates pulmonary hyperten‐
al., 2004). Supplemental betaine has been shown to decrease the sion, also known as ascites syndrome (Khajali et al., 2011), and plays
heterophil percentage and to increase the lymphocyte percentage, a protective role by scavenging reactive oxygen species such as su‐
leading to a decrease in the heterophil/lymphocyte ratio (Attia et peroxide and hydrogen peroxide (Scott & Bolton, 2000). It appears
al., 2011; Awad et al., 2014; Gudev et al., 2011; Nofal et al., 2015). that dietary betaine reduces heat stress by decreasing the plasma
Furthermore, dietary betaine supplementation increases the mono‐ corticosterone level.
cyte, erythrocyte, haemoglobin and haematocrit counts (e.g., Nofal Many studies have revealed that heat stress also decreases the
et al., 2015; Park & Kim, 2017). These findings indicate that betaine thyroid’s activity (Rosa et al., 2007; Singh et al., 2015). The activity
maintains certain levels of haematological indicators during a heat of thyroid hormones declines at high ambient temperatures result‐
wave and suggest that betaine may contribute to methionine bio‐ ing in reduced performance of birds. Based on the relationship of
synthesis and osmotic pressure control (Attia et al., 2005; Klasing the thyroid secretion rate with chickens’ growth, it is suggested that
et al., 2002; Mahmoudnia & Madani, 2012). In contrast, Gudev et the poorer performance of birds was partly due to the decreased
al. (2011) observed a decrease in erythrocyte counts in laying hens triiodothyronine activity (Leung, Taylor, & van Iderstine, 1984).
raised under warm weather and high air–ammonia concentrations. Betaine supplementation elevated the thyroid activity in broilers
Supplemental 0.07%–0.15% betaine exerts its effect by increas‐ and layers, as indicated by enhancements in the serum levels of
ing the erythrocyte volume in association with the observed de‐ triiodothyronine and thyrotrophic stimulating hormone (Attia et al.,
cline in erythrocyte number. In addition, it has been found that 2016; Nofal et al., 2015; Singh et al., 2015). Accordingly, Attia et al.
 |
1646       RATRIYANTO and MOSENTHIN

(2016) observed an increase in thyroid gland weight upon betaine ORCID

supplementation in laying hens, indicating a higher thyroid activity.
Adi Ratriyanto  http://orcid.org/0000-0001-9656-9135
In addition, betaine supplementation increased serum levels of total
protein and globulin in laying hens, indicating an enhancement of
immunity resulting from improved feed conversion, absorption and
REFERENCES
utilization of nutrients (Rao et al., 2011).
Ahmad, T., Mushtaq, T., Khan, M. A., Babar, M. E., Yousaf, M., Hasan,
It has been found that dietary betaine supplementation increases
Z. U., & Kamran, Z. (2009). Influence of varying dietary electrolyte
the acetic, propionic and total short‐chain fatty acid concentrations balance on broiler performance under tropical summer conditions.
in the caecal content of meat ducks exposed to heat stress, although Journal of Animal Physiology and Animal Nutrition, 93(5), 613–621.
the butyric and valeric acid concentrations are lower (Park & Kim, https://doi.org/10.1111/j.1439-0396.2008.00840.x
Ahmad, T., Sarwar, M., Nisa, M., Haq, A., & Hasan, Z. (2005). Influence of
2017). It is well known that betaine supports microbial survival and
varying sources of dietary electrolytes on the performance of broil‐
growth in the gastrointestinal tract (Eklund et al., 2005; Ratriyanto ers reared in a high temperature environment. Animal Feed Science
et al., 2009). Thus, the modification of short‐chain fatty acid profiles and Technology, 120(3–4), 277–298. https://doi.org/10.1016/J.
in the ceca following betaine supplementation may be an important ANIFEEDSCI.2005.02.028
indicator of improved immune indices (Klasing et al., 2002), which Akbarian, A., Michiels, J., Degroote, J., Majdeddin, M., Golian, A., &
De Smet, S. (2016). Association between heat stress and ox‐
can alleviate heat stress by adjusting the gut ecosystem (Attia et al.,
idative stress in poultry; mitochondrial dysfunction and di‐
2016; Park & Kim, 2017). etary interventions with phytochemicals. Journal of Animal
Science and Biotechnology, 7(1), 37. https://doi.org/10.1186/
s40104-016-0097-5
7 |  CO N C LU S I O N S Akhavan‐Salamat, H., & Ghasemi, H. A. (2016). Alleviation of chronic
heat stress in broilers by dietary supplementation of betaine and
turmeric rhizome powder: Dynamics of performance, leukocyte
In recent decades, many studies have been performed to investigate profile, humoral immunity, and antioxidant status. Tropical Animal
the efficacy of betaine in poultry under exposure to heat stress. High Health and Production, 48(1), 181–188. https://doi.org/10.1007/
ambient temperatures are deleterious to productive performance in s11250-015-0941-1
Alahgholi, M., Tabeidian, S. A., Toghyani, M., & Fosoul, S. S. A. S. (2014).
poultry. Due to its zwitterionic structure, betaine has osmoprotec‐
Effect of betaine as an osmolyte on broiler chickens exposed to dif‐
tive properties, which counteract the performance losses during ferent levels of water salinity. Archiv Tierzucht, 57(1), 1–12. https://
heat stress. There is conclusive evidence that betaine exerts a range doi.org/10.7482/0003-9438-57-004
of beneficial effects on poultry production traits during exposure Al‐Hassani, D., Al‐Rubaye, H., Zangana, B., & Hanash, N. (2014). Efficacy
of betaine supplemented with diet and sex response in carcas com‐
to heat stress. Betaine can improve feed intake, weight gain, feed
ponents of broiler chicken (Ross) breed under heat stress conditions.
efficiency and carcass characteristics in meat birds exposed to heat Iraqi Journal of Agriculture, 19, 140–149.
stress. Moreover, in layers kept under high ambient temperature, Al‐Hassani, D. H., & Al‐Shukri, A. Y. (2016). Comparative efficacy of
betaine improves egg production, feed efficiency and egg qual‐ different supplements with drinking water used to alleviate body
ity traits. Furthermore, betaine stabilizes the intestinal cells and temperature of heat‐stressed broiler chickens. The Iraqi Journal of
Agricultural Science, 47(Special Issue), 12–18.
intestinal microbes against osmotic variations which, in turn, may
Alirezaei, M., Gheisari, H. R., Ranjbar, V. R., & Hajibemani, A. (2012).
enhance nutrient digestibility. Any improvements in performance Betaine: A promising antioxidant agent for enhancement of broiler
under heat exposure are correlated with corresponding improve‐ meat quality. British Poultry Science, 53(5), 699–707. https://doi.org/1
ments of physiological and immune indices. For example, betaine 0.1080/00071668.2012.728283
Al‐Shukri, A. Y., Kaab, H. T., & Abdulwahab, H. M. (2012). Effect of be‐
reduces body temperature and increases antibody production and
taine on some productive traits of turkey under heat stress. Kufa
thyroid activity. Therefore, dietary application of betaine has proven Journal for Veterinary and Medical Sciences, 3(2), 12–20.
to be an efficient tool as part of a strategy to counter the effects of Amerah, A. M., Gimenez‐Rico, R. D., & Ravindran, V. (2013). Effect of
heat stress in poultry production. To efficiently prevent heat stress, heat stress and betaine source on growth performance and car‐
cass characteristics of broiler chickens fed corn based diets. World’s
betaine should be supplemented before and during heat stress. In
Poultry Science Journal, 69(Suppl.), 1–3.
this regard, the efficacy of betaine is correlated with the level of Apicella, J. M., Lee, E. C., Bailey, B. L., Saenz, C., Anderson, J. M., Craig, S.
other methyl group donors in the diet, with increasing levels of be‐ A. S., Maresh, C. M. (2013). Betaine supplementation enhances an‐
taine reducing its efficacy. Furthermore, the aforementioned studies abolic endocrine and Akt signaling in response to acute bouts of ex‐
ercise. European Journal of Applied Physiology, 113, 793–802. https://
were conducted at different temperatures and dietary betaine lev‐
doi.org/10.1007/s00421-012-2492-8
els to illustrate the effects of betaine on different types of poultry. Attia, Y. A., Abdallah, A. A., Briekaa, M. A., El‐Hamid, A. E. E. A., & Abou‐
However, many studies did not consider the relative humidity. Heat Shehema, B. M. (2011). Effect of betaine with or without two antiox‐
stress comprises combined effects of high ambient temperature and idants on the performance of dual purpose breeding hens exposed
to heat stress. Journal of Agriculture and Environmental Science, 10(1),
high relative humidity. Therefore, in future studies, measurements
73–106.
of relative humidity or the temperature humidity index should be Attia, Y. A., Abd‐El‐Hamid, A. E. E., Abedalla, A. A., Berika, M. A., Al‐
included to assess the effects of these variables on the results Harthi, M. A., Kucuk, O., Abou‐Shehema, B. M. (2016). Laying perfor‐
obtained. mance, digestibility and plasma hormones in laying hens exposed to
RATRIYANTO and MOSENTHIN |
      1647

chronic heat stress as affected by betaine, vitamin C, and/or vitamin Dai, N. V., Bessei, W., & Nasir, Z. (2009). The effect of sodium chlo‐
E supplementation. SpringerPlus, 5(1), 1619. https://doi.org/10.1186/ ride supplementation in the drinking water on water and feed in‐
s40064-016-3304-0 take and egg quality of laying hens under cyclic heat stress. Archiv
Attia, Y. A., Hassan, R. A., & Qota, E. M. A. (2009). Recovery from ad‐ Geflügelkunde, 73(4), 217–226.
verse effects of heat stress on slow‐growing chicks in the tropics 1: Dangi, S. S., Dangi, S. K., Chouhan, V. S., Verma, M. R., Kumar, P., Singh, G.,
Effect of ascorbic acid and different levels of betaine. Tropical Animal & Sarkar, M. (2016). Modulatory effect of betaine on expression dy‐
Health and Production, 41(5), 807–818. https://doi.org/10.1007/ namics of HSPs during heat stress acclimation in goat (Capra hircus).
s11250-008-9256-9 Gene, 575(2), 543–550. https://doi.org/10.1016/j.gene.2015.09.031
Attia, Y. A., Hassan, R. A., Shehatta, M. H., & Abd El‐Hady, S. B. Egbuniwe, I. C., Ayo, J. O., Kawu, M. U., & Mohammed, A. (2016). Effects
(2005). Growth, carcass quality and serum constituents of slow of betaine and ascorbic acid on tonic immobility, superoxide dis‐
growing chicks as affected by betaine addition to diets con‐ mutase and glutathione peroxidase in broiler chickens during the
taining 2. Different levels of methionine. International Journal hot‐dry season. Journal of Veterinary Behavior: Clinical Applications
of Poultry Science, 4(11), 856–865. https://doi.org/10.3923/ and Research, 12, 60–65. https://doi.org/10.1016/j.jveb.2015.11.001
ijps.2005.856.865 Eklund, M., Bauer, E., Wamatu, J., & Mosenthin, R. (2005). Potential nu‐
Awad, A. L., Ibrahim, A. F., Fahim, H. N., & Beshara, M. M. (2014). Effect tritional and physiological functions of betaine in livestock. Nutrition
of dietary betaine supplementation on growth performance and car‐ Research Reviews, 18(1), 31–48. https://doi.org/10.1079/NRR200493
cass traits of domyati ducklings under summer conditions. Egyptian Enting, H., Eissen, J., de Los Mozos, J., del Álamo, A. G., & de Ayala, P. P.
Poultry Science Journal, 34(34), 1019–1038. (2007). TNI‐Betain improves broiler chicken performance and car‐
Awwad, H. M., Kirsch, S. H., Geisel, J., & Obeid, R. (2014). Measurement of cass quality under heat stress conditions. In 16th European Symposium
concentrations of whole blood levels of choline, betaine, and dimethyl‐ on Poultry Nutrition (pp. 297–300). Strasbourg, France: World Poultry
glycine and their relations to plasma levels. Journal of Chromatography Science Association.
B, 957, 41–45. https://doi.org/10.1016/j.jchromb.2014.02.030 Etches, R. J. (1996). Reproduction in poultry. Wallingford, UK: CAB
Ayo, J. O., Egbuniwe, I., Kawu, M. U., & Sinkalu, V. O. (2014). Ameliorative International.
effects of betaine and ascorbic acid administration to broiler chick‐ Ezzat, W., Shoeib, M. S., Mousa, S. M. M., Bealish, A. M. A., & Ibrahiem,
ens during the hot‐dry season in Zaria: A review. African Journal Z. A. (2011). Impact of betaine, vitamin C and folic acid supplemen‐
of Biotechnology, 13(23), 2295–2306. https://doi.org/10.5897/ tations to the diet on productive and reproductive performance of
AJB2014.13789 matrouh poultry. Egyptian Poultry Science, 31(2), 521–537.
Borges, S. A., Fischer da Silva, A. V., Majorka, A., Hooge, D. M., & Farooqi, H. A. G., Khan, M. S., Khan, M. A., Rabbani, M., Pervez, K., &
Cummings, K. R. (2004). Physiological responses of broiler chickens Khan, J. A. (2005). Evaluation of betaine and vitamin C in allevia‐
to heat stress and dietary electrolyte balance (sodium plus potassium tion of heat stress in broilers. International Journal of Agriculture and
minus chloride, milliequivalents per kilogram). Poultry Science, 83(9), Biology, 7(5), 744–746.
1551–1558. https://doi.org/10.1093/ps/83.9.1551 Forman, H. J., Zhang, H., & Rinna, A. (2009). Glutathione: Overview of its
Butzner, D. J., Meddings, J. B., & Dalal, V. (1994). Inhibition of short‐ protective roles, measurement, and biosynthesis. Molecular Aspects
chain fatty acid absorption and Na+ absorption during acute coli‐ of Medicine, 30, 1–12. https://doi.org/10.1016/j.mam.2008.08.006
tis in the rabbit. Gastroenterology, 106, 1190–1198. https://doi. Ganesan, B., Rajesh, R., Anandan, R., & Dhandapani, N. (2007).
org/10.1016/0016-5085(94)90009-4 Biochemical studies on the protective effect of betaine on mitochon‐
Chand, N., Muhammad, S., Khan, R. U., Alhidary, I. A., & Rehman, Z. U. drial function in experimentally induced myocardial infarction in rats.
(2016). Ameliorative effect of synthetic γ‐aminobutyric acid (GABA) Journal of Health Science, 53(6), 671–681. https://doi.org/10.1248/
on performance traits, antioxidant status and immune response jhs.53.671
in broiler exposed to cyclic heat stress. Environmental Science and Ghareeb, K., Awad, W. A., Sid‐Ahmed, O. E., & Böhm, J. (2014). Insights
Pollution Research, 23, 23930–23935. https://doi.org/10.1007/ on the host stress, fear and growth responses to the deoxynivalenol
s11356-016-7604-2 feed contaminant in broiler chickens. PLoS One, 9(1), e87727. https://
Chand, N., Naz, S., Maris, H., Khan, R. U., Khan, S., & Qureshi, M. S. doi.org/10.1371/journal.pone.0087727
(2017). Effect of betaine supplementation on the performance Gu, X. H., Hao, Y., & Wang, X. L. (2012). Overexpression of heat shock
and immune response of heat stressed broilers. Pakistan Journal protein 70 and its relationship to intestine under acute heat stress in
of Zoology, 49, 1857–1862. https://doi.org/10.17582/journal. broilers: 2. Intestinal Oxidative Stress. Poultry Science, 91(4), 790–799.
pjz/2017.49.5.1857.1862 https://doi.org/10.3382/ps.2011-01628
Chendrimada, T. P., Neto, M. G., Pesti, G. M., Davis, A. J., & Bakalli, R. Gudev, D., Popova‐Ralcheva, S., Yanchev, I., Moneva, P., Petkov, E., &
I. (2002). Determination of the betaine content of feed ingredients Ignatova, M. (2011). Effect of betaine on egg performance and
using high‐performance liquid chromatography. Journal of the Science some blood constituents in laying hens reared indoor under natural
of Food and Agriculture, 82(13), 1556–1563. https://doi.org/10.1002/ summer temperatures and varying levels of air ammonia. Bulgarian
jsfa.1214 Journal of Agricultural Science, 17, 859–866.
Clow, K. A., Treberg, J. R., Brosnan, M. E., & Brosnan, J. T. (2008). Elevated Hamidi, H., Jahanian, R., & Pourreza, J. (2010). Effect of dietary beta‐
tissue betaine contents in developing rats are due to dietary betaine, ine on performance, immunocompetence and gut contents osmo‐
not to synthesis. Journal of Nutrition, 138(9), 1641–1646. https://doi. larity of broilers challenged with a mixed coccidial infection. Asian
org/10.1093/jn/138.9.1641 Journal of Animal and Veterinary Advances, 5(3), 193–201. https://doi.
Craig, S. A. S. (2004). Betaine in human nutrition. American Journal of org/10.3923/ajava.2010.193.201
Clinical Nutrition, 80, 539–549. https://doi.org/10.1002/jcp.25371 Han, Y. K., & Thacker, P. A. (2011). Influence of energy level and gly‐
Cronje, P. B. (2007). Gut health, osmoregulation and resilience to heat cine supplementation on performance, nutrient digestibility and egg
stress in poultry. In 19th Australian Poultry Science Symposium (pp. 9– quality in laying hens. Asian‐Austral Journal of Animal Science, 24,
13). Sydney: The Poultry Research Foundation, University of Sydney 1447–1455. https://doi.org/10.5713/ajas.2011.11123
& World’s Poultry Science Association, Australian Branch. Haryadi, J., Ratriyanto, A., Indreswari, R., & Nuhriawangsa, A. M. P.
Csonka, L. N. (1989). Physiological and genetic responses of bacteria to (2015). Performance of laying quails fed low‐protein diet supple‐
osmotic stress. Microbiological Reviews, 53(1), 121–147. mented with methyl donors. In National Seminar on Technology and
 |
1648       RATRIYANTO and MOSENTHIN

Animal Agribusiness III (pp. 217–221). Purwokerto: Faculty of Animal Khan, R. U., Naz, S., Nikousefat, Z., Tufarelli, V., Javdani, M., Rana, N.,
Science, Jenderal Soedirman University. & Laudadio, V. (2011). Effect of vitamin E in heat‐stressed poul‐
Hassan, R. A., Attia, Y. A., & El‐Ganzory, E. H. (2005). Growth, carcass try. World’s Poultry Science Journal, 67(3), 469–478. https://doi.
quality and serum constituents of slow growing chicks as affected org/10.1017/S0043933911000511
by betaine addition to diets containing 1. Different levels of choline. Khattak, F. M., Acamovic, T., Sparks, N., Pasha, T. N., Joiya, M. H., Hayat,
International Journal of Poultry Science, 4(11), 840–850. https://doi. Z., & Ali, Z. (2012). Comparative efficacy of different supplements
org/10.3923/ijps.2005.856.865 used to reduce heat stress in broilers. Pakistan Journal of Zoology,
Horio, M., Ito, A., Matsuoka, Y., Moriyama, T., Orita, Y., Takenaka, M., 44(1), 31–41.
& Imai, E. (2001). Apoptosis induced by hypertonicity in Madin Kidd, M. T., Ferket, P. R., & Garlich, J. D. (1997). Nutritional and osmo‐
Darley canine kidney cells: Protective effect of betaine. Nephrology, regulatory functions of betaine. World’s Poultry Science Journal, 53(2),
Dialysis, Transplantation, 16(3), 483–490. https://doi.org/10.1093/ 125–139. https://doi.org/10.1079/WPS19970013
ndt/16.3.483 Klasing, K. C., Adler, K. L., Remus, J. C., & Calvert, C. C. (2002). Dietary
Hundahl, C., Fago, A., Malte, H., & Weber, R. E. (2003). Allosteric effect of betaine increases intraepithelial lymphocytes in the duodenum
water in fish and human hemoglobins. Journal of Biological Chemistry, of coccidia‐infected chicks and increases functional properties of
278(44), 42769–42773. https://doi.org/10.1074/jbc.M307515200 phagocytes. The Journal of Nutrition, 132(8), 2274–2282. https://doi.
Jones, J. I., & Clemmons, D. R. (1995). Insulin‐like growth factors and org/10.1093/jn/132.8.2274
their binding proteins: Biological actions. Endocrine Reviews, 16(1), Konca, Y., Kirkpinar, F., Mert, S., & Yaylak, E. (2008). Effect of betaine
3–34. https://doi.org/10.1210/edrv-16-1-3 on performance, carcass, bone and blood characteristics of broilers
Jönsson, G., Midtvedt, A. C., Norman, A., & Midtvedt, T. (1995). Intestinal during natural summer temperatures. Journal of Animal and Veterinary
microbial bile acid transformation in healthy infants. Journal of Advances, 7, 930–937.
Pediatric Gastroenterology and Nutrition, 20(4), 394–402. https://doi. Kpodo, K. R. (2015). Dietary supplementation of choline and betaine in heat
org/10.1097/00005176-199505000-00004 stressed broilers. Knoxville, TN: The University of Tennessee.
Julian, R. J. (2000). Physiological, management and environmental trig‐ Krishnan, S., Ramakrishna, B. S., & Binder, H. J. (1999). Stimulation of
gers of the ascites syndrome: A review. Avian Pathology, 29(6), 519– sodium chloride absorption from secreting rat colon by short‐chain
527. https://doi.org/10.1080/03079450020016751 fatty acids. Digestive Diseases and Sciences, 44(9), 1924–1930. https://
Kempf, B., & Bremer, E. (1998). Uptake and synthesis of compatible sol‐ doi.org/10.1023/A:1018871412748
utes as microbial stress responses to high‐osmolality environments. Laudadio, V., Dambrosio, A., Normanno, G., Khan, R. U., Naz, S.,
Archives of Microbiology, 170(5), 319–330. https://doi.org/10.1007/ Rowghani, E., & Tufarelli, V. (2012). Effect of reducing dietary pro‐
s002030050649 tein level on performance responses and some microbiological as‐
Keskin, E., & Durgun, Z. (1997). Acid‐base balance, weight gain and feed pects of broiler chickens under summer environmental conditions.
intake in Japanese quails exposed to constant chronic heat stress. Avian Biology Research, 5(2), 88–92. https://doi.org/10.3184/17581
Pakistan Veterinary Journal, 17(2), 60–64. 5512X13350180713553
Kettunen, H., Peuranen, S., Jatila, H., Nurminen, P., Saarinen, M., & Leung, F. C., Taylor, J. E., & van Iderstine, A. (1984). Thyrotropin‐releas‐
Apajalahti, J. (1999). Effect of betaine on the microbiology of the ing hormone stimulates body weight gain and increases thyroid hor‐
chicken gastrointestinal tract. In R. P. Kwakkel (Ed.), Proceedings mones and growth hormone in plasma of cockerels. Endocrinology,
of the 12th European Symposium on Poultry Nutrition (p. 186). 115(2), 736–740. https://doi.org/10.1210/endo-115-2-736
Veldhoven, the Netherlands: World’s Poultry Science Association, Lipiński, K., Szramko, E., Jeroch, H., & Matusevičius, P. (2012). Effects
Dutch Branch. of betaine on energy utilization in growing pigs – A review. Annals
Kettunen, H., Peuranen, S., & Tiihonen, K. (2001). Betaine aids in the of Animal Science, 12(3), 291–300. https://doi.org/10.2478/
osmoregulation of duodenal epithelium of broiler chicks, and af‐ v10220-012-0024-4
fects the movement of water across the small intestinal epithelium Mahmoudnia, N., & Madani, Y. (2012). Effect of betaine on performance
in vitro. Comparative Biochemistry and Physiology ‐ A Molecular and and carcass composition of broiler chicken in warm weather – A
Integrative Physiology, 129(2–3), 595–603. https://doi.org/10.1016/ Review. International Journal of AgriScience, 2(August), 675–683.
S1095-6433(01)00298-7 Mashaly, M. M., Hendricks, G. L., Kalama, M. A., Gehad, A. E., Abbas, A.
Kettunen, H., Tiihonen, K., Peuranen, S., Saarinen, M. T., & Remus, J. C. O., & Patterson, P. H. (2004). Effect of heat stress on production pa‐
(2001). Dietary betaine accumulates in the liver and intestinal tissue rameters and immune responses of commercial laying hens. Poultry
and stabilizes the intestinal epithelial structure in healthy and coc‐ Science, 83(6), 889–894. https://doi.org/10.1093/ps/83.6.889
cidia‐infected broiler chicks. Comparative Biochemistry and Physiology Metzler‐Zebeli, B. U., Eklund, M., & Mosenthin, R. (2009). Impact of os‐
– A Molecular and Integrative Physiology, 130(4), 759–769. https://doi. moregulatory and methyl donor functions of betaine on intestinal
org/10.1016/S1095-6433(01)00410-X health and performance in poultry. World’s Poultry Science Journal,
Khajali, F., Tahmasebi, M., Hassanpour, H., Akbari, M. R., Qujeq, D., & 65(03), 419–442. https://doi.org/10.1017/S0043933909000300
Wideman, R. F. (2011). Effects of supplementation of canola meal‐ Moeckel, G. W., Shadman, R., Fogel, J. M., & Sadrzadeh, S. M. H. (2002).
based diets with arginine on performance, plasma nitric oxide, Organic osmolytes betaine, sorbitol and inositol are potent inhibitors
and carcass characteristics of broiler chickens grown at high al‐ of erythrocyte membrane ATPases. Life Sciences, 71(20), 2413–2424.
titude. Poultry Science, 90, 2287–2294. https://doi.org/10.3382/ https://doi.org/10.1016/S0024-3205(02)02035-0
ps.2011-01618 Monau, T. R., Vargas, V. E., Lubo Zhang, L., Myers, D. A., & Ducsay,
Khan, R. U., Naz, S., & Dharma, K. (2014). Chromium: Pharmacological C. A. (2010). Nitric oxide inhibits ACTH‐Induced cortisol pro‐
applications in heat‐stressed poultry. International Journal duction in near‐term, long‐term hypoxic ovine fetal adrenocor‐
of Pharmacology, 10, 213–217. https://doi.org/10.3923/ tical cells. Reproductive Sciences, 17(10), 955–962. https://doi.
ijp.2014.213.217 org/10.1177/1933719110376092
Khan, R. U., Naz, S., Nikousefat, Z., Selvaggi, M., Laudadio, V., & Tufarelli, Nakanishi, T., Turner, R. J., & Burg, M. B. (1990). Osmoregulation of be‐
V. (2012). Effect of ascorbic acid in heat‐stressed poultry. World’s taine transport in mammalian renal medullary cells. American Journal
Poultry Science Journal, 68(3), 477–489. https://doi.org/10.1017/ of Physiology‐Renal Physiology, 258(4), F1061–F1067. https://doi.
S004393391200058X org/10.1152/ajprenal.1990.258.4.F1061
RATRIYANTO and MOSENTHIN |
      1649

Nofal, M. E., Galal, M. A., Mousa, S. M. M., Yassein, D. M. M., & Bealsh, Yogyakarta, Indonesia: Faculty of Animal Science, Universitas
A. M. A. (2015). Effect of dietary betaine supplementation on pro‐ Gadjah Mada.
ductive, physiological and immunological performance and carcass Ratriyanto, A., Indreswari, R., & Sunarto. (2014a). Effects of protein lev‐
characteristic of growing developed chicks under the condition of els and supplementation of methyl group donor on nutrient digest‐
heat stress. Egyptian Poultry Science Journal, 5623(35), 237–259. ibility and performance of broiler chickens in the tropics. International
Oliva, J., Bardag‐Gorce, F., Tillman, B., & French, S. W. (2011). Journal of Poultry Science, 13(10), 575–581.
Protective effect of quercetin, EGCG, catechin and betaine against Ratriyanto, A., Indreswari, R., & Sunarto. (2014b). The effect of protein
oxidative stress induced by ethanol in vitro. Experimental and levels and betaine supplementation on digestible nutrient and small
Molecular Pathology, 90(3), 295–299. https://doi.org/10.1016/j. intestine characteristic of broilers. In D. Latipudin (Ed.), Proceedings
yexmp.2011.02.006 of the 6th National Conference on Sustainable Animal Agriculture
Pajares, M. A., & Pérez‐Sala, D. (2006). Betaine homocysteine S‐meth‐ Development (pp. 1–8). Bandung, Indonesia: Faculty of Animal
yltransferase: Just a regulator of homocysteine metabolism? Science, Padjadjaran University.
Cellular and Molecular Life Sciences, 63(23), 2792–2803. https://doi. Ratriyanto, A., Mosenthin, R., Bauer, E., & Eklund, M. (2009). Metabolic,
org/10.1007/s00018-006-6249-6 osmoregulatory and nutritional functions of betaine in monogastric
Park, S. O., & Kim, W. K. (2017). Effects of betaine on biological functions animals. Asian‐Australasian Journal of Animal Sciences, 22(10), 1461–
in meat‐type ducks exposed to heat stress. Poultry Science, 96(5), 1476. https://doi.org/10.5713/ajas.2009.80659
1212–1218. https://doi.org/10.3382/ps/pew359 Reddy, C. V. (2000). Maintaining growth and production. Poultry
Patel, V. B., & Mehta, K. (2015). Betaine in context. In V. R. Preedy (Ed.), International, 31, 36–40.
Betaine: Chemistry, analysis, function and effects (pp. 3–8). Cambridge, Rehman, Z. U., Chand, N., & Khan, R. U. (2017). The effect of vitamin E, L‐
UK: Royal Society of Chemistry. carnitine, and ginger on production traits, immune response, and an‐
Pech‐Waffenschmidt, V., Bogin, E., Avidar, Y., & Horst, P. (1995). tioxidant status in two broiler strains exposed to chronic heat stress.
Metabolic and biochemical changes during heat stress in relation to Environmental Science and Pollution Research, 24, 26851–26857.
the feathering degree of the domestic hen. Avian Pathology, 24(1), https://doi.org/10.1007/s11356-017-0304-8
33–44. https://doi.org/10.1080/03079459508419047 Remus, J. (2001). Betaine for increased breast meat yield in turkeys.
Petronini, P. G., de Angelis, E. M., Borghetti, P., Borghetti, A. F., & World Poultry, 17, 14–15.
Wheelert, K. P. (1992). Modulation by betaine of cellular responses Rørvik, K.‐A., Steien, S. H., Saltkjelsvik, B., & Thomassen, M. S. (2000).
to osmotic stress. Biochemistry Journal, 282, 69–73. https://doi. Urea and trimethylamine oxide in diets for seawater farmed rain‐
org/10.1042/bj2820069 bow trout: Effect on fat belching, skin vesicle, winter ulcer and
Powell, S., Bidner, T. D., & Southern, L. L. (2009). The interactive effects quality grading. Aquaculture Nutrition, 6(4), 247–254. https://doi.
of glycine, total sulfur amino acids, and lysine supplementation to org/10.1046/j.1365-2095.2000.00143.x
corn‐soybean meal diets on growth performance and serum uric acid Rosa, P. S., Faria Filho, D. E., Dahlke, F., Vieira, B. S., Macari, M., & Furlan,
and urea concentrations in broilers. Poultry Science, 88, 1407–1412. R. L. (2007). Performance and carcass characteristics of broiler
https://doi.org/10.3382/ps.2008-00433 chickens with different growth potential and submitted to heat
Rao, S. V. R., Raju, M. V. L. N., Panda, A. K., Saharia, P., & Sunder, G. stress. Revista Brasileira De Ciência Avícola, 9(3), 181–186. https://doi.
S. (2011). Effect of supplementing betaine on performance, car‐ org/10.1590/S1516-635X2007000300007
cass traits and immune responses in broiler chicken fed diets con‐ Ryu, M. S., Cho, K. H., Shin, W. J., & Ryu, K. S. (2002). Influence of di‐
taining different concentrations of methionine. Asian‐Australasian etary supplemental betaine on performance and egg quality of laying
Journal of Animal Sciences, 24(5), 662–669. https://doi.org/10.5713/ hens during the heat stress. Korean Journal of Poultry Science, 29(2),
ajas.2011.10286 117–123.
Ratriyanto, A., Indreswari, R., Dewanti, R., & Sofyan, A. (2012). Ryu, M. S., Park, J. H., Shin, K. H., Na, J. S., & Ryu, K. S. (2003). Effects
Nutrient digestibility and protein efficiency ratio in quail (Coturnix of dietary betaine supplementation on performance, lipid metabolic
coturnix japonica) fed high methionine diet with betaine supple‐ parameters, and blood and ileal osmolality in laying hens. Korean
mentation. InE. T. Marlina (Ed.), Proceedings of the 4th National Journal of Poultry Science, 30(4), 259–267.
Conference on Sustainable Animal Agriculture Development (pp. 146– Sahin, K., Ozbey, O., Onderci, M., Cikim, G., & Aysondu, M. H. (2002).
150). Bandung, Indonesia: Faculty of Animal Science, Padjadjaran Chromium supplementation can alleviate negative effects of heat
University. stress on egg production, egg quality and some serum metabolites
Ratriyanto, A., Indreswari, R., Dewanti, R., & Wahyuningsih, S. (2018). of laying Japanese quail. The Journal of Nutrition, 132(6), 1265–1268.
Egg quality of quails fed low methionine diet supplemented with be‐ https://doi.org/10.1093/jn/132.6.1265
taine. IOP Conference Series: Earth and Environmental Science, 142(1), Sakomura, N., Barbosa, N., Longo, F., da Silva, E., Bonato, M., & Fernandes,
012002. https://doi.org/10.1088/1755-1315/142/1/012002 J. (2013). Effect of dietary betaine supplementation on the perfor‐
Ratriyanto, A., Indreswari, R., & Nuhriawangsa, A. M. P. (2017). mance, carcass yield, and intestinal morphometrics of broilers sub‐
Effects of dietary protein level and betaine supplementation mitted to heat stress. Revista Brasileira De Ciência Avícola, 15(2), 105–
on nutrient digestibility and performance of Japanese quails. 112. https://doi.org/10.1590/S1516-635X2013000200005
Revista Brasileira De Ciencia Avicola, 19(3), 445–454. https://doi. Saunderson, C. L., & Mackinlay, J. (1990). Changes in body‐weight, com‐
org/10.1590/1806-9061-2016-0442 position and hepatic enzyme activities in response to dietary methi‐
Ratriyanto, A., Indreswari, R., Nuhriawangsa, A. M. P., & Arifin, A. A. onine, betaine and choline levels in growing chicks. The British Journal
(2017). Dietary metabolizable energy and methionine affect per‐ of Nutrition, 63(2), 339–349. https://doi.org/10.1079/BJN19900120
formance of quails. In Proceeding of the 1st International Conference Sayed, M. A. M., & Downing, J. (2011). The effects of water replacement
on Tropical Agriculture (pp. 329–335). Cham: Springer International by oral rehydration fluids with or without betaine supplementation
Publishing. on performance, acid‐base balance, and water retention of heat‐
Ratriyanto, A., Indreswari, R., Nuhriawangsa, A. M. P., & Haryanti, A. E. stressed broiler chickens. Poultry Science, 90(1), 157–167. https://doi.
(2015). Performance of Japanese quails fed different protein lev‐ org/10.3382/ps.2009-00594
els and supplemented with betaine. In C. T. Noviandi (Ed.), The 6th Scott, G. S., & Bolton, C. (2000). L‐arginine modifies free radical produc‐
International Seminar on Tropical Animal Production (pp. 118–122). tion and the development of experimental allergic encephalomyelitis.
 |
1650       RATRIYANTO and MOSENTHIN

Inflammation Research, 49, 720–726. https://doi.org/10.1007/ Yalçin, S., Özkan, S., Türkmut, L., & Siegel, P. B. (2001). Responses to
s000110050652 heat stress in commercial and local broiler stocks. 1. Performance
Sheikh‐Hamad, D., García‐Pérez, A., Ferraris, J. D., Peters, E. M., & Burg, traits. British Poultry Science, 42(2), 149–152. https://doi.
M. B. (1994). Induction of gene expression by heat shock versus os‐ org/10.1080/00071660120048375
motic stress. The American Journal of Physiology, 267(1 Pt 2), F28–F34. Yancey, P. H. (2001). Water stress, osmolytes and proteins. American
https://doi.org/10.1152/ajprenal.1994.267.1.F28 Zoologist, 41(4), 699–709. https://doi.org/10.1093/icb/41.4.699
Singh, K. A., Ghosh, T. A., Creswell, D. C., & Haldar, S. (2015). Effects of Yao, Z., & Vance, D. E. (1989). Head group specificity in the requirement
supplementation of betaine hydrochloride on physiological perfor‐ of phosphatidylcholine Biosynthesis for very low density lipopro‐
mances of broilers exposed to thermal stress. Open Access Animal tein secretion from cultured hepatocyte. The Journal of Biological
Physiology, 7, 111–120. https://doi.org/10.2147/OAAP.S83190 Chemistry, 264, 11373–11380.
Smith, M. O., & Teeter, R. G. (1987). Influence of feed intake and ambient Zhan, X. A., Li, J. X., Xu, Z. R., & Zhao, R. Q. (2006). Effects of methionine and
temperature stress on relative yield of broiler parts. Nutrition Reports betaine supplementation on growth performance, carcase composi‐
International, 35, 299–306. tion and metabolism of lipids in male broilers. British Poultry Science,
Tallentire, C. W., Leinonen, I., & Kyriazakis, I. (2016). Breeding for effi‐ 47(5), 576–580. https://doi.org/10.1080/00071660600963438
ciency in the broiler chicken: A review. Agronomy for Sustainable Zulkifli, I., Al‐Aqil, A., Omar, A. R., Sazili, A. Q., & Rajion, M. A. (2009).
Development, 36(4), https://doi.org/10.1007/s13593-016-0398-2 Crating and heat stress influence blood parameters and heat shock
Tucker, L. A., & Remus, J. (2001). The effect of betaine on performance, protein 70 expression in broiler chickens showing short or long tonic
water balance and gut integrity of coccidiosis–infected poultry immobility reactions. Poultry Science, 88(3), 471–476. https://doi.
and its potential benefit in AGP‐free diets. British Poultry Science, org/10.3382/ps.2008-00287
42(Suppl. 1), S108–S109. Zulkifli, I., Mysahra, S. A., & Jin, L. Z. (2004). Dietary supplementation
Wallis, I. R. (1999). Dietary supplements of methionine increase breast of betaine (Betafin (R)) and response to high temperature stress in
meat yield and decrease abdominal fat in growing broiler chickens. male broiler chickens. Asian‐Australasian Journal of Animal Sciences,
Australian Journal of Experimental Agriculture, 39, 131–141. https:// 17(1), 244–249.
doi.org/10.1071/EA98132
Wang, Y. Z., Xu, Z. R., & Feng, J. (2004). The effect of betaine and DL‐
methionine on growth performance and carcass characteristics in
How to cite this article: Ratriyanto A, Mosenthin R.
meat ducks. Animal Feed Science and Technology, 116(1–2), 151–159.
https://doi.org/10.1016/j.anifeedsci.2004.05.003
Osmoregulatory function of betaine in alleviating heat stress in
Wenk, C., Kölliker, R., & Messikommer, R. (1993). Whole maize plants in poultry. J Anim Physiol Anim Nutr. 2018;102:1634–1650.
diets for growing pigs: Effect of 3 different enzymes on the feed uti‐ https://doi.org/10.1111/jpn.12990
lization. In C. Wenk, & M. Boessinger (Eds.), 1st Symposium Enzymes
in Animal Nutrition (pp. 165–169). Zürich, Switzerland.
Yahav, S. (2009). Alleviating heat stress in domestic fowl: Different strat‐
egies. World’s Poultry Science Journal, 65(04), 719–732. https://doi.
org/10.1017/S004393390900049X