Meta-analysis recommended for Meta-analysis of recommended digestible lysine levels for primiparous lactating sows

: A meta-analysis was carried out to evaluate the recommended levels of digestible lysine and its influence on the productive performance of primiparous lactating sows. The database consisted of 26 publications, 138 diets and 3,820 sows was developed from articles on the association between, lysine, crude protein and lactating primiparous sows. The digestible lysine levels of the studies ranged from 0.22 to 1.43% with average values of 0.85% digestible lysine in the diet, with consumption of 41.25 g day -1 . The digestible lysine intake of sows was positively correlated (P<0.05) with feed intake, essential amino acids, crude protein, metabolizable energy, body weight loss sows, milk production, number and weight of piglets at weaning. Digestible lysine intake showed negative correlation (P<0.05) with backfat thickness at weaning and weaning to oestrus interval. It was observed a quadratic effect (P<0.01) of body weight loss sow and daily weight gain of piglets and a quadratic effect (P<0.01) in the weight of piglets at weaning due to increased dietary lysine level. The level of 1.04% of digestible lysine indicates less weight loss sows. The greater weight of piglets at weaning and increased daily weight gain of piglets was verified with the addition of 1.30 and 1.07% digestible lysine in the diet, respectively.


INTRODUCTION
Sow productivity has increased considerably in recent years, mainly owing to an increase in litter size, which has resulted in an increased metabolic demand for nutrients to support fetal growth and colostrum and milk production (TOKACH et al., 2019). However, this increase in nutritional requirements has not been accompanied by the pattern of sow intake, thus, sows undergo excessive mobilization of body protein during lactation (YANG et al., 2000a). This can affect the size of the subsequent litter via the reduction of follicular development (CLOWES et al., 2003). Garcia et al. Thus, the establishment of nutritional requirements for lactating sows is important to minimize the mobilization of body reserves (GOURLEY et al., 2017). Among the amino acids required by lactating sows, more than 70% are destined for the production of milk protein (PEdERSEN et al., 2016); therefore, the adequate consumption of amino acids and protein may increase milk production (STRATHE et al., 2017).
Among the amino acids, lysine stands out for its direct role in protein synthesis and as the first limiting amino acid in diets based on corn and soybean (GOURLEY et al., 2017), being used as a reference in the formulation (COTA et al., 2003). However, there is wide variation in the recommendations for lysine for lactating sows that can be attributed to several factors such as genetic differences (TU et al., 2010), sow parity (YANG et al., 2009), diet composition (COTA et al., 2003, room temperature (ROSTAGNO et al., 2017) and even the adopted response criteria (BOYd et al., 2000).
Several studies have been carried out to determine the lysine requirements for lactating sows and have generated a large amount of data. Based on this information, it is possible to carry out a meta-analysis that synthesizes study results in a reproducible and quantifiable manner (LOVATTO et al., 2007) and without experimental costs. Therefore, a meta-analysis was carried out to evaluate the recommended levels of digestible lysine and its influence on the productive performance of primiparous lactating sows.

MATERIALS AND METHODS
A meta-analysis was developed based on data from scientific articles on the association between lysine and crude protein levels in lactating primiparous sows. The methodology for defining the dependent and independent variables and coding the data followed a previous study (LOVATTO et al., 2007). One hundred publications were identified and 69 were excluded after reading the articles. Studies selected to compose the database met the following inclusion criteria: presented the chemical composition of experimental diets and evaluated different levels of amino acids and protein in diets of lactating sows.
Nutritional levels of digestible lysine, threonine, valine, and methionine + cystine, the level of crude protein, and the metabolizable energy used in the diets were estimated according to the centesimal composition of the experimental diets and the nutritional composition of the food, according to the Brazilian tables of nutritional requirements (ROSTAGNO et al., 2011).
Feed, lysine, threonine, valine, methionine + cystine, and crude protein intake; metabolizable energy; and lysine/metabolizable energy ratio were the evaluated response criteria. Lactating sow characteristics (weight at birth and weaning, fat thickness at birth and weaning, weaning-to-estrus interval, and milk production) and productive performance of sows (number of piglets at birth and weaning, weight of piglets, and weight gain at birth and weaning) were also evaluated.
Models for the analysis of variance and covariance used the factors with the highest correlation coefficients and codifications for inter-and intra-experiment effects, as performed in a previous study (LOVATTO et al., 2007). The regression equations were obtained through the analysis of variance and covariance.

RESULTS AND DISCUSSION
digestible lysine levels in the studies ranged from 0.22 to 1.43%, with average values of 0.85% of digestible lysine in the diets, with an intake of 41.25 g day -1 (Table 1). Additionally, the diets contained mean values of 16.76% crude protein, 0.51% digestible methionine + cystine, 0.57% digestible threonine, and 0.74% digestible valine, and 3,317 Kcal kg -1 of metabolizable energy. For these diets, the mean lysine/metabolizable energy ratio was 2.55.
From these results, it is possible to infer that there is high variation among the recommendations of digestible lysine for the diets of primiparous lactating sows. These variations can be attributed to several factors, such as genetic lines (TU et al., 2010), sow parity (YANG et al., 2009), diet composition (COTA et al., 2003, room temperature (ROSTAGNO et al., 2017), and even the adopted response criteria (BOYd et al., 2000).
According to the Brazilian tables of nutritional requirements (ROSTAGNO et al., 2011), the nutritional recommendation for lactating sows at a body weight of 180 kg with a weight loss of 0.5 kg day -1 to nurse a litter with a weight gain of 2.0 kg day -1 is 19.84% crude protein and 1.007% digestible lysine and recommended intake of 45.5 g day -1 digestible lysine. In a recent publication (ROSTAGNO et al., 2017), the nutritional recommendation for lactating sows at a body weight of 180 kg with weight loss of 0.5 kg day -1 and litter weight gain of 2.8 kg day -1 , is 21.20% crude protein and 1.075% digestible lysine and the recommended intake of 64.5 g day -1 digestible lysine.
To analyze the recommendations of the nutritional levels of lysine, the different requirements of individual lactating sows to promote litter growth and minimize the mobilization of body tissue must be considered. Generally, the requirement for lysine to minimize the loss of muscle mass during lactation and improve subsequent reproductive performance is higher than that for milk production and litter development (PAIVA et al., 2005). Thus, recent studies have tended to recommend higher levels of lysine in the diet of lactating sows than older studies. This development is reflected in the recommended nutritional requirements between ROSTAGNO et al. (2011) andROSTAGNO et al. (2017).
Feed intake of the primiparous lactating sows ranged from 1.92 to 7.20 kg day -1 , with an average value of 4.85 kg day -1 , with consumption of 41.25 g day -1 of digestible lysine (Table 2). Additionally, the studies showed average intake values of 16,073 Kcal day -1 of metabolizable energy, 804.62 g day -1 of crude protein, 24.75 g day -1 of digestible methionine + cystine, 27.51 g day -1 of digestible threonine, and 35.93 g day -1 of digestible valine. These average values are similar to those recommended by ROSTAGNO et al. (2011), in which 180 kg sows  should consume 4.52 kg day -1 of feed, 15,369 Kcal day -1 of metabolizable energy, and 45.5 g day -1 of digestible lysine. However, they are less than the recommendations presented by ROSTAGNO et al. (2017), in which 180 kg sows should consume 6.0 kg day -1 of feed, 20,400 Kcal day -1 of metabolizable energy, and 64.5 g day -1 of digestible lysine. Sow feed intake is one of the most important variables in lactation and must be constantly evaluated as it affects the availability of amino acids, which can determine whether a sow meets their nutritional requirements. It is influenced by sow parity (YOUNG et al., 2004), body composition (COOPER et al., 2001a), genetics (SAUBER et al., 1998), and environmental temperature (KIEFER et al., 2012). Currently, it is normal for lactating primiparous sows to achieve daily feed intake of less than the predetermined ideal values (COTA et al., 2003), and less than 18% of sows show the ideal pattern of feed intake during lactation (KOKETSU et al., 1996).
The digestible lysine intake of sows showed a positive correlation (P<0.05) with feed intake, essential amino acids, crude protein, metabolizable energy, sow body weight loss, milk production, and number and weight of piglets at weaning (Table 3). Correlations between the digestible lysine intake and the essential amino acids observed can be explained by the formulation of the diets, which are based on the ideal protein content and estimate various amino acid needs from the lysine requirement (TUITOEK et al., 1997).
Different ideal protein patterns are suggested for lactating sows according to the degree of muscle tissue mobilization. For sows with low voluntary feed intake and substantial tissue mobilization, the critical amino acid is threonine, whereas for those with high feed intake and little tissue mobilization, valine becomes more important. However, lysine remains the main and the first limiting amino acid in both cases (KIM et al., 2001;KIM et al., 2005).
However, COTA et al. (2003) showed a negative correlation between the level of lysine in the diet and sow body weight loss. Furthermore, HEO et al. (2008) observed that higher levels of lysine in the diet of primiparous lactating sows resulted in an increase in the weight of the litter at weaning compared with lactating sows with lower levels of lysine in the diet.
The digestible lysine intake in the present study had a negative correlation (P<0.05) with fat thickness at weaning and weaning-to-estrus interval; however, levels of digestible lysine did not correlate (P>0.05) with performance and weight gain of the   piglets. The correlation between digestible lysine intake and fat thickness can be explained by the increased intake of lysine resulting in increased milk production and, consequently, an increase in the number of weaned piglets. The increase in milk production, observed in larger litters, results in increased energy requirements and, in situations where this increase is not met by the intake of nutrients, there is an increase in the mobilization of body reserves, resulting in a reduction in the fat thickness. This response has also been observed by GILL (2006), in which higher levels of lysine decreased fat thickness, and MAES et al. (2004), in which sows that weaned a greater number of piglets showed a greater loss of fat thickness during lactation. Estimates by TOKACH et al. (2019) also show this response, that the increase in daily milk production, related to the increase in the number of piglets in the litter, increases the mobilization of body protein and fat and; consequently, increases weight loss during lactation.
The equations that best explain the productive performance of the sows present as covariables, in addition to the levels of digestible lysine and the sow's weight at birth (Table 4). There was a quadratic effect between sow body weight loss and daily weight gain of the piglets (P<0.01) and piglet weight at weaning (P<0.01) owing to the increase in the level of lysine in the diet. diets with 1.04% digestible lysine showed the lowest daily weight loss (0.57 kg day -1 ), whereas those with 1.30 and 1.07% digestible lysine resulted in a greater weight of piglets at weaning and greater daily weight gain of piglets, respectively. We can infer that the recommendations for the nutritional requirement of digestible lysine may vary for the same data set according to the response criteria used, as suggested by BOYd et al. (2000) and GOURLEY et al. (2019). Recommendation calculated in this study (1.04% digestible lysine) is slightly higher than the 1.01% digestible lysine established by ROSTAGNO et al. (2011) and slightly lower than the    (ROSTAGNO et al., 2017), which suggested a diet of 1.075% digestible lysine, with a similar pattern of estimated body weight loss during lactation (0.50 kg day -1 ). A level close to that of the present study was established by TU et al. (2010) who recommended 1.05% lysine for less loss of fat thickness and greater number and weight of weaned piglets.

CONCLUSION
In view of the variability in the database of this meta-analysis, the level of digestible lysine recommended varies according to the response criterion adopted. However, it is possible to recommend 1.04% for the lowest sow weight loss, 1.30% for the greatest weight of piglets at weaning, and 1.07% for the greatest daily weight gain of piglets.