**5. Available resources for (self-) maintenance**

Not only a producing but also a non-producing animal expends nutrients to maintain its life processes. Every animal assures these expenditures have been met before allocating ingested nutrients to any other use. When comparing species of differing size and body weight (BW), it is known that smaller animals have a higher demand for maintenance energy than larger animals. The percentage ratio of regression to BW is approximately 0.75 and this is the accepted common base for the expression of maintenance requirements for nutrients across species [25]. Theoretically, it is an easy approach for calculating energy requirements of farm animals. It requires only reliable information on BW. Given the large variation in BW between dairy cows within a herd, and due to substantial changes which occur during the lactation period [26, 27], gaining reliable BW figures would demand a regular recording of individual BWs. This however is seldom consistently carried out in dairy farming.

Furthermore, cows of similar BW, size and breed may vary considerably in their requirements for basal metabolism. For example, locomotion activity is often considered as part of the 'maintenance requirement' even though the extent of activity, e.g. foraging, can differ extensively between cows. This also applies to the requirements needed to maintain the body core temperature because metabolically busy animals do not need additional energy to maintain body core temperature at the same ambient temperature as metabolically less busy animals. Much more significant is the fact that meeting the energy requirements for the basal metabolic rate and its variation due to differences in BW, activity level or cold and heat stress does not cover the requirements that are needed to ensure self-maintenance of the animal when faced with the various threats they have to cope with. McEwen [28] coined the term "allostatic load" within the concept of allostasis to describe potential permanent overburdening of homeostatic processes. One can imagine allostatic load increasing due to the rising energy expenditure required to fuel regulatory processes. Accordingly, allostatic load is the sum of the energy required to maintain basic homeostasis and to acclimate to changing environmental conditions.

The immune system, as one of the body's sensory organs for controlling interactions with the environment, is integrated into the physiological regulatory mechanisms that maintain the integrity of the host in the face of diverse environmental threats. Immune responses are not only influenced by the nature of the pathogen but also by characteristics of the host: age, gender, passive immunity, prior exposure to the pathogen, concurrent infections, physiological status, micro and macro-nutrient status as well as the presence of concurrent stressors [29]. The author identified demands on the immune system related to, amongst other things: "increased metabolic activity - systemically during fever, locally during activation of immune system cells; reduced nutrient availability due to anorexia and/ or other sickness; altered priorities for nutrient utilization due to changes in the gradient during immune activation that reduce the capacity of many non-immune tissues to utilize nutrients".

Whatever their origin, e.g. the accumulation of pro-inflammatory processes in dairy cows around parturition, disorders and diseases implicate the need of energy and substrates. These are needed to adequately meet the requirements of the immune response to prevent severe health problems of dairy cows and to support

the overall goal of self-maintenance. According to Aitken et al. [30], "many aspects of the bovine immune system are compromised around the time of calving, especially the inflammatory responses". Immune suppression in the periparturient dairy cow is a commonly observed phenomenon and has been linked to poor metabolic status and negative energy balance [13, 31, 32]. Thus, attenuation of the immune response to the various challenges is, in the first place, the result of limitations in the availability of energy and substrates.

Besides energy, the organism requires protein, vitamins, minerals and trace elements in appropriate amounts in relation to the individual needs. Here the role of glucose must be emphasized: this substrate is used by the highly energy-demanding immune cells as a main source of fuel for immune defense and should therefore be considered the quantitatively most important fuel to fulfill the energy requirements of immune cells [33]. According to Ingvartsen and Moyes [34], "as glucose is the preferred fuel for immune cells, its low concentration during the transition period may partly explain the naturally occurring immunosuppression at this time". Another study [35] shows that ketones are not utilized by immune cells and in fact primarily act as inhibitors to immune responses when concentration is relatively high. In comparison with healthy controls, ketotic cows have increased circulating LPS prior to calving, and post-partum acute phase proteins such as LPS-binding protein, serum amyloid A and haptoglobin are also increased [35]. Endotoxin stimulates the immune system and activated leukocytes switch their metabolism away from oxidative phosphorylation to rely more on aerobic glycolysis [36]. The energetic cost of immune-activation is substantial but the ubiquitous nature of the immune system makes precise quantifying of the energetic demand difficult. Kvidera et al. [37] estimated approximately 1 kg of glucose is used by the immune system during a 12-hour period in which lactating dairy cows were challenged by LPS. This amounts to 2 kg of glucose per day for the immune system alone. This is more or less equivalent to the amount of glucose a cow withdraws in the form of lactose when producing an amount of 40 kg of milk per day [38]. In this context, it has to be considered that the synthesis of lactose alone utilizes 65–70% of the cow's total glucose turnover [39].

An increased immune system glucose utilization occurs simultaneously with infection induced decreased feed intake. This coupling of enhanced nutrient requirements with hypophagia further decreases the amount of nutrients available for the synthesis of milk. In the face of limited availability, glucose is allocated preferentially to a selected function at the expense of other functions, resulting in trade-offs and increased competitive pressure. Immune responses are contextspecific and the costs vary considerably depending on the pathogen, the environment and defense capacity of the host. Immune defense activities create highly individual outcomes depending on the initial and boundary conditions, and on the degree of the mismatch between demand and supply. The context-specific and individual nature of immune activation suggests that quantitative estimates of the costs of immune activation can be neither readily generalized nor predicted. This might explain why the costs of immune defense are not a prioritized issue of animal science. Apart from striving for an easy approach to asses energy requirements of farm animals, it is quite astonishing and disturbing to realize that the costs of selfmaintenance for farm animals are largely disregarded by the scientific discipline of animal nutrition. This may be due to the fact that feeding trials are generally conducted under standardized experimental conditions and usually on healthy animals which probably do not require high levels of additional energy and other substrates for the immune defense. Therefore, the results of feeding trials under experimental conditions enclose a high degree of uncertainty when transferred into practice on dairy farms where production diseases are frequently found.

**59**

*Nutrition and Health-Management in Dairy Production DOI: http://dx.doi.org/10.5772/intechopen.89447*

**6. Storage of energy and glucose resources**

liver causing cows to milk off their backs and lose condition.

metabolic stress and cause health disorders."

The 'barrel model', with its focus on energy demand and supply, considers neither the requirement of glucose for adaptation processes nor the need for a glucose buffer to fuel a short-term activation of the immune defense. Furthermore, it is obvious that the allocation of nutrients and energy resources for the various needs is not regulated independently, as assumed by the 'barrel model', but is highly interconnected. In the past, it may have been rational for the diet formulation to consider maintenance, growth and production as separate singular outputs. In face of increased knowledge, it is not justified to maintain these assumptions any longer.

Once nutrients are absorbed, they belong to the total energy and substrate pool and the stores of the body which make up the overall pool of resources. Metabolites in the form of carbohydrates, protein and fatty acids which are not needed in current metabolic processes are transformed and stored in the adipose tissues of the organism to serve as a reserve in periods of deficiencies. Fatty acids in the adipose tissues represent the main source of energy which the organism can fall back on when the supply does not meet the current needs. The 'barrel model' suggests that the energy balance is in general buffered by the storage capacity should the sum of the output rates not match the input [24]. Whenever intake is insufficient to support production – as in early lactation – energy is mobilized from body fat via the

According to Friggens et al. [40], "high-yielding dairy cows have been genetically selected to partition even more glucose into milk production with the effect that reliance on body reserves has dramatically increased". Patton et al. [41] stated: "Even in the case of higher dietary intake, the increased input will primarily result in greater milk production while having little effect on energy imbalance and no beneficial effects on body condition and reserves at all". Although the storage capacities in the adipose tissue may seem to be abundant, the mobilization of fat can cause problems if the lipolysis is accelerated too fast. Metabolic changes, e.g. the process of uncontrolled lipid mobilization in response to excessive negative energy balance, increase the risk of ketosis, hepatic lipidosis and infectious diseases [42, 43]. Sordillo and Raphael [13] addressed the possible connections between fat mobilization and dysfunctional inflammation responses that may contribute to increased morbidity and mortality in the transition phase. Failing to adapt physiologically to an increase in nutrient requirements needed for the onset of milk synthesis is equivalent to metabolic stress and a major underlying factor in the development of transition cow disorders [44]. The authors conclude: "The combined effects of altered nutrient metabolism, dysfunctional inflammatory responses and oxidative stress can form destructive feedback loops that exacerbate

As mentioned above, dairy cows have a high demand for glucose. The storage form of glucose is glycogen and although widely distributed throughout the mammalian body, quantitatively the liver and muscle account for most of the body's glycogen stores. The liver glycogen depot plays a central role in intermediary metabolism, by storing and mobilizing glycogen during the metabolic states, with these responses modulated during pregnancy, lactation and exercise [45]. Metabolizable energy intake is the key driver. The glycogen depot in the muscle on the other hand is particularly important for local energy homeostasis. Compared with simplestomached species, the rate of glycogen synthesis within ruminants is relatively low. Because ingested carbohydrates are efficiently fermented to short-chain fatty acids in the rumen, ruminants are required to meet the largest part of their glucose

*Livestock Health and Farming*

total glucose turnover [39].

the availability of energy and substrates.

the overall goal of self-maintenance. According to Aitken et al. [30], "many aspects of the bovine immune system are compromised around the time of calving, especially the inflammatory responses". Immune suppression in the periparturient dairy cow is a commonly observed phenomenon and has been linked to poor metabolic status and negative energy balance [13, 31, 32]. Thus, attenuation of the immune response to the various challenges is, in the first place, the result of limitations in

Besides energy, the organism requires protein, vitamins, minerals and trace elements in appropriate amounts in relation to the individual needs. Here the role of glucose must be emphasized: this substrate is used by the highly energy-demanding immune cells as a main source of fuel for immune defense and should therefore be considered the quantitatively most important fuel to fulfill the energy requirements of immune cells [33]. According to Ingvartsen and Moyes [34], "as glucose is the preferred fuel for immune cells, its low concentration during the transition period may partly explain the naturally occurring immunosuppression at this time". Another study [35] shows that ketones are not utilized by immune cells and in fact primarily act as inhibitors to immune responses when concentration is relatively high. In comparison with healthy controls, ketotic cows have increased circulating LPS prior to calving, and post-partum acute phase proteins such as LPS-binding protein, serum amyloid A and haptoglobin are also increased [35]. Endotoxin stimulates the immune system and activated leukocytes switch their metabolism away from oxidative phosphorylation to rely more on aerobic glycolysis [36]. The energetic cost of immune-activation is substantial but the ubiquitous nature of the immune system makes precise quantifying of the energetic demand difficult. Kvidera et al. [37] estimated approximately 1 kg of glucose is used by the immune system during a 12-hour period in which lactating dairy cows were challenged by LPS. This amounts to 2 kg of glucose per day for the immune system alone. This is more or less equivalent to the amount of glucose a cow withdraws in the form of lactose when producing an amount of 40 kg of milk per day [38]. In this context, it has to be considered that the synthesis of lactose alone utilizes 65–70% of the cow's

An increased immune system glucose utilization occurs simultaneously with infection induced decreased feed intake. This coupling of enhanced nutrient requirements with hypophagia further decreases the amount of nutrients available for the synthesis of milk. In the face of limited availability, glucose is allocated preferentially to a selected function at the expense of other functions, resulting in trade-offs and increased competitive pressure. Immune responses are contextspecific and the costs vary considerably depending on the pathogen, the environment and defense capacity of the host. Immune defense activities create highly individual outcomes depending on the initial and boundary conditions, and on the degree of the mismatch between demand and supply. The context-specific and individual nature of immune activation suggests that quantitative estimates of the costs of immune activation can be neither readily generalized nor predicted. This might explain why the costs of immune defense are not a prioritized issue of animal science. Apart from striving for an easy approach to asses energy requirements of farm animals, it is quite astonishing and disturbing to realize that the costs of selfmaintenance for farm animals are largely disregarded by the scientific discipline of animal nutrition. This may be due to the fact that feeding trials are generally conducted under standardized experimental conditions and usually on healthy animals which probably do not require high levels of additional energy and other substrates for the immune defense. Therefore, the results of feeding trials under experimental conditions enclose a high degree of uncertainty when transferred into practice on

dairy farms where production diseases are frequently found.

**58**

The 'barrel model', with its focus on energy demand and supply, considers neither the requirement of glucose for adaptation processes nor the need for a glucose buffer to fuel a short-term activation of the immune defense. Furthermore, it is obvious that the allocation of nutrients and energy resources for the various needs is not regulated independently, as assumed by the 'barrel model', but is highly interconnected. In the past, it may have been rational for the diet formulation to consider maintenance, growth and production as separate singular outputs. In face of increased knowledge, it is not justified to maintain these assumptions any longer.

## **6. Storage of energy and glucose resources**

Once nutrients are absorbed, they belong to the total energy and substrate pool and the stores of the body which make up the overall pool of resources. Metabolites in the form of carbohydrates, protein and fatty acids which are not needed in current metabolic processes are transformed and stored in the adipose tissues of the organism to serve as a reserve in periods of deficiencies. Fatty acids in the adipose tissues represent the main source of energy which the organism can fall back on when the supply does not meet the current needs. The 'barrel model' suggests that the energy balance is in general buffered by the storage capacity should the sum of the output rates not match the input [24]. Whenever intake is insufficient to support production – as in early lactation – energy is mobilized from body fat via the liver causing cows to milk off their backs and lose condition.

According to Friggens et al. [40], "high-yielding dairy cows have been genetically selected to partition even more glucose into milk production with the effect that reliance on body reserves has dramatically increased". Patton et al. [41] stated: "Even in the case of higher dietary intake, the increased input will primarily result in greater milk production while having little effect on energy imbalance and no beneficial effects on body condition and reserves at all". Although the storage capacities in the adipose tissue may seem to be abundant, the mobilization of fat can cause problems if the lipolysis is accelerated too fast. Metabolic changes, e.g. the process of uncontrolled lipid mobilization in response to excessive negative energy balance, increase the risk of ketosis, hepatic lipidosis and infectious diseases [42, 43]. Sordillo and Raphael [13] addressed the possible connections between fat mobilization and dysfunctional inflammation responses that may contribute to increased morbidity and mortality in the transition phase. Failing to adapt physiologically to an increase in nutrient requirements needed for the onset of milk synthesis is equivalent to metabolic stress and a major underlying factor in the development of transition cow disorders [44]. The authors conclude: "The combined effects of altered nutrient metabolism, dysfunctional inflammatory responses and oxidative stress can form destructive feedback loops that exacerbate metabolic stress and cause health disorders."

As mentioned above, dairy cows have a high demand for glucose. The storage form of glucose is glycogen and although widely distributed throughout the mammalian body, quantitatively the liver and muscle account for most of the body's glycogen stores. The liver glycogen depot plays a central role in intermediary metabolism, by storing and mobilizing glycogen during the metabolic states, with these responses modulated during pregnancy, lactation and exercise [45]. Metabolizable energy intake is the key driver. The glycogen depot in the muscle on the other hand is particularly important for local energy homeostasis. Compared with simplestomached species, the rate of glycogen synthesis within ruminants is relatively low. Because ingested carbohydrates are efficiently fermented to short-chain fatty acids in the rumen, ruminants are required to meet the largest part of their glucose

demand by de novo genesis [46]. A de novo generation of glucose by gluconeogenesis from non-carbohydrate precursors (e.g., lactate, glycerol, and amino acids) supplements the exogenous supply of glucose. Propionate is by far the predominant substrate for gluconeogenesis in ruminants [47]. The authors state that "the quantitatively most important adaption of metabolism to support the increased glucose demand in the immediate postpartum period is endogenous recycling of glucogenic carbon through lactate. This is mediated by a dual site of adaptation of metabolism in the liver and in the peripheral tissues, where the liver affinity for L-lactate is increased and glucose metabolism in peripheral tissues is shifted towards L-lactate formation over complete oxidation". Furthermore, the amino acid alanine is likely to contribute to liver release of glucose. If these adaptations fail, lipid metabolism may be altered. Increasing feed intake and provision of glucogenic precursors from the diet are important to ameliorate these disturbances. This applies in particular for an efficient gluconeogenesis because it is the major pathway for maintaining an adequate glucose supply. Glucose is, however, not only dedicated to the lactocytes in the udder, as emphasized by many animal scientists [39, 46], but is also as an essential fuel for many other cells and tissues of the organism. Thus, glucose needs to be permanently available at a sufficient level in the blood stream, and at the disposal of all cells which depend on it for their unimpaired operability. According to Bell [12], "daily requirements of glucose, amino acids, fatty acids and calcium for an early lactation cow are, respectively, more than 2.7, 2.0, 4.5 and 6.8 times greater than those needed for pregnancy. These differences represent changes in nutrient requirements over a short period of only one to two weeks, highlighting the tremendous metabolic alterations necessary to adequately support lactation." An imbalance in the glucose supply of high yielding cows in early lactation is unavoidable. The intensity of the imbalance is influenced not only by the level of milk yield and the degree of endogenous glucose provision but also by the demand of other essential tissues, inflammatory responses and, last but not least, by the immune defense.

In cases where dairy cows fail to cope with their living conditions due to the exceeding demands on their adaptation capacities, it is obvious that this is probably not only due to a lack of energy but also in particular to a lack of glucose. The concept of energy balance as represented in the 'barrel model' seriously neglects the role of glucose and especially the increased competition for it between the immune cells and the epithelial cells in the mammary gland. Furthermore, the 'barrel model' fails to consider that unpredictable events, including many biotic and abiotic stressors, need to be dealt with through immediate physiological and behavioral adjustments which can lead to situations in which the availabilities and the promptness of mobilization are overstressed.

#### **7. Regulation of resource allocation**

Biological regulation of the glucose balance within the organism involves a series of orchestrated changes; increased hepatic rates of gluconeogenesis, decreased glucose uptake and use by adipose tissue and muscle, a shift in whole-body nutrient oxidation so that less glucose is available as an energy source. First and foremost, the mobilization of essential resources requires well-functioning regulatory capacities to enable an efficient exploitation of resources to orchestrate a release of nutrients matching the requirements to a high degree and to deal with possible bottlenecks in metabolic pathways.

According to Baumgard et al. [39], the priority objective of the regulation is to ensure an adequate glucose supply to support lactation. A cow in a state of negative energy balance is considered "metabolically flexible" because she can depend upon

**61**

*Nutrition and Health-Management in Dairy Production DOI: http://dx.doi.org/10.5772/intechopen.89447*

alternative fuels (NEFA and ketones) to save glucose. In high yielding cows, the utilization of body energy reserves and the mobilization of body fat in the first month postpartum can be energetically equal to over one-third of the milk produced [48]. From a different perspective, the objective of regulation is to continually adjust the milieu to promote survival. Sterling and Eyer [49] introduced the term "allostasis" to refer to "changing regulatory systems ("stability through change"). Allostasis can be considered as the process of maximizing fitness in the face of environmental change and other unpredictable challenges. Regulatory mechanisms must change in order to maintain or achieve a state appropriate for the time of day or year and also in response to disturbances." From the perspective of the dairy cow, milk secretion is accompanied by substantial losses of energy and nutrients, particularly glucose from the body pool. A marked increase of cell differentiation and tissue hypertrophy in the udder is the starting point of an increase in milk yield [50]. According to Stefanon et al. [51], "the number of vital mammary epithelial cells control the initial conditions for the amount of milk produced as well as the amount of glucose needed for the production and secretion of lactose." Cows with a high genetic performance capacity for milk production are characterized by the ability to perform intensive gluconeogenesis and partitioning of the glucose into the udder while its contribution as a fuel source to extra-mammary tissues is decreased [12]. Because the uptake of glucose by the epithelial cells in the mammary gland is not insulin dependent, the cells have priority access to the glucose in the blood stream. According to Bauman et al. [52], "the productivity of this biological factory is extensive and in terms of the use of nutrients and energy, the cow should be viewed

as an "appendage to the mammary gland" rather than vice versa."

capacities are able to balance the trade-offs in their demands for glucose.

According to Lucy [54], "nutrient prioritization in early lactation to favor milk production over fertility is a reasonable strategy in biology. As nutrition becomes scarce, the lactating dam will preferentially invest the limited resources in the survival of living offspring rather than gambling on the oocyte that is yet to be ovulated, fertilized and cared for during an entire gestation. Selection for high milk yields takes advantage of the genetically programmed readiness of the dairy cow to enter into a negative energy balance at the onset of lactation and to mobilize resources from its body tissues." What is a natural biological process to ensure the maintenance of the offspring, however, might prove to be a self-harming trap when the selection process advances into dimensions that are far beyond the initial intention to ensure nutrient supply to the off-spring via milk. Dairy farming, and particularly breeding measures, takes advantage of the vulnerability of dairy cows

Due to a sudden increase of nutrient requirements for milk production postpartum, a time when dry matter intake and nutrient supply lag behind, nearly every high yielding cow faces the challenge of shortages in energy and nutrients. According to Eastridge [53], "increases in genetic merit for milk yield go together with increases in feed intake but the latter does not fully compensate for the extra energy demands during early lactation. This results in a more or less extended negative energy balance and increased mobilization of body reserves." In order to sustain the various life-preserving functions, a limited availability of glucose provokes severe competition between different tissues in their need for glucose. It follows that "limitations require partitioning, and partitioning requires prioritization in guiding the nutrient flow to ensure that the demands of other cells, tissues and organs within the organism are not completely neglected" [48]. Accordingly, there is a need to avoid ruinous competition between sub-systems to prevent them from being swamped by unwanted side reactions which affect the viability of the system. Parasitic reactions by single organs at the expense of other organs may cause the whole organism to collapse. The question is, how and to what degree the regulation

#### *Nutrition and Health-Management in Dairy Production DOI: http://dx.doi.org/10.5772/intechopen.89447*

*Livestock Health and Farming*

demand by de novo genesis [46]. A de novo generation of glucose by gluconeogenesis from non-carbohydrate precursors (e.g., lactate, glycerol, and amino acids) supplements the exogenous supply of glucose. Propionate is by far the predominant substrate for gluconeogenesis in ruminants [47]. The authors state that "the quantitatively most important adaption of metabolism to support the increased glucose demand in the immediate postpartum period is endogenous recycling of glucogenic carbon through lactate. This is mediated by a dual site of adaptation of metabolism in the liver and in the peripheral tissues, where the liver affinity for L-lactate is increased and glucose metabolism in peripheral tissues is shifted towards L-lactate formation over complete oxidation". Furthermore, the amino acid alanine is likely to contribute to liver release of glucose. If these adaptations fail, lipid metabolism may be altered. Increasing feed intake and provision of glucogenic precursors from the diet are important to ameliorate these disturbances. This applies in particular for an efficient gluconeogenesis because it is the major pathway for maintaining an adequate glucose supply. Glucose is, however, not only dedicated to the lactocytes in the udder, as emphasized by many animal scientists [39, 46], but is also as an essential fuel for many other cells and tissues of the organism. Thus, glucose needs to be permanently available at a sufficient level in the blood stream, and at the disposal of all cells which depend on it for their unimpaired operability. According to Bell [12], "daily requirements of glucose, amino acids, fatty acids and calcium for an early lactation cow are, respectively, more than 2.7, 2.0, 4.5 and 6.8 times greater than those needed for pregnancy. These differences represent changes in nutrient requirements over a short period of only one to two weeks, highlighting the tremendous metabolic alterations necessary to adequately support lactation." An imbalance in the glucose supply of high yielding cows in early lactation is unavoidable. The intensity of the imbalance is influenced not only by the level of milk yield and the degree of endogenous glucose provision but also by the demand of other essential tissues, inflammatory responses and, last but not least, by the immune defense. In cases where dairy cows fail to cope with their living conditions due to the exceeding demands on their adaptation capacities, it is obvious that this is probably not only due to a lack of energy but also in particular to a lack of glucose. The concept of energy balance as represented in the 'barrel model' seriously neglects the role of glucose and especially the increased competition for it between the immune cells and the epithelial cells in the mammary gland. Furthermore, the 'barrel model' fails to consider that unpredictable events, including many biotic and abiotic stressors, need to be dealt with through immediate physiological and behavioral adjustments which can lead to situations in which the availabilities and the prompt-

**60**

ness of mobilization are overstressed.

**7. Regulation of resource allocation**

bottlenecks in metabolic pathways.

Biological regulation of the glucose balance within the organism involves a series

According to Baumgard et al. [39], the priority objective of the regulation is to ensure an adequate glucose supply to support lactation. A cow in a state of negative energy balance is considered "metabolically flexible" because she can depend upon

of orchestrated changes; increased hepatic rates of gluconeogenesis, decreased glucose uptake and use by adipose tissue and muscle, a shift in whole-body nutrient oxidation so that less glucose is available as an energy source. First and foremost, the mobilization of essential resources requires well-functioning regulatory capacities to enable an efficient exploitation of resources to orchestrate a release of nutrients matching the requirements to a high degree and to deal with possible

alternative fuels (NEFA and ketones) to save glucose. In high yielding cows, the utilization of body energy reserves and the mobilization of body fat in the first month postpartum can be energetically equal to over one-third of the milk produced [48]. From a different perspective, the objective of regulation is to continually adjust the milieu to promote survival. Sterling and Eyer [49] introduced the term "allostasis" to refer to "changing regulatory systems ("stability through change"). Allostasis can be considered as the process of maximizing fitness in the face of environmental change and other unpredictable challenges. Regulatory mechanisms must change in order to maintain or achieve a state appropriate for the time of day or year and also in response to disturbances." From the perspective of the dairy cow, milk secretion is accompanied by substantial losses of energy and nutrients, particularly glucose from the body pool. A marked increase of cell differentiation and tissue hypertrophy in the udder is the starting point of an increase in milk yield [50]. According to Stefanon et al. [51], "the number of vital mammary epithelial cells control the initial conditions for the amount of milk produced as well as the amount of glucose needed for the production and secretion of lactose." Cows with a high genetic performance capacity for milk production are characterized by the ability to perform intensive gluconeogenesis and partitioning of the glucose into the udder while its contribution as a fuel source to extra-mammary tissues is decreased [12]. Because the uptake of glucose by the epithelial cells in the mammary gland is not insulin dependent, the cells have priority access to the glucose in the blood stream. According to Bauman et al. [52], "the productivity of this biological factory is extensive and in terms of the use of nutrients and energy, the cow should be viewed as an "appendage to the mammary gland" rather than vice versa."

Due to a sudden increase of nutrient requirements for milk production postpartum, a time when dry matter intake and nutrient supply lag behind, nearly every high yielding cow faces the challenge of shortages in energy and nutrients. According to Eastridge [53], "increases in genetic merit for milk yield go together with increases in feed intake but the latter does not fully compensate for the extra energy demands during early lactation. This results in a more or less extended negative energy balance and increased mobilization of body reserves." In order to sustain the various life-preserving functions, a limited availability of glucose provokes severe competition between different tissues in their need for glucose. It follows that "limitations require partitioning, and partitioning requires prioritization in guiding the nutrient flow to ensure that the demands of other cells, tissues and organs within the organism are not completely neglected" [48]. Accordingly, there is a need to avoid ruinous competition between sub-systems to prevent them from being swamped by unwanted side reactions which affect the viability of the system. Parasitic reactions by single organs at the expense of other organs may cause the whole organism to collapse. The question is, how and to what degree the regulation capacities are able to balance the trade-offs in their demands for glucose.

According to Lucy [54], "nutrient prioritization in early lactation to favor milk production over fertility is a reasonable strategy in biology. As nutrition becomes scarce, the lactating dam will preferentially invest the limited resources in the survival of living offspring rather than gambling on the oocyte that is yet to be ovulated, fertilized and cared for during an entire gestation. Selection for high milk yields takes advantage of the genetically programmed readiness of the dairy cow to enter into a negative energy balance at the onset of lactation and to mobilize resources from its body tissues." What is a natural biological process to ensure the maintenance of the offspring, however, might prove to be a self-harming trap when the selection process advances into dimensions that are far beyond the initial intention to ensure nutrient supply to the off-spring via milk. Dairy farming, and particularly breeding measures, takes advantage of the vulnerability of dairy cows

in their self-defense against an excessive load by the demands of the mammary gland. However, milk production to safeguard the off-spring on the one hand and self-preservation of the dam on the other can come into life-threatening conflicts. This is the case when the gap between demand and supply gets to the stage where metabolic regulations are at risk of failing to balance the capacity of gluconeogenesis with the secretion of lactose, and of failing to mobilize the body resources needed to compensate for the deficits between nutrient output and intake. In general, the partitioning of resources within the organism is an excellent example of how cooperation works as long as there are enough resources available and as long as one part of the whole does not make unlimited demands at the expense of other parts. Shortcomings and problems can occur within several steps of the adaptation process, particularly those involving the adipose tissue and the liver. Further details have been explained elsewhere [10].

Generally, three options exist to alleviate the frequency and effects of these shortcomings and problems: (i) promote the absorption of resources to enhance availability or (ii) increase efficiency in the use of resources by partitioning the resources to those tissues and organs with the highest priority for the overall objective of self-maintenance or (iii) reduce the use of resources from the body pool as far as possible to sustain essential body functions. As absorption and partitioning have been optimized through a long-lasting evolutionary process, the major weak point lies in the limited capabilities to restrict nutrient losses via milk when it is necessary for the prevention of exhaustion due to overwhelming demands, and for self-maintenance. While the liver and muscle tissue have glycogen stores at their disposal, the mammary gland and the immune system rely completely on the body glucose pool. The body pool allows efficient trade-offs, that is, the organs grant each other short-term loans. If each organ were independently self-regulated, they would require their own reserve capacity, and thus more digestive capacity, to support an expensive infrastructure rarely used [55]. Efficiency in the use of limited resources requires organs to trade-off resources, that is, to grant each other short-term loans. However, milk secretion does not have an underlying central counter regulation which would enable a throttling of energy and nutrient losses via milk to prevent the dams from exhaustion and emaciation which subsequently weakens their adaptation capacities and risks their self-preservation.

The 'barrel model' illustrates that milking opens the flood gate for the loss of energy and nutrients, particularly glucose, from the body pool. However, energy and substrate losses, particularly glucose losses, can be so high that the minimum level required to sustain essential functions of the organism for self-maintenance is not maintained. The model is lacking possibilities to detect the filling state of essential resources in the body pool and thus those who are in charge lack information to throttle the outputs via milk to a degree necessary to leave enough resources for the processes of self-maintenance.

#### **8. Dealing with inter- and intraindividual variation**

The average milk yield per cow has increased considerably over the last decades, primarily as the result of genetic selection based on the moderate to high heritability of most production traits and the corresponding improvements in feeding regimes. Although animal breeders have accomplished a great deal in the past, they are not satisfied with these accomplishments. Accordingly, it is no surprise that the partitioning of energy within the organisms has also raised their interest. For animal breeders, options that emerge from the fields of genomics, proteomics, etc. to incorporate genetic differences between animals into nutritional models represent

**63**

both energy and protein balance.

*Nutrition and Health-Management in Dairy Production DOI: http://dx.doi.org/10.5772/intechopen.89447*

an area of exciting opportunity to improve nutrient partitioning and productive efficiency [39, 56]. According to Baumgard et al. [39], it is in fact only when the coordination of nutrient use is inadequate or an imbalance occurs that animal well-being and performance are compromised. However, in contrast to the underlying assumptions that inadequate coordination and imbalances in nutrient supply are exceptions, there is profound evidence suggesting that this is in fact the rule. The reasons are multi-layered and encompass the degree of supply, the processes in intermediary metabolism, the total requirements, and their coordination at the farm and animal level. The main reason, however, is inherent in the production process and lies in the large variation in the living conditions within and between dairy farms and in the intra and inter-individual variation at the animal level. Dairy cows live under quite heterogeneous nutritional and environmental conditions and the individual animals themselves differ highly in their condition, their reaction and adaption capacities and, therefore, in their adaptive success. For example, while calculated energy balance is typically most negative within the first 12 days postpartum [57], differences amongst cows in time and extent of nadir and total energy deficits are large. In their study, the authors revealed that "over the course of 122 lactations mean values of total energy deficits during early lactation amounted to 1451 MJ NEL with a standard deviation of ±1062 MJ NEL. The postpartum interval to nadir of the estimated energy balance averaged 48 ± 29 days." Moreover, cows differ considerably with regard to the partitioning of energy and glucose between different physiological systems. Thus, cows with similar energy intakes and expenditures via the milk may actually experience differences in the burden of NEB and the shortage of glucose. This is not only based on genetic make-up (e.g. high v. low genetic merit) or the stage of lactation but varies greatly between individuals of the same genotype or in the same stage of lactation [58]. In their study, which allowed "discrimination between the roles of genotype (G), environment (E) (e.g. feed caloric density and milking frequency) and GxE interactions, the effects of genetic merit and milking frequency were significant only in the groups that were fed rations with high caloric density. However, signs of severe deficits in the availability of energy, poor protein balance and low body condition scores were not concentrated in the highest producing cows." Regardless of genotype, a reduced energy supply and extra milking had strong unfavorable effects on

Large variations exist not only in terms of input and output but also in the availability of the various nutrients within the body pool. Substantial day to day variations in digestion and fermentation processes in dairy cows cause considerable variations in the relative quantities and supply of essential nutritional elements from the intermediate metabolic processes. This variation in the size of supply represents a real challenge for the metabolism in the face of demands for milk production and self-maintenance. Animals kept under highly standardized conditions on a research farm showed remarkable differences in changes in the concentrations of metabolites and hormones during the postpartum period [59, 60]. These findings indicate that the ability to cope with metabolic stress varies considerably between individual cows. On the other hand, energy partitioning between milk and body tissue can be altered considerably by diets that differ in lipogenic and glucogenic nutrient content [61, 62]. In addition, animals show enormous differences when confronted with various biotic and abiotic stressors and pathogens. In their reactions to changes in the environment, animals are not only influenced by the specific initial and boundary conditions, they also react self-referentially [63]. Unlike machines, their individual reactions cannot be predicted due to the interconnectedness of the numerous variables interacting with each other in a way that can switch

from a more synergistic to an antagonistic relationship and vice versa.

*Livestock Health and Farming*

have been explained elsewhere [10].

adaptation capacities and risks their self-preservation.

**8. Dealing with inter- and intraindividual variation**

for the processes of self-maintenance.

in their self-defense against an excessive load by the demands of the mammary gland. However, milk production to safeguard the off-spring on the one hand and self-preservation of the dam on the other can come into life-threatening conflicts. This is the case when the gap between demand and supply gets to the stage where metabolic regulations are at risk of failing to balance the capacity of gluconeogenesis with the secretion of lactose, and of failing to mobilize the body resources needed to compensate for the deficits between nutrient output and intake. In general, the partitioning of resources within the organism is an excellent example of how cooperation works as long as there are enough resources available and as long as one part of the whole does not make unlimited demands at the expense of other parts. Shortcomings and problems can occur within several steps of the adaptation process, particularly those involving the adipose tissue and the liver. Further details

Generally, three options exist to alleviate the frequency and effects of these shortcomings and problems: (i) promote the absorption of resources to enhance availability or (ii) increase efficiency in the use of resources by partitioning the resources to those tissues and organs with the highest priority for the overall objective of self-maintenance or (iii) reduce the use of resources from the body pool as far as possible to sustain essential body functions. As absorption and partitioning have been optimized through a long-lasting evolutionary process, the major weak point lies in the limited capabilities to restrict nutrient losses via milk when it is necessary for the prevention of exhaustion due to overwhelming demands, and for self-maintenance. While the liver and muscle tissue have glycogen stores at their disposal, the mammary gland and the immune system rely completely on the body glucose pool. The body pool allows efficient trade-offs, that is, the organs grant each other short-term loans. If each organ were independently self-regulated, they would require their own reserve capacity, and thus more digestive capacity, to support an expensive infrastructure rarely used [55]. Efficiency in the use of limited resources requires organs to trade-off resources, that is, to grant each other short-term loans. However, milk secretion does not have an underlying central counter regulation which would enable a throttling of energy and nutrient losses via milk to prevent the dams from exhaustion and emaciation which subsequently weakens their

The 'barrel model' illustrates that milking opens the flood gate for the loss of energy and nutrients, particularly glucose, from the body pool. However, energy and substrate losses, particularly glucose losses, can be so high that the minimum level required to sustain essential functions of the organism for self-maintenance is not maintained. The model is lacking possibilities to detect the filling state of essential resources in the body pool and thus those who are in charge lack information to throttle the outputs via milk to a degree necessary to leave enough resources

The average milk yield per cow has increased considerably over the last decades, primarily as the result of genetic selection based on the moderate to high heritability of most production traits and the corresponding improvements in feeding regimes. Although animal breeders have accomplished a great deal in the past, they are not satisfied with these accomplishments. Accordingly, it is no surprise that the partitioning of energy within the organisms has also raised their interest. For animal breeders, options that emerge from the fields of genomics, proteomics, etc. to incorporate genetic differences between animals into nutritional models represent

**62**

an area of exciting opportunity to improve nutrient partitioning and productive efficiency [39, 56]. According to Baumgard et al. [39], it is in fact only when the coordination of nutrient use is inadequate or an imbalance occurs that animal well-being and performance are compromised. However, in contrast to the underlying assumptions that inadequate coordination and imbalances in nutrient supply are exceptions, there is profound evidence suggesting that this is in fact the rule. The reasons are multi-layered and encompass the degree of supply, the processes in intermediary metabolism, the total requirements, and their coordination at the farm and animal level. The main reason, however, is inherent in the production process and lies in the large variation in the living conditions within and between dairy farms and in the intra and inter-individual variation at the animal level.

Dairy cows live under quite heterogeneous nutritional and environmental conditions and the individual animals themselves differ highly in their condition, their reaction and adaption capacities and, therefore, in their adaptive success. For example, while calculated energy balance is typically most negative within the first 12 days postpartum [57], differences amongst cows in time and extent of nadir and total energy deficits are large. In their study, the authors revealed that "over the course of 122 lactations mean values of total energy deficits during early lactation amounted to 1451 MJ NEL with a standard deviation of ±1062 MJ NEL. The postpartum interval to nadir of the estimated energy balance averaged 48 ± 29 days." Moreover, cows differ considerably with regard to the partitioning of energy and glucose between different physiological systems. Thus, cows with similar energy intakes and expenditures via the milk may actually experience differences in the burden of NEB and the shortage of glucose. This is not only based on genetic make-up (e.g. high v. low genetic merit) or the stage of lactation but varies greatly between individuals of the same genotype or in the same stage of lactation [58]. In their study, which allowed "discrimination between the roles of genotype (G), environment (E) (e.g. feed caloric density and milking frequency) and GxE interactions, the effects of genetic merit and milking frequency were significant only in the groups that were fed rations with high caloric density. However, signs of severe deficits in the availability of energy, poor protein balance and low body condition scores were not concentrated in the highest producing cows." Regardless of genotype, a reduced energy supply and extra milking had strong unfavorable effects on both energy and protein balance.

Large variations exist not only in terms of input and output but also in the availability of the various nutrients within the body pool. Substantial day to day variations in digestion and fermentation processes in dairy cows cause considerable variations in the relative quantities and supply of essential nutritional elements from the intermediate metabolic processes. This variation in the size of supply represents a real challenge for the metabolism in the face of demands for milk production and self-maintenance. Animals kept under highly standardized conditions on a research farm showed remarkable differences in changes in the concentrations of metabolites and hormones during the postpartum period [59, 60]. These findings indicate that the ability to cope with metabolic stress varies considerably between individual cows. On the other hand, energy partitioning between milk and body tissue can be altered considerably by diets that differ in lipogenic and glucogenic nutrient content [61, 62]. In addition, animals show enormous differences when confronted with various biotic and abiotic stressors and pathogens. In their reactions to changes in the environment, animals are not only influenced by the specific initial and boundary conditions, they also react self-referentially [63]. Unlike machines, their individual reactions cannot be predicted due to the interconnectedness of the numerous variables interacting with each other in a way that can switch from a more synergistic to an antagonistic relationship and vice versa.

In light of the large variation in biological processes and the deriving high level of complexity, the "barrel model" approach seems to be comparatively too simple and thus is not suited to be used in breeding and system biology to deal with differences between animals in the partitioning of nutrients. The approach lacks appropriate options to assess and deal with the intra and inter-individual variation of animals in their ability to cope with the highly variable internal and external challenges. The large amount of data harvested by "omics" techniques are noncausal. Nevertheless, representatives of "omics" research claim to demonstrate functionality and to develop a more comprehensive understanding of the regulation of the physiological processes and their role in animal productivity and animal health while applying the descriptive information gained from their research [39]. However, without accounting for either the large intra and inter-individual variation at the animal level or the variation in the living conditions at the farm level, it seems rather over-ambitious and presumptuous to claim accurate interpretation of the correlated changes.

A recent study [64], conducted on rabbits, provides some interesting observations and conclusions. Observing the resource allocation in different maternal rabbit lines revealed that the so-called "generalists" were able to appropriately allocate their resources to production, reproduction and health under suboptimal environmental conditions. The so-called "specialists" with high prolificacy were not able to allocate sufficient resources into health and reproduction. The authors concluded that the environment in which the animals are selected clearly drives the interplay between functions within the organism. If the objective of a selection program is to improve the overall fitness of animals without impairing productivity, a strategy is required that strives to establish a line of generalists.

#### **9. Need for facts instead of assumptions**

While the success of breeding programs in increasing the performance of dairy cows is obvious, their contribution towards improving the capacity of the animals to cope with unbalanced metabolic situations and challenges remains questionable. Breeding follows a single-sided approach that does not cover the multifactorial development of disorders and diseases, i.e., the approach does not consider why some animals are able to cope better than others. Nor does the approach take into account the context in which the animals are challenged. This applies not only to the respective conditions in which they live but also to the resources they can rely on or are lacking. In general, an external validation is not carried out because within breeding programs it cannot be assessed whether failures of animals in coping with the challenges are related to the genome or to the respective living conditions or to the interactions between both. Due to the lack of casual relationships, breeding programs can provide correlations but not explanations. Breeding programs do not demand, and cannot provide, a solution for the problems in the here and now. However, focusing and counting on breeding has the unbeatable advantage that it requires a fundamental change neither in the living conditions nor in the willingness to accept responsibility for the living conditions of the animals.

Primary causes and disturbing influences which contribute to the development of production diseases are manifold. They vary considerably between farms and animals. Some farms do well whilst others fail quite markedly in reducing clinical and subclinical problems, irrespective of average milk yields [11]. However, little is known about the causal network between the various factors involved in the uptake, partitioning and excretion of energy and nutrients [10]. Compounding the problem is the fact that variables such as feed intake, body condition, postpartum health and

**65**

to single factors [10].

*Nutrition and Health-Management in Dairy Production DOI: http://dx.doi.org/10.5772/intechopen.89447*

performance vary so widely amongst individual cows. Disturbances like change in diet, climatic conditions (heat stress), pathogen pressure, access reduction to trophic resources caused by competition with other individuals, injuries, diseases and other challenges can occur slowly or abruptly. The effects are disruptive and may be cumulative over hours or days or weeks. Additionally, factors such as an animal's current state of health and social status etc. may influence how it goes about its routines and how it responds to disturbances. Despite the highly heterogenous situation on dairy farms and the inter and intra-individual variation between dairy cows, the dairy industry still anticipates more robust and mechanistic models for predicting supplies and requirements of absorbed nutrients and available energy. Such models are expected to be useful in allowing for increased efficiency in the use of feed resources. Given the numerous influencing factors, the meaningfulness of models based on a few quantifiable variables is questionable, particularly when it comes to predicting the real outcomes. As adaptive success depends on the interactions between the level and type of threat, and on the current individual responsiveness of the cow, modeling this process is barely an option, let alone it providing information that allows for dependable prediction of outcomes. Nevertheless, modeling is suited to providing orientation towards possible outcomes (see explanations below). High producing dairy cows are at a high risk of losing the capacity to cope with disadvantageous keeping and feeding conditions [58]. Diseases in animals are an indication that their physiological condition is out of balance [10]. This is often due to limitations and mismatches of resource allocation. Ingvartsen et al. [65] pointed out that evaluations found in literature on the relationship between performance and incidence of Pd are in all probability meaningless as inherent biological correlations – besides within and between-herd confounding effects – exist. According to Mulligan and Doherty [7], the hypothesis that high yielding cows automatically have higher levels of production diseases is likely to be as false as the hypothesis that lower yielding cows have lower levels of production diseases. Health problems are context-variable and need to be addressed in the context in which they emerge. Often, the degree of the clinical signs of disorders and diseases is neither assessed comprehensively nor monitored consistently, let alone always tracked down to the possible causes [66]. Achieving a low prevalence of production diseases is rarely considered as an independent production goal as it is easier to simply perceive them as being an unavoidable negative side effect of production processes. The multifactorial background of production diseases as the result of overstressed adaptation capacities hinders easy identification and solving of health problems. Commercial farms can seldom provide conditions that allow observations to be performed on a ceteris paribus basis as under experimental conditions. In contrast, impacts of the various influencing factors on the ability of farm animals to cope are not constant and do not emerge separately from one other. Adaptation is a functional and targetoriented process involving the whole organism and thus cannot be narrowed down

Instead of following general assumptions and mental associations about possible relationships between single variables and the impacts of management measures on these variables, an obvious step when striving to solve health problems in the here and now is to estimate the degree of metabolic disorders and associated comorbidities at an individual farm level. Doing this requires regular monitoring, an indispensable component of any serious attempts to develop context-specific strategies regarding the improvements of production diseases. This alone, however, is not enough. It needs to be supplemented with the acquisition of further data on individual cows, particularly the degree to which the energy and nutrient supply correlates to the individual needs of an animal according to its specific stage of life and living situation. Yet, generally speaking, even when available, farm management is often

#### *Nutrition and Health-Management in Dairy Production DOI: http://dx.doi.org/10.5772/intechopen.89447*

*Livestock Health and Farming*

the correlated changes.

required that strives to establish a line of generalists.

**9. Need for facts instead of assumptions**

In light of the large variation in biological processes and the deriving high level of complexity, the "barrel model" approach seems to be comparatively too simple and thus is not suited to be used in breeding and system biology to deal with differences between animals in the partitioning of nutrients. The approach lacks appropriate options to assess and deal with the intra and inter-individual variation of animals in their ability to cope with the highly variable internal and external challenges. The large amount of data harvested by "omics" techniques are noncausal. Nevertheless, representatives of "omics" research claim to demonstrate functionality and to develop a more comprehensive understanding of the regulation of the physiological processes and their role in animal productivity and animal health while applying the descriptive information gained from their research [39]. However, without accounting for either the large intra and inter-individual variation at the animal level or the variation in the living conditions at the farm level, it seems rather over-ambitious and presumptuous to claim accurate interpretation of

A recent study [64], conducted on rabbits, provides some interesting observations and conclusions. Observing the resource allocation in different maternal rabbit lines revealed that the so-called "generalists" were able to appropriately allocate their resources to production, reproduction and health under suboptimal environmental conditions. The so-called "specialists" with high prolificacy were not able to allocate sufficient resources into health and reproduction. The authors concluded that the environment in which the animals are selected clearly drives the interplay between functions within the organism. If the objective of a selection program is to improve the overall fitness of animals without impairing productivity, a strategy is

While the success of breeding programs in increasing the performance of dairy cows is obvious, their contribution towards improving the capacity of the animals to cope with unbalanced metabolic situations and challenges remains questionable. Breeding follows a single-sided approach that does not cover the multifactorial development of disorders and diseases, i.e., the approach does not consider why some animals are able to cope better than others. Nor does the approach take into account the context in which the animals are challenged. This applies not only to the respective conditions in which they live but also to the resources they can rely on or are lacking. In general, an external validation is not carried out because within breeding programs it cannot be assessed whether failures of animals in coping with the challenges are related to the genome or to the respective living conditions or to the interactions between both. Due to the lack of casual relationships, breeding programs can provide correlations but not explanations. Breeding programs do not demand, and cannot provide, a solution for the problems in the here and now. However, focusing and counting on breeding has the unbeatable advantage that it requires a fundamental change neither in the living conditions nor in the willing-

ness to accept responsibility for the living conditions of the animals.

Primary causes and disturbing influences which contribute to the development of production diseases are manifold. They vary considerably between farms and animals. Some farms do well whilst others fail quite markedly in reducing clinical and subclinical problems, irrespective of average milk yields [11]. However, little is known about the causal network between the various factors involved in the uptake, partitioning and excretion of energy and nutrients [10]. Compounding the problem is the fact that variables such as feed intake, body condition, postpartum health and

**64**

performance vary so widely amongst individual cows. Disturbances like change in diet, climatic conditions (heat stress), pathogen pressure, access reduction to trophic resources caused by competition with other individuals, injuries, diseases and other challenges can occur slowly or abruptly. The effects are disruptive and may be cumulative over hours or days or weeks. Additionally, factors such as an animal's current state of health and social status etc. may influence how it goes about its routines and how it responds to disturbances. Despite the highly heterogenous situation on dairy farms and the inter and intra-individual variation between dairy cows, the dairy industry still anticipates more robust and mechanistic models for predicting supplies and requirements of absorbed nutrients and available energy. Such models are expected to be useful in allowing for increased efficiency in the use of feed resources. Given the numerous influencing factors, the meaningfulness of models based on a few quantifiable variables is questionable, particularly when it comes to predicting the real outcomes. As adaptive success depends on the interactions between the level and type of threat, and on the current individual responsiveness of the cow, modeling this process is barely an option, let alone it providing information that allows for dependable prediction of outcomes. Nevertheless, modeling is suited to providing orientation towards possible outcomes (see explanations below).

High producing dairy cows are at a high risk of losing the capacity to cope with disadvantageous keeping and feeding conditions [58]. Diseases in animals are an indication that their physiological condition is out of balance [10]. This is often due to limitations and mismatches of resource allocation. Ingvartsen et al. [65] pointed out that evaluations found in literature on the relationship between performance and incidence of Pd are in all probability meaningless as inherent biological correlations – besides within and between-herd confounding effects – exist. According to Mulligan and Doherty [7], the hypothesis that high yielding cows automatically have higher levels of production diseases is likely to be as false as the hypothesis that lower yielding cows have lower levels of production diseases. Health problems are context-variable and need to be addressed in the context in which they emerge. Often, the degree of the clinical signs of disorders and diseases is neither assessed comprehensively nor monitored consistently, let alone always tracked down to the possible causes [66]. Achieving a low prevalence of production diseases is rarely considered as an independent production goal as it is easier to simply perceive them as being an unavoidable negative side effect of production processes. The multifactorial background of production diseases as the result of overstressed adaptation capacities hinders easy identification and solving of health problems. Commercial farms can seldom provide conditions that allow observations to be performed on a ceteris paribus basis as under experimental conditions. In contrast, impacts of the various influencing factors on the ability of farm animals to cope are not constant and do not emerge separately from one other. Adaptation is a functional and targetoriented process involving the whole organism and thus cannot be narrowed down to single factors [10].

Instead of following general assumptions and mental associations about possible relationships between single variables and the impacts of management measures on these variables, an obvious step when striving to solve health problems in the here and now is to estimate the degree of metabolic disorders and associated comorbidities at an individual farm level. Doing this requires regular monitoring, an indispensable component of any serious attempts to develop context-specific strategies regarding the improvements of production diseases. This alone, however, is not enough. It needs to be supplemented with the acquisition of further data on individual cows, particularly the degree to which the energy and nutrient supply correlates to the individual needs of an animal according to its specific stage of life and living situation. Yet, generally speaking, even when available, farm management is often

not able to correctly interpret data regarding the negative energy balance of the individual cows and thus cannot know which animals are at a higher or a lower risk, which animals are able to cope with the NEB and which ones are showing disorders as a sign of adaption stress due to whatever reasons.
