The transition period into lactation remains one of the most challenging and important phases of the production cycle in a dairy cow. It is a transient period around calving characterised by drastic changes in the hormonal status, 2 to 5-fold (Bradford, 2020) increases in nutrient demand and apportioning of 85% of body glucose to the mammary gland. Simultaneously, the requirement for specific fatty acids escalates by more than four times (Bell, 1995; McFadden and Rico, 2020). To put into context the magnitude of these changes, lactation accounts for up to 70% of total daily requirements for energy of the dairy cow (Moran, 2005; McFadden, 2020). Indeed, in his eminent review of the biology of dairy cows during transition period, Drackley (1999) came to a conclusion that the biology underlying the transition to lactation was the “final frontier” in our understanding of the dairy cow.
According to Drackley et al. (2001), NRC (2001) and Overton et al. (2004) the changes above are accentuated by increased hepatic gluconeogenesis and ketogenesis. The adaptive processes include enhanced blood supply to the mammary gland and restricted skeletal muscle protein growth and adipose tissue lipogenesis. There is also elevated adipose tissue lipolysis and plasma fatty acid levels, and greater utilisation of fatty acids and amino acids for oxidative metabolism in the liver. These increased metabolic dynamics occur when dry matter intake is at its lowest level, presenting something of a paradox in transition cow nutrition and management in many dairy farms.
In early lactation, the challenge for the cow to shift gear to accelerate copious milk production against loss of appetite results in nutrient deficiencies and subsequent negative energy balance leading to mobilisation of body reserves and compromised immunity (Fiore et al., 2017). Endocrine, adipose tissue, liver, digestive system and mammary gland are key components of the adaptations that dairy cows experience to achieve the necessary balance to adjust to the onset of sustained increasing milk production. If unchecked metabolic stress in the affected cows can burden dairy producers with increased poor cow health, infertility, culling rates, inefficient nutrient utilisation and economic loss.
Role of fatty acids
Among the nutritional interventions that are being researched closely to provide evidence to support product suitability for use in transition cow management is the impact of fatty acid nutrition.
Fatty acids are known to be more than just energy currency, constituents of cellular membranes or building blocks of triglycerides (Pires and Grummer, 2008). They are bioactive metabolites that signal and modulate a number of important biochemical processes in the dairy cow which can be manipulated as a part of the nutritional strategies to improve transition cow health and performance.
Immediately following calving, majority of cows in the transition period experience some form of impaired immune function which precipitates inflammation (Goff, 2008). A cascade of events which follows increases inflammatory molecules which are known to reduce appetite (Kuhla, 2020). At the same time the key rapid response immune cell types decline after calving. There is also some evidence to suggest compromised antibody production. In addition, Bradford et al. (2015) suggested that the onset of lactation opens new avenues for pathogenic infections. All these factors make it hard for the cow to combat disease pressure and perform well.
Increasing immune function is important to reproductive function. Postpartum excess fat accumulation in the oocytes and regenerating endometrial tissues reduces fertility as a result of increased embryo mortality caused by inflammation (Lorey et al., 2014). Those cows with strong uterine immune response post parturient tend to avoid chronic endometrial infections and exhibit better chances of becoming pregnant at breeding. In many situations, over 20% of cows are culled each lactation with failure to conceive being the main cause (Overton et al. 2004). Overall, fertility, mastitis related reasons and lameness together account for 44.7% of all culls (Forbes et al., 1999). Culling rate clearly has a major effect on the economic lifespan within a dairy herd.
The dilemma is that inflammation is a key part of immune response. It is therefore difficult to mitigate inflammation and promote immune reaction at the same time in order to fight diseases such as metritis and mastitis.
Helping the cow come out of the inflammatory state as quickly as possible has the potential to improve feed intake and increase supply of nutrients to drive milk production. Dietary fatty acids can be used as a part of nutrition strategy to strike a balance between the competing inflammatory and anti-inflammatory processes.
Fatty acids-bioactive nutrients
Current dairy cow nutrition research is driven by interest in understanding the role fatty acids as cellular signals and not only supply of fuel for the body. Indeed, there is evidence that links dietary fatty acids to a number of physiological processes in the dairy cow in a significant way (Bradford, 2020).
It has now been established, for example, that polyunsaturated fatty acids can alter gene expression (Pires and Grummer, (2008). The fatty acids and their metabolic derivatives are capable of binding to cellular surface receptors, modulate host genetic makeup and alter the functions of specific cells and organs.
Contreras and colleagues (2010) pointed out that increased concentrations of palmitic and stearic acids found in the blood during body fat mobilisation, for example, had been established to compromise body functions, including energy utilisation and immune response both of which can increase dairy cow’s susceptibility to disease. Palmitic acid in particular is capable of activating white blood cells in a negative way. It affects normal cell behaviour by altering intracellular communication, and making the immune cells more likely to promote rather than fight inflammation.
Accelerated body fat mobilisation in the transition period leads to elevation of non-esterified fatty acids (NEFAs) which have adverse foot prints in cellular and tissue functioning. The fatty acid metabolites are a risk factor for reduced dry matter intake, metabolic disorders, immunosuppression, decreased milk production and impaired fertility (Wankhade et al., 2017).
The primary goal of transition cow nutrition has now been clearly defined as that of controlled body condition. One may add feeding of appropriate and balanced fatty acids. No other factor than excessive body condition is a better predictor of disastrous transition period. A target BCS of 3 or even less at calving is advocated because the consequences of higher BCS have far more serious consequences than those of low BCS (Garnsworthy and Topps, 1982). Cows with fat cow syndrome suffer decreased dry matter intake, high NEFAs, and are more prone to extra clinical cases of a range of metabolic disorders and infectious diseases.
While supplemental dietary fat has been used to boost energy supply to dairy cows during early lactation this may not be beneficial in all cases particularly if the net outcome is reduced feed intake or increased body weight loss. Unsaturated fatty acids, if not rumen-inert or rumen–protected, can substantially disrupt rumen function and decrease dry matter intake (Mannai et al., 2016).
Bradford (2020) noted that in certain instances, supplementations of dairy cows with saturated fatty acids have resulted in improved feed consumption but increased loss of body condition. Overall, subsequent performance has been disappointing. Milk yield did not improve and instead there was a residual effect of diminished milk production by 8% after the experiment ended.
Recent work carried out by de Souza and Lock (2018) at Michigan State University in the US exploring feeding palmitic acid (C16:0) demonstrated increased milk fat yield in early lactation. There was no effect on feed intake or milk yield but the cows lost more weight and had higher levels of plasma NEFAs. These effects were carried forward into mid lactation with the cows continuing to lose body condition. It therefore may not be advisable to C16 fat to fresh cows due to the risk of increased mobilisation of body reserves and NEFA concentration in the plasma.
When the researchers supplemented fresh cow diets with palmitic acid with oleic acid (C18:1) at increasing replacement rates of 10, 20 and 30% there was a notable positive dose response to oleic acid. Dry matter intake increased in parallel with blood insulin while loss of body condition declined. Follow-up investigation to understand the oleic acid effect led them to postulate that there could be a link with reduced lipolysis of the adipose tissue and increased insulin sensitivity. This was hypothesised to promote lipid storage rather than body fat mobilisation.
In a number of studies (von Soosten et al., 2012; de Veth et al., 2006; and Bernal-Santos et al., 2003) partitioning energy towards body tissue has been observed with conjugated linoleic acids (CLA) which is a product of incomplete ruminal biohydrogenation process occasioned by excess unsaturated fatty acids and suboptimal level of fibre in the diet. Under practical feeding conditions, supplementation in early lactation with CLA to reduce milk fat and mitigate the impact of NEB may not be popular since some producers want higher milk fat for the premium price butterfat attracts. Moreover, feeding trials with CLA reported by Perfield II et al. (2002) and Sinclair et al. (2010) have simply increased milk yield and in some instances reduced DMI with no clear beneficial effect on body condition and improvement of subsequent reproductive performance (Schäfers et al., 2017).
Genetic breeding goals with less regard to cow’s wellbeing traits is probably one of the major missteps underlying causes of metabolic disorders in transition dairy cows which today is responsible for most of the culling in dairy herds. McFadden (2019) proposed that further investigations to exploit the potential benefits of partitioning energy toward body reconditioning in early stages of lactation may open up opportunities to balance nutrients to meet the cow needs for health, fertility and milk production in equal measure. This argument may hold merit since cows delivering calves and initiating lactation also need support for their health and welfare. Such an approach could improve reproductive efficiency, enhance longevity and increase dairy herd profitability.
Saturated fatty acids
The involvement of lipid metabolism in the cow’s stress and maternal adaptation during transition from gestation into lactation has received increased research attention in the recent past. In 2016, Rico and co-workers and later on Rico et al. (2018b) reported that an increase of C16:0 circulating in the blood increased NEFAs and ceramide levels and coincided with elevated insulin resistance in early lactation cows. There is a commonality between C16:0 and C18:0 in such responses (McFadden and Rico, 2020). Carnitine supplementation may be helpful in stimulating oxidation of palmitate and decrease liver fat accumulation in postpartum cows.
Ceramide is an interesting metabolite which is a type of sphingolipid found in tissues and is formed from primarily palmitic acid (Summers, 2006). Although ceramide can induce insulin resistance (Rico et al., 2018b; McFadden and Rico, 2019), fatty liver, and inflammation in dysfunctional metabolically challenged dairy cows, it may also block glucose uptake by the adipose tissues and shunt it toward mammary gland to improve lactation performance of clinically healthy animals (Rico et al. 2016).
There is emerging evidence of palmitoleic acid (C16:1) being antagonistic to ceramide production. This is of interest since the fatty acid has been shown to enhance insulin sensitivity in obese sheep according to Duckett et al. (2019).
The challenge is for nutritionists to manipulate dietary fatty acid supply, in particular C16:0 in early lactation cows to minimise ceramide synthesis in these cows due to the high risk of body condition loss immediately pre and post calving. This would help enhance peripheral insulin sensitivity and responsiveness, lower NEFAs and reduce the incidence of liver fat overload. On the other hand, promote ceramide production to spare glucose for milk production in mid- to late-lactation when the cows are in a positive energy balance.
Considered together there is a strong advocacy in striking a balance between cow health and milk production by restricting palmitic acid supplementation in early lactation and reserving C16:0-enriched supplements for mid lactation and beyond. Such an approach may hold merit in enhancing nutrient partitioning to increase milk production while ensuring optimal cow health and reproductive performance.
Omega-9 Oleic acid C18:1
As discussed earlier, oleic acid supplementation immediately postpartum may help in body reconditioning. This is thought to be mediated through reduced lipolysis and improved insulin sensitivity at adipose tissue level in early lactation (Laguna et al., 2019). Elevated blood lipid content is linked to metabolic diseases such as fatty liver and ketosis, and predisposes dairy cows to inflammatory diseases including mastitis, metritis, and lameness affecting herd welfare and profitability (Bradford et al., 2015).
Of potential benefit to the metabolism of dairy cow, dietary blend of palmitic and oleic acids stimulates insulin circulation in the blood whereas increased plasma concentrations of palmitic acid alone or a blend of palmitic and stearic (C18:0) acids has the opposite effect. This is the view of de Souza and Lock (2018) emanating from their research work, and is commensurate with the effect of C16 products in predisposing body condition loss as discussed earlier.
Elevated levels of oleic acid in the blood have been found to be predictive of metabolic diseases namely fatty liver and ketosis. Researchers in Poland (Nogalski et al., 2012) and The Netherlands (Jorjong et al., 2014) identified oleic acid as a biomarker for early diagnosis of higher than normal blood levels of NEFAs and BHB in the early stages of lactation among high-yielding dairy cows. The highest plasma levels of NEFAs and BHB of 1573 and 1116 µM/L respectively, were associated with the highest content of the fatty acids in milk fat. High concentrations of NEFAs and BHB postpartum are associated with immune dysfunction. It was determined that explicit occurrence of the metabolic disorders in cows becomes evident when milk fat content of C18:1cis-9 exceeds 24%.
During adipose tissue mobilisation, the liver accumulates greater amounts of palmitic acid, whereas levels of polyunsaturated fatty acids including arachidonic, EPA and DHA are depleted (Contreras et al. 2010). These changes may promote immune dysfunction as well as curtail insulin secretion and sensitivity compromising liver health of the dairy cow.
Omega-3 fatty acids
Key omega-3 fatty acids of interest in transition dairy cow nutrition are the essential fatty acids alpha linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). The main dietary sources are fresh grass and linseed for ALA and fish oil and marine algae for EPA and DHA. ALA serves as a substrate for elongation into the longer chain polyunsaturated relatives although the process is variable and inefficient. It is therefore more desirable to obtain EPA and DHA direct from the marine sources and supply them in rumen-inert in the diet.
Recently, Maollem (2018) carried out an extensive review of the role of the dietary omega-3 fatty acids in dairy cattle and highlighted key metabolic processes in which they are involved. Omega-3 fatty acids form a part of phospholipids of cell membranes where they perform anti-inflammatory functions through direct or indirect inhibitory mechanisms. These bioactive fatty acids make up most of the lipids in neutrophils, the key component of the first line of defence against inflammation. Selective uptake of omega-3 fatty acids has been demonstrated in ovarian tissues, in bull sperm and in the unborn calf through the placenta. In the reproductive system, EPA and DHA can help mitigate pro-inflammatory responses in transition cows suffering intense lipid mobilisation, and exert some positive effects on fertility.
Some fresh research work in Slovakia (Elbaz et al. 2019) involving supplementation of dairy cow diets with calcium salts of EPA and DHA from calving till the 60th day of lactation established that the fatty acids increased the energy balance of the fresh cows. The change was manifested in increased serum insulin and glucose levels (17.3 – 28.73%) accompanied with decreased NEFAs and BHB with progressive days into lactation. There was a concomitant improvement in humoral immunity exhibited in increased serum globulin and reduced inflammatory response post calving.
Contrary to the effects of saturated fatty acids, EPA and DHA counteract insulin resistance by stimulating mitochondrial function, reducing oxidative stress and preventing inflammation (Lepretti et al., 2018). To a lesser extent, linolenic acid appears to elicit pro-insulin action in the same manner as EPA and DHA. However, according to Contreras eta al. (2017), in transition cows experiencing reduced antioxidant potential, fatty acids may become vulnerable to peroxidation in the liver by hepatic oxylipids originating from pro-inflammatory omega-6 fatty acids arachidonic and linoleic. Therefore, adequate supply of effective antioxidants in the diet is essential to ensure these long chain polyunsaturated fatty acids remain stable in feed and at tissue level to be able to elicit the expected response.
There are challenges though in minimising rumen biohydrogenation of the unsaturated fatty acids and in particular, long chain polyunsaturated omega-3 fatty, and ensuring adequate absorption to produce metabolic effects in the dairy cow. Fortunately, there are available rumen-inert dryfat products incorporating omega-3 fatty acids, and rumen-protected calcium salts of fish oil to minimise metabolism of fatty acids in the rumen.
Inflammation cost of glucose utilisation
Immune cells depend primarily on circulating glucose to meet their energy needs, and poor cow health can lead to diversion of large amounts of energy that could otherwise be used for production and normal physiological functions. Insulin resistance, which is directly induced by inflammatory signals, is a mechanism driving this resource allocation. To put this into perspective acute immune activation can cost a cow more than 1 kg of glucose within 12 hours during which approximately 14kg milk synthesis is sacrificed (Kvidera et al, 2017).
Increased intake of linoleic acid has the potential to alter the fatty acid profile of the phospholipids of cell membranes causing increased proportions of linoleic and arachidonic acids. The metabolic events that follow lead to eicosanoids synthesis putting the cow in pro-inflammatory state (Raphael and Sordillo, 2013 and Kuhn et al., 2017). Eicosanoids include prostaglandins which are required for parturition and uterine involution in readiness for subsequent breeding. However, prolonged elevated levels of prostaglandins after parturition and during breeding can promote systemic inflammatory response risking degeneration of corpus luteum, and cessation of production of progesterone which is required for maintenance of pregnancy (Bradford et al., 2015). In a heightened inflammatory environment pathogenic infection of the reproductive duct is also likely.
Although a controlled inflammatory response normally leads to recovery from infection, unchecked or chronic inflammatory reactions perpetuated by high levels of prostaglandins in the blood can be detrimental to the cow health. Therefore, in an ideal inflammatory response, a rapid resolution phase following elimination of the infectious agents is vital to the healing process. Collectively, there is a delicate balance of robust response and inflammatory resolution mechanisms which must be maintained during the transition period to minimise metabolic disorders and reduce severity of infectious diseases.
Impacts of omega-6 and omega-3 on reproduction
Reproductive processes taking place during the transition period is a complex set of events involving nutrition, management, stress, diseases, environmental condition, toxins, and other factors that all interact to affect their outcome. Fatty acids play key roles in the processes and our understanding of how fat nutrition interacts with reproduction can enable us to manage nutrition and feeding to improve reproductive outcomes in dairy cows. Imbalanced nutrient supply, including fatty acids which are the substrates of the main reproductive hormones, in the pre- and post-parturient periods may lead to poor oestrus signals, delayed ovulation, decreased ovulation rate and increased embryonic mortality.
As mentioned earlier, prostaglandins, which are derived from omega-6 fatty acids play critical role during parturition. Once calving occurs, the innate immune competence of the uterus must be restored to successfully reject remaining placental tissues and to prevent bacterial growth explosion (Elmetwally, 2018). Thereafter prostaglandins are required to support involution of the ovary in readiness for subsequent breeding. However, protracted high levels of the hormones can lead to reproductive failure due to their known luteolytic effects.
Feeding supplemental fats high in omega-3 fatty acids, EPA and DHA, during the breeding season and early gestation increases progesterone levels which attenuates uterine prostaglandin production. Progesterone is required for the nutrition of the endometrial tissues and hence maintenance of pregnancy. It increases egg size and quality helping reduce embryo mortality. Altogether, enhanced progesterone production improves embryo mortality and pregnancy rates.
Elucidating the complexity of the of interaction of fatty acids may provide a new insight for understanding the mechanisms of their actions during the transition period so as to enable maintenance of an immunologically favourable, and at the same time create immunosuppressive environment in the uterus that is needed for embryo to thrive. In past experiments (Silvestre et al., 2011and Santos et al., 2012) the greatest proportion of pregnant cows following artificial inseminations was observed in those animals with a sequential supplementation with a source of omega-6 during the transition period followed by rumen-protected fish oil fed in the breeding period.
The residual effect of feeding omega-6 fatty acids in augmenting the beneficial activity of omega-3 fatty in dairy cows acids calls for strategic supplementation of both groups of fatty acids to benefit immune function early postpartum and exert immunosuppressive effects during breeding period. This would be beneficial to transition cow wellbeing and fertility. In those herds where blends of vegetable and fish oils, which are rumen-inert, have been fed to achieve the omega-6 to omega-3 ratio of 4:1 during early lactation, we have witnessed profound improvement in terms of milk yield, immune response and reproductive performance.
Research has continued to identify the influence specific fatty acids and their combinations may have on the metabolic processes that take place in the body of the transition cow, and how these dynamics can in turn impact on metabolic disorders, disease infections and reproductive performance. Carefully phased supplementation of transition cow diets with balanced fatty acid protected from rumen biohydrogenation can help mitigate metabolic diseases, control immune responses while supplying substrates that serve as precursors of reproductive hormones.
The transition period remains one of the most challenging and important phases of the production cycle in a dairy cow. It is a transient period around calving characterised by drastic changes in the hormonal status, elevated metabolic activities and immense increase in nutrient demand for foetal growth and copious milk synthesis. Transition period is also the time that dry matter intake is at its lowest level leading to negative energy balance and associated metabolic disorders which compromise cow health and reproductive performance. Research has identified specific fatty acids as bioactive metabolites that signal and modulate a number of important biochemical processes in the dairy cow which can be manipulated as a part of the nutritional strategies to improve transition cow health and performance. Of particular interested and requiring further research into their interactions and activities are the omega-3, omega-6 and omega-9 families of fatty acids. They are involved in reproductive processes, immune response and tissue regeneration among others all of which affect dairy cow productivity. The omega-3 omega-6 and omega-9 fatty acids provide subtle but effective means to balancing inflammatory and immune tone in transition cows. Further investigations to exploit the potential benefits of partitioning energy toward body reconditioning in early stages of lactation may open up opportunities to balance nutrients to meet the cow needs for health, fertility and milk production in equal measure. Equally, nutritionists need to formulate strategic fatty acid blends for use in transition cow feeding and management for productivity and wellbeing.