Jessica L. Gordon, BS, DVM^∗, Stephen J. LeBlanc, BSc, DVM, DVSc and Todd F. Duffield, DVM, DVSc,     Department of Population Medicine, Ontario Veterinary College, University of Guelph, 2509 Stewart Building (#45), Guelph, Ontario N1G2W1, Canada. E-mail address: jgordo04@uoguelph.ca ^∗Corresponding author.

This article provides an update on ketosis treatment regimens. The ketosis treatment literature is reviewed and the findings are summarized. Current treatment recommendations and areas for future research are provided.

Subclinical ketosis is a common disease of the transition period in dairy cattle, affecting approximately 40% of lactations in North America.1,2 The incidence on individual farms varies widely and may be as high as 80%.² The costs associated with ketosis include treatment of the disease, increased risk and treatment of other diseases, decreased milk production, worse reproductive performance, and higher risk of culling in the first 30 days of lactation.^3,4

Historically, ketosis was classified as primary or secondary based on when signs commenced and what concurrent diseases were facing the animal.⁵ Recently, this nomenclature has fallen out of favor, because most ketosis is seen in the first 10 days after calving in North America and may or may not be accompanied by other disease.¹ The terms subclinical and clinical are favored for ketosis definition. Clinical ketosis is characterized by an increase in blood, urine, or milk ketone bodies in conjunction with other visible signs, such as inappetence, obvious rapid weight loss, and dry manure. Subclinical ketosis is defined as an increase in blood, urine, or milk ketone bodies, above a threshold shown to be associated with undesirable outcomes, in the absence of obvious clinical signs.

Because of the housing system used in many North American dairies (large groups of loose-housed cattle), it has become difficult or impossible to determine if a specific animal is showing clinical signs of ketosis. Attempts have been made to classify ketosis as clinical or subclinical based on blood β-hydroxybutyrate (BHB) concentrations.³ However, our experience is that when examined, animals with high levels of ketonemia may show no clinical signs and animals with low levels may be obviously ill. The severity of clinical effect seems to depend on the individual animal’s ability to process and tolerate ketone bodies.⁵ The disease may therefore be best described as hyperketonemia rather than trying to distinguish clinical from subclinical.

Classification of ketosis is most relevant for clarity and consistency in comparing incidence risk rates. Depending on the methods and frequency of screening, incidence rates of clinical ketosis are expected to be 2% to 15% in the first month of lactation, whereas 40% cumulative incidence of subclinical ketosis is typical if cows are screened weekly during the same period.² There is some evidence that greater ketonemia is associated with higher risk of negative outcomes, such as subsequent disease and culling.¹ However, the importance of the distinction between clinical and subclinical ketosis with regard to treatment is unclear. To our knowledge, there are no well-designed studies that have shown a difference in efficacy of treatments based on the initial level of ketonemia.

When considering effective treatment of ketosis, it is critical to consider the physiology of the animal during this period. At the beginning of lactation, animals are faced with a sudden and drastic increase in energy demand.⁵ This demand is coupled with a decrease in feed intake, which generally starts in the dry period. The rate of increase of feed intake post partum lags behind the demands of lactation, leading to a period of negative energy balance. Fat is mobilized from body stores in the form of nonesterified fatty acids (NEFA) to meet energy requirements. NEFA travel to the liver destined for 1 of 3 pathways, complete oxidation for energy, incomplete oxidation to ketone bodies, or re-esterification to fatty acids. All of these pathways are stimulated in the transition animal, but the magnitude of fat breakdown and tolerance of the individual determine the relative distribution of the paths.⁵

In early lactation, homeorhesis is the driving physiologic force.⁶ Homeorhesis was defined by Bauman and Currie as “the orchestrated or coordinated changes in metabolism of body tissues necessary to support a physiologic state.”⁷ These processes facilitate breakdown of body stores of fat and protein in excess of what would be allowed based on homeostatic regulation. This situation leads to a period of insulin resistance, which is nearly universal in early lactation animals.⁶ Milk production requires large amounts of glucose. Because ruminants absorb only minimal amounts of glucose from their diet, gluconeogenesis is required to meet this need. This process is generally diminished in animals affected by ketosis, leading to hypoglycemia. Providing glucose, stimulating gluconeogenesis, and decreasing fat breakdown form the foundation for rational ketosis treatment.⁸