The transition to lactation period is the most challenging period in the dairy cow life cycle, specifically in terms of metabolic disorders. Cows with ketosis produce less milk, are more likely to develop a displaced abomasum, and are more likely to be culled from the herd. As with many disorders, ketosis has been historically separated into either clinical ketosis (hyperketonemia with clinical signs) or sub-clinical ketosis (hyperketonemia without clinical signs). Incidence of sub-clinical ketosis ranges from 40 to 60% of cows while clinical ketosis occurs in 2 to 15% of cows. It has been demonstrated that sub-clinical ketosis is just as costly and detrimental to animal health as clinical ketosis, largely because it can go undetected without active testing and management protocols. Each case of hyperketonemia costs approximately $361 and 247 for first calf heifers and cows, respectively.


Treatment and Detection Methods

Intravenous Dextrose

Historically, ketosis has been most commonly treated with intravenous dextrose. However, this treatment may not be ideal. The dose of glucose typically administered (500 mL of 50% dextrose) increases blood glucose concentrations 8 times the normal concentration immediately after administration; blood glucose then returns to pretreatment concentrations within 2 h (Sakai et al., 1996). This elevation in blood glucose initiates a regulatory cascade that begins with a 12-fold increase in insulin concentration and ends with downregulation of liver glucose production, decreased mobilization of fat stores, and decreased oxidation of mobilized NEFA within the liver. Glucose not transported into the cell during this insulin peak is excreted through the kidneys adding a risk of electrolyte imbalance. High glucose concentrations have also been linked to abomasal dysfunction, decreased mobility, and DA. The benefit of dextrose treatment is less than 24 h and therefore must be repeated for sustained benefit. Decreased liver production of glucose, coupled with quick disappearance of intravenous glucose sources, results in a secondary blood glucose “crash”. Thus it is recommended that IV dextrose treatments be reserved for clinical ketosis cases and be limited to 250 mL of 50% dextrose. Cows with clinical ketosis need the glucose boost provided by the IV dextrose and a 250 mL dose of 50% dextrose is not enough to downregulate liver metabolism.


Oral Drench Propylene Glycol

In contrast to treating ketosis with intravenous glucose, propylene glycol appears to have many advantages. Propylene glycol is delivered as an oral drench and serves as a glucose precursor to the animal and is delivered as an oral drench. In the rumen, propylene glycol is either converted to propionate or absorbed directly. Propylene glycol generated propionate and directly absorbed propylene glycol can enter the TCA cycle and gluconeogenesis to produce glucose. By providing a precursor that is still dependent on liver gluconeogenesis and TCA cycle oxidation, we are providing a fuel source without leading to a secondary “crash”. Collectively, metabolism of propylene glycol provides a glucose precursor that most closely mimics glucose metabolism in a healthy cow and requires liver metabolism to be maintained, providing an optimal treatment.

Application of current research regarding the negative impacts of ketosis and optimal treatment protocols to commercial dairy farm settings is absolutely dependent on accurate and practical detection methods. Ketones are transferred from blood into both urine and milk and concentrations that reflect hyperketonemia in all three fluids have been defined. Historically, on-farm ketosis testing was semi-quantitative and utilized urine and milk test strips. These tests have good specificity but poor to moderate sensitivity (27 to 78%) depending on the test. Milk test strips are typically the cheapest but is also the least sensitive. Recent availability and validation of the Precision Xtra meter has provided a new cowside test with a much better sensitivity of 95% and specificity of 94%. While this test costs more than the Ketostix urine test strips or KetoCheck powder for milk and about the same as the KetoTest milk test, it provides a highly sensitive on-farm diagnostic tool.


Thoughts on testing and treating:

Given the timing of how sub-clinical ketosis effects the cow, it is recommended to test cows once per week on a consistent day. In order to tailor a detection protocol to a farm, an approximate sub-clinical ketosis prevalence (how many cows have the disease on any one day) is needed. Start by testing fresh cows between 4 and 20 DIM (or a 30 to 40 cow subset of this group in larger herds) on a few separate dates to establish the prevalence. The average prevalence is around 15 to 25% (multiple prevalence by 2.5 to get incidence which represents the number of total cases in the herd). Testing every cow once, preferably between 4 and 11 days in milk, is economically justifiable on farms with prevalence above 10%. More aggressive testing protocols that test every fresh cow twice are justified in herds with higher prevalence. Work with the veterinarian and herdsman to update treatment protocols to ensure that cows are being treated appropriately, depending on disease severity. General guidelines are shown in the table below.


What’s causing the ketosis?

Better understanding the tissue-level metabolism that leads to ketosis onset has allowed for better understanding of the symptoms. Ketosis is an early-fresh cow disorder (onset most commonly detected within 4 to 9 days in milk) and is tightly related to energy balance at, and shortly after, calving. Decreased feed intake prior to and around the time of calving, coupled with increases in energy requirements to meet the needs of lactation, result in cows entering a state of negative energy balance (NEB) after calving. During periods of NEB, stored body fat is mobilized and transported to the liver to aid in meeting energy and glucose demands. Triglycerides mobilized from the adipose tissue are transported through the blood stream as nonesterified fatty acids (NEFA) and glycerol, and absorbed by the liver where fatty acids are broken down for four possible fates: complete oxidation through the tricarboxylic acid (TCA) cycle, incomplete oxidation through ketogenesis, TG synthesis and packaging as very-low density lipoprotein for export from the liver, or TG synthesis for storage as liver lipids. When available acetyl-CoA exceeds the capacity of the TCA cycle, there are increases in production of ketones and deposition of TG, leading to the onset of ketosis and fatty liver syndrome. Understanding the biology that leads to ketosis onset supports the etiology of this early-lactation disease.

While circulating ketones can be used to a certain extent as a fuel source by heart, brain, liver, and mammary tissue, excessive blood ketones can have negative effects. Widely accepted cutoffs for sub-clinical ketosis are blood BHBA > 1.2 mmol/L and for clinical ketosis blood BHBA > 3.0 mmol/L. These cutoffs have been established based on increased negative effects and increased relative risk for other diseases and complications (ex. DA, culling, decreased reproductive efficiency, lost milk production) as blood BHBA concentration increase beyond 1.2 mmol/L. Negative impacts and relative risk for other disorders are further increased based on 1. day of onset and 2. blood concentration of BHBA.  Cows with ketosis onset within the first week of lactation are at further increased risk for developing a DA and being culled. Additionally, increases in blood BHBA concentrations above 1.2 mmol/L increase risk for DA and culling as well as result in exponential milk losses. This highlights the importance of early detection and treatment protocols.


Author: Heather White, Ph.D., Assistant Professor, Nutritional Physiology

Department of Dairy Science, University of Wisconsin-Madison