Oral Glycerol as a Gluconeogenic Precursor in the Treatment of Ketosis and Fatty Liver

Introduction

Glycerol can be converted to glucose in the liver of cattle. Glycerol enters the gluconeogenic pathway at the level of dihydroxyacetone phosphate and 3-phosphoglyceraldehyde. This is several biochemical steps closer to glucose than the traditional gluconeogenic precursors, propionate and propylene glycol. Use of glycerol as an aid in the treatment of ketosis was suggested during the 1960's but not adopted due to high costs. However, newer methods for its production may have removed this barrier. In this study we examined the effect of glycerol administration on blood glucose and did a dose titration to find the toxic dose of glycerol as well in dry cows.

Materials and methods

Part 1a. Treatment groups consisted of 3 cows (one of which had a rumen fistula) which were given 1, 2 or 3 L of glycerol in 9.5 L of water via esophageal pump. Blood samples were taken hourly for the next 8 hrs and also at 24 hrs.

1b. Cows were given 1.5 L glycerol in either 9.5 or 37 L water and blood samples were obtained as described.

Part 2: The 1 L dose of glycerol was applied to two lactating cows with clinical ketosis. These cows had been previously treated for 2 or 3 d with IV glucose with little response suggesting fatty liver involvement.

Results of titration study

1a. At 0.5 hr after treatment mean blood glucose increased 16, 20, and 25% respectively over pre-treatment values at the 1, 2 and 3 L doses of glycerol. They remained elevated for the next 8 hrs. All cows had returned to baseline glucose values at 24 hrs. Two of three cows given the 3 liter glycerol dose exhibited staggering and depression which they recovered from within 4 hrs. Rumen pH was unaffected by treatment with glycerol. Diuresis was observed in all cows given the 2 and 3 L doses of glycerol.

1b. Diluting the glycerol in a larger volume of water had only a small negative effect on the increase in blood glucose concentration achieved with the less diluted glycerol. However blood glycerol concentrations were significantly reduced by administration in a larger volume of water.

Results of glycerol application to ketotic cows

In both cases ketone level in urine was reduced to trace amounts and milk production increased. In the first cow blood glucose increased from 48 mg/dl prior to treatment to 75 mg/dl 0.5 hr after treatment and was 109 mg/dl 5 hr after treatment. In the second cow the blood glucose did not increase until about 4 hr after treatment when it increased from 48 mg/dl to 74 mg/dl and was just 64 mg/dl 8 hr after treatment.

Conclusion

Glycerol offers another means of treating cows for ketosis which may have less toxic effects than a similar amount of propylene glycol. The toxicity seems to be due to high blood concentration of glycerol which has a hyperosmotic effect within the brain according to human medical studies. Administration of glycerol in larger volumes of water can make this treatment much safer while retaining most of the benefits.