Intravenous Infusions of Glycerol Versus Propylene Glycol for the Regulation of Negative Energy Balance in Sheep: A Randomized Trial

SIMPLE SUMMARY: Propylene glycol (PG) and glycerol are common energy substances used to supplement the feed of transitioning ruminants in order to minimize the development of metabolic disorders related to energy deficiency. Their effects on the energetic status of the animal have been, thus far, studied mostly by oral administration, which exposes them to substantial microbial metabolism in the rumen. This study compared the direct metabolic effects of these substances following their intravenous (IV) infusion. We found that glycerol was highly glucogenic and insulinotropic, as expected. However, surprisingly, PG had no significant effect on the circulating levels of glucose or insulin. Unlike glycerol, PG significantly raised circulating lactate levels and showed some potential tissue damage activity. Our study points to glycerol, rather than PG, as a potential IV treatment for efficient relief of hypoglycemia and hyperketonemia. ABSTRACT: Negative energy balance (NEB) is a state of insufficient dietary-energy consumption, characterized by the breakdown of adipose fat to meet the physiological energy expenditure. Extensive NEB, as common in high-yielding transitioning ruminants, drives significant metabolic disturbance and pathologies such as pregnancy toxemia and ketosis. Strategies to minimize the severity of NEB include the use of energy-dense feed supplements, like glycerol and propylene glycol (PG), or IV glucose infusion during severe hypoglycemia. PG and glycerol have been studied mainly by oral or ruminal administration, which exposes them to substantial metabolism in the digestive system. To investigate their direct benefits to mitigating NEB, we intravenously infused them into sheep induced into NEB by feed restriction. Sixteen 5-month-old ewe lambs at NEB were IV-treated with 170 mL isotonic saline containing 15% glycerol or 15% PG. Both PG and glycerol effectively reduced hyperketonemia by 57% and 61%, and inhibited adipose lipolysis by 73.6% and 73.3%, respectively. Surprisingly, only glycerol was glucogenic (p < 0.0001) and insulinotropic (p < 0.0075), while PG was primarily utilized for production of lactate (p < 0.0001). Tissue-damage biomarkers indicated hemolytic activity for PG. This study revealed glycerol as a superior IV treatment for effective relief of NEB. Since it carries no risk of glucose overloading, glycerol IV infusion may also have clinical advantages over glucose for treatment of pregnancy toxemia and ketosis.