Effects of Continuous Albuterol Inhalation on Serum Metabolome in Healthy Subjects: More Than Just Lactic Acid

Abstract

Treatment with β2-agonists may cause elevated lactic acid, the end product of anaerobic metabolism of glucose. It has been proposed that lactic acidosis associated with β2-agonists is caused by changes to direct biochemical impacts on glycolysis, gluconeogenesis, pyruvate metabolism, and free fatty acid production. However, much remains unknown, and there is a paucity of evidence regarding the underlying chemical changes associated with this lactic acidosis. The goal of our study was to investigate the impact of 1 hour of continuous albuterol on the untargeted serum metabolome of healthy subjects. Twenty-four healthy participants received 7.5 mg of continuous albuterol for 1 hour. Baseline, 1-hour, and 2-hour lactic acid levels were drawn. Samples obtained at baseline and 1 hour were sent for untargeted metabolomic profiling. Participants had a baseline lactic acid of 1.45 ± 0.46 mmol/L. On average, lactate levels increased 0.33 ± 0.67 mmol/L after 1 hour (P = .02) and remained elevated at 2 hours (0.32 ± 0.72 mmol/L, P = .02), although there was overlap in lactate levels across times. For metabolomic analysis, fatty acids, organic acids, and sugars were elevated, and amino acids were reduced. Lactic acid and pyruvic acid metabolites, however, did not significantly change (after false discovery rate adjustment). In healthy participants, continuous albuterol alters the serum metabolome, but this change may not be clinically significant. The data support recent hypotheses that β2-receptor activation stimulates lactic acid production, altering aerobic glycolysis, gluconeogenesis, and free fatty acid production.

NORAD Promotes the Viability, Migration, and Phenotypic Switch of Human Vascular Smooth Muscle Cells during Aortic Dissection via LIN28B-Mediated TGF-β Promotion and Subsequent Enhanced Glycolysis

“…This finding implies that the NORAD knockdown-induced reduction of VSMC growth and invasion needs TGF- β activity. According to existing research, a variety of biosynthetic processes may play a key role in the innate immune system of AD [ 26 ]. Solving key metabolic catalysts or sensors to restore normal metabolism may provide new treatment strategies for respiratory problems and dysfunction [ 27 ].…”

“…This finding implies that the NORAD knockdown-induced reduction of VSMC growth and invasion needs TGF-β activity. According to existing research, a variety of biosynthetic processes may play a key role in the innate immune system of AD [26].…”

Recent Progresses in Non-Dialysis Chronic Kidney Disease Patients with Hyperkalemia: Outcomes and Therapeutic Strategies

“…However, the common adverse reactions of beta-2 agonists include anxiety, tachycardia, palpitations, headache, and musculoskeletal tremors [ 49 , 50 ]. Albuterol administration could induce mild hyperglycemia, and a minor increase in serum lactate has also been shown [ 51 , 52 ].…”