Amino Acid Hydration Decreases Radiation-Induced Nausea in Mice: A Pica Model

Abstract

Nausea and diarrhea are common yet inconsistent side effects of abdominal and pelvic irradiation. Their frequency, chronicity, and severity vary greatly, and the reasons for inter-subject variability are unknown. We studied the potential for radiation-induced changes in amino acid absorption and mucosal barrier function to lead to gastrointestinal toxicity. We found profound and prolonged changes in the absorption and secretion of several electrolytes and nutrients, caused by changes in transporter function, after radiation doses as low as 1 to 3 Gy. After identifying absorbed and non-absorbed amino acids, we demonstrated the role of a beneficial amino acid drink to alleviate radiation-related gastrointestinal symptoms in a mouse model.

Randomized Study of enterade® to Reduce Diarrhea in Patients Receiving High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation

“…While nausea is an established GI toxicity experienced during ASCT, we did not anticipate that it would have such a profound impact on the conduct of this study. Previous preclinical and clinical data had shown that the use of enterade ® was associated with lower rates of nausea and anti-emetic use (Yin et al, 2017;Luque et al, 2020). However, the rates of significant nausea in the current study with high-dose chemotherapy proved to be a main barrier to twice daily oral rehydration, especially when subjects are able to receive intravenous hydration as basic supportive care.…”

“…Murine studies have demonstrated improvements in the absorptive capacity of the small intestine by rebuilding the villi and reducing antigenic translocation by tightening the mucosal barrier. These changes were associated with reduced nausea (reduced pica weight), improved body weight maintenance, and extended survival time with the administration of enterade ® (Yin et al, 2014;Yin et al, 2016;Yin et al, 2017;Gupta et al, 2020).…”

A double-blind clinical trial to compare the efficacy and safety of a multiple amino acid-based ORS with the standard WHO-ORS in the management of non-cholera acute watery diarrhea in infants and young children: “VS002A” trial protocol

“…Net absorption in the diseased intestine was improved by the use of Trioral ® ORS and even further improved by the use of VS002. The greater net absorption with VS002 relative to Trioral ® can be explained at least in part by the additional chloride secretion activity of even very small amounts of glucose present in Trioral ® , which has been demonstrated using chamber 36 Cl and 24 Na flux studies [30,38], and an increase in NHE3 (sodium absorption) and decrease in cystic fibrosis transmembrane conductance regulator (CFTR) (chloride secretion) activity in intestinal tissues incubated in VS002 and measured using western blot analysis [37].…”

“…Like glucose, EBS amino acids simultaneously also increase intestinal sodium flux through increased epithelial NHE3 (sodium-hydrogen antiporter 3). Unlike glucose, VS002 also decreases CFTR expression, which is an intestinal target protein that becomes heavily stimulated in response to infectious diarrhea [37]. As a consequence of increasing absorption and decreasing secretion, net intestinal absorption is superior to VS002 was used to treat diarrhea.…”

Can an amino acid mixture alleviate gastrointestinal symptoms in neuroendocrine tumor patients?

“…Carcinoid syndrome diarrhea can be distressing with many patients reporting bowel movements (BM) ranging from two to 30 or more per day [9]. Patients with NETs may also have moderate to severe diarrhea due to other etiologies including toxicity from chemotherapy, radiation and sequelae of gastrointestinal surgery [10][11][12][13][14][15][16][17].…”