(W1230-10-63) Clarifying the Impact of Advanced Age on the Physicochemical Characteristics of Gastric Contents in the Fasted State

Purpose: The advanced age population is currently under-represented in clinical studies [1] and evaluation of novel drugs for oral administration is typically performed in young adults. Potential alterations of gastric functions related to chronological aging can have an impact on gastric contents characteristics and, therefore, to oral drug product performance. However, advanced age is generally associated with higher incidence of morbidities which in combination with other confounding factors make investigation of the impact of aging on gastric contents characteristics complex and cumbersome [2]. For instance, diabetes mellitus may impact gastric emptying and gastric volumes [3], while atrophic gastritis, helicobacter pylori infection, and smoking were shown to affect basal acid output and basal pepsin output [4]. As part of a broader investigation on the impact of chronological aging on the characteristics of the upper gastrointestinal lumen, this work focuses specifically to the volume of resting gastric contents, and the pH, buffer capacity, osmolality, and pepsin activity in the fasting gastric contents.

Methods: The study was conducted after receiving approvals by the Ethics and Scientific committees (AP 664-February 15, 2022) and the Executive Committees (AP 12846-May 25, 2022) in consultation with the data protection officer of the Hospital. Individuals in advanced age (≥65 years) and young adults (18-45 years) who were visiting the Department of Gastroenterology on an outpatient basis for a prescribed gastroscopy were approached for their possible participation in the study. After confirming that they followed the protocol that had been provided by the medical personnel for preparation for gastroscopy (abstinence from food and drink for 12 hours prior to the gastroscopy) they provided their informed consent. Thirty-seven individuals in advanced age (65 – 87 years) and forty-eight young adults (18 – 45 years) were enrolled initially. Sixteen young adults and twelve older people participated in this study, after confirming that they were non-smokers (for at least one year), they were non-diabetic, they were non-frail (scored < 4 based on the Clinical Frailty scale [5]), and they were not receiving medications which impact gastric function (including gastric acid secretion reducing agents). In addition, atrophic gastritis (based on histological data), helicobacter pylori infection (based on biopsy data), malignancies (based medical history record), and gastric diseases potentially affecting gastric function (based on medical history record) were confirmed to be absent in all participants. Volume of aspirated contents, pH, and buffer capacity were measured immediately upon collection. Osmolality and pepsin activity were measured after one freeze-thaw cycle (-70 °C).

Results: After confirming the absence of potentially confounding factors such as smoking, diabetes, mobility impairment, intake of medications which impact gastric function, atrophic gastritis, helicobacter pylori infection, malignancies, and presence of gastric disease potentially affecting gastric function, data of this study (Table 1) indicate that chronological aging does not impact resting gastric contents, and pH, buffer capacity, osmolality, and pepsin activity in the fasting gastric contents, on average.

Conclusion: Chronological aging does not seem to impact gastric pH in the fasted state. The absence of impact of chronological aging on resting gastric volume, and on buffer capacity, osmolality and pepsin activity in the fasting gastric contents was also shown for first time.

References: 1. Liu et al. Clin Pharmacol Ther, 112, 210, 2022
2. Stillhart et al., Eur J Pharm Sci (in press).
3. Xiao et al., Br J Anaesth, 2021, 2, 224.
4. Feldman et al., Gastroenterology, 1996, 110, 1043.
5. Theou et al., Age Ageing, 2021, 4, 1406.

Acknowledgements: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 956146.

Table 1