Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans
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In non-febrile mouse models, high dose acetaminophen administration causes profound hypothermia. However, this potentially hazardous side-effect has not been confirmed in non-febrile humans. Thus, we sought to ascertain whether an acute therapeutic dose (20 mg⋅kg lean body mass) of acetaminophen would reduce non-febrile human core temperature in a sub-neutral environment. Ten apparently healthy (normal core temperature, no musculoskeletal injury, no evidence of acute illness) Caucasian males participated in a preliminary study (Study 1) to determine plasma acetaminophen concentration following oral ingestion of 20 mg⋅kg lean body mass acetaminophen. Plasma samples (every 20 min up to 2-hours post ingestion) were analyzed via enzyme linked immunosorbent assay. Thirteen (eight recruited from Study 1) apparently healthy Caucasian males participated in Study 2, and were passively exposed to 20°C, 40% r.h. for 120 min on two occasions in a randomized, repeated measures, crossover design. In a double blind manner, participants ingested acetaminophen (20 mg⋅kg lean body mass) or a placebo (dextrose) immediately prior to entering the environmental chamber. Rectal temperature, skin temperature, heart rate, and thermal sensation were monitored continuously and recorded every 10 min. In Study 1, the peak concentration of acetaminophen (14 ± 4 μg/ml) in plasma arose between 80 and 100 min following oral ingestion. In Study 2, acetaminophen ingestion reduced the core temperature of all participants, whereas there was no significant change in core temperature over time in the placebo trial. Mean core temperature was significantly lower in the acetaminophen trial compared with that of a placebo (p < 0.05). The peak reduction in core temperature in the acetaminophen trial was reached at 120 min in six of the thirteen participants, and ranged from 0.1 to 0.39°C (average peak reduction from baseline = 0.19 ± 0.09°C). There was no significant difference in skin temperature, heart rate, or thermal sensation between the acetaminophen and placebo trials (p > 0.05). The results indicate oral acetaminophen reduces core temperature of humans exposed to an environment beneath the thermal neutral zone. These results suggest that acetaminophen may inhibit the thermogenic mechanisms required to regulate core temperature during exposure to sub-neutral environments.
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Paracetamol-induced hypothermia in humans has been reported by several other research groups.
“Clinically, the paracetamolinduced hypothermia in humans has also been reported by several other research groups [140][141][142][143][144][145].”
From Paracetamol (acetaminophen): A familiar drug with an unexplained mechanism of action (2021) · cites this paper as [142]
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- Authors
- Foster, J., Mauger, A., Thomasson, K., White, S., & Taylor, L.
- Affiliations
- University of Bedfordshire (GB)
- University of Kent (GB)
- Corresponding author
- Taylor, Lee
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2016-03-14
- Volume
- 7
- Pages
- 54-54
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC4789353
- OpenAlex
- W2302827330
- Cited by
- 25
- References
- 38
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 2 · 2017: 4 · 2016: 1
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kent Academic Repository (University of Kent) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Portal (King's College London) (submittedVersion)
- Funders
- University of Bedfordshire
- University of Warwick
- Topics
- Health Sciences › Medicine › Physiology › Thermoregulation and physiological responses
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Infrared Thermography in Medicine
- Keywords
- paracetamol, thermoregulation, core body temperature, hypothermia, thermoneutral zone, adverse drug reactions, thermogenesis, healthy men, cold exposure, thermal sensation, heart rate, skin temperature, drug safety in pregnancy and lactation, drug safety in children
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