Effect of Short-Term Thyroxine Administration on Energy Metabolism and Mitochondrial Efficiency in Humans
Open accessAbstract
The physiologic effects of triiodothyronine (T3) on metabolic rate are well-documented; however, the effects of thyroxine (T4) are less clear despite its wide-spread use to treat thyroid-related disorders and other non-thyroidal conditions. Here, we investigated the effects of acute (3-day) T4 supplementation on energy expenditure at rest and during incremental exercise. Furthermore, we used a combination of in situ and in vitro approaches to measure skeletal muscle metabolism before and after T4 treatment. Ten healthy, euthyroid males were given 200 µg T4 (levothyroxine) per day for 3 days. Energy expenditure was measured at rest and during exercise by indirect calorimetry, and skeletal muscle mitochondrial function was assessed by in situ ATP flux ((31)P MRS) and in vitro respiratory control ratio (RCR, state 3/state 4 rate of oxygen uptake using a Clark-type electrode) before and after acute T4 treatment. Thyroxine had a subtle effect on resting metabolic rate, increasing it by 4% (p = 0.059) without a change in resting ATP demand (i.e., ATP flux) of the vastus lateralis. Exercise efficiency did not change with T4 treatment. The maximal capacity to produce ATP (state 3 respiration) and the coupled state of the mitochondria (RCR) were reduced by approximately 30% with T4 (p = 0.057 and p = 0.04, respectively). Together, the results suggest that T4, although less metabolically active than T3, reduces skeletal muscle efficiency and modestly increases resting metabolism even after short-term supplementation. Our findings may be clinically relevant given the expanding application of T4 to treat non-thyroidal conditions such as obesity and weight loss.
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Short-term studies of supraphysiologic thyroid hormone doses uniformly showed increased resting and 24-hour energy expenditure, but were too brief to document changes in body composition.
“These studies uniformly showed increased resting and 24-hour energy expenditure, but were too brief to document changes in body composition.”
From Effects of levothyroxine replacement or suppressive therapy on energy expenditure and body composition (2016) · cites this paper as [3]
Most prior studies of supraphysiologic thyroid hormone doses utilized high doses of levotriiodothyronine (LT3), not minimally suppressive doses of LT4.
“In addition, most utilized high doses of levotriiodothyronine (LT3), not minimally suppressive doses of LT4.”
From Effects of levothyroxine replacement or suppressive therapy on energy expenditure and body composition (2016) · cites this paper as [3]
Past studies have reported increased resting or 24-hour energy expenditure and whole body oxygen consumption with exogenous administration of pharmacologic doses of LT4 or LT3 to healthy humans due to increased expression of uncoupling proteins and decreased mitochondrial efficiency.
“Past studies have reported increased resting or 24-hour energy expenditure and whole body oxygen consumption with exogenous administration of pharmacologic doses of LT4 or LT3 to healthy humans (3-7) due to increased expression of uncoupling proteins and decreased mitochondrial efficiency (3,4,7).”
From Effects of levothyroxine replacement or suppressive therapy on energy expenditure and body composition (2016) · cites this paper as [3]
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- Authors
- Johannsen, D. L., Galgani, J. E., Johannsen, N. M., Zhang, Z., Covington, J. D., & Ravussin, E.
- Affiliations
- Pennington Biomedical Research Center (US)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-07-26
- Volume
- 7
- Issue
- 7
- Pages
- e40837
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3406028
- OpenAlex
- W2078283606
- Cited by
- 57
- References
- 35
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2023: 8 · 2022: 5 · 2021: 4 · 2020: 9 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 3 · 2014: 1 · 2013: 5
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- Nutrition Obesity Research Center, University of North Carolina
- National Institute on Aging (P01AG022064, P01AG22064)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK89005, K01DK089005, P30DK072476)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- thyroxine, levothyroxine, triiodothyronine, energy expenditure, resting metabolic rate, exercise efficiency, skeletal muscle metabolism, mitochondrial efficiency, respiratory control ratio, vastus lateralis, thyroid hormone replacement, obesity treatment
- MeSH terms
- Adult, Basal Metabolism, Energy Metabolism, Humans, Male, Mitochondria, Thyroxine, Time Factors, Exercise
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