Evidence map›Paper›PMID 40659571›Full record

ArticlePhysiological reports2025

Pharmacological prolyl hydroxylase inhibition enhances high-intensity exercise capacity in mice.

Koji Takemura, Motoki Odawara, Hiroshi Nishi, Takaaki Higashihara, Yoko Yoshida, Koichi Nakazato, Nobuharu L Fujii, Naokata Ishii, Reiko Inagi, Tetsuhiro Tanaka and 1 more

Abstract read
In one paragraph

Article in Physiological reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Koji TakemuraDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Motoki OdawaraDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Hiroshi NishiDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.ORCID 0000-0001-8415-7889
Takaaki HigashiharaDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Yoko YoshidaDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Koichi NakazatoDepartment of Exercise Physiology, Nippon Sport Science University, Tokyo, Japan.ORCID 0000-0002-2479-5771
Nobuharu L FujiiDepartment of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan.
Naokata IshiiDepartment of Life Sciences, The University of Tokyo Graduate School of Arts and Sciences, Tokyo, Japan.
Reiko InagiDivision of CKD Pathophysiology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.ORCID 0000-0001-7032-7736
Tetsuhiro TanakaDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Masaomi NangakuDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.

Funding

MEXT | Japan Society for the Promotion of Science (JSPS) 24K11425
6 · The paper itself

Abstract

Increased blood hemoglobin concentration theoretically promotes oxygen delivery to the periphery. Clinically, in addition to recombinant human erythropoietin analogs, prolyl hydroxylase (PH) inhibitors to stabilize the expression of hypoxia-inducible factor (HIF) protein were recently approved for the treatment of anemia in chronic kidney disease. However, whether the new agent helps enhance physical exercise capacity remains a matter of controversy. Treatment of C57BL/6J mice via oral gavage with roxadustat of 30 mg/kg three times per week for 5 weeks elevated the blood hemoglobin concentration, upregulated the HIF-downstream gene expression of the muscle, and enhanced a high-intensity exercise performance measured with a treadmill running exhaustion test, compared to those treated with vehicle, while total body weight or skeletal muscle mass was comparable. This physical effect depended on the increase in blood hemoglobin concentration, as confirmed by mice hemodiluted to control hemoglobin concentrations through phlebotomy followed by infusion of the approximate volume of phosphate-buffered saline. In conclusion, oral administration of the HIF-PH inhibitor to mice increased high-intensity exercise capacity as well as elevated blood hemoglobin concentration. The finding implies the versatile effects on humans taking HIF-PH inhibitors, as well as the risk of them being abused for blood doping.

Indexed as

Exercise ToleranceGlycineIsoquinolinesPhysical Conditioning, AnimalProlyl-Hydroxylase InhibitorsAnimalsHemoglobinsMaleMiceMice, Inbred C57BLMuscle, SkeletalGlycineHemoglobinsIsoquinolinesProlyl-Hydroxylase Inhibitorsroxadustatanemiaexercise capacityhemoglobinskeletal muscle

Identifiers

PMID40659571
PMCPMC12259342

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.