Evidence map›Paper›PMID 41893362›Full record

ArticleMetabolites2026

Preliminary Safety Assessment for Mandarin Orange Peel Administration to Dogs Based on Physical Conditions and Blood Examination Parameters.

Tomohiro Yonezawa, Yixue Lei, Cris Niño Bon B Marasigan, Mao Komori, Nanasa Fujiwara, Jun Nakahigashi, Eiji Kobayashi

Abstract read
In one paragraph

Article in Metabolites, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

7 authors.

Tomohiro YonezawaLaboratory of Veterinary Clinical Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Yixue LeiLaboratory of Veterinary Clinical Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Cris Niño Bon B MarasiganLaboratory of Veterinary Clinical Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.ORCID 0009-0005-5767-2881
Mao KomoriLaboratory of Veterinary Clinical Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Nanasa FujiwaraLaboratory of Veterinary Clinical Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Jun NakahigashiWellness Development Research Center, AIR WATER INC., 1-7, Tsukisamu Higashi 2-jo 16-chome, Toyohira-ku, Sapporo 062-0052, Japan.ORCID 0009-0009-7100-8935
Eiji KobayashiKobayashi Regenerative Research Institute, LLC, 1 Chayano-cho, Wakayama-shi 640-8263, Japan.ORCID 0000-0001-8617-3778

Funding

AIR WATER INC. None
6 · The paper itself

Abstract

BACKGROUND/

objectivesMandarin orange peel (MOP) is rich in bioactive polymethoxyflavones, including hesperidin and nobiletin, which have shown neuroprotective effects in rodent models. However, comprehensive safety data in dogs are required to support its development as a therapeutic intervention for canine cognitive dysfunction syndrome. In this study, the safety profile of a standardized MOP formulation was evaluated in four healthy Beagle dogs.

methodsInitially, compositional analysis was performed, and 202 pesticide residues and psoralens were screened to ensure compliance with Japanese pet food safety standards. Subsequently, a dose-escalation study was conducted in which dogs received oral MOP at 2, 6, and 10 g/head/day for 3-4 weeks at each dose level. Clinical signs, hematology, and serum biochemistry were monitored throughout the study period.

resultsThe MOP powder composition and residue levels remained within regulatory safety limits. In the dose-escalation study, no significant dose-dependent abnormalities were observed in physical or clinicopathological parameters. One dog exhibited transient loose stools at higher doses and a temporary elevation in alkaline phosphatase levels at 2 g/head/day; however, these symptoms resolved spontaneously despite continued administration.

conclusionsMOP was safe and well tolerated in dogs even at 10 g/head/day (787-952 mg/kg/day), which is approximately five times the anticipated clinical dose. The observed fluctuations in active ingredient concentrations remained within the acceptable range for natural products and did not affect overall safety. Combined with comprehensive screening for residues, these results indicate that MOP is a high-quality and safe dietary intervention for older dogs.

Indexed as

canine cognitive dysfunction syndromedose-escalation studyhesperidinmandarin orange peel (MOP)nobiletinpesticide residuespsoralenssafety assessment

Identifiers

PMID41893362
PMCPMC13027855

What OpenQuestion holds

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LicenceCC BY
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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.