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Here we hypothesized that vitamin D (VitD) deficiency is a lead factor in the development of the overtraining syndrome. To test this hypothesis, two groups of 60\u2010week\u2010old C57BL\/6 mice followed a 16\u2010week excessive eccentric\u2010based overtraining by excessive downhill running with or without dietary VitD depletion (EX and EX\u2010D<jats:sup>\u2212<\/jats:sup> groups). Two control groups were trained by uphill running at the same load with or without VitD depletion (CX and CX\u2010D<jats:sup>\u2212<\/jats:sup> groups). Handgrip strength decreased throughout the protocol for all groups but the decrease was sharper in EX\u2010D<jats:sup>\u2212<\/jats:sup> group (VitD\u2009\u00d7\u2009training, <jats:italic>p<\/jats:italic>\u2009=\u20090.0427). At the end of the protocol, the mass of <jats:italic>Triceps brachii<\/jats:italic> muscle, which is heavily stressed by eccentric contractions, was reduced in eccentric\u2010trained groups (training effect, <jats:italic>p<\/jats:italic>\u2009=\u20090.0107). This atrophy was associated with a lower concentration of the anabolic myokine IL\u201015 (training effect, <jats:italic>p<\/jats:italic>\u2009=\u20090.0314) and a tendency to a higher expression of the atrogene cathepsin\u2010L (training effect, <jats:italic>p<\/jats:italic>\u2009=\u20090.0628). VitD depletion led to a 50% decrease of the fractional protein synthesis rate in this muscle (VitD effect, <jats:italic>p<\/jats:italic>\u2009=\u20090.0004) as well as decreased FGF21 (VitD effect, <jats:italic>p<\/jats:italic>\u2009=\u20090.0351) and increased osteocrin (VitD effect, <jats:italic>p<\/jats:italic>\u2009=\u20090.038) concentrations that would lead to metabolic defects. Moreover, the proportion of anti\u2010inflammatory Th2 lymphocytes was significantly decreased by the combination of eccentric training with VitD depletion (vitD\u2009\u00d7\u2009training, <jats:italic>p<\/jats:italic>\u2009=\u20090.0249) suggesting a systemic inflammation. Finally, exploratory behavior time of mice was decreased by VitD depletion (VitD effect, <jats:italic>p<\/jats:italic>\u2009=\u20090.0146) suggesting a cognitive dysfunction. Our results suggest that VitD deficiency exacerbates the effects of overtraining.<\/jats:p>","DOI":"10.1111\/sms.14449","type":"journal-article","created":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T06:59:55Z","timestamp":1689404395000},"page":"2149-2165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Vitamin D deficiency contributes to overtraining syndrome in excessive trained <scp>C57BL<\/scp>\/6 mice"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7466-7874","authenticated-orcid":false,"given":"J.","family":"Talvas","sequence":"first","affiliation":[{"name":"Human Nutrition Unit, UMR 1019 INRAE\/UCA, CRNH\u2010Auvergne Clermont\u2010Ferrand France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Norgieux","sequence":"additional","affiliation":[{"name":"Human Nutrition Unit, UMR 1019 INRAE\/UCA, CRNH\u2010Auvergne Clermont\u2010Ferrand 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