{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:27:02Z","timestamp":1777498022140,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Culture, Sports, Science, and Technology","award":["20H03537"],"award-info":[{"award-number":["20H03537"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Some controversy remains on thresholds for deficiency or sufficiency of serum 25-hydroxyvitamin D (25(OH)D) levels. Moreover, 25(OH)D levels sufficient for bone health might differ from those required for cancer survival. This study aimed to explore these 25(OH)D threshold levels by applying the machine learning method of multivariable adaptive regression splines (MARS) in post hoc analyses using data from the AMATERASU trial, which randomly assigned Japanese patients with digestive tract cancer to receive vitamin D or placebo supplementation. Using MARS, threshold 25(OH)D levels were estimated as 17 ng\/mL for calcium and 29 ng\/mL for parathyroid hormone (PTH). Vitamin D supplementation increased calcium levels in patients with baseline 25(OH)D levels \u226417 ng\/mL, suggesting deficiency for bone health, but not in those &gt;17 ng\/mL. Vitamin D supplementation improved 5-year relapse-free survival (RFS) compared with placebo in patients with intermediate 25(OH)D levels (18\u201328 ng\/mL): vitamin D, 84% vs. placebo, 71%; hazard ratio, 0.49; 95% confidence interval, 0.25\u20130.96; p = 0.04. In contrast, vitamin D supplementation did not improve 5-year RFS among patients with low (\u226417 ng\/mL) or with high (\u226529 ng\/mL) 25(OH)D levels. MARS might be a reliable method with the potential to eliminate guesswork in the estimation of threshold values of biomarkers.<\/jats:p>","DOI":"10.3390\/nu14091689","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:22:43Z","timestamp":1650414163000},"page":"1689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Applying Machine Learning to Determine 25(OH)D Threshold Levels Using Data from the AMATERASU Vitamin D Supplementation Trial in Patients with Digestive Tract Cancer"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2322-3405","authenticated-orcid":false,"given":"Katharina","family":"Otani","sequence":"first","affiliation":[{"name":"Division of Molecular Epidemiology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan"},{"name":"Siemens Healthcare K.K., Osaki Gate City West Tower, 1-11-1 Osaki, Shinagawa-ku, Tokyo 114-8644, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuki","family":"Kanno","sequence":"additional","affiliation":[{"name":"Division of Molecular Epidemiology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3649-4519","authenticated-orcid":false,"given":"Taisuke","family":"Akutsu","sequence":"additional","affiliation":[{"name":"Division of Molecular Epidemiology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Ohdaira","sequence":"additional","affiliation":[{"name":"Department of Surgery, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara 329-2763, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Surgery, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara 329-2763, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7395-5831","authenticated-orcid":false,"given":"Mitsuyoshi","family":"Urashima","sequence":"additional","affiliation":[{"name":"Division of Molecular Epidemiology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nrendo.2017.31","article-title":"Comparative analysis of nutritional guidelines for vitamin D","volume":"13","author":"Bouillon","year":"2017","journal-title":"Nat. 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