{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T19:23:28Z","timestamp":1773170608280,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001466","name":"American Urological Association Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001466","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006495","name":"Dr. Robert C. and Veronica Atkins Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006495","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Prostate cancer (PC) is the second most lethal cancer for men. For metastatic PC, standard first\u2010line treatment is androgen deprivation therapy (ADT). While effective, ADT has many metabolic side effects. Previously, we found in serum metabolome analysis that ADT reduced androsterone sulfate, 3\u2010hydroxybutyric acid, acyl\u2010carnitines but increased serum glucose. Since ADT reduced ketogenesis, we speculate that low\u2010carbohydrate diets (LCD) may reverse many ADT\u2010induced metabolic abnormalities in animals and humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a multicenter trial of patients with PC initiating ADT randomized to no diet change (control) or LCD, we previously showed that LCD intervention led to significant weight loss, reduced fat mass, improved insulin resistance, and lipid profiles. To determine whether and how LCD affects ADT\u2010induced metabolic changes, we analyzed serum metabolites after 3\u2010, and 6\u2010months of ADT on LCD versus control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found androsterone sulfate was most consistently reduced by ADT and was slightly further reduced in the LCD arm. Contrastingly, LCD intervention increased 3\u2010hydroxybutyric acid and various acyl\u2010carnitines, counteracting their reduction during ADT. LCD also reversed the ADT\u2010reduced lactic acid, alanine, and S\u2010adenosyl methionine (SAM), elevating glycolysis metabolites and alanine. While the degree of androsterone reduction by ADT was strongly correlated with glucose and indole\u20103\u2010carboxaldehyde, LCD disrupted such correlations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Together, LCD intervention significantly reversed many ADT\u2010induced metabolic changes while slightly enhancing androgen reduction. Future research is needed to confirm these findings and determine whether LCD can mitigate ADT\u2010linked comorbidities and possibly delaying disease progression by further lowering androgens.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24136","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T15:13:40Z","timestamp":1620227620000},"page":"618-628","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The influence of low\u2010carbohydrate diets on the metabolic response to androgen\u2010deprivation therapy in prostate cancer"],"prefix":"10.1002","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3433-903X","authenticated-orcid":false,"given":"Jen\u2010Tsan","family":"Chi","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Center for Genomics and Computational Biology Duke University Medical Center  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pao\u2010Hwa","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Duke University Medical Center  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Tolstikov","sequence":"additional","affiliation":[{"name":"BERG  Framingham Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taofik","family":"Oyekunle","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Duke University Medical Center  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria C.","family":"Galvan","sequence":"additional","affiliation":[{"name":"Center for Integrated Research in Cancer and Lifestyle, Cedars\u2010Sinai  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adela","family":"Ramirez\u2010Torres","sequence":"additional","affiliation":[{"name":"Center for Integrated Research in Cancer and Lifestyle, Cedars\u2010Sinai  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily Y.","family":"Chen","sequence":"additional","affiliation":[{"name":"BERG  Framingham Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie","family":"Bussberg","sequence":"additional","affiliation":[{"name":"BERG  Framingham Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Center for Genomics and Computational Biology Duke University Medical Center  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bennett","family":"Greenwood","sequence":"additional","affiliation":[{"name":"BERG  Framingham Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rangaprasad","family":"Sarangarajan","sequence":"additional","affiliation":[{"name":"BERG  Framingham Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niven R.","family":"Narain","sequence":"additional","affiliation":[{"name":"BERG  Framingham Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Kiebish","sequence":"additional","affiliation":[{"name":"BERG  Framingham Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8104-6419","authenticated-orcid":false,"given":"Stephen J.","family":"Freedland","sequence":"additional","affiliation":[{"name":"Center for Integrated Research in Cancer and Lifestyle, Cedars\u2010Sinai  Los Angeles California USA"},{"name":"Durham VA Medical Center  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21442"},{"key":"e_1_2_10_3_1","unstructured":"SocietyAC. 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