BACKGROUND: Prostate cancer (PC) is the second most lethal cancer for men. For metastatic PC, standard first-line 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-hydroxybutyric acid, acyl-carnitines but increased serum glucose. Since ADT reduced ketogenesis, we speculate that low-carbohydrate diets (LCD) may reverse many ADT-induced metabolic abnormalities in animals and humans. METHODS: 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-induced metabolic changes, we analyzed serum metabolites after 3-, and 6-months of ADT on LCD versus control. RESULTS: We found androsterone sulfate was most consistently reduced by ADT and was slightly further reduced in the LCD arm. Contrastingly, LCD intervention increased 3-hydroxybutyric acid and various acyl-carnitines, counteracting their reduction during ADT. LCD also reversed the ADT-reduced lactic acid, alanine, and S-adenosyl methionine (SAM), elevating glycolysis metabolites and alanine. While the degree of androsterone reduction by ADT was strongly correlated with glucose and indole-3-carboxaldehyde, LCD disrupted such correlations. CONCLUSIONS: Together, LCD intervention significantly reversed many ADT-induced metabolic changes while slightly enhancing androgen reduction. Future research is needed to confirm these findings and determine whether LCD can mitigate ADT-linked comorbidities and possibly delaying disease progression by further lowering androgens.
BACKGROUND: Prostate cancer (PC) is the second most lethal cancer for men. For metastatic PC, standard first-line 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-hydroxybutyric acid, acyl-carnitines but increased serum glucose. Since ADT reduced ketogenesis, we speculate that low-carbohydrate diets (LCD) may reverse many ADT-induced metabolic abnormalities in animals and humans. METHODS: 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-induced metabolic changes, we analyzed serum metabolites after 3-, and 6-months of ADT on LCD versus control. RESULTS: We found androsterone sulfate was most consistently reduced by ADT and was slightly further reduced in the LCD arm. Contrastingly, LCD intervention increased 3-hydroxybutyric acid and various acyl-carnitines, counteracting their reduction during ADT. LCD also reversed the ADT-reduced lactic acid, alanine, and S-adenosyl methionine (SAM), elevating glycolysis metabolites and alanine. While the degree of androsterone reduction by ADT was strongly correlated with glucose and indole-3-carboxaldehyde, LCD disrupted such correlations. CONCLUSIONS: Together, LCD intervention significantly reversed many ADT-induced metabolic changes while slightly enhancing androgen reduction. Future research is needed to confirm these findings and determine whether LCD can mitigate ADT-linked comorbidities and possibly delaying disease progression by further lowering androgens.
Authors: Timothy R Koves; John R Ussher; Robert C Noland; Dorothy Slentz; Merrie Mosedale; Olga Ilkayeva; James Bain; Robert Stevens; Jason R B Dyck; Christopher B Newgard; Gary D Lopaschuk; Deborah M Muoio Journal: Cell Metab Date: 2008-01 Impact factor: 27.287
Authors: Darryl P Leong; Vincent Fradet; Bobby Shayegan; Emmanuelle Duceppe; Robert Siemens; Tamim Niazi; Laurence Klotz; Ian Brown; Joseph Chin; Luke Lavallee; Negareh Mousavi; Patrick Luke; Himu Lukka; Darin Gopaul; Philippe Violette; Rob J Hamilton; Margot K Davis; Sarah Karampatos; Rajibul Mian; Guila Delouya; Yves Fradet; Som Mukherjee; David Conen; Annabel Chen-Tournoux; Christopher Johnson; Amal Bessissow; George Dresser; Adnan Kazi Hameed; Husam Abdel-Qadir; Alp Sener; Raveen Pal; P J Devereaux; Jehonathan Pinthus Journal: J Urol Date: 2020-01-03 Impact factor: 7.450
Authors: Michael L Gatza; Hsiu-Ni Kung; Kimberly L Blackwell; Mark W Dewhirst; Jeffrey R Marks; Jen-Tsan Chi Journal: Breast Cancer Res Date: 2011-06-07 Impact factor: 6.466
Authors: Xiaohu Tang; Chao-Chieh Lin; Ivan Spasojevic; Edwin S Iversen; Jen-Tsan Chi; Jeffrey R Marks Journal: Breast Cancer Res Date: 2014-08-05 Impact factor: 6.466
Authors: Jen-Tsan Chi; Pao-Hwa Lin; Vladimir Tolstikov; Taofik Oyekunle; Emily Y Chen; Valerie Bussberg; Bennett Greenwood; Rangaprasad Sarangarajan; Niven R Narain; Michael A Kiebish; Stephen J Freedland Journal: Cancer Med Date: 2020-03-31 Impact factor: 4.452