Fatigue reduction diet in breast cancer survivors: a pilot randomized clinical trial
- 1k Downloads
Fatigue is a prevalent and burdensome effect of breast cancer. Fatigue has been linked to chronic inflammation, and diets high in antioxidant nutrients have been associated with lesser prevalence and severity of fatigue. Studies are needed, however, to test if antioxidant-rich diets could improve fatigue.
Pilot, randomized, trial conducted between January 2014 and April 2015, to investigate if a 3-month diet rich in fruit, vegetables, whole grains, and omega-3 fatty acid-rich foods, named the fatigue reduction diet (FRD), improved fatigue and sleep compared to an attention control, named the general health curriculum (GHC). 30 stage 0 to III breast cancer survivors, who had completed cancer treatments, were randomized: 15 receiving the FRD and 15 the GHC. Primary outcome was change in fatigue, as measured by the brief fatigue Inventory, from baseline to 3 months analyzed using linear mixed models. Secondary analyses were changes in sleep quality, serum carotenoids, and fatty acids.
From baseline to 3-month fatigue improved by 44 ± 39% in FRD compared to 8 ± 34% in GHC (p = 0.01); sleep quality improved by 2.5 ± 3.3 points in FRD, and diminished by 0.9 ± 2.3 in GHC (p = 0.03); serum total carotenoids (p < 0.01), β-cryptoxanthin (p = 0.02), lutein (p = 0.05), zeaxanthin (p = 0.01), lycopene (p = 0.05), omega-3 fatty acids (p < 0.01), and ratio of omega-3:omega-6 fatty acids (p = 0.02) were significantly increased, and percent saturated fatty acids were decreased (p = 0.04) in FRD; γ-tocopherol was significantly increased in GHC (p = 0.03), and there was a significant visit by group difference for α-carotene between the study groups (p = 0.05).
The FRD intervention improved fatigue and sleep in breast cancer survivors compared to the GHC. FRD diet could provide a non-toxic treatment strategy for persistent fatigue.
KeywordsCancer-related fatigue Sleep quality Breast cancer survivor Diet, omega-3 fatty acids Fruits Vegetables Whole grains Carotenoids
Fatigue reduction diet
General health curriculum
Healthy eating index
Brief fatigue inventory
Pittsburgh sleep quality index
Body mass index
Linear mixed models
Central nervous system
Michigan Clinical Research Unit
Interleukin 1 receptor antagonist
This study was supported by grants from the James Stuart and Barbara Padnos Research Funds for Cancer Research and the National Institutes of Health (NIH) CTSA Grant Number 2UL1TR000433-06. The funders had no role in the design of the study and collection, analysis, and interpretation of data, or the writing of the study. We would also like to thank Jianwei Ren for analyzing the blood samples.
Dr. Zick made substantial contributions to conception and design, data analysis and interpretation of data, and acquisition of data; was involved in drafting the manuscript revising the manuscript critically for important intellectual content and gave final approval of the version to be published. Dr. Djuric made substantial contributions to conception and design, data analysis, and interpretation of data, was involved in revising the manuscript critically for important intellectual content and gave final approval of the version to be published. Dr. Colacino made substantial contributions to conception and design, data analysis and interpretation of data, and he was involved in revising the manuscript critically for important intellectual content and gave final approval of the version to be published. Ms. Brash, Surnow, Khabir, Cornellier, and Mr. Ren made substantial contributions to acquisition of data, and were involved in revising the manuscript critically for important intellectual content and gave final approval of the version to be published.
Compliance with ethical standards
Conflicts of interest
Drs. Zick, Djuric and Colacino and Ms. Cornellier, Surnow and Khabir declare that they have neither financial nor non-financial competing interest to disclose nor do they have any conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- 1.Alfano CM, Day JM, Katz ML, Herndon JE 2nd, Bittoni MA, Oliveri JM, Donohue K, Paskett ED (2009) Exercise and dietary change after diagnosis and cancer-related symptoms in long-term survivors of breast cancer: CALGB 79804. Psycho-oncology 18:128–133. doi: 10.1002/pon.1378 CrossRefPubMedPubMedCentralGoogle Scholar
- 2.Alfano CM, Imayama I, Neuhouser ML, Kiecolt-Glaser JK, Smith AW, Meeske K, McTiernan A, Bernstein L, Baumgartner KB, Ulrich CM, Ballard-Barbash R (2012) Fatigue, inflammation, and omega-3 and omega-6 fatty acid intake among breast cancer survivors. J Clin Oncol 30:1280–1287. doi: 10.1200/JCO.2011.36.4109 CrossRefPubMedPubMedCentralGoogle Scholar
- 3.Ancoli-Israel S, Liu L, Rissling M, Natarajan L, Neikrug AB, Palmer BW, Mills PJ, Parker BA, Sadler GR, Maglione J (2014) Sleep, fatigue, depression, and circadian activity rhythms in women with breast cancer before and after treatment: a 1-year longitudinal study. Support Care Cancer 22:2535–2545. doi: 10.1007/s00520-014-2204-5 CrossRefPubMedPubMedCentralGoogle Scholar
- 4.Arthur AE, Peterson KE, Shen J, Djuric Z, Taylor JMG, Hebert JR, Duffy SA, Peterson LA, Bellile EL, Whitfield JR, Chepeha DB, Schipper MJ, Wolf GT, Rozek LS (2014) Diet and proinflammatory cytokine levels in head and neck squamous cell carcinoma. Cancer 120:2704–2712. doi: 10.1002/cncr.28778 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Box G, Cox DR (1964) An analysis of transformations. J R Stat Soc 26:211–252Google Scholar
- 15.Buysse D, Hall M, Strollo P, Kamarck T, Owens J, Lee L, Reis S, Matthews K (2008) Relationships between the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and clinical/polysomnographic measures in a community sample. J Clin Sleep Med 4:563–571PubMedPubMedCentralGoogle Scholar
- 16.Campbell DR, Gross MD, Martini MC, Grandits GA, Slavin JL, Potter JD (1994) Plasma carotenoids as biomarkers of vegetable and fruit intake. Cancer Epidemiol Biomark Prev 3:493–500Google Scholar
- 26.Galiano-Castillo N, Ariza-Garcia A, Cantarero-Villanueva I, Fernandez-Lao C, Diaz-Rodriguez L, Arroyo-Morales M (2014) Depressed mood in breast cancer survivors: associations with physical activity, cancer-related fatigue, quality of life, and fitness level. Eur J Oncol Nurs 18:206–210. doi: 10.1016/j.ejon.2013.10.008 CrossRefPubMedGoogle Scholar
- 27.George SM, Alfano CM, Neuhouser ML, Smith AW, Baumgartner RN, Baumgartner KB, Bernstein L, Ballard-Barbash R (2014) Better postdiagnosis diet quality is associated with less cancer-related fatigue in breast cancer survivors. J Cancer Surviv 8:680–687. doi: 10.1007/s11764-014-0381-3 CrossRefPubMedGoogle Scholar
- 34.Le Marchand L, Hankin JH, Carter FS, Essling C, Luffey D, Franke AA, Wilkens LR, Cooney RV, Kolonel LN (1994) A pilot study on the use of plasma carotenoids and ascorbic acid as markers of compliance to a high fruit and vegetable dietary intervention. Cancer Epidemiol Biomark Prev 3:245–251Google Scholar
- 41.Noal S, Levy C, Hardouin A, Rieux C, Heutte N, Segura C, Collet F, Allouache D, Switsers O, Delcambre C, Delozier T, Henry-Amar M, Joly F (2011) One-year longitudinal study of fatigue, cognitive functions, and quality of life after adjuvant radiotherapy for breast cancer. Int J Radiat Oncol Biol Phys 81:795–803. doi: 10.1016/j.ijrobp.2010.06.037 CrossRefPubMedGoogle Scholar
- 42.Palesh O, Aldridge-Gerry A, Ulusakarya A, Ortiz-Tudela E, Capuron L, Innominato PF (2013) Sleep disruption in breast cancer patients and survivors. J Natl Compr Cancer Netw 11:1523–1530Google Scholar
- 43.Pertl MM, Hevey D, Boyle NT, Hughes MM, Collier S, O’Dwyer AM, Harkin A, Kennedy MJ, Connor TJ (2013) C-reactive protein predicts fatigue independently of depression in breast cancer patients prior to chemotherapy. Brain Behav Immun 34:108–119. doi: 10.1016/j.bbi.2013.07.177 CrossRefPubMedGoogle Scholar
- 46.Saligan LN, Olson K, Filler K, Larkin D, Cramp F, Yennurajalingam S, Escalante CP, del Giglio A, Kober KM, Kamath J, Palesh O, Mustian K (2015) The biology of cancer-related fatigue: a review of the literature. Support Care Cancer 23:2461–2478. doi: 10.1007/s00520-015-2763-0 CrossRefPubMedPubMedCentralGoogle Scholar
- 49.Sen A, Ren J, Ruffin MT, Turgeon DK, Brenner DE, Sidahmed E, Rapai ME, Cornellier ML, Djuric Z (2013) Relationships between serum and colon concentrations of carotenoids and fatty acids in randomized dietary intervention trial. Cancer Prev Res (Philadelphia, PA) 6:558–565. doi: 10.1158/1940-6207.capr-13-0019 CrossRefGoogle Scholar
- 50.Sisti JS, Lindstrom S, Kraft P, Tamimi RM, Rosner BA, Wu T, Willett WC, Eliassen AH (2015) Premenopausal plasma carotenoids, fluorescent oxidation products, and subsequent breast cancer risk in the nurses’ health studies. Breast Cancer Res Treat 151:415–425. doi: 10.1007/s10549-015-3391-6 CrossRefPubMedPubMedCentralGoogle Scholar
- 51.Stern JH, Grant AS, Thomson CA, Tinker L, Hale L, Brennan KM, Woods NF, Chen Z (2014) Short sleep duration is associated with decreased serum leptin, increased energy intake and decreased diet quality in postmenopausal women. Obesity (Silver Spring, Md.) 22:E55–E61. doi: 10.1002/oby.20683 CrossRefGoogle Scholar
- 54.Yarlagadda A, Alfson E, Clayton AH (2009) The blood brain barrier and the role of cytokines in neuropsychiatry. Psychiatry (Edgmont) 6:18–22Google Scholar
- 56.Zick SM, Zwickey H, Wood L, Foerster B, Khabir T, Wright B, Ichesco E, Sen A, Harris RE (2014) Preliminary differences in peripheral immune markers and brain metabolites between fatigued and non-fatigued breast cancer survivors: a pilot study. Brain Imaging Behav 8:506–516. doi: 10.1007/s11682-013-9270-z CrossRefPubMedGoogle Scholar