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Fatigue reduction diet in breast cancer survivors: a pilot randomized clinical trial

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Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusions

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.

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Abbreviations

FRD:

Fatigue reduction diet

GHC:

General health curriculum

RD:

Registered dietitian

HEI-2010:

Healthy eating index

BFI:

Brief fatigue inventory

PSQI:

Pittsburgh sleep quality index

BMI:

Body mass index

EPA:

Eicosapentaenoic acid

CRP:

C-reactive protein

LMM:

Linear mixed models

CNS:

Central nervous system

ITT:

Intent-to-treat

MCRU:

Michigan Clinical Research Unit

IL-6:

Interleukin-6

IL-1RA:

Interleukin 1 receptor antagonist

References

  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

    Article  PubMed  PubMed Central  Google 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

    Article  CAS  PubMed  PubMed Central  Google 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

    Article  PubMed  PubMed Central  Google 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bandura A (2004) Health promotion by social cognitive means. Health Educ Behav 31:143–164. doi:10.1177/1090198104263660

    Article  PubMed  Google Scholar 

  6. Beck SL, Schwartz AL, Towsley G, Dudley W, Barsevick A (2004) Psychometric evaluation of the Pittsburgh Sleep Quality Index in cancer patients. J Pain Symptom Manag 27:140–148. doi:10.1016/j.jpainsymman.2003.12.002

    Article  Google Scholar 

  7. Bowen PE, Garg V, Stacewicz-Sapuntzakis M, Yelton L, Schreiner RS (1993) Variability of serum carotenoids in response to controlled diets containing six servings of fruits and vegetables per day. Ann N Y Acad Sci 691:241–243

    Article  CAS  PubMed  Google Scholar 

  8. Bower JE, Ganz PA, Aziz N, Fahey JL (2002) Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosom Med 64:604–611

    Article  PubMed  Google Scholar 

  9. Bower JE, Ganz PA, Aziz N, Fahey JL, Cole SW (2003) T-cell homeostasis in breast cancer survivors with persistent fatigue. J Natl Cancer Inst 95:1165–1168

    Article  PubMed  Google Scholar 

  10. Bower JE, Ganz PA, Desmond KA, Bernaards C, Rowland JH, Meyerowitz BE, Belin TR (2006) Fatigue in long-term breast carcinoma survivors: a longitudinal investigation. Cancer 106:751–758. doi:10.1002/cncr.21671

    Article  PubMed  Google Scholar 

  11. Bower JE, Lamkin DM (2013) Inflammation and cancer-related fatigue: mechanisms, contributing factors, and treatment implications. Brain Behav Immun 30(Suppl):S48–S57. doi:10.1016/j.bbi.2012.06.011

    Article  CAS  PubMed  Google Scholar 

  12. Box G, Cox DR (1964) An analysis of transformations. J R Stat Soc 26:211–252

    Google Scholar 

  13. Brownell KD, Cohen LR (1995) Adherence to dietary regimens. 2: components of effective interventions. Behav Med (Washington, DC) 20:155–164. doi:10.1080/08964289.1995.9933732

    Article  CAS  Google Scholar 

  14. Bullo M, Casas-Agustench P, Amigo-Correig P, Aranceta J, Salas-Salvado J (2007) Inflammation, obesity and comorbidities: the role of diet. Public Health Nutr 10:1164–1172. doi:10.1017/S1368980007000663

    Article  PubMed  Google 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 4:563–571

    PubMed  PubMed Central  Google 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 3:493–500

    CAS  Google Scholar 

  17. Casas R, Sacanella E, Estruch R (2014) The immune protective effect of the Mediterranean diet against chronic low-grade inflammatory diseases. Endocr Metab Immune Disord Drug Targets 14:245–254

    Article  CAS  PubMed  Google Scholar 

  18. Chai W, Conroy SM, Maskarinec G, Franke AA, Pagano IS, Cooney RV (2010) Associations between obesity and serum lipid-soluble micronutrients among premenopausal women. Nutr Res 30:227–232. doi:10.1016/j.nutres.2010.04.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Colacino JA, Arthur AE, Ferguson KK, Rozek LS (2014) Dietary antioxidant and anti-inflammatory intake modifies the effect of cadmium exposure on markers of systemic inflammation and oxidative stress. Environ Res 131:6–12. doi:10.1016/j.envres.2014.02.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Collado-Hidalgo A, Bower JE, Ganz PA, Cole SW, Irwin MR (2006) Inflammatory biomarkers for persistent fatigue in breast cancer survivors. Clin Cancer Res 12:2759–2766. doi:10.1158/1078-0432.CCR-05-2398

    Article  CAS  PubMed  Google Scholar 

  21. Cruz F, Munhoz B, Alves B, Gehrke F, Fonseca F, Kuniyoshi R, Cubero D, Peppone L, del Giglio A (2015) Biomarkers of fatigue related to adjuvant chemotherapy for breast cancer: evaluation of plasma and lymphocyte expression. Clin Trans Med 4:1–9. doi:10.1186/s40169-015-0051-8

    Article  CAS  Google Scholar 

  22. Dantzer R, Kelley KW (2007) Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun 21:153–160. doi:10.1016/j.bbi.2006.09.006

    Article  CAS  PubMed  Google Scholar 

  23. Demark-Wahnefried W, Campbell KL, Hayes SC (2012) Weight management and its role in breast cancer rehabilitation. Cancer 118:2277–2287. doi:10.1002/cncr.27466

    Article  PubMed  Google Scholar 

  24. Djuric Z, Ren J, Blythe J, VanLoon G, Sen A (2009) A Mediterranean dietary intervention in healthy American women changes plasma carotenoids and fatty acids in distinct clusters. Nutr Res 29:156–163. doi:10.1016/j.nutres.2009.03.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Eliassen AH, Liao X, Rosner B, Tamimi RM, Tworoger SS, Hankinson SE (2015) Plasma carotenoids and risk of breast cancer over 20 y of follow-up. Am J Clin Nutr 101:1197–1205. doi:10.3945/ajcn.114.105080

    Article  CAS  PubMed  PubMed Central  Google 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

    Article  PubMed  Google 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

    Article  PubMed  Google Scholar 

  28. Grandner MA, Jackson N, Gerstner JR, Knutson KL (2014) Sleep symptoms associated with intake of specific dietary nutrients. J Sleep Res 23:22–34. doi:10.1111/jsr.12084

    Article  PubMed  Google Scholar 

  29. Groenvold M, Petersen MA, Idler E, Bjorner JB, Fayers PM, Mouridsen HT (2007) Psychological distress and fatigue predicted recurrence and survival in primary breast cancer patients. Breast Cancer Res Treat 105:209–219. doi:10.1007/s10549-006-9447-x

    Article  PubMed  Google Scholar 

  30. Guest DD, Evans EM, Rogers LQ (2013) Diet components associated with perceived fatigue in breast cancer survivors. Eur J Cancer Care 22:51–59. doi:10.1111/j.1365-2354.2012.01368.x

    Article  CAS  Google Scholar 

  31. Harrington CB, Hansen JA, Moskowitz M, Todd BL, Feuerstein M (2010) It’s not over when it’s over: long-term symptoms in cancer survivors–a systematic review. Int J Psychiatry Med 40:163–181

    Article  PubMed  Google Scholar 

  32. Huang X, Zhang Q, Kang X, Song Y, Zhao W (2010) Factors associated with cancer-related fatigue in breast cancer patients undergoing endocrine therapy in an urban setting: a cross-sectional study. BMC Cancer 10:453. doi:10.1186/1471-2407-10-453

    Article  PubMed  PubMed Central  Google Scholar 

  33. Kim SH, Son BH, Hwang SY, Han W, Yang JH, Lee S, Yun YH (2008) Fatigue and depression in disease-free breast cancer survivors: prevalence, correlates, and association with quality of life. J Pain Symptom Manag 35:644–655. doi:10.1016/j.jpainsymman.2007.08.012

    Article  Google 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 3:245–251

    Google Scholar 

  35. Lee BN, Dantzer R, Langley KE, Bennett GJ, Dougherty PM, Dunn AJ, Meyers CA, Miller AH, Payne R, Reuben JM, Wang XS, Cleeland CS (2004) A cytokine-based neuroimmunologic mechanism of cancer-related symptoms. NeuroImmunoModulation 11:279–292. doi:10.1159/000079408

    Article  CAS  PubMed  Google Scholar 

  36. Mendoza TR, Wang XS, Cleeland CS, Morrissey M, Johnson BA, Wendt JK, Huber SL (1999) The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer 85:1186–1196

    Article  CAS  PubMed  Google Scholar 

  37. Meneses-Echavez JF, Gonzalez-Jimenez E, Ramirez-Velez R (2015) Effects of supervised exercise on cancer-related fatigue in breast cancer survivors: a systematic review and meta-analysis. BMC Cancer 15:77. doi:10.1186/s12885-015-1069-4

    Article  PubMed  PubMed Central  Google Scholar 

  38. Minton O, Stone P (2008) How common is fatigue in disease-free breast cancer survivors? A systematic review of the literature. Breast Cancer Res Treat 112:5–13. doi:10.1007/s10549-007-9831-1

    Article  CAS  PubMed  Google Scholar 

  39. Minton O, Stone P (2009) A systematic review of the scales used for the measurement of cancer-related fatigue (CRF). Ann Oncol 20:17–25. doi:10.1093/annonc/mdn537

    Article  CAS  PubMed  Google Scholar 

  40. Myers JS (2008) Proinflammatory cytokines and sickness behavior: implications for depression and cancer-related symptoms. Oncol Nurs Forum 35:802–807. doi:10.1188/08.ONF.802-807

    Article  PubMed  Google 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

    Article  PubMed  Google 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 11:1523–1530

    Google 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

    Article  CAS  PubMed  Google Scholar 

  44. Reinertsen KV, Cvancarova M, Loge JH, Edvardsen H, Wist E, Fossa SD (2010) Predictors and course of chronic fatigue in long-term breast cancer survivors. J Cancer Surviv 4:405–414. doi:10.1007/s11764-010-0145-7

    Article  PubMed  PubMed Central  Google Scholar 

  45. Romito F, Cormio C, Giotta F, Colucci G, Mattioli V (2012) Quality of life, fatigue and depression in Italian long-term breast cancer survivors. Support Care Cancer 20:2941–2948. doi:10.1007/s00520-012-1424-9

    Article  PubMed  Google 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

    Article  PubMed  PubMed Central  Google Scholar 

  47. Schubert C, Hong S, Natarajan L, Mills PJ, Dimsdale JE (2007) The association between fatigue and inflammatory marker levels in cancer patients: a quantitative review. Brain Behav Immun 21:413–427. doi:10.1016/j.bbi.2006.11.004

    Article  CAS  PubMed  Google Scholar 

  48. Segerstrom SC, Miller GE (2004) Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull 130:601–630. doi:10.1037/0033-2909.130.4.601

    Article  PubMed  PubMed Central  Google 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

    Article  CAS  Google 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

    Article  CAS  PubMed  PubMed Central  Google 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

    Article  CAS  Google Scholar 

  52. Wang L, Li B, Pan MX, Mo XF, Chen YM, Zhang CX (2014) Specific carotenoid intake is inversely associated with the risk of breast cancer among Chinese women. Br J Nutr 111:1686–1695. doi:10.1017/s000711451300411x

    Article  CAS  PubMed  Google Scholar 

  53. Wu HS, Harden JK (2015) Symptom burden and quality of life in survivorship: a review of the literature. Cancer Nurs 38:E29–E54. doi:10.1097/NCC.0000000000000135

    Article  PubMed  Google Scholar 

  54. Yarlagadda A, Alfson E, Clayton AH (2009) The blood brain barrier and the role of cytokines in neuropsychiatry. Psychiatry (Edgmont) 6:18–22

    Google Scholar 

  55. Zick SM, Sen A, Han-Markey TL, Harris RE (2013) Examination of the association of diet and persistent cancer-related fatigue: a pilot study. Oncol Nurs Forum 40:E41–E49. doi:10.1188/13.ONF.E41-E49

    Article  PubMed  Google 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

    Article  PubMed  Google Scholar 

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Acknowledgements

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.

Authors’ Contributions

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.

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Correspondence to Suzanna Maria Zick.

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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.

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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.

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Zick, S.M., Colacino, J., Cornellier, M. et al. Fatigue reduction diet in breast cancer survivors: a pilot randomized clinical trial. Breast Cancer Res Treat 161, 299–310 (2017). https://doi.org/10.1007/s10549-016-4070-y

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