Skip to main content
    • Aa
    • Aa

Energy restriction and the prevention of breast cancer

  • Michelle Harvie (a1) and Anthony Howell (a1)

Energy restriction (ER) to control weight is a potential strategy for breast cancer prevention. The protective effects of habitual continuous energy restriction (CER) and weight loss on breast tumour formation have been conclusively demonstrated in animal studies over the past 100 years, and more recently in women using data from observational studies and bariatric surgery. Intermittent energy restriction (IER) and intermittent fasting (IF) are possible alternative preventative approaches which may be easier for individuals to undertake and possibly more effective than standard CER. Here, we summarise the available data on CER, IER and IF with special emphasis on their potential for breast cancer prevention. In animals, IER is superior or equivalent to CER with the exception of carcinogen-induced tumour models when initiated soon after carcinogen exposure. There are no human data on IER and breast cancer risk, but three studies demonstrated IER and CER to be equivalent for weight loss. IF regimens also reduce mammary tumour formation in animal models and also led to weight loss in human subjects, but have not been directly compared with CER. Animal and some human data suggest that both IER and IF may differ mechanistically compared with CER and may bring about greater reduction in hepatic and visceral fat stores, insulin-like growth factor 1 (IGF-1) levels and cell proliferation, and increased insulin sensitivity and adiponectin levels. Although IER and IF were first studied 65 years ago, we conclude that further studies are required to assess their values compared with CER.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Energy restriction and the prevention of breast cancer
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Energy restriction and the prevention of breast cancer
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Energy restriction and the prevention of breast cancer
      Available formats
Corresponding author
*Corresponding author: Dr Michelle Harvie, email
Hide All
5. AH Eliassen , GA Colditz , B Rosner (2006) Adult weight change and risk of postmenopausal breast cancer. JAMA 296, 193201.

6. LR Teras , M Goodman , AV Patel (2011) Weight loss and postmenopausal breast cancer in a prospective cohort of overweight and obese US women. Cancer Causes Control 22, 573579.

7. RL Prentice , B Caan , RT Chlebowski (2006) Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 295, 629642.

10. ML Dansinger , JA Gleason , JL Griffith (2005) Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA 293, 4353.

11. A Vrieling , K Buck , R Kaaks (2010) Adult weight gain in relation to breast cancer risk by estrogen and progesterone receptor status: a meta-analysis. Breast Cancer Res Treat 123, 641649.

13. SA Silvera , M Jain , GR Howe (2006) Energy balance and breast cancer risk: a prospective cohort study. Breast Cancer Res Treat 97, 97–106.

16. S Camastra , A Gastaldelli , A Mari (2011) Early and longer term effects of gastric bypass surgery on tissue-specific insulin sensitivity and beta cell function in morbidly obese patients with and without type 2 diabetes. Diabetologia 54, 20932102.

18. L Sjostrom , K Narbro , CD Sjostrom (2007) Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 357, 741752.

19. HJ Thompson & A McTiernan (2011) Weight cycling and cancer: weighing the evidence of intermittent caloric restriction and cancer risk. Cancer Prev Res 4, 17361742.

20. SA French , AR Folsom , RW Jeffery (1997) Weight variability and incident disease in older women: the Iowa Women's Health Study. Int J Obes Relat Metab Disord 21, 217223.

21. A Trentham-Dietz , PA Newcomb , KM Egan (2000) Weight change and risk of postmenopausal breast cancer (United States). Cancer Causes Control 11, 533542.

22. SM Eng , MD Gammon , MB Terry (2005) Body size changes in relation to postmenopausal breast cancer among women on Long Island, New York. Am J Epidemiol 162, 229237.

25. L Gross & Y Dreyfuss (1984) Reduction in the incidence of radiation-induced tumors in rats after restriction of food intake. Proc Natl Acad Sci USA 81, 75967598.

28. RF Chen , RA Good , RW Engelman (1990) Suppression of mouse mammary tumor proviral DNA and protooncogene expression: association with nutritional regulation of mammary tumor development. Proc Natl Acad Sci USA 87, 23852389.

30. RP Shao , ML Dao , NK Day (1990) Dietary manipulation of mammary tumor development in adult C3H/Bi mice. Proc Soc Exp Biol Med 193, 313317.

31. RW Engelman , NK Day , RF Chen (1990) Calorie consumption level influences development of C3H/Ou breast adenocarcinoma with indifference to calorie source. Proc Soc Exp Biol Med 193, 2330.

32. I Siegel , TL Liu , N Nepomuceno (1988) Effects of short-term dietary restriction on survival of mammary ascites tumor-bearing rats. Cancer Invest 6, 677680.

33. KA Pape-Ansorge , JP Grande , TA Christensen (2002) Effect of moderate caloric restriction and/or weight cycling on mammary tumor incidence and latency in MMTV-Neu female mice. Nutr Cancer 44, 162168.

34. MP Cleary & ME Grossmann (2011) The manner in which calories are restricted impacts mammary tumor cancer prevention. J Carcinog 10, 21.

37. OP Rogozina , MJ Bonorden , JP Grande (2009) Serum insulin-like growth factor-I and mammary tumor development in ad libitum-fed, chronic calorie-restricted, and intermittent calorie-restricted MMTV-TGF-alpha mice. Cancer Prev Res 2, 712719.

39. RS Mehta , SR Harris , CA Gunnett (1993) The effects of patterned calorie-restricted diets on mammary tumor incidence and plasma endothelin levels in DMBA-treated rats. Carcinogenesis 14, 16931696.

41. AM Buison , MA Pellizzon , KE Brogan (2005) Weight cycling did not increase tumor incidence in high fat – fed rats treated with a low dose 7,12-dimethylbenzyl (1) anthracene. Nutr Res 25, 10971108.

49. KA Varady , S Bhutani , EC Church (2009) Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults. Am J Clin Nutr 90, 11381143.

50. MN Harvie , M Pegington , MP Mattson (2011) The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J Obes (Lond) 35(5), 714727.

52. KA Varady (2011) Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss? Obes Rev 12, e593e601.

53. E Kirk , DN Reeds , BN Finck (2009) Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology 136, 15521560.

55. KA Varady , DJ Roohk , YC Loe (2007) Effects of modified alternate-day fasting regimens on adipocyte size, triglyceride metabolism, and plasma adiponectin levels in mice. J Lipid Res 48, 22122219.

57. S Dogan , AC Johannsen , JP Grande (2011) Effects of intermittent and chronic calorie restriction on mammalian target of rapamycin (mTOR) and IGF-I signaling pathways in mammary fat pad tissues and mammary tumors. Nutr Cancer 63, 389401.

59. VC Musey , S Goldstein , PK Farmer (1993) Differential regulation of IGF-I and IGF-binding protein-1 by dietary composition in humans. Am J Med Sci 305, 131138.

60. L Fontana , EP Weiss , DT Villareal (2008) Long-term effects of calorie or protein restriction on serum IGF-I and IGFBP-3 concentration in humans. Aging Cell 7, 681687.

62. MC Klempel & KA Varady (2011) Reliability of leptin, but not adiponectin, as a biomarker for diet-induced weight loss in humans. Nutr Rev 69, 145154.

66. PG Morris , CA Hudis , D Giri (2011) Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer. Cancer Prev Res 4, 10211029.

67. KA Brown & ER Simpson (2010) Obesity and breast cancer: progress to understanding the relationship. Cancer Res 70, 47.

68. UE Martinez-Outschoorn , RG Pestell , A Howell (2011) Energy transfer in ‘parasitic’ cancer metabolism: mitochondria are the powerhouse and Achilles’ heel of tumor cells. Cell Cycle 10, 42084216.

69. KM Nieman , HA Kenny , CV Penicka (2011) Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med 17, 14981503.

70. E Sesca , F Premoselli , V Binasco (1998) Fasting-refeeding stimulates the development of mammary tumors induced by 7,12-dimethylbenz[a]anthracene. Nutr Cancer 30, 2530.

73. O Descamps , J Riondel , V Ducros (2005) Mitochondrial production of reactive oxygen species and incidence of age-associated lymphoma in OF1 mice: effect of alternate-day fasting. Mech Ageing Dev 126, 11851191.

76. MP Mattson (2008) Hormesis defined. Ageing Res Rev 7, 17.

77. LK Heilbronn , AE Civitarese , I Bogacka (2005) Glucose tolerance and skeletal muscle gene expression in response to alternate day fasting. Obes Res 13, 574581.

79. RR Henry , L Scheaffer & JM Olefsky (1985) Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 61, 917925.

80. JA Thomas , JA Antonelli , JC Lloyd (2010) Effect of intermittent fasting on prostate cancer tumor growth in a mouse model. Prostate Cancer Prostatic Dis 13, 350355.

81. O Carlson , B Martin , KS Stote (2007) Impact of reduced meal frequency without caloric restriction on glucose regulation in healthy, normal-weight middle-aged men and women. Metabolism 56, 17291734.

84. J Hsieh , AA Hayashi , J Webb (2008) Postprandial dyslipidemia in insulin resistance: mechanisms and role of intestinal insulin sensitivity. Atheroscler Suppl 9, 7–13.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Proceedings of the Nutrition Society
  • ISSN: 0029-6651
  • EISSN: 1475-2719
  • URL: /core/journals/proceedings-of-the-nutrition-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 105
Total number of PDF views: 1049 *
Loading metrics...

Abstract views

Total abstract views: 1884 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 17th October 2017. This data will be updated every 24 hours.

A correction has been issued for this article: