Dietary Fat, Eicosanoids and Breast Cancer Risk

The primary objective of this investigation is to determine whether diets designed to increase plasma n3 concentrations (a low fat diet, with or without n3 fatty acid enrichment), will favorably affect sex hormone distribution in women in a direction associated with reduced risk of sex hormone-mediated cancer development. Specifically, we hypothesize that an increased concentration of circulating n3 fatty acids will reduce the biochemical markers associated with increased risk for developing certain sex hormone mediated cancers such as breast cancer

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Other: Low Fat diet; Other: Low Fat high n3 diet; Other: High Fat Diet

Detailed Description

The guiding concept of our proposal is that both the total fat and the fatty acid composition of the diet contribute to a milieu associated with the risk for sex-hormone mediated cancers. Specifically, we hypothesize that an increased concentration of circulating n3 fatty acids will reduce the biochemical markers associated with increased risk for developing certain sex hormone mediated cancers such as breast cancer. When compared with the high fat diet, we expect n3 concentrations to increase and sex hormone levels to decrease after both low fat and low fat/n3 rich diets, with the greatest response in the low fat-n3 supplemented group. The aims of this project are: 1) to evaluate the effects of total fat and n3 fatty acid consumption on plasma and urine sex hormone concentrations in postmenopausal women, 2) to evaluate the relationship between plasma concentrations of fatty acids and plasma and urinary sex hormone concentrations, and 3) to evaluate the effects of total fat and n3 fatty acid consumption on the associations between sex hormone concentrations and urinary prostaglandin E2 and thromboxane B2 concentrations.

The primary objective of this investigation is to determine whether diets designed to increase plasma n3 concentrations (a low fat diet, with or without n3 fatty acid enrichment), will favorably affect sex hormone distribution in women in a direction associated with reduced risk of sex hormone-mediated cancer development. The primary endpoints to be evaluated include plasma and urinary sex hormone concentrations as follows:

Endpoints associates with increased risk factors for breast cancer risk: plasma estradiol (E2), estrone (E1), estrone sulfate (E1 sulfate), testosterone, androstenedione, sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), Measures of estrogen action: plasma follicle stimulating hormone (FSH), urinary estrogen metabolites.

Measures of systemic arachidonic acid-derived eicosanoids: urinary bicyclo-prostaglandin E2 (PGEa), 2,3-dinor thromboxane B2 (TXB2).

Measures reflecting influence of dietary fat and fatty acid intake: plasma phospholipid, cholesterol ester, triglyceride and free fatty acid composition.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Postmenopausal women
• 45 to 70 years old,
• at least one year since their last menstrual period
• not using hormone replacement therapy,
• BMI between 19 -29
• willingness to discontinue use of over-the-counter medications with anti-prostaglandin activity such as aspirin or non-steroidal anti-inflammatory medications
• consumption of a "Typical " American diet with no unusual dietary practices such as compliance with a strict vegetarian diet
• willingness to comply with the demands of the experimental protocol.

Exclusion Criteria:

• Smoking
• Known disease process, and 3) Use of prescription medications, including hormone replacement therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Fat, High Fat, Low Fat High Omega 3; See Intervention Description	Other: Low Fat diet; Low fat diet = 20% fat; Other: Low Fat high n3 diet; Low Fat high n3 diet = 20% fat + 3% n3; Other: High Fat Diet; High Fat Diet = 40% fat
Experimental: Low Fat, Low Fat High Omega 3, High Fat; See Intervention Description	Other: Low Fat diet; Low fat diet = 20% fat; Other: Low Fat high n3 diet; Low Fat high n3 diet = 20% fat + 3% n3; Other: High Fat Diet; High Fat Diet = 40% fat
Experimental: High Fat, Low Fat, Low Fat High Omega 3; See Intervention Description	Other: Low Fat diet; Low fat diet = 20% fat; Other: Low Fat high n3 diet; Low Fat high n3 diet = 20% fat + 3% n3; Other: High Fat Diet; High Fat Diet = 40% fat
Experimental: High Fat, Low fat High Omega 3, Low Fat; See Intervention Description	Other: Low Fat diet; Low fat diet = 20% fat; Other: Low Fat high n3 diet; Low Fat high n3 diet = 20% fat + 3% n3; Other: High Fat Diet; High Fat Diet = 40% fat
Experimental: Low Fat High Omega 3, High Fat, Low Fat; See Intervention Description	Other: Low Fat diet; Low fat diet = 20% fat; Other: Low Fat high n3 diet; Low Fat high n3 diet = 20% fat + 3% n3; Other: High Fat Diet; High Fat Diet = 40% fat
Experimental: Low Fat High Omega 3, Low Fat, High Fat; See Intervention Description	Other: Low Fat diet; Low fat diet = 20% fat; Other: Low Fat high n3 diet; Low Fat high n3 diet = 20% fat + 3% n3; Other: High Fat Diet; High Fat Diet = 40% fat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Sex Hormone Levels		8 weeks
E2	Estradiol	8 weeks

Collaborators and Investigators

• Sponsor: USDA Grand Forks Human Nutrition Research Center
• Investigators: Principal Investigator: Susan K Raatz, PhD, RD, USDA, GFHNRC

Publications and helpful links

General Publications

• McColley SP, Georgopoulos A, Young LR, Kurzer MS, Redmon JB, Raatz SK. A high-fat diet and the threonine-encoding allele (Thr54) polymorphism of fatty acid-binding protein 2 reduce plasma triglyceride-rich lipoproteins. Nutr Res. 2011 Jul;31(7):503-8. doi: 10.1016/j.nutres.2011.06.003.
• Raatz SK, Young LR, Picklo MJ Sr, Sauter ER, Qin W, Kurzer MS. Total dietary fat and fatty acid content modifies plasma phospholipid fatty acids, desaturase activity indices, and urinary prostaglandin E in women. Nutr Res. 2012 Jan;32(1):1-7. doi: 10.1016/j.nutres.2011.12.006.
• Young LR, Raatz SK, Thomas W, Redmon JB, Kurzer MS. Total dietary fat and omega-3 fatty acids have modest effects on urinary sex hormones in postmenopausal women. Nutr Metab (Lond). 2013 Apr 23;10(1):36. doi: 10.1186/1743-7075-10-36.
• Young LR, Kurzer MS, Thomas W, Redmon JB, Raatz SK. Effect of dietary fat and omega-3 fatty acids on urinary eicosanoids and sex hormone concentrations in postmenopausal women: a randomized controlled feeding trial. Nutr Cancer. 2011;63(6):930-9. doi: 10.1080/01635581.2011.589957. Epub 2011 Jul 11.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: April 1, 2013
• First Submitted That Met QC Criteria: April 1, 2013
• First Posted (Estimate): April 4, 2013

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 1, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: omega-3 fatty acids; sex hormones; urinary sex hormone metabolites
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: UMN914