A Pilot Study of Docosahexaenoic Acid (DHA) in Obese Menopausal Women
This study aims to determine if a supplement of an omega-3-fatty acid (docosahexaenoic - DHA) lowers inflammation in human fat tissue thereby lowering estrogen production and the potential risk for breast, rectal and colon cancers. The investigators also aim to study how this occurs to discover the basis for other potential treatments to lower estrogen production in fat tissue and decrease the risk of breast cancer. Additionally, this study will evaluate the effectiveness of DHA supplements in reducing inflammation and the risk for colon cancer.
Dietary Supplement: dietary intervention
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Docosahexaenoic Acid (DHA) Reduces Inflammation and Aromatase Expression in Subcutaneous Fat and Inflammation in the Rectosigmoid Mucosa in Obese Postmenopausal Women: A Pilot Study|
- Reduced subcutaneous fat [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]Reduced subcutaneous fat and colorectal mucosal inflammation changes between pre and post treatment as seen by histologic quantification of monocyte aggregations (crowns), CD68 and CD163 stained macrophages in fat biopsies, as well as, mediators of mucosal inflammatory and immune protein concentrations in rectosigmoid biopsies.
- multiplex bead assay/immunoassay [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Lowered aromatase expression in fat biopsies accompanied by decreases in the synthetic enzyme COX1-MPGES-1 and/or increase in the catabolic enzyme 15-PGDH and associated changes in BRAC-1 and SIRT-1 expression.
by immunohistochemical evaluation of CD68, CD168 and CD3 stained monocytes and through examination of the mRNA of imune inflammatory markers.
Alteration in serum estradiol and testosterone levels and/or changes in circulating cytokines/chemokines measured by multiplex bead assay and immuoassay.
|Study Start Date:||May 2010|
|Study Completion Date:||April 2013|
|Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Dietary Supplement: dietary intervention
Breast cancer and colorectal cancer are two of the most frequently seen cancers in the United States. Breast cancer occurs at all ages but is particularly common in post menopausal women. Obesity increases the risk of breast cancer primarily of the type that is stimulated by the female sex hormone estrogen. In obesity, fat cells produce estrogen which can alter breast tissue, while lowering blood estrogen reduces the incidence of breast cancer. Inflammation of fat tissue, the coronary blood vessels and the liver are also seen with obesity. Animal experiments have shown the inflammation in fat tissue increases the production of estrogen, thus reducing inflammation in fat tissue might lower estrogen levels and the risk of breast cancer in obese women. Obesity simultaneously increases the inflammation of colon tissue. Since chronic inflammation in the colon is a co-factor in rectal and colon cancers, reducing inflammation should lower the risk of developing these cancers as well. A diet high in omega-3-fatty acids, such as those found in fish oil, has been shown in mice to reduce inflammation and aromatase expression (rate limiting enzyme for estrogen synthesis) in fat tissue and to reduce inflammation in the colon of mice and humans.
This pilot study of five obese, postmenopausal women will include nutritional and medical evaluations, a four day inpatient hospital stay on a regular diet, and to measure the inflammation and the estrogen producing machinery and resting energy of each volunteer subject, as well as, biopsies of abdominal fat tissue and the inflammation in the sigmoid colon obtained by sigmoidoscopy. Following these baseline measurements, subjects will be provided DHA supplements to take daily for three months and requested to weigh themselves twice weekly at home with the goal of maintaining their weight. Telephone interviews will be performed at scheduled points to check-in with the subjects and after six weeks blood tests will be performed. At three months each subject will be readmitted to the hospital and repeat the tests performed before starting on the DHA supplement. If the study shows feasibility and positive results it will be extended to more subjects and other interventions in the future.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01127867
|United States, New York|
|The Rockefeller University|
|New York, New York, United States, 10065|
|Principal Investigator:||Peter Holt, MD||The Rockefeller University|