Docosahexaenoic Acid (DHA) Reduces Inflammation and Aromatase Expression in Subcutaneous Fat and Inflammation in the Rectosigmoid Mucosa in Obese Postmenopausal Women: A Pilot Study
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.
Interventional
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Reduced subcutaneous fat
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.
6 weeks
No
Peter Holt, MD
Principal Investigator
The Rockefeller University
United States: Institutional Review Board
PHO-0702
NCT01127867
May 2010
April 2013
Name | Location |
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The Rockefeller University | New York, New York 10065 |