A Pilot Study of Docosahexaenoic Acid (DHA) in Obese Menopausal Women

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.

Inclusion Criteria:

Post-menopausal defined as:

1. 24 consecutive months without a menstrual period AND

2. low serum estradiol level (<40 ng/ml) to be assessed at screening AND

3. not taking any medication known to induce ammenorhea AND

4. no known endocrine abnormality associated with irregular/absent menses.

5. BMI greater than 35.

Exclusion Criteria:

1. Currently taking any hormone therapy: oral, transplanted, vaginal, injected

2. Currently taking NSAIDS (if > once a week, stopped < 30 days ago)

3. Currently taking oral hypoglycemics

4. Currently taking anticoagulants or stopped < 30 days ago

5. Any history of a malignancy excluding basal and squamous cell skin cancer

6. Blood Pressure > 150/90 at screening

7. History of any bleeding disorder

8. LFT results > 2x normal upper limits

9. Renal lab value results > 2x normal upper limits

10. Any condition or situation which, in the investigator's opinion, puts the patient at
significant risk, could complicate the study results, or may interfere significantly
with participation in the study.

11. History of intestinal malabsorption

12. RBC's (red blood cells) on screening urinalysis

13. History of chronic diarrhea

14. Using any drug study medications or multiple medications that might change the bowel
lining.

15. On any medications that can alter fat stores or large bowel inflammation as deemed by
the principal investigator

16. History of inflammatory bowel disease

17. Abnormal thyroid function based on screening labs

18. Currently using any weight control medication

19. HIV positive as per POCT rapid test at screening

20. Currently taking fish oil, omega-3 supplements or other herbals that exceed the GRAS
(Generally Recognized As Safe)

21. Fasting blood sugar greater than 126 mg/dL at screening

22. Currently taking more than 3 antihypertensive medications