(27-04-10) Omega 3 Fatty acid supplements in women at high risk of breast cancer have dose-dependent effects
on breast adipose tissue fatty acid composition1,2,3
Lisa D Yee, Joanne L Lester, Rachel M Cole, Julia R Richardson, Jason C Hsu, Yan Li, Amy Lehman, Martha A Belury and Steven K Clinton
1 From the Departments of Surgery (LDY) Human Nutrition (RMC JRRMAB) Statistics (JCHYL)Internal Medicine (SKC)the College of Nursing (JLL)the Center for Biostatistics (AL) The Ohio State University Columbus OH.
2 Supported in part by the National Cancer Institute (subaward agreement under U10 CA37447P30 CA16058-29S1)General Clinical Research Center at The Ohio State University (M01-RR00034) from the National Center of Research Resources of the National Institutes of Health.
3 Address correspondence to LD Yee, N924 Doan Hall, 410 West 10th Avenue, Columbus, OH 43210. E-mail [email protected] .
Background: Preclinical evidence of the preventive benefits of -3 (n?3) polyunsaturated fatty acids (PUFAs) in breast cancer continues to fuel interest in the potential role of dietary fat content in reducing breast cancer risk. The dose of fish-oil/ -3 PUFAs needed to achieve maximal target tissue effects for breast cancer prevention remains undefined.
Objective: To determine the dose effects of -3 fatty acids on breast adipose tissue fatty acid profiles, we conducted a study of 4 doses of -3 PUFAs in women at high risk of breast cancer.
Design: In this 6-mo randomized open-label study, 48 women with increased breast cancer risk received 1, 3, 6, or 9 capsules/d of an -3 PUFA supplement that provided 0.84, 2.52, 5.04, and 7.56 g docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) daily, respectively. Subjects made monthly visits, at which time pill counts were made and fasting blood samples were collected to determine fatty acid profiles; anthropometric measurements were made, breast adipose tissue samples were collected, and laboratory tests of toxicity (alanine aminotransferase, LDL cholesterol, and platelet function) were made at baseline and at 3 and 6 mo.
Results: All doses led to increased serum and breast adipose tissue EPA and DHA concentrations, but the response to 0.84 g DHA+EPA/d was less than the maximum possible response with 2.52 g/d. Body mass index attenuated the dose response for serum tissue DHA and EPA (P = 0.015 and 0.027, respectively) and breast adipose tissue DHA (P = 0.0022) in all of the treatment groups. The incremental increase in DHA and EPA correlated inversely with baseline fat and serum values. Compliance over 6 mo was 92.9 ? 9.2% and was unaffected by treatment arm. No severe or serious toxicities were reported.
Conclusions: Daily doses up to 7.56 g DHA+EPA were well tolerated with excellent compliance in this cohort at high risk of breast cancer. Body mass index and baseline fatty acid concentrations modulated the dose-response effects of -3 PUFA supplements on serum EPA and DHA and breast adipose tissue DHA.
Source: Am J Clin Nutr 91: 1185-1194, 2010. First published March 24, 2010; doi:10.3945/ajcn.2009.29036
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