N-3 POLYUNSATURATED FATTY ACIDS AND HUMAN HEALTH AND DISEASE

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: HATCH
• Reporting Frequency: Annual
• Accession No.: 0227349
• Multistate No.: NC-1039
• Project Start Date: Oct 1, 2007
• Project End Date: Sep 30, 2012
• Program Code: [(N/A)]- (N/A)

Recipient Organization
UNIVERSITY OF WYOMING
1000 E UNIVERSITY AVE DEPARTMENT 3434
LARAMIE,WY 82071-2000

Performing Department
Family And Consumer Sciences

Non Technical Summary
Basal leptin was significantly higher in the PCOS group at 23.3 versus 10.9 ng/ml plasma in the non PCOS women (p<0.05), respectively, eventually shifting by 150% in both polycystic women and controls. However, polycystic women leptin levels consistently remained twice controls with exclusive n-3 PUFA ingestion. With vitamin D ingestion both groups shifted toward baseline though baseline was not achieved. The leptin dip toward baseline was sharper in polycystic women as control women continued to show an increase in leptin after an initial recovery rebound with vitamin D ingestion. Following five months of n-3 PUFA ingestion, control women attained the same level of leptin the polycystic women showed at baseline (P<0.05). With omega-3 ingestion only insulin and the HOMA index appeared to decrease, thoguh the difference was not significant. The initial HOMA index and initial and final insulin in women with increased visceral adiposity were significantly higher than levels in women with a WHR less than 0.8 (p = 0.02 and p = 0.03 respectively). Participants with a higher waist-to-hip ration (WHR) experienced a greater decrease in insulin and improvement in insulin sensitivity compared to their counterparts with a lower WHR. Total testosterone, estradiol, LH, and FSH did not change with n-3 PUFA intake. However, women with a normal WHR had a greater free estrogen index (FEI) decrease (p=0.12) than women with a high WHR (p=0.3). Although SHBG increased by 10% at three months, the difference was not significant. The average SHBG in women with a WHR<0.8 remained greater than that seen in women with a WHR>0.8 with n-3 PUFA intake. SHBG correlated with insulin where women with a normal WHR had a positive insulin to SHBG correlation (p=0.06) while women with a high WHR had a negative correlation (p=0.08).

Animal Health Component

(N/A)

Research Effort Categories

Basic

(N/A)

Applied

(N/A)

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
702	6010	1010	100%

Knowledge Area
702 - Requirements and Function of Nutrients and Other Food Components;

Subject Of Investigation
6010 - Individuals;

Field Of Science
1010 - Nutrition and metabolism;

Keywords

omega 3

polycystic ovarian syndrome

shbg

leptin

estradiol

testosterone

insulin

whr

Goals / Objectives
1.To determine the health promotion and disease prevention effects of both the forms and the amounts of n-3 fatty acids by correlation with tissue functions, and with alterations in biomarkers, relevant to optimal health and disease prevention. 2.To examine dietary levels of both form and amount of n-3 PUFA that promote health and reduce disease that are relevant and achievable in human diets using the human equivalent dose method (allometric scaling) in rodent models. 3.To develop, test and disseminate effective means for translating research on the health promoting and disease preventing effects of n-3 PUFA into consumer food choices.

Project Methods
Polycystic and non PCOS women were recruited for a study designed to assess the effect of 5-month n-3 PUFA supplementation on reproductive hormonal status with a 2 month overlap of vitamin D3. Exclusion criteria included previous diagnosis of cardiovascular disease or type 2 diabetes, history of smoking, pregnancy, breastfeeding, use of insulin-sensitizing medications and frequent use of nonsteroidal anti-inflammatory drugs (4 or less days/week). Subjects on oral contraceptives continued on the same dose. The study was approved by and conducted according to Institutional Review Board of the University of Wyoming. Women with regular menstrual cycles were assessed in the early follicular phase between days 1 and 7 after the onset of menses. Women with irregular menstrual cycles returned to the lab at regular monthly intervals. Women taking contraceptive pills were evaluated during the 7-day pill-free interval (between day 5 and day 7) at the time of the reestablished pituitary-ovarian activity. Daily supplements were given in the form of gelatin capsules containing 2.3 g of n-3 PUFA primarily in the form of EPA and DHA. For the final two months of the study all participants received 1000 IU 1,25 dihydroxyvitamin D3 (1,25(OH)2D3). Following an eight hour overnight fast, venous blood was collected by venipuncture into heparinized plasma separation tubes for assessment of initial and monthly leptin and adiponectin. Platelet rich plasma (PRP) and erythrocytes were separated by centrifugation for 15 min at 1500 x g at 25 degrees C. The recovered PRP was centrifuged at 5000 x g for 15 min at 25 degrees C to isolate plasma. Plasma was aliquoted and stored at -80 degrees C for subsequent analysis. Plasma was analyzed for glucose, LH, FSH, insulin, testosterone, estradiol and SHBG. Glucose was quantified with an Analox - Multiassay Analyser. Insulin, LH, FSH, testosterone, estradiol, adiponectin, leptin and SHBG were determined by ELISA. The homeostasis model assessment (HOMA) was used to assess insulin sensitivity by the following equation: insulin sensitivity = (fasting insulin(mU/L) x fasting glucose(mmol/L))/ 22.5. The free androgen index (FAI = testosterone/ SHBG x 100) and free estrogen index (FEI = estradiol x 0.367/SHBG) were used to estimate free testosterone and estradiol, respectively.

Progress 10/01/07 to 09/30/12

Outputs
OUTPUTS: Output has been in the form of six publications and 6 presentations at meetings specific to the topic of omega-3 fatty acids and ovulation. Data has also been utilized in the omega-3 E-xtension established by this group. An additional presentation was given at the annual meeting of the Wyoming Dietetics Association. PARTICIPANTS: PI Dr. K. Shane Broughton, MD-Graduate student Dr. Aleksandra Kuzmanov, PhD Dr. Daniel Rule, MD Dr. Eldon Handrich, PhD Dr. Bruce Culver, Graduate Student Jemilla Retta, Graduate Student Erica Ross, Graduate Student Brittney Hahn, Graduate Student Jayme Bayes, Graduate Student Yi Ye, Post Doc Xiong Zhang. Training for the following: Undergraduate aid Megan Driscoll, Undergraduate aid Tanya Halliday, Undergraduate aid Monte Lindmier, Undergraduate aid Jessica Platt, Undergraduate aid Nikki Peterson. TARGET AUDIENCES: The target audience is both Patients and MDs that work with or have reproductive issues/problems. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
As a direct result of the finding of these studies women with PCOS have initiated the intake of omega-3 fatty acids in an effort to ameliorate reproductive issues in many cases. This may also in part alleviate problems associated with the onset of type 2 diabetes in these individuals.

Publications

• Barber-Heidal K, Broughton KS, Hickner R, Malinaskis B. 2007 Co-morbidities Associated with Obesity and the Role of Omega-3 Fatty Acid Intake in Free-living Healthy Weight, Overweight and Obese College Students. FASEB J.
• Broughton KS, Rule DC, Handrich E. 2011. Prostaglandin E2 production in mice is reduced by consumption of range-fed sources of red meat. Nutrition Research. 31:907-914
• Platt J, Kuzmanov A, Halliday T, Lindmier M, Peterson N, Broughton KS. 2010. Omega-3 fatty acid and vitamin D ingestion and leptin and adiponectin in PCOS 13th World Congress on Controversies in Obstetrics, Gynecology and Infertility (COGI) 355-359
• Kuzmanov A, Broughton KS. 2010. Role of marine omega-3 fatty acids in PCOS cancer risk. 13th World Congress on Controversies in Obstetrics, Gynecology and Infertility (COGI) 349-354
• Broughton KS, Bayes J, Culver B. 2010. High alpha-linolenic acid and fish oil ingestion promotes ovulation to the same extent in rats. Nutrition Research. 30:731-738
• Broughton KS, Hahn B, Ross E. 2009. Docosahexaenoic acid and eicosapentaenoic acid differently affect ovarian prostaglandin levels in rats. Nutrition Research. 29:510-518
• Broughton KS, Rule DC, Ye Y, Zhang X,Driscoll M, Culver B. 2009. Dietary omega-3 fatty acids differentially influence ova release and ovarian COX-1 and COX-2 expression in rats. Nutrition Research. 29:197-205
• Kuzmanov A, Broughton KS. 2010. Influence of omega-3 fatty acid ingestion on hormones related to polycystic ovarian syndrome infertility. 13th World Congress on Controversies in Obstetrics, Gynecology and Infertility (COGI) November 4-7, Berlin, Germany
• Platt J, Kuzmanov A, Halliday T, Lindmier M, Peterson N, Broughton KS. 2010. Omega-3 fatty acid and vitamin D ingestion and leptin and adiponectin in PCOS. 13th World Congress on Controversies in Obstetrics, Gynecology and Infertility (COGI) November 4-7, Berlin, Germany
• Ross E, Broughton KS, Johnson K. 2009. Subclassification of Leukotriene-Based Asthmatics. FASEB J.
• Broughton KS, Hahn BL, Ross EC, Heidal KB. 2008. The Influence of Docosahexaenoic Acid DHA on Rat Ovulation. FASEB J.
• Heidal KB, Broughton KS, Malinauskas BM, Hickner RC, Duffrin MW. 2008. Relationship Among Omega-3 fatty acids, Anthropometrics, and Biochemical Markers in College Students. FASEB J.