Source: UNIVERSITY OF WYOMING submitted to NRP
N-3 POLYUNSATURATED FATTY ACIDS AND HUMAN HEALTH AND DISEASE
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1001456
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
NC-1199
Project Start Date
Oct 1, 2013
Project End Date
Sep 30, 2014
Grant Year
(N/A)
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
In a study on hypovitaminosis D with metabolic disturbances associated with PCOS, nearly half of the polycystic women were vitamin D deficient, demonstrating a strong relationship between body mass index (BMI) and vitamin D levels. Yildizhan et.al. reported that 25-OH Vitamin D levels were significantly lower in the obese than the non-obese PCOS women. In the present study plasma vitamin D3 levels in PCOS and non-PCOS women did not differ. In a novel finding, following omega-3 PUFA supplementation, both groups had an approximate 40% reduction in D3 that rebounded with supplemental D3. Surprisingly, plasma vitamin D2 was 2-fold higher in PCOS than non-PCOS women and remained consistent with combined omega-3 and vitamin D ingestion. Similar to the effect on D3, D2 was reduced with 3 month exclusive omega-3 supplementations but maintained reduced levels with vitamin D3 ingestion. In summary, exclusive omega-3 ingestion may lead to reduced plasma vitamin D in both PCOS and non-PCOS women. Supplemental vitamin D may be necessary in women consuming n-3 PUFA at elevated levels.
Animal Health Component
75%
Research Effort Categories
Basic
25%
Applied
75%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
30208101010100%
Knowledge Area
302 - Nutrient Utilization in Animals;

Subject Of Investigation
0810 - Finfish;

Field Of Science
1010 - Nutrition and metabolism;
Goals / Objectives
To determine the effects of omega-3 fatty acids on health-related outcomes in both human and rodent models. To define the mechanisms mediating the health promoting effects of omega-3 fatty acids.
Project Methods
Thirteen polycystic and eleven non-PCOS women were recruited for a study designed to assess the effect of 5-month n-3 PUFA supplementation on plasma vitamin D levels with an overlap of 1000 IU 1,25 dihydroxyvitamin D3 (vitamin D3) for the final two months. PCOS was diagnosed according to the Rotterdam consensus criteria by the participants' attending physician after the exclusion of other disorders with similar clinical presentation (8). 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 non-steroidal anti-inflammatory drugs (4≤ days/week). Subjects on oral contraceptives continued on the same dose. All women had typical fish consumption of less than twice weekly and did not take n-3 PUFA supplements previously. Subjects gave informed written consent and remained free-living and continued their usual activities. The study was approved by and conducted according to Institutional Review Board of the University of Wyoming. Twelve PCOS (average age 32.08 ± 1.72) and eight control (23.57±0.97) women completed the study. 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. Oral contraceptive users were evaluated during the 7-day pill-free interval (between day 5 and day 7) at the time of the reestablished pituitary-ovarian activity (9). Encapsulated n-3 PUFA supplements were provided by the Shaklee Corporation (Pleasanton, CA) containing 2.3 g of n-3 PUFA containing a total of 90.5% of the n-3 PUFA in the form of EPA and DHA. Following an eight hour overnight fast, venous blood was collected by venipuncture into heparinized tubes for assessment of initial, third, fourth, and fifth month plasma vitamin D levels. Plasma and erythrocytes were separated by centrifugation for 15 min at 5000 x g at 25 °C.. Extracted plasma was aliquoted and stored at -80 °C for subsequent vitamin D analysis by RP-HPLC with a 87:13 acetonitrile:methanol buffer. Basal and end of treatment vitamin D concentrations were compared using repeated measures ANOVA. Differences between means were assessed by ANOVA for a CRD using SAS. Significance of difference was determined at p < 0.05. Values are expressed as means ±SEM (n = 11 for PCOS, n=8 for control).

Progress 10/01/13 to 09/30/14

Outputs
Target Audience: Nothing Reported Changes/Problems: PD no longer faculty at University of Wyoming. What opportunities for training and professional development has the project provided? Undergraduate research training opportunities with associated presentation and publication. How have the results been disseminated to communities of interest? Meeting presentation. Manuscripts in preparation. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Impact: Switching from a normal Western diet to one elevated in the long-chain n-3 PUFA may improve reproduction without the need for elevated n-3 PUFA intake for fetal enrichment and impact when in utero. Previous studies indicate that women with Polycystic Ovarian Syndrome (PCOS) have compromised vitamin D status. Our data confirmed this finding and indicate that when polycystic women ingest a diet high in the long-chain n-3 HUFA, vitamin D status may be further compromised to a degree that is only marginally recoverable with vitamin D3 supplementation. However, in rodent studies it has been found that significant increased n-3 PUFA ingestion can enhance ovulation up to 1.4-fold. Thus, n-3 HUFA ingestion may be beneficial and problematic for reproduction in those with compromised reproductive capacity. In this regard we examined if switching to or remaining on an n-3 PUFA diet while altering ovulation affects rat litter size. While ovulation was enhanced with n-3 PUFA ingestion, n-3 PUFA provision in utero did not alter litter size in the rats at reproductive age versus control. However, switching diet after birth and weaning appears to influence litter size. When switched from Control to the n-3 PUFA based diet, litter size was enhanced. Similarly, when switched from n-3 PUFA in utero to a control, non n-3 PUFA based diet at weaning through maturation, rat litter size is reduced. It is intended that follow-up studies in rats will shed light on the mechanism of n-3 PUFA impact on plasma vitamin D status. While the n-3 PUFA in general have been shown at elevated levels to enhance ovulation in rats, contrary to inflammatory studies, typically only the long-chain have been shown to have a biological impact in humans. However, as alpha-linolenic acid (LNA) has been shown to alter ovulation in rats while not manifesting this inflammation related benefit, it is unknown what influence it may possess on PCOS related parameters in humans. As this is the typical n-3 PUFA consumed in humans, the influence of elevated LNA on PCOS parameters will be examined.

Publications

  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2013 Citation: Abdi J, Redinger D, Broughton KS. Vitamin D levels among women with and without PCOS Experimental Biology 2013 Boston, MA