Polycystic Ovarian Syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovulatory disorder, and polycystic changes in the ovaries.
Currently, the etiology of PCOS is not clear, but genetic, environmental, and dietary factors can play some roles in the pathogenesis of PCOS.
Omega-3 polyunsaturated fatty acids (PUFAs) can have beneficial effects on PCOS, including improving endothelial function, anti-obesity effects, glycemic and hormonal homeostasis, and anti-inflammatory effects. However, researchers on the metabolic effects of PUFAs in PCOS pathogenesis have had mixed results. In addition, no cohort or case-control study has directly assessed the associations between nutritional and serum omega-3 PUFAs and PCOS.
The aim of this study was therefore to investigate the association between omega-3 PUFAs from a normal diet and from serum phospholipids and PCOS prevalence in Chinese women in order to provide evidence of the strategic relevance of dietary assessment in the treatment of patients with PCOS .
This matched-case-control study examined the association between omega-3 PUFAs and PCOS prevalence in 325 pairs of PCOS cases and healthy controls (recruited from the First Affiliated Hospital of Chengdu Medical College, China).
On their first visit to the hospital, all participants conducted a computer-aided, personal interview with experienced nurses using a structured questionnaire. The following information was collected: (i) socio-demographic characteristics such as age and education; (ii) lifestyle habits such as smoking status, alcohol consumption, physical activity and food intake; (iii) history of chronic diseases; and (iv) use of nutritional supplements. In addition, 10 ml of fasting peripheral blood was collected overnight from all subjects.
For each case size, weight, waist circumference, hip circumference, blood pressure, fasting glucose, fasting insulin, total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), high-sensitivity C-reactive protein (hs-CRP ) and PCOS phenotypes were extracted from the medical records.
The 102-point Quantitative Food Frequency Questionnaire (FFQ) was used to assess food intake. The participants were asked to remember the foods they had eaten in the previous year before the diagnosis (cases) or the interview (controls).
Gas chromatography was used to obtain the concentrations of fatty acids in serum phospholipids, and the individual serum fatty acid levels were determined by lipid extraction followed by gas chromatographic analysis.
The results suggest that omega-3 PUFAs in serum phospholipids were inversely associated with PCOS prevalence, including total, long-chain, and individual PUFAs (e.g., docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) ).
Only long-chain omega-3 PUFAs, EPA and DHA were found to have significant inverse associations for the dietary intake of omega-3 PUFAs. Both food and serum omega-3 PUFAs, mainly EPA and DPA, correlated negatively with PCOS-related parameters such as BMI, fasting insulin, total testosterone, and highly sensitive C-reactive protein (hs-CRP), but positively with follicle-stimulating hormone (FSH) ) and sex hormone binding globulin (SHBG).
These results suggest inverse associations between omega-3 PUFAs, particularly long-chain omega-3 PUFAs, and PCOS prevalence. The researchers therefore conclude that a higher intake of omega-3 PUFAs in Chinese women could be viewed as a protective factor for PCOS.
They also point to a number of limitations in the study, including reliance on diet reminders, which would inevitably lead to some memory bias.
Mechanisms of action
There are currently several hypotheses about the effects of omega-3 PUFAs on the pathogenesis of PCOS. The first hypothesis is that supplementation with omega-3 PUFAs can lower the BMI in PCOS patients. Obesity negatively affects ovarian function due to its characteristics of tissue-specific chronic inflammation and oxidative stress. In obesity, adipocyte hypertrophy leads to hypoxia-induced necrosis of the adipocytes and infiltration of the adipose tissue with circulating macrophages and T-helper cells. Increased levels of macrophages can induce the secretion of proinflammatory cytokines such as TNF-α and ILs, which further produce more proinflammatory cytokines by activating the Nuclear Factor-κB (NF-κB) signaling pathway.
The second hypothesis is that omega-3 PUFAs have beneficial effects on insulin resistance in patients with PCOS. Omega-3 PUFAs could reduce endoplasmic reticulum stress caused by metabolic abnormalities in PCOS patients, reduce lipid deposition in cells, reduce levels of reactive oxygen species in cells, and improve insulin sensitivity to some extent. IGF-I is synthesized by the ovary and the IGF-I receptor, a tyrosine kinase, has considerable structural and functional homology with the insulin receptor. The hybrid heterotetramers, composed of α- and β-dimers of insulin and IGF-F receptor, can bind insulin and IGF-I and also mediate multiple insulin effects on the ovary.
Insulin, a reproductive and metabolic hormone, could not only modulate ovarian steroidogenesis, but also regulate the production of SHBG. Therefore, reducing insulin resistance can be beneficial in restoring ovulatory menstrual cycles.
The third hypothesis is that omega-3 PUFAs are beneficial because of their anti-inflammatory and anti-inflammatory effects. EPA and DHA decreased the lipopolysaccharide-induced expression levels of TNF-α and IL-6. In addition, DHA also significantly reduced expression levels of vascular endothelial adhesion factor-1 and vascular cell adhesion factor, suggesting that omega-3 PUFAs may have a potential mediation mechanism in vascular endothelial damage from inflammatory factors. In addition, DHA inhibited the expression of TNF-α and IL-6 by inhibiting the activity of the NF-κB signaling pathway, which was associated with an increase in PPAR-γ expression levels. These results show that omega-3 PUFAs have a significant protective effect on the abnormal expression of inflammatory factors in patients with PCOS.
Finally, omega-3 PUFAs can also affect hormone levels in PCOS patients. Omega-3 PUFAs inhibited the arachidonic acid-induced activation of the acute regulatory protein factor and also regulate the expression of LH. In addition, it can regulate testosterone activity in PCOS patients, inhibit testosterone production and create intervention effects.
Source: The British Journal of Nutrition
Ling Lu, Xiaoqin Li, Lin Lv, Yao Xu, Baohua Wu, and Chaolin Huang
“Polyunsaturated Omega-3 Fatty Acids and PCOS in Food and Serum: A Coordinated Case-Control Study”
DOI 10.1017 / S0007114521003007