Study links omega-3 consumption to PCOS risk

Polycystic ovary syndrome (PCOS) is a common endocrine disease that is characterized by hyperandrogenism, ovulation disorder and ovarian polycystic change. 

At present, the aetiology of PCOS is not clear, but genetic, environmental and dietary factors may play a certain role in the pathogenesis of PCOS.

Omega-3 polyunsaturated fatty acids (PUFAs) may exert beneficial effects on PCOS, including enhancement of endothelial function, anti-obesity effects, glycaemic and hormonal homeostasis, and anti-inflammatory effects. However, researcher into the metabolic effects of PUFAs in PCOS pathogenesis has created mixed results. What's more, no cohort or case-control study has directly assessed the associations between dietary and serum omega-3 PUFAs and PCOS.

Therefore, the purpose of this study was to explore the relationship between omega-3 PUFAs from a normal diet and from serum phospholipids and PCOS prevalence among Chinese women to provide evidence for the strategic relevance of nutritional assessment in the management of patients with PCOS. 

The study

This matched case-control study assessed the associations between omega-3 PUFAs and PCOS prevalence in 325 pairs of PCOS cases and healthy controls (recruited from recruited from the First Affiliated Hospital of Chengdu Medical College, China).

All participants completed a computer-assisted, face-to-face interview with experienced nurses using a structured questionnaire at the first visit to the hospital. The following information was collected: (i) sociodemographic characteristics, such as age and education; (ii) lifestyle habits, such as smoking status, alcohol drinking status, physical activities and dietary intakes; (iii) history of chronic diseases; and (iv) use of supplements. In addition, 10 ml of overnight fasting peripheral blood was collected from all subjects.

For each case, height, 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) levels and PCOS phenotypes were extracted from the medical records.

The 102 item quantitative food frequency questionnaire (FFQ) was used to assess dietary intake. The participants were interviewed to recall the food consumed over the past year before diagnosis (cases) or interview (controls).

Gas chromatography was used to obtain the concentrations of fatty acids in serum phospholipids and serum individual fatty acid levels were determined by lipid extraction and subsequent gas chromatography analysis.

Results

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)).

For dietary intake of omega-3 PUFAs, significant inverse associations were found only for long-chain omega-3 PUFAs, EPA and DHA. Both dietary and serum omega-3 PUFAs, mainly EPA and DPA, were negatively correlated with PCOS-related parameters, such as BMI, fasting insulin, total testosterone and high-sensitivity C-reactive protein (hs-CRP), but positively correlated with follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG).

These results indicate inverse associations between omega-3 PUFAs, especially long-chain omega-3 PUFAs, and PCOS prevalence. The researchers therefore conclude that higher intakes of omega-3 PUFAs might be considered a protective factor for PCOS among Chinese females.

They also note a number of limitations of the study, including the reliance of diet recall which would inevitably lead to some recall bias.

Mechanisms of action

At present, there are 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 reduce BMI in PCOS patients​. Obesity negatively impacts ovarian function due to its characteristics of tissue-specific chronic inflammation and oxidative stress. In obesity, adipocyte hypertrophy leads to hypoxia-induced necrosis of adipocytes and infiltration of adipose tissue with circulating macrophages and T helper cells. Increased levels of macrophages may 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) signal transduction pathway.

The second hypothesis is that omega-3 PUFAs have beneficial effects on insulin resistance in patients with PCOS​. Omega-3 PUFAs could reduce the endoplasmic reticulum stress caused by metabolic abnormalities in PCOS patients, reduce lipid deposition in cells, reduce reactive oxygen species levels in cells and improve insulin sensitivity to a certain extent. IGF-I is synthesized by the ovary and the IGF-I receptor, a tyrosine kinase, shares considerable structural and functional homology with the insulin receptor​. The hybrid heterotetramers assembled by α and β dimers of insulin and IGF-F receptor can bind insulin and IGF-I and further mediate several insulin actions 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 may be beneficial for restoring ovulatory menstrual cycles.

The third hypothesis is that omega-3 PUFAs are beneficial due to their anti-inflammatory and inflammation-resolving actions. EPA and DHA decreased the expression levels of TNF-α and IL-6 induced by lipopolysaccharide​. In addition, DHA also significantly reduced the expression levels of vascular endothelial adhesion factor-1 and vascular cell adhesion factor, which indicates that omega-3 PUFAs may have a potential mediation mechanism on vascular endothelial injury caused by inflammatory factors. In addition, DHA inhibited the expression of TNF-α and IL-6 by inhibiting the activity of the NF-κB signalling pathway, which was accompanied by an increase in PPAR-γ expression levels. These results show that omega-3 PUFAs have a significant protective effects on the abnormal expression of inflammatory factors in patients with PCOS.

Finally, omega-3 PUFAs may also have effects on the hormone levels of PCOS patients. Omega-3 PUFAs inhibited the arachidonic acid-induced activation of 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 produce intervention effects. 

Source: The British Journal of Nutrition​

Ling Lu, Xiaoqin Li,, Lin Lv, Yao Xu , Baohua Wu, and Chaolin Huang​

"Dietary and serum omega-3 polyunsaturated fatty acids and PCOS: A matched case-control study"​

DOI 10.1017/S0007114521003007