The Bioactive Effect  of Flaxseed on  Women with the  Polycystic Ovarian Syndrome

 

Shaimaa SH. Matar

Nutri. & Food Sci. Dept., Faculty of Home Economics,

Helwan University, Egypt

 

Ahmed A. Farrag

Nutri. & Food Sci. Dept., Faculty of Home Economics,

Helwan University, Egypt

 

Samar  M. Hafez

Pharmacology Dept.Faculty of Veterinary Medicine,

Cairo  University, Egypt

 

Radwa M. Fahmy

Obstetrics and Gynecology. Dept.,Faculty of Medicine

(Kasr Alainy),Cairo  University, Egypt

 

 

 

 

 

 

 

 

 

Abstract

The present study aimed to  to investigate the effect of the active substances found in flaxseed powder  on improving ovarian cysts, overcoming the symptoms and complications caused by this disease, and rebalancing the state of hormones in the body, the most important of which is the treatment of insulin resistance, lowering body weight all with the aim of desire and ambition to bring about pregnancy and childbirth   in women with  poly cystic ovarian syndrome (PCOS) .Thirty  women with PCOS, between 18 to 40 years  were  selected , women with PCOS were divided into 3 groups (10woman/group) All groups were subjected to a diet low in carbohydrates and protein to reduce weight, in addition to taking the basal medications, with the exception of metformin tablets,the experiment lasted for 3 months .  The results of the present study  showed that ground  flaxseed with the application and following of a diet low in carbohydrates and protein, all together have a significant positive effect in improving cases of polycystic ovaries, treating hormonal imbalance, regulating the occurrence of the menstrual cycle and the occurrence of pregnancy and childbearing in some women.

 

 

 

 

 

 

Introduction

 

Polycystic Ovary Syndrome (PCOS) is known as the most common endocrine disorder of women in reproductive ages. ( Haidari et al .,2020)

It is a hormonal imbalance and metabolic disorder affecting about 8-13% of all women during their reproductive age.  It leads to some of the major implications such as  anovulation, hyperandrogenism,polycystic ovary hyperinsulinism, hirsutism, and elevated concentrations of luteinizing hormone (LH) (Shamsi et al.,2020).

 

It is  amajor disorder characterized by elevated levels of male hormones (androgens), menstrual irregularities ,hypertrophy ovarian Volume , acne and hirsutism. It can even cause insulin resistance, anovulation ,infertility , hyperinsulinemia and dyslipidemia in addition to risk of heart disease and   type 2 of diabetes on the long run   .     Since PCOS is a curable disorder, it can be cured by use of natural remedies ( Haidari et al .,2020 ) in recent years, increasing evidence has shown that natural plant-based products may play a role in the treatment and management of PCOS. (Mina et al., 2020  and  Lei et al., 2018)

 

Flaxseed is one of the oldest crops, having been cultivated

since the beginning of civilization. The Latin name of the flaxseed is Linum usitatissimum, which means “very useful” (Laux, 2011).

 

Flaxseed is emerging as an important functional food ingredient because of its rich contents of α-linolenic acid (ALA, omega-3 fatty acid), lignans, and fiber. Flaxseed oil, fibers and flax lignans have potential health benefits such as in reduction of cardiovascular disease, atherosclerosis, diabetes, cancer, arthritis, osteoporosis,autoimmune and neurological disorders. Flax protein helps in the prevention and treatment of heart disease and in supporting the immune system (Sepidarkish et al.,2019).

 

Flaxseed supplementation has resulted in significant reduction in ovarian volume and number of follicles in polycystic ovaries, improvement in frequency of menstrual cycles , body weight, blood sugar and hirsutism. The positive effect of FSP could be due to   its content of lignan and alpha- linolenic acid (ALA)(active compounds)  which  they are responsible for the reduction in testosterone, oestrogen, LH and insulin levels contributing to follicular maturation and the anti-inflammatory actions to the reduction in ovarian volume. Considering the  improvement in ovarian function and menstrual cycle, Flax seed  appear to be an alternative source of future drug development for PCOS (Farzana  et al., 2014).

               Therefore,the present study Possible  therapeutic  ability of flaxseed powder on decrease biochemical parameters especially Hyperinsulinemia, Insulin resistance, Hyperandrogenism in addition to Loss  of weight and regulation of menstrual cycle and regulating ovulation hormones and estrogen, and regulating the the menstrual cycle, all with the aim of desire and ambition to bring about pregnancy and childbirth   in cases of  poly cystic ovarian syndrome (PCOS) .

Chemical Analysis Of Bioactive Substances:

Chemical Composition for flaxseed and Nutrition Value.

Source : Diane , 2007:Flax Counc'l of Canada

Photo (1): Chemical composition of Flax Seed

 

Materials and Methods

Subjects :

Flaxseed (Linum Usitatisimum) was obtained from the Agriculture Research Center,then it was ground .

 

 

 

 

Methods:

Preparation of Flaxseed :

Eighteen kg of flaxseeds were purchased and milled in a local mill. They were filled in jars, each package weighed 300 g. It was distributed to patients at a rate of two packages per patient per month for 3 consecutive months.

 

Experimental design:

               Thirty -five woman with PCOS, between 18 to 40 years  were  selected  from the department of  obstetrics /gynaecology and Radiology department, Al Qasr Al Ainy Hospital Hospital , Cairo .

Exclusion Criteria :pregnant , lactating and women with hypertension will be excluded from the  samples .

Women with PCOS were divided into 3 groups (10 woman/group) All groups  were subjected to a diet low in carbohydrates and protein to reduce weight, in addition to taking the basal medications, with the exception of metformin tablets,the experiment lasted for 3 months  as follows: 

Group (1) : control, The women had taken the basal medication  in addition to metformin tablets.

Group (2) : The women had taken the basal  medication exception  metformin tablets . 

Group (3):  women were   provided with flax seed powder and instructed to take orally 20 gram of flax seed powder (10g in the morning and 10 g  in the evening ) with a spoon provided, in lemon juice before meals.

The used dosage were  an average dosage based on the previous studies

 (Farzana  et al., 2014 ) .

 

Cases were followed up and communicated with their daily via  mobile .

Five of the thirty-five women withdrew from the experiment due to their travel and distance from Al Qasr Al Ainy Hospital Hospital , Cairo .

Blood samples were taken from cases of polycystic ovaries before the beginning of the experiment and at the end of the experiment. The blood samples were separated and transferred to a serum for the necessary analysis .

Analysis For PCOS :

Ovulation evaluation may be broken down into types:

Hormones Tests:

These Hormonal  Tests Include The Following :

Luteinizing Hormone (LH):

Luteinizing Hormone (LH) was determined according to Sherman et al., (1976).

Follicle Stimulating Hormone(FSH):

Follicle Stimulating Hormone(FSH)was analyzed  according to Rose et al., (2000).

Anti-Mulirian Hormone (AMH):

Anti-Mulirian Hormone (AMH)  was estimated according to Tobler et al.,(2015).

Fasting Insulin( F.Insulin):

Fasting Insulin( F.Insulin)  was analyzed according to  Young  et al.,(1972)

Cortisol AM :

Cortisol AM  was determined according to  Casals and  Hanzu (2020)

 

Estradiol(E₂) :

Estradiol  was estimated  according to  Scott  et al.,(1993)

Free Testosterone :

Free Testosterone was analyzed according to Salameh et al.,(2010)

Random blood sugar  :

Random blood sugar  was determined according to Young  et al.,(1972)

These  biochemical  analysis were performed in biochemical Analysis Laboratory of   El-kasr Elini Hospital .

 

Dietary Studies :

1- Body weight, Height  and  body mass index  (BMI) .

Diet history including food habits was taken during an interview with patients including food likes and dislikes .

Nutrients intake :

Two types of menus were designed according to patients BMI . Daily energy and nutrients intake ( e.g., protein , fat , vitamins , minerals were calculated for all patients using food intake analysis system  FIAS) .

2-Anthropometric Measurements :

Measurements of height, weight , and body mass index .

Height was measured to the nearest 0.5 centimeter with subject standing with head , shoulder , but tocks and heals vertically aligned and bare footed.

Weight was measured to the nearest 0.1 kg with light clothing and without shoes . Body weights of all participants were recorded at the base line after 6 and 12 weeks of the following regimen .

Body mass index (BMI) was calculated according to Mitch and Klahr,(1993), as the weight (kg)/height (m²). The prevalence of overweight or obesity was determined.

3- Presence of hirsutism.

4-Menstrual cycle History included age at menarche, frequency, duration and severity of menstrual flow and history of dysmenorrheal. In addition, information on history of difficulty in conception were collected ( Debra et al.,2007).

A healthy diet to reduce weight provided for cases of polycystic ovary syndrome  Regimen  diets low in carbohydrates and protein  presented to women with polycystic ovarian syndrome PCOS :

Provided 1500 k.calories :

( 40%  Carbohydrate , 20% protein  and  40% fats )

The diet is divided into three meals per day ( Breakfast ,  Lunch  and Dinner )

Breakfast :

100 g Grilled cauliflower cooked  in the oven,5 spoons of baba ghanouj salad  and  100 g Cucumber slices.

or

100g Grilled falafel in the oven, 5spoons (100g) cooked fava beans

And  agreen salad plate(20g onions+50g coriander +50g lettuce+50g Cucumber+20g tomatoes +1 tps olive oil ) 

or

100g of lentils soup ,60g boiled egg and  agreen salad plate(30g onions+50g coriander +50g lettuce+50g Cucumber+20g tomatoes +1 tps olive oil )  . 

or

100 g Koshari dish without rice, vermicelli and pasta ,60g boiled egg

 And agreen salad plate(20g onions+50g coriander +50g lettuce+50g Cucumber+20g tomatoes +1 tps olive oil )   .

Between Each Meal :

Intermittent fasting  which you drink  warm unsweetened drinks.

 Warm drinks:

Big cup of 200ml (Cinnamon with cloves or ginger with lemon or sage with marjoram  aor fennel anise) .

Twenty minutes before lunch :

100g apple  or  100g orange  or  100g five strawberries .

Lunch :

150g  fish grilled or cooked in the oven, preferably (mackerel - tuna - catfish - tilapia) , A plate of green salad and  60g three spoons of rice or grits .

Or

Vegetable soup plate ( 50g cabbage leaf – 50gcelery – 50g green coriander - - 100g  zucchini – 100g  green beans   ) 150 g  1/4 chicken, and  green salad plate .

Or

 280g  stuffed dish of  vine leaves or cabbage or Stuffed assorted vegetables(zucchini, eggplant, bell pepper and green pepper) stuffed with(100g  leafy vegetables ,50g onions ,100g  minced chicken meat,30g  sunflower oil )  and  100g  Yogurt salad with cucumber, green coriander, garlic and pickled olives .

Or

250 g dish of  lentil soup with carrots and zucchini (mashed), 60g  a boiled local , baladi egg and a green salad dish .

Dinner:

60g  (3tps) of raw sesame or Pumpkin seeds and pulp or Sunflower seeds and pulp or almonds or walnuts  with adish of green salad with 1 tps olive oil   .

A day of detox:

It is done at a rate of three times every week, after every two days of eating the previous meals.

At  Detox  Day  the following is addressed:

Vegetable soup two twice aday  and green juice (watercress, lettuce, green coriander, cucumber, mint and anise)  and  previous warm drinks without sugar  .

Statistical analysis:

The obtained data were statistically analyzed using SPSS-PC statistical package software  and the type of test is ANOVA followed by Duncale  at  0.05 significant (SAS , 2004). 

 

Results and Discussion

Nutritional Studies

Body Mass Index(BMI):

Results in table (1) indicated that a total of  35  woman with polycystic  ovarian syndrome( PCOS)  were included in the final analysis,there were married ,women with PCOS who treated with oral dietary supplement of 20 g  of flaxseed powder / day  had the lowest mean body mass index ,this is agreement with (Mohammadi-Sartang et al.,2018)   then followed by women who have been on a diet low in carbohydrates and protein compared  to the control group at post treatment , the differences between  the groups were significant  and this was in agreement with(Yuan et al and Wong et al., 2016) .   

 

Also, results revealed that PCOS womens  who were subjected to only drug administration  had the highest mean body mass  index and lowest weight loss . The decrease of body mass index (weight  loss )was attributed to the active constituent  of  flaxseed  such as adietary fiber  lignan  and essential fatty acid  omega-3 ,phenolic  compounds and vitamins  which play an important role  in decrease of insulin resistance ,consequently ,an increase  in fat metabolism  and its burn in the body  leads to weight loss and decrease of body mass index  .These results are agreement with  (Yari etal.,2021)

 

Biochemical Analysis

1. Follicular  Stimulating Hormone (FSH) , Leutinizing  Hormone (LH) and Anti-Mulirian Hormone (AMH):

Analysis presented in table(2) illustrated that almost of treated groups induced increase of follicular stimulating hormone (FSH) compared to the control group ,and the control group inducedthe greatest increase in (FSH) was obtained  by supplementation  with flaxseed powder  then followed by Women who have been on a diet low in carbohydrates and protein,the differences between groups were significant  and  these results  were agreed with (Mehrabani  et al.,2012)  .

               Concerning  leutinizing  hormone (LH)  and antimullerian hormone (AMH), data analysis revealed that  almost of treated groups  induced decrease in (LH and AMH)compared to the control group .The greatest  decrease in (LH and AMH ) was obtained by supplementation  with flaxseed powder compared to the other tested  groups , this decrease was significant  and this was  agreed with (Farzana et al.,2014 ). The women who consumed ground flaxseed, four of them became pregnant, just as the menstrual cycle was regular for the majority of the women of this group, then followed by women who have been on a diet low in carbohydrates and protein compared  to the control group  and  two of them became pregnant and the menstrual cycle was regular for the majority of them while the group that lost weight ,loss two of them became pregnant and had regular ,the menstrual cycle when most of them. Whereas, women in the group that took metformin did not get pregnant, with irregular menstruation.

 

An increase of (FSH) and the decrease of (LH and AMH) by almost of treated groups may be attributed to   the good effects of flaxseed powder and red beets   which they contain  antioxidant properities  and essential fatty acids  such as omega -3 ,especially at flaxseed powder  and low carbohydrate and low protein diet  , all of these factors  each to other resulted in  hypoinsulinemia  and  an increase of the receptors sensitivity  of the body cells to insulin hormone  ,consequently ,hypoandrogenism ,increase of (FSH) hormone and decrease of (LH and AMH ) hormones .These results  was  agreed with (Vickova et al.,2018)  .

 

 

3. Fasting Insulin Hormone (F.Insulin), Cortisol , Estradiol (E2), Free  Testosterone (F.Testosterone) and  Glucose :

 

Data presented in  table (3a and 3b) illustrated that almost of treated groups induced decrease of glucose level ,insulin hormone  and decrease of  cortisol AM  at post treatment compared to  pre  treatment and the differences between groups were significant These results were agreed with(Haidari et al., 2020) . 

 

 

The greatest decrease of glucose level and insulin hormone  were obtained by supplementation with flaxseed powder then followed by the group of  women who have been on a diet low in carbohydrates and protein. These results were agreed with(Haidari et al., 2020) and these  may be attributed bioactive substances such as oil, essential fatty acid especially omega -3, protein, dietary fiber, lignansand  phenolic compounds,vitamins (A, C, F and E) and mineral (P, Mg, K, Na, Fe, Cu,Mn and Zn) (  Jheimbach and  Port Royal ,2009).

 

These essential fatty acids especially  are very popular because of their antihyperglycaemic  effects, Potential efficacy of omega-3 on carbohydrate metabolism and glucose homeostasis  may offer unique treatment modalities for various aspects of type 2 diabetes( Andrica et al., 2015).  Sidika  et al.,2016  found that  the novel possibility that dietary PUFA may alter glucose indirectly, secondary to its effects on the  aromatic aminoacids (AA) metabolism. Alternatively, alterations in AA metabolism can be the consequence of the PUFA-induced changes in insulin sensitivity ,consequently ,reduction in blood glucose level . The reduction in blood glucose stimulated the release of cortisol as a counter regulatory mechanism  ( Olumese and Oboh, 2016) . The correlation studies revealed a weak relationship between glucose and cortisol.Cortisol, a stress hormone has been reported to increase gluconeogenesis, decrease peripheral glucose utilization and increase the availability of fuel substances by the mobilization of glucose, free fatty acids, and amino acids from endogenous stores. The results from this study showed that cortisol correlated posititively with insulin(Olumese and Oboh, 2016).

 

Concerning estrogen hormone and free testosterone  hormone ,the analysis revealed that almost of supplemented groups induced increase of estrogene hormone level compared to the control group and decrease of  free testosterone level at post treatment compared to pretreatment  .

               The greatest decrease of  free testosterone and increase of estrogen level  was obtained by supplementation with flaxseed powder then followed by women who who only underwent a low-protein, low-carbohydrate diet with the medication compared to the control group ,the differences between groups were significant and these results were agreed with(Kuranova et al.,2020) .

       The positive effect of  flaxseed powder (FSP) could be due to reduction in testosterone, estrogen, LH and insulin levels contributing to follicular maturation and the anti inflammatory actions to the reduction in ovarian volume (Farzana et al.,2014 and Kuranova et al.,2020).

4.Thyroid Stimulating Hormone(TSH), Triiodothyronine (T3) and

Thyroxine(T4) :

Results in table (4a) and table (4b) showed that  almost of treated  groups induced increase within normal range (TSH) hormone,(T3) and (T4) at post treatment  compared to pre treatment between groups especially control group and the differences between groups were significant .The greatest increase of TSH,T3 and T4 hormones were obtained by supplementation with flaxseed powder then followed by women who have been low carbohydrate low protein diet  compared to the control group,this was agreed with (Faris et al.,2020) .

 

The greatest decrease of TSH,T3 and T4 was obtained by control group .The increase induced in TSH,T3 and T4 hormones in all treated groups may be attributed to their antioxidant  properties of their bioactive constituents In addition ,the decrease in TSH,T3 and T4 may be interpreted as  adverse metformin  medication  impact on thyroid gland. Since,adding flaxseed ,intermitting fasting and low carbohydrate low protein diet  caused a significant decrease of testosterone, increased estradiol concentration, also each of growth hormone and TSH hormones increased significantly(Chiofalo etal.,2017)..

 

As decrease in genomic DNA concentration with flaxseed supplementation may due to one of the mechanisms by which phytoestrogens may influence reproductive physiology that involve inhibition of enzymes essential for DNA replication.These results are agreement with  (Yousif ,2019) .

 

 

In  conclusion,  the results of the present study  showed that flaxseed powder improved body mass index (BMI), follicular stimulating hormone (FSH), Leutinizing Hormone (LH) ,  anti-mulirian hormone (AMH), insulin hormone, cortisol, estradiol(E₂) , free testosterone, glucose, and thyroid gland hormones in women who have been on alow carbohydrate low protein diet . The flaxseed powder have given  better results in improving the cases of polycystic ovaries, achieving a balance in hormones and producing pregnancy and childbearing compared to the rest of the experiment groups.

 

Table (1) : Effect of Flaxseed and Diet Regimen between all Groups (pre and post ) on Body Mass Index(Weight Loss)  .

Data expressed as mean ± SD, significant differences at  P < 0.05
No significant differences between  the values had the same letter in each column .

 

Table (2) : Effect of  Flaxseed and Diet Regimen between all Groups (pre and post ) on Ovulation Hormones , Follicular  Stimulating Hormone (FSH) , Leutinizing Hormone (LH) and Anti-Mulirian Hormone (AMH).

Data expressed as mean ± SD, significant differences at  P < 0.05
No significant differences between  the values had the same letter in each column .

Table (3a) : Effect of Flaxseed and Diet Regimen between all Groups (pre and post ) on Fasting  Insulin  Hormone(F.Insulin), Cortisol and Estradiol (E2).

 

Data expressed as mean ± SD, significant differences at  P < 0.05
No significant differences between  the values had the same letter in each column .

 

 

Table (3b) : Effect of Flaxseed and Diet Regimen between all Groups (pre and post ) on Free  Testosterone (F.Testosterone) and  Glucose .

Data expressed as mean ± SD, significant differences at  P < 0.05
No significant differences between  the values had the same letter in each column .

 

 

Table (4) : Effect Of Flaxseed And Diet Regimen Between All Groups  (pre and post ) On Thyroid Gland Analysis (Thyroid Stimulating Hormone(TSH), Triiodothyronine (T3) and Thyroxine(T4) .

Data expressed as mean ± SD, significant differences at  P < 0.05
No significant differences between  the values had the same letter in each column .

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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قسم النسا والتوليد – کلية طب القصر العينى –جامعة القاهرة

 

الملخص العربى

 

                 استهدفت الدراسة الحالية معرفة تأثير المواد الفعالة الموجودة في بذر الکتان المطحون على تحسين حالات  النساء المصابات بمتلازمة  تکيس المبايض (PCOS) ، أى متلازمة خلل الهرمونات الذى يترتب عليه خلل فى عملية التمثيل الغذائى وخلل فى حرق الدهون وحدوث الالتهابات بالجسم وتأخر الحمل وعدم انتظام الدورة الشهرية   ، والتغلب على الأعراض والمضاعفات التي يسببها هذا المرض ، وإعادة التوازن إلى حالة الهرمونات في الجسم ، وأهمها علاج مقاومة الأنسولين وخفض وزن الجسم بهدف تحقيق الحمل والإنجاب  عند هؤلاء النساء.

 

                 تم اختيار خمسة وثلاثون امرأة مصابة بمتلازمة تکيس المبايض ، تتراوح أعمارهن بين 18 إلى 40 عامًا ، وتم تقسيم النساء المصابات بمتلازمة تکيس المبايض إلى 3 مجموعات (10 نساء / مجموعة). استمرت التجربة لمدة 3 أشهر  خضعت المجموعات الثلاث إلى اتباع نظام غذائى منخفض النشويات والبروتين مع تطبيق صيام متقطع  بجانب تناول الأدوية الطبية جميعها  ما عدا عقار الميتفورمين  باستثناء المجموعة الأولى فقط ( المجموعة الضابطة ) هى المجموعة الوحيدة فقط التى تناولت  أقراص الميتفورمين ضمن العلاج الدوائى . وقد أظهرت نتائج الدراسة الحالية أن  تناول20 جم من بذر الکتان المطحون مع تطبيق واتباع نظام غذائي منخفض النشويات  والبروتينات لهما تأثير إيجابي کبير في تحسين حالات تکيس المبايض ، وعلاج خلل الهرمونات ، وتنظيم حدوث الدورة الشهرية. وقد حدثت بعض حالات  الحمل والإنجاب  للمرة الأولى عند بعض النساء بنسبة أعلى وأفضل من باقى المجموعات جميعها  وکان له افضل الأثر فى علاج بعض هذه الحالات  بعد العديد من المحاولات الطبية السابقة التى کانت قد استمرت ستة أعوام دون جدوى .

 

الکلمات المفتاحية: متلازمة تکيس المبايض (PCOS) ، بذر الکتان  والخصوبة ، مقاومة الإنسولين والتکيس  ، السمنة ، الکورتيزول والتکيس ، هرمونات الغدة الدرقية  والتکيس ، مؤشر کتلة الجسم (BMI) ،الهرمونات المسؤولة عن التبويض ، سکر الدم العشوائي.

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