Ignite Creation Date:
2024-10-26 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06551285
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-07-31
Brief Title:
Study of the Effect of a Nutritional Supplement on Microbiota Metabolic Control Inflammatory Profile and Quality of Life in Patients With Polycystic Ovary Syndrome
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Study of the Effect of a Nutritional Supplement on Microbiota Metabolic Control Inflammatory Profile and Quality of Life in Patients With Polycystic Ovary Syndrome
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Polycystic Ovary Syndrome PCOS is a complex endocrine-metabolic disorder characterized by elevated androgen levels due to ovarian overproduction Although the pathophysiology of PCOS is not fully understood it is estimated that insulin resistance IR occurs in 70-80 of PCOS cases which may contribute to hyperandrogenism in affected women
Women with PCOS and IR are more likely to develop metabolic syndrome increasing the risk of diabetes cardiovascular diseases lipid profile deterioration elevated inflammation levels and greater oxidative stress
The symptoms of PCOS are varied and differ among patients Common symptoms include androgenic alopecia hirsutism acne abdominal fat accumulation and fertility issues These physical manifestations and related problems have been associated with reduced quality of life and self-esteem in these women The symptoms of PCOS can be improved through lifestyle changes aimed at enhancing insulin sensitivity such as proper nutrition and regular physical exercise
Some supplements such as a combination of Myo-inositol and D-chiro-inositol in a 401 ratio are being used to support the management of PCOS because they appear to improve insulin sensitivity as well as reduce underlying inflammation and oxidative stress
To determine whether nutritional intervention combined with inositol supplementation improves PCOS symptoms various variables will be analyzed to assess improvements in oxidative stress markers inflammation lipid profile hormonal profile and microbiota Additionally if the metabolic profile improves it is hypothesized that this could also enhance quality of life and self-esteem
Women with PCOS and IR are more likely to develop metabolic syndrome increasing the risk of diabetes cardiovascular diseases lipid profile deterioration elevated inflammation levels and greater oxidative stress
The symptoms of PCOS are varied and differ among patients Common symptoms include androgenic alopecia hirsutism acne abdominal fat accumulation and fertility issues These physical manifestations and related problems have been associated with reduced quality of life and self-esteem in these women The symptoms of PCOS can be improved through lifestyle changes aimed at enhancing insulin sensitivity such as proper nutrition and regular physical exercise
Some supplements such as a combination of Myo-inositol and D-chiro-inositol in a 401 ratio are being used to support the management of PCOS because they appear to improve insulin sensitivity as well as reduce underlying inflammation and oxidative stress
To determine whether nutritional intervention combined with inositol supplementation improves PCOS symptoms various variables will be analyzed to assess improvements in oxidative stress markers inflammation lipid profile hormonal profile and microbiota Additionally if the metabolic profile improves it is hypothesized that this could also enhance quality of life and self-esteem
Detailed Description:
Polycystic Ovary Syndrome PCOS is an endocrine-metabolic disorder that affects many women of reproductive age PCOS is not just a reproductive disorder but a systemic condition as cases of PCOS have been described even in menopause although its prevalence in post-reproductive stages is not high The diagnosis of PCOS is made using the Rotterdam criteria agreed upon in 2003 by ESHRE and ASRM European Society for Human Reproduction and EmbryologyAmerican Society for Reproductive Medicine According to these criteria a patient must meet two of the following three criteria to be diagnosed with PCOS oligo-anovulation clinical or biochemical hyperandrogenism and polycystic ovarian appearance
The Rotterdam criteria are widely used but can sometimes lead to an erroneous diagnosis of PCOS Therefore in 2006 the AES Androgen Excess Society decided that in addition to the 2003 Rotterdam criteria hyperandrogenism-either physical or biochemical-was necessary for a PCOS diagnosis Depending on the criteria used and the diversity of the population studied epidemiological results can vary Despite this variability it is estimated that PCOS affects 6-12 of women of reproductive age
The most common manifestations of PCOS include androgenic alopecia hirsutism acne irregular cycles or periods of amenorrhea An ultrasound image showing polycystic ovarian morphology alone is insufficient for diagnosing PCOS In polycystic ovaries more than 12 follicles of 2-9 mm in size and increased ovarian volume 10 ml should be visualized using transvaginal ultrasound Despite the complex and not fully understood pathophysiology of PCOS two main types of alterations are identified On one hand there is an accelerated release of gonadotropin-releasing hormone GnRH which leads to an increased release of luteinizing hormone LH resulting in greater androgen production altered folliculogenesis and long menstrual cycles or amenorrhea On the other hand there is an alteration in ovarian steroidogenesis and folliculogenesis due to increased activity of cytochrome P450c17 an enzyme involved in the synthesis of ovarian and adrenal androgens leading to elevated androgen levels
In 70-80 of PCOS cases women present insulin resistance IR with 30-50 of these also exhibiting obesity High body fat percentage and hyperinsulinemia play significant roles in the development and progression of PCOS Chronically elevated insulin levels can be associated with elevated androgen levels in a bidirectional manner Elevated insulin levels may stimulate LH production and increase the activity of the P450c17 enzyme in the ovaries and adrenal glands resulting in reduced hepatic production of sex hormone-binding globulin SHBG which increases the amount of free androgens Conversely elevated androgens are associated with increased insulin resistance in the muscles leading to poorer glucose uptake
Obesity is considered an amplifying factor in the pathophysiology of PCOS Adipose tissue is an endocrine organ and a high amount of adipose tissue increases the production of inflammatory cytokines which can worsen IR by interfering with glucose uptake While 70-80 of women with PCOS have IR there is a 20-30 subgroup without metabolic involvement Women with PCOS who have a healthy body fat percentage also present with insulin resistance suggesting that obesity is not the cause of PCOS
PCOS is a syndrome with a significant genetic basis complex and multifactorial pathophysiology Lifestyle benefits in improving symptoms and the syndromes progression are an important therapeutic tool PCOS directly affects the quality of life of patients due to the long-term symptoms and comorbidities associated with this condition such as obesity type 2 diabetes mellitus T2DM metabolic syndrome MS and psychological and emotional issues Consequently women with PCOS generally have poorer health compared to those without the condition Furthermore comorbidities directly impact quality of life and individual perception of it
To improve symptoms and prevent the comorbidities the first line of treatment for patients with PCOS and IR should involve lifestyle modifications Nutritional intervention and physical exercise are fundamental in maintaining a proper body composition which can prevent the worsening of PCOS symptoms The quality and composition of the diet are crucial beyond the implications of body weight A hypocaloric diet including low glycemic load foods has been shown to improve the homeostatic model assessment of insulin resistance HOMA-IR low-density lipoprotein LDL levels triglycerides TGC cholesterol and free androgen index FAI Improving lifestyle will directly impact body fat percentage which in turn will improve hyperandrogenism and ovarian function
Mental health disorders are highly prevalent among women with PCOS particularly anxiety depression and sleep disorders Sleep disturbances impact the onset and progression of anxiety and depression in PCOS patients thus treating sleep-related issues should be part of the overall treatment Sleep deprivation is associated with an increased risk of IR obesity and type 2 diabetes T2D It has been observed that patients with PCOS have decreased melatonin levels in follicular fluid Melatonin is a potent antioxidant that protects ovarian follicles during maturation Therefore sleep disorders can worsen insulin resistance and consequently exacerbate PCOS with metabolic involvement
Additionally the microbiota through the production of various metabolites impacts complex mechanisms such as hunger and satiety regulation carbohydrate and lipid metabolism which can directly affect body composition and PCOS symptoms The gut microbiota can regulate up to 10 of the transcriptome and host genes involved in metabolism proliferation and immune response Moreover diet can modulate the gut microbiota composition in patients with PCOS and IR as an increase in bifidobacteria correlates with improved insulin sensitivity and reduced inflammation Short-chain fatty acids SCFAs such as acetate and butyrate produced by beneficial gut microbiota influence glycemia Given the role of these metabolites in carbohydrate and lipid metabolism achieving a healthy microbiota state could be a therapeutic goal to reduce systemic inflammation and improve IR
The two specific inositol stereoisomers Myo-inositol MI and D-chiro-inositol DCI act as second messengers of insulin MI transforms into an insulin second messenger Myo-inositol phosphoglycan MI-IPG which is involved in cellular glucose uptake while DCI converts into another insulin second messenger DCI-IPG which is involved in glycogen synthesis In patients with PCOS there appears to be an increased epimerization of Myo-inositol MI to D-chiro-inositol DCI at the ovarian level due to insulins effect Consequently there is an excess of DCI and a deficiency of MI which can affect follicle-stimulating hormone FSH signaling and deteriorate oocyte quality Therefore inositol supplementation is considered an effective and safe method for improving PCOS symptoms by enhancing insulin sensitivity follicular development and oocyte maturation This insulin-sensitizing effect of inositol can help normalize blood androgen levels and improve glycemia Metformin is a common treatment for women with PCOS and IR Recent results show that Myo-inositol can be as effective as metformin without its side effects Both inositol and metformin can improve the metabolic and clinical profile of PCOS patients as well as metabolic disorders related to diabetes
Additionally adequate vitamin D levels should also be considered in patients with PCOS as vitamin D is involved in increasing the synthesis and release of insulin enhances insulin receptor presence and improves insulin response in glucose transport Vitamin D indirectly affects carbohydrate metabolism by normalizing extracellular calcium levels and parathyroid hormone concentration It also impacts systemic inflammation by inhibiting the production of pro-inflammatory cytokines which could contribute to the development of IR Patients with PCOS who took 20000 IU of cholecalciferol Vitamin D weekly benefited from improved carbohydrate metabolism and better menstrual frequency Combined supplementation of magnesium zinc calcium and vitamin D in another study led to a significant reduction in total testosterone compared to placebo although it did not affect sex hormone-binding globulin SHBG levels or the free androgen index FAI However the combination of vitamin D and fish oil reduced inflammation markers in the body such as serum C-reactive protein CRP downregulated interleukin 1 IL-1 and total testosterone levels A beneficial effect on mental health parameters was also observed assessed through the Beck Depression Inventory Available literature shows that zinc supplementation may be indicated in patients with PCOS as zinc plays an important role in glucose and lipid metabolism Zinc deficiency may play a significant role in PCOS pathophysiology and also serve as a prognostic marker for the syndrome It appears that zinc levels in PCOS patients are significantly lower compared to healthy controls Low zinc intake in individuals with high body fat percentage is associated with hyperinsulinemia low-grade inflammation and deterioration of the lipid profile Zinc ions can act as insulin mimetics in adipocytes stimulating lipogenesis and glucose transport through the translocation of glucose transporter 4 GLUT4 to the plasma membrane
In PCOS patients there is known to be higher oxidative stress which could worsen the symptoms of PCOS Curcumin extracted from turmeric Curcuma longa is a biologically active phytochemical with antioxidant properties Studies with curcumin in animals have shown promising results but in PCOS patients the literature is inconclusive and it is limited to suggesting that curcumin may have beneficial effects in the clinical management of PCOS symptoms
The Rotterdam criteria are widely used but can sometimes lead to an erroneous diagnosis of PCOS Therefore in 2006 the AES Androgen Excess Society decided that in addition to the 2003 Rotterdam criteria hyperandrogenism-either physical or biochemical-was necessary for a PCOS diagnosis Depending on the criteria used and the diversity of the population studied epidemiological results can vary Despite this variability it is estimated that PCOS affects 6-12 of women of reproductive age
The most common manifestations of PCOS include androgenic alopecia hirsutism acne irregular cycles or periods of amenorrhea An ultrasound image showing polycystic ovarian morphology alone is insufficient for diagnosing PCOS In polycystic ovaries more than 12 follicles of 2-9 mm in size and increased ovarian volume 10 ml should be visualized using transvaginal ultrasound Despite the complex and not fully understood pathophysiology of PCOS two main types of alterations are identified On one hand there is an accelerated release of gonadotropin-releasing hormone GnRH which leads to an increased release of luteinizing hormone LH resulting in greater androgen production altered folliculogenesis and long menstrual cycles or amenorrhea On the other hand there is an alteration in ovarian steroidogenesis and folliculogenesis due to increased activity of cytochrome P450c17 an enzyme involved in the synthesis of ovarian and adrenal androgens leading to elevated androgen levels
In 70-80 of PCOS cases women present insulin resistance IR with 30-50 of these also exhibiting obesity High body fat percentage and hyperinsulinemia play significant roles in the development and progression of PCOS Chronically elevated insulin levels can be associated with elevated androgen levels in a bidirectional manner Elevated insulin levels may stimulate LH production and increase the activity of the P450c17 enzyme in the ovaries and adrenal glands resulting in reduced hepatic production of sex hormone-binding globulin SHBG which increases the amount of free androgens Conversely elevated androgens are associated with increased insulin resistance in the muscles leading to poorer glucose uptake
Obesity is considered an amplifying factor in the pathophysiology of PCOS Adipose tissue is an endocrine organ and a high amount of adipose tissue increases the production of inflammatory cytokines which can worsen IR by interfering with glucose uptake While 70-80 of women with PCOS have IR there is a 20-30 subgroup without metabolic involvement Women with PCOS who have a healthy body fat percentage also present with insulin resistance suggesting that obesity is not the cause of PCOS
PCOS is a syndrome with a significant genetic basis complex and multifactorial pathophysiology Lifestyle benefits in improving symptoms and the syndromes progression are an important therapeutic tool PCOS directly affects the quality of life of patients due to the long-term symptoms and comorbidities associated with this condition such as obesity type 2 diabetes mellitus T2DM metabolic syndrome MS and psychological and emotional issues Consequently women with PCOS generally have poorer health compared to those without the condition Furthermore comorbidities directly impact quality of life and individual perception of it
To improve symptoms and prevent the comorbidities the first line of treatment for patients with PCOS and IR should involve lifestyle modifications Nutritional intervention and physical exercise are fundamental in maintaining a proper body composition which can prevent the worsening of PCOS symptoms The quality and composition of the diet are crucial beyond the implications of body weight A hypocaloric diet including low glycemic load foods has been shown to improve the homeostatic model assessment of insulin resistance HOMA-IR low-density lipoprotein LDL levels triglycerides TGC cholesterol and free androgen index FAI Improving lifestyle will directly impact body fat percentage which in turn will improve hyperandrogenism and ovarian function
Mental health disorders are highly prevalent among women with PCOS particularly anxiety depression and sleep disorders Sleep disturbances impact the onset and progression of anxiety and depression in PCOS patients thus treating sleep-related issues should be part of the overall treatment Sleep deprivation is associated with an increased risk of IR obesity and type 2 diabetes T2D It has been observed that patients with PCOS have decreased melatonin levels in follicular fluid Melatonin is a potent antioxidant that protects ovarian follicles during maturation Therefore sleep disorders can worsen insulin resistance and consequently exacerbate PCOS with metabolic involvement
Additionally the microbiota through the production of various metabolites impacts complex mechanisms such as hunger and satiety regulation carbohydrate and lipid metabolism which can directly affect body composition and PCOS symptoms The gut microbiota can regulate up to 10 of the transcriptome and host genes involved in metabolism proliferation and immune response Moreover diet can modulate the gut microbiota composition in patients with PCOS and IR as an increase in bifidobacteria correlates with improved insulin sensitivity and reduced inflammation Short-chain fatty acids SCFAs such as acetate and butyrate produced by beneficial gut microbiota influence glycemia Given the role of these metabolites in carbohydrate and lipid metabolism achieving a healthy microbiota state could be a therapeutic goal to reduce systemic inflammation and improve IR
The two specific inositol stereoisomers Myo-inositol MI and D-chiro-inositol DCI act as second messengers of insulin MI transforms into an insulin second messenger Myo-inositol phosphoglycan MI-IPG which is involved in cellular glucose uptake while DCI converts into another insulin second messenger DCI-IPG which is involved in glycogen synthesis In patients with PCOS there appears to be an increased epimerization of Myo-inositol MI to D-chiro-inositol DCI at the ovarian level due to insulins effect Consequently there is an excess of DCI and a deficiency of MI which can affect follicle-stimulating hormone FSH signaling and deteriorate oocyte quality Therefore inositol supplementation is considered an effective and safe method for improving PCOS symptoms by enhancing insulin sensitivity follicular development and oocyte maturation This insulin-sensitizing effect of inositol can help normalize blood androgen levels and improve glycemia Metformin is a common treatment for women with PCOS and IR Recent results show that Myo-inositol can be as effective as metformin without its side effects Both inositol and metformin can improve the metabolic and clinical profile of PCOS patients as well as metabolic disorders related to diabetes
Additionally adequate vitamin D levels should also be considered in patients with PCOS as vitamin D is involved in increasing the synthesis and release of insulin enhances insulin receptor presence and improves insulin response in glucose transport Vitamin D indirectly affects carbohydrate metabolism by normalizing extracellular calcium levels and parathyroid hormone concentration It also impacts systemic inflammation by inhibiting the production of pro-inflammatory cytokines which could contribute to the development of IR Patients with PCOS who took 20000 IU of cholecalciferol Vitamin D weekly benefited from improved carbohydrate metabolism and better menstrual frequency Combined supplementation of magnesium zinc calcium and vitamin D in another study led to a significant reduction in total testosterone compared to placebo although it did not affect sex hormone-binding globulin SHBG levels or the free androgen index FAI However the combination of vitamin D and fish oil reduced inflammation markers in the body such as serum C-reactive protein CRP downregulated interleukin 1 IL-1 and total testosterone levels A beneficial effect on mental health parameters was also observed assessed through the Beck Depression Inventory Available literature shows that zinc supplementation may be indicated in patients with PCOS as zinc plays an important role in glucose and lipid metabolism Zinc deficiency may play a significant role in PCOS pathophysiology and also serve as a prognostic marker for the syndrome It appears that zinc levels in PCOS patients are significantly lower compared to healthy controls Low zinc intake in individuals with high body fat percentage is associated with hyperinsulinemia low-grade inflammation and deterioration of the lipid profile Zinc ions can act as insulin mimetics in adipocytes stimulating lipogenesis and glucose transport through the translocation of glucose transporter 4 GLUT4 to the plasma membrane
In PCOS patients there is known to be higher oxidative stress which could worsen the symptoms of PCOS Curcumin extracted from turmeric Curcuma longa is a biologically active phytochemical with antioxidant properties Studies with curcumin in animals have shown promising results but in PCOS patients the literature is inconclusive and it is limited to suggesting that curcumin may have beneficial effects in the clinical management of PCOS symptoms
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None